Sleep modifications in a Drosophila melanogaster model of Fragile X syndrome

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disabilities, disruptions in sleep, and autism in humans. Mutations in Fragile X Mental Retardation gene 1 (FMR1), which codes for a protein that modifies the expression of many target proteins, are primarily responsible for this disorder. Genetic modifications of FMR1 can increase or decrease the overall amount of sleep in humans. A potential pharmaceutical target of FXS is dopamine, a critical neurotransmitter in the regulation of sleep and wakefulness. In fruit flies (Drosophila melanogaster) dopamine has been shown to alter sleep. The mushroom body, a structure in the Drosophila brain that regulates sleep and memory, is innervated by dopaminergic neurons and is heavily impacted by low expression of dFMR1. In this study, a Drosophila Activity Monitoring system (DAMs) was used to measure sleep and locomotor activity in Drosophila models of FXS. We found that fruit flies with underexpression of dFMR1 slept more than their control but in shorter periods, which may lead to impaired memory consolidation. Furthermore, the activity of these flies when they are awake is reduced, leaving them with fewer chances to feed, court, and mate. In addition, the mushroom body specific overexpression of dFMR1 in a null background was able to rescue sleep deficits. Further studies on dFMR1 in Drosophila will help us understand how sleep is disrupted and how these changes lead to modifications in behavior

Characterization of NOD2 agonists in vitro and in vivo in the context of Alzheimer's Disease

La maladie d'Alzheimer (MA) et l'angiopathie amyloïde cérébrale (AAC) sont les deux formes les plus courantes de démence liée à l'âge qui partagent de nombreuses caractéristiques moléculaires, notamment l'accumulation de bêta-amyloïde (Aβ) dans les parois des vaisseaux sanguins cérébraux. Les cellules du système immunitaire inné, telles que les monocytes patrouilleurs, sont capables de surveiller les vaisseaux sanguins cérébraux et de phagocyter la bêta-amyloïde vasculaire ainsi que d'autres substances. Les monocytes patrouilleurs sont devenus une cible thérapeutique dans la MA, et leur phagocytose de l'Aβ permettrait une redistribution à l'équilibre entre le parenchyme et les espaces périvasculaires et vasculaires, ce qui réduirait ensuite la charge dans le parenchyme. Des recherches antérieures ont démontré que les monocytes peuvent être convertis du phénotype inflammatoire au phénotype de patrouille en utilisant la liaison du MDP à NOD2 (Lessard et al., 2017). Nous émettons l'hypothèse que le développement d'analogues de la MDP ayant des effets immunomodulateurs similaires à ceux de la MDP pourrait conduire à un médicament préventif dans la MA. Nous avons utilisé les lignées cellulaires HEK-Blue NOD2 et HEK-Blue TLR2 pour détecter les analogues qui se lient à NOD2. Nous avons également utilisé le test MTS sur des PBMC et des cellules HepG2 pour évaluer la viabilité cellulaire et la cytométrie perlée pour caractériser les cytokines et les interférons libérés par les cellules exposées aux analogues du MDP. Nous avons effectué des tests de phagocytose pour évaluer si les analogues du MDP modifiaient le taux de phagocytose par les monocytes. De plus, nous avons effectué des tests in vivo sur des souris WT pour évaluer si les analogues de la MDP pouvaient provoquer des changements phénotypiques dans les monocytes et si ces changements phénotypiques se produisaient chez les souris NOD2 KO. Les analogues de la MDP ont le potentiel de devenir un médicament préventif de la MA en augmentant la phagocytose de l'Aβ et en diminuant l'Aβ vasculaire. D'autres recherches sont nécessaires pour mieux comprendre le rôle exact des monocytes patrouillant dans la MA

Spectral and Imaging Diagnostics of Spatially-Extended Turbulent Electron Acceleration and Transport in Solar Flares

Solar flares are efficient particle accelerators with a large fraction of released magnetic energy (10-50%) converted into energetic particles such as hard X-ray producing electrons. This energy transfer process is not well constrained, with competing theories regarding the acceleration mechanism(s), including MHD turbulence. We perform a detailed parameter study examining how various properties of the acceleration region, including its spatial extent and the spatial distribution of turbulence, affect the observed electron properties, such as those routinely determined from X-ray imaging and spectroscopy. Here, a time-independent Fokker-Planck equation is used to describe the acceleration and transport of flare electrons through a coronal plasma of finite temperature. Motivated by recent non-thermal line broadening observations that suggested extended regions of turbulence in coronal loops, an extended turbulent acceleration region is incorporated into the model. We produce outputs for the density weighted electron flux, a quantity directly related to observed X-rays, modelled in energy and space from the corona to chromosphere. We find that by combining several spectral and imaging diagnostics (such as spectral index differences or ratios, energy or spatial-dependent flux ratios, and electron depths into the chromosphere) the acceleration properties, including the timescale and velocity dependence, can be constrained alongside the spatial properties. Our diagnostics provide a foundation for constraining the properties of acceleration in an individual flare from X-ray imaging spectroscopy alone, and can be applied to past, current and future observations including those from RHESSI and Solar Orbiter.Comment: ApJ Accepte

The food consumption habits of 145 Iowa farm families

The food consumption habits of 145 Iowa farm families were studied from records of expenditures for food and of food produced by farms during one year. Forty-three families in the central part of the state near Ames, 49 families in the southwestern part near Corning, and 53 families near Oelwein in the northeastern part of the state cooperated in the study. The nutritive values of the respective diets were calculated for the families in the Ames group and for the average of the families in each of the other two groups. The energy values of these diets and their content of protein, calcium, phosphorus and iron were calculated and contrasted with the standard allowances” on a per man per day basis

Abortion provision in Northern Ireland: the views of health professionals working in obstetrics and gynaecology units

Introduction: Abortion became decriminalised in Northern Ireland in October 2019. Until that point there existed no evidence concerning the views of health professionals on decriminalisation or on their willingness to be involved in abortion care. The purpose of this study was to address this lack of evidence, including all categories of health professionals working in obstetrics and gynaecology units in Northern Ireland. Methods: The online survey was targeted at medical, nursing and midwifery staff working in the obstetrics and gynaecology units in each Health and Social Care (HSC) Trust in Northern Ireland. The survey was issued via clinical directors in each Trust using the REDCap platform. Results: The findings showed widespread support for decriminalisation of abortion up until 24 weeks’ gestation (n=169, 54%). The majority of clinicians stated they were willing to provide abortions in certain circumstances (which were undefined) (n=188, 60% medical abortions; n=157, 50% surgical abortions). Despite regional variation, the results show that there are sufficient numbers of clinicians to provide a service within each HSC Trust. The results indicate that many clinicians who report a religious affiliation are also supportive of decriminalisation (n=46, 51% Catholic; n=53, 45% Protestant) and are willing to provide care, countering the assumption that those of faith would all raise conscientious objections to service provision. Conclusions: The findings of this study are very encouraging for the development, implementation and delivery of local abortion care within HSC Trusts in Northern Ireland and should be of value in informing commissioners and providers about the design of a service model and its underpinning training programmes

Family attitudes, actions, decisions and experiences following implementation of deemed consent and the Human Transplantation (Wales) Act 2013:mixed-method study protocol

IntroductionThe Human Transplantation (Wales) Act 2013 (the Act) introduced a ‘soft opt-out’ system of organ donation on 1 December 2015. Citizens are encouraged to make their organ donation decision known during their lifetime. In order to work, the Act and media campaign need to create a context, whereby organ donation becomes the norm, and create a mechanism for people to behave as intended (formally register their decision; consider appointing a representative; convey their donation decision to their families and friends or do nothing—deemed consent). In addition, family members/appointed representatives need to be able to put their own views aside to support the decision of their loved one. The aim of this study is to evaluate initial implementation, outcomes and impact on families and appointed representatives who were approached about organ donation during the first 18 months.Methods and analysisProspective mixed-method coproductive study undertaken with National Health Service Blood and Transplant (NHSBT), and multiple patient/public representatives. The study is designed to collect information on all cases who meet specified criteria (≥18 years, deceased person voluntarily resident in Wales and died in Wales or England) whose family were approached between 1 December 2015 and 31 June 2017). Data for analysis include: NHSBT routinely collected anonymised audit data on all cases; Specialist Nurse in Organ Donation (SNOD) completed anonymised form for all cases documenting their perception of the families’ understanding of the Act, media campaign and outcome of the donation approach; questionnaires and depth interviews with any family member or appointed representative (minimum 50 cases). Additional focus groups and interviews with SNODs. Anonymised donation outcomes and registration activity reports for Wales provide additional context.Ethics and disseminationApproved by NHSBT Research, Innovation and Technology Advisory Group on 23 October 2015; Wales Research Ethics Committee 5 (IRAS190066; Rec Reference 15/WA/0414) on 25 November 2015 and NHSBT R&amp;D Committee (NHSBT ID: AP-15–02) on 24 November 2015.RegistrationThe protocol is registered on the Health and Care Research Wales Clinical Research Portfolio. Study ID number 34396, www.ukctg.nihr.ac.uk</jats:sec

CLAM-Accelerated K-Nearest Neighbors Entropy-Scaling Search of Large High-Dimensional Datasets via an Actualization of the Manifold Hypothesis

Many fields are experiencing a Big Data explosion, with data collection rates outpacing the rate of computing performance improvements predicted by Moore's Law. Researchers are often interested in similarity search on such data. We present CAKES (CLAM-Accelerated $K$-NN Entropy Scaling Search), a novel algorithm for $k$-nearest-neighbor ($k$-NN) search which leverages geometric and topological properties inherent in large datasets. CAKES assumes the manifold hypothesis and performs best when data occupy a low dimensional manifold, even if the data occupy a very high dimensional embedding space. We demonstrate performance improvements ranging from hundreds to tens of thousands of times faster when compared to state-of-the-art approaches such as FAISS and HNSW, when benchmarked on 5 standard datasets. Unlike locality-sensitive hashing approaches, CAKES can work with any user-defined distance function. When data occupy a metric space, CAKES exhibits perfect recall.Comment: As submitted to IEEE Big Data 202