370 research outputs found

    Mechanism of Nucleic Acid Unwinding by SARS-CoV Helicase

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    The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA (dsRNA) or DNA (dsDNA) with a 5′→3′ polarity, using the energy of nucleotide hydrolysis. We determined the minimal mechanism of helicase function by nsp13. We showed a clear unwinding lag with increasing length of the double-stranded region of the nucleic acid, suggesting the presence of intermediates in the unwinding process. To elucidate the nature of the intermediates we carried out transient kinetic analysis of the nsp13 helicase activity. We demonstrated that the enzyme unwinds nucleic acid in discrete steps of 9.3 base-pairs (bp) each, with a catalytic rate of 30 steps per second. Therefore the net unwinding rate is ∼280 base-pairs per second. We also showed that nsp12, the SARS-CoV RNA-dependent RNA polymerase (RdRp), enhances (2-fold) the catalytic efficiency of nsp13 by increasing the step size of nucleic acid (RNA/RNA or DNA/DNA) unwinding. This effect is specific for SARS-CoV nsp12, as no change in nsp13 activity was observed when foot-and-mouth-disease virus RdRp was used in place of nsp12. Our data provide experimental evidence that nsp13 and nsp12 can function in a concerted manner to improve the efficiency of viral replication and enhance our understanding of nsp13 function during SARS-CoV RNA synthesis

    Urban agriculture: a global analysis of the space constraint to meet urban vegetable demand

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    Urban agriculture (UA) has been drawing a lot of attention recently for several reasons: the majority of the world population has shifted from living in rural to urban areas; the environmental impact of agriculture is a matter of rising concern; and food insecurity, especially the accessibility of food, remains a major challenge. UA has often been proposed as a solution to some of these issues, for example by producing food in places where population density is highest, reducing transportation costs, connecting people directly to food systems and using urban areas efficiently. However, to date no study has examined how much food could actually be produced in urban areas at the global scale. Here we use a simple approach, based on different global-scale datasets, to assess to what extent UA is constrained by the existing amount of urban space. Our results suggest that UA would require roughly one third of the total global urban area to meet the global vegetable consumption of urban dwellers. This estimate does not consider how much urban area may actually be suitable and available for UA, which likely varies substantially around the world and according to the type of UA performed. Further, this global average value masks variations of more than two orders of magnitude among individual countries. The variations in the space required across countries derive mostly from variations in urban population density, and much less from variations in yields or per capita consumption. Overall, the space required is regrettably the highest where UA is most needed, i.e., in more food insecure countries. We also show that smaller urban clusters (i.e., <100 km2 each) together represent about two thirds of the global urban extent; thus UA discourse and policies should not focus on large cities exclusively, but should also target smaller urban areas that offer the greatest potential in terms of physical space

    Fusarium graminearum in a Papilloma Virus Infected Friesian Bull in Vom, Nigeria: Case Report

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    Importation of exotic cattle to improve the yield and productivityof the local 'White Fulani' breed of cattle has been on the rise inNigeria. The problem most farmers faces with the Friesian hasalways been the adaptation to the weather and endemic diseaseconditions in Nigeria. Fungal infections represent an importantcomplication for immunosuppressed animals and are associatedwith high morbidity and mortality (De Pauw and Meunier, 1999).Fusarium is one of the most important fungal genera, whichincludes many species that are pathogenic to plants and responsible for a broad range of diseases while others are highly mycotoxigenic (Viquez et al., ) and some cause opportunistic infections in humans and in farm animals. Fusarium graminearum (Gibberella zeae) is an importantpathogen of commercial crops such as wheat, maize, and rice.Infection with F. graminearum causes yield losses in grains anddegrades their nutritive, physical and chemical qualities, resultingin their being used for animal feed rather than for human consumption (Charmley et al., 1994). A contaminated crop can be salvaged by feeding it to livestock or poultry, but further losses may be incurred due to the negative effects of mycotoxins on animal performance. Potent toxins such as the estrogenic toxin zearalenone (F-2) have been reported by Vesonder and Hesseltine, (1980) but the most common mycotoxins produced byF. graminearum are deoxynivalenol (DON, also known as vomitoxin), 15-acetyldeoxynivalenol, and nivalenol belonging to a group of compounds known as trichothecenes (Homdork et al., 2000; Council for Agricultural Science and Technology, CAST, 2003). These mycotoxins are known to diminish feed consumption in domestic livestock, especially swine (CAST 2003). Because of their apparent tolerance for higher levels of dietary DON, Fusarium-infested grains are often fed to cattle or sheep asopportunity feeds. This may be due to little or insufficient information describing the pathogenesis and the ability of this plant pathogen to survive as they move through the gastrointestinal tract of cattle or on a compromised skin (Kedar and Gemerlyn, 2008)

    Intelligent Sensors for Sustainable Food and Drink Manufacturing

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    Food and drink is the largest manufacturing sector worldwide and has significant environmental impact in terms of resource use, emissions, and waste. However, food and drink manufacturers are restricted in addressing these issues due to the tight profit margins they operate within. The advances of two industrial digital technologies, sensors and machine learning, present manufacturers with affordable methods to collect and analyse manufacturing data and enable enhanced, evidence-based decision making. These technologies will enable manufacturers to reduce their environmental impact by making processes more flexible and efficient in terms of how they manage their resources. In this article, a methodology is proposed that combines online sensors and machine learning to provide a unified framework for the development of intelligent sensors that work to improve food and drink manufacturers' resource efficiency problems. The methodology is then applied to four food and drink manufacturing case studies to demonstrate its capabilities for a diverse range of applications within the sector. The case studies included the monitoring of mixing, cleaning and fermentation processes in addition to predicting key quality parameter of crops. For all case studies, the methodology was successfully applied and predictive models with accuracies ranging from 95 to 100% were achieved. The case studies also highlight challenges and considerations which still remain when applying the methodology, including efficient data acquisition and labelling, feature engineering, and model selection. This paper concludes by discussing the future work necessary around the topics of new online sensors, infrastructure, data acquisition and trust to enable the widespread adoption of intelligent sensors within the food and drink sector

    Health and economic benefits of achieving contraceptive and maternal health targets in small island developing states in the Pacific and Caribbean

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    INTRODUCTION: Reducing unmet need for modern contraception and expanding access to quality maternal health (MH) services are priorities for improving women's health and economic empowerment. To support investment decisions, we estimated the additional cost and expected health and economic benefits of achieving the United Nations targets of zero unmet need for modern contraceptive choices and 95% coverage of MH services by 2030 in select Small Island Developing States. METHODS: Five Pacific (Kiribati, Samoa, Solomon Islands, Tonga and Vanuatu) and four Caribbean (Barbados, Guyana, Jamaica and Saint Lucia) countries were considered based on population survey data availability. For each country, the Lives Saved Tool was used to model costs, health outcomes and economic benefits for two scenarios: business-as-usual (BAU) (coverage maintained) and coverage-targets-achieved, which scaled linearly from 2022 (following COVID-19 disruptions) coverage of evidence-based family planning and MH interventions to reach United Nations targets, including modern contraceptive methods and access to complete antenatal, delivery and emergency care. Unintended pregnancies, maternal deaths, stillbirths and newborn deaths averted by the coverage-targets-achieved scenario were converted to workforce, education and social economic benefits; and benefit-cost ratios were calculated. RESULTS: The coverage-targets-achieved scenario required an additional US12.6M(US12.6M (US10.8M-US15.9M)over20202030forthefivePacificcountries(1515.9M) over 2020-2030 for the five Pacific countries (15% more than US82.4M to maintain BAU). This additional investment was estimated to avert 126 000 (40%) unintended pregnancies, 2200 (28%) stillbirths and 121 (29%) maternal deaths and lead to a 15-fold economic benefit of US190.6M(US190.6M (US67.0M-US304.5M)by2050.ForthefourCaribbeancountries,anadditionalUS304.5M) by 2050. For the four Caribbean countries, an additional US17.8M (US15.3MUS15.3M-US22.4M) was needed to reach the targets (4% more than US405.4MtomaintainBAU).Thiswasestimatedtoavert127000(23405.4M to maintain BAU). This was estimated to avert 127 000 (23%) unintended pregnancies, 3600 (23%) stillbirths and 221 (25%) maternal deaths and lead to a 24-fold economic benefit of US426.2M (US138.6MUS138.6M-US745.7M) by 2050. CONCLUSION: Achieving full coverage of contraceptive and MH services in the Pacific and Caribbean is likely to have a high return on investment

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

    Neoliberalism and University Education in Sub-Saharan Africa

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    This article reviews the history of university development in Sub-Saharan Africa (SSA) and discusses the impact of neoliberal policies. This will be followed by an examination of the problems facing universities in the region. The following questions will be explored: (a) Are the existing universities in SSA serving the development needs of the region? (b) Are these universities up to the task of moving SSA out of the predicaments it faces such as famine, HIV/AIDS, poverty, diseases, debt, and human rights abuses? Finally, the article argues that for universities to play a role in the development of the region, a new paradigm that makes university education a public good should be established

    Health workforce and governance: the crisis in Nigeria

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    Background In Nigeria, several challenges have been reported within the health sector, especially in training, funding, employment, and deployment of the health workforce. We aimed to review recent health workforce crises in the Nigerian health sector to identify key underlying causes and provide recommendations toward preventing and/or managing potential future crises in Nigeria. Methods We conducted a scoping literature search of PubMed to identify studies on health workforce and health governance in Nigeria. A critical analysis, with extended commentary, on recent health workforce crises (2010–2016) and the health system in Nigeria was conducted. Results The Nigerian health system is relatively weak, and there is yet a coordinated response across the country. A number of health workforce crises have been reported in recent times due to several months’ salaries owed, poor welfare, lack of appropriate health facilities and emerging factions among health workers. Poor administration and response across different levels of government have played contributory roles to further internal crises among health workers, with different factions engaged in protracted supremacy challenge. These crises have consequently prevented optimal healthcare delivery to the Nigerian population. Conclusions An encompassing stakeholders’ forum in the Nigerian health sector remain essential. The national health system needs a solid administrative policy foundation that allows coordination of priorities and partnerships in the health workforce and among various stakeholders. It is hoped that this paper may prompt relevant reforms in health workforce and governance in Nigeria toward better health service delivery in the country
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