4-Benzoyl-4-methyl-1, 2-epoxypentane, An attempted synthesis

The object of this research was to prepare first the simplest homologue of the epoxy-ketone considered by Russell to have been his product. If this homologue, 4-benzoyl-4-methyl-1,2-epoxypentane, could be prepared and caused to form a cyclic derivative of the type given by 1,4-diketones with 2,4-dinitrophenylhydrazone, the organic chemist would be given a new approach to substituted 1,2-diazines as well as a previously unreported reaction of the epoxide grouping. If this reaction could be made to occur, other epoxides of this series would be prepared and treated in the same manner. It was decided that the shortest route to 4-benzoyl-4-methyl-1,2-epoxypentane would be the direct condensation of epichlorohydrin with isobutyrophenone. There was also the possibility of condensing isobutyrophenone with allyl halides to produce 4-benzoyl-4-methyl-1-pentene. This could then be converted to the halohydrin followed by treatment with base to form the epoxide, or it could be treated with a peracid to form the epoxide directly --Introduction, pages 2-3

Mouse Estrous Cycle Identification Tool and Images

The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus. Visual observation of the vagina is the quickest method, requires no special equipment, and is best used when only proestrus or estrus stages need to be identified. Strain to strain differences, especially in coat color can make it difficult to determine the stage of the estrous cycle accurately by visual observation. Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J), agouti (CByB6F1/J) and albino (BALB/cByJ). When all 4 stages (proestrus, estrus, metestrus, and diestrus) need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology

Structural Basis for the Autoinhibition and STI-571 Inhibition of c-Kit Tyrosine Kinase

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Fifteen species in one: deciphering the Brachionus plicatilis species complex (Rotifera, Monogononta) through DNA taxonomy

Understanding patterns and processes in biological diversity is a critical task given current and rapid environmental change. Such knowledge is even more essential when the taxa under consideration are important ecological and evolutionary models. One of these cases is the monogonont rotifer cryptic species complex Brachionus plicatilis, which is by far the most extensively studied group of rotifers, is widely used in aquaculture, and is known to host a large amount of unresolved diversity. Here we collate a dataset of previously available and newly generated sequences of COI and ITS1 for 1273 isolates of the B. plicatilis complex and apply three approaches in DNA taxonomy (i.e. ABGD, PTP, and GMYC) to identify and provide support for the existence of 15 species within the complex. We used these results to explore phylogenetic signal in morphometric and ecological traits, and to understand correlation among the traits using phylogenetic comparative models. Our results support niche conservatism for some traits (e.g. body length) and phylogenetic plasticity for others (e.g. genome size)

Advancing an interdisciplinary framework to study seed dispersal ecology

Although dispersal is generally viewed as a crucial determinant for the fitness of any organism, our understanding of its role in the persistence and spread of plant populations remains incomplete. Generalizing and predicting dispersal processes are challenging due to context dependence of seed dispersal, environmental heterogeneity and interdependent processes occurring over multiple spatial and temporal scales. Current population models often use simple phenomenological descriptions of dispersal processes, limiting their ability to examine the role of population persistence and spread, especially under global change. To move seed dispersal ecology forward, we need to evaluate the impact of any single seed dispersal event within the full spatial and temporal context of a plant’s life history and environmental variability that ultimately influences a population’s ability to persist and spread. In this perspective, we provide guidance on integrating empirical and theoretical approaches that account for the context dependency of seed dispersal to improve our ability to generalize and predict the consequences of dispersal, and its anthropogenic alteration, across systems. We synthesize suitable theoretical frameworks for this work and discuss concepts, approaches and available data from diverse subdisciplines to help operationalize concepts, highlight recent breakthroughs across research areas and discuss ongoing challenges and open questions. We address knowledge gaps in the movement ecology of seeds and the integration of dispersal and demography that could benefit from such a synthesis. With an interdisciplinary perspective, we will be able to better understand how global change will impact seed dispersal processes, and potential cascading effects on plant population persistence, spread and biodiversity

Prediction models for diagnosis and prognosis of covid-19: : systematic review and critical appraisal

Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 3 of the original article published on 7 April 2020 (BMJ 2020;369:m1328). Previous updates can be found as data supplements (https://www.bmj.com/content/369/bmj.m1328/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity. Funding: LW, BVC, LH, and MDV acknowledge specific funding for this work from Internal Funds KU Leuven, KOOR, and the COVID-19 Fund. LW is a postdoctoral fellow of Research Foundation-Flanders (FWO) and receives support from ZonMw (grant 10430012010001). BVC received support from FWO (grant G0B4716N) and Internal Funds KU Leuven (grant C24/15/037). TPAD acknowledges financial support from the Netherlands Organisation for Health Research and Development (grant 91617050). VMTdJ was supported by the European Union Horizon 2020 Research and Innovation Programme under ReCoDID grant agreement 825746. KGMM and JAAD acknowledge financial support from Cochrane Collaboration (SMF 2018). KIES is funded by the National Institute for Health Research (NIHR) School for Primary Care Research. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. GSC was supported by the NIHR Biomedical Research Centre, Oxford, and Cancer Research UK (programme grant C49297/A27294). JM was supported by the Cancer Research UK (programme grant C49297/A27294). PD was supported by the NIHR Biomedical Research Centre, Oxford. MOH is supported by the National Heart, Lung, and Blood Institute of the United States National Institutes of Health (grant R00 HL141678). ICCvDH and BCTvB received funding from Euregio Meuse-Rhine (grant Covid Data Platform (coDaP) interref EMR187). The funders played no role in study design, data collection, data analysis, data interpretation, or reporting.Peer reviewedPublisher PD

Defining the Role of the MHC in Autoimmunity: A Review and Pooled Analysis

The major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. However, identification of causal variants within the MHC for the majority of these diseases has remained difficult due to the great variability and extensive linkage disequilibrium (LD) that exists among alleles throughout this locus, coupled with inadequate study design whereby only a limited subset of about 20 from a total of approximately 250 genes have been studied in small cohorts of predominantly European origin. We have performed a review and pooled analysis of the past 30 years of research on the role of the MHC in six genetically complex disease traits – multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn's disease (CD), and rheumatoid arthritis (RA) – in order to consolidate and evaluate the current literature regarding MHC genetics in these common autoimmune and inflammatory diseases. We corroborate established MHC disease associations and identify predisposing variants that previously have not been appreciated. Furthermore, we find a number of interesting commonalities and differences across diseases that implicate both general and disease-specific pathogenetic mechanisms in autoimmunity

Clinical features and management of human monkeypox: a retrospective observational study in the UK

Background Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. Methods In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. Findings We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22–39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. Interpretation Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant