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101.
Vasavada RC Garcia-Ocaña A Zawalich WS Sorenson RL Dann P Syed M Ogren L Talamantes F Stewart AF 《The Journal of biological chemistry》2000,275(20):15399-15406
The factors that regulate pancreatic beta cell proliferation are not well defined. In order to explore the role of murine placental lactogen (PL)-I (mPL-I) in islet mass regulation in vivo, we developed transgenic mice in which mPL-I is targeted to the beta cell using the rat insulin II promoter. Rat insulin II-mPL-I mice displayed both fasting and postprandial hypoglycemia (71 and 105 mg/dl, respectively) as compared with normal mice (92 and 129 mg/dl; p < 0.00005 for both). Plasma insulin concentrations were inappropriately elevated, and insulin content in the pancreas was increased 2-fold. Glucose-stimulated insulin secretion by perifused islets was indistinguishable from controls at 7.5, 15, and 20 mm glucose. Beta cell proliferation rates were twice normal (p = 0. 0005). This hyperplasia, together with a 20% increase in beta cell size, resulted in a 2-fold increase in islet mass (p = 0.0005) and a 1.45-fold increase in islet number (p = 0.0012). In mice, murine PL-I is a potent islet mitogen, is capable of increasing islet mass, and is associated with hypoglycemia over the long term. It can be targeted to the beta cell using standard gene targeting techniques. Potential exists for beta cell engineering using this strategy. 相似文献
102.
Identification of an N-Terminal Region of Sigma 54 Required for Enhancer Responsiveness 总被引:4,自引:3,他引:1 下载免费PDF全文
Sigma 54 associates with bacterial core RNA polymerase and converts it into an enhancer-responsive enzyme. Deletion of the N-terminal 40 amino acids is known to result in loss of the ability to respond to enhancer binding proteins. In this work PCR mutagenesis and genetic screens were used to identify a small patch, from amino acids 33 to 37, that is required for proper response to activator in vivo. Site-directed single point mutants within this segment were constructed and studied. Two of these were defective in responding to the enhancer binding protein in vitro. The mutants could still direct the polymerase to bind to DNA and initiate transient melting. However, they failed in directing activator-dependent formation of a heparin-stable open complex. Thus, amino acid region 33 to 37 includes critical activation response determinants. This region overlaps the larger leucine patch negative-control region, suggesting that anti-inhibition and positive activation are closely coupled events. 相似文献
103.
Gao, Xiao-Pei, Syed R. Akhter, and Israel Rubinstein.Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters. J. Appl.Physiol. 84(1): 169-176, 1998.The purpose ofthis study was to determine whether bradykinin mediatesovalbumin-induced increase in macromolecular efflux from the nasalmucosa of ovalbumin-sensitized hamsters in vivo and, if so, whether theL-arginine/nitric oxidebiosynthetic pathway transduces, in part, this response. We found thatsuffusion of ovalbumin onto the in situ nasal mucosa ofovalbumin-sensitized hamsters, but not of controls, elicited asignificant time- and concentration-dependent increase in clearance offluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa;P < 0.05). HOE-140, but notdes-Arg9,[Leu8]-bradykinin,andNG-L-argininemethyl ester (L-NAME), but notNG-D-argininemethyl ester, significantly attenuated ovalbumin-induced responses.L-Arginine, but notD-arginine, abolished the effects ofL-NAME.L-NAME also significantlyattenuated bradykinin-, but not adenosine- induced increase inmacromolecular efflux from the in situ nasal mucosa. Overall, thesedata suggest that ovalbumin increases macromolecular efflux from the insitu nasal mucosa of ovalbumin-sensitized hamsters, in part, byproducing bradykinin with subsequent activation of theL-arginine/nitric oxidebiosynthetic pathway. 相似文献
104.
A Ca2+‐binding protein with numerous roles and uses: parvalbumin in molecular biology and physiology
Syed Hasan Arif 《BioEssays : news and reviews in molecular, cellular and developmental biology》2009,31(4):410-421
Parvalbumins (PVs) are acidic, intracellular Ca2+‐binding proteins of low molecular weight. They are associated with several Ca2+‐mediated cellular activities and physiological processes. It has been suggested that PV might function as a “Ca2+ shuttle” transporting Ca2+ from troponin‐C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus, PV may contribute to the performance of rapid, phasic movements by accelerating the contraction–relaxation cycle of fast‐twitch muscle fibers. Interestingly, PVs promote the generation of power stroke in fish by speeding up the rate of relaxation and thus provide impetus to attain maximal sustainable speeds. However, immunological monitoring of diverse tissues demonstrated that PVs are also present in non‐muscle cells. The axoplasmic transport and various intracellular secretory mechanisms including the endocrine secretions seem to be controlled by the Ca2+ regulation machinery. Any defect in the Ca2+ handling apparatus may cause several clinical problems; for instance, PV deficiency alters the neuronal activity, a key mechanism leading to epileptic seizures. Moreover, atypical relaxation of the heart results in diastolic dysfunction, which is a major cause of heart failure predominantly among the aged people. PV may offer a unique potential to correct defective relaxation in energetically compromised failing hearts through PV gene transfer. Consequently, PV gene transfer may present a new therapeutic approach to correct cellular disturbances in Ca2+ signaling pathways of diseased organs. Hence, PVs appear to be amazingly useful candidate proteins regulating a variety of cellular functions through action on Ca2+ flux management. 相似文献
105.
Asma Iqbal Mahmoud Labib Darija Muharemagic Syed Sattar Brent R. Dixon Maxim V. Berezovski 《PloS one》2015,10(9)
There are currently no standard methods for the detection of Cryptosporidium spp., or other protozoan parasites, in foods, and existing methods are often inadequate, with low and variable recovery efficiencies. Food testing is difficult due to the low concentrations of parasites, the difficulty in eluting parasites from some foods, the lack of enrichment methods, and the presence of PCR inhibitors. The main objectives of the present study were to obtain DNA aptamers binding to the oocyst wall of C. parvum, and to use the aptamers to detect the presence of this parasite in foods. DNA aptamers were selected against C. parvum oocysts using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Ten rounds of selection led to the discovery of 14 aptamer clones with high affinities for C. parvum oocysts. For detecting parasite-bound aptamers, a simple electrochemical sensor was employed, which used a gold nanoparticle-modified screen-printed carbon electrode. This aptasensor was fabricated by self-assembling a hybrid of a thiolated ssDNA primer and the anti- C. parvum aptamer. Square wave voltammetry was employed to quantitate C. parvum in the range of 150 to 800 oocysts, with a detection limit of approximately 100 oocysts. The high sensitivity and specificity of the developed aptasensor suggests that this novel method is very promising for the detection and identification of C. parvum oocysts on spiked fresh fruits, as compared to conventional methods such as microscopy and PCR. 相似文献
106.
107.
Madhur D. Shastri Niall Stewart Mathew Eapen Gregory M. Peterson Syed Tabish R. Zaidi Nuri Gueven Sukhwinder Singh Sohal Rahul P. Patel 《PloS one》2015,10(3)
Background
T-cell-mediated inflammatory cytokines, such as interleukin (IL)-4, IL-5, IL-13 and tumor necrosis factor-alpha (TNF-α), play an important role in the initiation and progression of inflammatory airways diseases. Low-molecular-weight heparins (LMWHs), widely used anticoagulants, possess anti-inflammatory properties making them potential treatment options for inflammatory diseases, including asthma. In the current study, we investigated the modulating effects of two LMWHs (enoxaparin and dalteparin) on the release of cytokines from stimulated peripheral blood mononuclear cells (PBMCs) of asthmatic subjects to identify the specific components responsible for the effects.Methods
PBMCs from asthmatic subjects (consist of ~75% of T-cells) were isolated from blood taken from ten asthmatic subjects. The PBMCs were pre-treated in the presence or absence of different concentrations of LMWHs, and were then stimulated by phytohaemagglutinin for the release of IL-4, IL-5, IL-13 and TNF-α. LMWHs were completely or selectively desulfated and their anticoagulant effect, as well as the ability to modulate cytokine release, was determined. LMWHs were chromatographically fractionated and each fraction was tested for molecular weight determination along with an assessment of anticoagulant potency and effect on cytokine release.Results
Enoxaparin inhibited cytokine release by more than 48%, whereas dalteparin increased their release by more than 25%. The observed anti-inflammatory effects of enoxaparin were independent of their anticoagulant activities. Smaller fractions, in particular dp4 (four saccharide units), were responsible for the inhibitory effect of enoxaparin. Whereas, the larger fractions, in particular dp22 (twenty two saccharide units), were associated with the stimulatory effect of dalteparin.Conclusion
Enoxaparin and dalteparin demonstrated opposing effects on inflammatory markers. These observed effects could be due to the presence of structurally different components in the two LMWHs arising from different methods of depolymerisation. This study provides a platform for further studies investigating the usefulness of enoxaparin in various inflammatory diseases. 相似文献108.
Andrew S. Azman Justin Lessler Syed Moinuddin Satter Michael V. Mckay Azharul Khan Dilruba Ahmed Emily S. Gurley 《PLoS neglected tropical diseases》2015,9(12)
Background
In Bangladesh, pharmacy-purchased oral rehydration solution (ORS) is often used to treat diarrhea, including cholera. Over-the-counter sales have been used for epidemiologic surveillance in the past, but rarely, if ever, in low-income countries. With few early indicators for cholera outbreaks in endemic areas, diarrhea-related product sales may serve as a useful surveillance tool.Methodology/Principal Findings
We tracked daily ORS sales at 50 pharmacies and drug-sellers in an urban Bangladesh community of 129,000 for 6-months while simultaneously conducting surveillance for diarrhea hospitalizations among residents. We developed a mobile phone based system to track the sales of ORS and deployed it in parallel with a paper-based system. Our objectives were to determine if the mobile phone system was practical and acceptable to pharmacists and drug sellers, whether data were reported accurately compared to a paper-based system, and whether ORS sales were associated with future incidence of cholera hospitalizations within the community. We recorded 47,215 customers purchasing ORS, and 315 hospitalized diarrhea cases, 22% of which had culture-confirmed cholera. ORS sales and diarrhea incidence were independently associated with the mean daily temperature; therefore both unadjusted and adjusted models were explored. Through unadjusted cross-correlation statistics and generalized linear models, we found increases in ORS sales were significantly associated with increases in hospitalized diarrhea cases up to 9-days later and hospitalized cholera cases up to one day later. After adjusting for mean daily temperature, ORS was significantly associated with hospitalized diarrhea two days later and hospitalized cholera one day later.Conclusions/Significance
Pharmacy sales data may serve as a feasible and useful surveillance tool. Given the relatively short lagged correlation between ORS sales and diarrhea, rapid and accurate sales data are key. More work is needed in creating actionable algorithms that make use of this data and in understanding the generalizability of our findings to other settings. 相似文献109.
Syed G. Dastager Rahul Mawlankar Shan-Kun Tang Krishnamurthi Srinivasan V. Venkata Ramana Yogesh S. Shouche 《Antonie van Leeuwenhoek》2014,105(1):199-206
A novel bacterial strain, designated SGD-1123T was isolated from Chorao Island, in Goa Province, India. The strain was found to be able to grow at 15–42 °C, pH 5–12 and 0–12 % (w/v) NaCl. The whole cell hydrolysates were found to contain meso-diaminopimelic acid, galactose and arabinose. The major fatty acids were identified as iso-C15:0 and anteiso-C15:0, MK-7 was identified as the predominant menaquinone and the predominant polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified aminolipid. The genomic DNA G+C content was determined to be 44.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences placed the isolate within the genus Bacillus and further revealed that strain SGD-1123T had highest sequence similarity with Bacillus aquimaris, and forms a separate clade with its closest relatives i.e. B. aquimaris, Bacillus vietnamensis and Bacillus marisflavi, with which it shares 94.5, 94.1 and 94.1 % similarity respectively. The phylogenetic, chemotaxonomic and phenotypic analyses indicated that strain SGD-1123T represents a novel species within the genus Bacillus, for which the name Bacillus enclensis is proposed. The type strain is SGD-1123T (NCIM 5450T=CCTCC AB 2011125T). 相似文献
110.
Muhammad Ajmal Waqas Ahmed Ahmed Sadeque Syeda Hafiza Benish Ali Syed Habib Bokhari Nuzhat Ahmed Raheel Qamar 《Molecular biology reports》2010,37(8):3869-3875
Familial Hypercholesterolemia (FH) results in elevated levels of blood lipids including total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) with normal triglycerides (TG). This disease is one of the major contributors towards an early onset of coronary heart disease (CHD). The aim of the present study was to identify the genes responsible for causing FH in Pakistani population, for this purpose a large consanguineous FH family was selected for genetic analysis. Serum lipid levels, including TC, TG, LDL-C and high density lipoprotein cholesterol (HDL-C), were determined in patients and healthy controls. In order to find the causative mutation in this family, direct sequencing of the low density lipoprotein receptor (LDLR) gene was performed. In addition the part of the Apolipoprotein-B (APOB) gene containing the mutations R3500Q and R3500W was also sequenced. Affected individuals of the family were found to have raised TC and LDL-C levels. Sequencing revealed an insertion mutation (c.2416_2417InsG) in exon 17 of the LDLR gene in all the affected individuals of the family. Common FH causing APOB mutations were not present in this family. Heterozygous individuals had TC levels ranging from ~300–500 mg/dl and the only homozygous individual with typical xanthomas had TC levels exceeding 900 mg/dl. This is the first report of a known LDLR gene mutation causing FH in the Pakistani population. Despite a large heterogeneity of LDLR mutations there are still some common mutations which are responsible for FH throughout the world. 相似文献