Multiple innovations underpinned branching form diversification in mosses

International audienceBroad-scale evolutionary comparisons have shown that branching forms arose by convergencein vascular plants and bryophytes, but the trajectory of branching form diversificationin bryophytes is unclear. Mosses are the most species-rich bryophyte lineage andtwo sub-groups are circumscribed by alternative reproductive organ placements. In one,reproductive organs form apically, terminating growth of the primary shoot (gametophore)axis. In the other, reproductive organs develop on very short lateral branches. Aswitch from apical to lateral reproductive organ development is proposed to have primedbranching form diversification. Moss gametophores have modular development and each module develops from a singleapical cell. Here we define the architectures of 175 mosses by the number of module classes,branching patterns and the pattern in which similar modules repeat. Using ancestral characterstate reconstruction we identify two stages of architectural diversification. During a first stage there were sequential changes in the module repetition pattern, reproductiveorgan position, branching pattern and the number of module classes. During a secondstage, vegetative changes occurred independently of reproductive fate. The results pinpoint the nature of developmental change priming branching form diversificationin mosses and provide a framework for mechanistic studies of architectural diversificatio

Timing of detachment faulting in the Bullfrog Hills and Bare Mountain area, southwest Nevada: Inferences from 40Ar/39Ar, K-Ar, U-Pb and fission track thermochronology

Crustal extension in the Bullfrog Hills and Bare Mountain area of southwest Nevada is associated with movement along a regional detachment fault. Normal faulting in the upper plate and rapid cooling (denudation) of the lower plate were coeval with Miocene silicic volcanism and with west-northwest transport along the detachment fault. A west-northwest progression of tilting along upper plate normal faults is indicated by ages of the volcanic rocks in relation to angular unconformities. Near the breakaway, tilting in the upper plate occurred between 12.7 and 11.6 Ma, continued less strongly past 10.7 Ma, and was over by 8.2 Ma. Ten to 20 km west of the breakaway, tilting occurred between 10.7 and 10.33 Ma, continued less strongly after 10.33 Ma, and was over by 8.1 Ma. The cooling histories of the lower plate metamorphic rocks were determined by thermochronologic dating methods: K-Ar and Ar-40/(39)A on muscovite, biotite, and hornblende, Ar-40/(39)A on K-feldspar, U-Pb on apatite, zircon, and sphene, and fission track on apatite, zircon, and sphene. Lower plate rocks 10 km west of the breakaway cooled slowly from Early Cretaceous lower-amphibolite facies conditions through 350+/-50 degrees to 300+/-50 degrees C between 57 and 38 Ma, then cooled rapidly from 205+/-50 degrees to 120+/-5O degrees C between 12.6+/-1.6 and 11.1+/-1.9 Ma. Lower plate rocks 20 km west of the breakaway cooled slowly from Early Cretaceous upper-amphibolite facies conditions through 500+/-50 degrees C at 78-67 Ma, passed through 350+/-50 degrees to 300+/-50 degrees C between 16.3+/-0.4 and 10.5+/-0.3 Ma, then cooled rapidly from 285+/-50 degrees to 120+/-50 degrees C between 10.2 and 8.6 Ma. Upper plate tilting and rapid cooling (denudation) of the lower plate occurred simultaneously in the respective areas. The early slow-cooling part of the lower plate thermal histories was probably related to erosion at the Earth's surface, which stripped off about 9 km of material in 50 to 100 m.y. The results indicate an initial fault dip greater than or equal to 30 degrees and a 12 mm yr(-1) west-northwest migration of the locus of rapid tilting in the upper plate

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Ribosomal scanning on the 5′-untranslated region of the human immunodeficiency virus RNA genome

Translation initiation on most eukaryotic mRNAs occurs via a cap-dependent scanning mechanism and its efficiency is modulated by their 5′-untranslated regions (5′-UTR). The human immunodeficiency virus type 1 (HIV-1) 5′-UTR contains a stable TAR hairpin directly at its 5′-end, which possibly masks the cap structure. In addition, the 5′-UTR is relatively long and contains several stable RNA structures that are essential for viral replication. These characteristics may interfere with ribosomal scanning and suggest that translation is initiated via internal entry of ribosomes. Literature on the HIV-1 5′-UTR-driven translation initiation mechanism is controversial. Both scanning and internal initiation have been shown to occur in various experimental systems. To gain further insight in the translation initiation process, we determined which part of the 5′-UTR is scanned. To do so, we introduced upstream AUGs at various positions across the 5′-UTR and determined the effect on expression of a downstream reporter gene that was placed under control of the gag start codon. This strategy allowed us to determine the window of ribosomal scanning on the HIV-1 5′-UTR

Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA–binding moieties together direct DRM to its target genes. Chromatin immunoprecipitation and gene expression profiling reveals conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find that LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, C. elegans DRM does not act uniformly throughout the genome: the DRM recruitment motif, DRM binding, and DRM-regulated embryonic genes are all under-represented on the X chromosome. However, germline genes down-regulated in lin-54 mutants are over-represented on the X chromosome. We discuss models for how loss of autosome-bound DRM may enhance germline X chromosome silencing. We propose that autosome-enriched binding of DRM arose in C. elegans as a consequence of germline X chromosome silencing and the evolutionary redistribution of germline-expressed and essential target genes to autosomes. Sex chromosome gene regulation may thus have profound evolutionary effects on genome organization and transcriptional regulatory networks.National Institutes of Health (U.S.) (grant GM24663)National Institutes of Health (U.S.) (grant DK068429)National Institutes of Health (U.S.) (grant GM082971)National Institutes of Health (U.S.) (grant GM076378

A sensorimotor control framework for understanding emotional communication and regulation

JHGW and CFH are supported by the Northwood Trust. TEVR was supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (1088785). RP and MW were supported by the the Australian Research Council (ARC) Centre of Excellence for Cognition and its Disorders (CE110001021)Peer reviewedPublisher PD

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

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