Mycobacterium smegmatis But Not Mycobacterium avium subsp. hominissuis Causes Increased Expression of the Long Non-Coding RNA MEG3 in THP-1-Derived Human Macrophages and Associated Decrease of TGF-β

Pathogenic mycobacteria are able to persist intracellularly in macrophages, whereas non-pathogenic mycobacteria are effectively combated and eliminated after their phagocytosis. It is known that TGF-β plays an important role in this context. Infection with pathogenic mycobacteria such as Mycobacterium tuberculosis or M. avium leads to production of active TGF-β, which blocks the ability of IFN-γ and TNF-α to inhibit intracellular replication. On the other hand, it is known that the long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is involved in the regulation of TGF-β. In this study, we show how the infection of THP-1-derived human macrophages with the saprophytic M. smegmatis but not with the facultatively pathogenic M. avium subsp. hominissuis leads to increased MEG3 expression. This is associated with the downregulation of DNA methyltransferases (DNMT) 1 and 3b, which are known to regulate MEG3 expression via promoter hypermethylation. Consequently, we observe a significant downregulation of TGF-β in M. smegmatis-infected macrophages but not in M. avium subsp. hominissuis pointing to lncRNAs as novel mediators of host cell response during mycobacterial infections

Functional analysis and transcriptional output of the Göttingen minipig genome

In the past decade the Göttingen minipig has gained increasing recognition as animal model in pharmaceutical and safety research because it recapitulates many aspects of human physiology and metabolism. Genome-based comparison of drug targets together with quantitative tissue expression analysis allows rational prediction of pharmacology and cross-reactivity of human drugs in animal models thereby improving drug attrition which is an important challenge in the process of drug development.; Here we present a new chromosome level based version of the Göttingen minipig genome together with a comparative transcriptional analysis of tissues with pharmaceutical relevance as basis for translational research. We relied on mapping and assembly of WGS (whole-genome-shotgun sequencing) derived reads to the reference genome of the Duroc pig and predict 19,228 human orthologous protein-coding genes. Genome-based prediction of the sequence of human drug targets enables the prediction of drug cross-reactivity based on conservation of binding sites. We further support the finding that the genome of Sus scrofa contains about ten-times less pseudogenized genes compared to other vertebrates. Among the functional human orthologs of these minipig pseudogenes we found HEPN1, a putative tumor suppressor gene. The genomes of Sus scrofa, the Tibetan boar, the African Bushpig, and the Warthog show sequence conservation of all inactivating HEPN1 mutations suggesting disruption before the evolutionary split of these pig species. We identify 133 Sus scrofa specific, conserved long non-coding RNAs (lncRNAs) in the minipig genome and show that these transcripts are highly conserved in the African pigs and the Tibetan boar suggesting functional significance. Using a new minipig specific microarray we show high conservation of gene expression signatures in 13 tissues with biomedical relevance between humans and adult minipigs. We underline this relationship for minipig and human liver where we could demonstrate similar expression levels for most phase I drug-metabolizing enzymes. Higher expression levels and metabolic activities were found for FMO1, AKR/CRs and for phase II drug metabolizing enzymes in minipig as compared to human. The variability of gene expression in equivalent human and minipig tissues is considerably higher in minipig organs, which is important for study design in case a human target belongs to this variable category in the minipig. The first analysis of gene expression in multiple tissues during development from young to adult shows that the majority of transcriptional programs are concluded four weeks after birth. This finding is in line with the advanced state of human postnatal organ development at comparative age categories and further supports the minipig as model for pediatric drug safety studies.; Genome based assessment of sequence conservation combined with gene expression data in several tissues improves the translational value of the minipig for human drug development. The genome and gene expression data presented here are important resources for researchers using the minipig as model for biomedical research or commercial breeding. Potential impact of our data for comparative genomics, translational research, and experimental medicine are discussed

Discoveries from La Manche : five years of early prehistoric research in the Channel Island of Jersey

Grateful thanks to the AHRC, NERC, the Leverhulme Foundation and the Calleva FoundationSince 2010 a new field project drawn from major UK institutions including the UCL Institute of Archaeology, has focused research on the Palaeolithic and Mesolithic record of the Channel Island of Jersey. In this retrospective of five years of research the history of the project to date, its focus on the Middle Palaeolithic site of La Cotte de St Brelade and its growth into an international research team is charted. The formation of the La Manche Prehistorique research network in 2015 marks a new chapter in the development of this project. With its wider focus, but continued commitment to research in the Channel Islands, the research group are working towards a unified early prehistoric research framework for the English Channel region.Publisher PDFPeer reviewe

Enhancing Knowledge and Confidence in a Retail Clinic Setting of Practitioners in Treating Primary and Secondary Hypertension

Many adult and adolescent patients in primary care settings are diagnosed with primary hypertension, however the workup often does not include an evaluation of secondary causes. The purpose of this Doctor of Nursing Practice (DNP) project was to improve the diagnosis and treatment of hypertension for patients seeking health care in a retail clinic setting. The PICOT question was, what is the effect of an educational offering on hypertension standards of care in enhancing knowledge and confidence for providers working in a retail health clinic setting? The sampling frame was 40 Nurse Practitioners and Physician Assistants employed at CVS Minute Clinic in Region 38, North Carolina. A 60-minute PowerPoint presentation was developed by the project leader on guidelines for the diagnosis and treatment of primary and secondary hypertension. Provider knowledge and confidence levels (dependent variables) were measured pre- and post-education using an authorcreated tool using valid questions from the literature. Nine providers (22.5%) completed the pre-survey and only one provider completed the post-survey. Pre-survey results revealed knowledge deficits in using current standards and guidelines for the diagnosis and long-term treatment of primary and secondary hypertension. Providers reported being only moderately confident (33%) and somewhat confident (67%) in their ability to diagnose and treat hypertension and secondary hypertension. These findings are congruent with the literature and with Orem’s concept of nursing agency. Nursing agencies can be promoted through comprehensive provider education and additional time and resources for nurse practitioners and physician assistants working in retail clinic 4 settings. The use of best practice standards will enhance hypertensive care for the community

Pre- and post-selection, weak values, and contextuality

By analyzing the concept of contextuality (Bell-Kochen-Specker) in terms of pre-and-post-selection (PPS), it is possible to assign definite values to observables in a new and surprising way. Physical reasons are presented for restrictions on these assignments. When measurements are performed which do not disturb the pre- and post-selection (i.e. weak measurements), then novel experimental aspects of contextuality can be demonstrated including a proof that every PPS-paradox with definite predictions implies contextuality. Certain results of these measurements (eccentric weak values with e.g. negative values outside the spectrum), however, cannot be explained by a "classical-like" hidden variable theory.Comment: Identical content; stream-lined verbal presentatio

Resilience in the face of food insecurity and food crises : bringing the experiences of women's organizations to the development and humanitarian table; final technical report

This research initiative aimed to contribute to the body of knowledge on resilience-building and disaster risk reduction from a gender and women’s rights perspective. Investments in resilience will not “trickle down” to women if deep-rooted gender inequality and the disproportionate burdens placed on women remain unaddressed. The vulnerabilities people experience are linked to structures of oppression and discrimination. The study focused on how women’s organizations define resilience, identify risk, and implement resilience-building strategies. This paper reviews project activities, outputs, outcomes and recommendations, and includes an annotated bibliography, along with an annex list of women’s organizations

Suivi GPS de Pteropus Lylei à l’interface chauves-souris humains : intérêt pour la conservation et l’étude du risque d’émergence du virus Nipah au Cambodge

Trois espèces de roussettes ont été observées au Cambodge mais peu de données sont disponibles concernant leur écologie et leur déplacement. Les roussettes sont considérées comme le principal réservoir du virus Nipah (NiV). Détecté pour la première fois en Malaisie en 1998 chez les porcs, ce virus émergent a provoqué l’abattage massif de millions de porcs afin de stopper la diffusion du virus. Par la suite, le NiV a été transmis des porcs aux humains, entrainant l’apparition de 265 cas humain en Malaisie causant la mort de 105 personnes. Depuis 2001, des ré-émergences ont été observées au Bangladesh et en Inde provoquant l’apparition de 200 cas humains, fatal dans plus de 70% des cas. L’évidence de la circulation du NiV chez les Pteropodidae a été rapportée en Asie du Sud-est et une distribution saisonnière a été suggérée en Thaïlande. Au Cambodge, l’évidence de la circulation du virus NiV chez les roussettes a préalablement été rapportée mais peu de données existent concernant l’épidémiologie du virus. L’objectif de cette étude sera de décrire la distribution et les mouvements des Pteropus lylei capturées au site dortoir de la province de Kandal à une échelle locale via l’utilisation de 14 émetteurs. Ces émetteurs fourniront la localisation des chauves- souris permettant ainsi de caractériser l’habitat des P.lylei et par conséquent l’interface entre les chauves- souris et les activités humaines, fournissant ainsi d’importantes informations pour la conservation de ces espèces et pour l’estimation du risque de transmission d’agents pathogènes à l’interface Homme chauves-souris

Resilience in times of food insecurity : reflecting on the experiences of women's organizations

French version available in IDRC Digital Library: Résilience et sécurité alimentaire : apprendre de l'expérience des organisations de femmesSpanish version available in IDRC Digital Library: Resiliencia y seguridad alimentaria : aprendiendo de las experiencias de las organizaciones de mujeresResilience is about more than technical fixes, it requires social transformation in the broadest sense. Investments in resilience will not ‘trickle down’ to women if they do not address deep-rooted gender inequality and the disproportionate burden placed on the shoulders of women living in poverty. Ultimately, a transformative approach to building resilience implies moving beyond the status quo and tackling the systemic forms of discrimination that put women at risk in the first place. The international community should recognize women’s organizations as val-ued partners that can bring unique perspectives to resilience policy and practice