The strong enhancer element in the immediate early region of the human cytomegalovirus genome

The human cytomegalovirus (HCMV), a member of the herpesvirus group, was found to possess a strong transcription enhancer in the immediate early gene region. Co-transfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-like recombinant viruses , each containing HCMV DNA fragments that were substituting for the missing SV40 enhancer. The two inserts , 341 and 262 bp in length , are overlapping segments of genuine viral DNA representing part of the 5'flanking region of the major immedistte early gene i n HCMV. Studies with deletion mutants showed that different nonoverlapping subsets of the HCMV enhancer region can substitute for the 72 bp repeats of SV40. Transient expression assays indicated that the HCMV enhancer is significantly stronger than the SV40 element, activating cis-linked heterologous promoters in a wide spectrum of cultured cells. It appears that the HCMV enhancer is positively regulated by viral immediate early genes

Genetic architecture of a key reproductive isolation trait differs between sympatric and non-sympatric sister species of Lake Victoria cichlids

One hallmark of the East African cichlid radiations is the rapid evolution of reproductive isolation that is robust to full sympatry of many closely related species. Theory predicts that species persistence and speciation in sympatry with gene flow are facilitated if loci of large effect or physical linkage (or pleiotropy) underlie traits involved in reproductive isolation. Here, we investigate the genetic architecture of a key trait involved in behavioural isolation, male nuptial coloration, by crossing two sister species pairs of Lake Victoria cichlids of the genus Pundamilia and mapping nuptial coloration in the F2 hybrids. One is a young sympatric species pair, representative of an axis of colour motif differentiation, red-dorsum versus blue, that is highly recurrent in closely related sympatric species. The other is a species pair representative of colour motifs, red-chest versus blue, that are common in allopatric but uncommon in sympatric closely related species. We find significant quantitative trait loci (QTLs) with moderate to large effects (some overlapping) for red and yellowin the sympatric red-dorsum× blue cross, whereas we find no significant QTLs in the non-sympatric red-chest × blue cross. These findings are consistent with theory predicting that large effect loci or linkage/pleiotropy underlying mating trait differentiation could facilitate speciation and species persistence with gene flow in sympatry

3rd Annual Conference of the Leverhulme Centre for Integrative Research on Agriculture and Health (LCIRAH), Developing methods in agriculture and health research, London, 13–14 June 2013

Non-PRIFPRI3; ISI; CRP4; B Promoting healthy food systemsPHND; A4NHCGIAR Research Program on Agriculture for Nutrition and Health (A4NH

Experimental parasite infection causes genome-wide changes in DNA methylation

Parasites are arguably among the strongest drivers of natural selection, constraining hosts to evolve resistance and tolerance mechanisms. Although, the genetic basis of adaptation to parasite infection has been widely studied, little is known about how epigenetic changes contribute to parasite resistance and eventually, adaptation. Here, we investigated the role of host DNA methylation modifications to respond to parasite infections. In a controlled infection experiment, we used the three-spined stickleback fish, a model species for host-parasite studies, and their nematode parasite Camallanus lacustris. We showed that the levels of DNA methylation are higher in infected fish. Results furthermore suggest correlations between DNA methylation and shifts in key fitness and immune traits between infected and control fish, including respiratory burst and functional trans-generational traits such as the concentration of motile sperm. We revealed that genes associated with metabolic, developmental and regulatory processes (cell death and apoptosis) were differentially methylated between infected and control fish. Interestingly, genes such as the neuropeptide FF receptor 2 and the integrin alpha 1 as well as molecular pathways including the Th1 and Th2 cell differentiation were hypermethylated in infected fish, suggesting parasite-mediated repression mechanisms of immune responses. Altogether, we demonstrate that parasite infection contributes to genome-wide DNA methylation modifications. Our study brings novel insights into the evolution of vertebrate immunity and suggests that epigenetic mechanisms are complementary to genetic responses against parasite-mediated selection

Morbiditäts- und Mortalitätskonferenzen in Niedersachsen: Status quo und Weiterentwicklungsbedarf

BACKGROUND Morbidity and mortality conferences (M&MC) are a tool to foster individual and organizational learning in hospitals, and they are important to improve patient safety. So far, no data has been available about the implementation of M&MC in Lower Saxony and the characteristics of M&MCs. The aim of this study was to assess the status quo of M&MC in Lower Saxony and to identify the potential for improvement. METHODS A cross-sectional survey study was conducted among chief physicians in surgery, internal medicine, anesthesiology/intensive care, gynecology/obstetrics and pediatrics (response rate: 50 %). RESULTS Apart from technical topics (37 %), the main issues addressed are process (92 %) and teamwork (64 %) issues. The results also show a strong heterogeneity in terms of structures and processes of implemented M&MC in Lower Saxony. Despite a high level of satisfaction (85 %) and perceived effectiveness (93 %), most participants see potential for improvement of "their" M&MC (58 %). CONCLUSION Chief physicians in Lower Saxony report both a high level of acceptance and the need for further improvement of the M&MCs, which represents good preconditions for further development towards effective M&MCs.Zusammenfassung Hintergrund Morbiditäts- und Mortalitätskonferenzen (MMK) sind ein Instrument sowohl des individuellen als auch des organisationalen Lernens in Krankenhäusern und wichtig für die Verbesserung der Patientensicherheit. Bisher war allerdings unklar, wie verbreitet die MMK in Niedersachsen ist und wie sie umgesetzt wird. Das Ziel der Studie war, den Status Quo der MMK in Niedersachsen zu erfassen und Verbesserungspotenzial zu eruieren. Methode Es wurde eine Querschnittstudie mittels Online-Befragung von Chefärztinnen und -ärzten der chirurgischen Fächer, internistischen Fächer, der Anästhesiologie/Intensivmedizin, der Gynäkologie/Geburtshilfe und Pädiatrie durchgeführt (Rücklauf-Quote: 50%). Resultate In den MMK werden neben fachlichen Themen (37%) zunehmend Probleme in den Prozessen (92%) und der Zusammenarbeit (64%) besprochen. Die Resultate zeigen auch, dass die MMK in Niedersachsen bezüglich Struktur und Prozessen sehr heterogen sind. Trotz hoher Zufriedenheit (85%) und subjektiv eingeschätzter Wirksamkeit (93%) der MMK sehen die meisten Teilnehmenden Verbesserungspotenzial (58%). Schlussfolgerung Da generell sowohl eine hohe Akzeptanz als auch das Bedürfnis nach einer Weiterentwicklung sichtbar sind, existieren gute Voraussetzungen, die MMK weiterzuentwickeln

Capturing systematically users' experience of evaluation tools for integrated AMU and AMR surveillance

Tackling antimicrobial resistance (AMR) is a goal for many countries. Integrated surveillance of antimicrobial use (AMU) and resistance is a prerequisite for effective risk mitigation. Regular evaluation of any surveillance is needed to ensure its effectiveness and efficiency. The question is how to evaluate specifically integrated surveillance for AMU and AMR. In an international network called CoEvalAMR, we have developed guidelines for selection of the most appropriate tools for such an evaluation. Moreover, we have assessed different evaluation tools as examples using a country case format and a methodology with a focus on the user's experience. This paper describes the updated methodology, which consists of a brief introduction to the case and to the tool separately. Moreover, there are 12 functional aspects and nine content themes which should be scored using a 4-tiered scale. Additionally, four Strengths, Weaknesses, Opportunities, Threats (SWOT) questions should be addressed. Results are illustrated using radar diagrams. An example of application of the updated methodology is given using the ECoSur evaluation tool. No tool can cover all evaluation aspects comprehensively in a user-friendly manner, so the choice of tool must be based upon the specific evaluation purpose. Moreover, adequate resources, time and training are needed to obtain useful outputs from the evaluation. Our updated methodology can be used by tool users to share their experience with available tools, and hereby assist other users in identifying the most suited tool for their evaluation purpose. Additionally, tool developers can get valuable information for further improvements of their tool

A functional methylome map of ulcerative colitis

The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation

Livestock trade networks for guiding animal health surveillance

BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users

The role of food systems in improving maternal and child nutrition in challenging African low-income settings

Purpose Overcrowded cities in developing countries present challenging environments for health, where zoonoses and food safety are difficult to control. Whilst animal source foods (ASF) have a well-recognized role in nutrition of vulnerable populations, their availability, safety and quality are often compromised, and nutrition outcomes are rarely considered in livestock studies. We developed and tested a framework to study the association between consumers’ access to and use of different ASF and livestock value chains, and poor nutritional status, to inform decisions on interventions and policies. Methods This multidisciplinary study combined quantitative and qualitative methodologies to address unexplored linkages between value chain and nutrition. 205 households and 222 retailers in two Nairobi slums were surveyed to 1) measure consumption and undernutrition; 2) examine ASF role in adequate diets using linear programming; and 3) investigate value chain links with nutrition. For each ASF, consumption patterns, acceptability factors of products and retailers, demand variation with price and availability (expansion potential of value chain) were combined to provide a holistic picture and identify target chains. Results and conclusions 74% of the children and 26% of the women were anaemic, and had low intakes of several micronutrients. Linear programing analysis indicated that food-based interventions could ensure women’s dietary adequacy for women, for all of these nutrients except iron, as long as intakes of milk and other ASF could be increased from median intakes. Milk was the most consumed ASF (98.5% of the households, 5.5 times/wk). Demand for beef was least sensitive to changes in its price and its supply chain had limited expansion potential. Demand for chicken was more responsive to price changes while its supply chains could be expanded quickly. Consumption was often based on ‘taste’ and ‘nutrition’, indicating a potential role for nutrition education. Relevance Nutrition sensitive agriculture being key to fight malnutrition, we will show the importance of the value chain approach to assess feasibility and upscaling of safe ASF food system-based interventions