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91.
Objective
Paraoxonase-1 (PON1), an HDL-C associated enzyme, protects lipoproteins from oxidation. There is evidence that PON1 enzyme activity is reduced in the patients with type 2 diabetes mellitus (T2DM). North-West Indian Punjabis, a distinct ethnic group has high incidence of T2DM. However till date there is no information regarding PON1 enzyme activities and PON1 polymorphisms in T2DM patients of this ethnic group.Methods
We identified polymorphisms in the coding Q192R, L55M and promoter − 909G/C, − 162A/G, − 108C/T of the PON1 gene by using PCR-RFLP, multiplex PCR and allele specific oligonucleotide PCR assays in 250 T2DM patients and 300 healthy controls. We also assessed paraoxonase (PONase) and arylesterase (AREase) activities of PON1 enzyme.Results
The serum PONase (114.2 vs. 178.0 nmol/min/ml) and AREase (62.7 vs. 82.5 μmol/min/ml) activities were significantly lower (p < 0.0001) in patients as compared to controls. PONase activity was affected by all the studied PON1 polymorphisms. However, AREase activity was not affected by any of these polymorphisms. Coding Q192R and promoter − 909G/C polymorphisms showed significant differences in genotypic distribution. QR, RR (Q192R) and GC, CC (− 909G/C) genotypes and L-C-A-R-G, L-T-A-R-G, L-T-G-Q-C haplotypes showed significant association with type 2 diabetes. No significant linkage disequilibrium was observed among the five polymorphisms.Conclusion
Both PONase and AREase activities are lower in patients and this could lead to increased lipid peroxidation and accelerated atherosclerosis in them. PONase activity, but not AREase activity is influenced by PON1 polymorphisms. QR, RR, GC, CC genotypes and L-C-A-R-G, L-T-A-R-G, L-T-G-Q-C haplotypes are commoner in diabetics as compared to controls and may be related to genetic susceptibility to type 2 diabetes. 相似文献92.
Pseudomonas putida CSV86 utilizes benzyl alcohol via catechol and methylnaphthalenes through detoxification pathway via hydroxymethylnaphthalenes
and naphthaldehydes. Based on metabolic studies, benzyl alcohol dehydrogenase (BADH) and benzaldehyde dehydrogenase (BZDH)
were hypothesized to be involved in the detoxification pathway. BADH and BZDH were purified to apparent homogeneity and were
(1) homodimers with subunit molecular mass of 38 and 57 kDa, respectively, (2) NAD+ dependent, (3) broad substrate specific accepting mono- and di-aromatic alcohols and aldehydes but not aliphatic compounds,
and (4) BADH contained iron and magnesium, while BZDH contained magnesium. BADH in the forward reaction converted alcohol
to aldehyde and required NAD+, while in the reverse reaction it reduced aldehyde to alcohol in NADH-dependent manner. BZDH showed low K
m value for benzaldehyde as compared to BADH reverse reaction. Chemical cross-linking studies revealed that BADH and BZDH do
not form multi-enzyme complex. Thus, the conversion of aromatic alcohol to acid is due to low K
m and high catalytic efficiency of BZDH. Phylogenetic analysis revealed that BADH is a novel enzyme and diverged during the
evolution to gain the ability to utilize mono- and di-aromatic compounds. The wide substrate specificity of these enzymes
enables strain to detoxify methylnaphthalenes to naphthoic acids efficiently. 相似文献
93.
Folding of naturally occurring proteins has eluded a universal molecular level explanation till date. Rather, there is an abundance of diverse views on dominant factors governing protein folding. Through rigorous analyses of several thousand crystal structures, we observe that backbones of folded proteins display some remarkable invariant features. Folded proteins are characterized by spatially well-defined, distance dependent, and universal, neighborhoods of amino acids which defy any of the conventionally prevalent views. These findings present a compelling case for a newer view of protein folding which takes into account solvent mediated and amino acid shape and size assisted optimization of the tertiary structure of the polypeptide chain to make a functional protein. 相似文献
94.
Leif Brottem Matthew D. Turner Bilal Butt Aditya Singh 《Human ecology: an interdisciplinary journal》2014,42(3):351-365
This paper focuses on a conundrum that has dominated the literature on pastoral mobility and institutions in dryland regions of the world, where livestock production is the main livelihood system. High spatiotemporal variability of rainfall and forage resources are seen to require flexible rules and porous social boundaries to facilitate pastoral mobility—characteristics that run counter to conventional views of the requirements for effective common property institutions. We seek to explore this paradox by investigating the spatiotemporal variability of forage availability (using satellite derived vegetation indices as a proxy for green forage) in four transhumance zones (“transhumance sheds”) in Mali, West Africa. For each transhumance shed, three characteristics with important institutional implications are evaluated over an eleven-year period between 2000 and 2010: the inter-annual variability of forage phenology, seasonal changes in connectivity of green forage patches, and the degree to which key forage locations exist in the form of consistently early green-up and/or late senescence. Periods of vegetation green-up and senescence, which determine the timing of transhumant livestock movements, are found to be sufficiently regular from year to year to be governed by conventional institutions. Seasonal changes in the north-south connectivity of green patches are sufficiently rapid for customary systems of sharing of pasture information to be effective (rather than more technologically sophisticated systems of pasture information). Moreover, transhumance sheds contain key pastoral forage sites, which because of their consistently early greening or late senescence, are strong candidates for territorial protection from alternative land uses such as agriculture. These findings support local herders’ views of transhumance as composed of regular patterns of herd movements along prescribed corridors between key pastoral sites. The seasonal regularity of key pastoral resources has been obscured by an overemphasis on environmental unpredictability that characterizes dryland systems at certain spatial and temporal scales. This paper suggests that policies directed at improving pastoral resource governance must focus instead on securing pastoralists’ access rights to movement corridors, specific pastures and water points. 相似文献
95.
Sivaram Vedantam Rita Rani Monica Garg Suresh K. Atreja 《Molecular biology reports》2014,41(4):1959-1965
The purpose of this study was to determine the role of Ang-II in buffalo spermatozoa; localize angiotensin type 1 (AT1) receptors on the sperm surface and understand the signaling mechanisms involved therein. Immunoblotting and immunocytochemistry using polyclonal Rabbit anti-AT1 (N-10) IgG were performed to confirm the presence of AT1 receptors. Intracellular levels of cyclic adenosine monophosphate (cAMP) were determined by non-radioactive enzyme immunoassay, while that of Calcium [Ca2+] were estimated by fluorimetry using Fura2AM dye. The results obtained showed that AT1 receptors were found on the post-acrosomal region, neck and tail regions. Immunoblotting revealed a single protein band with molecular weight of 40 kDa. Ang-II treated cells produced significantly higher level of cAMP compared to untreated cells (22.66 ± 2.4 vs. 10.8 ± 0.98 pmol/108 cells, p < 0.01). The mean levels of Ca2+ were also higher in Ang-II treated cells compared to control (117.4 ± 6.1 vs. 61.15 ± 4.2 nmol/108 cells; p < 0.01). The stimulatory effect of Ang-II in both the cases was significantly inhibited in the presence of Losartan (AT1 antagonist; p < 0.05) indicating the involvement of AT1 receptors. Further, presence of neomycin (protein kinase C inhibitor) inhibited significantly the Ang-II mediated rise in Ca2+ indicating the involvement of PKC pathway. These findings confirm the presence of AT1 receptors in buffalo spermatozoa and that Ang-II mediates its actions via the activation of these receptors. Ang-II stimulates the rise in intracellular levels of cAMP and Ca2+ during capacitation. 相似文献
96.
Life history parameters of the freshwater chironomid species Kiefferulus calligaster (Kieffer, 1911) were investigated under laboratory conditions, with the use of larval development time and wing length as key features. An index of fitness was derived using these two parameters to represent the fitness of adults as a function of the larval development. Survivorship, deduced from the data on the mortality of larval stages, was related to developmental time as—(survivorship, lx) y = 1.16 ? 0.04 × (days). The larval development time varied between males and females with a minimum of 8 and a maximum of 12 days from first instar larva to eclosion of imagine. The average wing length of adult females was larger than males (3.9 mm ± 0.03 S.E. vs. 3.36 mm ± 0.02 S.E.), for both early and late emerging individuals. The degree of dimorphism between the sexes was prominent for wing length and larval development time. The index of fitness for the early and late emerging adults differed significantly (P < 0.05) in both the sexes. 相似文献
97.
Usman Sumo Friend Tambunan Hilyatuz Zahroh Bimo Budi Utomo Arli Aditya Parikesit 《Bioinformation》2014,10(1):23-27
Dengue has become a major global health threat, especially in tropical and subtropical regions. The development of antiviral agent
targeting viral replication is really needed at this time. NS5 methyltransferase presents as a novel antiviral target. This enzyme
plays an important role in the methylation of 5''-cap mRNA. Inhibition of the NS5 methyltransferase could inhibit dengue virus
replication. In this research, two sites of NS5 methyltransferase (S-Adenosyl methionine/SAM binding site and RNA-cap site) were
used as targets for inhibition. As much as 300 commercial cyclic peptides were screened to these target sites by means of molecular
docking. Analysis of ligand-enzyme binding free energy and pharmacological prediction revealed two best ligands, namely
[Tyr123] Prepro Endothelin (110-130), amide, human and Urotensin II, human. According to molecular dynamic simulation, both
ligands maintain a stable complex conformation between enzyme and ligand at temperature 310 K and 312 K. Hence, Urotensin II,
human is more reactive at 312 K than at 310 K. However, both ligands can be used as potential inhibitor candidates against NS5
methyltransferase of dengue virus with Urotensin II, human exposes more promising activity at 312 K. 相似文献
98.
Aditya Saxena Barry Denholm Stephanie Bunt Marcus Bischoff Krishnaswamy VijayRaghavan Helen Skaer 《PLoS biology》2014,12(12)
Most epithelial tubes arise as small buds and elongate by regulated morphogenetic processes including oriented cell division, cell rearrangements, and changes in cell shape. Through live analysis of Drosophila renal tubule morphogenesis we show that tissue elongation results from polarised cell intercalations around the tubule circumference, producing convergent-extension tissue movements. Using genetic techniques, we demonstrate that the vector of cell movement is regulated by localised epidermal growth factor (EGF) signalling from the distally placed tip cell lineage, which sets up a distal-to-proximal gradient of pathway activation to planar polarise cells, without the involvement for PCP gene activity. Time-lapse imaging at subcellular resolution shows that the acquisition of planar polarity leads to asymmetric pulsatile Myosin II accumulation in the basal, proximal cortex of tubule cells, resulting in repeated, transient shortening of their circumferential length. This repeated bias in the polarity of cell contraction allows cells to move relative to each other, leading to a reduction in cell number around the lumen and an increase in tubule length. Physiological analysis demonstrates that animals whose tubules fail to elongate exhibit abnormal excretory function, defective osmoregulation, and lethality. 相似文献
99.
Sonal Jaydeep Sidhaye Mandar Phatak Shamik Banerjee Aditya Mulay Ojas Deshpande Sourabh Bhide Tressa Jacob Ines Gehring Christiane Nuesslein-Volhard Mahendra Sonawane 《PLoS genetics》2014,10(9)
The epidermis is a stratified epithelium, which forms a barrier to maintain the internal milieu in metazoans. Being the outermost tissue, growth of the epidermis has to be strictly coordinated with the growth of the embryo. The key parameters that determine tissue growth are cell number and cell size. So far, it has remained unclear how the size of epidermal cells is maintained and whether it contributes towards epidermal homeostasis. We have used genetic analysis in combination with cellular imaging to show that zebrafish goosepimples/myosin Vb regulates plasma membrane homeostasis and is involved in maintenance of cell size in the periderm, the outermost epidermal layer. The decrease in peridermal cell size in Myosin Vb deficient embryos is compensated by an increase in cell number whereas decrease in cell number results in the expansion of peridermal cells, which requires myosin Vb (myoVb) function. Inhibition of cell proliferation as well as cell size expansion results in increased lethality in larval stages suggesting that this two-way compensatory mechanism is essential for growing larvae. Our analyses unravel the importance of Myosin Vb dependent cell size regulation in epidermal homeostasis and demonstrate that the epidermis has the ability to maintain a dynamic balance between cell size and cell number. 相似文献
100.
Aditya Kulkarni Kannan Alpadi Tirupataiah Sirupangi Christopher Peters 《Traffic (Copenhagen, Denmark)》2014,15(5):558-571
The convergence of the antagonistic reactions of membrane fusion and fission at the hemifusion/hemifission intermediate has generated a captivating enigma of whether Soluble N‐ethylmaleimide sensitive factor Attachment Protein Receptor (SNAREs) and dynamin have unusual counter‐functions in fission and fusion, respectively. SNARE‐mediated fusion and dynamin‐driven fission are fundamental membrane flux reactions known to occur during ubiquitous cellular communication events such as exocytosis, endocytosis and vesicle transport. Here we demonstrate the influence of the dynamin homolog Vps1 (Vacuolar protein sorting 1) on lipid mixing and content mixing properties of yeast vacuoles, and on the incorporation of SNAREs into fusogenic complexes. We propose a novel concept that Vps1, through its oligomerization and SNARE domain binding, promotes the hemifusion‐content mixing transition in yeast vacuole fusion by increasing the number of trans‐SNAREs . 相似文献