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Int. J. Mol. Sci., Volume 16, Issue 1 (January 2015), Pages 1-2268

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Open AccessArticle Inhibition of the IgE-Mediated Activation of RBL-2H3 Cells by TIPP, a Novel Thymic Immunosuppressive Pentapeptide
Int. J. Mol. Sci. 2015, 16(1), 2252-2268; https://doi.org/10.3390/ijms16012252
Received: 12 November 2014 / Accepted: 12 January 2015 / Published: 20 January 2015
Cited by 13 | PDF Full-text (5297 KB) | HTML Full-text | XML Full-text
Abstract
TIPP is a novel thymic immunosuppressive pentapeptide originally obtained from calf thymic immunosuppressive extract. The present study aimed to investigate the inhibitory activity of TIPP on IgE-mediated activation of RBL-2H3 cells. Release of β-hexosaminidase and histamine, intracellular calcium, membrane ruffling, mRNA levels of
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TIPP is a novel thymic immunosuppressive pentapeptide originally obtained from calf thymic immunosuppressive extract. The present study aimed to investigate the inhibitory activity of TIPP on IgE-mediated activation of RBL-2H3 cells. Release of β-hexosaminidase and histamine, intracellular calcium, membrane ruffling, mRNA levels of cytokines, cyclooxygenase-2 (COX-2) expression, and activation of mitogen-activated protein kinases (MAP kinases) and NF-κB were determined by colorimetric assay, fluorescence spectrophotometer, confocal fluorescence microscope, quantification PCR, and Western blot, respectively. The results showed that TIPP significantly inhibited the degranulation in IgE-antigen complex-stimulated RBL-2H3 cells without cytotoxicity. TIPP significantly suppressed the increase of intracellular calcium and the rearrangement of F-actin, attenuated the transcription of pro-inflammatory cytokines (IL-3, -4, -6, -13, TNF-α, and monocyte chemotactic protein-1 (MCP-1)), and decreased the expression of COX-2. Western blot analysis showed that TIPP had an inhibitory activity on the phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and ERK kinase 1/2 (MEK1/2), and inhibited the activation of NF-κB. The data suggested that TIPP effectively suppressed IgE-mediated activation of RBL-2H3 cells via blocking MEK/ERK and NF-κB signaling pathways. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Mechanical and Anticorrosive Properties of Graphene/Epoxy Resin Composites Coating Prepared by in-Situ Method
Int. J. Mol. Sci. 2015, 16(1), 2239-2251; https://doi.org/10.3390/ijms16012239
Received: 14 October 2014 / Accepted: 16 December 2014 / Published: 20 January 2015
Cited by 24 | PDF Full-text (1430 KB) | HTML Full-text | XML Full-text
Abstract
The graphene nanosheets-based epoxy resin coating (0, 0.1, 0.4 and 0.7 wt %) was prepared by a situ-synthesis method. The effect of polyvinylpyrrolidone/reduced graphene oxide (PVP-rGO) on mechanical and thermal properties of epoxy resin coating was investigated using nanoindentation technique and thermogravimetric analysis,
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The graphene nanosheets-based epoxy resin coating (0, 0.1, 0.4 and 0.7 wt %) was prepared by a situ-synthesis method. The effect of polyvinylpyrrolidone/reduced graphene oxide (PVP-rGO) on mechanical and thermal properties of epoxy resin coating was investigated using nanoindentation technique and thermogravimetric analysis, respectively. A significant enhancement (ca. 213% and 73 °C) in the Young modulus and thermal stability of epoxy resin coating was obtained at a loading of 0.7 wt %, respectively. Furthermore, the erosion resistance of graphene nanosheets-based epoxy resin coating was investigated by electrochemical measurement. The results showed also that the Rrcco (ca. 0.3 mm/year) of graphene nanosheets-based epoxy resin coating was far lower than neat epoxy resin (1.3 mm/year). Thus, this approach provides a novel route for improving erosion resistance and mechanical-thermal stability of polymers coating, which is expected to be used in mechanical-thermal-corrosion coupling environments. Full article
(This article belongs to the Section Materials Science)
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Open AccessArticle De Novo Assembly and Characterization of Narrow-Ridged Finless Porpoise Renal Transcriptome and Identification of Candidate Genes Involved in Osmoregulation
Int. J. Mol. Sci. 2015, 16(1), 2220-2238; https://doi.org/10.3390/ijms16012220
Received: 20 October 2014 / Revised: 8 December 2014 / Accepted: 13 January 2015 / Published: 20 January 2015
Cited by 5 | PDF Full-text (1770 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
During the evolutionary transition from land to water, cetaceans have undergone numerous critical challenges, with osmoregulation being the major one. Two subspecies of the narrow-ridged finless porpoise (Neophocaena asiaeorientalis), the freshwater Yangtze finless porpoise (N. a. asiaeorientalis, NAA) and
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During the evolutionary transition from land to water, cetaceans have undergone numerous critical challenges, with osmoregulation being the major one. Two subspecies of the narrow-ridged finless porpoise (Neophocaena asiaeorientalis), the freshwater Yangtze finless porpoise (N. a. asiaeorientalis, NAA) and the marine East Asian finless porpoise (N. a. sunameri, NAS), provide excellent subjects to understand the genetic basis of osmoregulatory divergence between freshwater and marine mammals. The kidney plays an important and well-established role in osmoregulation in marine mammals and thus, herein, we utilized RNA-seq to characterize the renal transcriptome and preliminarily analyze the divergence between the NAA and the NAS. Approximately 48.98 million clean reads from NAS and 49.40 million clean reads from NAA were obtained by RNA-Seq. And 73,449 (NAS) and 68,073 (NAA) unigenes were assembled. Among these annotations, 22,231 (NAS) and 21,849 (NAA) unigenes were annotated against the NCBI nr protein database. The ion channel complex GO term and four pathways were detected as relevant to osmoregulation by GO and KEGG pathway classification of these annotated unigenes. Although the endangered status of the study species prevented analysis of biological replicates, we identified nine differentially expressed genes (DEGs) that may be vital in the osmoregulation of the narrow-ridged finless porpoise and worthwhile for future studies. Of these DEGs, the differential expression and distribution of the aquaporin-2 (AQP2) in the collecting duct were verified using immunohistochemical experiments. Together, this work is the first report of renal transcriptome sequencing in cetaceans, and it will provide a valuable resource for future molecular genetics studies on cetacean osmoregulation. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Identification and Analysis of Differentially-Expressed microRNAs in Japanese Encephalitis Virus-Infected PK-15 Cells with Deep Sequencing
Int. J. Mol. Sci. 2015, 16(1), 2204-2219; https://doi.org/10.3390/ijms16012204
Received: 2 December 2014 / Accepted: 12 January 2015 / Published: 20 January 2015
Cited by 17 | PDF Full-text (1450 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Japanese encephalitis virus (JEV), a mosquito-borne Flavivirus, causes acute viral encephalitis with high morbidity and mortality in humans and animals. MicroRNAs (miRNAs) are small noncoding RNAs that are important modulators of the intricate host-pathogen interaction networks. However, our knowledge of the changes
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Japanese encephalitis virus (JEV), a mosquito-borne Flavivirus, causes acute viral encephalitis with high morbidity and mortality in humans and animals. MicroRNAs (miRNAs) are small noncoding RNAs that are important modulators of the intricate host-pathogen interaction networks. However, our knowledge of the changes that occur in miRNAs in host cells after JEV infection is still limited. To understand the molecular pathogenesis of JEV at the level of posttranscriptional regulation, we used Illumina deep sequencing to sequence two small RNA libraries prepared from PK-15 cells before and after JEV infection. We identified 522 and 427 miRNAs in the infected and uninfected cells, respectively. Overall, 132 miRNAs were expressed significantly differently after challenge with JEV: 78 were upregulated and 54 downregulated. The sequencing results for selected miRNAs were confirmed with RT-qPCR. GO analysis of the host target genes revealed that these dysregulated miRNAs are involved in complex cellular pathways, including the metabolic pathway, inflammatory response and immune response. To our knowledge, this is the first report of the comparative expression of miRNAs in PK-15 cells after JEV infection. Our findings will underpin further studies of miRNAs’ roles in JEV replication and identify potential candidates for antiviral therapies against JEV. Full article
(This article belongs to the Section Biochemistry)
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Open AccessReview Experimental Confirmation of a Whole Set of tRNA Molecules in Two Archaeal Species
Int. J. Mol. Sci. 2015, 16(1), 2187-2203; https://doi.org/10.3390/ijms16012187
Received: 26 November 2014 / Accepted: 14 January 2015 / Published: 20 January 2015
Cited by 1 | PDF Full-text (1467 KB) | HTML Full-text | XML Full-text
Abstract
Based on the genomic sequences for most archaeal species, only one tRNA gene (isodecoder) is predicted for each triplet codon. This observation promotes analysis of a whole set of tRNA molecules and actual splicing patterns of interrupted tRNA in one organism. The entire
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Based on the genomic sequences for most archaeal species, only one tRNA gene (isodecoder) is predicted for each triplet codon. This observation promotes analysis of a whole set of tRNA molecules and actual splicing patterns of interrupted tRNA in one organism. The entire genomic sequences of two Creanarchaeota, Aeropyrum pernix and Sulfolobus tokodaii, were determined approximately 15 years ago. In these genome datasets, 47 and 46 tRNA genes were detected, respectively. Among them, 14 and 24 genes, respectively, were predicted to be interrupted tRNA genes. To confirm the actual transcription of these predicted tRNA genes and identify the actual splicing patterns of the predicted interrupted tRNA molecules, RNA samples were prepared from each archaeal species and used to synthesize cDNA molecules with tRNA sequence-specific primers. Comparison of the nucleotide sequences of cDNA clones representing unspliced and spliced forms of interrupted tRNA molecules indicated that some introns were located at positions other than one base 3' from anticodon region and that bulge-helix-bulge structures were detected around the actual splicing sites in each interrupted tRNA molecule. Whole-set analyses of tRNA molecules revealed that the archaeal tRNA splicing mechanism may be essential for efficient splicing of all tRNAs produced from interrupted tRNA genes in these archaea. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
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Open AccessArticle Transgenic Plants as Low-Cost Platform for Chemotherapeutic Drugs Screening
Int. J. Mol. Sci. 2015, 16(1), 2174-2186; https://doi.org/10.3390/ijms16012174
Received: 30 November 2014 / Accepted: 9 January 2015 / Published: 20 January 2015
Cited by 3 | PDF Full-text (2734 KB) | HTML Full-text | XML Full-text
Abstract
In this work we explored the possibility of using genetically modified Arabidopsis thaliana plants as a rapid and low-cost screening tool for evaluating human anticancer drugs action and efficacy. Here, four different inhibitors with a validated anticancer effect in humans and distinct mechanism
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In this work we explored the possibility of using genetically modified Arabidopsis thaliana plants as a rapid and low-cost screening tool for evaluating human anticancer drugs action and efficacy. Here, four different inhibitors with a validated anticancer effect in humans and distinct mechanism of action were screened in the plant model for their ability to interfere with the cytoskeletal and endomembrane networks. We used plants expressing a green fluorescent protein (GFP) tagged microtubule-protein (TUA6-GFP), and three soluble GFPs differently sorted to reside in the endoplasmic reticulum (GFPKDEL) or to accumulate in the vacuole through a COPII dependent (AleuGFP) or independent (GFPChi) mechanism. Our results demonstrated that drugs tested alone or in combination differentially influenced the monitored cellular processes including cytoskeletal organization and endomembrane trafficking. In conclusion, we demonstrated that A. thaliana plants are sensitive to the action of human chemotherapeutics and can be used for preliminary screening of drugs efficacy. The cost-effective subcellular imaging in plant cell may contribute to better clarify drugs subcellular targets and their anticancer effects. Full article
(This article belongs to the Special Issue Plant Cell Compartmentation and Volume Control)
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Open AccessArticle Molecular Characterization of a New Wheat-Thinopyrum intermedium Translocation Line with Resistance to Powdery Mildew and Stripe Rust
Int. J. Mol. Sci. 2015, 16(1), 2162-2173; https://doi.org/10.3390/ijms16012162
Received: 8 December 2014 / Revised: 7 January 2015 / Accepted: 9 January 2015 / Published: 20 January 2015
Cited by 3 | PDF Full-text (3874 KB) | HTML Full-text | XML Full-text
Abstract
A new wheat-Thinopyrum translocation line CH13-21 was selected from the progenies derived from a cross between wheat-Th. intermedium partial amphiploid TAI7047 and wheat line Mianyang11. CH13-21 was characterized by using genomic in situ hybridization (GISH), multicolor-GISH (mc-GISH), multicolor-fluorescence in situ hybridization
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A new wheat-Thinopyrum translocation line CH13-21 was selected from the progenies derived from a cross between wheat-Th. intermedium partial amphiploid TAI7047 and wheat line Mianyang11. CH13-21 was characterized by using genomic in situ hybridization (GISH), multicolor-GISH (mc-GISH), multicolor-fluorescence in situ hybridization (mc-FISH) and chromosome-specific molecular markers. When inoculated with stripe rust and powdery mildew isolates, CH13-21 displayed novel resistance to powdery mildew and stripe rust which inherited from its Thinopyrum parent. The chromosomal counting analyses indicated that CH13-21 has 42 chromosomes, with normal bivalent pairing at metaphase I of meiosis. GISH probed by Th. intermedium genomic DNA showed that CH13-21 contained a pair of wheat-Th. intermedium translocated chromosomes. Sequential mc-FISH analyses probed by pSc119.2 and pAs1 clearly revealed that chromosome arm 6BS of CH13-21 was replaced by Thinopyrum chromatin in the translocation chromosome. The molecular markers analysis further confirmed that the introduced Th. intermedium chromatin in CH13-21 belonged to the long arm of homoeologous group 6 chromosome. Therefore, CH13-21 was a new T6BS.6Ai#1L compensating Robertsonian translocation line. It concludes that CH13-21 is a new genetic resource for wheat breeding programs providing novel variation for disease resistances. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessArticle Unravelling Genes and Pathways Implicated in Working Memory of Schizophrenia in Han Chinese
Int. J. Mol. Sci. 2015, 16(1), 2145-2161; https://doi.org/10.3390/ijms16012145
Received: 13 October 2014 / Revised: 5 November 2014 / Accepted: 12 January 2015 / Published: 20 January 2015
Cited by 2 | PDF Full-text (1518 KB) | HTML Full-text | XML Full-text
Abstract
Working memory deficit is the core neurocognitive disorder in schizophrenia patients. To identify the factors underlying working memory deficit in schizophrenia patients and to explore the implication of possible genes in the working memory using genome-wide association study (GWAS) of schizophrenia, computerized delay-matching-to-sample
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Working memory deficit is the core neurocognitive disorder in schizophrenia patients. To identify the factors underlying working memory deficit in schizophrenia patients and to explore the implication of possible genes in the working memory using genome-wide association study (GWAS) of schizophrenia, computerized delay-matching-to-sample (DMS) and whole genome genotyping data were obtained from 100 first-episode, treatment-naïve patients with schizophrenia and 140 healthy controls from the Mental Health Centre of the West China Hospital, Sichuan University. A composite score, delay-matching-to-sample total correct numbers (DMS-TC), was found to be significantly different between the patients and control. On associating quantitative DMS-TC with interactive variables of groups × genotype, one SNP (rs1411832), located downstream of YWHAZP5 in chromosome 10, was found to be associated with the working memory deficit in schizophrenia patients with lowest p-value (p = 2.02 × 10−7). ConsensusPathDB identified that genes with SNPs for which p values below the threshold of 5 × 10−5 were significantly enriched in GO:0007155 (cell adhesion, p < 0.001). This study indicates that working memory, as an endophenotype of schizophrenia, could improve the efficacy of GWAS in schizophrenia. However, further study is required to replicate the results from our study. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Running Exercise Alleviates Pain and Promotes Cell Proliferation in a Rat Model of Intervertebral Disc Degeneration
Int. J. Mol. Sci. 2015, 16(1), 2130-2144; https://doi.org/10.3390/ijms16012130
Received: 5 December 2014 / Accepted: 12 January 2015 / Published: 19 January 2015
Cited by 7 | PDF Full-text (3184 KB) | HTML Full-text | XML Full-text
Abstract
Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD) patients. However, the mechanism underlying the analgesic effects of physical
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Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD) patients. However, the mechanism underlying the analgesic effects of physical exercise on DDD remains largely unclear. The results of the present study showed that mechanical withdrawal thresholds of bilateral hindpaw were significantly decreased beginning on day three after intradiscal complete Freund’s adjuvant (CFA) injection and daily running exercise remarkably reduced allodynia in the CFA exercise group beginning at day 28 compared to the spontaneous recovery group (controls). The hindpaw withdrawal thresholds of the exercise group returned nearly to baseline at the end of experiment, but severe pain persisted in the control group. Histological examinations performed on day 70 revealed that running exercise restored the degenerative discs and increased the cell densities of the annulus fibrosus (AF) and nucleus pulposus (NP). Furthermore, immunofluorescence labeling revealed significantly higher numbers of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the exercise group on days 28, 42, 56 and 70, which indicated more rapid proliferation compared to the control at the corresponding time points. Taken together, these results suggest that running exercise might alleviate the mechanical allodynia induced by intradiscal CFA injection via disc repair and cell proliferation, which provides new evidence for future clinical use. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Regeneration and Tissue Repair)
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Open AccessArticle Prevention of Osteoporosis by Oral Administration of Phytate-Removed and Deamidated Soybean β-Conglycinin
Int. J. Mol. Sci. 2015, 16(1), 2117-2129; https://doi.org/10.3390/ijms16012117
Received: 16 November 2014 / Accepted: 13 January 2015 / Published: 19 January 2015
Cited by 5 | PDF Full-text (1230 KB) | HTML Full-text | XML Full-text
Abstract
Phytate-removed and deamidated soybean β-conglycinin (PrDS) prepared by ion-exchange resins was supplemented to be 4% in the diet administered to ovariectomized rats to investigate its preventive effect on osteoporosis. The apparent calcium absorption rate decreased following ovariectomy and was not replenished by oral
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Phytate-removed and deamidated soybean β-conglycinin (PrDS) prepared by ion-exchange resins was supplemented to be 4% in the diet administered to ovariectomized rats to investigate its preventive effect on osteoporosis. The apparent calcium absorption rate decreased following ovariectomy and was not replenished by oral administration of phytate-removed soybean β-conglycinin (PrS) or casein. On the other hand, administration of PrDS restored the calcium absorption rate to the same level as the sham group. Markers of bone resorption, such as serum parathyroid hormone (PTH) and urinary deoxypyridinoline (DPD), increased, and the bone mineral density and breaking stress decreased following ovariectomy. However, PrDS supplementation suppressed the changes caused by the decrease in calcium absorption from the small intestine. Therefore, PrDS supplementation shows promise for the prevention of postmenopausal osteoporosis. Full article
(This article belongs to the Special Issue Bioactive Proteins and Peptides Derived from Food)
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Open AccessReview Antimicrobial Polymers with Metal Nanoparticles
Int. J. Mol. Sci. 2015, 16(1), 2099-2116; https://doi.org/10.3390/ijms16012099
Received: 24 November 2014 / Accepted: 9 January 2015 / Published: 19 January 2015
Cited by 131 | PDF Full-text (1416 KB) | HTML Full-text | XML Full-text
Abstract
Metals, such as copper and silver, can be extremely toxic to bacteria at exceptionally low concentrations. Because of this biocidal activity, metals have been widely used as antimicrobial agents in a multitude of applications related with agriculture, healthcare, and the industry in general.
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Metals, such as copper and silver, can be extremely toxic to bacteria at exceptionally low concentrations. Because of this biocidal activity, metals have been widely used as antimicrobial agents in a multitude of applications related with agriculture, healthcare, and the industry in general. Unlike other antimicrobial agents, metals are stable under conditions currently found in the industry allowing their use as additives. Today these metal based additives are found as: particles, ions absorbed/exchanged in different carriers, salts, hybrid structures, etc. One recent route to further extend the antimicrobial applications of these metals is by their incorporation as nanoparticles into polymer matrices. These polymer/metal nanocomposites can be prepared by several routes such as in situ synthesis of the nanoparticle within a hydrogel or direct addition of the metal nanofiller into a thermoplastic matrix. The objective of the present review is to show examples of polymer/metal composites designed to have antimicrobial activities, with a special focus on copper and silver metal nanoparticles and their mechanisms. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
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Open AccessArticle Insecticide-Mediated Up-Regulation of Cytochrome P450 Genes in the Red Flour Beetle (Tribolium castaneum)
Int. J. Mol. Sci. 2015, 16(1), 2078-2098; https://doi.org/10.3390/ijms16012078
Received: 11 November 2014 / Accepted: 9 January 2015 / Published: 19 January 2015
Cited by 6 | PDF Full-text (2373 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Some cytochrome P450 (CYP) genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes.
[...] Read more.
Some cytochrome P450 (CYP) genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR) revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively), permethrin (2.00- and 2.03-fold) and lambda-cyhalothrin (1.73- and 1.81-fold), whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold) when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification. Full article
(This article belongs to the Section Molecular Toxicology)
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Open AccessArticle Variation and Genetic Structure in Platanus mexicana (Platanaceae) along Riparian Altitudinal Gradient
Int. J. Mol. Sci. 2015, 16(1), 2066-2077; https://doi.org/10.3390/ijms16012066
Received: 4 September 2014 / Accepted: 17 November 2014 / Published: 19 January 2015
Cited by 2 | PDF Full-text (1252 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Platanus mexicana is a dominant arboreal species of riparian ecosystems. These ecosystems are associated with altitudinal gradients that can generate genetic differences in the species, especially in the extremes of the distribution. However, studies on the altitudinal effect on genetic variation to riparian
[...] Read more.
Platanus mexicana is a dominant arboreal species of riparian ecosystems. These ecosystems are associated with altitudinal gradients that can generate genetic differences in the species, especially in the extremes of the distribution. However, studies on the altitudinal effect on genetic variation to riparian species are scarce. In Mexico, the population of P. mexicana along the Colipa River (Veracruz State) grows below its reported minimum altitude range, possibly the lowest where this tree grows. This suggests that altitude might be an important factor in population genetics differentiation. We examined the genetic variation and population structuring at four sites with different altitudes (70, 200, 600 and 1700 m a.s.l.) using ten inter-simple sequence repeats (ISSR) markers. The highest value for Shannon index and Nei’s gene diversity was obtained at 1700 m a.s.l. (He = 0.27, Ne = 1.47, I = 0.42) and polymorphism reached the top value at the middle altitude (% p = 88.57). Analysis of molecular variance (AMOVA) and STRUCTURE analysis indicated intrapopulation genetic differentiation. The arithmetic average (UPGMA) dendrogram identified 70 m a.s.l. as the most genetically distant site. The genetic structuring resulted from limited gene flow and genetic drift. This is the first report of genetic variation in populations of P. mexicana in Mexico. This research highlights its importance as a dominant species, and its ecological and evolutionary implications in altitudinal gradients of riparian ecosystems. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessArticle Isolation and Characterization of Six AP2/ERF Transcription Factor Genes in Chrysanthemum nankingense
Int. J. Mol. Sci. 2015, 16(1), 2052-2065; https://doi.org/10.3390/ijms16012052
Received: 19 November 2014 / Revised: 12 December 2014 / Accepted: 5 January 2015 / Published: 19 January 2015
Cited by 10 | PDF Full-text (3588 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The AP2/ERF family of plant transcription factors (TFs) regulate a variety of developmental and physiological processes. Here, we report the isolation of six AP2/ERF TF family genes from Chrysanthemum nankingense. On the basis of sequence similarity, one of these belonged to the Ethylene
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The AP2/ERF family of plant transcription factors (TFs) regulate a variety of developmental and physiological processes. Here, we report the isolation of six AP2/ERF TF family genes from Chrysanthemum nankingense. On the basis of sequence similarity, one of these belonged to the Ethylene Responsive Factor (ERF) subfamily and the other five to the Dehydration Responsive Element Binding protein (DREB) subfamily. A transient expression experiment showed that all six AP2/ERF proteins localized to the nucleus. A yeast-one hybrid assay demonstrated that CnDREB1-1, 1-2 and 1-3 all function as transactivators, while CnERF1, CnDREB3-1 and 3-2 have no transcriptional activation ability. The transcription response of the six TFs in response to wounding, salinity and low temperature stress and treatment with abscisic acid (ABA), salicylic acid (SA) and jasmonic acid (JA) showed that CnERF1 was up-regulated by wounding and low temperature stress but suppressed by salinity stress. The transcription of CnDREB1-1, 1-2 and 1-3 was down-regulated by ABA and JA to varying degrees. CnDREB3-1 and 3-2 was moderately increased or decreased by wounding and SA treatment, suppressed by salinity stress and JA treatment, and enhanced by low temperature stress and ABA treatment. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessArticle Efficient Synthesis of a Maghemite/Gold Hybrid Nanoparticle System as a Magnetic Carrier for the Transport of Platinum-Based Metallotherapeutics
Int. J. Mol. Sci. 2015, 16(1), 2034-2051; https://doi.org/10.3390/ijms16012034
Received: 11 December 2014 / Accepted: 13 January 2015 / Published: 16 January 2015
Cited by 5 | PDF Full-text (1996 KB) | HTML Full-text | XML Full-text
Abstract
The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH3)2Cl2], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of
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The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH3)2Cl2], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of maghemite/gold nanoparticles (mag/Au) coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic acid) and functionalized by activated cisplatin in the form of cis-[Pt(NH3)2(H2O)2]2+ (CDDP*). The relevant techniques (XPS, EDS, ICP-MS) proved the incorporation of the platinum-containing species on the surface of the studied hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical with an average size of 12 nm, while their superparamagnetic feature was proven by 57Fe Mössbauer spectroscopy. In the case of mag/Au, mag/Au–HLA and mag/Au–LA–CDDP*, weaker magnetic interactions among the Fe3+ centers of maghemite, as compared to maghemite nanoparticles (mag), were detected, which can be associated with the non-covalent coating of the maghemite surface by gold. The pH and time-dependent stability of the mag/Au–LA–CDDP* system in different media, represented by acetate (pH 5.0), phosphate (pH 7.0) and carbonate (pH 9.0) buffers and connected with the release of the platinum-containing species, showed the ability of CDDP* to be released from the functionalized nanosystem. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Open AccessArticle Designed Surface Residue Substitutions in [NiFe] Hydrogenase that Improve Electron Transfer Characteristics
Int. J. Mol. Sci. 2015, 16(1), 2020-2033; https://doi.org/10.3390/ijms16012020
Received: 11 December 2014 / Accepted: 12 January 2015 / Published: 16 January 2015
Cited by 3 | PDF Full-text (1578 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Photobiological hydrogen production is an attractive, carbon-neutral means to convert solar energy to hydrogen. We build on previous research improving the Alteromonas macleodii “Deep Ecotype” [NiFe] hydrogenase, and report progress towards creating an artificial electron transfer pathway to supply the hydrogenase with electrons
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Photobiological hydrogen production is an attractive, carbon-neutral means to convert solar energy to hydrogen. We build on previous research improving the Alteromonas macleodii “Deep Ecotype” [NiFe] hydrogenase, and report progress towards creating an artificial electron transfer pathway to supply the hydrogenase with electrons necessary for hydrogen production. Ferredoxin is the first soluble electron transfer mediator to receive high-energy electrons from photosystem I, and bears an electron with sufficient potential to efficiently reduce protons. Thus, we engineered a hydrogenase-ferredoxin fusion that also contained several other modifications. In addition to the C-terminal ferredoxin fusion, we truncated the C-terminus of the hydrogenase small subunit, identified as the available terminus closer to the electron transfer region. We also neutralized an anionic patch surrounding the interface Fe-S cluster to improve transfer kinetics with the negatively charged ferredoxin. Initial screening showed the enzyme tolerated both truncation and charge neutralization on the small subunit ferredoxin-binding face. While the enzyme activity was relatively unchanged using the substrate methyl viologen, we observed a marked improvement from both the ferredoxin fusion and surface modification using only dithionite as an electron donor. Combining ferredoxin fusion and surface charge modification showed progressively improved activity in an in vitro assay with purified enzyme. Full article
(This article belongs to the Special Issue Photosynthesis and Biological Hydrogen Production)
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Open AccessArticle Meshless Method with Operator Splitting Technique for Transient Nonlinear Bioheat Transfer in Two-Dimensional Skin Tissues
Int. J. Mol. Sci. 2015, 16(1), 2001-2019; https://doi.org/10.3390/ijms16012001
Received: 25 November 2014 / Accepted: 7 January 2015 / Published: 16 January 2015
Cited by 1 | PDF Full-text (1499 KB) | HTML Full-text | XML Full-text
Abstract
A meshless numerical scheme combining the operator splitting method (OSM), the radial basis function (RBF) interpolation, and the method of fundamental solutions (MFS) is developed for solving transient nonlinear bioheat problems in two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity caused
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A meshless numerical scheme combining the operator splitting method (OSM), the radial basis function (RBF) interpolation, and the method of fundamental solutions (MFS) is developed for solving transient nonlinear bioheat problems in two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity caused by linear and exponential relationships of temperature-dependent blood perfusion rate (TDBPR) is taken into consideration. In the analysis, the OSM is used first to separate the Laplacian operator and the nonlinear source term, and then the second-order time-stepping schemes are employed for approximating two splitting operators to convert the original governing equation into a linear nonhomogeneous Helmholtz-type governing equation (NHGE) at each time step. Subsequently, the RBF interpolation and the MFS involving the fundamental solution of the Laplace equation are respectively employed to obtain approximated particular and homogeneous solutions of the nonhomogeneous Helmholtz-type governing equation. Finally, the full fields consisting of the particular and homogeneous solutions are enforced to fit the NHGE at interpolation points and the boundary conditions at boundary collocations for determining unknowns at each time step. The proposed method is verified by comparison of other methods. Furthermore, the sensitivity of the coefficients in the cases of a linear and an exponential relationship of TDBPR is investigated to reveal their bioheat effect on the skin tissue. Full article
(This article belongs to the Special Issue Advances in Anisotropic and Smart Materials)
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Open AccessReview Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel Perspective from a New Mouse Model
Int. J. Mol. Sci. 2015, 16(1), 1980-2000; https://doi.org/10.3390/ijms16011980
Received: 10 December 2014 / Accepted: 7 January 2015 / Published: 16 January 2015
Cited by 5 | PDF Full-text (1131 KB) | HTML Full-text | XML Full-text
Abstract
Autoimmune hepatitis (AIH) is an immune-mediated disorder that affects the liver parenchyma. Diagnosis usually occurs at the later stages of the disease, complicating efforts towards understanding the causes of disease development. While animal models are useful for studying the etiology of autoimmune disorders,
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Autoimmune hepatitis (AIH) is an immune-mediated disorder that affects the liver parenchyma. Diagnosis usually occurs at the later stages of the disease, complicating efforts towards understanding the causes of disease development. While animal models are useful for studying the etiology of autoimmune disorders, most of the existing animal models of AIH do not recapitulate the chronic course of the human condition. In addition, approaches to mimic AIH-associated liver inflammation have instead led to liver tolerance, consistent with the high tolerogenic capacity of the liver. Recently, we described a new mouse model that exhibited spontaneous and chronic liver inflammation that recapitulated the known histopathological and immunological parameters of AIH. The approach involved liver-extrinsic genetic engineering that interfered with the induction of T-cell tolerance in the thymus, the very process thought to inhibit AIH induction by liver-specific expression of exogenous antigens. The mutation led to depletion of specialized thymic epithelial cells that present self-antigens and eliminate autoreactive T-cells before they exit the thymus. Based on our findings, which are summarized below, we believe that this mouse model represents a relevant experimental tool towards elucidating the cellular and molecular aspects of AIH development and developing novel therapeutic strategies for treating this disease. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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Open AccessReview Ligand-Induced Dynamics of Neurotrophin Receptors Investigated by Single-Molecule Imaging Approaches
Int. J. Mol. Sci. 2015, 16(1), 1949-1979; https://doi.org/10.3390/ijms16011949
Received: 30 November 2014 / Accepted: 5 January 2015 / Published: 16 January 2015
Cited by 5 | PDF Full-text (883 KB) | HTML Full-text | XML Full-text
Abstract
Neurotrophins are secreted proteins that regulate neuronal development and survival, as well as maintenance and plasticity of the adult nervous system. The biological activity of neurotrophins stems from their binding to two membrane receptor types, the tropomyosin receptor kinase and the p75 neurotrophin
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Neurotrophins are secreted proteins that regulate neuronal development and survival, as well as maintenance and plasticity of the adult nervous system. The biological activity of neurotrophins stems from their binding to two membrane receptor types, the tropomyosin receptor kinase and the p75 neurotrophin receptors (NRs). The intracellular signalling cascades thereby activated have been extensively investigated. Nevertheless, a comprehensive description of the ligand-induced nanoscale details of NRs dynamics and interactions spanning from the initial lateral movements triggered at the plasma membrane to the internalization and transport processes is still missing. Recent advances in high spatio-temporal resolution imaging techniques have yielded new insight on the dynamics of NRs upon ligand binding. Here we discuss requirements, potential and practical implementation of these novel approaches for the study of neurotrophin trafficking and signalling, in the framework of current knowledge available also for other ligand-receptor systems. We shall especially highlight the correlation between the receptor dynamics activated by different neurotrophins and the respective signalling outcome, as recently revealed by single-molecule tracking of NRs in living neuronal cells. Full article
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Open AccessArticle BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis
Int. J. Mol. Sci. 2015, 16(1), 1928-1948; https://doi.org/10.3390/ijms16011928
Received: 6 November 2014 / Accepted: 8 January 2015 / Published: 16 January 2015
Cited by 28 | PDF Full-text (3366 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in
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Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Melatonin Stimulates Dendrite Formation and Complexity in the Hilar Zone of the Rat Hippocampus: Participation of the Ca++/Calmodulin Complex
Int. J. Mol. Sci. 2015, 16(1), 1907-1927; https://doi.org/10.3390/ijms16011907
Received: 31 July 2014 / Accepted: 7 January 2015 / Published: 16 January 2015
Cited by 13 | PDF Full-text (6414 KB) | HTML Full-text | XML Full-text
Abstract
Melatonin (MEL), the main product synthesized by the pineal gland, stimulates early and late stages of neurodevelopment in the adult brain. MEL increases dendrite length, thickness and complexity in the hilar and mossy neurons of hippocampus. Dendrite formation involves activation of Ca2+
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Melatonin (MEL), the main product synthesized by the pineal gland, stimulates early and late stages of neurodevelopment in the adult brain. MEL increases dendrite length, thickness and complexity in the hilar and mossy neurons of hippocampus. Dendrite formation involves activation of Ca2+/Calmodulin (CaM)-dependent kinase II (CaMKII) by CaM. Previous work showed that MEL increased the synthesis and translocation of CaM, suggesting that MEL activates CaM-dependent enzymes by this pathway. In this work we investigated whether MEL stimulates dendrite formation by CaMKII activation in organotypic cultures from adult rat hippocampus. We found that the CaMKII inhibitor, KN-62, abolished the MEL stimulatory effects on dendritogenesis and that MEL increased the relative amount of CaM in the soluble fraction of hippocampal slices. Also, PKC inhibition abolished dendritogenesis, while luzindole, an antagonist of MEL receptors (MT1/2), partially blocked the effects of MEL. Moreover, autophosphorylation of CaMKII and PKC was increased in presence of MEL, as well as phosphorylation of ERK1/2. Our results indicate that MEL stimulates dendrite formation through CaMKII and the translocation of CaM to the soluble fraction. Dendritogenesis elicited by MEL also required PKC activation, and signaling through MT1/2 receptors was partially involved. Data strongly suggest that MEL could repair the loss of hippocampal dendrites that occur in neuropsychiatric disorders by increasing CaM levels and activation of CaMKII. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)
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Open AccessArticle Isolation and Expression of NAC Genes during Persimmon Fruit Postharvest Astringency Removal
Int. J. Mol. Sci. 2015, 16(1), 1894-1906; https://doi.org/10.3390/ijms16011894
Received: 9 December 2014 / Accepted: 9 January 2015 / Published: 15 January 2015
Cited by 7 | PDF Full-text (2232 KB) | HTML Full-text | XML Full-text
Abstract
NAC genes have been characterized in numerous plants, where they are involved in responses to biotic and abiotic stress, including low oxygen stress. High concentration of CO2 is one of the most effective treatments to remove astringency of persimmon fruit owing to
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NAC genes have been characterized in numerous plants, where they are involved in responses to biotic and abiotic stress, including low oxygen stress. High concentration of CO2 is one of the most effective treatments to remove astringency of persimmon fruit owing to the action of the accumulated anoxia metabolite acetaldehyde. In model plants, NAC genes have been identified as being responsive to low oxygen. However, the possible relationship between NAC transcription factors and persimmon astringency removal remains unexplored. In the present research, treatment with a high concentration of CO2 (95%) effectively removed astringency of “Mopan” persimmon fruit by causing decreases in soluble tannin. Acetaldehyde content increased in response to CO2 treatment concomitantly with astringency removal. Using RNA-seq and Rapid amplification of cDNA ends (RACE), six DkNAC genes were isolated and studied. Transcriptional analysis indicated DkNAC genes responded differentially to CO2 treatment; DkNAC1, DkNAC3, DkNAC5 and DkNAC6 were transiently up-regulated, DkNAC2 was abundantly expressed 3 days after treatment, while the DkNAC4 was suppressed during astringency removal. It is proposed that DkNAC1/3/5/6 could be important candidates as regulators of persimmon astringency removal and the roles of other member are also discussed. Full article
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Open AccessReview Surveillance and Cleavage of Eukaryotic tRNAs
Int. J. Mol. Sci. 2015, 16(1), 1873-1893; https://doi.org/10.3390/ijms16011873
Received: 19 December 2014 / Accepted: 9 January 2015 / Published: 15 January 2015
Cited by 22 | PDF Full-text (1327 KB) | HTML Full-text | XML Full-text
Abstract
Beyond their central role in protein synthesis, transfer RNAs (tRNAs) have many other crucial functions. This includes various roles in the regulation of gene expression, stress responses, metabolic processes and priming reverse transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among
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Beyond their central role in protein synthesis, transfer RNAs (tRNAs) have many other crucial functions. This includes various roles in the regulation of gene expression, stress responses, metabolic processes and priming reverse transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among the most stable molecules. Nevertheless, they are not eternal. As key elements of cell function, tRNAs need to be continuously quality-controlled. Two tRNA surveillance pathways have been identified. They act on hypo-modified or mis-processed pre-tRNAs and on mature tRNAs lacking modifications. A short overview of these two pathways will be presented here. Furthermore, while the exoribonucleases acting in these pathways ultimately lead to complete tRNA degradation, numerous tRNA-derived fragments (tRFs) are present within a cell. These cleavage products of tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs) and are suspected to have important regulatory functions. The tRFs are evolutionarily widespread and created by cleavage at different positions by various endonucleases. Here, we review our present knowledge on the biogenesis and function of tRFs in various organisms. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
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Open AccessArticle Structural Diversity of the Microbial Surfactin Derivatives from Selective Esterification Approach
Int. J. Mol. Sci. 2015, 16(1), 1855-1872; https://doi.org/10.3390/ijms16011855
Received: 6 November 2014 / Accepted: 23 December 2014 / Published: 15 January 2015
Cited by 7 | PDF Full-text (2696 KB) | HTML Full-text | XML Full-text
Abstract
Surfactin originated from genus Bacillus is composed of a heptapeptide moiety bonded to the carboxyl and hydroxyl groups of a β-hydroxy fatty acid and it can be chemically modified to prepare the derivatives with different structures, owing to the existence of two free
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Surfactin originated from genus Bacillus is composed of a heptapeptide moiety bonded to the carboxyl and hydroxyl groups of a β-hydroxy fatty acid and it can be chemically modified to prepare the derivatives with different structures, owing to the existence of two free carboxyl groups in its peptide loop. This article presents the chemical modification of surfactin esterified with three different alcohols, and nine novel surfactin derivatives have been separated from products by the high performance liquid chromatography (HPLC). The novel derivatives, identified with Fourier transform infrared spectroscopy (FT-IR) and electrospray ionization mass spectrometry (ESI-MS), are the mono-hexyl-surfactin C14 ester, mono-hexyl-surfactin C15 ester, mono-2-methoxy-ethyl-surfactin C14 ester, di-hexyl-surfactin C14 ester, di-hexyl-surfactin ester C15, di-2-methoxy-ethyl-surfactin ester C14, di-2-methoxy-ethyl-surfactin ester C15, di-6-hydoxyl-hexyl-surfactin C14 ester and, di-6-hydoxyl-hexyl-surfactin C15 ester. The reaction conditions for esterification were optimized and the dependence of yields on different alcohols and catalysts were discussed. This study shows that esterification is one of the most efficient ways of chemical modification for surfactin and it can be used to prepare more derivatives to meet the needs of study in biological and interfacial activities. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
Int. J. Mol. Sci. 2015, 16(1), 1840-1854; https://doi.org/10.3390/ijms16011840
Received: 3 November 2014 / Accepted: 6 January 2015 / Published: 14 January 2015
Cited by 4 | PDF Full-text (837 KB) | HTML Full-text | XML Full-text
Abstract
While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily
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While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessArticle Non-Classical Gluconeogenesis-Dependent Glucose Metabolism in Rhipicephalus microplus Embryonic Cell Line BME26
Int. J. Mol. Sci. 2015, 16(1), 1821-1839; https://doi.org/10.3390/ijms16011821
Received: 7 October 2014 / Accepted: 31 December 2014 / Published: 14 January 2015
Cited by 4 | PDF Full-text (1721 KB) | HTML Full-text | XML Full-text
Abstract
In this work we evaluated several genes involved in gluconeogenesis, glycolysis and glycogen metabolism, the major pathways for carbohydrate catabolism and anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and catalytic control of the genes and enzymes associated with these pathways
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In this work we evaluated several genes involved in gluconeogenesis, glycolysis and glycogen metabolism, the major pathways for carbohydrate catabolism and anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by alterations in energy resource availability (primarily glucose). BME26 cells in media were investigated using three different glucose concentrations, and changes in the transcription levels of target genes in response to carbohydrate utilization were assessed. The results indicate that several genes, such as glycogen synthase (GS), glycogen synthase kinase 3 (GSK3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6 phosphatase (GP) displayed mutual regulation in response to glucose treatment. Surprisingly, the transcription of gluconeogenic enzymes was found to increase alongside that of glycolytic enzymes, especially pyruvate kinase, with high glucose treatment. In addition, RNAi data from this study revealed that the transcription of gluconeogenic genes in BME26 cells is controlled by GSK-3. Collectively, these results improve our understanding of how glucose metabolism is regulated at the genetic level in tick cells. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Specificity Protein 1 Regulates Gene Expression Related to Fatty Acid Metabolism in Goat Mammary Epithelial Cells
Int. J. Mol. Sci. 2015, 16(1), 1806-1820; https://doi.org/10.3390/ijms16011806
Received: 5 December 2014 / Accepted: 6 January 2015 / Published: 14 January 2015
Cited by 22 | PDF Full-text (1626 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Specificity protein 1 (SP1) is a ubiquitous transcription factor that plays an important role in controlling gene expression. Although important in mediating the function of various hormones, the role of SP1 in regulating milk fat formation remains unknown. To investigate the sequence and
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Specificity protein 1 (SP1) is a ubiquitous transcription factor that plays an important role in controlling gene expression. Although important in mediating the function of various hormones, the role of SP1 in regulating milk fat formation remains unknown. To investigate the sequence and expression information, as well as its role in modulating lipid metabolism, we cloned SP1 gene from mammary gland of Xinong Saanen dairy goat. The full-length cDNA of the SP1 gene is 4376 bp including 103 bp of 5'UTR, 2358 bp of ORF (HM_236311) and 1915 bp of 3'UTR, which is predicted to encode a 786 amino acids polypeptide. Phylogenetic tree analysis showed that goat SP1 has the closest relationship with sheep, followed by bovines (bos taurus, odobenus and ceratotherium), pig, primates (pongo, gorilla, macaca and papio) and murine (rattus and mus), while the furthest relationship was with canis and otolemur. Expression was predominant in the lungs, small intestine, muscle, spleen, mammary gland and subcutaneous fat. There were no significant expression level differences between the mammary gland tissues collected at lactation and dry-off period. Overexpression of SP1 in goat mammary epithelial cells (GMECs) led to higher mRNA expression level of peroxisome proliferator-activated receptor-γ (PPARγ) and lower liver X receptor α (LXRα) mRNA level, both of which were crucial in regulating fatty acid metabolism, and correspondingly altered the expression of their downstream genes in GMECs. These results were further enhanced by the silencing of SP1. These findings suggest that SP1 may play an important role in fatty acid metabolism. Full article
(This article belongs to the Section Biochemistry)
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Open AccessReview Cellular Disulfide Bond Formation in Bioactive Peptides and Proteins
Int. J. Mol. Sci. 2015, 16(1), 1791-1805; https://doi.org/10.3390/ijms16011791
Received: 24 November 2014 / Accepted: 2 January 2015 / Published: 14 January 2015
Cited by 17 | PDF Full-text (1358 KB) | HTML Full-text | XML Full-text
Abstract
Bioactive peptides play important roles in metabolic regulation and modulation and many are used as therapeutics. These peptides often possess disulfide bonds, which are important for their structure, function and stability. A systematic network of enzymes—a disulfide bond generating enzyme, a disulfide bond
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Bioactive peptides play important roles in metabolic regulation and modulation and many are used as therapeutics. These peptides often possess disulfide bonds, which are important for their structure, function and stability. A systematic network of enzymes—a disulfide bond generating enzyme, a disulfide bond donor enzyme and a redox cofactor—that function inside the cell dictates the formation and maintenance of disulfide bonds. The main pathways that catalyze disulfide bond formation in peptides and proteins in prokaryotes and eukaryotes are remarkably similar and share several mechanistic features. This review summarizes the formation of disulfide bonds in peptides and proteins by cellular and recombinant machinery. Full article
(This article belongs to the Special Issue Bioactive Carbohydrates and Peptides)
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Open AccessReview Mechanisms and Implications of Dual-Acting Methotrexate in Folate-Targeted Nanotherapeutic Delivery
Int. J. Mol. Sci. 2015, 16(1), 1772-1790; https://doi.org/10.3390/ijms16011772
Received: 23 December 2014 / Accepted: 5 January 2015 / Published: 13 January 2015
Cited by 19 | PDF Full-text (1916 KB) | HTML Full-text | XML Full-text
Abstract
The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one
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The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one as a targeting ligand, and the other as a therapeutic agent to be delivered to the diseased cell. However, an alternative simplified approach can be used, in which a single type of molecule displaying dual function as both a targeting ligand and therapeutic agent is conjugated to the nanoparticle. In this review, we evaluate the validity of this new strategy by using methotrexate, which displays multifunctional mechanisms of action. Methotrexate binds to the folate receptor, a surface biomarker frequently overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an enzyme critical for cell survival and division. Thus we describe a series of fifth generation poly(amido amine) dendrimers conjugated with methotrexate, and discuss several lines of evidence supporting the efficacy of this new platform strategy based on surface plasmon resonance spectroscopy, enzyme activity assays, and cell-based studies with folate receptor (+) KB cancer cells. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Open AccessArticle Novel Transcription Factor Variants through RNA-Sequencing: The Importance of Being “Alternative”
Int. J. Mol. Sci. 2015, 16(1), 1755-1771; https://doi.org/10.3390/ijms16011755
Received: 3 November 2014 / Accepted: 26 December 2014 / Published: 13 January 2015
Cited by 2 | PDF Full-text (6491 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alternative splicing is a pervasive mechanism of RNA maturation in higher eukaryotes, which increases proteomic diversity and biological complexity. It has a key regulatory role in several physiological and pathological states. The diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has exponentially empowered
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Alternative splicing is a pervasive mechanism of RNA maturation in higher eukaryotes, which increases proteomic diversity and biological complexity. It has a key regulatory role in several physiological and pathological states. The diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has exponentially empowered the identification of novel transcripts revealing that more than 95% of human genes undergo alternative splicing. The highest rate of alternative splicing occurs in transcription factors encoding genes, mostly in Krüppel-associated box domains of zinc finger proteins. Since these molecules are responsible for gene expression, alternative splicing is a crucial mechanism to “regulate the regulators”. Indeed, different transcription factors isoforms may have different or even opposite functions. In this work, through a targeted re-analysis of our previously published RNA-Sequencing datasets, we identified nine novel transcripts in seven transcription factors genes. In silico analysis, combined with RT-PCR, cloning and Sanger sequencing, allowed us to experimentally validate these new variants. Through computational approaches we also predicted their novel structural and functional properties. Our findings indicate that alternative splicing is a major determinant of transcription factor diversity, confirming that accurate analysis of RNA-Sequencing data can reliably lead to the identification of novel transcripts, with potentially new functions. Full article
(This article belongs to the Special Issue Pre-mRNA Splicing)
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