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551.
Michelle J Groome MBBCh Nicola Page Margaret M Cortese Jocelyn Moyes Prof Heather J Zar Constant N Kapongo Christine Mulligan Ralph Diedericks Cheryl Cohen Jessica A Fleming Mapaseka Seheri Prof Jeffrey Mphahlele Sibongile Walaza Kathleen Kahn Dr Meera ChhaganA Duncan Steele PhD Umesh D Parashar Elizabeth R Zell Prof Shabir A Madhi 《The Lancet infectious diseases》2014,14(11):1096-1104
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Shazia Perveen Ji Seon Yang Tae Joung Ha Shin Hee Yoon 《The Korean journal of physiology & pharmacology》2014,18(4):297-305
Flavonoids have an ability to suppress various ion channels. We determined whether one of flavonoids, cyanidin-3-glucoside, affects adenosine 5''-triphosphate (ATP)-induced calcium signaling using digital imaging methods for intracellular free Ca2+ concentration ([Ca2+]i), reactive oxygen species (ROS) and mitochondrial membrane potential in PC12 cells. Treatment with ATP (100µM) for 90 sec induced [Ca2+]i increases in PC12 cells. Pretreatment with cyanidin-3-glucoside (1µ g/ml to 100µg/ml) for 30 min inhibited the ATP-induced [Ca2+]i increases in a concentration-dependent manner (IC50=15.3µg/ml). Pretreatment with cyanidin-3-glucoside (15µg/ml) for 30 min significantly inhibited the ATP-induced [Ca2+]i responses following removal of extracellular Ca2+ or depletion of intracellular [Ca2+]i stores. Cyanidin-3-glucoside also significantly inhibited the relatively specific P2X2 receptor agonist 2-MeSATP-induced [Ca2+]i responses. Cyanidin-3-glucoside significantly inhibited the thapsigargin or ATP-induced store-operated calcium entry. Cyanidin-3-glucoside significantly inhibited the ATP-induced [Ca2+]i responses in the presence of nimodipine and ω-conotoxin. Cyanidin-3-glucoside also significantly inhibited KCl (50 mM)-induced [Ca2+]i increases. Cyanidin-3-glucoside significantly inhibited ATP-induced mitochondrial depolarization. The intracellular Ca2+ chelator BAPTA-AM or the mitochondrial Ca2+ uniporter inhibitor RU360 blocked the ATP-induced mitochondrial depolarization in the presence of cyanidin-3-glucoside. Cyanidin-3-glucoside blocked ATP-induced formation of ROS. BAPTA-AM further decreased the formation of ROS in the presence of cyanidin-3-glucoside. All these results suggest that cyanidin-3-glucoside inhibits ATP-induced calcium signaling in PC12 cells by inhibiting multiple pathways which are the influx of extracellular Ca2+ through the nimodipine and ω-conotoxin-sensitive and -insensitive pathways and the release of Ca2+ from intracellular stores. In addition, cyanidin-3-glucoside inhibits ATP-induced formation of ROS by inhibiting Ca2+-induced mitochondrial depolarization. 相似文献
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Shazia Anjum Manish Bathla Saminder Panchal Gurvinder Pal Singh Manpreet Singh 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2018,12(2):135-140
Introduction
Research in the last decade tried to focus on natural and unnatural causes of death in schizophrenic patients, but recent few years has focussed on emerging cardio-metabolic risk factors, as a cause of mortality in such patients.Aim of the study
To assess the determinant of metabolic syndrome in drug naïve schizophrenic patients.Methodology
It was a cross sectional study; 30 indoor patients with diagnosis of schizophrenia were included. Height, weight, waist circumference and Blood pressure assessment was done by using standard protocol. Fasting Blood Glucose (FBG), Triglyceride (TGs), High Density Lipoprotein (HDL) cholesterol, Low Density Lipoprotein (LDL) total cholesterol were measured. International Diabetes Federation (IDF) criteria was considered for establishing metabolic syndrome. Statistical analysis was done by using chi square and ANOVA.Results
Majority of the patients were females; hailing from rural area; unskilled professional; educated up to below primary level; were single and Hindu by religion. Most common metabolic abnormality was low HDL in 76.6%; High TGs in 26.6%; High SBP ≥130 mm Hg in 16.67%; DBP>85 mm Hg in 13.33%; High FBS 10% of the patients.In risk assessment strongest risk factors for metabolic syndrome were high waist circumference, FBS and TGs. BMI, total cholesterol, LDL and VLDL were also observed as a risk factors in drug naïve schizophrenic patients.Conclusion
HDL, FBS, TGs, waist circumference and BMI are all the strong risk factors for development of metabolic syndrome in drug naïve schizophrenia patients. 相似文献555.
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Shazia Aslam Man-Chiu Poon Vivien C. Yee Derrick J. Bowen Graham R. Standen 《British journal of haematology》1995,91(2):452-457
Summary. Molecular analysis performed on a Canadian family with congenital factor XIII deficiency revealed a homozygous missense mutation (Leu667Pro) in exon 14 of the A subunit gene in three affected siblings. The mutation results from a T-to-C transition at nucleotide position 2087 and generates a new Msp1 restriction site. Digestion of an amplified fragment containing exon 14 with this restriction enzyme enabled the heterozygous allele to be identified in both parents (who were third cousins) and three other family members. SSCP analysis detected no additional mutations in the coding or consensus splice sequences of the A subunit gene. The mutant nucleotide substitution was absent in 60 normal alleles and 10 unrelated patients with XIIIA deficiency. Leu667 is located in the carboxyl terminal beta barrel 2 domain of the A subunit molecule. Computer modelling based on 3D crystallographic data predicts that the mutant protein has aberrant folding and is likely to be rapidly degraded following translation. 相似文献
559.
Immacolata Venditto Ana S. Luis Maja Rydahl Julia Schückel Vania O. Fernandes Silvia Vidal-Melgosa Pedro Bule Arun Goyal Virginia M. R. Pires Catarina G. Dourado Luís M. A. Ferreira Pedro M. Coutinho Bernard Henrissat J. Paul Knox Arnaud Baslé Shabir Najmudin Harry J. Gilbert William G. T. Willats Carlos M. G. A. Fontes 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(26):7136-7141
The breakdown of plant cell wall (PCW) glycans is an important biological and industrial process. Noncatalytic carbohydrate binding modules (CBMs) fulfill a critical targeting function in PCW depolymerization. Defining the portfolio of CBMs, the CBMome, of a PCW degrading system is central to understanding the mechanisms by which microbes depolymerize their target substrates. Ruminococcus flavefaciens, a major PCW degrading bacterium, assembles its catalytic apparatus into a large multienzyme complex, the cellulosome. Significantly, bioinformatic analyses of the R. flavefaciens cellulosome failed to identify a CBM predicted to bind to crystalline cellulose, a key feature of the CBMome of other PCW degrading systems. Here, high throughput screening of 177 protein modules of unknown function was used to determine the complete CBMome of R. flavefaciens. The data identified six previously unidentified CBM families that targeted β-glucans, β-mannans, and the pectic polysaccharide homogalacturonan. The crystal structures of four CBMs, in conjunction with site-directed mutagenesis, provide insight into the mechanism of ligand recognition. In the CBMs that recognize β-glucans and β-mannans, differences in the conformation of conserved aromatic residues had a significant impact on the topology of the ligand binding cleft and thus ligand specificity. A cluster of basic residues in CBM77 confers calcium-independent recognition of homogalacturonan, indicating that the carboxylates of galacturonic acid are key specificity determinants. This report shows that the extended repertoire of proteins in the cellulosome of R. flavefaciens contributes to an extended CBMome that supports efficient PCW degradation in the absence of CBMs that specifically target crystalline cellulose.Plant cell walls (PCWs) consist of interlinked polysaccharides, often impregnated with lignin that evolved to restrict access to enzyme attack. Thus, the recycling of photosynthetically fixed carbon is a slow biological process. Reflecting the intricacy of PCWs, microorganisms that degrade these composite structures produce extensive repertoires of carbohydrate active enzymes (CAZymes) (1), which are of increasing industrial significance (2).CAZymes acting on recalcitrant carbohydrates are frequently appended with noncatalytic carbohydrate binding modules (CBMs). CBMs potentiate the activity of the associated catalytic modules through substrate targeting (see ref. 3 for a review). CBMs and CAZymes are classified into sequence-based families in the CAZy database (www.cazy.org/) (4). Based on their binding mode, CBMs have been classified into three types. Type A CBMs display a planar surface that binds to crystalline polysaccharides; type B modules accommodate internal regions of glycan chains within open clefts; and type C CBMs recognize the termini of glycans (exo-type) in a binding site that adopts a pocket topology (3).Efficient hydrolysis of PCW polysaccharides has been fine-tuned over millions of years in ecological niches that are subjected to intensive selective pressures exemplified by the rumen of mammalian herbivores. A cohort of rumen anaerobic bacteria assemble their PCW degrading apparatus into multiprotein complexes termed cellulosomes (5). Cellulosome assembly is through the interaction of cohesin modules located on the noncatalytic protein, the scaffoldin, and dockerin modules on each enzyme subunit (5). Clostridial cellulosomes bind tightly to PCWs through a scaffoldin family 3 CBM. The repertoire of cellulosomal enzymes expressed by an individual bacterium constitutes a highly selected consortium of biocatalysts optimized to degrade PCWs. Genome sequencing of Ruminococcus flavefaciens strain FD-1 (6), the most abundant ruminal cellulolytic bacterium, revealed an elaborate assembly of scaffoldins, indicating that the bacterium’s cellulosome is an intricate and versatile PCW degrading system. Commensurate with this proposed cellulosomal complexity, the genome of R. flavefaciens FD-1 encodes ∼230 dockerin-containing proteins, which are likely to integrate into the multienzyme complex (6). A large number of the protein modules identified in the R. flavefaciens cellulosome are of unknown function and may reflect an extended capacity to recognize carbohydrates through an extended CBM profile.One of the major challenges facing postgenomic analysis of organisms is the identification of the function of the large number of predicted proteins derived from genomic sequencing. To bridge this gap in knowledge requires the development of high throughput methodologies (HTPMs). Here, we have explored how HTPMs can be used to interrogate the functional complexity of the R. flavefaciens cellulosome. The data support the hypothesis that protein diversity in the R. flavefaciens cellulosome contributes to an expansion in glycan recognition, which is mediated by a ruminococcal-specific cohort of protein modules. 相似文献
560.