Patterns of variability of retinol levels in a harbour porpoise population from an unpolluted environment

Organochlorine compounds (OC) are known to induce vitamin A (retinoids) deficiency in mammals, which may be associated with impairment of immunocompetence, reproduction and growth. This makes retinoids a potentially useful biomarker of organochlorine impact on marine mammals. However, use of retinoids as a biomarker requires knowledge about its intrapopulation patterns of variation in natural conditions, information which is not currently available. We investigated these patterns in a cetacean population living in an unpolluted environment. 100 harbour porpoises Phocoena phocoena from West Greenland were sampled during the 1995 hunting season. Sex, age, morphometrics, nutritive condition, and retinol (following saponification) and OC levels in blubber were determined for each individual. OC levels found were extremely low and therefore considered unlikely to affect the population adversely: mean blubber concentrations, expressed on an extractable basis, were 2.04 (SD = 1.1) ppm for PCBs and 2.76 (SD = 1.66) ppm for tDDT. The mean blubber retinol concentration for the overall population was 59.66 (SD = 45.26) mu g g(-1). Taking into account the high contribution of blubber to body mass, blubber constitutes a significant body site for retinoid deposition in harbour porpoises. Retinol concentrations did not differ significantly between geographical regions or sexes, but they did correlate significantly (p <0.001) with age. Body condition, measured by determining the lipid content of the blubber, did not have a significant effect on retinol levels but the individuals examined were considered to be in an overall good nutritive condition. It is concluded that measurement of retinol concentrations in blubber samples is feasible and has a potential for use as a biomarker of organochlorine exposure in cetaceans. However, in order to do so, biological information, particularly age, is critical for the correct assessment of physiological impac

LES-based Study of the Roughness Effects on the Wake of a Circular Cylinder from Subcritical to Transcritical Reynolds Numbers

This paper investigates the effects of surface roughness on the flow past a circular cylinder at subcritical to transcritical Reynolds numbers. Large eddy simulations of the flow for sand grain roughness of size k/D = 0.02 are performed (D is the cylinder diameter). Results show that surface roughness triggers the transition to turbulence in the boundary layer at all Reynolds numbers, thus leading to an early separation caused by the increased momentum deficit, especially at transcritical Reynolds numbers. Even at subcritical Reynolds numbers, boundary layer instabilities are triggered in the roughness sublayer and eventually lead to the transition to turbulence. The early separation at transcritical Reynolds numbers leads to a wake topology similar to that of the subcritical regime, resulting in an increased drag coefficient and lower Strouhal number. Turbulent statistics in the wake are also affected by roughness; the Reynolds stresses are larger due to the increased turbulent kinetic energy production in the boundary layer and separated shear layers close to the cylinder shoulders.We acknowledge “Red Española de Surpercomputación” (RES) for awarding us access to the MareNostrum III machine based in Barcelona, Spain (Ref. FI-2015-2-0026 and FI-2015-3-0011). We also acknowledge PRACE for awarding us access to Fermi and Marconi Supercomputers at Cineca, Italy (Ref. 2015133120). Oriol Lehmkuhl acknowledges a PDJ 2014 Grant by AGAUR (Generalitat de Catalunya). Ugo Piomelli acknowledges the support of the Natural Sciences and Engineering Research Council (NSERC) of Canada under the Discovery Grant Programme (Grant No. RGPIN-2016-04391). Ricard Borrell acknowledges a Juan de la Cierva postdoctoral grant (IJCI-2014-21034). Ivette Rodriguez, Oriol Lehmkuhl, Ricard Borrell and Assensi Oliva acknowledge Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación, Spain (ref. ENE2014-60577-R).Peer ReviewedPostprint (author's final draft

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus

Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor typ

Acceptability and feasibility of a virtual community of practice to primary care professionals regarding patient empowerment: A qualitative pilot study

Background: Virtual communities of practice (vCoPs) facilitate online learning via the exchange of experiences and knowledge between interested participants. Compared to other communities, vCoPs need to overcome technological structures and specific barriers. Our objective was to pilot the acceptability and feasibility of a vCoP aimed at improving the attitudes of primary care professionals to the empowerment of patients with chronic conditions. Methods: We used a qualitative approach based on 2 focus groups: one composed of 6 general practitioners and the other of 6 practice nurses. Discussion guidelines on the topics to be investigated were provided to the moderator. Sessions were audio-recorded and transcribed verbatim. Thematic analysis was performed using the ATLAS-ti software. Results: The available operating systems and browsers and the lack of suitable spaces and time were reported as the main difficulties with the vCoP. The vCoP was perceived to be a flexible learning mode that provided up-to-date resources applicable to routine practice and offered a space for the exchange of experiences and approaches. Conclusions: The results from this pilot study show that the vCoP was considered useful for learning how to empower patients. However, while vCoPs have the potential to facilitate learning and as shown create professional awareness regarding patient empowerment, attention needs to be paid to technological and access issues and the time demands on professionals. We collected relevant inputs to improve the features, content and educational methods to be included in further vCoP implementation. Trial registration: ClinicalTrials.gov, NCT02757781. Registered on 25 April 2016.This study was financed by Instituto de Salud Carlos III and Cofinanced by Fondo Europeo de Desarrollo Regional (FEDER). Ministerio de Economía y Competitividad. Gobierno de España. (PI15/00164, PI15/00586, PI15/00566

Agency and responsibility over virtual movements controlled through different paradigms of brain−computer interface

Agency is the attribution of an action to the self and is a prerequisite for experiencing responsibility over its consequences. Here we investigated agency and responsibility by studying the control of movements of an embodied avatar, via brain computer interface (BCI) technology, in immersive virtual reality. After induction of virtual body ownership by visuomotor correlations, healthy participants performed a motor task with their virtual body. We compared the passive observation of the subject's ‘own’ virtual arm performing the task with (1) the control of the movement through activation of sensorimotor areas (motor imagery) and (2) the control of the movement through activation of visual areas (steady‐state visually evoked potentials). The latter two conditions were carried out using a brain–computer interface (BCI) and both shared the intention and the resulting action. We found that BCI‐control of movements engenders the sense of agency, which is strongest for sensorimotor areas activation. Furthermore, increased activity of sensorimotor areas, as measured using EEG, correlates with levels of agency and responsibility. We discuss the implications of these results for the neural basis of agency

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)

PCB pollution continues to impact populations of orcas and other dolphins in European waters

Organochlorine (OC) pesticides and the more persistent polychlorinated biphenyls (PCBs) have well-established dose-dependent toxicities to birds, fish and mammals in experimental studies, but the actual impact of OC pollutants on European marine top predators remains unknown. Here we show that several cetacean species have very high mean blubber PCB concentrations likely to cause population declines and suppress population recovery. In a large pan-European meta-analysis of stranded (n = 929) or biopsied (n = 152) cetaceans, three out of four species:- striped dolphins (SDs), bottlenose dolphins (BNDs) and killer whales (KWs) had mean PCB levels that markedly exceeded all known marine mammal PCB toxicity thresholds. Some locations (e.g. western Mediterranean Sea, south-west Iberian Peninsula) are global PCB "hotspots" for marine mammals. Blubber PCB concentrations initially declined following a mid-1980s EU ban, but have since stabilised in UK harbour porpoises and SDs in the western Mediterranean Sea. Some small or declining populations of BNDs and KWs in the NE Atlantic were associated with low recruitment, consistent with PCB-induced reproductive toxicity. Despite regulations and mitigation measures to reduce PCB pollution, their biomagnification in marine food webs continues to cause severe impacts among cetacean top predators in European seas

Genome-wide association study of male sexual orientation

Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10 -5 , including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10 -7 ) and 14 (p = 4.7 × 10 -7 ). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10 -3 ) for a SNP association previously reported (rs77013977, p = 7.1 × 10 -8 ), with the combined analysis yielding p = 6.7 × 10 -9 , i.e., a genome-wide significant association