Midwater fish data report for warm-core Gulf Stream rings cruises 1981-1982

This data report is for midwater fishes collected during the multidisciplinary Warm-Core Rings Program in 1981 and 1982. Stations were made in and near three warm-core rings on five cruises within a period of 14 months. On Atlantis II cruise 110 (September-October 1981) six stations were made in and around ring 81-D (age two months). Stations were made in the vicinity of ring 82-B on three cruises in 1982--twelve stations during Oceanus 118 (April) when the ring was two months old, 15 stations during Oceanus 121 (June) at age four months, and 19 stations during Oceanus 125 (August) at age 5.5 months. Finally, twelve stations were made in and near meander/ring 82-H (age 0) during Knorr 98 in September/October 1982 (Tables 1-10). The collections were made with a new midwater trawl - the MOCNESS-20 (MOC-20) (Wiebe et al., 1985), a scaled-up version of the MOCNESS-1 (an apparatus for collecting zooplankton; Wiebe et al., 1976) and successor to the MOCNESS-10 (like the MOC-20, a midwater trawl). (The number forming the distinctive part of the name of these nets is equal to the area of the projected mouth in square meters when the apparatus is in a common fishing attitude.) The MOC-20 consists of a set of 3-mm mesh rectangular nets that can be opened and closed by command from the surface via a signal-conducting towing warp. Apparatus attached to the net frame measures and transmits depth, temperature, conductivity, flow, and net-frame angle to the towing ship's laboratory. Flow (net speed), vertical velocity, and net-frame angle allow computation of the water volume filtered . On the WCR cruises a set of five or six nets was used. One net (not used for quantitative analyses) was fished down to 1000 m, then closed and a second net opened. The second and successive nets were closed and opened sequentially at intervals as the apparatus was brought back to the surface. A surface-to-surface cycle with the gear is referred to as a station, the contents of a single net as a collection. In addition to be1ng described by latitude and longitude, stat1ons are located in the same radial coordinate system used to composite the warm-core rings physical data, that is, by distance and bearing from the moving ring center.Funding was provided by the National Scten.ce Foundation under Grant Numbers OCE 80-17270 and OCE 86-20402

Digital Mental Health and Social Connectedness

A detailed understanding of the mental health needs of people from refugee backgrounds is crucial for the design of inclusive mental health technologies. We present a qualitative account of the digital mental health experiences of women from refugee backgrounds. Working with community members and community workers of a charitable organisation for refugee women in the UK, we identify social and structural challenges, including loneliness and access to mental health technologies. Participants' accounts document their collective agency in addressing these challenges and supporting social connectedness and personal wellbeing in daily life: participants reported taking part in community activities as volunteers, sharing technological expertise, and using a wide range of non-mental health-focused technologies to support their mental health, from playing games to supporting religious practices. Our findings suggest that, rather than focusing only on individual self-care, research also needs to leverage community-driven approaches to foster social mental health experiences, from altruism to connectedness and belonging

Using Gene Expression Signatures to Identify Novel Treatment Strategies in Gulf War Illness

Background Gulf War Illness (GWI) is a complex multi-symptom disorder that affects up to one in three veterans of this 1991 conflict and for which no effective treatment has been found. Discovering novel treatment strategies for such a complex chronic illness is extremely expensive, carries a high probability of failure and a lengthy cycle time. Repurposing Food and Drug Administration approved drugs offers a cost-effective solution with a significantly abbreviated timeline. Methods Here, we explore drug re-purposing opportunities in GWI by combining systems biology and bioinformatics techniques with pharmacogenomic information to find overlapping elements in gene expression linking GWI to successfully treated diseases. Gene modules were defined based on cellular function and their activation estimated from the differential expression of each module’s constituent genes. These gene modules were then cross-referenced with drug atlas and pharmacogenomic databases to identify agents currently used successfully for treatment in other diseases. To explore the clinical use of these drugs in illnesses similar to GWI we compared gene expression patterns in modules that were significantly expressed in GWI with expression patterns in those same modules in other illnesses. Results We found 19 functional modules with significantly altered gene expression patterns in GWI. Within these modules, 45 genes were documented drug targets. Illnesses with highly correlated gene expression patterns overlapping considerably with GWI were found in 18 of the disease conditions studied. Brain, muscular and autoimmune disorders composed the bulk of these. Conclusion Of the associated drugs, immunosuppressants currently used in treating rheumatoid arthritis, and hormone based therapies were identified as the best available candidates for treating GWI symptoms

Explanation before Adoption: Supporting Informed Consent for Complex Machine Learning and IoT Health Platforms

Explaining health technology platforms to non-technical members of the public is an important part of the process of informed consent. Complex technology platforms that deal with safety-critical areas are particularly challenging, often operating within private domains (e.g. health services within the home) and used by individuals with various understandings of hardware, software, and algorithmic design. Through two studies, the first an interview and the second an observational study, we questioned how experts (e.g. those who designed, built, and installed a technology platform) supported provision of informed consent by participants. We identify a wide range of tools, techniques, and adaptations used by experts to explain the complex SPHERE sensor-based home health platform, provide implications for the design of tools to aid explanations, suggest opportunities for interactive explanations, present the range of information needed, and indicate future research possibilities in communicating technology platforms

The publics of public health in Africa

How do we understand the public character of public health in contemporary Africa? What are the parameters of community engagement in health care delivery, medical research and disease control programmes? To what extent is public health in Africa a project led by African Governments? Through what political processes and deliberative practices can African publics influence the priorities of research in health sciences and interventions which aim in broad terms to improve the health of such publics? Drawing insight from empirical research conducted with African scientists, nurses, community members, clinical trialists and policy-makers, this special section examines the multiple ways in which the public comes into being around public health provisioning and investigation in sub-Saharan Africa, its role and political reach. Collectively, these papers show how contestation and negotiation around different ideas about who the public is and what being public means can lead to the emergence of conflicting understandings, with implications for who and what is seen to represent the public interest, and for the acceptance of research and other interventions

Targeted Deletion of the Ileal Bile Acid Transporter Eliminates Enterohepatic Cycling of Bile Acids in Mice

The ileal apical sodium bile acid cotransporter participates in the enterohepatic circulation of bile acids. In patients with primary bile acid malabsorption, mutations in the ileal bile acid transporter gene (Slc10a2) lead to congenital diarrhea, steatorrhea, and reduced plasma cholesterol levels. To elucidate the quantitative role of Slc10a2 in intestinal bile acid absorption, the Slc10a2 gene was disrupted by homologous recombination in mice. Animals heterozygous (Slc10a2+/-) and homozygous (Slc10a2-/-) for this mutation were physically indistinguishable from wild type mice. In the Slc10a2-/- mice, fecal bile acid excretion was elevated 10- to 20-fold and was not further increased by feeding a bile acid binding resin. Despite increased bile acid synthesis, the bile acid pool size was decreased by 80% and selectively enriched in cholic acid in the Slc10a2-/- mice. On a low fat diet, the Slc10a2-/- mice did not have steatorrhea. Fecal neutral sterol excretion was increased only 3-fold, and intestinal cholesterol absorption was reduced only 20%, indicating that the smaller cholic acid-enriched bile acid pool was sufficient to facilitate intestinal lipid absorption. Liver cholesteryl ester content was reduced by 50% in Slc10a2-/- mice, and unexpectedly plasma high density lipoprotein cholesterol levels were slightly elevated. These data indicate that Slc10a2 is essential for efficient intestinal absorption of bile acids and that alternative absorptive mechanisms are unable to compensate for loss of Slc10a2 function

A National Population-Based E-cohort of People with Psychosis (PsyCymru) Linkage of Phenotypical and Genetic Data to Routinely Collected Records

Introduction PsyCymru was established to investigate the feasibility of linking a prospectively ascertained, well characterised (linked clinical cohort) of people with psychosis in Wales, UK with large amounts of anonymised routinely collected health record data. We are now additionally linking genetic data. Objectives and Approach PsyCymru aimed to create a research platform for psychosis research in Wales by establishing two cohorts. The first was a well-characterised clinically assessed cohort with genetic data. Consented individuals underwent structured interviews using well-validated questionnaires and gave blood sample for DNA extraction, sequencing, and candidate gene identification. This data was then linked to routinely collected health and social datasets with identity encryption. The second is a larger e-cohort of prevalent psychosis cases created using a validated algorithm applied to anonymised routine data. Both cohorts were tracked prospectively and retrospectively in the Secure Anonymised Information Linkage (SAIL) databank. Results In total, data from 958 individuals for the clinical cohort were imported to SAIL. Among these individuals, genetic data for 740 were analysed. The genetic data included robust loci for schizophrenia, pathogenic copy-number variations (CNVs) for various conditions (e.g., autism, intellectual disability, congenital malformations), polygenic risks scores for schizophrenia, as well as pathogenic/non-pathogenic duplications or deletions of chromosome spanning more than 500kb or 1Mb. For the e-cohort, 29,797 individuals were found having a psychosis diagnosis from primary and secondary care between 2004 to 2013. Social demographic data for both cohorts were also analysed based on sex, age, area deprivation, urbanicity, and employment status. Conclusion/Implications This unique platform pooled data together from multiple sources; linking clinical, psychological, biological, genetic, and health care factors to address assorted research questions. This resource will continue to expand over the coming years in size, breadth and depth of data, with continued recruitment and additional measures planned

Genetic Mapping of Multiple Metabolic Traits Identifies Novel Genes for Adiposity, Lipids and Insulin Secretory Capacity in Outbred Rats

Despite the successes of human genome-wide association studies, the causal genes underlying most metabolic traits remain unclear. We used outbred heterogeneous stock (HS) rats, coupled with expression data and mediation analysis, to identify quantitative trait loci (QTLs) and candidate gene mediators for adiposity, glucose tolerance, serum lipids, and other metabolic traits. Physiological traits were measured in 1519 male HS rats, with liver and adipose transcriptomes measured in over 410 rats. Genotypes were imputed from low coverage whole genome sequence. Linear mixed models were used to detect physiological and expression QTLs (pQTLs and eQTLs, respectively), employing both SNP- and haplotype-based models for pQTL mapping. Genes with cis-eQTLs that overlapped pQTLs were assessed as causal candidates through mediation analysis. We identified 14 SNP-based pQTLs and 19 haplotype-based pQTLs, of which 10 were in common. Using mediation, we identified the following genes as candidate mediators of pQTLs: Grk5 for a fat pad weight pQTL on Chr1, Krtcap3 for fat pad weight and serum lipids pQTLs on Chr6, Ilrun for a fat pad weight pQTL on Chr20 and Rfx6 for a whole pancreatic insulin content pQTL on Chr20. Furthermore, we verified Grk5 and Ktrcap3 using gene knock-down/out models, thereby shedding light on novel regulators of obesity

APOL1 Kidney-Risk Variants Induce Mitochondrial Fission

IntroductionAPOL1 G1 and G2 nephropathy-risk variants cause mitochondrial dysfunction and contribute to kidney disease. Analyses were performed to determine the genetic regulation of APOL1 and elucidate potential mechanisms in APOL1-nephropathy.MethodsA global gene expression analysis was performed in human primary renal tubule cell lines derived from 50 African American individuals. Follow-up gene knock out, cell-based rescue, and microscopy experiments were performed.ResultsAPOL1 genotypes did not alter APOL1 expression levels in the global gene expression analysis. Expression quantitative trait locus (eQTL) analysis in polyinosinic-polycytidylic acid (poly IC)-stimulated renal tubule cells revealed that single nucleotide polymorphism (SNP) rs513349 adjacent to BAK1 was a trans eQTL for APOL1 and a cis eQTL for BAK1; APOL1 and BAK1 were co-expressed in cells. BAK1 knockout in a human podocyte cell line resulted in diminished APOL1 protein, supporting a pivotal effect for BAK1 on APOL1 expression. Because BAK1 is involved in mitochondrial dynamics, mitochondrial morphology was examined in primary renal tubule cells and HEK293 Tet-on cells of various APOL1 genotypes. Mitochondria in APOL1 wild-type (G0G0) tubule cells maintained elongated morphology when stimulated by low-dose poly IC, whereas those with G1G1, G2G2, and G1G2 genotypes appeared to fragment. HEK293 Tet-on cells overexpressing APOL1 G0, G1, and G2 were created; G0 cells appeared to promote mitochondrial fusion, whereas G1 and G2 induced mitochondrial fission. The mitochondrial dynamic regulator Mdivi-1 significantly preserved cell viability and mitochondrial cristae structure and reversed mitochondrial fission induced by overexpression of G1 and G2.ConclusionResults suggest the mitochondrial fusion/fission pathway may be a therapeutic target in APOL1-nephropathy