-
Falk Sharp posted an update 1 year, 7 months ago
HCV NS3, a non-structural hepatitis C viral protein is used as one of the potential targets for inhibition by direct-acting antivirals. It is known that the success rate for HCV genotype-1 treatment remained very high, however, treatment of genotype-3a (GT-3a), is still quite challenging. In the current study, the HCV GT-3a full-length NS3 gene was amplified and sequenced. The complete nucleotide sequence was translated into the amino acid sequence and homology models of HCV-NS3 GT-3a were generated by HCV-NS3 genotype-1b as a template. The objective of the study was to screen novel therapeutic hits from large databases. For this aim, various small molecule databases including, BindingDB (∼45.000 compounds), NCI (∼265.000 compounds), and Specs-SC (∼212.000 compounds) were used. Firstly, all of the compounds were screened using binary-QSAR models from the MetaCore/MetaDrug server, and compounds were filtered based on therapeutic activity predictions by the anti-viral QSAR model. Filtered molecules were used in 26 different toxicity QSAR models and active non-toxic compounds were identified. These selected molecules were then used in docking and molecular dynamics (MD) simulations studies at the binding cavities of the NS3 protease domain of the GT-3a. Results were compared with known inhibitors and novel molecules are proposed against HCV-NS3 GT-3a. These molecules have high ligand efficiencies as compared to the reference molecules suggesting a better alternate to the existing suite of inhibitors. Thus, this study will be a step ahead in the development of new potential compounds as antiviral drugs for the GT-3a target.Low- and middle-income countries have the largest health burdens associated with air pollution exposure, and are particularly vulnerable to climate change impacts. Substantial opportunities have been identified to simultaneously improve air quality and mitigate climate change due to overlapping sources of greenhouse gas and air pollutant emissions and because a subset of pollutants, short-lived climate pollutants (SLCPs), directly contribute to both impacts. However, planners in low- and middle-income countries often lack practical tools to quantify the air pollution and climate change impacts of different policies and measures. This paper presents a modelling framework implemented in the Low Emissions Analysis Platform – Integrated Benefits Calculator (LEAP-IBC) tool to develop integrated strategies to improve air quality, human health and mitigate climate change. The framework estimates emissions of greenhouse gases, SLCPs and air pollutants for historical years, and future projections for baseline and miti2030 compared to a baseline scenario. These emission reductions could reduce population-weighted ambient PM2.5 concentrations in Bangladesh by 18% in 2030, and avoid approximately 12,000 and 100,000 premature deaths attributable to ambient and household PM2.5 exposures, respectively, in 2030. As countries are simultaneously planning to achieve the climate goals in the Paris Agreement, improve air quality to reduce health impacts and achieve the Sustainable Development Goals, the LEAP-IBC tool provides a practical framework by which planners can develop integrated strategies, achieving multiple air quality and climate benefits.During the last decades, thermophilic spore counts became a very important quality parameter for manufacturers with regard to powdered dairy products. Low-spore count powders are highly demanded but challenging to produce when high production volume and long process times are intended. In this study a detailed monitoring of microbial levels in three skim milk powder plants was conducted. Anoxybacillus flavithermus was found to be primarily responsible for increased spore levels with increasing spore numbers being detected after 6-8 h already during initial processing steps. Simultaneously, the species composition shifted from a diverse bulk tank milk microbiota where different Bacillus species represented around 90% of the thermophilic bacteria to a dominance of A. flavithermus in the end product. The analysis of A. flavithermus isolates from different powder batches with RAPD PCR revealed recurring patterns in each of the eight German manufacturers sampled over several months. The high relatedness of isolates exhibiting identical RAPD patterns was exemplified by cgMLST based on whole genome sequences. We assume that A. flavithermus strains persisted in production plants and were not eliminated by cleaning. It is concluded that such persisting strains recurrently recontaminated subsequent powder productions. The data highlight that a targeted optimization of cleaning and disinfection procedures is the most promising measure to effectively reduce thermophilic spore counts in German dairy powders.Wildlife and human health are at risk of lead exposure from spent hunting ammunition. Lead exposure persists for bald eagles due to bullet fragments in game animal gut piles and unretrieved carcasses, and is also a human health risk when wild game is procured using lead ammunition. Programs encouraging the voluntary use of nonlead ammunition have become a popular approach mitigating these effects. This study explored attitudes and experiences of United States Fish and Wildlife Service (USFWS) staff implementing an outreach program encouraging deer hunters to voluntary use nonlead ammunition on 54 National Wildlife Refuges (NWRs) in the Upper Midwest, U.S. to understand factors affecting program implementation. We conducted 29 semi-structured interviews of USFWS staff along with 60 responses from an open-ended survey question. Twelve themes emerged from the data and were grouped into three broad categories (1) challenges of dealing with complex issues, (2) importance of messengers and messages, and (3) resistance from staff. Challenges of dealing with complex issues included administrative restraint and uncertainty, scope and scale of program, human health not an agency responsibility, contextual political influences, and public-private collaborations. Importance of messengers and messages included the importance of experience, and salience of human health risk. GSK2643943A price Finally, resistance from staff included skepticism of the science and motives behind the program, competing priorities for refuge staff, differing perceptions of regulatory and voluntary approaches, cost and availability of nonlead ammunition, and disregard by some about lead ammunition and human health risks. Staff identified numerous challenges implementing the program, many of which were external factors beyond the control of the participants. Understanding the factors affecting program implementation may help guide future efforts encouraging the voluntary use of nonlead ammunition.

