Role of Charged Residues in the Catalytic Sites of Escherichia coli ATP Synthase

Here we describe the role of charged amino acids at the catalytic sites of Escherichia coli ATP synthase. There are four positively charged and four negatively charged residues in the vicinity of of E. coli ATP synthase catalytic sites. Positive charges are contributed by three arginine and one lysine, while negative charges are contributed by two aspartic acid and two glutamic acid residues. Replacement of arginine with a neutral amino acid has been shown to abrogate phosphate binding, while restoration of phosphate binding has been accomplished by insertion of arginine at the same or a nearby location. The number and position of positive charges plays a critical role in the proper and efficient binding of phosphate. However, a cluster of many positive charges inhibits phosphate binding. Moreover, the presence of negatively charged residues seems a requisite for the proper orientation and functioning of positively charged residues in the catalytic sites. This implies that electrostatic interactions between amino acids are an important constituent of initial phosphate binding in the catalytic sites. Significant loss of function in growth and ATPase activity assays in mutants generated through charge modulations has demonstrated that precise location and stereochemical interactions are of paramount importance

Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase

Material Characterization and Real-Time Wear Evaluation of Pistons and Cylinder Liners of the Tiger 131 Military Tank

Material characterisation and wear evaluation of the original and replacement pistons and cylinder-liners of Tiger 131 is reported. Original piston and cylinder-liner were operative in the Tigers’ engine during WWII. The replacement piston and cylinder-liner were used as substitutes and were obtained after failure in two hours of operation in the actual engine. Material characterisation revealed that the original piston was aluminium silicon hypereutectic alloy whereas the replacement piston was aluminium copper alloy with very low silicon content. Both original and replacement cylinder-liners consisted of mostly iron which is indicative of cast iron, a common material for this application. The replacement piston average surface roughness was found to be 9.09 μm while for replacement cylinder-liner it was 5.78 μm

Bioregulators can improve biomass production, photosynthetic efficiency, and ornamental quality of gazania rigens L

Gazania rigens L. is a perennial herbaceous plant that belongs to the Asteraceae family, widely used as bedding or ornamental potted plants. The environmental and economic sustainability of ornamental production can be enhanced using environmentally friendly bioregulators. A pot experiment was conducted to evaluate the influence of key bioregulators gibberellic acid ((GA3) at 50, 100 or 150 mg L 121), humic acid ((HA) at 100, 300 or 600 mg L 121), and ascorbic acid ((AA) at 50, 100 or 200 mg L 121)), on the growth, leaf gas exchange, and ornamental quality of G. rigens. The results indicated that plants treated with foliar applications of GA3, HA, or AA exhibited higher plant fresh and dry biomass, plant height, leaf area, and leaf area ratio, root-shoot ratio, root-shoot mass fractions, and number of flowers, as well as the flowers display time. All bioregulator treatments enhanced the vegetative and floral characteristics of Gazania plants. The GA3 was the most efficient at the concentration of 100 mg L 121. The highest efficacy of HA and AA treatments was observed at the higher concentrations, 600 and 200 mg L 121, respectively. These results were associated with higher photosynthetic rate (A), transpiration rate (E) as well as stomatal conductance (gs), and water use efficiency (WUE). In conclusion, the results suggest that foliar-applied bioregulators to Gazania are promising and represent sustainable strategies to enhance growth, flowering, and flower display time of Gazania plants

Multiple-micronutrient supplementation: Evidence from large-scale prenatal programmes on coverage, compliance and impact

Micronutrient deficiencies during pregnancy pose important challenges for public-health, given the potential adverse outcomes not only during pregnancy but across the life-course. Provision of iron-folic acid (IFA) supplements is the strategy most commonly practiced and recommended globally. How to successfully implement IFA and multiple micronutrient supplementation interventions among pregnant women and to achieve sustainable/permanent solutions to prenatal micronutrient deficiencies remain unresolved issues in many countries. This paper aims to analyse available experiences of prenatal IFA and multiple micronutrient interventions to distil learning for their effective planning and large-scale implementation. Relevant articles and programme-documentation were comprehensively identified from electronic databases, websites of major-agencies and through hand-searching of relevant documents. Retrieved documents were screened and potentially relevant reports were critically examined by the authors with the aim of identifying a set of case studies reflecting regional variation, a mix of implementation successes and failures, and a mix of programmes and large-scale experimental studies. Information on implementation, coverage, compliance, and impact was extracted from reports of large-scale interventions in Central America, Southeast Asia, South Asia, and Sub-Saharan Africa. The WHO/CDC Logic-Model for Micronutrient Interventions in Public Health was used as an organizing framework for analysing and presenting the evidence. Our findings suggest that to successfully implement supplementation interventions and achieve sustainable-permanent solutions efforts must focus on factors and processes related to quality, cost-effectiveness, coverage, utilization, demand, outcomes, impacts, and sustainability of programmes including strategic analysis, management, collaborations to pilot a project, and careful monitoring, midcourse corrections, supervision and logistical-support to gradually scaling it up

Directing diarrhoeal disease research towards disease-burden reduction

Despite gains in controlling mortality relating to diarrhoeal disease, the burden of disease remains unacceptably high. To refocus health research to target disease-burden reduction as the goal of research in child health, the Child Health and Nutrition Research Initiative developed a systematic strategy to rank health research options. This priority-setting exercise included listing of 46 competitive research options in diarrhoeal disease and their critical and quantitative appraisal by 10 experts based on five criteria for research that reflect the ability of the research to be translated into interventions and achieved disease-burden reduction. These criteria included the answerability of the research questions, the efficacy and effectiveness of the intervention resulting from the research, the maximal potential for disease-burden reduction of the interventions derived from the research, the affordability, deliverability, and sustainability of the intervention supported by the research, and the overall effect of the research-derived intervention on equity. Experts scored each research option independently to delineate the best investments for diarrhoeal disease control in the developing world to reduce the burden of disease by 2015. Priority scores obtained for health policy and systems research obtained eight of the top 10 rankings in overall scores, indicating that current investments in health research are significantly different from those estimated to be the most effective in reducing the global burden of diarrhoeal disease by 2015

The extracellular matrix, p53 and estrogen compete to regulate cell-surface Fas/Apo-1 suicide receptor expression in proliferating embryonic cerebral cortical precursors, and reciprocally, Fas-ligand modifies estrogen control of cell-cycle proteins

BACKGROUND: Apoptosis is important for normal cerebral cortical development. We previously showed that the Fas suicide receptor was expressed within the developing cerebral cortex, and that in vitro Fas activation resulted in caspase-dependent death. Alterations in cell-surface Fas expression may significantly influence cortical development. Therefore, in the following studies, we sought to identify developmentally relevant cell biological processes that regulate cell-surface Fas expression and reciprocal consequences of Fas receptor activation. RESULTS: Flow-cytometric analyses identified two distinct neural sub-populations that expressed Fas on their cell surface at high (Fas(Hi)) or moderate (Fas(Mod)) levels. The anti-apoptotic protein FLIP further delineated a subset of Fas-expressing cells with potential apoptosis-resistance. Fas(Mod )precursors were mainly in G0, while Fas(Hi )precursors were largely apoptotic. However, birth-date analysis indicated that neuroblasts express the highest levels of cell-surface Fas at the end of S-phase, or after their final round of mitosis, suggesting that Fas expression is induced at cell cycle checkpoints or during interkinetic nuclear movements. Fas(Hi )expression was associated with loss of cell-matrix adhesion and anoikis. Activation of the transcription factor p53 was associated with induction of Fas expression, while the gonadal hormone estrogen antagonistically suppressed cell-surface Fas expression. Estrogen also induced entry into S-phase and decreased the number of Fas-expressing neuroblasts that were apoptotic. Concurrent exposure to estrogen and to soluble Fas-ligand (sFasL) suppressed p21/waf-1 and PCNA. In contrast, estrogen and sFasL, individually and together, induced cyclin-A expression, suggesting activation of compensatory survival mechanisms. CONCLUSIONS: Embryonic cortical neuronal precursors are intrinsically heterogeneous with respect to Fas suicide-sensitivity. Competing intrinsic (p53, cell cycle, FLIP expression), proximal (extra-cellular matrix) and extrinsic factors (gonadal hormones) collectively regulate Fas suicide-sensitivity either during neurogenesis, or possibly during neuronal migration, and may ultimately determine which neuroblasts successfully contribute neurons to the differentiating cortical plate

Understanding the factors affecting the humanitarian health and nutrition response for women and children in Somalia since 2000: A case study

Background: Somalia has been ravaged by more than two decades of armed conflict causing immense damage to the country\u27s infrastructure and mass displacement and suffering among its people. An influx of humanitarian actors has sought to provide basic services, including health services for women and children, throughout the conflict. This study aimed to better understand the humanitarian health response for women and children in Somalia since 2000.Methods: The study utilized a mixed-methods design. We collated intervention coverage data from publically available large-scale household surveys and we conducted 32 interviews with representatives from government, UN agencies, NGOs, and health facility staff. Qualitative data were analyzed using latent content analysis.Results: The available quantitative data on intervention coverage in Somalia are extremely limited, making it difficult to discern patterns or trends over time or by region. Underlying sociocultural and other contextual factors most strongly affecting the humanitarian health response for women and children included clan dynamics and female disempowerment. The most salient operational influences included the assessment of population needs, donors\u27 priorities, and insufficient and inflexible funding. Key barriers to service delivery included chronic commodity and human resource shortages, poor infrastructure, and limited access to highly vulnerable populations, all against the backdrop of ongoing insecurity. Various strategies to mitigate these barriers were discussed. In-country coordination of humanitarian health actors and their activities has improved over time, with federal and state-level ministries of health playing increasingly active roles.Conclusions: Emerging recommendations include further exploration of government partnerships with private-sector service providers to make services available throughout Somalia free of charge, with further research on innovative uses of technology to help reaches remote and inaccessible areas. To mitigate chronic skilled health worker shortages, more operational research is needed on the expanded use of community health workers. Persistent gaps in service provision across the continuum must be addressed, including for adolescents, for example. The is also a clear need for longer term development focus to enable the provision of health and nutrition services for women and children beyond those included in recurrent emergency response

The case for launch of an international DNA-based birth cohort study

The global health agenda beyond 2015 will inevitably need to broaden its focus from mortality reduction to the social determinants of deaths, growing inequities among children and mothers, and ensuring the sustainability of the progress made against the infectious diseases. New research tools, including technologies that enable high-throughput genetic and ‘-omics’ research, could be deployed for better understanding of the aetiology of maternal and child health problems. The research needed to address those challenges will require conceptually different studies than those used in the past. It should be guided by stringent ethical frameworks related to the emerging collections of biological specimens and other health related information. We will aim to establish an international birth cohort which should assist low- and middle-income countries to use emerging genomic research technologies to address the main problems in maternal and child health, which are still major contributors to the burden of disease globally