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  • Articles  (32)
  • BioMed Central  (27)
  • American Geophysical Union  (3)
  • American Association for the Advancement of Science (AAAS)
  • 2010-2014  (24)
  • 2005-2009  (6)
  • 2000-2004  (2)
  • Biology  (32)
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  • Articles  (32)
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  • 1
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    A novel GPR40 agonist, CNX-011-67, suppresses glucagon secretion in pancreatic islets under chronic glucolipotoxic conditions in vitro (2014)
    BioMed Central
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    Publication Date: 2014-09-04
    Description: Background: Elevated glucose concentrations lead to increased insulin secretion and suppression of glucagon secretion. In fact, insulin is a physiological inhibitor of glucagon secretion. Type 2 diabetes mellitus (T2DM) patients have defects in insulin secretion. In addition to this, lack of suppression of glucagon secretion under elevated glucose concentrations is also observed in T2DM patients. We have earlier shown that GPR40 activation by CNX-011-67 stimulates glucose stimulated insulin secretion (GSIS). Here we extended our studies to examine the impact of GPR40 activation by CNX-011-67 on glucagon secretion from intact islets under both normal and glucolipotoxic conditions.FindingsGlucagon secretion from intact rat islets was suppressed under elevated glucose concentration. Activation of GPR40 by CNX-011-67 further suppressed glucagon secretion. Culturing islets under chronic glucolipotoxic (GL) conditions, we have observed increased high glucose mediated glucagon secretion and content which were reduced with GPR40 activation by CNX-011-67. Interestingly, expression of pre-proglucagon gene (GCG) remained unchanged under glucolipotoxicity in the presence or absence of GPR40 activation. Conclusion: Activation of GPR40 by CNX-011-67 can reduce glucagon secretion from pancreatic islets.
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
    Published by BioMed Central
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  • 2
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    Molecular cloning and in-silico characterization of high temperature stress responsive pAPX gene isolated from heat tolerant Indian wheat cv. Raj 3765 (2014)
    BioMed Central
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    Publication Date: 2014-10-11
    Description: Background: Heat stress leads to accelerated production of reactive oxygen species (ROS) which causes a huge amount of oxidative damage to the cellular components of plants. A large number of heat stress related genes as HSPs, catalases, peroxidases are overexpressed at the time of stress. A potent stress responsive gene peroxisomal ascorbate peroxidase (TapAPX) obtained from heat stress (42[degree sign]C) responsive subtractive cDNA library from a thermo tolerant wheat cv. Raj3765 at anthesis stage was cloned, characterized and its role was validated under heat stress by proteomics and in-silico studies.. In the present study we report the characterization at molecular and in-silico level of peroxisomal TapAPX gene isolated from heat tolerant wheat cultivar of India. Results: qPCR studies of TapAPX gene displayed up to 203 fold level of expression at 42[degree sign]C heat stress exposure. A full length cDNA of 876 bp obtained by RACE deduced a protein of 292 amino acid residues which gives a complete 3D structure of pAPX by homology modeling. TapAPX cDNA was cloned in expression vector pET28 (a+) and the recombinant protein over-expressed in E. coli BL21 showed highest homology with APX protein as deduced by peptide mass fingerprinting. Conclusions: TapAPX gene from wheat cv Raj3765 has a distinct role in conferring thermo tolerance to the plants and thus can be used in crop improvement programmes for development of crops tolerant to high temperature.
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
    Published by BioMed Central
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  • 3
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    Procalcitonin as a prognostic marker for sepsis: a prospective observational study (2014)
    BioMed Central
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    Publication Date: 2014-07-18
    Description: Background: Procalcitonin is useful for the diagnosis of sepsis but its prognostic value regarding mortality is unclear. This prospective observational study was designed to study the prognostic value of procalcitonin in prediction of 28 day mortality in patients of sepsis. Fifty-four consecutive patients of sepsis, severe sepsis and septic shock defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria from medical Intensive Care Unit (ICU) of a tertiary care center in New Delhi, India were enrolled from July 2011 to June 2013. Procalcitonin (PCT), C-reactive protein (CRP) measurements were recorded on day 1, day 7 and day 28 of follow up. Results: Procalcitonin value was a better predictor of all-cause short-term mortality than C-reactive protein. Those patients with Procalcitonin levels
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
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  • 4
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    Direct observation of percolation in a manganite thin film (2002)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2002-09-21
    Description: Upon cooling, the isolated ferromagnetic domains in thin films of La0.33Pr0.34Ca0.33MnO3 start to grow and merge at the metal-insulator transition temperature TP1, leading to a steep drop in resistivity, and continue to grow far below TP1. In contrast, upon warming, the ferromagnetic domain size remains unchanged until near the transition temperature. The jump in the resistivity results from the decrease in the average magnetization. The ferromagnetic domains almost disappear at a temperature TP2 higher than TP1, showing a local magnetic hysteresis in agreement with the resistivity hysteresis. Even well above TP2, some ferromagnetic domains with higher transition temperatures are observed, indicating magnetic inhomogeneity. These results may shed more light on the origin of the magnetoresistance in these materials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Liuwan -- Israel, Casey -- Biswas, Amlan -- Greene, R L -- de Lozanne, Alex -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):805-7. Epub 2002 Sep 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of Texas, Austin, TX 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12242450" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Comment on "Influence of HLA-C expression level on HIV control" (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-09-14
    Description: Apps et al. (Reports, 5 April 2013, p. 87) found that high human leukocyte antigen C (HLA-C) expression favors HIV-1 control. However, as noted here, HLA-C was assessed with a monoclonal antibody (DT9) that cross-reacts with HLA-E. In the context of the available evidence, this is consistent with the idea that the two leukocyte antigens collaborate to keep the HIV-1 virus at bay.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lo Monaco, Elisa -- Tremante, Elisa -- Biswas, Priscilla -- Cranage, Martin P -- Zipeto, Donato -- Beretta, Alberto -- Giacomini, Patrizio -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1175. doi: 10.1126/science.1241266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Istituto Nazionale Tumori Regina Elena, Via delle Messi d'Oro 156, 00158 Roma, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24031002" target="_blank"〉PubMed〈/a〉
    Keywords: *Gene Expression Regulation ; HIV/*immunology ; HIV Infections/*genetics/*immunology ; HLA-C Antigens/*genetics ; Humans ; T-Lymphocytes, Cytotoxic/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity (2013)
    BioMed Central
    Details
    Publication Date: 2013-07-02
    Description: Background: In the progression towards diabetes, glucolipotoxicity is one of the main causes of pancreatic beta cell pathology. The aim of this study was to examine the in vitro effects of chronic glucolipotoxic conditions on cellular responses in pancreatic islets, including glucose and fat metabolism, Calcium mobilization, insulin secretion and insulin content. Results: Exposure of islets to chronic glucolipotoxic conditions decreased glucose stimulated insulin secretion in vitro. Reduced protein levels of Glut2/slc2a2, and decreased glucokinase and pyruvate carboxylase mRNA levels indicated a significant lowering in glucose sensing. Concomitantly, both fatty acid uptake and triglyceride accumulation increased significantly while fatty acid oxidation decreased. This general suppression in glucose metabolism correlated well with a decrease in mitochondrial number and activity, reduction in cellular ATP content and dampening of the TCA cycle. Further, we also observed a decrease in IP3 levels and lower Calcium mobilization in response to glucose. Importantly, chronic glucolipotoxic conditions in vitro decreased insulin gene expression, insulin content, insulin granule docking (to the plasma membrane) and insulin secretion. Conclusions: Our results present an integrated view of the effects of chronic glucolipotoxic conditions on known and novel signaling events, in vitro, that results in reduced glucose responsiveness and insulin secretion.
    Electronic ISSN: 1471-2121
    Topics: Biology , Medicine
    Published by BioMed Central
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  • 7
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    Helical ambivalency induced by point mutations (2013)
    BioMed Central
    Details
    Publication Date: 2013-05-16
    Description: Background Mutation of amino acid sequences in a protein may have diverse effects on its structure and function. Point mutations ofeven a single amino acid residue in the helices of thenon-redundant database may lead to sequentially identical peptides whichadopt different secondary structures in different proteins. However, variousphysico-chemical factors which govern the formation of these ambivalent helices generated by point mutationsof a sequence are not clearly known.Results Sequences generated by point mutations of helices are mapped on to theirnon-helical counterparts in the SCOP database. The results show thatshort helices are prone to transform into non-helical conformations upon pointmutations. Mutation of amino acid residues by helix breakerspreferentially yield non-helical conformations, while mutation withresidues of intermediate helix propensity display least preferences fornon-helical conformations. Differences in the solvent accessibility of themutating/mutated residues are found to be a major criteria for these sequencesto conform to non-helical conformations. Even with minimal differencesin the amino acid distributions of the sequences flanking the helicaland non-helical conformations, helix-flanking sequences are found bemore solvent accessible.Conclusions All types of mutations from helicalto non-helical conformations are investigated. The primary factorsattributing such changes in conformation can be: i) type/propensity ofthe mutating and mutant residues ii) solvent accessibility of the residue at the mutation siteiii) context/environment dependence of the flanking sequences. Theresults from the present study may be used to design de novoproteins via point mutations.
    Electronic ISSN: 1472-6807
    Topics: Biology
    Published by BioMed Central
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  • 8
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    Structural insights into Resveratrol's antagonist and partial agonist actions on estrogen receptor alpha (2013)
    BioMed Central
    Details
    Publication Date: 2013-10-27
    Description: Background: Resveratrol, a naturally occurring stilbene, has been categorized as phytoestrogen due to its capability to compete with natural estrogens for binding to estrogen receptor alpha (ERalpha) and thus modulating the biological responses exerted by the receptor. Biological effects of resveratrol (RES) on estrogen receptor alpha (ERalpha) remain highly controversial, since both estrogenic and anti-estrogenic properties were observed. Results: Here, we provide insight into the structural basis of the agonist/antagonist effects of RES on ERalpha ligand binding domain (LBD). Using atomistic simulation, we found that RES bound ERalpha monomer in antagonist conformation, where Helix 12 moves away from the ligand pocket and orients into the co-activator binding groove of LBD, is more stable than RES bound ERalpha in agonist conformation, where Helix 12 lays over the ligand binding pocket. Upon dimerization, the agonistic conformation of RES-ERalpha dimer becomes more stable compared to the corresponding monomer but still remains less stable compared to the corresponding dimer in antagonist conformation. Interestingly, while the binding pocket and the binding contacts of RES to ERalpha are similar to those of pure agonist diethylstilbestrol (DES), the binding energy is much less and the hydrogen bonding contacts also differ providing clues for the partial agonistic character of RES on ERalpha. Conclusions: Our Molecular Dynamics simulation of RES-ERalpha structures with agonist and antagonist orientations of Helix 12 suggests RES action is more similar to Selective Estrogen Receptor Modulator (SERM) opening up the importance of cellular environment and active roles of co-regulator proteins in a given system. Our study reveals that potential co-activators must compete with the Helix 12 and displace it away from the activator binding groove to enhance the agonistic activity.
    Electronic ISSN: 1472-6807
    Topics: Biology
    Published by BioMed Central
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  • 9
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    Scan for Motifs: a webserver for the analysis of post-transcriptional regulatory elements in the 3[prime] untranslated regions (3[prime] UTRs) of mRNAs (2014)
    BioMed Central
    Details
    Publication Date: 2014-06-09
    Description: Background: Gene expression in vertebrate cells may be controlled post-transcriptionally through regulatory elements in mRNAs. These are usually located in the untranslated regions (UTRs) of mRNA sequences, particularly the 3[prime]UTRs. Results: Scan for Motifs (SFM) simplifies the process of identifying a wide range of regulatory elements on alignments of vertebrate 3[prime]UTRs. SFM includes identification of both RNA Binding Protein (RBP) sites and targets of miRNAs. In addition to searching pre-computed alignments, the tool provides users the flexibility to search their own sequences or alignments. The regulatory elements may be filtered by expected value cutoffs and are cross-referenced back to their respective sources and literature. The output is an interactive graphical representation, highlighting potential regulatory elements and overlaps between them. The output also provides simple statistics and links to related resources for complementary analyses. The overall process is intuitive and fast. As SFM is a free web-application, the user does not need to install any software or databases. Conclusions: Visualisation of the binding sites of different classes of effectors that bind to 3[prime]UTRs will facilitate the study of regulatory elements in 3[prime] UTRs.
    Electronic ISSN: 1471-2105
    Topics: Biology , Computer Science
    Published by BioMed Central
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  • 10
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    Procalcitonin as a prognostic marker for sepsis: a prospective observational study (2014)
    BioMed Central
    Details
    Publication Date: 2014-07-22
    Description: Background: Procalcitonin is useful for the diagnosis of sepsis but its prognostic value regarding mortality is unclear. This prospective observational study was designed to study the prognostic value of procalcitonin in prediction of 28 day mortality in patients of sepsis. Fifty-four consecutive patients of sepsis, severe sepsis and septic shock defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria from medical Intensive Care Unit (ICU) of a tertiary care center in New Delhi, India were enrolled from July 2011 to June 2013. Procalcitonin (PCT), C-reactive protein (CRP) measurements were recorded on day 1, day 7 and day 28 of follow up. Results: Procalcitonin value was a better predictor of all-cause short-term mortality than C-reactive protein. Those patients with Procalcitonin levels
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
    Published by BioMed Central
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