Single-molecule-binding studies of antivirals targeting the hepatitis C virus core protein.

IMPORTANCE: The hepatitis C virus is associated with nearly 300,000 deaths annually. At the core of the virus is an RNA-protein complex called the nucleocapsid, which consists of the viral genome and many copies of the core protein. Because the assembly of the nucleocapsid is a critical step in viral replication, a considerable amount of effort has been devoted to identifying antiviral therapeutics that can bind to the core protein and disrupt assembly. Although several candidates have been identified, little is known about how they interact with the core protein or how those interactions alter the structure and thus the function of this viral protein. Our work biochemically characterizes several of these binding interactions, highlighting both similarities and differences as well as strengths and weaknesses. These insights bolster the notion that this viral protein is a viable target for novel therapeutics and will help to guide future developments of these candidate antivirals.

Poor and Unsatisfactory Disposal of Expired and Unused Pharmaceuticals: A Global Issue.

Pharmaceuticals are beneficial to humankind and emerged as crucial arms to treat/manage multiple disease pathogenesis in the present era. In analogous, these medicines/ medical devices should be used cautiously as they possess a potential threat to induce multiple undesired effects that may be related to human health or the environment. Daunting effects may arise due to the improper disposal of unused/expired medicines. Hence, to minimize such harm, there should be adequate knowledge and practice among the population regarding the safe disposal of unused/expired medicines or related pharmaceutical devices. The lack of approved information regarding safe disposal of such substances may invite serious concerns like environmental pollution, which may induce immediate health hazards to the present population and upcoming future generations. There are numerous ways to dispose of, or manage the unused and expired pharmaceutical substances. Sharing the medicines among siblings, friends, and family members are never free from serious health risks. Storing the unused and expired medicines in the home increases the risk of intentional or accidental ingestion of such substances and may create a health emergency. Disposing medicines like household and municipal waste may lead to environmental pollution and harm to humans and animals. The present review finds the multiple unsafe ways of disposal of unutilized medications/tools. Furthermore, it also summarizes the disposal pattern of unutilized medications among the few developed and undeveloped nations.

Growth, Cell Division, and Gene Expression of Escherichia coli at Elevated Concentrations of Magnesium Sulfate: Implications for Habitability of Europa and Mars.

We perform quantitative studies of the growth, death, and gene expression of Escherichia coli in a wide range of magnesium sulfate (MgSO 4 ) concentrations (0-2.5 M). Elevated concentration of MgSO 4 causes the inhibition of cell growth, leading to an increase in the population doubling time. We find that cells exhibit three distinct morphological phenotypes-(i) normal, (ii) filamentous, and (iii) small cells at 1 . 25 M MgSO 4 . Filamentous cells arise due to the lack of cell division, while the small cells arise due to the partial plasmolysis of the cells. We further find that cell death starts for salt concentrations >1.25 M and increases with an increasing concentration of MgSO 4 . For salt concentrations ≥1.66 M, the growth of cells stops and all the cells become smaller than the control cells, suggesting the plasmolysis of the population. Cells grown at salt concentration up to 2 . 07 M are reversible in both the growth rate and morphology upon the removal of the salt stress. The time scale of reversibility increases with increasing salt concentration. Finally, we investigate the expression of an osmotically inducible gene (osmC), genes involved in magnesium transport (corA), sulfate transport (cysP), and osmotically driven transport of water (aqpZ). We find that a high concentration of magnesium sulfate leads to the upregulation of cysP and osmC.

Results from Nepal's 2018 Report Card on Physical Activity for Children and Youth.

BACKGROUND/OBJECTIVE: Nepal's Report Card on Physical Activity for Children and Youth summarises the available evidence on ten physical activity-related indicators among Nepalese children and youth. METHODS: Published scientific papers on physical activity of Nepalese children and youth (5-17 years) were searched systematically in four databases (Medline, Embase, PsycINFO, and PubMed Central) while some survey reports were manually searched. Letter grades were assigned to ten indicators (Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behaviours, Physical Fitness, Family and Peers, School, Community and Environment, and Government) by the country's report card team based on available data. RESULTS: Among the ten indicators, five indicators were successfully graded based on available data. Overall Physical Activity was graded as D+. Active Transportation and Family and Peers were assigned as A- and A, respectively. Community and Environment was graded as C-. The other five indicators could not be graded due to insufficient data. CONCLUSIONS: Though a majority of Nepalese children and youth use active modes of transport and have adequate support for physical activity from family and peers, overall participation in physical activity appears to be low. Lack of data identified with five incomplete indicators reflects the need for further research. Studies with larger sample, more rigorous study design and objective assessment of physical activity is recommended for future physical activity surveillance in Nepal.

Dynamics of phenotypic switching of bacterial cells with temporal fluctuations in pressure.

Phenotypic switching is one of the mechanisms by which bacteria thrive in ever changing environmental conditions around them. Earlier studies have shown that the application of steady high hydrostatic pressure leads to stochastic switching of mesophilic bacteria from a cellular phenotype having a normal cell cycle to another phenotype lacking cell division. Here, we have studied the dynamics of this phenotypic switching with fluctuating periodic pressure using a set of experiments and a theoretical model. Our results suggest that the phenotypic switching rate from high-pressure phenotype to low-pressure phenotype in the reversible regime is larger as compared to the switching rate from low-pressure phenotype to high-pressure phenotype. Furthermore, we find that even though the cell division and elongation are presumably regulated by a large number of genes the underlying physics of the dynamics of stochastic switching at high pressure is captured reasonably well by a simple two-state model.