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Int. J. Mol. Sci., Volume 12, Issue 10 (October 2011) – 56 articles , Pages 6367-7285

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631 KiB  
Review
Eighteen Years of Molecular Genotyping the Hemophilia Inversion Hotspot: From Southern Blot to Inverse Shifting-PCR
by Liliana C. Rossetti, Claudia P. Radic, Miguel M. Abelleyro, Irene B. Larripa and Carlos D. De Brasi
Int. J. Mol. Sci. 2011, 12(10), 7271-7285; https://doi.org/10.3390/ijms12107271 - 24 Oct 2011
Cited by 23 | Viewed by 11046
Abstract
The factor VIII gene (F8) intron 22 inversion (Inv22) is a paradigmatic duplicon-mediated rearrangement, found in about one half of patients with severe hemophilia A worldwide. The identification of this prevalent cause of hemophilia was delayed for nine years after the [...] Read more.
The factor VIII gene (F8) intron 22 inversion (Inv22) is a paradigmatic duplicon-mediated rearrangement, found in about one half of patients with severe hemophilia A worldwide. The identification of this prevalent cause of hemophilia was delayed for nine years after the F8 characterization in 1984. The aim of this review is to present the wide diversity of practical approaches that have been developed for genotyping the Inv22 (and related int22h rearrangements) since discovery in 1993. The sequence—Southern blot, long distance-PCR and inverse shifting-PCR—for Inv22 genotyping is an interesting example of scientific ingenuity and evolution in order to resolve challenging molecular diagnostic problems. Full article
(This article belongs to the Special Issue Advances in Molecular Diagnostics)
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75 KiB  
Short Note
Isolation and Characterization of 11 New Microsatellite Loci in Erigeron breviscapus (Asteraceae), an Important Chinese Traditional Herb
by Xiang Li, Kexian Song, Junbo Yang and Tingshuang Yi
Int. J. Mol. Sci. 2011, 12(10), 7265-7270; https://doi.org/10.3390/ijms12107265 - 24 Oct 2011
Cited by 8 | Viewed by 5466
Abstract
Erigeron breviscapus (Vant.) Hand.-Mazz. (Asteraceae) is a species endemic to southwestern China and an important traditional Chinese herb for cardiovascular and cerebral vessel diseases. Applying a modified biotin-streptavidin capture method, 11 microsatellite loci were discovered. Polymorphism of each locus was assessed in 24 [...] Read more.
Erigeron breviscapus (Vant.) Hand.-Mazz. (Asteraceae) is a species endemic to southwestern China and an important traditional Chinese herb for cardiovascular and cerebral vessel diseases. Applying a modified biotin-streptavidin capture method, 11 microsatellite loci were discovered. Polymorphism of each locus was assessed in 24 individuals collected from five wild populations. The number of alleles per locus ranged from 2 to 7, with an average of 4.273. The observed (HO) and expected (HE) heterozygosities varied from 0.250 to 0.958 and from 0.337 to 0.786, respectively. Over half of these loci were successfully amplified in two congeneric species. The developed microsatellite markers will be useful for future population genetics and conservation studies, as well as accurate identification of different varieties. Full article
(This article belongs to the Special Issue Advances in Molecular Ecology)
174 KiB  
Article
Estimating the Octanol/Water Partition Coefficient for Aliphatic Organic Compounds Using Semi-Empirical Electrotopological Index
by Erica Silva Souza, Laize Zaramello, Carlos Alberto Kuhnen, Berenice da Silva Junkes, Rosendo Augusto Yunes and Vilma Edite Fonseca Heinzen
Int. J. Mol. Sci. 2011, 12(10), 7250-7264; https://doi.org/10.3390/ijms12107250 - 24 Oct 2011
Cited by 45 | Viewed by 7838
Abstract
A new possibility for estimating the octanol/water coefficient (log P) was investigated using only one descriptor, the semi-empirical electrotopological index (ISET). The predictability of four octanol/water partition coefficient (log P) calculation models was compared using a set of [...] Read more.
A new possibility for estimating the octanol/water coefficient (log P) was investigated using only one descriptor, the semi-empirical electrotopological index (ISET). The predictability of four octanol/water partition coefficient (log P) calculation models was compared using a set of 131 aliphatic organic compounds from five different classes. Log P values were calculated employing atomic-contribution methods, as in the Ghose/Crippen approach and its later refinement, AlogP; using fragmental methods through the ClogP method; and employing an approach considering the whole molecule using topological indices with the MlogP method. The efficiency and the applicability of the ISET in terms of calculating log P were demonstrated through good statistical quality (r > 0.99; s < 0.18), high internal stability and good predictive ability for an external group of compounds in the same order as the widely used models based on the fragmental method, ClogP, and the atomic contribution method, AlogP, which are among the most used methods of predicting log P. Full article
(This article belongs to the Special Issue Advances in Molecular Electronic Structure Calculations)
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875 KiB  
Article
Use of Oligonucleotides Carrying Photolabile Groups for the Control of the Deposition of Nanoparticles in Surfaces and Nanoparticle Association
by Brendan Manning and Ramon Eritja
Int. J. Mol. Sci. 2011, 12(10), 7238-7249; https://doi.org/10.3390/ijms12107238 - 24 Oct 2011
Cited by 3 | Viewed by 6323
Abstract
An oligodeoxynucleotide hairpin containing a photolabile 2-nitrobenzyl group in the loop and terminated with a thiol function was prepared. The photocleavage of such a hairpin on gold yields a surface activated with a single stranded oligonucleotide which can be utilised to direct the [...] Read more.
An oligodeoxynucleotide hairpin containing a photolabile 2-nitrobenzyl group in the loop and terminated with a thiol function was prepared. The photocleavage of such a hairpin on gold yields a surface activated with a single stranded oligonucleotide which can be utilised to direct the assembly of nanoparticles conjugated with a complementary strand. Analysis of photocleaved surfaces gives nanoparticle coverage one order of magnitude higher than nonphotocleaved surfaces. This illustrates the ability of photocleavable hairpins to direct the assembly of nanomaterials on conducting materials. The conjugation of the photocleavable hairpin to a gold nanoparticle allows the observation of intermolecular interactions between hairpins linked in different nanoparticles, by comparing the thermal dissociations of a hairpin-nanoparticle conjugates at 260 nm and 520 nm. We have also shown that it is possible to permanently alter the physiochemical properties of DNA-nanoparticles by the introduction of a photocleavable group. Indeed for the first time it has been shown that by exposure to UV light the disassembly of nanoparticle aggregates can be induced. Full article
(This article belongs to the Section Materials Science)
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928 KiB  
Article
Optimal Production and Biochemical Properties of a Lipase from Candida albicans
by Dongming Lan, Shulin Hou, Ning Yang, Chris Whiteley, Bo Yang and Yonghua Wang
Int. J. Mol. Sci. 2011, 12(10), 7216-7237; https://doi.org/10.3390/ijms12107216 - 24 Oct 2011
Cited by 10 | Viewed by 7953
Abstract
Lipases from microorganisms have multi-faceted properties and play an important role in ever-growing modern biotechnology and, consequently, it is of great significance to develop new ones. In the present work, a lipase gene from Candida albicans (CaLIP10) was cloned and two non-unusual CUG [...] Read more.
Lipases from microorganisms have multi-faceted properties and play an important role in ever-growing modern biotechnology and, consequently, it is of great significance to develop new ones. In the present work, a lipase gene from Candida albicans (CaLIP10) was cloned and two non-unusual CUG serine codons were mutated into universal codons, and its expression in Pichia pastoris performed optimally, as shown by response surface methodology. Optimal conditions were: initial pH of culture 6.86, temperature 25.53 °C, 3.48% of glucose and 1.32% of yeast extract. The corresponding maximal lipolytic activity of CaLIP10 was 8.06 U/mL. The purified CaLIP10 showed maximal activity at pH 8.0 and 25 °C, and a good resistance to non-ionic surfactants and polar organic solvent was noticed. CaLIP10 could effectively hydrolyze coconut oil, but exhibited no obvious preference to the fatty acids with different carbon length, and diacylglycerol was accumulated in the reaction products, suggesting that CaLIP10 is a potential lipase for the oil industry. Full article
(This article belongs to the Section Biochemistry)
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199 KiB  
Review
Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia
by Shang-Der Chen, Ding-I Yang, Tsu-Kung Lin, Fu-Zen Shaw, Chia-Wei Liou and Yao-Chung Chuang
Int. J. Mol. Sci. 2011, 12(10), 7199-7215; https://doi.org/10.3390/ijms12107199 - 21 Oct 2011
Cited by 278 | Viewed by 14766
Abstract
The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. [...] Read more.
The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC1-α). PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis. Full article
(This article belongs to the Special Issue Oxidative Stress and Mitochondria)
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Article
Metal Complexes of Diisopropylthiourea: Synthesis, Characterization and Antibacterial Studies
by Peter A. Ajibade and Nonkululeko H. Zulu
Int. J. Mol. Sci. 2011, 12(10), 7186-7198; https://doi.org/10.3390/ijms12107186 - 21 Oct 2011
Cited by 24 | Viewed by 7022
Abstract
Co(II), Cu(II), Zn(II) and Fe(III) complexes of diisopropylthiourea have been synthesized and characterized by elemental analyses, molar conductivity, magnetic susceptibility, FTIR and electronic spectroscopy. The compounds are non-electrolytes in solution and spectroscopic data of the complexes are consistent with 4-coordinate geometry for the [...] Read more.
Co(II), Cu(II), Zn(II) and Fe(III) complexes of diisopropylthiourea have been synthesized and characterized by elemental analyses, molar conductivity, magnetic susceptibility, FTIR and electronic spectroscopy. The compounds are non-electrolytes in solution and spectroscopic data of the complexes are consistent with 4-coordinate geometry for the metal(II) complexes and six coordinate octahedral for Fe(III) complex. The complexes were screened for their antibacterial activities against six bacteria: Escherichia coli, Pseudomonas auriginosa, Klebsiella pneumoniae, Bacillus cereus, Staphylococcus aureus and Bacillus pumilus. The complexes showed varied antibacterial activities and their minimum inhibitory concentrations (MICs) were determined. Full article
(This article belongs to the Section Materials Science)
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544 KiB  
Review
Mitochondrial Peroxiredoxin III is a Potential Target for Cancer Therapy
by In-Sung Song, Hyoung-Kyu Kim, Seung-Hun Jeong, Sung-Ryul Lee, Nari Kim, Byoung Doo Rhee, Kyung Soo Ko and Jin Han
Int. J. Mol. Sci. 2011, 12(10), 7163-7185; https://doi.org/10.3390/ijms12107163 - 21 Oct 2011
Cited by 47 | Viewed by 10178
Abstract
Mitochondria are involved either directly or indirectly in oncogenesis and the alteration of metabolism in cancer cells. Cancer cells contain large numbers of abnormal mitochondria and produce large amounts of reactive oxygen species (ROS). Oxidative stress is caused by an imbalance between the [...] Read more.
Mitochondria are involved either directly or indirectly in oncogenesis and the alteration of metabolism in cancer cells. Cancer cells contain large numbers of abnormal mitochondria and produce large amounts of reactive oxygen species (ROS). Oxidative stress is caused by an imbalance between the production of ROS and the antioxidant capacity of the cell. Several cancer therapies, such as chemotherapeutic drugs and radiation, disrupt mitochondrial homeostasis and release cytochrome c, leading to apoptosome formation, which activates the intrinsic pathway. This is modulated by the extent of mitochondrial oxidative stress. The peroxiredoxin (Prx) system is a cellular defense system against oxidative stress, and mitochondria in cancer cells are known to contain high levels of Prx III. Here, we review accumulating evidence suggesting that mitochondrial oxidative stress is involved in cancer, and discuss the role of the mitochondrial Prx III antioxidant system as a potential target for cancer therapy. We hope that this review will provide the basis for new strategic approaches in the development of effective cancer treatments. Full article
(This article belongs to the Special Issue Oxidative Stress and Mitochondria)
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567 KiB  
Review
Manganese Superoxide Dismutase: Guardian of the Powerhouse
by Aaron K. Holley, Vasudevan Bakthavatchalu, Joyce M. Velez-Roman and Daret K. St. Clair
Int. J. Mol. Sci. 2011, 12(10), 7114-7162; https://doi.org/10.3390/ijms12107114 - 21 Oct 2011
Cited by 210 | Viewed by 15535
Abstract
The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site [...] Read more.
The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component. Full article
(This article belongs to the Special Issue Oxidative Stress and Mitochondria)
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405 KiB  
Article
Cardioprotective Effects of Glycyrrhizic Acid Against Isoproterenol-Induced Myocardial Ischemia in Rats
by Nagaraja Haleagrahara, Julian Varkkey and Srikumar Chakravarthi
Int. J. Mol. Sci. 2011, 12(10), 7100-7113; https://doi.org/10.3390/ijms12107100 - 21 Oct 2011
Cited by 48 | Viewed by 6794
Abstract
The aim of the present study was to look into the possible protective effects of glycyrrhizic acid (GA) against isoproterenol-induced acute myocardial infarction in Sprague-Dawley rats. The effect of three doses of glycyrrhizic acid in response to isoproterenol (ISO)-induced changes in 8-isoprostane, lipid [...] Read more.
The aim of the present study was to look into the possible protective effects of glycyrrhizic acid (GA) against isoproterenol-induced acute myocardial infarction in Sprague-Dawley rats. The effect of three doses of glycyrrhizic acid in response to isoproterenol (ISO)-induced changes in 8-isoprostane, lipid hydroperoxides, super oxide dismutase and total glutathione were evaluated. Male Sprague-Dawley rats were divided into control, ISO-control, glycyrrhizic acid alone (in three doses-5, 10 and 20 mg/kg BW) and ISO with glycyrrhizic acid (in three doses) groups. ISO was administered at 85 mg/kg BW at two consecutive days and glycyrrhizic acid was administered intraperitoneally for 14 days. There was a significant increase in 8-isoprostane (IP) and lipid hydroperoxide (LPO) level in ISO-control group. A significant decrease in total superoxide dismutase (SOD) and total glutathione (GSH) was seen with ISO-induced acute myocardial infarction. Treatment with GA significantly increased SOD and GSH levels and decreased myocardial LPO and IP levels. Histopathologically, severe myocardial necrosis and nuclear pyknosis and hypertrophy were seen in ISO-control group, which was significantly reduced with GA treatment. Gycyrrhizic acid treatment proved to be effective against isoproterenol-induced acute myocardial infarction in rats and GA acts as a powerful antioxidant and reduces the myocardial lipid hydroperoxide and 8-isoprostane level. Full article
(This article belongs to the Section Biochemistry)
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261 KiB  
Review
Biomarkers in Tumor Angiogenesis and Anti-Angiogenic Therapy
by Andreas Pircher, Wolfgang Hilbe, Isabel Heidegger, Joachim Drevs, André Tichelli and Michael Medinger
Int. J. Mol. Sci. 2011, 12(10), 7077-7099; https://doi.org/10.3390/ijms12107077 - 21 Oct 2011
Cited by 69 | Viewed by 10340
Abstract
Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial [...] Read more.
Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial relevance. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. However not all patients are likely to respond to these therapies, but to date there are no reliable biomarkers available to predict therapy response. Many studies integrated biomarker programs in their study protocols, thus several potential biomarkers have been identified which are currently under clinical investigation in prospective randomized studies. This review intends to give an overview of the described potential biomarkers as well as different imaging techniques such as ultrasound and magnetic resonance imaging that can indicate benefit, resistance and toxicity to anti-angiogenic therapies. Full article
(This article belongs to the Special Issue Biomarkers 2011)
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719 KiB  
Article
Anti-UVC Irradiation and Metal Chelation Properties of 6-Benzoyl-5,7-dihydroxy-4-phenyl-chromen-2-one: An Implications for Anti-Cataract Agent
by Jiahn-Haur Liao, Tzu-Hua Wu, Feng-Lin Hsu, Yi-Shiang Huang, Po-Hung Chiang, Zih-You Huang, Chi-Hsien Huang, Shih-Hsiung Wu and Mei-Hsiang Lin
Int. J. Mol. Sci. 2011, 12(10), 7059-7076; https://doi.org/10.3390/ijms12107059 - 21 Oct 2011
Cited by 5 | Viewed by 8298
Abstract
Coumarin derivative 1, 5,7-dihydroxy-6-(3-methyl-1-butyryl)-4-phenyl-chromen-2-one, has been reported to possess radical scavenging activity and DNA protection. We have synthesized a series of coumarins with structural modifications at positions C4, C5, C6 and C7 and evaluated them for their anti-UVC properties. Coumarin 7, 6-benzoyl-5,6-dihydroxy-4-phenyl-chromen-2-one, was [...] Read more.
Coumarin derivative 1, 5,7-dihydroxy-6-(3-methyl-1-butyryl)-4-phenyl-chromen-2-one, has been reported to possess radical scavenging activity and DNA protection. We have synthesized a series of coumarins with structural modifications at positions C4, C5, C6 and C7 and evaluated them for their anti-UVC properties. Coumarin 7, 6-benzoyl-5,6-dihydroxy-4-phenyl-chromen-2-one, was found to have the most potent activity in protecting porcine γ-crystallin against UVC insults. Results of fluorescence assays indicated that compound 7 was capable of decreasing the loss of intensity while lens crystallins and DNA PUC19 were irradiated with UVC. Presence of compound 7 decreased hydroxyl radical levels determined by probe 1b and the free iron concentrations determined by Ferrozine reagent. The chelation assay showed that compound 7 was chelated to metal via 6-CO and 5-OH on the benzopyrone ring. The observed protective effects of compound 7 towards crystallins from insults of UVC and free radicals may be due to its iron-chelating activity and its peak absorption at 254 nm. Full article
(This article belongs to the Special Issue Antioxidants)
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133 KiB  
Article
Biological Potential of Sixteen Legumes in China
by Yang Yao, Xuzhen Cheng, Lixia Wang, Suhua Wang and Guixing Ren
Int. J. Mol. Sci. 2011, 12(10), 7048-7058; https://doi.org/10.3390/ijms12107048 - 20 Oct 2011
Cited by 80 | Viewed by 9306
Abstract
Phenolic acids have been identified in a variety of legumes including lima bean, broad bean, common bean, pea, jack bean, goa bean, adzuki bean, hyacinth bean, chicking vetch, garbanzo bean, dral, cow bean, rice bean, mung bean and soybean. The present study was [...] Read more.
Phenolic acids have been identified in a variety of legumes including lima bean, broad bean, common bean, pea, jack bean, goa bean, adzuki bean, hyacinth bean, chicking vetch, garbanzo bean, dral, cow bean, rice bean, mung bean and soybean. The present study was carried out with the following aims: (1) to identify and quantify the individual phenolic acid and determine the total phenolic content (TPC); (2) to assess their antioxidant activity, inhibition activities of α-glucosidase, tyrosinase, and formation of advanced glycation endproducts; and (3) to investigate correlations among the phytochemicals and biological activity. Common bean possesses the highest antioxidant activity and advanced glycation endproducts formation inhibition activity. Adzuki bean has the highest α-glucosidase inhibition activity, and mung bean has the highest tyrosinase inhibition activity. There are significant differences in phytochemical content and functional activities among the bean species investigated. Selecting beans can help treat diseases such as dermatological hyperpigmentation illness, type 2 diabetes and associated cardiovascular diseases. Full article
(This article belongs to the Section Biochemistry)
512 KiB  
Article
Candida Colonization Index in Patients Admitted to an ICU
by Giuseppina Caggiano, Filomena Puntillo, Caterina Coretti, Mariateresa Giglio, Ilaria Alicino, Fabio Manca, Francesco Bruno and Maria Teresa Montagna
Int. J. Mol. Sci. 2011, 12(10), 7038-7047; https://doi.org/10.3390/ijms12107038 - 20 Oct 2011
Cited by 24 | Viewed by 9851
Abstract
Multiple-site colonization with Candida spp is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At [...] Read more.
Multiple-site colonization with Candida spp is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp at T0 and six of them had CI ≥0.5. Three patients developed candidemia; they had CI ≥0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Article
Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment
by Xin Zhao, Minsheng Chen, Biyun Huang, Hong Ji and Mu Yuan
Int. J. Mol. Sci. 2011, 12(10), 7022-7037; https://doi.org/10.3390/ijms12107022 - 20 Oct 2011
Cited by 36 | Viewed by 7622
Abstract
The α1A-adrenergic receptor (α1A-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α1A-AR antagonists of N-aryl and N-nitrogen [...] Read more.
The α1A-adrenergic receptor (α1A-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α1A-AR antagonists of N-aryl and N-nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-one-out cross-validation correlation coefficients were q2CoMFA = 0.840 and q2CoMSIA = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r2pred/CoMFA = 0.694; r2pred/CoMSIA = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other α1A-AR antagonists. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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1484 KiB  
Article
Structural Determinants of CX-4945 Derivatives as Protein Kinase CK2 Inhibitors: A Computational Study
by Hongbo Liu, Xia Wang, Jian Wang, Jinghui Wang, Yan Li, Ling Yang and Guohui Li
Int. J. Mol. Sci. 2011, 12(10), 7004-7021; https://doi.org/10.3390/ijms12107004 - 20 Oct 2011
Cited by 12 | Viewed by 7515
Abstract
Protein kinase CK2, also known as casein kinase-2, is involved in a broad range of physiological events including cell growth, proliferation and suppression of apoptosis which are related to human cancers. A series of compounds were identified as CK2 inhibitors and their inhibitory [...] Read more.
Protein kinase CK2, also known as casein kinase-2, is involved in a broad range of physiological events including cell growth, proliferation and suppression of apoptosis which are related to human cancers. A series of compounds were identified as CK2 inhibitors and their inhibitory activities varied depending on their structures. In order to explore the structure-activity correlation of CX-4945 derivatives as inhibitors of CK2, in the present study, a set of ligand- and receptor-based 3D-QSAR models were developed employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). The optimum CoMFA (Rcv2 = 0.618, Rpred2 = 0.892) and CoMSIA (Rcv2 = 0.681, Rpred2 = 0.843) models exhibited reasonable statistical characteristics for CX-4945 derivatives. The results indicated that electrostatic effects contributed the most to both CoMFA and CoMSIA models. The combination of docking analysis and molecular dynamics (MD) simulation showed that Leu45, Lys68, Glu81, Val116, Asp175 and Trp176 of CK2 which formed several direct or water-bridged H-bonds with CX-4945 are crucial for CX-4945 derivatives recognition to CK2. These results can offer useful theoretical references for designing more potent CK2 inhibitors. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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576 KiB  
Review
Protein Misdirection Inside and Outside Motor Neurons in Amyotrophic Lateral Sclerosis (ALS): A Possible Clue for Therapeutic Strategies
by Akemi Ido, Hidenao Fukuyama and Makoto Urushitani
Int. J. Mol. Sci. 2011, 12(10), 6980-7003; https://doi.org/10.3390/ijms12106980 - 19 Oct 2011
Cited by 19 | Viewed by 8342
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive muscle wasting and weakness with no effective cure. Emerging evidence supports the notion that the abnormal conformations of ALS-linked proteins play a central role in triggering the motor neuron degeneration. In [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive muscle wasting and weakness with no effective cure. Emerging evidence supports the notion that the abnormal conformations of ALS-linked proteins play a central role in triggering the motor neuron degeneration. In particular, mutant types of superoxide dismutase 1 (SOD1) and TAR DNA binding protein 43kDa (TDP-43) are key molecules involved in the pathogenesis of familial and sporadic ALS, respectively. The commonalities of the two proteins include a propensity to aggregate and acquire detrimental conformations through oligomerization, fragmentation, or post-translational modification that may drive abnormal subcellular localizations. Although SOD1 is a major cytosolic protein, mutated SOD1 has been localized to mitochondria, endoplasmic reticulum, and even the extracellular space. The nuclear exclusion of TDP-43 is a pathological hallmark for ALS, although the pathogenic priority remains elusive. Nevertheless, these abnormal behaviors based on the protein misfolding are believed to induce diverse intracellular and extracellular events that may be tightly linked to non-cell-autonomous motor neuron death. The generation of mutant- or misfolded protein-specific antibodies would help to uncover the distribution and propagation of the ALS-linked proteins, and to design a therapeutic strategy to clear such species. Herein we review the literature regarding the mislocalization of ALS-linked proteins, especially mutant SOD1 and TDP-43 species, and discuss the rationale of molecular targeting strategies including immunotherapy. Full article
(This article belongs to the Special Issue Studies of Motor Molecules)
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721 KiB  
Article
Environmental Dependence of Artifact CD Peaks of Chiral Schiff Base 3d-4f Complexes in Soft Mater PMMA Matrix
by Yu Okamoto, Keisuke Nidaira and Takashiro Akitsu
Int. J. Mol. Sci. 2011, 12(10), 6966-6979; https://doi.org/10.3390/ijms12106966 - 19 Oct 2011
Cited by 10 | Viewed by 6712
Abstract
Four chiral Schiff base binuclear 3d-4f complexes (NdNi, NdCu, GdNi, and GdCu) have been prepared and characterized by means of electronic and CD spectra, IR spectra, magnetic measurements, and X-ray crystallography (NdNi). A so-called artifact peak of solid state CD spectra, which was [...] Read more.
Four chiral Schiff base binuclear 3d-4f complexes (NdNi, NdCu, GdNi, and GdCu) have been prepared and characterized by means of electronic and CD spectra, IR spectra, magnetic measurements, and X-ray crystallography (NdNi). A so-called artifact peak of solid state CD spectra, which was characteristic of oriented molecules without free molecular rotation, appeared at about 470 nm. Magnetic data of the complexes in the solid state (powder) and in PMMA cast films or solutions indicated that only GdCu preserved molecular structures in various matrixes of soft maters. For the first time, we have used the changes of intensity of artifact CD peaks to detect properties of environmental (media solid state (KBr pellets), PMMA cast films, concentration dependence of PMMA in acetone solutions, and pure acetone solution) for chiral 3d-4f complexes (GdCu). Rigid matrix keeping anisotropic orientation exhibited a decrease in the intensity of the artifact CD peak toward negative values. The present results suggest that solid state artifact CD peaks can be affected by environmental viscosity of a soft mater matrix. Full article
(This article belongs to the Special Issue Applications of Circular Dichroism)
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392 KiB  
Article
In Vitro Anti-Listerial Activities of Crude n-Hexane and Aqueous Extracts of Garcinia kola (heckel) Seeds
by Dambudzo Penduka and Anthony I. Okoh
Int. J. Mol. Sci. 2011, 12(10), 6952-6965; https://doi.org/10.3390/ijms12106952 - 19 Oct 2011
Cited by 5 | Viewed by 6025
Abstract
We assessed the anti-Listerial activities of crude n-hexane and aqueous extracts of Garcinia kola seeds against a panel of 42 Listeria isolates previously isolated from wastewater effluents in the Eastern Cape Province of South Africa and belonging to Listeria monocytogenes, Listeria [...] Read more.
We assessed the anti-Listerial activities of crude n-hexane and aqueous extracts of Garcinia kola seeds against a panel of 42 Listeria isolates previously isolated from wastewater effluents in the Eastern Cape Province of South Africa and belonging to Listeria monocytogenes, Listeria grayi and Listeria ivanovii species. The n-hexane fraction was active against 45% of the test bacteria with zones of inhibition ranging between 8–17 mm, while the aqueous fraction was active against 29% with zones of inhibition ranging between 8–11 mm. The minimum inhibitory concentrations (MIC) were within the ranges of 0.079–0.625 mg/mL for the n-hexane extract and 10 to >10 mg/mL for the aqueous extract. The rate of kill experiment carried out for the n-hexane extract only, revealed complete elimination of the initial bacterial population for L. grayi (LAL 15) at 3× and 4× MIC after 90 and 60 min; L. monocytogenes (LAL 8) at 3× and 4× MIC after 60 and 15 min; L. ivanovii (LEL 18) at 3× and 4× MIC after 120 and 15 min; L. ivanovii (LEL 30) at 2, 3 and 4× MIC values after 105, 90 and 15 min exposure time respectively. The rate of kill activities were time- and concentration-dependant and the extract proved to be bactericidal as it achieved a more than 3log10 decrease in viable cell counts after 2 h exposure time for all of the four test organisms at 3× and 4× MIC values. The results therefore show the potential presence of anti-Listerial compounds in Garcinia kola seeds that can be exploited in effective anti-Listerial chemotherapy. Full article
(This article belongs to the Section Biochemistry)
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268 KiB  
Article
N-Acetylcysteine Reduces Markers of Differentiation in 3T3-L1 Adipocytes
by Pablo Calzadilla, Daiana Sapochnik, Soledad Cosentino, Virginia Diz, Lelia Dicelio, Juan Carlos Calvo and Liliana N. Guerra
Int. J. Mol. Sci. 2011, 12(10), 6936-6951; https://doi.org/10.3390/ijms12106936 - 19 Oct 2011
Cited by 83 | Viewed by 8435
Abstract
Oxidative stress plays a critical role in the pathogenesis of diabetes, hypertension and atherosclerosis. Some authors reported that fat accumulation correlates to systemic oxidative stress in humans and mice, but the relationship of lipid production and oxidative metabolism is still unclear. In our [...] Read more.
Oxidative stress plays a critical role in the pathogenesis of diabetes, hypertension and atherosclerosis. Some authors reported that fat accumulation correlates to systemic oxidative stress in humans and mice, but the relationship of lipid production and oxidative metabolism is still unclear. In our laboratory we used 3T3-L1 preadipocytes, which are able to differentiate into mature adipocytes and accumulate lipids, as obesity model. We showed that intracellular reactive oxygen species (ROS) and antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased in parallel with fat accumulation. Meanwhile N-acetylcysteine (NAC), a well known antioxidant and Glutathione (GSH) precursor, inhibited ROS levels as well as fat accumulation in a concentration-dependent manner. NAC also inhibited both adipogenic transcription factors CCAAT/enhancer binding protein beta (C/EBP β) and peroxisomal proliferator activated receptor gamma (PPAR γ) expression; we suggested that intracellular GSH content could be responsible for these effects. Full article
(This article belongs to the Special Issue Antioxidants)
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420 KiB  
Article
Evaluation of Antioxidant Compounds and Total Sugar Content in a Nectarine [Prunus persica (L.) Batsch] Progeny
by Walid Abidi, Sergio Jiménez, María Ángeles Moreno and Yolanda Gogorcena
Int. J. Mol. Sci. 2011, 12(10), 6919-6935; https://doi.org/10.3390/ijms12106919 - 19 Oct 2011
Cited by 66 | Viewed by 8374
Abstract
Epidemiological studies suggest that consumption of fruit rich in phenolic compounds is associated with health-protective effects due to their antioxidant properties. For these reasons quality evaluation has become an important issue in fruit industry and in breeding programs. Phytochemical traits such as total [...] Read more.
Epidemiological studies suggest that consumption of fruit rich in phenolic compounds is associated with health-protective effects due to their antioxidant properties. For these reasons quality evaluation has become an important issue in fruit industry and in breeding programs. Phytochemical traits such as total phenolics, flavonoids, anthocyanins, L-ascorbic acid, sugar content and relative antioxidant capacity (RAC) were analyzed over four years in flesh fruit of an F1 population “Venus” × “Big Top” nectarines. Other traits such as harvesting date, yield, fruit weight, firmness, soluble solids concentration (SSC), pH, titratable acidity (TA) and ripening index (RI) were also determined in the progeny. Results showed high variability among genotypes for all analyzed traits. Total phenolics and flavonoids showed significant positive correlations with RAC implying that both are important antioxidant bioactive compounds in peaches. We found genotypes with enhanced antioxidant capacity and a better performance than progenitors, and in consequence the best marketability. Full article
(This article belongs to the Section Biochemistry)
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649 KiB  
Review
Metal-Induced Oxidative Stress and Plant Mitochondria
by Els Keunen, Tony Remans, Sacha Bohler, Jaco Vangronsveld and Ann Cuypers
Int. J. Mol. Sci. 2011, 12(10), 6894-6918; https://doi.org/10.3390/ijms12106894 - 18 Oct 2011
Cited by 157 | Viewed by 11192
Abstract
A general status of oxidative stress in plants caused by exposure to elevated metal concentrations in the environment coincides with a constraint on mitochondrial electron transport, which enhances ROS accumulation at the mitochondrial level. As mitochondria are suggested to be involved in redox [...] Read more.
A general status of oxidative stress in plants caused by exposure to elevated metal concentrations in the environment coincides with a constraint on mitochondrial electron transport, which enhances ROS accumulation at the mitochondrial level. As mitochondria are suggested to be involved in redox signaling under environmental stress conditions, mitochondrial ROS can initiate a signaling cascade mediating the overall stress response, i.e., damage versus adaptation. This review highlights our current understanding of metal-induced responses in plants, with focus on the production and detoxification of mitochondrial ROS. In addition, the potential involvement of retrograde signaling in these processes will be discussed. Full article
(This article belongs to the Special Issue Oxidative Stress and Mitochondria)
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133 KiB  
Review
Malignant Catarrhal Fever: Understanding Molecular Diagnostics in Context of Epidemiology
by Hong Li, Cristina W. Cunha and Naomi S. Taus
Int. J. Mol. Sci. 2011, 12(10), 6881-6893; https://doi.org/10.3390/ijms12106881 - 18 Oct 2011
Cited by 32 | Viewed by 8815
Abstract
Malignant catarrhal fever (MCF) is a frequently fatal disease, primarily of ruminants, caused by a group of gammaherpesviruses. Due to complexities of pathogenesis and epidemiology in various species, which are either clinically-susceptible or reservoir hosts, veterinary clinicians face significant challenges in laboratory diagnostics. [...] Read more.
Malignant catarrhal fever (MCF) is a frequently fatal disease, primarily of ruminants, caused by a group of gammaherpesviruses. Due to complexities of pathogenesis and epidemiology in various species, which are either clinically-susceptible or reservoir hosts, veterinary clinicians face significant challenges in laboratory diagnostics. The recent development of specific assays for viral DNA and antibodies has expanded and improved the inventory of laboratory tests and opened new opportunities for use of MCF diagnostics. Issues related to understanding and implementing appropriate assays for specific diagnostic needs must be addressed in order to take advantage of molecular diagnostics in the laboratory. Full article
(This article belongs to the Special Issue Advances in Molecular Diagnostics)
137 KiB  
Article
Assessing Molecular Signature for Some Potential Date (Phoenix dactylifera L.) Cultivars from Saudi Arabia, Based on Chloroplast DNA Sequences rpoB and psbA-trnH
by Fahad Al-Qurainy, Salim Khan, Fahad M. Al-Hemaid, M. Ajmal Ali, M. Tarroum and M. Ashraf
Int. J. Mol. Sci. 2011, 12(10), 6871-6880; https://doi.org/10.3390/ijms12106871 - 17 Oct 2011
Cited by 34 | Viewed by 7682
Abstract
Phoenix dactylifera L. (date palm), being economically very important, is widely cultivated in the Middle East and North Africa, having about 400 different cultivars. Assessment of date cultivars under trading and farming is a widely accepted problem owing to lack of a unique [...] Read more.
Phoenix dactylifera L. (date palm), being economically very important, is widely cultivated in the Middle East and North Africa, having about 400 different cultivars. Assessment of date cultivars under trading and farming is a widely accepted problem owing to lack of a unique molecular signature for specific date cultivars. In the present study, eight different cultivars of dates viz., Khodry, Khalas, Ruthana, Sukkari, Sefri, Segae, Ajwa and Hilali were sequenced for rpoB and psbA-trnH genes and analyzed using bioinformatics tools to establish a cultivar-specific molecular signature. The combined aligned data matrix was of 1147 characters, of which invariable and variable sites were found to be 958 and 173, respectively. The analysis clearly reveals three major groups of these cultivars: (i) Khodary, Sefri, Ajwa, Ruthana and Hilali (58% BS); (ii) Sukkari and Khalas (64% BS); and (iii) Segae. The economically most important cultivar Ajwa showed similarity with Khodary and Sefri (67% BS).The sequences of the date cultivars generated in the present study showed bootstrap values between 38% and 70% so these sequences could be carefully used as molecular signature for potential date cultivars under trading and selection of genuine cultivars at the seedling stage for farming. Full article
(This article belongs to the Section Biochemistry)
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327 KiB  
Article
Supercritical Carbon Dioxide Extraction of Bioactive Compounds from Ampelopsis grossedentata Stems: Process Optimization and Antioxidant Activity
by Yuefei Wang, Le Ying, Da Sun, Shikang Zhang, Yuejin Zhu and Ping Xu
Int. J. Mol. Sci. 2011, 12(10), 6856-6870; https://doi.org/10.3390/ijms12106856 - 14 Oct 2011
Cited by 29 | Viewed by 7741
Abstract
Supercritical carbon dioxide (SC-CO2) extraction of bioactive compounds including flavonoids and phenolics from Ampelopsis grossedentata stems was carried out. Extraction parameters such as pressure, temperature, dynamic time and modifier, were optimized using an orthogonal array design of L9 (34 [...] Read more.
Supercritical carbon dioxide (SC-CO2) extraction of bioactive compounds including flavonoids and phenolics from Ampelopsis grossedentata stems was carried out. Extraction parameters such as pressure, temperature, dynamic time and modifier, were optimized using an orthogonal array design of L9 (34), and antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and ferrous ion chelating (FIC) assay. The best conditions obtained for SC-CO2 extraction of flavonoids was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:3, v/v), and that for phenolics extraction was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:1, v/v). Meantime, flavonoids and phenolics were found to be mainly responsible for the DPPH scavenging activity of the extracts, but not for the chelating activity on ferrous ion according to Pearson correlation analysis. Furthermore, several unreported flavonoids such as apigenin, vitexin, luteolin, etc., have been detected in the extracts from A. grossedentata stems. Full article
(This article belongs to the Section Biochemistry)
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763 KiB  
Article
Nuclei of Tsuga canadensis: Role of Flavanols in Chromatin Organization
by Walter Feucht, Markus Schmid and Dieter Treutter
Int. J. Mol. Sci. 2011, 12(10), 6834-6855; https://doi.org/10.3390/ijms12106834 - 14 Oct 2011
Cited by 4 | Viewed by 5996
Abstract
Needle primordia of Tsuga canadensis (hemlock) arising from flank meristems of a shoot apex, form cell lineages consisting of four or eight cells. Within a recently established lineage there is striking uniformity in the pattern of nuclear flavanols. This fact points to an [...] Read more.
Needle primordia of Tsuga canadensis (hemlock) arising from flank meristems of a shoot apex, form cell lineages consisting of four or eight cells. Within a recently established lineage there is striking uniformity in the pattern of nuclear flavanols. This fact points to an identical transcriptional expression of these flavanols during cell cycling. However two lineages, even if located close together within the same meristem, can be very different in the expression of both cell shape and nuclear flavanol pattern, indicating that epigenetic positional signals are operating in a collective specification of cell lineage development. There is a wide range of nuclear flavanol patterning from a mosaic-like distribution in an activated cell type to a homogenous appearance in silenced cell types. Single cells deriving from lineages are desynchronized because they underlie a signaling network at a higher tissue level which results in stronger epigenetic modifications of their nuclear flavanols. As an extreme case of epigenetic modulation, transient drought conditions caused a drastic reduction of nuclear flavanols. Upon treatment with sucrose or cytokinin, these nuclear flavanols could be fully restored. Analytical determination of the flavanols revealed 3.4 mg/g DW for newly sprouting needles and 19.6 mg/g DW for anthers during meiosis. The roughly 6-fold difference in flavanols is apparently a reflection of the highly diverging organogenetic processes. Collectively, the studies provide strong evidence for combinatorial interplay between cell fate and nuclear flavanols. Full article
(This article belongs to the Section Biochemistry)
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Graphical abstract

1135 KiB  
Review
Far from Equilibrium Percolation, Stochastic and Shape Resonances in the Physics of Life
by Nicola Poccia, Alessio Ansuini and Antonio Bianconi
Int. J. Mol. Sci. 2011, 12(10), 6810-6833; https://doi.org/10.3390/ijms12106810 - 14 Oct 2011
Cited by 9 | Viewed by 9307
Abstract
Key physical concepts, relevant for the cross-fertilization between condensed matter physics and the physics of life seen as a collective phenomenon in a system out-of-equilibrium, are discussed. The onset of life can be driven by: (a) the critical fluctuations at the protonic percolation [...] Read more.
Key physical concepts, relevant for the cross-fertilization between condensed matter physics and the physics of life seen as a collective phenomenon in a system out-of-equilibrium, are discussed. The onset of life can be driven by: (a) the critical fluctuations at the protonic percolation threshold in membrane transport; (b) the stochastic resonance in biological systems, a mechanism that can exploit external and self-generated noise in order to gain efficiency in signal processing; and (c) the shape resonance (or Fano resonance or Feshbach resonance) in the association and dissociation processes of bio-molecules (a quantum mechanism that could play a key role to establish a macroscopic quantum coherence in the cell). Full article
(This article belongs to the Special Issue Origin of Life 2011)
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331 KiB  
Article
Nuclear Markers of Danube Sturgeons Hybridization
by Andreea Dudu, Radu Suciu, Marian Paraschiv, Sergiu Emil Georgescu, Marieta Costache and Patrick Berrebi
Int. J. Mol. Sci. 2011, 12(10), 6796-6809; https://doi.org/10.3390/ijms12106796 - 14 Oct 2011
Cited by 35 | Viewed by 8543
Abstract
Acipenseriformes are composed of 25 sturgeon species and two paddlefish species distributed exclusively in the northern hemisphere. The Danube River and the Black Sea were originally inhabited by six sturgeon species but two are extinct and only four are still reproducing currently in [...] Read more.
Acipenseriformes are composed of 25 sturgeon species and two paddlefish species distributed exclusively in the northern hemisphere. The Danube River and the Black Sea were originally inhabited by six sturgeon species but two are extinct and only four are still reproducing currently in the Lower Danube: Huso huso, Acipenser stellatus, A. gueldenstaedtii and A. ruthenus. Sturgeon species hybridize more easily than other fish and the determination of pure species or hybrid status is important for conservation and for breeding in fish farms. This survey demonstrated that morphological determination of this status is not reliable and a molecular tool, based on eight microsatellites genotypes is proposed. This method, based on three successive statistical analyses including Factorial Correspondence Analysis (FCA), Structure assignation and NewHybrids status determination, showed a high efficiency in discriminating pure species specimens from F1, F2 and two kinds of backcross individuals involving three of the four reproducing Lower Danube sturgeon species. Full article
(This article belongs to the Section Biochemistry)
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1190 KiB  
Article
The Stimulation of IGF-1R Expression by Lewis(y) Antigen Provides a Powerful Development Mechanism of Epithelial Ovarian Carcinoma
by Dawo Liu, Juanjuan Liu, Changzhi Wang, Bei Lin, Qing Liu, Yingying Hao, Shulan Zhang and Masao Iwamori
Int. J. Mol. Sci. 2011, 12(10), 6781-6795; https://doi.org/10.3390/ijms12106781 - 14 Oct 2011
Cited by 19 | Viewed by 6441
Abstract
Objective: This study aimed to measure and correlate the expression of insulin-like growth factor receptor-1 (IGF-1R) and the Lewis(y) antigen in ovarian cancer cell lines and tissue samples. Methods: Reverse transcriptase PCR (RT-PCR), Western blotting, immunoprecipitation, immunohistochemistry, and immunofluorescence double-labeling techniques were applied [...] Read more.
Objective: This study aimed to measure and correlate the expression of insulin-like growth factor receptor-1 (IGF-1R) and the Lewis(y) antigen in ovarian cancer cell lines and tissue samples. Methods: Reverse transcriptase PCR (RT-PCR), Western blotting, immunoprecipitation, immunohistochemistry, and immunofluorescence double-labeling techniques were applied to detect and measure the expression of Lewis(y) and IGF-1R. Results: In α1,2-fucosyltransferase (α1,2-FT)-transfected cells, IGF-1R expression was significantly upregulated compared with cells that do not overexpress α1,2-FT (P < 0.05). The amount of Lewis(y) expressed on IGF-1R increased 1.81-fold in α1,2-FT-overexpressing cells (P < 0.05), but the ratio of Lewis(y) expressed on IGF-1R to total IGF-1R was unaltered between two cells (P > 0.05). In malignant epithelial ovarian tumors, the positivity rates of Lewis(y) and IGF-1R detection were 88.3% and 93.33%, respectively, which is higher than the positivity rates in marginal (60.00% and 63.33%, all P < 0.05), benign (33.00% and 53.33%, all P < 0.01), and normal (0% and 40%, all P 0.05). Both IGF-1R and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P < 0.05). Conclusion: Overexpression of Lewis(y) results in overexpression of IGF-1R. Both IGF-1R and Lewis(y) are associated with the occurrence and development of ovarian cancers. Full article
(This article belongs to the Section Biochemistry)
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2067 KiB  
Article
A Novel Cold-Adapted Lipase from Sorangium cellulosum Strain So0157-2: Gene Cloning, Expression, and Enzymatic Characterization
by Yuan-Yuan Cheng, Yun-Kai Qian, Zhi-Feng Li, Zhi-Hong Wu, Hong Liu and Yue-Zhong Li
Int. J. Mol. Sci. 2011, 12(10), 6765-6780; https://doi.org/10.3390/ijms12106765 - 13 Oct 2011
Cited by 17 | Viewed by 9227
Abstract
Genome sequencing of cellulolytic myxobacterium Sorangium cellulosum reveals many open-reading frames (ORFs) encoding various degradation enzymes with low sequence similarity to those reported, but none of them has been characterized. In this paper, a predicted lipase gene (lipA) was cloned from [...] Read more.
Genome sequencing of cellulolytic myxobacterium Sorangium cellulosum reveals many open-reading frames (ORFs) encoding various degradation enzymes with low sequence similarity to those reported, but none of them has been characterized. In this paper, a predicted lipase gene (lipA) was cloned from S. cellulosum strain So0157-2 and characterized. lipA is 981-bp in size, encoding a polypeptide of 326 amino acids that contains the pentapeptide (GHSMG) and catalytic triad residues (Ser114, Asp250 and His284). Searching in the GenBank database shows that the LipA protein has only the 30% maximal identity to a human monoglyceride lipase. The novel lipA gene was expressed in Escherichia coli BL21 and the recombinant protein (r-LipA) was purified using Ni-NTA affinity chromatography. The enzyme hydrolyzed the p-nitrophenyl (pNP) esters of short or medium chain fatty acids (≤C10), and the maximal activity was on pNP acetate.The r-LipA is a cold-adapted lipase, with high enzymatic activity in a wide range of temperature and pH values. At 4 °C and 30 °C, the Km values of r-LipA on pNP acetate are 0.037 ± 0.001 and 0.174 ± 0.006 mM, respectively. Higher pH and temperature conditions promoted hydrolytic activity toward the pNP esters with longer chain fatty acids. Remarkably, this lipase retained much of its activity in the presence of commercial detergents and organic solvents. The results suggest that the r-LipA protein has some new characteristics potentially promising for industrial applications and S. cellulosum is an intriguing resource for lipase screening. Full article
(This article belongs to the Section Biochemistry)
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