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91.
Khadikar PV Mather KC Singh S Phadnis A Shrivastava A Mandaloi M 《Bioorganic & medicinal chemistry》2002,10(6):1761-1766
Hydrophobicity (logP) as well as quantiative structure-toxicity relationships (QSTRs) of some benzene derivatives acting by narcosis have been established based on narcotic mechanisms of action and toxicity data to the fathead minnow, Daphnia magna and Vibrio fischeri using information-theoretic topological index (Id). Excellent results are obtained in multiparametric regression upon introduction of dummy parameters (indicator variables). Consistent increase in R(2)(A) values indicated that inspite of collinarity between Id and one of the indicator variables (I(3-6)) the proposed models are statistically significant. 相似文献
92.
Molecular dynamics simulations of a bacterial potassium channel (KcsA) embedded in a phospholipid bilayer reveal significant differences in interactions of the selectivity filter with K(+) compared with Na(+) ions. K(+) ions and water molecules within the filter undergo concerted single-file motion in which they translocate between adjacent sites within the filter on a nanosecond timescale. In contrast, Na(+) ions remain bound to sites within the filter and do not exhibit translocation on a nanosecond timescale. Furthermore, entry of a K(+) ion into the filter from the extracellular mouth is observed, whereas this does not occur for a Na(+) ion. Whereas K(+) ions prefer to sit within a cage of eight oxygen atoms of the filter, Na(+) ions prefer to interact with a ring of four oxygen atoms plus two water molecules. These differences in interactions in the selectivity filter may contribute to the selectivity of KcsA for K(+) ions (in addition to the differences in dehydration energy between K(+) and Na(+)) and the block of KcsA by internal Na(+) ions. In our simulations the selectivity filter exhibits significant flexibility in response to changes in ion/protein interactions, with a somewhat greater distortion induced by Na(+) than by K(+) ions. 相似文献
93.
Isolated pore-lining helices derived from three types of K-channel have been analyzed in terms of their structural and dynamic features in nanosecond molecular dynamics (MD) simulations while spanning a lipid bilayer. The helices were 1) M1 and M2 from the bacterial channel KcsA (Streptomyces lividans), 2) S5 and S6 from the voltage-gated (Kv) channel Shaker (Drosophila melanogaster), and 3) M1 and M2 from the inward rectifier channel Kir6.2 (human). In the case of the Kv and Kir channels, for which x-ray structures are not known, both short and long models of each helix were considered. Each helix was incorporated into a lipid bilayer containing 127 palmitoyloleoylphosphatidylcholine molecules, which was solvated with approximately 4000 water molecules, yielding approximately 20, 000 atoms in each system. Nanosecond MD simulations were used to aid the definition of optimal lengths for the helix models from Kv and Kir. Thus the study corresponds to a total simulation time of 10 ns. The inner pore-lining helices (M2 in KcsA and Kir, S6 in Shaker) appear to be slightly more flexible than the outer pore-lining helices. In particular, the Pro-Val-Pro motif of S6 results in flexibility about a molecular hinge, as was suggested by previous in vacuo simulations (, Biopolymers. 39:503-515). Such flexibility may be related to gating in the corresponding intact channel protein molecules. Analysis of H-bonds revealed interactions with both water and lipid molecules in the water/bilayer interfacial region. Such H-bonding interactions may lock the helices in place in the bilayer during the folding of the channel protein (as is implicit in the two-stage model of membrane protein folding). Aromatic residues at the extremities of the helices underwent complex motions on both short (<10 ps) and long (>100 ps) time scales. 相似文献
94.
A number of ion channels contain transmembrane (TM) alpha-helices that contain proline-induced molecular hinges. These TM helices include the channel-forming peptide alamethicin (Alm), the S6 helix from voltage-gated potassium (Kv) channels, and the D5 helix from voltage-gated chloride (CLC) channels. For both Alm and KvS6, experimental data implicate hinge-bending motions of the helix in an aspect of channel gating. We have compared the hinge-bending motions of these TM helices in bilayer-like environments by multi-nanosecond MD simulations in an attempt to describe motions of these helices that may underlie possible modes of channel gating. Alm is an alpha-helical channel-forming peptide, which contains a central kink associated with a Gly-x-x-Pro motif in its sequence. Simulations of Alm in a TM orientation for 10 ns in an octane slab indicate that the Gly-x-x-Pro motif acts as a molecular hinge. The S6 helix from Shaker Kv channels contains a Pro-Val-Pro motif. Modeling studies and recent experimental data suggest that the KvS6 helix may be kinked in the vicinity of this motif. Simulations (10 ns) of an isolated KvS6 helix in an octane slab and in a POPC bilayer reveal hinge-bending motions. A pattern-matching approach was used to search for possible hinge-bending motifs in the TM helices of other ion channel proteins. This uncovered a conserved Gly-x-Pro motif in TM helix D5 of CLC channels. MD simulations of a model of hCLC1-D5 spanning an octane slab suggest that this channel also contains a TM helix that undergoes hinge-bending motion. In conclusion, our simulations suggest a model in which hinge-bending motions of TM helices may play a functional role in the gating mechanisms of several different families of ion channels. 相似文献
95.
Thomas Callender Mark Woodward Gregory Roth Farshad Farzadfar Jean-Christophe Lemarie Stéphanie Gicquel John Atherton Shadi Rahimzadeh Mehdi Ghaziani Maaz Shaikh Derrick Bennett Anushka Patel Carolyn S. P. Lam Karen Sliwa Antonio Barretto Bambang Budi Siswanto Alejandro Diaz Daniel Herpin Henry Krum Thomas Eliasz Anna Forbes Alastair Kiszely Rajit Khosla Tatjana Petrinic Devarsetty Praveen Roohi Shrivastava Du Xin Stephen MacMahon John McMurray Kazem Rahimi 《PLoS medicine》2014,11(8)
Background
Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs.Methods and Findings
Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%–64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%–41%) with beta-blockers, and 32% (95% CI: 25%–39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%–7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%–10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified.Conclusions
The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors'' Summary 相似文献96.
Hairy roots, a plant disease caused by Agrobacterium rhizogenes, show distinctive features such as high growth rate, unlimited branching, and biochemical and genetic stability. Hairy roots resemble normal roots in terms of differentiated morphology and biosynthetic machinery, producing similar secondary metabolites compared to wild‐type roots. As a result, hairy roots have been a topic of intense research for the past three decades, fueling innumerable attempts to develop in vitro hairy root cultures for a large number of plants for the commercial‐scale production of secondary metabolites. The same characteristics have now led to further applications, such as using hairy root cultures as experimental systems for secondary metabolic pathway elucidation studies. Although the trend is relatively new, it has already gained momentum. This review summarizes these developments. The following discussion focuses on the rationale and advantages of using hairy root cultures for secondary metabolic pathway elucidation studies, the methods used, and the results that have been obtained so far. 相似文献
97.
Anil K. Singh T. N. Athmaram Saurabh Shrivastava S. Merwyn G. S. Agarwal N. Gopalan 《Journal of industrial microbiology & biotechnology》2013,40(7):687-695
Malaria represents the world’s greatest public health problem in terms of number of people affected, levels of morbidity and mortality in tropical and subtropical countries. Malaria parasites are members of the Apicomplexa, family of Plasmodiidae. Histidine-rich protein-II secreted by Plasmodium falciparum is known to be a compelling marker in malaria diagnosis and follow-up. In our present study, we have optimized the batch fermentation and downstream process for large scale production of recombinant P. falciparum HRP-II 62 kDa protein for diagnostic application. The culture broth was effectively induced with IPTG twice at different time intervals to sustain induction for a long period. Batch fermentation resulted in a wet weight of 61.34 g/L and dry cell biomass 12.81 g/L. With the improved downstream process, purified recombinant protein had a yield of 304.60 mg/L. The authenticity of the purified recombinant protein was confirmed via western blotting using indigenously developed HRP-II specific monoclonal antibodies and known positive human clinical sera samples. Further, the reactivity of recombinant HRP-II protein was validated using commercially available immuno chromatographic strips. Indirect ELISA using recombinant purified protein recognized the P. falciparum specific antibodies in suspected human sera samples. Our results clearly suggest that the recombinant HRP-II protein produced via batch fermentation has immense potential for routine diagnostic application. 相似文献
98.
Sarita Pandey A. K. Shrivastava V. K. Singh R. Rai P. K. Singh S. Rai L. C. Rai 《Functional & integrative genomics》2013,13(1):43-55
In silico analysis followed by experimental validation leads us to propose that the predicted protein All0195 of Anabaena sp. PCC7120 showing enhanced expression under sodium arsenate (Na2HAsO4) stress belongs to the thioredoxin superfamily with structural similarity to bacterial arsenate reductase. The All0195 protein demonstrated C-X-TC-X-K, NTSG-X2-YR, and D-X2-L-X-KRP as functional motifs that show similarity to seven known bacterial arsenate reductase family protein homologs with Cys, Arg, and Pro as conserved residues. In view of physicochemical properties, such as aliphatic index, ratio of Glu?+?Lys to Gln?+?His, and secondary structure, it was evident that All0195 was also a thermostable protein. The predicted three-dimensional structure on molecular docking with arsenate oxyanion ( $ HAsO_4^{- 2 } $ ) revealed its interaction with conserved Cys residue as also known for other bacterial arsenate reductase. In silico derived properties were experimentally attested by cloning and heterologous expression of all0195. Furthermore, this protein functionally complemented the arsenate reductase-deficient sodium arsenate-hypersensitive phenotype of Escherichia coli strainWC3110 (ΔarsC) and depicted arsenate reductase activity on purification. In view of the above properties, All0195 appears to be a new arsenate reductase involved in arsenic detoxification in Anabaena sp. PCC7120. 相似文献
99.
100.
Patel Swati R. Joshi Aruna G. Pathak Ashutosh R. Shrivastava Neeta Sharma Sonal 《Plant Cell, Tissue and Organ Culture》2021,145(1):173-189
Plant Cell, Tissue and Organ Culture (PCTOC) - Leptadenia reticulata (Retz.) Wight and Arn is an important medicinal plant of Asclepiadaceae family. In the present study regeneration was attempted... 相似文献