Virtual screening and evaluation of Ketol-Acid Reducto-Isomerase (KARI) as a putative drug target for Aspergillosis

Aspergillus is a leading causative agent for fungal morbidity and mortality in immuno-compromised patients. To identify a putative target to design or identify new antifungal drug, against Aspergillus is required. In our previous work, we have analyzed the various biochemical pathways, and we found Ketol Acid Reducto-Isomerase (KARI) an enzyme involves in the amino acid biosynthesis, could be a better target. This enzyme was found to be unique by comparing to host proteome through BLASTp analysis. A homology based model of KARI was generated by Swiss model server. The generated model had been validated by PROCHECK and WHAT IF programs. The Zinc library was generated within the limitation of the Lipinski rule of five, for docking study. Based on the dock-score six molecules have been studied for ADME/TOX analysis and subjected for pharmacophore model generation. The Zinc ID of the potential inhibitors is ZINC00720614, ZINC01068126, ZINC0923, ZINC02090678, ZINC00663057 and ZINC02284065 and found to be pharmacologically active agonist and antagonist of KARI. This study is an attempt to Insilco evaluation of the KARI as a drug target and the screened inhibitors could help in the development of the better drug against Aspergillus

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

OBILJEŽJA POČINITELJA NASILNIČKIH DELIKATA NA PODRUČJU PRIMORSKO-GORANSKE ŽUPANIJE OBZIROM NA POVRAT

Availability of sophisticated statistical modelling for developing robust reference equations has improved interpretation of lung function results. In 2012, the Global Lung function Initiative(GLI) published the first global all-age, multi-ethnic reference equations for spirometry but these lacked equations for those originating from the Indian subcontinent (South-Asians). The aims of this study were to assess the extent to which existing GLI-ethnic adjustments might fit South-Asian paediatric spirometry data, assess any similarities and discrepancies between South-Asian datasets and explore the feasibility of deriving a suitable South-Asian GLI-adjustment. Methods: Spirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n=110). Results: Following exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5-17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4-19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The ‘GLI-Other’ equation fitted data from North India reasonably well while ‘GLI-Black’ equations provided a better approximation for South-Asian data than the ‘GLI-White’ equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment. Conclusion: Until improved and more robust prediction equations can be derived, we recommend the use of ‘GLI-Black’ equations for interpreting most South-Asian data, although ‘GLI-Other’ may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required

Cardio-pulmonary status of treated cases of pulmonary tuberculosis

A preliminary study to assess the cardio-pulmonary status of the treated cases of pulmonary tuberculosis was undertaken at ICMR Tuberculosis Research Centre, Madras. The study was carried out in 40 cases of treated pulmonary tuberculosis. These patients were selected from the follow up clinic of the Tuberculosis Research Centre and were all sputum negative for A.F.B, for a period of varying from one to four years, with radiographic evidence of parenchymal lesions in the lungs and all complained of dyspnoea of varying grades. Pulmonary function tests were carried out and electrocardiograms were recorded in all patients. In 75% of cases the FVC was markedly reduced (below 75% predicted). However in 75% of cases, the FEV1% was within normal limits. Eighteen percent patients studied had electrocardiographic evidence of Cor-pulmonale. Another interesting finding in the electrocardiograms was the presence of tall T waves in leads V2 and V3 in 37% of cases, the significance of which was unknown