Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by phosphopeptides derived from Abi1/Hssh3bp1

Here we report c-Abl kinase inhibition mediated by a phosphotyrosine located in trans in the c-Abl substrate, Abi1. The mechanism, which is pertinent to the nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif to the Abl SH3 domain. Abi1 regulation of c-Abl in vivo appears to play a critical role, as demonstrated by inhibition of pY412 phosphorylation of the nonmyristoylated Abl by coexpression of Abi1. Pervanadate-induced c-Abl kinase activity was also reduced upon expression of the wild type Abi1 but not by expression of the Y213 to F213 mutant Abi1 in LNCaP cells, which are naturally deficient in the regulatory pY213. Our findings suggest a novel mechanism by which Abl kinase is regulated in cells.     

Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : Understanding the basis of differential inhibition and the role of water

Background  

This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK) and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI) of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition.     

Pharmacological activities of crude acetone extract and purified constituents of Salvia moorcraftiana Wall.

The crude acetone extract of aerial parts of Salvia moorcraftiana Wall. was screened for various biological activities including Lemna bioassay, antifungal, antibacterial, leishmanicidal, insecticidal activities and brine shrimp cytotoxicity. It was found to possess strong phytotoxic activity against Lemna aequinoctials Welve. and moderate antifungal activity against animal and plant pathogens. The purified chemical constituents were tested for enzyme inhibition activity. Two constituents (compounds 3 and 8) were found to be effective inhibitors of alpha-glucosidase.     

Validity of the work productivity and activity impairment questionnaire - general health version in patients with rheumatoid arthritis

Introduction  

The Work Productivity and Activity Impairment (WPAI) questionnaire is a well validated instrument to measure impairments in work and activities. However, its validation among patients with rheumatoid arthritis (RA) has not been well established. The present study's purpose is to evaluate the construct validity of the WPAI-general health version among RA patients and its ability to differentiate between RA patients with varying health status.     

First Report of bla CTX-M-15-Type ESBL-Producing Klebsiella pneumoniae in Wild Migratory Birds in Pakistan

EcoHealth - We investigated wild migratory birds faecal swabs for extended-spectrum β-lactamases-producing Klebsiella pneumoniae (ESBL-K. pneumoniae) from wetland habitats in Pakistan. ESBL-K....     

The key roles of salicylic acid and sulfur in plant salinity stress tolerance

Journal of Plant Growth Regulation - The salinization of agriculture soils over the globe has become one of the most devastating stresses and is significantly limiting cultivated land area, and...     

An Update on Genetic Modification of Chickpea for Increased Yield and Stress Tolerance

Chickpea is a highly nutritious grain legume crop, widely appreciated as a health food, especially in the Indian subcontinent. The major constraints on chickpea production are biotic (Helicoverpa, bruchid, aphid, ascochyta) and abiotic (drought, heat, salt, cold) stresses, which reduce the yield by up to 90%. Various strategies like conventional breeding, molecular breeding, and modern plant breeding have been used to overcome these problems. Conventionally, breeding programs aim at development of varieties that combine maximum number of traits through inter-specific hybridization, wide hybridization, and hybridization involving more than two parents. Breeding is difficult in this crop because of its self-pollinating nature and limited genetic variation. Recent advances in in vitro culture and gene technologies offer unique opportunities to realize the full potential of chickpea production. However, as of date, no transgenic chickpea variety has been approved for cultivation in the world. In this review, we provide an update on the development of genetically modified chickpea plants, including those resistant to Helicoverpa armigera, Callosobruchus maculatus, Aphis craccivora, as well as to drought and salt stress. The genes utilized for development of resistance against pod borer, bruchid, aphid, drought, and salt tolerance, namely, Bt, alpha amylase inhibitor, ASAL, P5CSF129A, and P5CS, respectively, are discussed.     

Chemometric Evaluation of Elemental Imbalances in the Scalp Hair of Valvular Heart Disease Patients in Comparison with Healthy Donors

The present study deals with the plausible association between the trace elemental imbalances and the emergence of valvular heart disease (VHD). A total of 14 elements including Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Pb, Sr and Zn in the scalp hair of VHD patients and healthy donors were analysed by flame atomic absorption spectrophometry employing wet acid digestion methodology. Median levels of Cu, Fe, Mg, Mn and Sr in the scalp hair of patients were significantly higher compared to those of the healthy donors, while the median concentrations of K and Na were found to be considerably higher in the scalp hair of the healthy donors. In addition, substantially elevated Cu/Zn value in patients indicated the prevalence of inflammatory processes inside the body. The correlation coefficients among the elements in the hair of VHD patients were significantly diverse compared to those of the healthy donors. Multivariate statistical methods showed noticeably dissimilar apportionment of the elements in the two groups. Variations in the elemental levels were also observed with gender, habitat, dietary/smoking habits and occupations of both donor groups. Overall, the study revealed significant imbalances among the essential and toxic elements in the scalp hair of VHD patients compared to those of the healthy subjects.