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Int. J. Mol. Sci., Volume 14, Issue 3 (March 2013), Pages 4375-6528

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Open AccessArticle Expression and Genetic Analysis of MicroRNAs Involved in Multiple Sclerosis
Int. J. Mol. Sci. 2013, 14(3), 4375-4384; doi:10.3390/ijms14034375
Received: 5 December 2012 / Revised: 19 February 2013 / Accepted: 20 February 2013 / Published: 25 February 2013
Cited by 23 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text
Abstract
Evidence underlines the importance of microRNAs (miRNAs) in the pathogenesis of multiple sclerosis (MS). Based on the fact that miRNAs are present in human biological fluids, we previously showed that miR-223, miR-23a and miR-15b levels were downregulated in the sera of MS patients
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Evidence underlines the importance of microRNAs (miRNAs) in the pathogenesis of multiple sclerosis (MS). Based on the fact that miRNAs are present in human biological fluids, we previously showed that miR-223, miR-23a and miR-15b levels were downregulated in the sera of MS patients versus controls. Here, the expression levels of these candidate miRNAs were determined in peripheral blood mononuclear cells (PBMCs) and the serum of MS patients, in addition to three genotyped single nucleotide polymorphisms (SNPs). Mapping in the genomic regions of miR-223, miR-23a and miR-15b genes, 399 cases and 420 controls were tested. Expression levels of miR-223 and miR-23a were altered in PBMCs from MS patients versus controls. Conversely, there were no differences in the expression levels of miR-15b. A significantly decreased genotypic frequency of miR-223 rs1044165 T/T genotype was observed in MS patients. Moreover, the allelic frequency of miR-23a rs3745453 C allele was significantly increased in patients versus controls. In contrast, there were no differences in the distribution of miR-15b SNP. In conclusion, our results suggest that miR-223 and miR-23a could play a role in the pathogenesis of MS. Moreover, miR-223 rs1044165 polymorphism likely acts as a protective factor, while miR-23a rs3745453 variant seems to act as a risk factor for MS. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Different Forms of Selenoprotein M Differentially Affect Aβ Aggregation and ROS Generation
Int. J. Mol. Sci. 2013, 14(3), 4385-4399; doi:10.3390/ijms14034385
Received: 31 December 2012 / Revised: 21 January 2013 / Accepted: 22 January 2013 / Published: 25 February 2013
Cited by 9 | PDF Full-text (2417 KB) | HTML Full-text | XML Full-text
Abstract
Selenoprotein M (SelM), one of the executants of selenium in vivo, is highly expressed in human brain and most probably involved in antioxidation, neuroprotection, and intracellular calcium regulation, which are the key factors for preventing the onset and progression of Alzheimer’s disease
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Selenoprotein M (SelM), one of the executants of selenium in vivo, is highly expressed in human brain and most probably involved in antioxidation, neuroprotection, and intracellular calcium regulation, which are the key factors for preventing the onset and progression of Alzheimer’s disease (AD). In this paper, human SelM was successfully overexpressed in human embryonic kidney cells HEK293T. Sodium selenite (Na2SeO3 0.5 μmol/L) increased the expression of full-length SelM and inhibited the expression of truncated SelM. The full-length SelM exhibited higher antioxidant activity than its selenocysteine-to-cysteine mutation form SelM', whereas the truncated SelM had an adverse effect that increased the oxidative stress level of cells. When β-amyloid (Aβ42, an AD relevant peptide) was cotransfected with the empty expression vector, SelM, or SelM' under the induction of 0.5 μmol/L Na2SeO3, the intracellular Aβ42 aggregation rates were detected to be 57.9% ± 5.5%, or 22.3% ± 2.6%, or 26.3% ± 2.1%, respectively, showing the inhibitory effects on Aβ aggregation by the full-length SelM and SelM'. Meanwhile, the intumescentia of mitochondria caused by 42 transfection was significantly mitigated by the cotransfection of SelM or SelM′ with 42 under the induction of 0.5 μmol/L Na2SeO3. On the contrary, cotransfection of SelM and 42 without the induction of Na2SeO3 increased Aβ42 aggregation rate to 65.1% ± 3.2%, and it could not inhibit the Aβ-induced intumescent mitochondria. In conclusion, full-length SelM and SelM¢ might prevent Aβ aggregation by resisting oxidative stress generated during the formation of Aβ oligomers in cells. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
Open AccessArticle Ribosomal Initiation Complex Assembly within the Wild-Strain of Coxsackievirus B3 and Live-Attenuated Sabin3-like IRESes during the Initiation of Translation
Int. J. Mol. Sci. 2013, 14(3), 4400-4418; doi:10.3390/ijms14034400
Received: 17 January 2013 / Revised: 16 February 2013 / Accepted: 19 February 2013 / Published: 25 February 2013
Cited by 4 | PDF Full-text (294 KB) | HTML Full-text | XML Full-text
Abstract
Coxsackievirus B3 (CVB3) is an enterovirus of the family of Picornaviridae. The Group B coxsackieviruses include six serotypes (B1 to B6) that cause a variety of human diseases, including myocarditis, meningitis, and diabetes. Among the group B, the B3 strain is mostly
[...] Read more.
Coxsackievirus B3 (CVB3) is an enterovirus of the family of Picornaviridae. The Group B coxsackieviruses include six serotypes (B1 to B6) that cause a variety of human diseases, including myocarditis, meningitis, and diabetes. Among the group B, the B3 strain is mostly studied for its cardiovirulence and its ability to cause acute and persistent infections. Translation initiation of CVB3 RNA has been shown to be mediated by a highly ordered structure of the 5’-untranslated region (5’UTR), which harbors an internal ribosome entry site (IRES). Translation initiation is a complex process in which initiator tRNA, 40S and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the initiation codon of the mRNA. We have previously addressed the question of whether the attenuating mutations of domain V of the poliovirus IRES were specific for a given genomic context or whether they could be transposed and extrapolated to a genomic related virus, i.e., CVB3 wild-type strain. In this context, we have described that Sabin3-like mutation (U473→C) introduced in CVB3 genome led to a defective mutant with a serious reduction in translation efficiency. In this study, we analyzed the efficiency of formation of ribosomal initiation complexes 48S and 80S through 10%–30% and 10%–50% sucrose gradients using rabbit reticulocyte lysates (RRLs) and stage-specific translation inhibitors: 5'-Guanylyl-imidodiphosphate (GMP-PNP) and Cycloheximide (CHX), respectively. We demonstrated that the interaction of 48S and 80S ribosomal complexes within the mutant CVB3 RNA was abolished compared with the wild-type RNA by ribosome assembly analysis. Taken together, it is possible that the mutant RNA was unable to interact with some trans-acting factors critical for enhanced IRES function. Full article
Open AccessArticle Characterization of the Expression Profile and Genetic Polymorphism of the Cellular Retinol-Binding Protein (CRBP IV) Gene in Erlang Mountainous Chickens
Int. J. Mol. Sci. 2013, 14(3), 4432-4443; doi:10.3390/ijms14034432
Received: 31 December 2012 / Revised: 6 February 2013 / Accepted: 19 February 2013 / Published: 25 February 2013
Cited by 4 | PDF Full-text (303 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we cloned the coding sequence of chicken CRBP IV, quantified the mRNA expression in Erlang Mountainous Chickens, and investigated a polymorphism in this gene and its association with egg production traits among 349 individuals. The cloned fragment contained a 384
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In this study, we cloned the coding sequence of chicken CRBP IV, quantified the mRNA expression in Erlang Mountainous Chickens, and investigated a polymorphism in this gene and its association with egg production traits among 349 individuals. The cloned fragment contained a 384 bp open reading frame, which encoded a predicted protein of 127 amino acids and was highly conserved among species. Expression of CRBP IV mRNA was detected in all eight tissues (small intestine, heart, liver, kidney, oviduct, ovary, pituitary, and hypothalamus) at different ages (12, 24, 32 and 45 w). High expression was found in small intestine, pituitary, kidney and liver, whereas it was low in the heart (p < 0.05). The CRBP IV mRNA levels changed with age in the various tissues, and were highly expressed in all tissues at 32 w, except for the heart. We identified one nucleotide substitution (c. 826T>C) in the second exon, which caused an amino acid change (p. S49L). Genotypes (TT, TC and CC) had significant effects on the age at first egg (AFE), total eggs for 300 days (TE300) and highest continuous laying days (HCLD). The CC genotype would be genetically advantageous to improve egg production traits due to earlier AFE, more TE300, and longer HCLD. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Synthesis and Structural Characterization of Substituted 2-Phenacylbenzoxazoles
Int. J. Mol. Sci. 2013, 14(3), 4444-4460; doi:10.3390/ijms14034444
Received: 10 January 2013 / Revised: 4 February 2013 / Accepted: 16 February 2013 / Published: 25 February 2013
PDF Full-text (461 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
1H and 13C NMR spectra of eleven 2-phenacylbenzoxazoles (ketimine form) show that their CDCl3-solutions contains also (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolimine form). Intramolecular hydrogen bonding in the latter tautomer was found to be significantly weaker than that one
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1H and 13C NMR spectra of eleven 2-phenacylbenzoxazoles (ketimine form) show that their CDCl3-solutions contains also (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolimine form). Intramolecular hydrogen bonding in the latter tautomer was found to be significantly weaker than that one in respective (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines. Integrals of the 1H NMR signals were used to evaluate the molar ratio of the tautomers. Strong electron-donating substituents were found to stabilize the ketimine tautomer. pKT (negative logarithm of the equilibrium constant, KT = [ketimine]/[enolimine]) was found to be linearly dependent on the Hammett substituent constant σ. The results of the MP2 ab initio calculations reveal enolimine including an intramolecular OHN hydrogen bond to be the most stable form both with electron-donor and electron-acceptor substituents. The stability of ketimines is an intermediate of those found for enolimines and enaminones i.e., (E)-2-(benzo[d]oxazol-2(3H)-ylidene)-1-phenylethanones. 13C CPMAS NMR spectral data reveal that in the crystalline state the ketimine tautomer is predominant in p-NMe2 substituted congener. On the other hand, enolimine forms were detected there when the substituent has less electron-donating character or when it is an electron-acceptor by character. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle A Steroidal Saponin from Ophiopogon japonicus Extends the Lifespan of Yeast via the Pathway Involved in SOD and UTH1
Int. J. Mol. Sci. 2013, 14(3), 4461-4475; doi:10.3390/ijms14034461
Received: 14 January 2013 / Revised: 16 February 2013 / Accepted: 18 February 2013 / Published: 25 February 2013
Cited by 6 | PDF Full-text (357 KB) | HTML Full-text | XML Full-text
Abstract
Nolinospiroside F is a steroidal saponin isolated from Ophiopogon japonicus (O. japonicus). In this study, we found that nolinospiroside F significantly extends the replicative lifespan of K6001 yeast at doses of 1, 3 and 10 μM, indicating that it has an
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Nolinospiroside F is a steroidal saponin isolated from Ophiopogon japonicus (O. japonicus). In this study, we found that nolinospiroside F significantly extends the replicative lifespan of K6001 yeast at doses of 1, 3 and 10 μM, indicating that it has an anti-aging effect. This may be attributed to its anti-oxidative effect, as nolinospiroside F could increase yeast survival under oxidative stress conditions and decrease the level of malondialdehyde (MDA), an oxidative stress biomarker. It could also increase anti-oxidative stress genes, SOD1 and SOD2, expression, and the activity of superoxide dismutase (SOD). It increase the activity of SIRT1, an upstream inducer of SOD2 expression. In sod1 and sod2 mutant yeast strains, nolinospiroside F failed to extend their replicative lifespan. These results indicate that SOD participates in the anti-aging effect of nolinospiroside F. Furthermore, nolinospiroside F inhibited the expression of UTH1, a yeast-aging gene that is involved in the oxidative stress of yeast, and failed to extend the replicative lifespan of uth1 or skn7 mutant yeast cells. SKN7 is the transcriptional activator of UTH1. We also demonstrate that SOD and UTH1 regulate each other’s expression. Together, these results suggest that SOD and UTH1 genes are required for and play interactive roles in nolinospiroside F-mediated yeast lifespan extension. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
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Open AccessArticle Molecular Self-Assembly at Metal-Electrolyte Interfaces
Int. J. Mol. Sci. 2013, 14(3), 4498-4524; doi:10.3390/ijms14034498
Received: 8 January 2013 / Revised: 10 February 2013 / Accepted: 16 February 2013 / Published: 25 February 2013
Cited by 7 | PDF Full-text (5861 KB) | HTML Full-text | XML Full-text
Abstract
The self-assembly of molecular layers has become an important strategy in modern design of functional materials. However, in particular, large organic molecules may no longer be sufficiently volatile to be deposited by vapor deposition. In this case, deposition from solution may be a
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The self-assembly of molecular layers has become an important strategy in modern design of functional materials. However, in particular, large organic molecules may no longer be sufficiently volatile to be deposited by vapor deposition. In this case, deposition from solution may be a promising route; in ionic form, these molecules may even be soluble in water. In this contribution, we present and discuss results on the electrochemical deposition of viologen- and porphyrin molecules as well as their co-adsorption on chloride modified Cu(100) and Cu(111) single crystal electrode surfaces from aqueous acidic solutions. Using in situ techniques like cyclic voltametry and high resolution scanning tunneling microscopy, as well as ex-situ photoelectron spectroscopy data the highly ordered self-assembled organic layers are characterized with respect to their electrochemical behavior, lateral order and inner conformation as well as phase transitions thereof as a function of their redox-state and the symmetry of the substrate. As a result, detailed structure models are derived and are discussed in terms of the prevailing interactions. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
Open AccessArticle Molecular Analysis of RNA-RNA Interactions between 5’ and 3’ Untranslated Regions during the Initiation of Translation of a Cardiovirulent and a Live-Attenuated Coxsackievirus B3 Strains
Int. J. Mol. Sci. 2013, 14(3), 4525-4544; doi:10.3390/ijms14034525
Received: 23 January 2013 / Revised: 16 February 2013 / Accepted: 20 February 2013 / Published: 25 February 2013
Cited by 3 | PDF Full-text (560 KB) | HTML Full-text | XML Full-text
Abstract
Coxsackievirus B3 (CVB3) is a causative agent of viral myocarditis, meningitis and pancreatitis. CVB3 overcome their host cells by usurping the translation machinery to benefit viral gene expression. This is accomplished through alternative translation initiation in a cap independent manner at the viral
[...] Read more.
Coxsackievirus B3 (CVB3) is a causative agent of viral myocarditis, meningitis and pancreatitis. CVB3 overcome their host cells by usurping the translation machinery to benefit viral gene expression. This is accomplished through alternative translation initiation in a cap independent manner at the viral internal ribosomal entry site. The 5’ untranslated region (5’UTR) of CVB3 genomic RNA is highly structured. It is the site of multiple RNA-protein and RNA-RNA interactions and it plays a critical role during translation initiation. Similar to the 5’UTR, CVB3 3’ untranslated region (3’UTR) also contains secondary structural elements consisting of three stem-loops followed by a poly (A) tail sequence. Long-range RNA-RNA interactions between 5’ and 3’ ends of some viral genomes have been observed. Because of their dual role in translation and replication, the 5’ and 3’UTRs represent promising candidates for the study of CVB3 cardiovirulence. Taking into account that efficient initiation of mRNA translation depends on a temporally and spatially orchestrated sequence of protein-protein, protein-RNA and RNA-RNA interactions, and that, at present, little is known about RNA-RNA interactions between CVB3 5’ and 3’UTRs, we aimed in the present study, to assess a possible RNA-RNA interaction between 5’ and 3’UTRs during the initiation of translation of a wild-type and a previously characterized mutant (Sabin3-like) CVB3 strains and to investigate the effect of the Sabin3-like mutation on these potential interactions. For this purpose, “Electrophoretic Mobility Shift” assays were carried out. Data obtained did not show any RNA-RNA direct interactions between the 5’- and 3’- ends. Therefore, we can suggest that the possible mechanism by which 3’UTR enhances CVB3 IRES activity may be by bridging the 5’ to the 3’ end through RNA-protein interaction and not through RNA-RNA direct contact. However, these findings need to be confirmed by carrying out further experiments. Full article
Open AccessArticle Cesium Inhibits Plant Growth through Jasmonate Signaling in Arabidopsis thaliana
Int. J. Mol. Sci. 2013, 14(3), 4545-4559; doi:10.3390/ijms14034545
Received: 25 December 2012 / Revised: 25 January 2013 / Accepted: 6 February 2013 / Published: 25 February 2013
Cited by 11 | PDF Full-text (2336 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
It has been suggested that cesium is absorbed from the soil through potassium uptake machineries in plants; however, not much is known about perception mechanism and downstream response. Here, we report that the jasmonate pathway is required in plant response to cesium. Jasmonate
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It has been suggested that cesium is absorbed from the soil through potassium uptake machineries in plants; however, not much is known about perception mechanism and downstream response. Here, we report that the jasmonate pathway is required in plant response to cesium. Jasmonate biosynthesis mutant aos and jasmonate-insensitive mutant coi1-16 show clear resistance to root growth inhibition caused by cesium. However, the potassium and cesium contents in these mutants are comparable to wild-type plants, indicating that jasmonate biosynthesis and signaling are not involved in cesium uptake, but involved in cesium perception. Cesium induces expression of a high-affinity potassium transporter gene HAK5 and reduces potassium content in the plant body, suggesting a competitive nature of potassium and cesium uptake in plants. It has also been found that cesium-induced HAK5 expression is antagonized by exogenous application of methyl-jasmonate. Taken together, it has been indicated that cesium inhibits plant growth via induction of the jasmonate pathway and likely modifies potassium uptake machineries. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Brain Activity of Thioctic Acid Enantiomers: In Vitro and in Vivo Studies in an Animal Model of Cerebrovascular Injury
Int. J. Mol. Sci. 2013, 14(3), 4580-4595; doi:10.3390/ijms14034580
Received: 18 January 2013 / Revised: 19 February 2013 / Accepted: 20 February 2013 / Published: 26 February 2013
Cited by 15 | PDF Full-text (5732 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress is an imbalance between the production of free radicals and antioxidant defense mechanisms, potentially leading to tissue damage. Oxidative stress has a key role in the development of cerebrovascular and/or neurodegenerative diseases. This phenomenon is mainly mediated by an enhanced superoxide
[...] Read more.
Oxidative stress is an imbalance between the production of free radicals and antioxidant defense mechanisms, potentially leading to tissue damage. Oxidative stress has a key role in the development of cerebrovascular and/or neurodegenerative diseases. This phenomenon is mainly mediated by an enhanced superoxide production by the vascular endothelium with its consequent dysfunction. Thioctic, also known as alpha-lipoic acid (1,2-dithiolane-3-pentanoic acid), is a naturally occurring antioxidant that neutralizes free radicals in the fatty and watery regions of cells. Both the reduced and oxidized forms of the compound possess antioxidant ability. Thioctic acid has two optical isomers designated as (+)- and (−)-thioctic acid. Naturally occurring thioctic acid is the (+)-thioctic acid form, but the synthetic compound largely used in the market for stability reasons is a mixture of (+)- and (−)-thioctic acid. The present study was designed to compare the antioxidant activity of the two enantiomers versus the racemic form of thioctic acid on hydrogen peroxide-induced apoptosis in a rat pheochromocytoma PC12 cell line. Cell viability was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and free oxygen radical species (ROS) production was assessed by flow cytometry. Antioxidant activity of the two enantiomers and the racemic form of thioctic acid was also evaluated in spontaneously hypertensive rats (SHR) used as an in vivo model of increased oxidative stress. A 3-h exposure of PC12 cells to hydrogen peroxide (H2O2) significantly decreased cell viability and increased levels of intracellular ROS production. Pre-treatment with racemic thioctic acid or (+)-enantiomer significantly inhibited H2O2-induced decrease in cell viability from the concentration of 50 μmol/L and 20 μmol/L, respectively. Racemic thioctic acid and (+)-salt decreased levels of intracellular ROS, which were unaffected by (−)-thioctic acid. In the brain of SHR, the occurrence of astrogliosis and neuronal damage, with a decreased expression of neurofilament 200 kDa were observed. Treatment of SHR for 30 days with (+)-thioctic acid reduced the size of astrocytes and increased the neurofilament immunoreaction. The above findings could contribute to clarify the role played by thioctic acid in central nervous system injury related to oxidative stress. The more pronounced effect of (+)-thioctic acid observed in this study may have practical therapeutic implications worthy of being investigated in further preclinical and clinical studies. Full article
(This article belongs to the Special Issue Advances in Free Radicals in Biology and Medicine)
Open AccessArticle Covalent Immobilization of Bacillus licheniformis γ-Glutamyl Transpeptidase on Aldehyde-Functionalized Magnetic Nanoparticles
Int. J. Mol. Sci. 2013, 14(3), 4613-4628; doi:10.3390/ijms14034613
Received: 15 January 2013 / Revised: 20 February 2013 / Accepted: 21 February 2013 / Published: 26 February 2013
Cited by 13 | PDF Full-text (1738 KB) | HTML Full-text | XML Full-text
Abstract
This work presents the synthesis and use of surface-modified iron oxide nanoparticles for the covalent immobilization of Bacillus licheniformis γ-glutamyl transpeptidase (BlGGT). Magnetic nanoparticles were prepared by an alkaline solution of divalent and trivalent iron ions, and they were subsequently treated
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This work presents the synthesis and use of surface-modified iron oxide nanoparticles for the covalent immobilization of Bacillus licheniformis γ-glutamyl transpeptidase (BlGGT). Magnetic nanoparticles were prepared by an alkaline solution of divalent and trivalent iron ions, and they were subsequently treated with 3-aminopropyltriethoxysilane (APES) to obtain the aminosilane-coated nanoparticles. The functional group on the particle surface and the amino group of BlGGT was then cross-linked using glutaraldehyde as the coupling reagent. The loading capacity of the prepared nanoparticles for BlGGT was 34.2 mg/g support, corresponding to 52.4% recovery of the initial activity. Monographs of transmission electron microscopy revealed that the synthesized nanoparticles had a mean diameter of 15.1 ± 3.7 nm, and the covalent cross-linking of the enzyme did not significantly change their particle size. Fourier transform infrared spectroscopy confirmed the immobilization of BlGGT on the magnetic nanoparticles. The chemical and kinetic behaviors of immobilized BlGGT are mostly consistent with those of the free enzyme. The immobilized enzyme could be recycled ten times with 36.2% retention of the initial activity and had a comparable stability respective to free enzyme during the storage period of 30 days. Collectively, the straightforward synthesis of aldehyde-functionalized nanoparticles and the efficiency of enzyme immobilization offer wide perspectives for the practical use of surface-bound BlGGT. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
Open AccessArticle New Anti-Inflammatory Aromatic Components from Antrodia camphorata
Int. J. Mol. Sci. 2013, 14(3), 4629-4639; doi:10.3390/ijms14034629
Received: 9 January 2013 / Revised: 5 February 2013 / Accepted: 10 February 2013 / Published: 26 February 2013
Cited by 6 | PDF Full-text (252 KB) | HTML Full-text | XML Full-text
Abstract
Three new benzenoids, 3-isopropenyl-2-methoxy-6-methyl-4,5-methylenedioxy- phenol (1), 2-hydroxy-4,4'-dimethoxy-3,3'-dimethyl-5,6,5',6'-bimethylenedioxybiphenyl (2), 4,4'-dihydroxy-3,3'-dimethoxy-2,2'-dimethyl-5,6,5',6'-bimethylenedioxybiphenyl (3), together with two known benzenoids, 2,3,6-trimethoxy-5-methylphenol (4) and 2,3-methylenedioxy- 4-methoxy-5-methylphenol (5), were isolated from Antrodia camphorata. Our results support that compounds 1
[...] Read more.
Three new benzenoids, 3-isopropenyl-2-methoxy-6-methyl-4,5-methylenedioxy- phenol (1), 2-hydroxy-4,4'-dimethoxy-3,3'-dimethyl-5,6,5',6'-bimethylenedioxybiphenyl (2), 4,4'-dihydroxy-3,3'-dimethoxy-2,2'-dimethyl-5,6,5',6'-bimethylenedioxybiphenyl (3), together with two known benzenoids, 2,3,6-trimethoxy-5-methylphenol (4) and 2,3-methylenedioxy- 4-methoxy-5-methylphenol (5), were isolated from Antrodia camphorata. Our results support that compounds 15 potently inhibited LPS (lipopolysaccharide)-induced nitric oxide (NO) production in a dose-dependent manner. The IC50 values of compounds 1, 3 and 5 were 1.8 ± 0.2, 18.8 ± 0.6 and 0.8 ± 0.3 μg/mL, respectively. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Incidence of Bacteriocins Produced by Food-Related Lactic Acid Bacteria Active towards Oral Pathogens
Int. J. Mol. Sci. 2013, 14(3), 4640-4654; doi:10.3390/ijms14034640
Received: 8 October 2012 / Revised: 1 February 2013 / Accepted: 18 February 2013 / Published: 26 February 2013
Cited by 8 | PDF Full-text (578 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present study we investigated the incidence of bacteriocins produced by 236 lactic acid bacteria (LAB) food isolates against pathogenic or opportunistic pathogenic oral bacteria. This set of LAB contained several strains (≥17%) producing bacteriocins active against food-related bacteria. Interestingly only Streptococcus
[...] Read more.
In the present study we investigated the incidence of bacteriocins produced by 236 lactic acid bacteria (LAB) food isolates against pathogenic or opportunistic pathogenic oral bacteria. This set of LAB contained several strains (≥17%) producing bacteriocins active against food-related bacteria. Interestingly only Streptococcus macedonicus ACA-DC 198 was able to inhibit the growth of Streptococcus oralis, Streptococcus sanguinis and Streptococcus gordonii, while Lactobacillus fermentum ACA-DC 179 and Lactobacillus plantarun ACA-DC 269 produced bacteriocins solely against Streptococcus oralis. Thus, the percentage of strains that were found to produce bacteriocins against oral bacteria was ~1.3%. The rarity of bacteriocins active against oral LAB pathogens produced by food-related LAB was unexpected given their close phylogenetic relationship. Nevertheless, when tested in inhibition assays, the potency of the bacteriocin(s) of S. macedonicus ACA-DC 198 against the three oral streptococci was high. Fourier-transform infrared spectroscopy combined with principal component analysis revealed that exposure of the target cells to the antimicrobial compounds caused major alterations of key cellular constituents. Our findings indicate that bacteriocins produced by food-related LAB against oral LAB may be rare, but deserve further investigation since, when discovered, they can be effective antimicrobials. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Irradiated Human Dermal Fibroblasts Are as Efficient as Mouse Fibroblasts as a Feeder Layer to Improve Human Epidermal Cell Culture Lifespan
Int. J. Mol. Sci. 2013, 14(3), 4684-4704; doi:10.3390/ijms14034684
Received: 19 December 2012 / Revised: 7 February 2013 / Accepted: 19 February 2013 / Published: 26 February 2013
Cited by 14 | PDF Full-text (688 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A fibroblast feeder layer is currently the best option for large scale expansion of autologous skin keratinocytes that are to be used for the treatment of severely burned patients. In a clinical context, using a human rather than a mouse feeder layer is
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A fibroblast feeder layer is currently the best option for large scale expansion of autologous skin keratinocytes that are to be used for the treatment of severely burned patients. In a clinical context, using a human rather than a mouse feeder layer is desirable to reduce the risk of introducing animal antigens and unknown viruses. This study was designed to evaluate if irradiated human fibroblasts can be used in keratinocyte cultures without affecting their morphological and physiological properties. Keratinocytes were grown either with or without a feeder layer in serum-containing medium. Our results showed that keratinocytes grown either on an irradiated human feeder layer or irradiated 3T3 cells (i3T3) can be cultured for a comparable number of passages. The average epithelial cell size and morphology were also similar. On the other hand, keratinocytes grown without a feeder layer showed heavily bloated cells at early passages and stop proliferating after only a few passages. On the molecular aspect, the expression level of the transcription factor Sp1, a useful marker of keratinocytes lifespan, was maintained and stabilized for a high number of passages in keratinocytes grown with feeder layers whereas Sp1 expression dropped quickly without a feeder layer. Furthermore, gene profiling on microarrays identified potential target genes whose expression is differentially regulated in the absence or presence of an i3T3 feeder layer and which may contribute at preserving the growth characteristics of these cells. Irradiated human dermal fibroblasts therefore provide a good human feeder layer for an effective expansion of keratinocytes in vitro that are to be used for clinical purposes. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
Open AccessArticle Exploration of the Protection of Riboflavin Laurate on Oral Mucositis Induced by Chemotherapy or Radiotherapy at the Cellular Level: What Is the Leading Contributor?
Int. J. Mol. Sci. 2013, 14(3), 4722-4733; doi:10.3390/ijms14034722
Received: 21 January 2013 / Revised: 21 February 2013 / Accepted: 22 February 2013 / Published: 27 February 2013
Cited by 2 | PDF Full-text (1749 KB) | HTML Full-text | XML Full-text
Abstract
Oral or gastrointestinal mucositis is a frequent phenomenon in cancer patients receiving chemotherapy or radiotherapy. In addition, several clinical investigations have demonstrated in recent years that riboflavin laurate has the potential to protect the patients from the disease induced by chemotherapy or radiotherapy.
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Oral or gastrointestinal mucositis is a frequent phenomenon in cancer patients receiving chemotherapy or radiotherapy. In addition, several clinical investigations have demonstrated in recent years that riboflavin laurate has the potential to protect the patients from the disease induced by chemotherapy or radiotherapy. In our studies, it is observed that riboflavin laurate can ameliorate either chemotherapy- or radiotherapy-induced toxicities on Helf cells, and the effect is greater than that of riboflavin. In addition, riboflavin laurate is able to transport through the Caco-2 cell monolayer as the prototype, indicating the protective effects may be produced by the prototype of riboflavin laurate, rather than simply by the released riboflavin. Full article
Open AccessArticle Gonadotropins Activate Oncogenic Pathways to Enhance Proliferation in Normal Mouse Ovarian Surface Epithelium
Int. J. Mol. Sci. 2013, 14(3), 4762-4782; doi:10.3390/ijms14034762
Received: 31 January 2013 / Revised: 21 February 2013 / Accepted: 25 February 2013 / Published: 28 February 2013
Cited by 11 | PDF Full-text (1830 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian cancer is the most lethal gynecological malignancy affecting American women. The gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been implicated as growth factors in ovarian cancer. In the present study, pathways activated by FSH and LH in normal ovarian
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Ovarian cancer is the most lethal gynecological malignancy affecting American women. The gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been implicated as growth factors in ovarian cancer. In the present study, pathways activated by FSH and LH in normal ovarian surface epithelium (OSE) grown in their microenvironment were investigated. Gonadotropins increased proliferation in both three-dimensional (3D) ovarian organ culture and in a two-dimensional (2D) normal mouse cell line. A mouse cancer pathway qPCR array using mRNA collected from 3D organ cultures identified Akt as a transcriptionally upregulated target following stimulation with FSH, LH and the combination of FSH and LH. Activation of additional pathways, such as Birc5, Cdk2, Cdk4, and Cdkn2a identified in the 3D organ cultures, were validated by western blot using the 2D cell line. Akt and epidermal growth factor receptor (EGFR) inhibitors blocked gonadotropin-induced cell proliferation in 3D organ and 2D cell culture. OSE isolated from 3D organ cultures stimulated with LH or hydrogen peroxide initiated growth in soft agar. Hydrogen peroxide stimulated colonies were further enhanced when supplemented with FSH. LH colony formation and FSH promotion were blocked by Akt and EGFR inhibitors. These data suggest that the gonadotropins stimulate some of the same proliferative pathways in normal OSE that are activated in ovarian cancers. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessArticle Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors: Correlation to Mucin-1 and Galectin-3 Expression
Int. J. Mol. Sci. 2013, 14(3), 4783-4792; doi:10.3390/ijms14034783
Received: 8 January 2013 / Revised: 8 February 2013 / Accepted: 19 February 2013 / Published: 28 February 2013
Cited by 2 | PDF Full-text (1831 KB) | HTML Full-text | XML Full-text
Abstract
Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has been described. Tyrosine phosphorylation is a key mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study
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Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has been described. Tyrosine phosphorylation is a key mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study was to evaluate the phosphorylation of epithelial growth factor-receptor (EGFR) in normal myometrium, uterine myomas and uterine leiomyosarcomas. Formalin-fixed paraffin-embedded tissue samples from normal myometrium, leiomyomas and leiomyosarcomas were studied. Samples were immunohistochemically (IHC) assessed using the anti-EGFR phosphorylation of Y845 (pEGFR-Y845) and anti-pEGFR-Y1173 phosphorylation-specific antibodies. IHC staining was evaluated using a semiquantitative score. The expression of pEGFR-Y845 was significantly upregulated in leiomyosarcomas (p < 0.001) compared to leiomyomas and normal myometrium. In contrast, pEGFR-Y1173 did not differ significantly between the three groups of the study. Correlation analysis revealed an overall positive correlation between pEGFR Y845 and mucin 1 (MUC1). Further subgroup analysis within the tumoral group (myomas and leiomyosarcomas) revealed an additional negative correlation between pEGFR Y845 and galectin-3 (gal-3) staining. On the contrary no significant correlation was noted within the non-tumoral group. An upregulated EGFR phosphorylation of Y845 in leiomyosarcomas compared to leiomyomas implicates EGFR activation at this special receptor site. Due to these pEGFR-Y845 variations, it can be postulated that MUC1 interacts with it, whereas gal-3 seems to be cleaved from Y845 phosphorylated EGFR. Further research on this field could focus on differences in EGFR pathways as a potentially advantageous diagnostic tool for investigation of benign and malignant signal transduction processes. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Rapid Microsatellite Marker Development Using Next Generation Pyrosequencing to Inform Invasive Burmese Python—Python molurus bivittatus—Management
Int. J. Mol. Sci. 2013, 14(3), 4793-4804; doi:10.3390/ijms14034793
Received: 4 January 2013 / Revised: 6 February 2013 / Accepted: 13 February 2013 / Published: 28 February 2013
Cited by 7 | PDF Full-text (204 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Invasive species represent an increasing threat to native ecosystems, harming indigenous taxa through predation, habitat modification, cross-species hybridization and alteration of ecosystem processes. Additionally, high economic costs are associated with environmental damage, restoration and control measures. The Burmese python, Python molurus bivittatus,
[...] Read more.
Invasive species represent an increasing threat to native ecosystems, harming indigenous taxa through predation, habitat modification, cross-species hybridization and alteration of ecosystem processes. Additionally, high economic costs are associated with environmental damage, restoration and control measures. The Burmese python, Python molurus bivittatus, is one of the most notable invasive species in the US, due to the threat it poses to imperiled species and the Greater Everglades ecosystem. To address population structure and relatedness, next generation sequencing was used to rapidly produce species-specific microsatellite loci. The Roche 454 GS-FLX Titanium platform provided 6616 di-, tri- and tetra-nucleotide repeats in 117,516 sequences. Using stringent criteria, 24 of 26 selected tri- and tetra-nucleotide loci were polymerase chain reaction (PCR) amplified and 18 were polymorphic. An additional six cross-species loci were amplified, and the resulting 24 loci were incorporated into eight PCR multiplexes. Multi-locus genotypes yielded an average of 61% (39%–77%) heterozygosity and 3.7 (2–6) alleles per locus. Population-level studies using the developed microsatellites will track the invasion front and monitor population-suppression dynamics. Additionally, cross-species amplification was detected in the invasive Ball, P. regius, and Northern African python, P. sebae. These markers can be used to address the hybridization potential of Burmese pythons and the larger, more aggressive P. sebae. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Granulocyte Colony-Stimulating Factor Promotes Atherosclerosis in High-Fat Diet Rabbits
Int. J. Mol. Sci. 2013, 14(3), 4805-4816; doi:10.3390/ijms14034805
Received: 10 October 2012 / Revised: 28 January 2013 / Accepted: 19 February 2013 / Published: 28 February 2013
Cited by 2 | PDF Full-text (1215 KB) | HTML Full-text | XML Full-text
Abstract
Granulocyte-colony stimulating factor (G-CSF) has been reported to improve the function of infarcted heart, but its effects on atherosclerosis are unclear. Here we examined the effects and the potential mechanisms in the high-fat diet rabbit model. Six-month-old male New Zealand white rabbits, fed
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Granulocyte-colony stimulating factor (G-CSF) has been reported to improve the function of infarcted heart, but its effects on atherosclerosis are unclear. Here we examined the effects and the potential mechanisms in the high-fat diet rabbit model. Six-month-old male New Zealand white rabbits, fed a high-cholesterol diet or a normal diet for 10 weeks, were treated with vehicle or G-CSF. G-CSF increased lesion area in the thoracic aorta and the plasma levels of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) at the early phase in the high-fat diet group. High-fat diet-induced arterial endothelium damage and apoptosis were greatly aggravated by G-CSF treatment. In vivo, G-CSF impaired apoptosis induced by oxidized low density lipoprotein (OX-LDL) but it had little effect on cultured endothelial cells (ECs) with vehicle treatment. Further research revealed that G-CSF promoted the upregulation of endothelin-1 (ET-1) and the downregulation of endothelial nitric oxide synthase (eNOS) of thoracic aortae induced by a high-fat diet. In vitro, the effects of G-CSF on expression of ET-1 and eNOS in cultured ECs were consistent with those in vivo. Our results suggested that G-CSF exacerbates lipid abnormity and endothelium damage in hyperlipidemia rabbits, thereby resulting in the deterioration of atherosclerosis and that the ET-1/eNOS system may regulate the progression. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Active Silver Nanoparticles for Wound Healing
Int. J. Mol. Sci. 2013, 14(3), 4817-4840; doi:10.3390/ijms14034817
Received: 23 December 2012 / Revised: 5 February 2013 / Accepted: 10 February 2013 / Published: 1 March 2013
Cited by 55 | PDF Full-text (2203 KB) | HTML Full-text | XML Full-text
Abstract
In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat™ Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient. The in vitro results show that Ag NPs greatly reduce mitochondrial
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In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat™ Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient. The in vitro results show that Ag NPs greatly reduce mitochondrial activity, while cellular staining techniques show that nuclear integrity is maintained, with no signs of cell death. For the first time, transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) analyses were carried out on skin biopsies taken from a single patient during treatment. The results show that Ag NPs are released as aggregates and are localized in the cytoplasm of fibroblasts. No signs of cell death were observed, and the nanoparticles had different distributions within the cells of the upper and lower dermis. Depth profiles of the Ag concentrations were determined along the skin biopsies. In the healed sample, most of the silver remained in the surface layers, whereas in the unhealed sample, the silver penetrated more deeply. The Ag concentrations in the cell cultures were also determined. Clinical observations and experimental data collected here are consistent with previously published articles and support the safety of Ag NP-based dressing in wound treatment. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
Open AccessArticle Vascular Endothelial Growth Factor Receptor Family in Ascidians, Halocynthia roretzi (Sea Squirt). Its High Expression in Circulatory System-Containing Tissues
Int. J. Mol. Sci. 2013, 14(3), 4841-4853; doi:10.3390/ijms14034841
Received: 20 November 2012 / Revised: 7 February 2013 / Accepted: 15 February 2013 / Published: 1 March 2013
Cited by 2 | PDF Full-text (657 KB) | HTML Full-text | XML Full-text
Abstract
The vascular endothelial growth factor (VEGF)-VEGF Receptor (VEGFR) system is an important pathway for regulation of angiogenesis. However, its evolutionary development, particularly the step from invertebrates to vertebrates, is still largely unknown. Here, we molecularly cloned the VEGFR-like gene from Halocynthia roretzi, a
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The vascular endothelial growth factor (VEGF)-VEGF Receptor (VEGFR) system is an important pathway for regulation of angiogenesis. However, its evolutionary development, particularly the step from invertebrates to vertebrates, is still largely unknown. Here, we molecularly cloned the VEGFR-like gene from Halocynthia roretzi, a species belonging to the Tunicata, the chordate subphylum recently considered the sister group of vertebrates. The cDNA encoded a homolog of human VEGFR, including the transmembrane domain, and the tyrosine kinase domain with a kinase-insert region, which was designated S. sq VEGFR (GenBank AB374180). Similar to Tunicates including ascidians in the phylogenetic tree, the Amphioxus, another chordate, is located close to vertebrates. However, S. sq VEGFR has a higher homology than the Amphioxus VEGFR-like molecule (GenBank AB025557) to human VEGFR in the kinase domain-2 region. The S. sq VEGFR mRNA was expressed at highest levels in circulatory system-containing tissues, suggesting that S. sq VEGFR plays an important role in the formation or maintenance of circulatory system in Tunicates, Halocynthia roretzi. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
Open AccessArticle Differential Protein Expression in Response to Abiotic Stress in Two Potato Species: Solanum commersonii Dun and Solanum tuberosum L.
Int. J. Mol. Sci. 2013, 14(3), 4912-4933; doi:10.3390/ijms14034912
Received: 22 December 2012 / Revised: 8 February 2013 / Accepted: 13 February 2013 / Published: 1 March 2013
Cited by 12 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Better knowledge on responses to dehydration stress could help to improve the existing cryopreservation protocols for potato, since plant tissues processed for cryopreservation are often submitted to similar in vitro stress conditions. Cryopreservation (the best method of conservation for vegetatively propagated plants) of
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Better knowledge on responses to dehydration stress could help to improve the existing cryopreservation protocols for potato, since plant tissues processed for cryopreservation are often submitted to similar in vitro stress conditions. Cryopreservation (the best method of conservation for vegetatively propagated plants) of potato still needs to be standardized to make it available and to conserve the wide diversity of this crop. In the present work, the response to osmotic stress and chilling temperature was investigated in two potato species, Solanum tuberosum and its relative, frost-tolerant S. commersonii. After 14 days of exposure, different growth parameters, such as shoot length and number of leaves, were measured. Furthermore, differentially abundant proteins were identified after performing 2-fluorescence difference gel electrophoresis (2-DIGE) experiments, and soluble carbohydrates were analyzed by High Performance Anion Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD). The results show different responses in both species depending on the stress treatment. Focusing on the differences in growth parameters during the treatments, Solanum commersonii seems to be more affected than S. tuberosum cv. Désirée. At the molecular level, there are some differences and similarities between the two potato species studied that are dependent on the type of stressor. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Development and Antibacterial Activity of Cashew Gum-Based Silver Nanoparticles
Int. J. Mol. Sci. 2013, 14(3), 4969-4981; doi:10.3390/ijms14034969
Received: 26 November 2012 / Revised: 11 January 2013 / Accepted: 6 February 2013 / Published: 1 March 2013
Cited by 15 | PDF Full-text (1097 KB) | HTML Full-text | XML Full-text
Abstract
The present study describes the development of a green synthesis of silver nanoparticles reduced and stabilized by exuded gum from Anacardium occidentale L. and evaluates in vitro their antibacterial and cytotoxic activities. Characterization of cashew gum-based silver nanoparticles (AgNPs) was carried out based
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The present study describes the development of a green synthesis of silver nanoparticles reduced and stabilized by exuded gum from Anacardium occidentale L. and evaluates in vitro their antibacterial and cytotoxic activities. Characterization of cashew gum-based silver nanoparticles (AgNPs) was carried out based on UV–Vis spectroscopy, transmission electron microscopy and dynamic light scattering analysis which revealed that the synthesized silver nanoparticles were spherical in shape, measuring about 4 nm in size with a uniform dispersal. AgNPs presented antibacterial activity, especially against Gram-negative bacteria, in concentrations where no significant cytotoxicity was observed. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
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Open AccessArticle Genetic Analysis of HIV-1 Integrase Sequences from Treatment Naive Individuals in Northeastern South Africa
Int. J. Mol. Sci. 2013, 14(3), 5013-5024; doi:10.3390/ijms14035013
Received: 25 December 2012 / Revised: 18 February 2013 / Accepted: 21 February 2013 / Published: 1 March 2013
Cited by 3 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
Abstract
Raltegravir, an integrase inhibitor, is not a component of the current South African antiretroviral treatment guidelines, but it could be introduced in the near future as cases of virological failures from current treatment regimens begin to occur. The aim of this study was
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Raltegravir, an integrase inhibitor, is not a component of the current South African antiretroviral treatment guidelines, but it could be introduced in the near future as cases of virological failures from current treatment regimens begin to occur. The aim of this study was to analyze the complete HIV integrase gene obtained from individuals at two treatment sites in northeastern South Africa for the presence of Raltegravir associated drug resistant mutations and viral subtypes based on the integrase gene. Examination for mutations against other integrase inhibitors, such as Elvitegravir and Dolutegravir, was also done. Viruses from 127 treatment naive individuals were analyzed. Genetic drug resistance mutations were determined using the Stanford HIV Drug Resistance Interpretation program and the International AIDS society-USA guidelines. Viral subtyping was done by phylogenetic analysis, and recombinants were determined using the REGA, jpHMM and RIP tools. No major resistance mutations were detected. However, 7% of the sequences had minor mutations and polymorphisms. The majority (99%) of the viruses were HIV-1 C. Recombination analysis showed that the polymerase gene of one virus was likely composed of HIV-1 subtype A1 and C sequences. The present study indicates that Raltegravir, Elvitegravir and Dolutegravir resistant mutations may be absent in the study communities and further indicates the presence of recombinant viruses in northeastern South Africa. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Isolation and Functional Analysis of ZmLTP3, a Homologue to Arabidopsis LTP3
Int. J. Mol. Sci. 2013, 14(3), 5025-5035; doi:10.3390/ijms14035025
Received: 23 January 2013 / Revised: 13 February 2013 / Accepted: 19 February 2013 / Published: 1 March 2013
Cited by 4 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
Plant lipid transfer proteins (LTPs) are encoded by multigene families and play important roles in plant physiology. One full-length cDNA encoding an Arabidopsis LTP3 homologue was isolated from maize by RT-PCR and named as ZmLTP3. RT-PCR analysis indicated that the ZmLTP3 expression
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Plant lipid transfer proteins (LTPs) are encoded by multigene families and play important roles in plant physiology. One full-length cDNA encoding an Arabidopsis LTP3 homologue was isolated from maize by RT-PCR and named as ZmLTP3. RT-PCR analysis indicated that the ZmLTP3 expression is induced by salicylic acid (SA), mannitol and salt. Furthermore, in different tissues the ZmLTP3 displayed different expression patterns, indicating that ZmLTP3 may play multiple roles in stress resistance. Over-expression of ZmLTP3 in wild-type Arabidopsis resulted in the increased salt tolerance. Under salt stress condition, compared to wild-type (WT) plants, transgenic Arabidopsis grew better, had higher seedling fresh (FW), dry weight (DW), seed yields, proline content and lower MDA content and relative electric conductivity level. Our results suggest that maize ZmLTP3 might encode a member of LTPs family and play roles in salt resistance. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Secretory Phospholipases A2 in Durum Wheat (Triticum durum Desf.): Gene Expression, Enzymatic Activity, and Relation to Drought Stress Adaptation
Int. J. Mol. Sci. 2013, 14(3), 5146-5169; doi:10.3390/ijms14035146
Received: 18 January 2013 / Revised: 13 February 2013 / Accepted: 18 February 2013 / Published: 1 March 2013
Cited by 11 | PDF Full-text (1401 KB) | HTML Full-text | XML Full-text
Abstract
Phospholipases A2 (PLA2s) are known to mediate signaling cascades during plant growth and development, as well as biotic and abiotic stress responses. In this context, the present study provides extensive characterization of specific PLA2s in durum wheat, and
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Phospholipases A2 (PLA2s) are known to mediate signaling cascades during plant growth and development, as well as biotic and abiotic stress responses. In this context, the present study provides extensive characterization of specific PLA2s in durum wheat, and assesses their involvement in durum wheat response to drought stress. In durum wheat leaves, four full-length expressed sequences encoding putative PLA2s were isolated and characterized as belonging to the class of secretory PLA2s (sPLA2s): TdsPLA2I, TdsPLA2II, TdsPLA2III and TdsPLA2IV. PLA2 activity was also detected, the characteristics of which resemble those of previously characterized plant sPLA2s: strong preference for phospholipids; requirement for millimolar Ca2+ concentrations; optimal activity at basic pH; heat stability; and inhibition by the reducing agent dithiothreitol. With drought stress imposed at both the vegetative and reproductive stages, accumulation of TdsPLA2I and TdsPLA2III transcripts, and to a lesser extent of TdsPLA2IV transcript, paralleled increased PLA2 activity; both transcript levels and enzymatic activity decreased as a consequence of stress recovery. Consistently, free fatty acid analysis of drought-stressed leaves revealed increased linoleate, linolenate and palmitate contents, which were reversed by plant re-watering. Overall, these findings strongly suggest that there are inducible sPLA2 isoforms in durum wheat that have roles in orchestrating the plant response to drought stress. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
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Open AccessArticle EGFR Expression and KRAS and BRAF Mutational Status in Intestinal-Type Sinonasal Adenocarcinoma
Int. J. Mol. Sci. 2013, 14(3), 5170-5181; doi:10.3390/ijms14035170
Received: 7 February 2013 / Revised: 20 February 2013 / Accepted: 25 February 2013 / Published: 4 March 2013
Cited by 8 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
Accumulation of molecular alterations, including EGFR overexpression and mutations in KRAS and BRAF, contribute to colorectal carcinogenesis. Since intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinus has morphologic and phenotypic features that are usually indistinguishable from colorectal cancer (CRC), it is
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Accumulation of molecular alterations, including EGFR overexpression and mutations in KRAS and BRAF, contribute to colorectal carcinogenesis. Since intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinus has morphologic and phenotypic features that are usually indistinguishable from colorectal cancer (CRC), it is likely that both tumor types share equivalent genetic alterations. Data from a series of 43 patients treated surgically for ITAC in Montpellier, France between November 1998 and December 2012 were collected. Tumors were characterized for mutations in KRAS and BRAF as well as EGFR overexpression. Kaplan-Meier survival curves were constructed using overall survival as the primary end points. Patient survival was analyzed using the hazards ratio. Twenty seven tumors (63%) showed EGFR positivity and 30% exhibited a high expression level (+2/+3). KRAS mutations were detected in 43% of cases. BRAF mutations were identified in 3.6% of specimens. Patients with age superior to 60 years, metastatic status, and KRAS mutations had significant overall survival values (p = 0.026, p = 0.001 and p = 0.03, respectively). Our results indicate that KRAS mutations and EGFR expression are frequent in ITAC and that KRAS mutations predict good patient prognosis in ITAC. Finally, EGFR directed molecular treatments could be investigated in a subset of patients affected by ITAC. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Blood Translation Elongation Factor-1δ Is a Novel Marker for Cadmium Exposure
Int. J. Mol. Sci. 2013, 14(3), 5182-5197; doi:10.3390/ijms14035182
Received: 24 December 2012 / Revised: 14 January 2013 / Accepted: 15 January 2013 / Published: 4 March 2013
Cited by 5 | PDF Full-text (1967 KB) | HTML Full-text | XML Full-text
Abstract
Translation elongation factor-1d (TEF-1δ) has been identified as a novel cadmium-responsive proto-oncogene. However, it is still unclear whether TEF-1δ could be a potential biomarker of cadmium exposure. Rats were treated with CdCl2 at different concentrations (high dose 1.225, mid-dose 0.612 and low
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Translation elongation factor-1d (TEF-1δ) has been identified as a novel cadmium-responsive proto-oncogene. However, it is still unclear whether TEF-1δ could be a potential biomarker of cadmium exposure. Rats were treated with CdCl2 at different concentrations (high dose 1.225, mid-dose 0.612 and low dose 0.306 mg/kg body weight, respectively) for 14 weeks, and the cadmium levels, weight coefficients, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urine protein (24hPro), urinary creatinine (Cr) and pathological features were determined. The TEF-1δ expression in white blood cells and multiple organs were examined by reverse transcription polymerase chain reaction (PCR) and were also confirmed with fluorescence quantitative PCR. A cadmium dose-dependent increase (p < 0.05) of cadmium levels in blood, urine, liver, kidney, heart and lung, and the weight coefficients was observed. The liver and renal function indictors including AST, ALT, SCR, BUN and 24hPro, were elevated in a cadmium dose-dependent manner (p < 0.05). Significant pathological changes in liver, kidney, heart and lung were indicated. The TEF-1δ expression was up-regulated in both blood and organs (p < 0.05). Moreover, the expression level of blood TEF-1δ was positively correlated to TEF-1δ expression level, cadmium level and toxicity in the organs (p < 0.01). This study indicates that blood TEF-1δ is a novel valuable biomarker for cadmium exposure and its organ toxicity. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle Comparative Analysis of the Symbiotic Efficiency of Medicago truncatula and Medicago sativa under Phosphorus Deficiency
Int. J. Mol. Sci. 2013, 14(3), 5198-5213; doi:10.3390/ijms14035198
Received: 28 January 2013 / Revised: 14 February 2013 / Accepted: 26 February 2013 / Published: 4 March 2013
Cited by 9 | PDF Full-text (238 KB) | HTML Full-text | XML Full-text
Abstract
Phosphorus (P)-deficiency is a major abiotic stress that limits legume growth in many types of soils. The relationship between Medicago and Sinorhizobium, is known to be affected by different environmental conditions. Recent reports have shown that, in combination with S. meliloti 2011, Medicago
[...] Read more.
Phosphorus (P)-deficiency is a major abiotic stress that limits legume growth in many types of soils. The relationship between Medicago and Sinorhizobium, is known to be affected by different environmental conditions. Recent reports have shown that, in combination with S. meliloti 2011, Medicago truncatula had a lower symbiotic efficiency than Medicago sativa. However, little is known about how Medicago–Sinorhizobium is affected by P-deficiency at the whole-plant level. The objective of the present study was to compare and characterize the symbiotic efficiency of N2 fixation of M. truncatula and M. sativa grown in sand under P-limitation. Under this condition, M. truncatula exhibited a significantly higher rate of N2 fixation. The specific activity of the nodules was much higher in M. truncatula in comparison to M. sativa, partially as a result of an increase in electron allocation to N2 versus H+. Although the main organic acid, succinate, exhibited a strong tendency to decrease under P-deficiency, the more efficient symbiotic ability observed in M. truncatula coincided with an apparent increase in the content of malate in its nodules. Our results indicate that the higher efficiency of the M. truncatula symbiotic system is related to the ability to increase malate content under limited P-conditions. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Insight into Differential Responses of Upland and Paddy Rice to Drought Stress by Comparative Expression Profiling Analysis
Int. J. Mol. Sci. 2013, 14(3), 5214-5238; doi:10.3390/ijms14035214
Received: 9 January 2013 / Revised: 30 January 2013 / Accepted: 5 February 2013 / Published: 4 March 2013
Cited by 9 | PDF Full-text (1103 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, the drought responses of two genotypes, IRAT109 and Zhenshan 97 (ZS97), representing upland and paddy rice, respectively, were systematically compared at the morphological, physiological and transcriptional levels. IRAT109 has better performance in traits related to drought avoidance, such as leaf
[...] Read more.
In this study, the drought responses of two genotypes, IRAT109 and Zhenshan 97 (ZS97), representing upland and paddy rice, respectively, were systematically compared at the morphological, physiological and transcriptional levels. IRAT109 has better performance in traits related to drought avoidance, such as leaf rolling, root volumes, the ratio of leaf water loss and relative conductivity. At the transcriptional level, more genes were induced by drought in IRAT109 at the early drought stage, but more genes had dynamic expression patterns in ZS97 at different drought degrees. Under drought conditions, more genes related to reproductive development and establishment of localization were repressed in IRAT109, but more genes involved in degradation of cellular components were induced in ZS97. By checking the expression patterns of 36 drought-responsive genes (located in 14 quantitative trail loci [QTL] intervals) in ZS97, IRAT109 and near isogenic lines (NILs) of the QTL intervals, we found that more than half of these genes had their expression patterns or expression levels changed in the NILs when compared to that in ZS97 or IRAT109. Our results may provide valuable information for dissecting the genetic bases of traits related to drought resistance, as well as for narrowing the candidate genes for the traits. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue
Int. J. Mol. Sci. 2013, 14(3), 5239-5249; doi:10.3390/ijms14035239
Received: 7 January 2013 / Revised: 30 January 2013 / Accepted: 27 February 2013 / Published: 4 March 2013
Cited by 6 | PDF Full-text (236 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or
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We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessArticle The Study of Dynamical Potentials of Highly Excited Vibrational States of HOBr
Int. J. Mol. Sci. 2013, 14(3), 5250-5263; doi:10.3390/ijms14035250
Received: 24 December 2012 / Revised: 31 January 2013 / Accepted: 8 February 2013 / Published: 5 March 2013
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Abstract
The vibrational nonlinear dynamics of HOBr in the bending and O–Br stretching coordinates with anharmonicity and Fermi 2:1 coupling are studied with dynamical potentials in this article. The result shows that the H–O stretching vibration mode has significantly different effects on the coupling
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The vibrational nonlinear dynamics of HOBr in the bending and O–Br stretching coordinates with anharmonicity and Fermi 2:1 coupling are studied with dynamical potentials in this article. The result shows that the H–O stretching vibration mode has significantly different effects on the coupling between the O–Br stretching mode and the H–O–Br bending mode under different Polyad numbers. The dynamical potentials and the corresponding phase space trajectories are obtained when the Polyad number is 27, for instance, and the fixed points in the dynamical potentials of HOBr are shown to govern the various quantal environments in which the vibrational states lie. Furthermore, it is also found that the quantal environments could be identified by the numerical values of action integrals, which is consistent with former research. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle Inhibition of Human Transthyretin Aggregation by Non-Steroidal Anti-Inflammatory Compounds: A Structural and Thermodynamic Analysis
Int. J. Mol. Sci. 2013, 14(3), 5284-5311; doi:10.3390/ijms14035284
Received: 8 January 2013 / Revised: 5 February 2013 / Accepted: 7 February 2013 / Published: 6 March 2013
Cited by 12 | PDF Full-text (4307 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Transthyretin (TTR) is a homotetrameric protein that circulates in plasma and cerebral spinal fluid (CSF) whose aggregation into amyloid fibrils has been associated with at least two different amyloid diseases: senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP). In SSA aggregates are
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Transthyretin (TTR) is a homotetrameric protein that circulates in plasma and cerebral spinal fluid (CSF) whose aggregation into amyloid fibrils has been associated with at least two different amyloid diseases: senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP). In SSA aggregates are composed of WT-TTR, while in FAP more than 100 already-described variants have been found in deposits. Until now, TTR-related diseases have been untreatable, although a new drug called Tafamidis has been approved only in Europe to specifically treat V30M patients. Thus, new strategies are still necessary to treat FAP caused by other variants of TTR. TTR has two channels in the dimer interface that bind to the hormone thyroxin and that have been used to accommodate anti-amyloidogenic compounds. These compounds stabilize the tetramers, rendering TTR less amyloidogenic. Here, we investigated the effects of three non-steroidal anti-inflammatory compounds—sulindac (SUL), indomethacin (IND) and lumiracoxib (LUM)—as tetramer stabilizers and aggregation inhibitors. WT-TTR and the very aggressive TTR variant L55P were used as models. These compounds were able to stabilize TTR against high hydrostatic pressure (HHP), increasing the ΔGf by several kcal. They were also effective in inhibiting WT-TTR and L55P acid- or HHP-induced aggregation; in particular, LUM and IND were very effective, inhibiting almost 100% of the aggregation of both proteins under certain conditions. The species formed when aggregation was performed in the presence of these compounds were much less toxic to cells in culture. The crystal structures of WT-TTR bound to the three compounds were solved at high resolution, allowing the identification of the relevant protein:drug interactions. We discuss here the ligand-binding features of LUM, IND and SUL to TTR, emphasizing the critical interactions that render the protein more stable and less amyloidogenic. Full article
(This article belongs to the collection Protein Folding)
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Open AccessArticle Water Deficit and Heat Affect the Tolerance to High Illumination in Hibiscus Plants
Int. J. Mol. Sci. 2013, 14(3), 5432-5444; doi:10.3390/ijms14035432
Received: 22 January 2013 / Revised: 1 March 2013 / Accepted: 4 March 2013 / Published: 7 March 2013
Cited by 8 | PDF Full-text (387 KB) | HTML Full-text | XML Full-text
Abstract
This work studies the effects of water deficit and heat, as well as the involvement of chlororespiration and the ferredoxin-mediated cyclic pathway, on the tolerance of photosynthesis to high light intensity in Hibiscus rosa-sinensis plants. Drought and heat resulted in the down–regulation of
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This work studies the effects of water deficit and heat, as well as the involvement of chlororespiration and the ferredoxin-mediated cyclic pathway, on the tolerance of photosynthesis to high light intensity in Hibiscus rosa-sinensis plants. Drought and heat resulted in the down–regulation of photosynthetic linear electron transport in the leaves, although only a slight decrease in variable fluorescence (Fv)/maximal fluorescence (Fm) was observed, indicating that the chloroplast was protected by mechanisms that dissipate excess excitation energy to prevent damage to the photosynthetic apparatus. The incubation of leaves from unstressed plants under high light intensity resulted in an increase of the activity of electron donation by nicotinamide adenine dinucleotide phosphate (NADPH) and ferredoxin to plastoquinone, but no increase was observed in plants exposed to water deficit, suggesting that cyclic electron transport was stimulated by high light only in control plants. In contrast, the activities of the chlororespiration enzymes (NADH dehydrogenase (NDH) complex and plastid terminal oxidase (PTOX)) increased after incubation under high light intensity in leaves of the water deficit plants, but not in control plants, suggesting that chlororespiration was stimulated in stressed plants. The results indicate that the relative importance of chlororespiration and the cyclic electron pathway in the tolerance of photosynthesis to high illumination differs under stress conditions. When plants were not subjected to stress, the contribution of chlororespiration to photosynthetic electron flow regulation was not relevant, and another pathway, such as the ferredoxin-mediated cyclic pathway, was more important. However, when plants were subjected to water deficit and heat, chlororespiration was probably essential. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Preparation and Evaluation of Dental Resin with Antibacterial and Radio-Opaque Functions
Int. J. Mol. Sci. 2013, 14(3), 5445-5460; doi:10.3390/ijms14035445
Received: 10 January 2013 / Revised: 26 February 2013 / Accepted: 4 March 2013 / Published: 7 March 2013
Cited by 14 | PDF Full-text (1262 KB) | HTML Full-text | XML Full-text
Abstract
In order to prepare antibacterial and radio-opaque dental resin, a methacrylate monomer named 2-Dimethyl-2-dodecyl-1-methacryloxyethyl ammonium iodine (DDMAI) with both antibacterial and radio-opaque activities was added into a 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropyl)-phenyl]propane (Bis-GMA)/methyl methacrylate (MMA) dental resin system. Degree of conversion (DC), flexural strength (FS) and modulus
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In order to prepare antibacterial and radio-opaque dental resin, a methacrylate monomer named 2-Dimethyl-2-dodecyl-1-methacryloxyethyl ammonium iodine (DDMAI) with both antibacterial and radio-opaque activities was added into a 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropyl)-phenyl]propane (Bis-GMA)/methyl methacrylate (MMA) dental resin system. Degree of conversion (DC), flexural strength (FS) and modulus (FM), water sorption (WS) and solubility (WSL), antibacterial activity, and radio-opacity (ROX) of the obtained dental resin system were investigated. Bis-GMA/MMA resin system without DDMAI was used as a control. The results showed that DDMAI could endow BIS-GMA/MMA resin system with good antibacterial (p < 0.05) and radio-opaque function without influencing the DC (p > 0.05). However, incorporating DDMAI into Bis-GMA/MMA resin could reduce mechanical properties (p < 0.05) and increase WS and WSL (p < 0.05), thus further work is needed in order to optimize the resin formulation. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
Open AccessArticle The Role of the Conjugate Bridge in Electronic Structures and Related Properties of Tetrahydroquinoline for Dye Sensitized Solar Cells
Int. J. Mol. Sci. 2013, 14(3), 5461-5481; doi:10.3390/ijms14035461
Received: 7 December 2012 / Revised: 11 January 2013 / Accepted: 4 February 2013 / Published: 8 March 2013
Cited by 23 | PDF Full-text (2118 KB) | HTML Full-text | XML Full-text
Abstract
To understand the role of the conjugate bridge in modifying the properties of organic dye sensitizers in solar cells, the computations of the geometries and electronic structures for 10 kinds of tetrahydroquinoline dyes were performed using density functional theory (DFT), and the electronic
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To understand the role of the conjugate bridge in modifying the properties of organic dye sensitizers in solar cells, the computations of the geometries and electronic structures for 10 kinds of tetrahydroquinoline dyes were performed using density functional theory (DFT), and the electronic absorption and fluorescence properties were investigated via time dependent DFT. The population analysis, molecular orbital energies, radiative lifetimes, exciton binding energies (EBE), and light harvesting efficiencies (LHE), as well as the free energy changes of electron injection ( ) and dye regeneration ( ) were also addressed. The correlation of charge populations and experimental open-circuit voltage (Voc) indicates that more charges populated in acceptor groups correspond to larger Voc. The elongating of conjugate bridge by thiophene units generates the larger oscillator strength, higher LHE, larger absolute value of , and longer relative radiative lifetime, but it induces the decreasing of EBE and . So the extending of conjugate bridge with thiopene units in organic dye is an effective way to increase the harvest of solar light, and it is also favorable for electron injection due to their larger . While the inversely correlated relationship between EBE and LHE implies that the dyes with lower EBE produce more efficient light harvesting. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner
Int. J. Mol. Sci. 2013, 14(3), 5482-5500; doi:10.3390/ijms14035482
Received: 17 December 2012 / Revised: 16 February 2013 / Accepted: 26 February 2013 / Published: 8 March 2013
Cited by 4 | PDF Full-text (2710 KB) | HTML Full-text | XML Full-text
Abstract
Previous investigations have implicated glutathione S-transferases (GSTs) as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin,
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Previous investigations have implicated glutathione S-transferases (GSTs) as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST) and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9) as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle MUSTN1 mRNA Abundance and Protein Localization is Greatest in Muscle Tissues of Chinese Meat-Quality Chickens
Int. J. Mol. Sci. 2013, 14(3), 5545-5559; doi:10.3390/ijms14035545
Received: 3 December 2012 / Revised: 19 January 2013 / Accepted: 31 January 2013 / Published: 8 March 2013
Cited by 4 | PDF Full-text (948 KB) | HTML Full-text | XML Full-text
Abstract
The Mustang, Musculoskeletal Temporally Activated Novel-1 Gene (MUSTN1) plays an important role in regulating musculoskeletal development in mammals. We evaluated the developmental and tissue-specific regulation of MUSTN1 mRNA and protein abundance in Erlang Mountainous (EM) chickens. Results indicated that MUSTN1 mRNA/protein
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The Mustang, Musculoskeletal Temporally Activated Novel-1 Gene (MUSTN1) plays an important role in regulating musculoskeletal development in mammals. We evaluated the developmental and tissue-specific regulation of MUSTN1 mRNA and protein abundance in Erlang Mountainous (EM) chickens. Results indicated that MUSTN1 mRNA/protein was expressed in most tissues with especially high expression in heart and skeletal muscle. The MUSTN1 protein localized to the nucleus in myocardium and skeletal muscle fibers. There were significant differences in mRNA and protein abundance among tissues, ages and between males and females. In conclusion, MUSTN1 was expressed the greatest in skeletal muscle where it localized to the nucleus. Thus, in chickens MUSTN1 may play a vital role in muscle development. Full article
Open AccessArticle Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer’s Disease
Int. J. Mol. Sci. 2013, 14(3), 5576-5586; doi:10.3390/ijms14035576
Received: 20 December 2012 / Revised: 4 February 2013 / Accepted: 16 February 2013 / Published: 11 March 2013
Cited by 21 | PDF Full-text (1215 KB) | HTML Full-text | XML Full-text
Abstract
The Amyloid-β (Aβ)-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer's disease (AD) in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation plays an important role in
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The Amyloid-β (Aβ)-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer's disease (AD) in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation plays an important role in long-term memory. In this study, we isolated naringin from Pomelo peel (a Citrus species) and studied its effect on long-term memory in the APPswe/PS1dE9 transgenic mouse model of AD. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg body weight/day) groups, or an Aricept (2 mg/kg body weight/day) group. After 16 weeks of treatment, we observed that treatment with naringin (100 mg/kg body weight/day) enhanced the autophosphorylation of CaMKII, increased the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor at a CaMKII-dependent site and improved long-term learning and memory ability. These findings suggest that the increase in CaMKII activity may be one of the mechanisms by which naringin improves long-term cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD. Full article
Open AccessArticle Structure-Based Search for New Inhibitors of Cholinesterases
Int. J. Mol. Sci. 2013, 14(3), 5608-5632; doi:10.3390/ijms14035608
Received: 28 December 2012 / Revised: 31 January 2013 / Accepted: 28 February 2013 / Published: 11 March 2013
Cited by 26 | PDF Full-text (643 KB) | HTML Full-text | XML Full-text
Abstract
Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer’s disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed
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Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer’s disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological evaluation of selected candidates confirmed that the designed compounds were acetylcholinesterase inhibitors with IC50 values in the mid-nanomolar to low micromolar range, and some of them were also butyrylcholinesterase inhibitors. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Open AccessArticle Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
Int. J. Mol. Sci. 2013, 14(3), 5633-5649; doi:10.3390/ijms14035633
Received: 19 December 2012 / Revised: 22 February 2013 / Accepted: 28 February 2013 / Published: 11 March 2013
Cited by 11 | PDF Full-text (456 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we
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The NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress. We found that Sirt2 knock down changed expression of 340 genes, which are mainly involved in cellular processes including actin binding, cellular amino acid metabolic process, transmembrane receptor protein serine/threonine kinase signaling, ferrous iron transport, protein transport and localization, cell morphogenesis, and functions associated with endosome membrane and the trans-Golgi network. These genes and associated functions were largely non-overlapping with those altered by Sirt1 knock down. Moreover, we showed that pharmacological inhibition of Sirt2 attenuated oxidant-induced cell toxicity in endothelial cells. These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress, and may have a primarily distinct role as compared to Sirt1. Our results may provide a basis for future studies aiming to dissect the specific signaling pathway(s) that mediates specific Sirt2 functions in endothelial cells. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
Open AccessArticle Proteogenomic Characterization of Novel x-Type High Molecular Weight Glutenin Subunit 1Ax1.1
Int. J. Mol. Sci. 2013, 14(3), 5650-5667; doi:10.3390/ijms14035650
Received: 5 November 2012 / Revised: 12 February 2013 / Accepted: 25 February 2013 / Published: 11 March 2013
Cited by 5 | PDF Full-text (4887 KB) | HTML Full-text | XML Full-text
Abstract
Analysis of Portuguese wheat (Triticum aestivum L.) landrace ‘Barbela’ revealed the existence of a new x-type high molecular weight-glutenin subunit (HMW-GS) encoded at the Glu-A1 locus, which we named 1Ax1.1. Using one-dimensional and two-dimensional electrophoresis and mass spectrometry, we compared subunit
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Analysis of Portuguese wheat (Triticum aestivum L.) landrace ‘Barbela’ revealed the existence of a new x-type high molecular weight-glutenin subunit (HMW-GS) encoded at the Glu-A1 locus, which we named 1Ax1.1. Using one-dimensional and two-dimensional electrophoresis and mass spectrometry, we compared subunit 1Ax1.1 with other subunits encoded at the Glu-A1 locus. Subunit 1Ax1.1 has a theoretical molecular weight of 93,648 Da (or 91,508 Da for the mature protein) and an isoelectric point (pI) of about 5.7, making it the largest and most acidic HMW-GS known to be encoded at Glu-A1. Specific primers were designed to amplify and sequence 2601 bp of the Glu-A1 locus from the ‘Barbela 28’ wheat genome. A very high level of identity was found between the sequence encoding 1Ax1.1 and those encoding other alleles of the locus. The major difference found was an insertion of 36 amino acids in the central repetitive domain. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessCommunication Potential of Nitrogen Gas (N2) Flushing to Extend the Shelf Life of Cold Stored Pasteurised Milk
Int. J. Mol. Sci. 2013, 14(3), 5668-5685; doi:10.3390/ijms14035668
Received: 9 October 2012 / Revised: 31 January 2013 / Accepted: 4 March 2013 / Published: 11 March 2013
Cited by 5 | PDF Full-text (291 KB) | HTML Full-text | XML Full-text
Abstract
For different reasons, the amount of food loss for developing and developed countries is approximately equivalent. Altogether, these losses represent approximately 1/3 of the global food production. Significant amounts of pasteurised milk are lost due to bad smell and unpleasant taste. Currently, even
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For different reasons, the amount of food loss for developing and developed countries is approximately equivalent. Altogether, these losses represent approximately 1/3 of the global food production. Significant amounts of pasteurised milk are lost due to bad smell and unpleasant taste. Currently, even under the best cold chain conditions, psychrotolerant spore-forming bacteria, some of which also harbour virulent factors, limit the shelf life of pasteurised milk. N2 gas-based flushing has recently been of interest for improving the quality of raw milk. Here, we evaluated the possibility of addressing bacterial growth in pasteurised milk during cold storage at 6 °C and 8 °C. Clearly, the treatments hindered bacterial growth, in a laboratory setting, when N2-treated milk were compared to the corresponding controls, which suggests that N2-flushing treatment constitutes a promising option to extend the shelf life of pasteurised milk. Full article
(This article belongs to the Special Issue Green Biocides)
Open AccessArticle Role of Thermal Process on Self-Assembled Structures of 4'-([2,2':6',2''-Terpyridin]-4'-Yl)-[1,1'-Biphenyl]-4-Carboxylic Acid on Au(III)
Int. J. Mol. Sci. 2013, 14(3), 5686-5693; doi:10.3390/ijms14035686
Received: 23 November 2012 / Revised: 24 January 2013 / Accepted: 18 February 2013 / Published: 11 March 2013
Cited by 2 | PDF Full-text (4031 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The role of dynamic processes on self-assembled structures of 4'-([2,2':6', 2''-terpyridin]-4'-yl)-[1,1'-biphenyl]-4-carboxylic acid (l) molecules on Au(III) has been studied by scanning tunneling microscopy. The as-deposited monolayer is closed-packed and periodic in a short-range due to dipole forces. A thermal annealing process at 110
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The role of dynamic processes on self-assembled structures of 4'-([2,2':6', 2''-terpyridin]-4'-yl)-[1,1'-biphenyl]-4-carboxylic acid (l) molecules on Au(III) has been studied by scanning tunneling microscopy. The as-deposited monolayer is closed-packed and periodic in a short-range due to dipole forces. A thermal annealing process at 110 degrees drives such disordered monolayer into ordered chain-like structures, determined by the combination of the dipole forces and hydrogen bonding. Further annealing at 130 degrees turns the whole monolayer into a bowknot-like structure in which hydrogen bonding plays the dominant role in the formation of assembled structures. Such dependence of an assembled structure on the process demonstrates that an assembled structure can be regulated and controlled not only by the molecular structure but also by the thermal process to form the assembled structure. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
Open AccessArticle Development and Validation of Single Nucleotide Polymorphisms (SNPs) Markers from Two Transcriptome 454-Runs of Turbot (Scophthalmus maximus) Using High-Throughput Genotyping
Int. J. Mol. Sci. 2013, 14(3), 5694-5711; doi:10.3390/ijms14035694
Received: 3 December 2012 / Revised: 17 February 2013 / Accepted: 22 February 2013 / Published: 12 March 2013
Cited by 13 | PDF Full-text (252 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The turbot (Scophthalmus maximus) is a commercially valuable flatfish and one of the most promising aquaculture species in Europe. Two transcriptome 454-pyrosequencing runs were used in order to detect Single Nucleotide Polymorphisms (SNPs) in genes related to immune response and gonad
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The turbot (Scophthalmus maximus) is a commercially valuable flatfish and one of the most promising aquaculture species in Europe. Two transcriptome 454-pyrosequencing runs were used in order to detect Single Nucleotide Polymorphisms (SNPs) in genes related to immune response and gonad differentiation. A total of 866 true SNPs were detected in 140 different contigs representing 262,093 bp as a whole. Only one true SNP was analyzed in each contig. One hundred and thirteen SNPs out of the 140 analyzed were feasible (genotyped), while Ш were polymorphic in a wild population. Transition/transversion ratio (1.354) was similar to that observed in other fish studies. Unbiased gene diversity (He) estimates ranged from 0.060 to 0.510 (mean = 0.351), minimum allele frequency (MAF) from 0.030 to 0.500 (mean = 0.259) and all loci were in Hardy-Weinberg equilibrium after Bonferroni correction. A large number of SNPs (49) were located in the coding region, 33 representing synonymous and 16 non-synonymous changes. Most SNP-containing genes were related to immune response and gonad differentiation processes, and could be candidates for functional changes leading to phenotypic changes. These markers will be useful for population screening to look for adaptive variation in wild and domestic turbot. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Synthesis of Thieno[2,3-b]thiophene Containing Bis-Heterocycles-Novel Pharmacophores
Int. J. Mol. Sci. 2013, 14(3), 5712-5722; doi:10.3390/ijms14035712
Received: 27 November 2012 / Revised: 1 February 2013 / Accepted: 18 February 2013 / Published: 12 March 2013
Cited by 15 | PDF Full-text (347 KB) | HTML Full-text | XML Full-text
Abstract
Thioenethiophene derivatives represent an important class of compounds with diverse biological activities. We describe here the synthesis of a new series of thieno[2,3-b]thiophene containing bis-heterocyclic compounds 37. All the compounds were evaluated for their in vitro antioxidant
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Thioenethiophene derivatives represent an important class of compounds with diverse biological activities. We describe here the synthesis of a new series of thieno[2,3-b]thiophene containing bis-heterocyclic compounds 37. All the compounds were evaluated for their in vitro antioxidant potential, α-glucosidase and β-glucuronidase inhibiton and anticancer activity against PC-3 cell lines. Compounds 2b (IC50 = 1.3 ± 0.2 μM), 5a (IC50 = 2.3 ± 0.4 μM) and 5b (IC50 = 8.7 ± 0.1 μM) showed a potent inhibition of β-glucuronidase enzyme, more active than the standard d-saccharic acid 1,4-lactone (IC50 = 45.8 ± 2.5 μM). Compounds 5a (IC50 = 22.0 ± 0.3 μM) and 5b (IC50 = 58.4 ± 1.2 μM) were also found to be potent α-glucosidase inhibitors as compared to standard drug (acarbose, IC50 = 841 ± 1.7 μM). Full article
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Open AccessArticle 9G DNAChip Technology: Self-Assembled Monolayer (SAM) of ssDNA for Ultra-Sensitive Detection of Biomarkers
Int. J. Mol. Sci. 2013, 14(3), 5723-5733; doi:10.3390/ijms14035723
Received: 8 December 2012 / Revised: 1 February 2013 / Accepted: 4 March 2013 / Published: 12 March 2013
Cited by 5 | PDF Full-text (6600 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers. Using a 9G DNAChip, biomarker in the concentration range of 4
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A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers. Using a 9G DNAChip, biomarker in the concentration range of 4 pg/mL to 40 fg/mL can be easily differentiated in the buffer matrix. Moreover, it is the first time that a biomarker with a concentration of 40 fg/mL has been detected in a mixture of proteins without use of any signal amplification technique. Full article
Open AccessArticle Batch and Continuous Ultrasound Assisted Extraction of Boldo Leaves (Peumus boldus Mol.)
Int. J. Mol. Sci. 2013, 14(3), 5750-5764; doi:10.3390/ijms14035750
Received: 29 January 2013 / Revised: 28 February 2013 / Accepted: 5 March 2013 / Published: 12 March 2013
Cited by 9 | PDF Full-text (3791 KB) | HTML Full-text | XML Full-text
Abstract
Vegetal extracts are widely used as primary ingredients for various products from creams to perfumes in the pharmaceutical, nutraceutic and cosmetic industries. Having concentrated and active extract is essential, as the process must extract as much soluble material as possible in a minimum
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Vegetal extracts are widely used as primary ingredients for various products from creams to perfumes in the pharmaceutical, nutraceutic and cosmetic industries. Having concentrated and active extract is essential, as the process must extract as much soluble material as possible in a minimum time, using the least possible volume of solvent. The boldo leaves extract is of great interest for the industry as it holds a great anti-oxidant activity due to high levels of flavonoids and alkaloids such as boldine. Ultrasound Assisted Extraction (UAE) has been used to improve the efficiency of the plant extraction, reducing extraction time, increasing the concentration of the extract with the same amount of solvent and plant material. After a preliminary study, a response surface method has been used to optimize the extraction of soluble material from the plant. The results provided by the statistical analysis revealed that the optimized conditions were: sonication power 23 W/cm2 for 40 min and a temperature of 36 °C. The optimized parameters of the UAE provide a better extraction compared to a conventional maceration in terms of process time (30 min instead of 120 min), higher yield, more energy saving, cleanliness, safety and product quality. Full article
(This article belongs to the Section Green Chemistry)
Open AccessArticle Quick, Selective and Reversible Photocrosslinking Reaction between 5-Methylcytosine and 3-Cyanovinylcarbazole in DNA Double Strand
Int. J. Mol. Sci. 2013, 14(3), 5765-5774; doi:10.3390/ijms14035765
Received: 20 December 2012 / Revised: 12 February 2013 / Accepted: 26 February 2013 / Published: 12 March 2013
Cited by 7 | PDF Full-text (1433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Selective photocrosslinking reaction between 3-cyanovinylcarbazole nucleoside (CNVK) and 5-methylcytosine (mC), which is known as epigenetic modification in genomic DNA, was developed. The reaction was completely finished within 5 s of 366 nm irradiation, and the rate of this photocrosslinking
[...] Read more.
Selective photocrosslinking reaction between 3-cyanovinylcarbazole nucleoside (CNVK) and 5-methylcytosine (mC), which is known as epigenetic modification in genomic DNA, was developed. The reaction was completely finished within 5 s of 366 nm irradiation, and the rate of this photocrosslinking reaction was ca. 30-fold higher than that in the case of unmodified normal cytosine. There were no significant differences in the thermodynamic parameters and the kinetics of hybrid formation of oligonucleotide (ODN) containing CNVK and its complementary ODN containing C or mC at the photocrosslinking site, and suggesting that the quick and selective photoreaction has potential for the selective detection of mC in the DNA strand via the photocrosslinking reaction. Full article
(This article belongs to the Special Issue Molecular Cut and Paste)
Open AccessCommunication Exploiting BSA to Inhibit the Fibrous Aggregation of Magnetic Nanoparticles under an Alternating Magnetic Field
Int. J. Mol. Sci. 2013, 14(3), 5775-5783; doi:10.3390/ijms14035775
Received: 26 November 2012 / Revised: 6 February 2013 / Accepted: 15 February 2013 / Published: 12 March 2013
Cited by 3 | PDF Full-text (495 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The alternating magnetic field was discovered to be capable of inducing the fibrous aggregation of magnetic nanoparticles. However, this anisotropic aggregation may be unfavorable for practical applications. Here, we reported that the adsorption of BSA (bovine serum albumin) on the surfaces of magnetic
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The alternating magnetic field was discovered to be capable of inducing the fibrous aggregation of magnetic nanoparticles. However, this anisotropic aggregation may be unfavorable for practical applications. Here, we reported that the adsorption of BSA (bovine serum albumin) on the surfaces of magnetic nanoparticles can effectively make the fibrous aggregation of γ-Fe2O3 nanoparticles turn into a more isotropic aggregation in the presence of the alternating magnetic field. Also, the heating curves with and without BSA adsorption under different pH conditions were measured to show the influence of the colloidal aggregation states on the collective calorific behavior of magnetic nanoparticles. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
Open AccessArticle Reaction of Stabilized Criegee Intermediates from Ozonolysis of Limonene with Water: Ab Initio and DFT Study
Int. J. Mol. Sci. 2013, 14(3), 5784-5805; doi:10.3390/ijms14035784
Received: 5 January 2013 / Revised: 7 February 2013 / Accepted: 4 March 2013 / Published: 12 March 2013
Cited by 5 | PDF Full-text (2737 KB) | HTML Full-text | XML Full-text
Abstract
The mechanism of the chemical reaction of H2O with three stabilized Criegee intermediates (stabCI-OO, stabCI-CH3-OO and stabCIx-OO) produced via the limonene ozonolysis reaction has been investigated using ab initio and DFT (Density Functional Theory) methods. It has
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The mechanism of the chemical reaction of H2O with three stabilized Criegee intermediates (stabCI-OO, stabCI-CH3-OO and stabCIx-OO) produced via the limonene ozonolysis reaction has been investigated using ab initio and DFT (Density Functional Theory) methods. It has been shown that the formation of the hydrogen-bonded complexes is followed by two different reaction pathways, leading to the formation of either OH radicals via water-catalyzed H migration or of α-hydroxy hydroperoxide. Both pathways were found to be essential sources of atmospheric OH radical and H2O2 making a significant contribution to the formation of secondary aerosols in the Earth’s atmosphere. The activation energies at the CCSD(T)/6-31G(d) + CF level of theory were found to be in the range of 14.70–21.98 kcal mol−1. The formation of α-hydroxy hydroperoxide for the reaction of stabCIx-OO and H2O with the activation energy of 14.70 kcal mol−1 is identified as the most favorable pathway. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Open AccessArticle Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC)
Int. J. Mol. Sci. 2013, 14(3), 5806-5816; doi:10.3390/ijms14035806
Received: 23 October 2012 / Revised: 17 January 2013 / Accepted: 17 January 2013 / Published: 12 March 2013
Cited by 9 | PDF Full-text (458 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM)
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Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action. As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death. In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells. Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM. Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27. Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease
Int. J. Mol. Sci. 2013, 14(3), 5879-5898; doi:10.3390/ijms14035879
Received: 13 December 2012 / Revised: 19 January 2013 / Accepted: 1 March 2013 / Published: 13 March 2013
Cited by 14 | PDF Full-text (967 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alzheimer’s disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the
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Alzheimer’s disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the Aβ domain. Therefore, an increase in α-secretase activity is an attractive therapeutic target for AD treatment. APP and the APP-cleaving secretases are all transmembrane proteins, thus local membrane lipid composition is proposed to influence APP processing. Although several studies have focused on γ-secretase, the effect of the membrane lipid microenvironment on α-secretase is poorly understood. In the present study, we systematically investigated the effect of fatty acid (FA) acyl chain length (10:0, 12:0, 14:0, 16:0, 18:0, 20:0, 22:0, 24:0), membrane polar lipid headgroup (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine), saturation grade and the FA double-bond position on α-secretase activity. We found that α-secretase activity is significantly elevated in the presence of FAs with short chain length and in the presence of polyunsaturated FAs, whereas variations in the phospholipid headgroups, as well as the double-bond position, have little or no effect on α-secretase activity. Overall, our study shows that local lipid membrane composition can influence α-secretase activity and might have beneficial effects for AD. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
Open AccessArticle A Rice Immunophilin Gene, OsFKBP16-3, Confers Tolerance to Environmental Stress in Arabidopsis and Rice
Int. J. Mol. Sci. 2013, 14(3), 5899-5919; doi:10.3390/ijms14035899
Received: 30 January 2013 / Revised: 4 March 2013 / Accepted: 5 March 2013 / Published: 13 March 2013
Cited by 6 | PDF Full-text (2060 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The putative thylakoid lumen immunophilin, FKBP16-3, has not yet been characterized, although this protein is known to be regulated by thioredoxin and possesses a well-conserved CxxxC motif in photosynthetic organisms. Here, we characterized rice OsFKBP16-3 and examined the role of this gene in
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The putative thylakoid lumen immunophilin, FKBP16-3, has not yet been characterized, although this protein is known to be regulated by thioredoxin and possesses a well-conserved CxxxC motif in photosynthetic organisms. Here, we characterized rice OsFKBP16-3 and examined the role of this gene in the regulation of abiotic stress in plants. FKBP16-3s are well conserved in eukaryotic photosynthetic organisms, including the presence of a unique disulfide-forming CxxxC motif in their N-terminal regions. OsFKBP16-3 was mainly expressed in rice leaf tissues and was upregulated by various abiotic stresses, including salt, drought, high light, hydrogen peroxide, heat and methyl viologen. The chloroplast localization of OsFKBP16-3-GFP was confirmed through the transient expression of OsFKBP16-3 in Nicotiana benthamiana leaves. Transgenic Arabidopsis and transgenic rice plants that constitutively expressed OsFKBP16-3 exhibited increased tolerance to salinity, drought and oxidative stresses, but showed no change in growth or phenotype, compared with vector control plants, when grown under non-stressed conditions. This is the first report to demonstrate the potential role of FKBP16-3 in the environmental stress response, which may be regulated by a redox relay process in the thylakoid lumen, suggesting that artificial regulation of FKBP16-3 expression is a candidate for stress-tolerant crop breeding. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Study of Fungal Colonization of Wheat Kernels in Syria with a Focus on Fusarium Species
Int. J. Mol. Sci. 2013, 14(3), 5938-5951; doi:10.3390/ijms14035938
Received: 27 December 2012 / Revised: 4 March 2013 / Accepted: 11 March 2013 / Published: 14 March 2013
Cited by 6 | PDF Full-text (956 KB) | HTML Full-text | XML Full-text
Abstract
Wheat is one of the main crops in Mediterranean countries, and its cultivation has an important role in the Syrian economy. In Syria, Fusarium head blight (FHB) has not been reported so far. Mycological analysis of 48 samples of wheat kernels collected from
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Wheat is one of the main crops in Mediterranean countries, and its cultivation has an important role in the Syrian economy. In Syria, Fusarium head blight (FHB) has not been reported so far. Mycological analysis of 48 samples of wheat kernels collected from cultivation areas with different climatic conditions were performed in 2009 and 2010. Fungal isolates were identified at the genus level morphologically; Fusarium species were characterized morphologically and by species-specific PCR. The most frequent fungal genera found were Alternaria spp. and Cladosporium spp., with frequencies of 24.7% and 8.1%, respectively, while the frequency of Fusarium spp. was 1.5% of kernels. Most frequent Fusarium species were F. tricinctum (30% of all Fusarium isolates), F. culmorum (18%), F. equiseti (14%) and F. graminearum (13%). The mycotoxin production potential of selected Fusarium isolates was assessed by HPLC-MS analysis of rice cultures; chemotyping by PCR was carried out for comparison. All six F. graminearum strains tested produced small amounts (<3 mg/kg) of nivalenol (NIV). All ten F. culmorum strains tested produced large amounts of trichothecenes (>100 mg/kg); four strains produced NIV and six strains produced deoxynivalenol (DON) and 3-acetyl-deoxynivalenol (3Ac-DON). PCR chemotyping lead to an oversimplified picture, because all 3Ac-DON chemotype strains produced more DON than 3Ac-DON; furthermore, the strongest NIV producers produced significant amounts of DON. All tested strains of F. culmorum, F. graminearum, F. pseudograminearum (two strains) and most F. equiseti strains (five of six strains) produced zearalenone. Grains of durum wheat were more frequently colonized by Fusarium spp. than grains of soft wheat. Incidence of Fusarium spp. in irrigated fields was higher than in rainfed fields. The incidence of Fusarium strains producing mycotoxins raises concerns about the risk of Fusarium head blight to Syria and its consequences for public health. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Synthesis and Evaluation of Molecularly Imprinted Silica Gel for 2-Hydroxybenzoic Acid in Aqueous Solution
Int. J. Mol. Sci. 2013, 14(3), 5952-5965; doi:10.3390/ijms14035952
Received: 13 November 2012 / Revised: 12 January 2013 / Accepted: 13 February 2013 / Published: 14 March 2013
Cited by 4 | PDF Full-text (671 KB) | HTML Full-text | XML Full-text
Abstract
A molecularly imprinted silica gel sorbent for selective removal of 2-Hydroxybenzoic acid (2-HA) was prepared by a surface imprinting technique with a sol-gel process. The 2-HA molecularly imprinted silica gel (2-HA-MISG) sorbent was evaluated by various parameters, including the influence of pH, static,
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A molecularly imprinted silica gel sorbent for selective removal of 2-Hydroxybenzoic acid (2-HA) was prepared by a surface imprinting technique with a sol-gel process. The 2-HA molecularly imprinted silica gel (2-HA-MISG) sorbent was evaluated by various parameters, including the influence of pH, static, kinetic adsorption and selectivity experiments. The optimum adsorption capacity to the 2-HA appeared to be around pH 2 by the polymer. Morevoer, the imprinted sorbent displayed fast uptake kinetics, obtained within 20 min. The adsorption capacity of the 2-HA-MISG (76.2 mg g−1) was higher than that of the non-imprinted silica gel (NISG) (42.58 mg g−1). This indicates that the 2-HA-MISG offers a higher affinity for 2-HA than the NISG. The polymer displays good selectivity and exhibits good reusability. Experimental results show the potential of molecularly imprinted silica sorbent for selective removal of 2-HA. Full article
(This article belongs to the Section Molecular Recognition)
Open AccessArticle The Effects of Inhibiting Hedgehog Signaling Pathways by Using Specific Antagonist Cyclopamine on the Chondrogenic Differentiation of Mesenchymal Stem Cells
Int. J. Mol. Sci. 2013, 14(3), 5966-5977; doi:10.3390/ijms14035966
Received: 18 January 2013 / Revised: 5 March 2013 / Accepted: 7 March 2013 / Published: 14 March 2013
Cited by 6 | PDF Full-text (437 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to investigate the effects of cyclopamine, a specific inhibitor of Hedgehog signaling pathways, on the chondrogenic differentiation of mesenchymal stem cells (MSCs). During culture, the experimental groups were treated with cyclopamine and their cell proliferation status was assessed using the
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This study aimed to investigate the effects of cyclopamine, a specific inhibitor of Hedgehog signaling pathways, on the chondrogenic differentiation of mesenchymal stem cells (MSCs). During culture, the experimental groups were treated with cyclopamine and their cell proliferation status was assessed using the MTT test. The extra-bone cellular matrix (ECM) and Collagen II (Col II) was detected by toluidine blue staining and immunohistochemistry of cells. The concentrations of Col II and aggrecan in the culture solution and cytosol were detected using ELISA on the 7th, 14th, and 21st days of cyclopamine induction. Gene and protein expression of Col II and aggrecan were analyzed on the 14th day of cyclopamine induction using real-time PCR and western blot analyses. No significant differences in proliferation of mesenchymal stem cells were found between the control group and the group treated with cyclopamine. Compared to the blank control group, the ECM level was low and the protein and mRNA concentrations of Collagen II (Col II) and aggrecan in the culture solution and cytosol, respectively, were significantly reduced in the experimental group. The Smo acted as a key point in the regulations of Hedgehog signaling pathway on the chondrogenic differentiation of rabbit MSCs. Full article
Open AccessArticle Alteration of Podocyte Protein Expression and Localization in the Early Stage of Various Hemodynamic Conditions
Int. J. Mol. Sci. 2013, 14(3), 5998-6011; doi:10.3390/ijms14035998
Received: 18 January 2013 / Revised: 3 March 2013 / Accepted: 5 March 2013 / Published: 15 March 2013
Cited by 4 | PDF Full-text (4329 KB) | HTML Full-text | XML Full-text
Abstract
Given that podocalyxin (PCX) and nestin play important roles in podocyte morphogenesis and the maintenance of structural integrity, we examined whether the expression and localization of these two podocyte proteins were influenced in the early stage of various hemodynamic conditions. Mice kidney tissues
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Given that podocalyxin (PCX) and nestin play important roles in podocyte morphogenesis and the maintenance of structural integrity, we examined whether the expression and localization of these two podocyte proteins were influenced in the early stage of various hemodynamic conditions. Mice kidney tissues were prepared by in vivo cryotechnique (IVCT). The distribution of glomeruli and podocyte proteins was visualized with DAB staining, confocal laser scanning microscopy and immunoelectron microscopy. The mRNA levels were examined by real-time quantitative PCR. The results showed the following: Under the normal condition, PCX stained intensely along glomerular epithelial cells, whereas nestin was clearly staining in the endothelial cells and appeared only weakly in the podocytes. Under the acute hypertensive and cardiac arrest conditions, PCX and nestin staining was not clear, with a disarranged distribution, but the colocalization of PCX and nestin was apparent under this condition. In addition, under the acute hypertensive and cardiac arrest conditions, the mRNA levels of PCX and nestin were significantly decreased. Collectively, the abnormal redistribution and decreased mRNA expressions of PCX and nestin are important molecular events at the early stage of podocyte injury during hemodynamic disorders. IVCT may have more advantages for morphological analysis when researching renal diseases. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
Open AccessArticle Inhibitory Effect of Baicalin and Baicalein on Ovarian Cancer Cells
Int. J. Mol. Sci. 2013, 14(3), 6012-6025; doi:10.3390/ijms14036012
Received: 16 January 2013 / Revised: 25 February 2013 / Accepted: 26 February 2013 / Published: 15 March 2013
Cited by 25 | PDF Full-text (567 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant
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Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70) cell lines and a normal ovarian cell line (IOSE-364) were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD50 values in the range of 45–55 µM for baicalin and 25–40 µM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD50 values of 177 µM for baicalin and 68 µM for baicalein. Baicalin decreased expression of VEGF (20 µM), cMyc (80 µM), and NFkB (20 µM); baicalein decreased expression of VEGF (10 µM), HIF-1α (20 µM), cMyc (20 µM), and NFkB (40 µM). Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessArticle HE4 (WFDC2) Promotes Tumor Growth in Endometrial Cancer Cell Lines
Int. J. Mol. Sci. 2013, 14(3), 6026-6043; doi:10.3390/ijms14036026
Received: 22 January 2013 / Revised: 7 February 2013 / Accepted: 25 February 2013 / Published: 15 March 2013
Cited by 16 | PDF Full-text (695 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
HE4, also known as WFDC2, is a useful biomarker for ovarian cancer when either used alone or in combination with CA125. HE4 is also overexpressed in endometrial cancer (EC), but its function in cancer cells is not clear. In this study, we investigate
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HE4, also known as WFDC2, is a useful biomarker for ovarian cancer when either used alone or in combination with CA125. HE4 is also overexpressed in endometrial cancer (EC), but its function in cancer cells is not clear. In this study, we investigate the role of HE4 in EC progression. An HE4-overexpression system was established by cloning the HE4 prototypic mRNA variant (HE4-V0) into a eukaryotic expression vector. Following transfection, stable clones in two EC cell lines were selected. The effects of HE4 overexpression on cell growth and function were measured with the use of cell proliferation assay, matrigel invasion, and soft agar gel colony formation assays. HE4-induced cancer cell proliferation in vivo was examined in a mouse xenograft model. HE4 overexpression significantly enhanced EC cell proliferation, matrigel invasion, and colony formation in soft agar. Moreover, HE4 overexpression promoted tumor growth in the mouse xenograft model. HE4 overexpression enhanced several malignant phenotypes in cell culture and in a mouse model. These results are consistent with our previous observation that high levels of serum HE4 closely correlate with the stage, myometrial invasion and tumor size in patients with EC. This study provides evidence that HE4 overexpression directly impacts tumor progression in endometrial cancer. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessArticle Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats
Int. J. Mol. Sci. 2013, 14(3), 6074-6089; doi:10.3390/ijms14036074
Received: 14 January 2013 / Revised: 3 February 2013 / Accepted: 28 February 2013 / Published: 15 March 2013
Cited by 19 | PDF Full-text (1787 KB) | HTML Full-text | XML Full-text
Abstract
Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise
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Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise on apoptosis induced by ischemia. Adult SD rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion model (MCAO) and were randomly divided into early exercise group, non-exercise group and sham group. Early exercise group received forced treadmill training initiated at 24 h after operation. Fourteen days later, the cell apoptosis were detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and Fluoro-Jade-B staining (F-J-B). Caspase-3, cleaved caspase-3 and Bcl-2 were determined by western blotting. Cerebral infarct volume and motor function were evaluated by cresyl violet staining and foot fault test respectively. The results showed that early exercise decreased the number of apoptotic cells (118.74 ± 6.15 vs. 169.65 ± 8.47, p < 0.05, n = 5), inhibited the expression of caspase-3 and cleaved caspase-3 (p < 0.05, n = 5), and increased the expression of Bcl-2 (p < 0.05, n = 5). These data were consistent with reduced infarct volume and improved motor function. These results suggested that early exercise could provide neuroprotection through inhibiting neuron apoptosis. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
Open AccessArticle PAX2 Expression in Ovarian Cancer
Int. J. Mol. Sci. 2013, 14(3), 6090-6105; doi:10.3390/ijms14036090
Received: 25 January 2013 / Revised: 5 March 2013 / Accepted: 13 March 2013 / Published: 15 March 2013
Cited by 8 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two
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PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessArticle Comparative Analysis of Serum (Anti)oxidative Status Parаmeters in Healthy Persons
Int. J. Mol. Sci. 2013, 14(3), 6106-6115; doi:10.3390/ijms14036106
Received: 31 December 2012 / Revised: 5 March 2013 / Accepted: 7 March 2013 / Published: 18 March 2013
Cited by 18 | PDF Full-text (204 KB) | HTML Full-text | XML Full-text
Abstract
Five antioxidant and two oxidative stress assays were applied to serum samples of 43 healthy males. The antioxidant tests showed different inter-assay correlations. A very good correlation of 0.807 was observed between the ferric reducing ability of plasma (FRAP) and total antioxidant status
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Five antioxidant and two oxidative stress assays were applied to serum samples of 43 healthy males. The antioxidant tests showed different inter-assay correlations. A very good correlation of 0.807 was observed between the ferric reducing ability of plasma (FRAP) and total antioxidant status (TAS) assay and also a fair correlation of 0.501 between the biological antioxidant potential (BAP) and TAS assay. There was no statistically significant correlation between the BAP and FRAP assay. The anti-oxidant assays have a high correlation with uric acid, especially the TAS (0.922) and FRAP assay (0.869). The BAP assay has a much lower and no statistically significant correlation with uric acid (0.302), which makes BAP more suitable for the antioxidant status. The total thiol assay showed no statistically significant correlation with uric acid (0.114). The total thiol assay, which is based on a completely different principle, showed a good and statistically significant correlation with the BAP assay (0.510) and also to the TAS assay, but to a lower and not significant extent (0.279) and not with the FRAP assay (−0.008). The oxy-adsorbent test (OXY) assay has no correlation with any of the other assays tested. The oxidative stress assays, reactive oxygen metabolites (ROM) and total oxidant status (TOS), based on a different principle, do not show a statistically significant correlation with the serum samples in this study. Both assays showed a negative, but not significant, correlation with the antioxidant assays. In conclusion, the ROM, TOS, BAP and TTP assays are based on different principles and will have an additional value when a combination of these assays will be applied in large-scale population studies. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
Open AccessArticle LC-MS/MS Determination of Isoprostanes in Plasma Samples Collected from Mice Exposed to Doxorubicin or Tert-Butyl Hydroperoxide
Int. J. Mol. Sci. 2013, 14(3), 6157-6169; doi:10.3390/ijms14036157
Received: 10 January 2013 / Revised: 5 February 2013 / Accepted: 6 March 2013 / Published: 18 March 2013
Cited by 7 | PDF Full-text (649 KB) | HTML Full-text | XML Full-text
Abstract
Isoprostanes are stable products of arachidonic acid peroxidation and are regarded as the most reliable markers of oxidative stress in vivo. Here we describe the LC-MS/MS procedure enabling simultaneous determination of four regioisomers (8-iso prostaglandin F, 8-iso-15(R)-prostaglandin
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Isoprostanes are stable products of arachidonic acid peroxidation and are regarded as the most reliable markers of oxidative stress in vivo. Here we describe the LC-MS/MS procedure enabling simultaneous determination of four regioisomers (8-iso prostaglandin F, 8-iso-15(R)-prostaglandin F, 11β-prostaglandin F, 15(R)-prostaglandin F) in plasma samples collected from mice. The four plasma isoprostanes are determined by LC–ESI-MS/MS with deuterated 8-iso-PGF-d4 as an internal standard (I.S.). For plasma samples spiked with the isoprostanes at a level of 200 pg/mL each, the method imprecision has been below 7.1% and mean inaccuracy equaled 8.7%. The applicability of the proposed approach has been verified by the assessment of changes in isoprostane levels in plasma samples derived from mice exposed to tert-butyl hydroperoxide (TBHP), a model inducer of oxidative stress, or to antitumor drug doxorubicin (DOX) known for potent stimulation of redox cycling. Compared to the control group of mice, both oxidative stress inducers tested increased the levels of three out of four isoprostanes in exposed animals; 11β-prostaglandin F being the exception. The greatest rise was observed in the case of 15(R)-prostaglandin F, by about 50% and 70% in plasma samples derived from mice exposed to DOX and TBHP, respectively. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
Open AccessArticle A Novel Moderate Constitutive Promoter Derived from Poplar (Populus tomentosa Carrière)
Int. J. Mol. Sci. 2013, 14(3), 6187-6204; doi:10.3390/ijms14036187
Received: 21 November 2012 / Revised: 5 February 2013 / Accepted: 6 March 2013 / Published: 18 March 2013
Cited by 6 | PDF Full-text (1255 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel sequence that functions as a promoter element for moderate constitutive expression of transgenes, designated as the PtMCP promoter, was isolated from the woody perennial Populus tomentosa. The PtMCP promoter was fused to the GUS reporter gene to characterize its expression
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A novel sequence that functions as a promoter element for moderate constitutive expression of transgenes, designated as the PtMCP promoter, was isolated from the woody perennial Populus tomentosa. The PtMCP promoter was fused to the GUS reporter gene to characterize its expression pattern in different species. In stable Arabidopsis transformants, transcripts of the GUS reporter gene could be detected by RT-PCR in the root, stem, leaf, flower and silique. Further histochemical and fluorometric GUS activity assays demonstrated that the promoter could direct transgene expression in all tissues and organs, including roots, stems, rosette leaves, cauline leaves and flowers of seedlings and maturing plants. Its constitutive expression pattern was similar to that of the CaMV35S promoter, but the level of GUS activity was significantly lower than in CaMV35S promoter::GUS plants. We also characterized the promoter through transient expression in transgenic tobacco and observed similar expression patterns. Histochemical GUS staining and quantitative analysis detected GUS activity in all tissues and organs of tobacco, including roots, stems, leaves, flower buds and flowers, but GUS activity in PtMCP promoter::GUS plants was significantly lower than in CaMV35S promoter::GUS plants. Our results suggested that the PtMCP promoter from poplar is a constitutive promoter with moderate activity and that its function is presumably conserved in different species. Therefore, the PtMCP promoter may provide a practical choice to direct moderate level constitutive expression of transgenes and could be a valuable new tool in plant genetic engineering. Full article
Open AccessArticle Combinatorial Analysis of Secretory Immunoglobulin A (sIgA) Expression in Plants
Int. J. Mol. Sci. 2013, 14(3), 6205-6222; doi:10.3390/ijms14036205
Received: 3 December 2012 / Revised: 4 January 2013 / Accepted: 27 February 2013 / Published: 18 March 2013
Cited by 11 | PDF Full-text (1063 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Delivery of secretory immunoglobulin A (sIgA) to mucosal surfaces as a passive immunotherapy agent is a promising strategy to prevent infectious diseases. Recombinant sIgA production in plants requires the co-expression of four transcriptional units encoding the light chain (LC), heavy chain (HC), joining
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Delivery of secretory immunoglobulin A (sIgA) to mucosal surfaces as a passive immunotherapy agent is a promising strategy to prevent infectious diseases. Recombinant sIgA production in plants requires the co-expression of four transcriptional units encoding the light chain (LC), heavy chain (HC), joining chain (JC) and secretory component (SC). As a way to optimize sIgA production in plants, we tested the combinatorial expression of 16 versions of a human sIgA against the VP8* rotavirus antigen in Nicotiana benthamiana, using the recently developed GoldenBraid multigene assembly system. Each sIgA version was obtained by combining one of the two types of HC (α1 and α2) with one of the two LC types (k and λ) and linking or not a KDEL peptide to the HC and/or SC. From the analysis of the anti-VP8* activity, it was concluded that those sIgA versions carrying HCα1 and LCλ provided the highest yields. Moreover, ER retention significantly increased antibody production, particularly when the KDEL signal was linked to the SC. Maximum expression levels of 32.5 μg IgA/g fresh weight (FW) were obtained in the best performing combination, with an estimated 33% of it in the form of a secretory complex. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Gold-Coated Iron Composite Nanospheres Targeted the Detection of Escherichia coli
Int. J. Mol. Sci. 2013, 14(3), 6223-6240; doi:10.3390/ijms14036223
Received: 28 November 2012 / Revised: 28 February 2013 / Accepted: 28 February 2013 / Published: 18 March 2013
Cited by 14 | PDF Full-text (3443 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report the preparation and characterization of spherical core-shell structured Fe3O4–Au magnetic nanoparticles, modified with two component self-assembled monolayers (SAMs) consisting of 3–mercaptophenylboronic acid (3–MBA) and 1–decanethiol (1–DT). The rapid and room temperature synthesis of magnetic nanoparticles was achieved
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We report the preparation and characterization of spherical core-shell structured Fe3O4–Au magnetic nanoparticles, modified with two component self-assembled monolayers (SAMs) consisting of 3–mercaptophenylboronic acid (3–MBA) and 1–decanethiol (1–DT). The rapid and room temperature synthesis of magnetic nanoparticles was achieved using the hydroxylamine reduction of HAuCl4 on the surface of ethylenediaminetetraacetic acid (EDTA)-immobilized iron (magnetite Fe3O4) nanoparticles in the presence of an aqueous solution of hexadecyltrimetylammonium bromide (CTAB) as a dispersant. The reduction of gold on the surface of Fe3O4 nanoparticles exhibits a uniform, highly stable, and narrow particle size distribution of Fe3O4–Au nanoparticles with an average diameter of 9 ± 2 nm. The saturation magnetization value for the resulting nanoparticles was found to be 15 emu/g at 298 K. Subsequent surface modification with SAMs against glucoside moieties on the surface of bacteria provided effective magnetic separation. Comparison of the bacteria capturing efficiency, by means of different molecular recognition agents 3–MBA, 1–DT and the mixed monolayer of 3–MBA and 1–DT was presented. The best capturing efficiency of E. coli was achieved with the mixed monolayer of 3–MBA and 1–DT-modified nanoparticles. Molecular specificity and selectivity were also demonstrated by comparing the surface-enhanced Raman scattering (SERS) spectrum of E. coli-nanoparticle conjugates with bacterial growth media. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
Open AccessArticle Adsorption and Orientation of Human Islet Amyloid Polypeptide (hIAPP) Monomer at Anionic Lipid Bilayers: Implications for Membrane-Mediated Aggregation
Int. J. Mol. Sci. 2013, 14(3), 6241-6258; doi:10.3390/ijms14036241
Received: 18 February 2013 / Revised: 11 March 2013 / Accepted: 12 March 2013 / Published: 19 March 2013
Cited by 13 | PDF Full-text (1822 KB) | HTML Full-text | XML Full-text
Abstract
Protein misfolding and aggregation cause serious degenerative diseases, such as Alzheimer’s and type II diabetes. Human islet amyloid polypeptide (hIAPP) is the major component of amyloid deposits found in the pancreas of type II diabetic patients. Increasing evidence suggests that β-cell death is
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Protein misfolding and aggregation cause serious degenerative diseases, such as Alzheimer’s and type II diabetes. Human islet amyloid polypeptide (hIAPP) is the major component of amyloid deposits found in the pancreas of type II diabetic patients. Increasing evidence suggests that β-cell death is related to the interaction of hIAPP with the cellular membrane, which accelerates peptide aggregation. In this study, as a first step towards understanding the membrane-mediated hIAPP aggregation, we investigate the atomic details of the initial step of hIAPP-membrane interaction, including the adsorption orientation and conformation of hIAPP monomer at an anionic POPG lipid bilayer by performing all-atom molecular dynamics simulations. We found that hIAPP monomer is quickly adsorbed to bilayer surface, and the adsorption is initiated from the N-terminal residues driven by strong electrostatic interactions of the positively-charged residues K1 and R11 with negatively-charged lipid headgroups. hIAPP binds parallel to the lipid bilayer surface as a stable helix through residues 7–22, consistent with previous experimental study. Remarkably, different simulations lead to the same binding orientation stabilized by electrostatic and H-bonding interactions, with residues R11, F15 and S19 oriented towards membrane and hydrophobic residues L12, A13, L16 and V17 exposed to solvent. Implications for membrane-mediated hIAPP aggregation are discussed. Full article
(This article belongs to the collection Protein Folding)
Open AccessArticle Abnormal Skeletal Growth in Adolescent Idiopathic Scoliosis Is Associated with Abnormal Quantitative Expression of Melatonin Receptor, MT2
Int. J. Mol. Sci. 2013, 14(3), 6345-6358; doi:10.3390/ijms14036345
Received: 7 January 2013 / Revised: 13 March 2013 / Accepted: 13 March 2013 / Published: 19 March 2013
Cited by 5 | PDF Full-text (531 KB) | HTML Full-text | XML Full-text
Abstract
The defect of the melatonin signaling pathway has been proposed to be one of the key etiopathogenic factors in adolescent idiopathic scoliosis (AIS). A previous report showed that melatonin receptor, MT2, was undetectable in some AIS girls. The present study aimed to investigate
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The defect of the melatonin signaling pathway has been proposed to be one of the key etiopathogenic factors in adolescent idiopathic scoliosis (AIS). A previous report showed that melatonin receptor, MT2, was undetectable in some AIS girls. The present study aimed to investigate whether the abnormal MT2 expression in AIS is quantitative or qualitative. Cultured osteoblasts were obtained from 41 AIS girls and nine normal controls. Semi-quantification of protein expression by Western blot and mRNA expression by TaqMan real-time PCR for both MT1 and MT2 were performed. Anthropometric parameters were also compared and correlated with the protein expression and mRNA expression of the receptors. The results showed significantly lower protein and mRNA expression of MT2 in AIS girls compared with that in normal controls (p = 0.02 and p = 0.019, respectively). No differences were found in the expression of MT1. When dichotomizing the AIS girls according to their MT2 expression, the group with low expression was found to have a significantly longer arm span (p = 0.036). The results of this study showed for the first time a quantitative change of MT2 in AIS that was also correlated with abnormal arm span as part of abnormal systemic skeletal growth. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessArticle Thermostable Mismatch-Recognizing Protein MutS Suppresses Nonspecific Amplification during Polymerase Chain Reaction (PCR)
Int. J. Mol. Sci. 2013, 14(3), 6436-6453; doi:10.3390/ijms14036436
Received: 31 January 2013 / Revised: 28 February 2013 / Accepted: 11 March 2013 / Published: 21 March 2013
Cited by 5 | PDF Full-text (2137 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polymerase chain reaction (PCR)-related technologies are hampered mainly by two types of error: nonspecific amplification and DNA polymerase-generated mutations. Here, we report that both errors can be suppressed by the addition of a DNA mismatch-recognizing protein, MutS, from a thermophilic bacterium. Although it
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Polymerase chain reaction (PCR)-related technologies are hampered mainly by two types of error: nonspecific amplification and DNA polymerase-generated mutations. Here, we report that both errors can be suppressed by the addition of a DNA mismatch-recognizing protein, MutS, from a thermophilic bacterium. Although it had been expected that MutS has a potential to suppress polymerase-generated mutations, we unexpectedly found that it also reduced nonspecific amplification. On the basis of this finding, we propose that MutS binds a mismatched primer-template complex, thereby preventing the approach of DNA polymerase to the 3' end of the primer. Our simple methodology improves the efficiency and accuracy of DNA amplification and should therefore benefit various PCR-based applications, ranging from basic biological research to applied medical science. Full article
(This article belongs to the Special Issue Molecular Cut and Paste)
Open AccessArticle Differential Expression of Genes Associated with the Progression of Renal Disease in the Kidneys of Liver-Specific Glucokinase Gene Knockout Mice
Int. J. Mol. Sci. 2013, 14(3), 6467-6486; doi:10.3390/ijms14036467
Received: 30 January 2013 / Revised: 18 March 2013 / Accepted: 19 March 2013 / Published: 21 March 2013
Cited by 2 | PDF Full-text (2226 KB) | HTML Full-text | XML Full-text
Abstract
Liver glucokinase (GCK) deficient mice possess mild renal complications associated with diabetes. To investigate the progression of kidney disease and identify candidate genes involved in the pathogenesis of renal damage, we examined changes in tissue structure and gene expression in the kidneys of
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Liver glucokinase (GCK) deficient mice possess mild renal complications associated with diabetes. To investigate the progression of kidney disease and identify candidate genes involved in the pathogenesis of renal damage, we examined changes in tissue structure and gene expression in the kidneys of liver-specific GCK knockout (gckw/−) mice and age-matched normal wild-type control (gckw/w) mice as they aged. Suppression subtractive hybridization (SSH) was used to identify candidate genes that showed a pattern of differential expression between kidneys of gckw/− and gckw/w mice at 60 weeks of age. Differential expression of the candidate genes was examined by real-time qPCR in liver-specific gckw/− and gckw/w mice at 16, 26, 40, 60, and 85 weeks of age. Among the candidate genes, only glutathione peroxidase-3 (GPX3) was confirmed to show differential expression by qPCR in the 60-week old mice, however two others genes, MALAT1 and KEG, showed significant changes at other ages. This study shows that liver-specific glucokinase deficient mice display changes in kidney morphology by 40 weeks of age, and that renal complication may be correlated with a reduction in GPX3 levels. Since decreased GPX3 mRNA expression was observed at 26 weeks, which is younger than the age when pathological changes can be seen in kidney biopsies, GPX3 may serve as an early marker for kidney damage. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
Open AccessArticle Preparation of a Paeonol-Containing Temperature-Sensitive In Situ Gel and Its Preliminary Efficacy on Allergic Rhinitis
Int. J. Mol. Sci. 2013, 14(3), 6499-6515; doi:10.3390/ijms14036499
Received: 10 October 2012 / Revised: 25 February 2013 / Accepted: 26 February 2013 / Published: 22 March 2013
Cited by 5 | PDF Full-text (4682 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, the optimal composition of a paeonol temperature-sensitive in situ gel composed of poloxamer 407 (P407) was determined, and a preliminary study of its effect on allergic rhinitis was performed. The optimal composition of the paeonol temperature-sensitive in situ gel included
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In this paper, the optimal composition of a paeonol temperature-sensitive in situ gel composed of poloxamer 407 (P407) was determined, and a preliminary study of its effect on allergic rhinitis was performed. The optimal composition of the paeonol temperature-sensitive in situ gel included 2% paeonol inclusion, 22% P407, 2% poloxamer 188 (P188) and 2% PEG6000, as assessed by thermodynamic and rheological studies. The toad palate model was employed to study the toxicity of the paeonol temperature-sensitive in situ gel on the nasal mucosa. The result of this experiment showed low toxicity to cilia, which allows the gel to be used for nasal administration. The Franz diffusion cell method was used to study the in vitro release of paeonol and suggested that the in vitro release was in line with the Higuchi equation. This result suggests that the paeonol could be absorbed into the body through mucous membranes and had some characteristics of a sustained effect. Finally, the guinea pig model of ovalbumin sensitized allergic rhinitis was used to evaluate the preliminary efficacy of the gel, with the paeonol temperature-sensitive in situ gel showing a significant effect on the guinea pig model of sensitized allergic rhinitis (AR). Full article
Open AccessArticle Identification of Amplified Fragment Length Polymorphism (AFLP) Markers Tightly Associated with Drought Stress Gene in Male Sterile and Fertile Salvia miltiorrhiza Bunge
Int. J. Mol. Sci. 2013, 14(3), 6518-6528; doi:10.3390/ijms14036518
Received: 28 January 2013 / Revised: 22 February 2013 / Accepted: 25 February 2013 / Published: 22 March 2013
Cited by 1 | PDF Full-text (1133 KB) | HTML Full-text | XML Full-text
Abstract
Consistent grain yield in drought environment has attracted wide attention due to global climate change. However, the important drought-related traits/genes in crops have been rarely reported. Many near-isogenic lines (NILs) of male sterile and fertile Salvia miltiorrhiza have been obtained in our previous
[...] Read more.
Consistent grain yield in drought environment has attracted wide attention due to global climate change. However, the important drought-related traits/genes in crops have been rarely reported. Many near-isogenic lines (NILs) of male sterile and fertile Salvia miltiorrhiza have been obtained in our previous work through testcross and backcross in continuous field experiments conducted in 2006–2009. Both segregating sterile and fertile populations were subjected to bulked segregant analysis (BSA) and amplified fragment length polymorphism (AFLP) with 384 and 170 primer combinations, respectively. One out of 14 AFLP markers (E9/M3246) was identified in treated fertile population as tightly linked to the drought stress gene with a recombination frequency of 6.98% and at a distance of 7.02 cM. One of 15 other markers (E2/M5357) was identified in a treated sterile population that is closely associated with the drought stress gene. It had a recombination frequency of 4.65% and at a distance of 4.66 cM. Interestingly, the E9/M3246 fragment was found to be identical to another AFLP fragment E11/M4208 that was tightly linked to the male sterile gene of S. miltiorrhiza with 95% identity and e-value 4 × 10−93. Blastn analysis suggested that the drought stress gene sequence showed higher identity with nucleotides in Arabidopsis chromosome 1–5. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)

Review

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Open AccessReview The Apolipoprotein M–Sphingosine-1-Phosphate Axis: Biological Relevance in Lipoprotein Metabolism, Lipid Disorders and Atherosclerosis
Int. J. Mol. Sci. 2013, 14(3), 4419-4431; doi:10.3390/ijms14034419
Received: 5 December 2012 / Revised: 17 January 2013 / Accepted: 5 February 2013 / Published: 25 February 2013
Cited by 11 | PDF Full-text (213 KB) | HTML Full-text | XML Full-text
Abstract
Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. ApoM
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Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. ApoM was identified as a carrier of the bioactive lipid sphingosine-1-phosphate (S1P). S1P activates five different G-protein-coupled receptors, known as the S1P-receptors 1–5 and, hence, affects a wide range of biological processes, such as lymphocyte trafficking, angiogenesis, wound repair and even virus suppression and cancer. The ability of apoM to bind S1P is due to a lipophilic binding pocket within the lipocalin structure of the apoM molecule. Mice overexpressing apoM have increased plasma S1P concentrations, whereas apoM-deficient mice have decreased S1P levels. ApoM-S1P is able to activate the S1P-receptor-1, affecting the function of endothelial cells, and apoM-deficient mice display impaired endothelial permeability in the lung. This review will focus on the putative biological roles of the new apoM–S1P axis in relation to lipoprotein metabolism, lipid disorders and atherosclerosis. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
Open AccessReview From Identification to Characterization of the Multiple Sclerosis Susceptibility Gene CLEC16A
Int. J. Mol. Sci. 2013, 14(3), 4476-4497; doi:10.3390/ijms14034476
Received: 16 January 2013 / Revised: 5 February 2013 / Accepted: 15 February 2013 / Published: 25 February 2013
Cited by 11 | PDF Full-text (480 KB) | HTML Full-text | XML Full-text
Abstract
Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals, probably triggered by common environmental factors. Human leukocyte antigen (HLA) loci were early shown to confer the strongest genetic associations in MS. Now, more
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Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals, probably triggered by common environmental factors. Human leukocyte antigen (HLA) loci were early shown to confer the strongest genetic associations in MS. Now, more than 50 non-HLA MS susceptibility loci are identified, of which the majority are located in immune-regulatory genes. Single nucleotide polymorphisms (SNPs) in the C-type lectin-like domain family 16A (CLEC16A) gene were among the first non-HLA genetic variants that were confirmed to be associated with MS. Fine-mapping has indicated a primary association in MS and also other autoimmune diseases to intronic CLEC16A SNPs. Here, we review the identification of MS susceptibility variants in the CLEC16A gene region, functional studies of the CLEC16A molecule and the recent progress in understanding the implications thereof for MS development. This may serve as an example of the importance for further molecular investigation of the loci identified in genetic studies, with the aim to translate this knowledge into the clinic. Full article
(This article belongs to the Special Issue Recent Advances in the Research of Multiple Sclerosis)
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Open AccessReview Small Regulatory RNAs in the Control of Motility and Biofilm Formation in E. coli and Salmonella
Int. J. Mol. Sci. 2013, 14(3), 4560-4579; doi:10.3390/ijms14034560
Received: 18 January 2013 / Revised: 10 February 2013 / Accepted: 16 February 2013 / Published: 26 February 2013
Cited by 45 | PDF Full-text (990 KB) | HTML Full-text | XML Full-text
Abstract
Biofilm formation in Escherichia coli and other enteric bacteria involves the inverse regulation of the synthesis of flagella and biofilm matrix components such as amyloid curli fibres, cellulose, colanic acid and poly-N-acetylglucosamine (PGA). Physiologically, these processes reflect the transition from growth
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Biofilm formation in Escherichia coli and other enteric bacteria involves the inverse regulation of the synthesis of flagella and biofilm matrix components such as amyloid curli fibres, cellulose, colanic acid and poly-N-acetylglucosamine (PGA). Physiologically, these processes reflect the transition from growth to stationary phase. At the molecular level, they are tightly controlled by various sigma factors competing for RNA polymerase, a series of transcription factors acting in hierarchical regulatory cascades and several nucleotide messengers, including cyclic-di-GMP. In addition, a surprisingly large number of small regulatory RNAs (sRNAs) have been shown to directly or indirectly modulate motility and/or biofilm formation. This review aims at giving an overview of these sRNA regulators and their impact in biofilm formation in E. coli and Salmonella. Special emphasis will be put on sRNAs, that have known targets such as the mRNAs of the flagellar master regulator FlhDC, the stationary phase sigma factor σS (RpoS) and the key biofilm regulator CsgD that have recently been shown to act as major hubs for regulation by multiple sRNAs. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessReview Atypical Protein Phosphatases: Emerging Players in Cellular Signaling
Int. J. Mol. Sci. 2013, 14(3), 4596-4612; doi:10.3390/ijms14034596
Received: 25 January 2013 / Revised: 18 February 2013 / Accepted: 20 February 2013 / Published: 26 February 2013
Cited by 8 | PDF Full-text (1117 KB) | HTML Full-text | XML Full-text
Abstract
It has generally been considered that protein phosphatases have more diverse catalytic domain structures and mechanisms than protein kinases; however, gene annotation efforts following the human genome project appeared to have completed the whole array of protein phosphatases. Ser/Thr phosphatases are divided into
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It has generally been considered that protein phosphatases have more diverse catalytic domain structures and mechanisms than protein kinases; however, gene annotation efforts following the human genome project appeared to have completed the whole array of protein phosphatases. Ser/Thr phosphatases are divided into three subfamilies that have different structures from each other, whereas Tyr phosphatases and dual-specificity phosphatases targeting Tyr, Ser and Thr belong to a single large family based on their common structural features. Several years of research have revealed, however, the existence of unexpected proteins, designated here as “atypical protein phosphatases”, that have structural and enzymatic features different from those of the known protein phosphatases and are involved in important biological processes. In this review, we focus on the identification and functional characterization of atypical protein phosphatases, represented by eyes absent (EYA), suppressor of T-cell receptor signaling (Sts) and phosphoglycerate mutase family member 5 (PGAM5) and discuss their biological significance in cellular signaling. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
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Open AccessReview Long Non-Coding RNA in Cancer
Int. J. Mol. Sci. 2013, 14(3), 4655-4669; doi:10.3390/ijms14034655
Received: 1 November 2012 / Revised: 3 January 2013 / Accepted: 31 January 2013 / Published: 26 February 2013
Cited by 81 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. LncRNAs are deregulated in a number of cancers, demonstrating both oncogenic
[...] Read more.
Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. LncRNAs are deregulated in a number of cancers, demonstrating both oncogenic and tumor suppressive roles, thus suggesting their aberrant expression may be a substantial contributor in cancer development. In this review, we will summarize their emerging role in human cancer and discuss their perspectives in diagnostics as potential biomarkers. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Open AccessReview Regulation of Translation Initiation under Biotic and Abiotic Stresses
Int. J. Mol. Sci. 2013, 14(3), 4670-4683; doi:10.3390/ijms14034670
Received: 15 January 2013 / Revised: 20 February 2013 / Accepted: 20 February 2013 / Published: 26 February 2013
Cited by 11 | PDF Full-text (194 KB) | HTML Full-text | XML Full-text
Abstract
Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges,
[...] Read more.
Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessReview Interplay between Hepatitis C Virus and Redox Cell Signaling
Int. J. Mol. Sci. 2013, 14(3), 4705-4721; doi:10.3390/ijms14034705
Received: 17 January 2013 / Revised: 13 February 2013 / Accepted: 17 February 2013 / Published: 26 February 2013
Cited by 8 | PDF Full-text (242 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis C virus (HCV) infects approximately 3% of the world’s population. Currently licensed treatment of HCV chronic infection with pegylated-interferon-α and ribavirin, is not fully effective against all HCV genotypes and is associated to severe side effects. Thus, development of novel therapeutics and
[...] Read more.
Hepatitis C virus (HCV) infects approximately 3% of the world’s population. Currently licensed treatment of HCV chronic infection with pegylated-interferon-α and ribavirin, is not fully effective against all HCV genotypes and is associated to severe side effects. Thus, development of novel therapeutics and identification of new targets for treatment of HCV infection is necessary. Current opinion is orienting to target antiviral drug discovery to the host cell pathways on which the virus relies, instead of against viral structures. Many intracellular signaling pathways manipulated by HCV for its own replication are finely regulated by the oxido-reductive (redox) state of the host cell. At the same time, HCV induces oxidative stress that has been found to affect both virus replication as well as progression and severity of HCV infection. A dual role, positive or negative, for the host cell oxidized conditions on HCV replication has been reported so far. This review examines current information about the effect of oxidative stress on HCV life cycle and the main redox-regulated intracellular pathways activated during HCV infection and involved in its replication. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
Open AccessReview Low Oxygen Response Mechanisms in Green Organisms
Int. J. Mol. Sci. 2013, 14(3), 4734-4761; doi:10.3390/ijms14034734
Received: 29 January 2013 / Revised: 20 February 2013 / Accepted: 21 February 2013 / Published: 27 February 2013
Cited by 22 | PDF Full-text (872 KB) | HTML Full-text | XML Full-text
Abstract
Low oxygen stress often occurs during the life of green organisms, mostly due to the environmental conditions affecting oxygen availability. Both plants and algae respond to low oxygen by resetting their metabolism. The shift from mitochondrial respiration to fermentation is the hallmark of
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Low oxygen stress often occurs during the life of green organisms, mostly due to the environmental conditions affecting oxygen availability. Both plants and algae respond to low oxygen by resetting their metabolism. The shift from mitochondrial respiration to fermentation is the hallmark of anaerobic metabolism in most organisms. This involves a modified carbohydrate metabolism coupled with glycolysis and fermentation. For a coordinated response to low oxygen, plants exploit various molecular mechanisms to sense when oxygen is either absent or in limited amounts. In Arabidopsis thaliana, a direct oxygen sensing system has recently been discovered, where a conserved N-terminal motif on some ethylene responsive factors (ERFs), targets the fate of the protein under normoxia/hypoxia. In Oryza sativa, this same group of ERFs drives physiological and anatomical modifications that vary in relation to the genotype studied. The microalga Chlamydomonas reinhardtii responses to low oxygen seem to have evolved independently of higher plants, posing questions on how the fermentative metabolism is modulated. In this review, we summarize the most recent findings related to these topics, highlighting promising developments for the future. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessReview Mitogen-Activated Protein (MAP) Kinase Scaffolding Proteins: A Recount
Int. J. Mol. Sci. 2013, 14(3), 4854-4884; doi:10.3390/ijms14034854
Received: 21 January 2013 / Revised: 17 February 2013 / Accepted: 21 February 2013 / Published: 1 March 2013
Cited by 20 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text
Abstract
The mitogen-activated protein kinase (MAPK) pathway is the canonical signaling pathway for many receptor tyrosine kinases, such as the Epidermal Growth Factor Receptor. Downstream of the receptors, this pathway involves the activation of a kinase cascade that culminates in a transcriptional response and
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The mitogen-activated protein kinase (MAPK) pathway is the canonical signaling pathway for many receptor tyrosine kinases, such as the Epidermal Growth Factor Receptor. Downstream of the receptors, this pathway involves the activation of a kinase cascade that culminates in a transcriptional response and affects processes, such as cell migration and adhesion. In addition, the strength and duration of the upstream signal also influence the mode of the cellular response that is switched on. Thus, the same components can in principle coordinate opposite responses, such as proliferation and differentiation. In recent years, it has become evident that MAPK signaling is regulated and fine-tuned by proteins that can bind to several MAPK signaling proteins simultaneously and, thereby, affect their function. These so-called MAPK scaffolding proteins are, thus, important coordinators of the signaling response in cells. In this review, we summarize the recent advances in the research on MAPK/extracellular signal-regulated kinase (ERK) pathway scaffolders. We will not only review the well-known members of the family, such as kinase suppressor of Ras (KSR), but also put a special focus on the function of the recently identified or less studied scaffolders, such as fibroblast growth factor receptor substrate 2, flotillin-1 and mitogen-activated protein kinase organizer 1. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview Metabolomics as a Tool to Investigate Abiotic Stress Tolerance in Plants
Int. J. Mol. Sci. 2013, 14(3), 4885-4911; doi:10.3390/ijms14034885
Received: 31 December 2012 / Revised: 18 February 2013 / Accepted: 20 February 2013 / Published: 1 March 2013
Cited by 66 | PDF Full-text (527 KB) | HTML Full-text | XML Full-text
Abstract
Metabolites reflect the integration of gene expression, protein interaction and other different regulatory processes and are therefore closer to the phenotype than mRNA transcripts or proteins alone. Amongst all –omics technologies, metabolomics is the most transversal and can be applied to different organisms
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Metabolites reflect the integration of gene expression, protein interaction and other different regulatory processes and are therefore closer to the phenotype than mRNA transcripts or proteins alone. Amongst all –omics technologies, metabolomics is the most transversal and can be applied to different organisms with little or no modifications. It has been successfully applied to the study of molecular phenotypes of plants in response to abiotic stress in order to find particular patterns associated to stress tolerance. These studies have highlighted the essential involvement of primary metabolites: sugars, amino acids and Krebs cycle intermediates as direct markers of photosynthetic dysfunction as well as effectors of osmotic readjustment. On the contrary, secondary metabolites are more specific of genera and species and respond to particular stress conditions as antioxidants, Reactive Oxygen Species (ROS) scavengers, coenzymes, UV and excess radiation screen and also as regulatory molecules. In addition, the induction of secondary metabolites by several abiotic stress conditions could also be an effective mechanism of cross-protection against biotic threats, providing a link between abiotic and biotic stress responses. Moreover, the presence/absence and relative accumulation of certain metabolites along with gene expression data provides accurate markers (mQTL or MWAS) for tolerant crop selection in breeding programs. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
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Open AccessReview Non-Coding RNAs: Functional Aspects and Diagnostic Utility in Oncology
Int. J. Mol. Sci. 2013, 14(3), 4934-4968; doi:10.3390/ijms14034934
Received: 10 December 2012 / Revised: 9 February 2013 / Accepted: 18 February 2013 / Published: 1 March 2013
Cited by 18 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text
Abstract
Noncoding RNAs (ncRNAs) have been found to have roles in a large variety of biological processes. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined, holding great promise for use in diagnostic, prognostic, and therapeutic applications. Within ncRNAs,
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Noncoding RNAs (ncRNAs) have been found to have roles in a large variety of biological processes. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined, holding great promise for use in diagnostic, prognostic, and therapeutic applications. Within ncRNAs, microRNAs (miRNAs) are the most widely studied and characterized. They have been implicated in initiation and progression of a variety of human malignancies, including major pathologies such as cancers, arthritis, neurodegenerative disorders, and cardiovascular diseases. Their surprising stability in serum and other bodily fluids led to their rapid ascent as a novel class of biomarkers. For example, several properties of stable miRNAs, and perhaps other classes of ncRNAs, make them good candidate biomarkers for early cancer detection and for determining which preneoplastic lesions are likely to progress to cancer. Of particular interest is the identification of biomarker signatures, which may include traditional protein-based biomarkers, to improve risk assessment, detection, and prognosis. Here, we offer a comprehensive review of the ncRNA biomarker literature and discuss state-of-the-art technologies for their detection. Furthermore, we address the challenges present in miRNA detection and quantification, and outline future perspectives for development of next-generation biodetection assays employing multicolor alternating-laser excitation (ALEX) fluorescence spectroscopy. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
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Open AccessReview p53 and Ceramide as Collaborators in the Stress Response
Int. J. Mol. Sci. 2013, 14(3), 4982-5012; doi:10.3390/ijms14034982
Received: 26 December 2012 / Revised: 22 January 2013 / Accepted: 1 February 2013 / Published: 1 March 2013
Cited by 9 | PDF Full-text (3569 KB) | HTML Full-text | XML Full-text
Abstract
The sphingolipid ceramide mediates various cellular processes in response to several extracellular stimuli. Some genotoxic stresses are able to induce p53-dependent ceramide accumulation leading to cell death. However, in other cases, in the absence of the tumor suppressor protein p53, apoptosis proceeds partly
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The sphingolipid ceramide mediates various cellular processes in response to several extracellular stimuli. Some genotoxic stresses are able to induce p53-dependent ceramide accumulation leading to cell death. However, in other cases, in the absence of the tumor suppressor protein p53, apoptosis proceeds partly due to the activity of this “tumor suppressor lipid”, ceramide. In the current review, we describe ceramide and its roles in signaling pathways such as cell cycle arrest, hypoxia, hyperoxia, cell death, and cancer. In a specific manner, we are elaborating on the role of ceramide in mitochondrial apoptotic cell death signaling. Furthermore, after highlighting the role and mechanism of action of p53 in apoptosis, we review the association of ceramide and p53 with respect to apoptosis. Strikingly, the hypothesis for a direct interaction between ceramide and p53 is less favored. Recent data suggest that ceramide can act either upstream or downstream of p53 protein through posttranscriptional regulation or through many potential mediators, respectively. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases)
Open AccessReview Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations
Int. J. Mol. Sci. 2013, 14(3), 5036-5129; doi:10.3390/ijms14035036
Received: 4 December 2012 / Revised: 24 January 2013 / Accepted: 25 January 2013 / Published: 1 March 2013
Cited by 13 | PDF Full-text (1156 KB) | HTML Full-text | XML Full-text
Abstract
The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are
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The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are likely to take place in tissues other than in bones and teeth under specific pathological conditions. For instance, vascular calcification in arteries of patients with renal failure, diabetes mellitus or atherosclerosis recapitulates the mechanisms of bone formation. Osteoporosis—a bone resorbing disease—and rheumatoid arthritis originating from the inflammation in the synovium are also affected by cellular lipid metabolism. The focus is on the lipid metabolism due to the effects of dietary lipids on bone health. These and other phenomena indicate that phospholipases may participate in bone remodelling as evidenced by their expression in smooth muscle cells, in bone forming osteoblasts, chondrocytes and in bone resorbing osteoclasts. Among various enzymes involved, phospholipases A1 or A2, phospholipase C, phospholipase D, autotaxin and sphingomyelinase are engaged in membrane lipid remodelling during early stages of mineralization and cell maturation in mineralization-competent cells. Numerous experimental evidences suggested that phospholipases exert their action at various stages of mineralization by affecting intracellular signaling and cell differentiation. The lipid metabolites—such as arachidonic acid, lysophospholipids, and sphingosine-1-phosphate are involved in cell signaling and inflammation reactions. Phospholipases are also important members of the cellular machinery engaged in matrix vesicle (MV) biogenesis and exocytosis. They may favour mineral formation inside MVs, may catalyse MV membrane breakdown necessary for the release of mineral deposits into extracellular matrix (ECM), or participate in hydrolysis of ECM. The biological functions of phospholipases are discussed from the perspective of animal and cellular knockout models, as well as disease implications, development of potent inhibitors and therapeutic interventions. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
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Open AccessReview Wnt Secretion and Gradient Formation
Int. J. Mol. Sci. 2013, 14(3), 5130-5145; doi:10.3390/ijms14035130
Received: 31 January 2013 / Revised: 20 February 2013 / Accepted: 22 February 2013 / Published: 1 March 2013
Cited by 10 | PDF Full-text (1373 KB) | HTML Full-text | XML Full-text
Abstract
Concentration gradients formed by the lipid-modified morphogens of the Wnt family are known for their pivotal roles during embryogenesis and adult tissue homeostasis. Wnt morphogens are also implicated in a variety of human diseases, especially cancer. Therefore, the signaling cascades triggered by Wnts
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Concentration gradients formed by the lipid-modified morphogens of the Wnt family are known for their pivotal roles during embryogenesis and adult tissue homeostasis. Wnt morphogens are also implicated in a variety of human diseases, especially cancer. Therefore, the signaling cascades triggered by Wnts have received considerable attention during recent decades. However, how Wnts are secreted and how concentration gradients are formed remains poorly understood. The use of model organisms such as Drosophila melanogaster has provided important advances in this area. For instance, we have previously shown that the lipid raft-associated reggie/flotillin proteins influence Wnt secretion and spreading in Drosophila. Our work supports the notion that producing cells secrete Wnt molecules in at least two pools: a poorly diffusible one and a reggie/flotillin-dependent highly diffusible pool which allows morphogen spreading over long distances away from its source of production. Here we revise the current views of Wnt secretion and spreading, and propose two models for the role of the reggie/flotillin proteins in these processes: (i) reggies/flotillins regulate the basolateral endocytosis of the poorly diffusible, membrane-bound Wnt pool, which is then sorted and secreted to apical compartments for long-range diffusion, and (ii) lipid rafts organized by reggies/flotillins serve as “dating points” where extracellular Wnt transiently interacts with lipoprotein receptors to allow its capture and further spreading via lipoprotein particles. We further discuss these processes in the context of human breast cancer. A better understanding of these phenomena may be relevant for identification of novel drug targets and therapeutic strategies. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview Caffeic Acid Phenethyl Ester as a Potential Treatment for Advanced Prostate Cancer Targeting Akt Signaling
Int. J. Mol. Sci. 2013, 14(3), 5264-5283; doi:10.3390/ijms14035264
Received: 30 January 2013 / Revised: 19 February 2013 / Accepted: 28 February 2013 / Published: 6 March 2013
Cited by 11 | PDF Full-text (692 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the fifth most common cancer overall in the world. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, most prostate cancer patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant tumors within 1–3 years after treatment.
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Prostate cancer is the fifth most common cancer overall in the world. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, most prostate cancer patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant tumors within 1–3 years after treatment. The median overall survival time is 1–2 years after tumor relapse. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling, indicating that inhibition of PI3K/Akt might be a potential therapy for advanced prostate tumors. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. CAPE is a well-known NF-κB inhibitor. CAPE has been used in folk medicine as a potent anti-inflammatory agent. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. We discuss the potential of using CAPE as a treatment for patients with advanced prostate cancer targeting Akt signaling pathway in this review article. Full article
Open AccessReview Cold Signaling and Cold Response in Plants
Int. J. Mol. Sci. 2013, 14(3), 5312-5337; doi:10.3390/ijms14035312
Received: 31 January 2013 / Revised: 26 February 2013 / Accepted: 26 February 2013 / Published: 6 March 2013
Cited by 73 | PDF Full-text (473 KB) | HTML Full-text | XML Full-text
Abstract
Plants are constantly exposed to a variety of environmental stresses. Freezing or extremely low temperature constitutes a key factor influencing plant growth, development and crop productivity. Plants have evolved a mechanism to enhance tolerance to freezing during exposure to periods of low, but
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Plants are constantly exposed to a variety of environmental stresses. Freezing or extremely low temperature constitutes a key factor influencing plant growth, development and crop productivity. Plants have evolved a mechanism to enhance tolerance to freezing during exposure to periods of low, but non-freezing temperatures. This phenomenon is called cold acclimation. During cold acclimation, plants develop several mechanisms to minimize potential damages caused by low temperature. Cold response is highly complex process that involves an array of physiological and biochemical modifications. Furthermore, alterations of the expression patterns of many genes, proteins and metabolites in response to cold stress have been reported. Recent studies demonstrate that post-transcriptional and post-translational regulations play a role in the regulation of cold signaling. In this review article, recent advances in cold stress signaling and tolerance are highlighted. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessReview Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications
Int. J. Mol. Sci. 2013, 14(3), 5338-5366; doi:10.3390/ijms14035338
Received: 29 January 2013 / Revised: 25 February 2013 / Accepted: 28 February 2013 / Published: 6 March 2013
Cited by 60 | PDF Full-text (495 KB) | HTML Full-text | XML Full-text
Abstract
Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell
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Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years, however, a considerable amount of experimental evidence has demonstrated the occurrence of a sophisticated method of cell communication based on the release of specialized membranous nano-sized vesicles termed exosomes. Exosome biogenesis involves the endosomal compartment, the multivesicular bodies (MVB), which contain internal vesicles packed with an extraordinary set of molecules including enzymes, cytokines, nucleic acids and different bioactive compounds. In response to stimuli, MVB fuse with the plasma membrane and vesicles are released in the extracellular space where they can interact with neighboring cells and directly induce a signaling pathway or affect the cellular phenotype through the transfer of new receptors or even genetic material. This review will focus on exosomes as intercellular signaling organelles involved in a number of physiological as well as pathological processes and their potential use in clinical diagnostics and therapeutics. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview Endometriosis-Associated Ovarian Cancer: A Review of Pathogenesis
Int. J. Mol. Sci. 2013, 14(3), 5367-5379; doi:10.3390/ijms14035367
Received: 30 January 2013 / Revised: 21 February 2013 / Accepted: 26 February 2013 / Published: 6 March 2013
Cited by 44 | PDF Full-text (186 KB) | HTML Full-text | XML Full-text
Abstract
Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion,
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Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC). Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC) develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessReview Roles of Melatonin in Fetal Programming in Compromised Pregnancies
Int. J. Mol. Sci. 2013, 14(3), 5380-5401; doi:10.3390/ijms14035380
Received: 17 February 2013 / Revised: 25 February 2013 / Accepted: 25 February 2013 / Published: 6 March 2013
Cited by 22 | PDF Full-text (304 KB) | HTML Full-text | XML Full-text
Abstract
Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may
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Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessReview Mass Spectrometry-Based Proteomics for the Analysis of Chromatin Structure and Dynamics
Int. J. Mol. Sci. 2013, 14(3), 5402-5431; doi:10.3390/ijms14035402
Received: 7 November 2012 / Revised: 24 January 2013 / Accepted: 20 February 2013 / Published: 6 March 2013
Cited by 18 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
Chromatin is a highly structured nucleoprotein complex made of histone proteins and DNA that controls nearly all DNA-dependent processes. Chromatin plasticity is regulated by different associated proteins, post-translational modifications on histones (hPTMs) and DNA methylation, which act in a concerted manner to enforce
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Chromatin is a highly structured nucleoprotein complex made of histone proteins and DNA that controls nearly all DNA-dependent processes. Chromatin plasticity is regulated by different associated proteins, post-translational modifications on histones (hPTMs) and DNA methylation, which act in a concerted manner to enforce a specific “chromatin landscape”, with a regulatory effect on gene expression. Mass Spectrometry (MS) has emerged as a powerful analytical strategy to detect histone PTMs, revealing interplays between neighbouring PTMs and enabling screens for their readers in a comprehensive and quantitative fashion. Here we provide an overview of the recent achievements of state-of-the-art mass spectrometry-based proteomics for the detailed qualitative and quantitative characterization of histone post-translational modifications, histone variants, and global interactomes at specific chromatin regions. This synopsis emphasizes how the advances in high resolution MS, from “Bottom Up” to “Top Down” analysis, together with the uptake of quantitative proteomics methods by chromatin biologists, have made MS a well-established method in the epigenetics field, enabling the acquisition of original information, highly complementary to that offered by more conventional, antibody-based, assays. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessReview Understanding Resolvin Signaling Pathways to Improve Oral Health
Int. J. Mol. Sci. 2013, 14(3), 5501-5518; doi:10.3390/ijms14035501
Received: 31 December 2012 / Revised: 19 February 2013 / Accepted: 22 February 2013 / Published: 8 March 2013
Cited by 5 | PDF Full-text (540 KB) | HTML Full-text | XML Full-text
Abstract
The discovery of resolvins has been a major breakthrough for understanding the processes involved in resolution of inflammation. Resolvins belong to a family of novel lipid mediators that possess dual anti-inflammatory and pro-resolution actions. Specifically, they protect healthy tissue during immune-inflammatory responses to
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The discovery of resolvins has been a major breakthrough for understanding the processes involved in resolution of inflammation. Resolvins belong to a family of novel lipid mediators that possess dual anti-inflammatory and pro-resolution actions. Specifically, they protect healthy tissue during immune-inflammatory responses to infection or injury, thereby aiding inflammation resolution and promoting tissue healing. One of the major concerns in modern medicine is the management and treatment of oral diseases, as they are related to systemic outcomes impacting the quality of life of many patients. This review summarizes known signaling pathways utilized by resolvins to regulate inflammatory responses associated with the oral cavity. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview MicroRNAs in Human Placental Development and Pregnancy Complications
Int. J. Mol. Sci. 2013, 14(3), 5519-5544; doi:10.3390/ijms14035519
Received: 21 January 2013 / Revised: 26 February 2013 / Accepted: 4 March 2013 / Published: 8 March 2013
Cited by 36 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs, which function as critical posttranscriptional regulators of gene expression by promoting mRNA degradation and translational inhibition. Placenta expresses many ubiquitous as well as specific miRNAs. These miRNAs regulate trophoblast cell differentiation, proliferation, apoptosis, invasion/migration, and angiogenesis, suggesting
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MicroRNAs (miRNAs) are small non-coding RNAs, which function as critical posttranscriptional regulators of gene expression by promoting mRNA degradation and translational inhibition. Placenta expresses many ubiquitous as well as specific miRNAs. These miRNAs regulate trophoblast cell differentiation, proliferation, apoptosis, invasion/migration, and angiogenesis, suggesting that miRNAs play important roles during placental development. Aberrant miRNAs expression has been linked to pregnancy complications, such as preeclampsia. Recent research of placental miRNAs focuses on identifying placental miRNA species, examining differential expression of miRNAs between placentas from normal and compromised pregnancies, and uncovering the function of miRNAs in the placenta. More studies are required to further understand the functional significance of miRNAs in placental development and to explore the possibility of using miRNAs as biomarkers and therapeutic targets for pregnancy-related disorders. In this paper, we reviewed the current knowledge about the expression and function of miRNAs in placental development, and propose future directions for miRNA studies. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessReview Mirk/dyrk1B Kinase in Ovarian Cancer
Int. J. Mol. Sci. 2013, 14(3), 5560-5575; doi:10.3390/ijms14035560
Received: 29 January 2013 / Revised: 28 February 2013 / Accepted: 1 March 2013 / Published: 8 March 2013
Cited by 8 | PDF Full-text (4073 KB) | HTML Full-text | XML Full-text
Abstract
Mirk/dyrk1B kinase is expressed in about 75% of resected human ovarian cancers and in most ovarian cancer cell lines with amplification in the OVCAR3 line. Mirk (minibrain-related kinase) is a member of the Minibrain/dyrk family of related serine/threonine kinases. Mirk maintains cells in
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Mirk/dyrk1B kinase is expressed in about 75% of resected human ovarian cancers and in most ovarian cancer cell lines with amplification in the OVCAR3 line. Mirk (minibrain-related kinase) is a member of the Minibrain/dyrk family of related serine/threonine kinases. Mirk maintains cells in a quiescent state by stabilizing the CDK inhibitor p27 and by inducing the breakdown of cyclin D isoforms. Mirk also stabilizes the DREAM complex, which maintains G0 quiescence by sequestering transcription factors needed to enter cycle. By entering a quiescent state, tumor cells can resist the nutrient deficiencies, hypoxic and acidic conditions within the tumor mass. Mirk maintains the viability of quiescent ovarian cancer cells by reducing intracellular levels of reactive oxygen species. CDKN2A-negative ovarian cancer cells treated with a Mirk kinase inhibitor escaped G0/G1 quiescence, entered cycle with high ROS levels and underwent apoptosis. The ROS scavenger N-acetyl cysteine reduced the extent of cancer cell loss. In contrast, the Mirk kinase inhibitor slightly reduced the fraction of G0 quiescent diploid epithelial cells and fibroblasts, and the majority of the cells pushed into cycle accumulated in G2 + M. Apoptotic sub-G0/G1 cells were not detected. Thus, normal cells were spared because of their expression of CDK inhibitors that blocked unregulated cycling and Mirk kinase inhibitor-treated normal diploid cells were about as viable as untreated controls. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
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Open AccessReview MicroRNAs Involved in Anti-Tumour Immunity
Int. J. Mol. Sci. 2013, 14(3), 5587-5607; doi:10.3390/ijms14035587
Received: 30 October 2012 / Revised: 26 November 2012 / Accepted: 19 February 2013 / Published: 11 March 2013
Cited by 9 | PDF Full-text (262 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are a category of small RNAs that constitute a new layer of complexity to gene regulation within the cell, which has provided new perspectives in understanding cancer biology. The deregulation of miRNAs contributes critically to the development and pathophysiology of a
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MicroRNAs (miRNAs) are a category of small RNAs that constitute a new layer of complexity to gene regulation within the cell, which has provided new perspectives in understanding cancer biology. The deregulation of miRNAs contributes critically to the development and pathophysiology of a number of cancers. miRNAs have been found to participate in cell transformation and multiplication by acting as tumour oncogenes or suppressors; therefore, harnessing miRNAs may provide promising cancer therapeutics. Another major function of miRNAs is their activity as critical regulatory vehicles eliciting important regulatory processes in anti-tumour immunity through their influence on the development, differentiation and activation of various immune cells of both innate and adaptive immunity. This review aims to summarise recent findings focusing on the regulatory mechanisms of the development, differentiation, and proliferative aspects of the major immune populations by a diverse profile of miRNAs and may enrich our current understanding of the involvement of miRNAs in anti-tumour immunity. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessReview Structural Biology of a Major Signaling Network that Regulates Plant Abiotic Stress: The CBL-CIPK Mediated Pathway
Int. J. Mol. Sci. 2013, 14(3), 5734-5749; doi:10.3390/ijms14035734
Received: 31 January 2013 / Revised: 27 February 2013 / Accepted: 28 February 2013 / Published: 12 March 2013
Cited by 13 | PDF Full-text (2199 KB) | HTML Full-text | XML Full-text
Abstract
The Arabidopsis SOS2 family of twenty-six protein kinases (CIPKs), their interacting activators, the SOS3 family of ten calcium-binding proteins (CBLs) and protein phosphatases type 2C (PP2C), function together in decoding calcium signals elicited by different environmental stimuli. Biochemical data suggest that stable CBL-CIPK
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The Arabidopsis SOS2 family of twenty-six protein kinases (CIPKs), their interacting activators, the SOS3 family of ten calcium-binding proteins (CBLs) and protein phosphatases type 2C (PP2C), function together in decoding calcium signals elicited by different environmental stimuli. Biochemical data suggest that stable CBL-CIPK or CIPK-PP2C complexes may be regulating the activity of various substrates controlling ion homeostasis. The available structural information provides a general regulatory mechanism in which calcium perception by CBLs and kinase activation is coupled. The structural basis of this molecular mechanism and the specificity of the network is reviewed and discussed in detail. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
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Open AccessReview Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction
Int. J. Mol. Sci. 2013, 14(3), 5817-5841; doi:10.3390/ijms14035817
Received: 17 February 2013 / Revised: 1 March 2013 / Accepted: 4 March 2013 / Published: 12 March 2013
Cited by 8 | PDF Full-text (347 KB) | HTML Full-text | XML Full-text
Abstract
The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and
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The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organs, without necessarily involving the melatonin feedback to the suprachiasmatic nucleus. Experiments with melatonin-deficient mouse strains, pinealectomized animals and melatonin receptor knockouts, as well as phase-shifting experiments with explants, reveal a chronobiological role of melatonin in various tissues. In addition to directly steering melatonin-regulated gene expression, the pineal hormone is required for the rhythmic expression of circadian oscillator genes in peripheral organs and to enhance the coupling of parallel oscillators within the same tissue. It exerts additional effects by modulating the secretion of other hormones. The importance of melatonin for numerous organs is underlined by the association of various diseases with gene polymorphisms concerning melatonin receptors and the melatonin biosynthetic pathway. The possibilities and limits of melatonergic treatment are discussed with regard to reductions of melatonin during aging and in various diseases. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessReview Structure, Function and Networks of Transcription Factors Involved in Abiotic Stress Responses
Int. J. Mol. Sci. 2013, 14(3), 5842-5878; doi:10.3390/ijms14035842
Received: 4 February 2013 / Revised: 5 March 2013 / Accepted: 5 March 2013 / Published: 13 March 2013
Cited by 62 | PDF Full-text (2014 KB) | HTML Full-text | XML Full-text
Abstract
Transcription factors (TFs) are master regulators of abiotic stress responses in plants. This review focuses on TFs from seven major TF families, known to play functional roles in response to abiotic stresses, including drought, high salinity, high osmolarity, temperature extremes and the phytohormone
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Transcription factors (TFs) are master regulators of abiotic stress responses in plants. This review focuses on TFs from seven major TF families, known to play functional roles in response to abiotic stresses, including drought, high salinity, high osmolarity, temperature extremes and the phytohormone ABA. Although ectopic expression of several TFs has improved abiotic stress tolerance in plants, fine-tuning of TF expression and protein levels remains a challenge to avoid crop yield loss. To further our understanding of TFs in abiotic stress responses, emerging gene regulatory networks based on TFs and their direct targets genes are presented. These revealed components shared between ABA-dependent and independent signaling as well as abiotic and biotic stress signaling. Protein structure analysis suggested that TFs hubs of large interactomes have extended regions with protein intrinsic disorder (ID), referring to their lack of fixed tertiary structures. ID is now an emerging topic in plant science. Furthermore, the importance of the ubiquitin-proteasome protein degradation systems and modification by sumoylation is also apparent from the interactomes. Therefore; TF interaction partners such as E3 ubiquitin ligases and TF regions with ID represent future targets for engineering improved abiotic stress tolerance in crops. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessReview Functions and Mechanisms of Fibroblast Growth Factor (FGF) Signalling in Drosophila melanogaster
Int. J. Mol. Sci. 2013, 14(3), 5920-5937; doi:10.3390/ijms14035920
Received: 1 February 2013 / Revised: 5 March 2013 / Accepted: 12 March 2013 / Published: 14 March 2013
Cited by 11 | PDF Full-text (381 KB) | HTML Full-text | XML Full-text
Abstract
Intercellular signalling via growth factors plays an important role in controlling cell differentiation and cell movements during the development of multicellular animals. Fibroblast Growth Factor (FGF) signalling induces changes in cellular behaviour allowing cells in the embryo to move, to survive, to divide
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Intercellular signalling via growth factors plays an important role in controlling cell differentiation and cell movements during the development of multicellular animals. Fibroblast Growth Factor (FGF) signalling induces changes in cellular behaviour allowing cells in the embryo to move, to survive, to divide or to differentiate. Several examples argue that FGF signalling is used in multi-step morphogenetic processes to achieve and maintain a transitional state of the cells required for the control of cell fate. In the genetic model Drosophila melanogaster, FGF signalling via the receptor tyrosine kinases Heartless (Htl) and Breathless (Btl) is particularly well studied. These FGF receptors affect gene expression, cell shape and cell–cell interactions during mesoderm layer formation, caudal visceral muscle (CVM) formation, tracheal morphogenesis and glia differentiation. Here, we will address the current knowledge of the biological functions of FGF signalling in the fly on the tissue, at a cellular and molecular level. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
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Open AccessReview Integration of Multiple Signaling Pathways Determines Differences in the Osteogenic Potential and Tissue Regeneration of Neural Crest-Derived and Mesoderm-Derived Calvarial Bones
Int. J. Mol. Sci. 2013, 14(3), 5978-5997; doi:10.3390/ijms14035978
Received: 6 February 2013 / Revised: 5 March 2013 / Accepted: 12 March 2013 / Published: 15 March 2013
Cited by 7 | PDF Full-text (594 KB) | HTML Full-text | XML Full-text
Abstract
The mammalian skull vault, a product of a unique and tightly regulated evolutionary process, in which components of disparate embryonic origin are integrated, is an elegant model with which to study osteoblast biology. Our laboratory has demonstrated that this distinct embryonic origin of
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The mammalian skull vault, a product of a unique and tightly regulated evolutionary process, in which components of disparate embryonic origin are integrated, is an elegant model with which to study osteoblast biology. Our laboratory has demonstrated that this distinct embryonic origin of frontal and parietal bones confer differences in embryonic and postnatal osteogenic potential and skeletal regenerative capacity, with frontal neural crest derived osteoblasts benefitting from greater osteogenic potential. We outline how this model has been used to elucidate some of the molecular mechanisms which underlie these differences and place these findings into the context of our current understanding of the key, highly conserved, pathways which govern the osteoblast lineage including FGF, BMP, Wnt and TGFβ signaling. Furthermore, we explore recent studies which have provided a tantalizing insight into way these pathways interact, with evidence accumulating for certain transcription factors, such as Runx2, acting as a nexus for cross-talk. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview The Role of Metallothionein in Oxidative Stress
Int. J. Mol. Sci. 2013, 14(3), 6044-6066; doi:10.3390/ijms14036044
Received: 14 January 2013 / Revised: 14 February 2013 / Accepted: 20 February 2013 / Published: 15 March 2013
Cited by 99 | PDF Full-text (1712 KB) | HTML Full-text | XML Full-text
Abstract
Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can
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Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs) as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
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Open AccessReview Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)?
Int. J. Mol. Sci. 2013, 14(3), 6116-6143; doi:10.3390/ijms14036116
Received: 24 December 2012 / Revised: 4 February 2013 / Accepted: 20 February 2013 / Published: 18 March 2013
Cited by 57 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative
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Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative stress depends on the dose, duration and frequency of Cd exposure. Also the presence or absence of serum in experimental conditions, type of cells and their antioxidant capacity, as well as the speciation of Cd are important determinants. At the cellular level, the Cd-induced oxidative stress either leads to oxidative damage or activates signal transduction pathways to initiate defence responses. This balance is important on how different organ systems respond to Cd stress and ultimately define the pathological outcome. In this review, we highlight the Cd-induced oxidant/antioxidant status as well as the damage versus signalling scenario in relation to Cd toxicity. Emphasis is addressed to Cd-induced pathologies of major target organs, including a section on cell proliferation and carcinogenesis. Furthermore, attention is paid to Cd-induced oxidative stress in undifferentiated stem cells, which can provide information for future therapies in preventing Cd-induced pathologies. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
Open AccessReview The Lipid Transfer Protein StarD7: Structure, Function, and Regulation
Int. J. Mol. Sci. 2013, 14(3), 6170-6186; doi:10.3390/ijms14036170
Received: 7 December 2012 / Revised: 17 February 2013 / Accepted: 22 February 2013 / Published: 18 March 2013
Cited by 7 | PDF Full-text (621 KB) | HTML Full-text | XML Full-text
Abstract
The steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain proteins constitute a family of evolutionarily conserved and widely expressed proteins that have been implicated in lipid transport, metabolism, and signaling. The 15 well-characterized mammalian START domain-containing proteins are grouped into six subfamilies.
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The steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain proteins constitute a family of evolutionarily conserved and widely expressed proteins that have been implicated in lipid transport, metabolism, and signaling. The 15 well-characterized mammalian START domain-containing proteins are grouped into six subfamilies. The START domain containing 7 mRNA encodes StarD7, a member of the StarD2/phosphatidylcholine transfer protein (PCTP) subfamily, which was first identified as a gene overexpressed in a choriocarcinoma cell line. Recent studies show that the StarD7 protein facilitates the delivery of phosphatidylcholine to the mitochondria. This review summarizes the latest advances in StarD7 research, focusing on the structural and biochemical features, protein-lipid interactions, and mechanisms that regulate StarD7 expression. The implications of the role of StarD7 in cell proliferation, migration, and differentiation are also discussed. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
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Open AccessReview Annexin A2 Heterotetramer: Structure and Function
Int. J. Mol. Sci. 2013, 14(3), 6259-6305; doi:10.3390/ijms14036259
Received: 4 February 2013 / Revised: 2 March 2013 / Accepted: 5 March 2013 / Published: 19 March 2013
Cited by 51 | PDF Full-text (1548 KB) | HTML Full-text | XML Full-text
Abstract
Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane
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Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane organization, ion channel conductance, and also to link F-actin cytoskeleton to the plasma membrane. Despite an impressive list of potential binding partners and regulatory activities, it was somewhat unexpected that the annexin A2-null mouse should show a relatively benign phenotype. Studies with the annexin A2-null mouse have suggested important functions for annexin A2 and the heterotetramer in fibrinolysis, in the regulation of the LDL receptor and in cellular redox regulation. However, the demonstration that depletion of annexin A2 causes the depletion of several other proteins including S100A10, fascin and affects the expression of at least sixty-one genes has confounded the reports of its function. In this review we will discuss the annexin A2 structure and function and its proposed physiological and pathological roles. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
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Open AccessReview Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology
Int. J. Mol. Sci. 2013, 14(3), 6306-6344; doi:10.3390/ijms14036306
Received: 10 January 2013 / Revised: 8 March 2013 / Accepted: 11 March 2013 / Published: 19 March 2013
Cited by 34 | PDF Full-text (1223 KB) | HTML Full-text | XML Full-text
Abstract
The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites
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The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites by mitochondria and other cellular compartments. However, this dogma was challenged when these species were demonstrated to modulate cellular responses through altering signaling pathways. In fact, since this discovery of a dichotomous role of reactive species in immune function and signal transduction, research in this field grew at an exponential pace and the pursuit for mechanisms involved began. Due to a significant number of review articles present on the reactive species mediated cell death, we have focused on emerging novel pathways such as autophagy, signaling and maintenance of the mitochondrial network. Despite its role in several processes, increased reactive species generation has been associated with the origin and pathogenesis of a plethora of diseases. While it is tempting to speculate that anti-oxidant therapy would protect against these disorders, growing evidence suggests that this may not be true. This further supports our belief that these reactive species play a fundamental role in maintenance of cellular and tissue homeostasis. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
Open AccessReview Ubiquitinations in the Notch Signaling Pathway
Int. J. Mol. Sci. 2013, 14(3), 6359-6381; doi:10.3390/ijms14036359
Received: 1 February 2013 / Revised: 11 March 2013 / Accepted: 14 March 2013 / Published: 19 March 2013
Cited by 10 | PDF Full-text (1058 KB) | HTML Full-text | XML Full-text
Abstract
The very conserved Notch pathway is used iteratively during development and adulthood to regulate cell fates. Notch activation relies on interactions between neighboring cells, through the binding of Notch receptors to their ligands, both transmembrane molecules. This inter-cellular contact initiates a cascade of
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The very conserved Notch pathway is used iteratively during development and adulthood to regulate cell fates. Notch activation relies on interactions between neighboring cells, through the binding of Notch receptors to their ligands, both transmembrane molecules. This inter-cellular contact initiates a cascade of events eventually transforming the cell surface receptor into a nuclear factor acting on the transcription of specific target genes. This review highlights how the various processes undergone by Notch receptors and ligands that regulate the pathway are linked to ubiquitination events. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
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Open AccessReview The Influence of Metal Stress on the Availability and Redox State of Ascorbate, and Possible Interference with Its Cellular Functions
Int. J. Mol. Sci. 2013, 14(3), 6382-6413; doi:10.3390/ijms14036382
Received: 1 February 2013 / Revised: 6 March 2013 / Accepted: 8 March 2013 / Published: 20 March 2013
Cited by 8 | PDF Full-text (827 KB) | HTML Full-text | XML Full-text
Abstract
Worldwide, metals have been distributed to excessive levels in the environment due to industrial and agricultural activities. Plants growing on soils contaminated with excess levels of metals experience a disturbance of the cellular redox balance, which leads to an augmentation of reactive oxygen
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Worldwide, metals have been distributed to excessive levels in the environment due to industrial and agricultural activities. Plants growing on soils contaminated with excess levels of metals experience a disturbance of the cellular redox balance, which leads to an augmentation of reactive oxygen species (ROS). Even though the increased ROS levels can cause cellular damage, controlled levels play an important role in modulating signaling networks that control physiological processes and stress responses. Plants control ROS levels using their antioxidative defense system both under non-stress conditions, as well as under stress conditions such as exposure to excess metals. Ascorbate (AsA) is a well-known and important component of the plant’s antioxidative system. As primary antioxidant, it can reduce ROS directly and indirectly via ascorbate peroxidase in the ascorbate–glutathione cycle. Furthermore, AsA fulfills an essential role in physiological processes, some of which are disturbed by excess metals. In this review, known direct effects of excess metals on AsA biosynthesis and functioning will be discussed, as well as the possible interference of metals with the role of AsA in physiological and biochemical processes. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessReview Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy
Int. J. Mol. Sci. 2013, 14(3), 6414-6435; doi:10.3390/ijms14036414
Received: 1 November 2012 / Revised: 13 March 2013 / Accepted: 15 March 2013 / Published: 20 March 2013
Cited by 47 | PDF Full-text (979 KB) | HTML Full-text | XML Full-text
Abstract
The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations. Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in
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The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations. Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in the context of global warming. UV rays first encounter the uppermost epidermal keratinocytes causing apoptosis. The molecular mechanisms of UV-induced apoptosis of keratinocytes include direct DNA damage (intrinsic), clustering of death receptors on the cell surface (extrinsic), and generation of ROS. When apoptotic keratinocytes are processed by adjacent immature Langerhans cells (LCs), the inappropriately activated Langerhans cells could result in immunosuppression. Furthermore, UV can deplete LCs in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis. Intriguingly, receptor activator of NF-κB (RANK) activation of LCs by UV can induce the pro-survival and anti-apoptotic signals due to the upregulation of Bcl-xL, leading to the generation of regulatory T cells. Meanwhile, a physiological dosage of UV can also enhance melanocyte survival and melanogenesis. Analogous to its effect in keratinocytes, a therapeutic dosage of UV can induce cell cycle arrest, activate antioxidant and DNA repair enzymes, and induce apoptosis through translocation of the Bcl-2 family proteins in melanocytes to ensure genomic integrity and survival of melanocytes. Furthermore, UV can elicit the synthesis of vitamin D, an important molecule in calcium homeostasis of various types of skin cells contributing to DNA repair and immunomodulation. Taken together, the above-mentioned effects of UV on apoptosis and its related biological effects such as proliferation inhibition, melanin synthesis, and immunomodulations on skin residential cells have provided an integrated biochemical and molecular biological basis for phototherapy that has been widely used in the treatment of many dermatological diseases. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
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Open AccessReview UPR Signal Activation by Luminal Sensor Domains
Int. J. Mol. Sci. 2013, 14(3), 6454-6466; doi:10.3390/ijms14036454
Received: 30 January 2013 / Revised: 15 March 2013 / Accepted: 18 March 2013 / Published: 21 March 2013
Cited by 11 | PDF Full-text (522 KB) | HTML Full-text | XML Full-text
Abstract
The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor
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The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK, and ATF6, which then propagate the signal to the cytosol. In this review, we discuss the various mechanisms of action that have been proposed on how the sensor domains detect the presence of unfolded protein to activate downstream UPR signaling. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview RUFY, Rab and Rap Family Proteins Involved in a Regulation of Cell Polarity and Membrane Trafficking
Int. J. Mol. Sci. 2013, 14(3), 6487-6498; doi:10.3390/ijms14036487
Received: 31 December 2012 / Revised: 11 March 2013 / Accepted: 15 March 2013 / Published: 21 March 2013
Cited by 6 | PDF Full-text (204 KB) | HTML Full-text | XML Full-text
Abstract
Cell survival, homeostasis and cell polarity rely on the control of membrane trafficking pathways. The RUN domain (comprised of the RPIP8, UNC-14, and NESCA proteins) has been suggested to be implicated in small GTPase-mediated membrane trafficking and cell polarity. Accumulating evidence supports the
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Cell survival, homeostasis and cell polarity rely on the control of membrane trafficking pathways. The RUN domain (comprised of the RPIP8, UNC-14, and NESCA proteins) has been suggested to be implicated in small GTPase-mediated membrane trafficking and cell polarity. Accumulating evidence supports the hypothesis that the RUN domain-containing proteins might be responsible for an interaction with a filamentous network linked to actin cytoskeleton and/or microtubules. In addition, several downstream molecules of PI3K are involved in regulation of the membrane trafficking by interacting with vesicle-associated RUN proteins such as RUFY family proteins. In this review, we summarize the background of RUN domain research with an emphasis on the interaction between RUN domain proteins including RUFY proteins (designated as RUN and FYVE domain-containing proteins) and several small GTPases with respect to the regulation of cell polarity and membrane trafficking on filamentous network Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)

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Open AccessCase Report A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies
Int. J. Mol. Sci. 2013, 14(3), 6067-6073; doi:10.3390/ijms14036067
Received: 17 February 2013 / Revised: 11 March 2013 / Accepted: 12 March 2013 / Published: 15 March 2013
Cited by 5 | PDF Full-text (2733 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies.
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Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies. A 53-year-old Japanese woman was diagnosed with stage IIIc ovarian clear cell adenocarcinoma with marked chemoresistance to conventional regimens. She demonstrated a partial response to a multikinase inhibitor. The tumor was resistant to PI3K/mTOR pathway inhibitors despite harboring a PIK3CA mutation. The present case suggests a role for targeted therapies in the treatment of OCCC and a need for the identification of biomarkers that will predict response to targeted therapies. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessLetter CentroidAlign-Web: A Fast and Accurate Multiple Aligner for Long Non-Coding RNAs
Int. J. Mol. Sci. 2013, 14(3), 6144-6156; doi:10.3390/ijms14036144
Received: 20 November 2012 / Revised: 28 January 2013 / Accepted: 28 February 2013 / Published: 18 March 2013
Cited by 4 | PDF Full-text (639 KB) | HTML Full-text | XML Full-text
Abstract
Due to the recent discovery of non-coding RNAs (ncRNAs), multiple sequence alignment (MSA) of those long RNA sequences is becoming increasingly important for classifying and determining the functional motifs in RNAs. However, not only primary (nucleotide) sequences, but also secondary structures of ncRNAs
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Due to the recent discovery of non-coding RNAs (ncRNAs), multiple sequence alignment (MSA) of those long RNA sequences is becoming increasingly important for classifying and determining the functional motifs in RNAs. However, not only primary (nucleotide) sequences, but also secondary structures of ncRNAs are closely related to their function and are conserved evolutionarily. Hence, information about secondary structures should be considered in the sequence alignment of ncRNAs. Yet, in general, a huge computational time is required in order to compute MSAs, taking secondary structure information into account. In this paper, we describe a fast and accurate web server, called CentroidAlign-Web, which can handle long RNA sequences. The web server also appropriately incorporates information about known secondary structures into MSAs. Computational experiments indicate that our web server is fast and accurate enough to handle long RNA sequences. CentroidAlign-Web is freely available from http://centroidalign.ncrna.org/. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessCorrection Correction: Liang, J., et al. Antisense Oligonucleotide Against Clusterin Regulates Human Hepatocellular Carcinoma Invasion Through Transcriptional Regulation of Matrix Metalloproteinase-2 and E-Cadherin. Int. J. Mol. Sci. 2012, 13, 10594-10607
Int. J. Mol. Sci. 2013, 14(3), 6516-6517; doi:10.3390/ijms14036516
Received: 19 March 2013 / Revised: 20 March 2013 / Accepted: 20 March 2013 / Published: 22 March 2013
PDF Full-text (19 KB) | HTML Full-text | XML Full-text
Abstract
The original version of the paper reports that “OGX-011 is a second generation 21-mer oligonucleotide with a 20-O-(2-methoxy)-ethyl modification, generously provided by OncoGenex Technologies (OncoGenex, Vancouver, Canada)” [1] (p. 10602). OGX-011 was not provided by OncoGenex Technologies directly. Therefore, we would
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The original version of the paper reports that “OGX-011 is a second generation 21-mer oligonucleotide with a 20-O-(2-methoxy)-ethyl modification, generously provided by OncoGenex Technologies (OncoGenex, Vancouver, Canada)” [1] (p. 10602). OGX-011 was not provided by OncoGenex Technologies directly. Therefore, we would like to correct the wording to: “OGX-011 was obtained without the benefit of an agreement with OncoGenex, or The University British Columbia, or any other party”. The authors would like to apologize for any inconvenience this may have caused to the readers of this journal. [...] Full article

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