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91.
Vinod Jani Uddhavesh B. Sonavane Rajendra Joshi 《Journal of biomolecular structure & dynamics》2013,31(6):845-860
Abstract Reaching the experimental time scale of millisecond is a grand challenge for protein folding simulations. The development of advanced Molecular Dynamics techniques like Replica Exchange Molecular Dynamics (REMD) makes it possible to reach these experimental timescales. In this study, an attempt has been made to reach the multi microsecond simulation time scale by carrying out folding simulations on a three helix bundle protein, Villin, by combining REMD and Amber United Atom model. Twenty replicas having different temperatures ranging from 295 K to 390 K were simulated for 1.5 μs each. The lowest Root Mean Square Deviation (RMSD) structure of 2.5 Å was obtained with respect to native structure (PDB code 1VII), with all the helices formed. The folding population landscapes were built using segment-wise RMSD and Principal Components as reaction coordinates. These analyses suggest the two-stage folding for Villin. The combination of REMD and Amber United Atom model may be useful to understand the folding mechanism of various fast folding proteins 相似文献
92.
Morten Lillemo Arun K. Joshi Ravindra Prasad Ramesh Chand Ravi P. Singh 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2013,126(3):711-719
Spot blotch caused by Bipolaris sorokiniana is a major disease of wheat in warm and humid wheat growing regions of the world including south Asian countries such as India, Nepal and Bangladesh. The CIMMYT bread wheat line Saar which carries the leaf tip necrosis (LTN)-associated rust resistance genes Lr34 and Lr46 has exhibited a low level of spot blotch disease in field trials conducted in Asia and South America. One hundred and fourteen recombinant inbred lines (RILs) of Avocet (Susceptible) × Saar, were evaluated along with parents in two dates of sowing in India for 3 years (2007–2008 to 2009–2010) to identify quantitative trait loci (QTL) associated with spot blotch resistance, and to determine the potential association of Lr34 and Lr46 with resistance to this disease. Lr34 was found to constitute the main locus for spot blotch resistance, and explained as much as 55 % of the phenotypic variation in the mean disease data across the six environments. Based on the large effect, the spot blotch resistance at this locus has been given the gene designation Sb1. Two further, minor QTL were detected in the sub-population of RILs not containing Lr34. The first of these was located about 40 cM distal to Lr34 on 7DS, and the other corresponded to Lr46 on 1BL. A major implication for wheat breeding is that Lr34 and Lr46, which are widely used in wheat breeding to improve resistance to rust diseases and powdery mildew, also have a beneficial effect on spot blotch. 相似文献
93.
Manasi Mishra Rakesh S. Joshi Sushama Gaikwad Vidya S. Gupta Ashok P. Giri 《Biochemical and biophysical research communications》2013,430(3):1060-1065
Pin-II protease inhibitors (PIs) are the focus of research interest because of their large structural–functional diversity and relevance in plant defense. Two representative Capsicum annuum PI genes (CanPI-15 and -7) comprising one and four inhibitory repeat domains, respectively, were expressed and recombinant proteins were characterized. β-Sheet and unordered structure was found predominant in CanPI-15 while -7 also displayed the signatures of polyproline fold, as revealed by circular dichroism studies. Inhibition kinetics against bovine trypsin indicated three times higher potency of CanPI-7 (Ki ~ 57 μM) than -15 (~184 μM). Activity and structural stability of these CanPIs were revealed under various conditions of pH, temperature and denaturing agent. Structure prediction, docking studies with proteases and mass spectroscopy revealed the organization of multiple reactive site loops of multi domain PIs in space as well as the steric hindrances imposed while binding to proteases due to their close proximity. 相似文献
94.
Nicholas E. Dickenson Shyamal P. Choudhari Philip R. Adam Ryan M. Kramer Sangeeta B. Joshi C. Russell Middaugh Wendy L. Picking William D. Picking 《Protein science : a publication of the Protein Society》2013,22(5):614-627
The Shigella flexneri Type III secretion system (T3SS) senses contact with human intestinal cells and injects effector proteins that promote pathogen entry as the first step in causing life threatening bacillary dysentery (shigellosis). The Shigella Type III secretion apparatus (T3SA) consists of an anchoring basal body, an exposed needle, and a temporally assembled tip complex. Exposure to environmental small molecules recruits IpaB, the first hydrophobic translocator protein, to the maturing tip complex. IpaB then senses contact with a host cell membrane, forming the translocon pore through which effectors are delivered to the host cytoplasm. Within the bacterium, IpaB exists as a heterodimer with its chaperone IpgC; however, IpaB's structural state following secretion is unknown due to difficulties isolating stable protein. We have overcome this by coexpressing the IpaB/IpgC heterodimer and isolating IpaB by incubating the complex in mild detergents. Interestingly, preparation of IpaB with n‐octyl‐oligo‐oxyethylene (OPOE) results in the assembly of discrete oligomers while purification in N,N‐dimethyldodecylamine N‐oxide (LDAO) maintains IpaB as a monomer. In this study, we demonstrate that IpaB tetramers penetrate phospholipid membranes to allow a size‐dependent release of small molecules, suggesting the formation of discrete pores. Monomeric IpaB also interacts with liposomes but fails to disrupt them. From these and additional findings, we propose that IpaB can exist as a tetramer having inherent flexibility, which allows it to cooperatively interact with and insert into host cell membranes. This event may then lay the foundation for formation of the Shigella T3SS translocon pore. 相似文献
95.
96.
V. Sheeba V. Kumar Sharma M.K. Chandrashekaran A. Joshi 《Biological Rhythm Research》2013,44(4):424-433
Egg to eclosion development time and survivorship were assayed on four laboratory populations of Drosophila melanogaster that had been reared for over 600 generations in continuous light (LL) and constant temperature. The assays were performed in three environments: continuous light (LL), periodically varying light/dark cycles (LD 12:12 hr), and continuous darkness (DD). Development time in LL was significantly less than that in LD, which, in turn, was significantly less than that in DD, whereas survivorship did not differ significantly among the three treatments. The results indicate that individuals from Drosophila populations routinely maintained in LL do not suffer any deleterious effects of LL treatment on pre-adult fitness. Other studies on these populations have shown that free-running period (t) of the eclosion rhythm in DD is greater than that in LD. Our results are, thus, also consistent with the notion that development time may be a function of the free-running period. 相似文献
97.
Devarsetty?PraveenEmail author Anushka?Patel Stephen?McMahon Dorairaj?Prabhakaran Gari?D.?Clifford Pallab?K.?Maulik Rohina?Joshi Stephen?Jan Stephane?Heritier David?Peiris 《Implementation science : IS》2013,8(1):137
Background
Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed.Methods
We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension’s region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation.Expected outcomes
The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations.Significance
The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings.Trial registration
Clinical Trial Registry India CTRI/2013/06/003753.98.
99.