Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.We acknowledge the Wellcome Trust for supporting this work. H.B was supported by a Wellcome Trust clinical PhD fellowship. We acknowledge the Research Foundation Flanders (FWO) (FWO-G.A093.11 and FWO-G.0924.15 to T.V.; the travel grant V.4.140.10.N.00 to T.V.; N.V.d.A., E.F.G. and K.T. are Ph.D. students supported by FWO 1.1.H.28.12, FWO G.0924.15 and FWO 1126016N, respectively) and KU Leuven SymBioSys (PFV/10/016 to T.V.; P.K. is a PhD. student supported with PFV/10/016).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1116

Foraging distribution of breeding northern fulmars is predicted by commercial fisheries

Acknowledgements. J.H.D. was funded by the Irish Re- search Council Enterprise Partnership Scheme, supported by the Petroleum Infrastructure Program. Field work on Lit- tle Saltee in 2018 and 2019 and S.d.G. were funded by the BlueFish project, funded by the European Regional Devel- opment fund through the Ireland Wales Co-operation Pro- gramme 2014−2020. Fieldwork on Eynhallow and St. Kilda was supported by Orkney Islands Council, the University of Aberdeen, the National Trust for Scotland and Talisman Energy (UK) Ltd. E.W.J.E. was funded by a Marine Alliance for Science and Technology for Scotland and University of Aberdeen studentship. Fieldwork elsewhere was funded by the EU Atlantic area INTERREG program via the Future of the Atlantic Marine Environment (FAME) project and by the RSPB, JNCC, Fair Isle Bird Observatory Trust and Marine Scotland, through the Seabird Tracking And Research (STAR) project. We are grateful for field assistance from Ash Bennison, Cian Luck, Yvan Satge, Juliet Lamb, Chris Bell, Mara Nydegger, Robert Hughes, Elizabeth Mackley, Richard Bufton, Jenni Border, Derren Fox, Tegan Newman, Daisy Burnell, Antoine Grissott and Chris Taylor. Marine Scotland Science and the Marine Institute provided access to anony- mized VMS data. G.E.A. was funded by the MarPAMM pro- ject supported by the EU INTERREG VA Programme, man- aged by the Special EU Programmes Body (SEUPB). The views and opinions expressed in this manuscript do not nec- essarily reflect those of the European Commission or the SEUPB. Go raibh míle maith agaibh, Pat and Liezel of Little Saltee for their outstanding support and hospitality.Peer reviewedPublisher PD

Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

Regulating peroxisome–ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β

This is the final version. Available on open access from Rockefeller University Press via the DOI in this recordData availability All raw data and original Mascot result files have been deposited to the ProteomeXchange Consortium (http://proteomecentral. proteomexchange.org) via the PRIDE partner repository (http:// www.ebi.ac.uk/pride/archive/login; Perez-Riverol et al., 2019) with the dataset identifier PXD018005. The research data supporting this publication are provided within this paper, as supplementary information, or are deposited on PRIDE.Peroxisomes and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism. They form membrane contacts through interaction of the peroxisomal membrane protein ACBD5 (acyl-coenzyme A–binding domain protein 5) and the ER-resident protein VAPB (vesicle-associated membrane protein–associated protein B). ACBD5 binds to the major sperm protein domain of VAPB via its FFAT-like (two phenylalanines [FF] in an acidic tract) motif. However, molecular mechanisms, which regulate formation of these membrane contact sites, are unknown. Here, we reveal that peroxisome–ER associations via the ACBD5-VAPB tether are regulated by phosphorylation. We show that ACBD5-VAPB binding is phosphatase-sensitive and identify phosphorylation sites in the flanking regions and core of the FFAT-like motif, which alter interaction with VAPB—and thus peroxisome–ER contact sites—differently. Moreover, we demonstrate that GSK3β (glycogen synthase kinase-3 β) regulates this interaction. Our findings reveal for the first time a molecular mechanism for the regulation of peroxisome–ER contacts in mammalian cells and expand the current model of FFAT motifs and VAP interaction.Biotechnology and Biological Sciences Research Council (BBSRC)Medical Research Council (MRC)UKRIRoyal SocietyUniversity of ExeterEuropean Union Horizon 2020Deutsche Forschungsgemeinschaf

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

The quality of communication about older patients between hospital physicians and general practitioners: a panel study assessment

<p>Abstract</p> <p>Background</p> <p>Optimal care of patients is dependent on good professional interaction between general practitioners and general hospital physicians. In Norway this is mainly based upon referral and discharge letters. The main objectives of this study were to assess the quality of the written communication between physicians and to estimate the number of patients that could have been treated at primary care level instead of at a general hospital.</p> <p>Methods</p> <p>This study comprised referral and discharge letters for 100 patients above 75 years of age admitted to orthopaedic, pulmonary and cardiological departments at the city general hospital in Trondheim, Norway. The assessments were done using a Delphi technique with two expert panels, each with one general hospital specialist, one general practitioner and one public health nurse using a standardised evaluation protocol with a visual analogue scale (VAS). The panels assessed the quality of the description of the patient's actual medical condition, former medical history, signs, medication, Activity of Daily Living (ADL), social network, need of home care and the benefit of general hospital care.</p> <p>Results</p> <p>While information in the referral letters on actual medical situation, medical history, symptoms, signs and medications was assessed to be of high quality in 84%, 39%, 56%, 56% and 39%, respectively, the corresponding information assessed to be of high quality in discharge letters was for actual medical situation 96%, medical history 92%, symptoms 60%, signs 55% and medications 82%. Only half of the discharge letters had satisfactory information on ADL. Some two-thirds of the patients were assessed to have had large health benefits from the general hospital care in question. One of six patients could have been treated without a general hospital admission. The specialists assessed that 77% of the patients had had a large benefit from the general hospital care; however, the general practitioners assessment was only 59%. One of four of the discharge letters did not describe who was responsible for follow-up care.</p> <p>Conclusion</p> <p>In this study from one general hospital both referral and discharge letters were missing vital medical information, and referral letters to such an extent that it might represent a health hazard for older patients. There was also low consensus between health professionals at primary and secondary level of what was high benefit of care for older patients at a general hospital.</p

Quality gap of educational services in viewpoints of students in Hormozgan University of medical sciences

<p>Abstract</p> <p>Background</p> <p>Higher education is growing fast and every day it becomes more and more exposed to globalization processes. The aim of this study was to determine the quality gap of educational services by using a modified SERVQUAL instrument among students in Hormozgan University of Medical Sciences.</p> <p>Methods</p> <p>A cross-sectional study was carried out at Hormozgan University of Medical Sciences in 2007. In this study, a total of 300 students were selected randomly and asked to complete a questionnaire that was designed according to SERVQUAL methods. This questionnaire measured students' perceptions and expectations in five dimensions of service that consists of assurance, responsiveness, empathy, reliability and tangibles. The quality gap of educational services was determined based on differences between students' perceptions and expectations.</p> <p>Results</p> <p>The results demonstrated that in each of the five SERVQUAL dimensions, there was a negative quality gap. The least and the most negative quality gap means were in the reliability (-0.71) and responsiveness (-1.14) dimensions respectively. Also, there were significant differences between perceptions and expectations of students in all of the five SERVQUAL dimensions (p < 0.001).</p> <p>Conclusion</p> <p>Negative quality gaps mean students' expectations exceed their perceptions. Thus, improvements are needed across all five dimensions.</p