Evolved solar systems in Praesepe

"Copyright 2011 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics." Original paper can be found at: http://scitation.aip.org/"We have obtained near-IR photometry for the 11 Praesepe white dwarfs, to search for an excess indicative of a dusty debris disk. All the white dwarfs are in the DAZ temperature regime, however we find no indications of a disk around any white dwarf. We have, however determined that the radial velocity variable white dwarf WD0837+185 could have an unresolved T8 dwarf companion that would not be seen as a near-IR excess.Final Accepted Versio

New stellar members of the Coma Berenices open star cluster

We present the results of a survey of the Coma Berenices open star cluster (Melotte 111), undertaken using proper motions from the USNO-B1.0 and photometry from the 2MASS Point Source catalogues. We have identified 60 new candidate members with masses in the range 1.007<M<$0.269M_solar. For each we have estimated a membership probability by extracting control clusters from the proper motion vector diagram. All 60 are found to have greater than 60 per cent probability of being clusters more than doubling the number of known cluster members. The new luminosity function for the cluster peaks at bright magnitudes, but is rising at K~12, indicating that it is likely lower mass members may exist. The mass function also supports this hypothesis.Comment: accepted for MNRA

Remodelling of Cortical Actin Where Lytic Granules Dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy

Super-resolution 3D imaging reveals remodeling of the cortical actin meshwork at the natural killer cell immune synapse, which is likely to be important for secretion of lytic granules

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

EUV observations of opacities along the lines of sight to and in the photospheres of hot hydrogen rich white dwarfs

EUV spectral observations provide an excellent means with which to examine the composition and physical state of gas along the line of sight to and in the atmospheres of hot hydrogen rich white dwarfs. Here I present the results of an analysis of a large number of spectra of hot DA type white dwarfs in the temperature range 25000K ≲ Teff ≲ 55000K obtained with the Extreme Ultraviolet Explorer satellite. No evidence for the presence of photospheric helium is found in the spectra of any of the sample objects, adding to the growing body of observations which argues against the one channel evolutionary hypothesis of Fontaine & Wesemael (1987). Furthermore, it is found that contrary to theoretical predictions and the results of earlier photometric studies, the majority of the opacity of EUV radiation observed towards those DAs with 40000K ≲ Teff ≲ 50000K is provided by HI, HeI and HeII along the line of sight as opposed to photospheric heavy metals. The 228A Lyman edge of HeII is detected in the spectra of 6 of the sample objects allowing a direct measurement of the line of sight averaged ionization fractions of hydrogen and helium. The ionization fractions towards these 6 stars can be consistent with a conclusion of a uniformly ionized ISM with weighted means of fH = 0.37 +/- 0.1 fHe = 0.28 +/- 0.04. The limits placed on the fractions towards the remaining sample objects do not contradict such a conclusion. The observed high level of helium ionization can be consistent with a model in which the blast from a nearby supernova shock ionized the gas of the LISM some million or so years ago. The most peculiar line of sight characteristics towards the DAO+dM binary RE J0720-318 revealed by the unusually large HeI edge at 504A(e.g. fH ~ 0.9; Burleigh, Barstow & Dobbie 1997), has been attributed to the presence of an ionized cloud lying along this line of sight at a distance of 123-170 pc