Superimposé: a 3D structural superposition server

The Superimposé webserver performs structural similarity searches with a preference towards 3D structure-based methods. Similarities can be detected between small molecules (e.g. drugs), parts of large structures (e.g. binding sites of proteins) and entire proteins. For this purpose, a number of algorithms were implemented and various databases are provided. Superimposé assists the user regarding the selection of a suitable combination of algorithm and database. After the computation on our server infrastructure, a visual assessment of the results is provided. The structure-based in silico screening for similar drug-like compounds enables the detection of scaffold-hoppers with putatively similar effects. The possibility to find similar binding sites can be of special interest in the functional analysis of proteins. The search for structurally similar proteins allows the detection of similar folds with different backbone topology. The Superimposé server is available at: http://bioinformatics.charite.de/superimpose

Spatial distribution of podoconiosis in relation to environmental factors in Ethiopia: a historical review

BACKGROUND An up-to-date and reliable map of podoconiosis is needed to design geographically targeted and cost-effective intervention in Ethiopia. Identifying the ecological correlates of the distribution of podoconiosis is the first step for distribution and risk maps. The objective of this study was to investigate the spatial distribution and ecological correlates of podoconiosis using historical and contemporary survey data. METHODS Data on the observed prevalence of podoconiosis were abstracted from published and unpublished literature into a standardized database, according to strict inclusion and exclusion criteria. In total, 10 studies conducted between 1969 and 2012 were included, and data were available for 401,674 individuals older than 15 years of age from 229 locations. A range of high resolution environmental factors were investigated to determine their association with podoconiosis prevalence, using logistic regression. RESULTS The prevalence of podoconiosis in Ethiopia was estimated at 3.4% (95% CI 3.3%-3.4%) with marked regional variation. We identified significant associations between mean annual Land Surface Temperature (LST), mean annual precipitation, topography of the land and fine soil texture and high prevalence of podoconiosis. The derived maps indicate both widespread occurrence of podoconiosis and a marked variability in prevalence of podoconiosis, with prevalence typically highest at altitudes >1500 m above sea level (masl), with >1500 mm annual rainfall and mean annual LST of 19-21°C. No (or very little) podoconiosis occurred at altitudes 24°C. CONCLUSION Podoconiosis remains a public health problem in Ethiopia over considerable areas of the country, but exhibits marked geographical variation associated in part with key environmental factors. This is work in progress and the results presented here will be refined in future work

Soft x ray tomoholography

We demonstrate an x ray imaging method that combines Fourier transform holography with tomography tomoholography for threedimensional 3D microscopic imaging. A 3D image of a diatom shell with a spatial resolution of 140 nm is presented. The experiment is realized by using a small gold sphere as the reference wave source for holographic imaging. This setup allows us to rotate the sample and to collect a number of 2D projections for tomograph

Biochemical indices and life traits of loggerhead turtles (Caretta caretta) from Cape Verde Islands

The loggerhead turtle (Caretta caretta) is an endangered marine reptile for whom assessing population health requires knowledge of demographic parameters such as individual growth rate. In Cape Verde, as within several populations, adult female loggerhead sea turtles show a size-related behavioral and trophic dichotomy. While smaller females are associated with oceanic habitats, larger females tend to feed in neritic habitats, which is reflected in their physiological condition and in their offspring. The ratio of RNA/DNA provides a measure of cellular protein synthesis capacity, which varies depending on changes in environmental conditions such as temperature and food availability. The purpose of this study was to evaluate the combined use of morphometric data and biochemical indices as predictors of the physiological condition of the females of distinct sizes and hatchlings during their nesting season and how temperature may influence the physiological condition on the offspring. Here we employed biochemical indices based on nucleic acid derived indices (standardized RNA/DNA ratio-sRD, RNA concentration and DNA concentration) in skin tissue as a potential predictor of recent growth rate in nesting females and hatchling loggerhead turtles. Our major findings were that the physiological condition of all nesting females (sRD) decreased during the nesting season, but that females associated with neritic habitats had a higher physiological condition than females associated with oceanic habitats. In addition, the amount of time required for a hatchling to right itself was negatively correlated with its physiological condition (sRD) and shaded nests produced hatchlings with lower sRD. Overall, our results showed that nucleic acid concentrations and ratios of RNA to DNA are an important tool as potential biomarkers of recent growth in marine turtles. Hence, as biochemical indices of instantaneous growth are likely temperature-, size- and age-dependent, the utility and validation of these indices on marine turtles stocks deserves further study.The authors thank the Cape Verde Ministry of Environment (General Direction for the Environment), INDP (National Fisheries Institution), the Canary Islands Government (D.G. Africa and D.G. Research and Universities), ICCM (Canarian Institution for Marine Sciences), the Andalusian Government (Andalusian Environmental Office) and AEGINA PROJECT (INTERREG IIIB) for funding and hosting them during this study. The authors also thank the European Regional Development Fund (ERDF) through the COMPETE - Operational Competitiveness Programme, and national funds through FCT - PEst-C/MAR/LA0015/2011 for supporting the biochemical analysis

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

BACKGROUND: Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. METHODS: Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 10(6 )structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. RESULTS: The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. CONCLUSION: Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs

Developing evidence-based ethical policies on the migration of health workers: conceptual and practical challenges

It is estimated that in 2000 almost 175 million people, or 2.9% of the world's population, were living outside their country of birth, compared to 100 million, or 1.8% of the total population, in 1995. As the global labour market strengthens, it is increasingly highly skilled professionals who are migrating. Medical practitioners and nurses represent a small proportion of highly skilled workers who migrate, but the loss of health human resources for developing countries can mean that the capacity of the health system to deliver health care equitably is compromised. However, data to support claims on both the extent and the impact of migration in developing countries is patchy and often anecdotal, based on limited databases with highly inconsistent categories of education and skills. The aim of this paper is to examine some key issues related to the international migration of health workers in order to better understand its impact and to find entry points to developing policy options with which migration can be managed. The paper is divided into six sections. In the first, the different types of migration are reviewed. Some global trends are depicted in the second section. Scarcity of data on health worker migration is one major challenge and this is addressed in section three, which reviews and discusses different data sources. The consequences of health worker migration and the financial flows associated with it are presented in section four and five, respectively. To illustrate the main issues addressed in the previous sections, a case study based mainly on the United Kingdom is presented in section six. This section includes a discussion on policies and ends by addressing the policy options from a broader perspective

Global epidemiology of podoconiosis: a systematic review

Background Podoconiosis is one of the few diseases that could potentially be eliminated within one generation. Nonetheless, the global distribution of the disease remains largely unknown. The global atlas of podoconiosis was conceived to define the epidemiology and distribution of podoconiosis through dedicated surveys and assembling the available epidemiological data. Methods We have synthesized the published literature on the epidemiology of podoconiosis. Through systematic searches in SCOPUS and MEDLINE from inception to February 14, 2018, we identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used case reports and presence data. For a study to be included in the prevalence synthesis, it needed to be a population-based survey that involved all residents within a specific area. Studies that did not report original data were excluded. We undertook descriptive analyses of the extracted data. This study is registered with PROSPERO, number CRD42018084959. Results We identified 3,260 records, of which 27 studies met the inclusion criteria. Podoconiosis was described to exist or be endemic in 32 countries, 18 from the African Region, 3 from Asia and 11 from Latin America. Overall, podoconiosis prevalence ranged from 0·10% to 8.08%, was highest in the African region, and was substantially higher in adults than in children and adolescents. The highest reported prevalence values were in Africa (8.08% in Cameroon, 7.45% in Ethiopia, 4.52% in Uganda, 3.87% in Kenya and 2.51% in Tanzania). In India, a single prevalence of 0.21% was recorded from Manipur, Mizoram and Rajasthan states. None of the Latin American countries reported prevalence data. Conclusion Our data suggest that podoconiosis is more widespread in the African Region than in the rest of the regions, although this could be related to the fact that most podoconiosis epidemiological research has been focused in the African continent. The assembled dataset confirms that comprehensive podoconiosis control strategies such as promotion of footwear and personal hygiene are urgently needed in endemic parts of Africa. Mapping, active surveillance and a systematic approach to the monitoring of disease burden must accompany the implementation of podoconiosis control activities

Effect of Acinetobacter sp on Metalaxyl Degradation and Metabolite Profile of Potato Seedlings (Solanum tuberosum L.) Alpha Variety

One of the most serious diseases in potato cultivars is caused by the pathogen Phytophthora infestans, which affects leaves, stems and tubers. Metalaxyl is a fungicide that protects potato plants from Phytophthora infestans. In Mexico, farmers apply metalaxyl 35 times during the cycle of potato production and the last application is typically 15 days before harvest. There are no records related to the presence of metalaxyl in potato tubers in Mexico. In the present study, we evaluated the effect of Acinetobacter sp on metalaxyl degradation in potato seedlings. The effect of bacteria and metalaxyl on the growth of potato seedlings was also evaluated. A metabolite profile analysis was conducted to determine potential molecular biomarkers produced by potato seedlings in the presence of Acinetobacter sp and metalaxyl. Metalaxyl did not affect the growth of potato seedlings. However, Acinetobacter sp strongly affected the growth of inoculated seedlings, as confirmed by plant length and plant fresh weights which were lower in inoculated potato seedlings (40% and 27%, respectively) compared to the controls. Acinetobacter sp also affected root formation. Inoculated potato seedlings showed a decrease in root formation compared to the controls. LC-MS/MS analysis of metalaxyl residues in potato seedlings suggests that Acinetobacter sp did not degrade metalaxyl. GC–TOF–MS platform was used in metabolic profiling studies. Statistical data analysis and metabolic pathway analysis allowed suggesting the alteration of metabolic pathways by both Acinetobacter sp infection and metalaxyl treatment. Several hundred metabolites were detected, 137 metabolites were identified and 15 metabolic markers were suggested based on statistical change significance found with PLS-DA analysis. These results are important for better understanding the interactions of putative endophytic bacteria and pesticides on plants and their possible effects on plant metabolism