Phylogenetic incongruence and homoplasy in the appendages and bodies of arthropods::Why broad character sampling is best

Notwithstanding the rapidly increasing sampling density of molecular sequence data, morphological characters still make an important contribution to our understanding of the evolutionary relationships of arthropod groups. In many clades, characters relating to the number and morphological specialization of appendages are ascribed particular phylogenetic significance and may be preferentially sampled. However, previous studies have shown that partitions of morphological character matrices often imply significantly different phylogenies. Here, we ask whether a similar incongruence is observed in the appendage and non-appendage characters of arthropods. We apply tree length (incongruence length difference, ILD) and tree distance (incongruence relationship difference, IRD) tests to these partitions in an empirical sample of 53 published neontological datasets for arthropods. We find significant incongruence about one time in five: more often than expected, but markedly less often than in previous partition studies. We also find similar levels of homoplasy in limb and non-limb characters, both in terms of internal consistency and consistency relative to molecular trees. Taken together, these findings imply that sampled limb and non-limb characters are of similar phylogenetic utility and quality, and that a total evidence approach to their analysis is preferable.</p

Sirius B Imaged in the Mid-Infrared: No Evidence for a Remnant Planetary System

Evidence is building that remnants of solar systems might orbit a large percentage of white dwarfs, as the polluted atmospheres of DAZ and DBZ white dwarfs indicate the very recent accretion of metal-rich material. (Zuckerman et al. 2010). Some of these polluted white dwarfs are found to have large mid-infrared excesses from close-in debris disks that are thought to be reservoirs for the metal accretion. These systems are coined DAZd white dwarfs (von Hippel et al. 2007). Here we investigate the claims of Bonnet-Bidaud & Pantin (2008) that Sirius B, the nearest white dwarf to the Sun, might have an infrared excess from a dusty debris disk. Sirius B's companion, Sirius A is commonly observed as a mid-infrared photometric standard in the Southern hemisphere. We combine several years of Gemini/T-ReCS photometric standard observations to produce deep mid-infrared imaging in five ~10 micron filters (broad N + 4 narrowband), which reveal the presence of Sirius B. Our photometry is consistent with the expected photospheric emission such that we constrain any mid-infrared excess to <10% of the photosphere. Thus we conclude that Sirius B does not have a large dusty disk, as seen in DAZd white dwarfs.Comment: 13 pages, 3 figures, accepted to Ap

Bird clades with less complex appendicular skeletons tend to have higher species richness

Species richness is strikingly uneven across taxonomic groups at all hierarchical levels, but the reasons for this heterogeneity are poorly understood. It is well established that morphological diversity (disparity) is decoupled from taxonomic diversity, both between clades, and across geological time. Morphological complexity has been much less studied, but there is theory linking complexity with differential diversity across groups. Here we devise an index of complexity from the differentiation of the fore and hind limb pairs for a sample of 983 species of extant birds. We test the null hypothesis that this index of morphological complexity is uncorrelated with clade diversity, revealing a significant and negative correlation between the species richness of clades, and the mean morphological complexity of those clades. Further, we find that more complex clades tend to occupy a smaller number of dietary and habitat niches, and that this proxy for greater ecological specialisation correlates with lower species richness. Greater morphological complexity in the appendicular skeleton therefore appears to hinder the generation and maintenance of species diversity. This may result from entrenchment into morphologies and ecologies that are less capable of yielding further diversity

A planet within the debris disk around the pre-main-sequence star AU Microscopii

AU Microscopii (AU Mic) is the second closest pre main sequence star, at a distance of 9.79 parsecs and with an age of 22 million years. AU Mic possesses a relatively rare and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star, and with clumps exhibiting non-Keplerian motion. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic activity on the star. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3 sigma confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.Comment: Nature, published June 24th [author spelling name fix

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease