Antarctic Relic Microbial Mat Community Revealed by Metagenomics and Metatranscriptomics

Buried upslope from the modern lakes in the McMurdo Dry Valleys of Antarctica are relict lake deposits embedded in valley walls. Within these relict deposits, ancient microbial mats, or paleomats, have been preserved under extremely arid and cold conditions since the receding of larger paleolakes thousands of years ago, and now serve as a sheltered niche for microbes in a highly challenging oligotrophic environment. To explore whether paleomats could be repositories for ancient lake cells or were later colonized by soil microbes, determine what types of metabolic pathways might be present, analyze potential gene expression, and explore whether the cells are in a vegetative or dormant state, we collected paleomat samples from ancient lake facies on the northern slopes of Lake Vanda in Wright Valley in December 2016. Using a gentle lysis technique optimized to preserve longer molecules, combined with a polyenzymatic treatment to maximize yields from different cell types, we isolated high-molecular weight DNA and RNA from ancient paleomat samples. Community composition analysis suggests that the paleomat community may retain a population of indigenous mat cells that may flourish once more favorable conditions are met. In addition to harboring a diverse microbial community, paleomats appear to host heterotrophs in surrounding soils utilizing the deposits as a carbon source. Whole genome long-read PacBio sequencing of native DNA and Illumina metagenomic sequencing of size-sorted DNA (>2,500 nt) indicated possible cell viability, with mat community composed of bacterial taxa. Metagenome assemblies identified genes with predicted roles in nitrogen cycling and complex carbohydrate degradation, and we identified key metabolic pathways such as stress response, DNA repair, and sporulation. Metatranscriptomic data revealed that the most abundant transcripts code for products involved in genetic information processing pathways, particularly translation, DNA replication, and DNA repair. Our results lend new insight into the functional ecology of paleomat deposits, with implications for our understanding of cell biology, Antarctic microbiology and biogeography, and the limits of life in extremely harsh environments

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment

Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues.

X-linked myotubular myopathy (XLMTM), a severe congenital myopathy, is caused by mutations in the MTM1 gene located on the X chromosome. A majority of affected males die in the early postnatal period, whereas female carriers are believed to be usually asymptomatic. Nevertheless, several affected females have been reported. To assess the phenotypic and pathological spectra of carrier females and to delineate diagnostic clues, we characterized 17 new unrelated affected females and performed a detailed comparison with previously reported cases at the clinical, muscle imaging, histological, ultrastructural and molecular levels. Taken together, the analysis of this large cohort of 43 cases highlights a wide spectrum of clinical severity ranging from severe neonatal and generalized weakness, similar to XLMTM male, to milder adult forms. Several females show a decline in respiratory function. Asymmetric weakness is a noteworthy frequent specific feature potentially correlated to an increased prevalence of highly skewed X inactivation. Asymmetry of growth was also noted. Other diagnostic clues include facial weakness, ptosis and ophthalmoplegia, skeletal and joint abnormalities, and histopathological signs that are hallmarks of centronuclear myopathy such as centralized nuclei and necklace fibers. The histopathological findings also demonstrate a general disorganization of muscle structure in addition to these specific hallmarks. Thus, MTM1 mutations in carrier females define a specific myopathy, which may be independent of the presence of an XLMTM male in the family. As several of the reported affected females carry large heterozygous MTM1 deletions not detectable by Sanger sequencing, and as milder phenotypes present as adult-onset limb-girdle myopathy, the prevalence of this myopathy is likely to be greatly underestimated. This report should aid diagnosis and thus the clinical management and genetic counseling of MTM1 carrier females. Furthermore, the clinical and pathological history of this cohort may be useful for therapeutic projects in males with XLMTM, as it illustrates the spectrum of possible evolution of the disease in patients surviving long term

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0â5·5) with an incidence of respiratory critical events of 3·1% (2·9â3·3). Cardiovascular instability occurred in 1·9% (1·7â2·1), with an immediate poor outcome in 5·4% (3·7â7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86â0·90; p<0·0001), medical history, and physical condition (1·60, 1·40â1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981â0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97â0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. Funding European Society of Anaesthesiology

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6.35 years (SD 4.50) were included. The incidence of perioperative severe critical events was 5.2% (95% CI 5.0-5.5) with an incidence of respiratory critical events of 3.1% (2.9-3.3). Cardiovascular instability occurred in 1.9% (1.7-2.1), with an immediate poor outcome in 5.4% (3.7-7.5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0.88, 95% CI 0.86-0.90; p<0.0001), medical history, and physical condition (1.60, 1.40-1.82; p<0.0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0.99, 0.981-0.997; p<0.0048 for respiratory critical events, and 0.98, 0.97-0.99; p=0.0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

The inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$

Search for exotic decays of the Higgs boson to a pair of pseudoscalars in the μμ\mu\mubb and ττ\tau\taubb final states

A search for exotic decays of the Higgs boson (H) with a mass of 125 GeV to a pair of light pseudoscalars $\mathrm{a}_1$ is performed in final states where one pseudoscalar decays to two b quarks and the other to a pair of muons or $\tau$ leptons. A data sample of proton-proton collisions at $\sqrt{s}$ = 13 TeV corresponding to an integrated luminosity of 138 fb$^{-1}$ recorded with the CMS detector is analyzed. No statistically significant excess is observed over the standard model backgrounds. Upper limits are set at 95% confidence level (CL) on the Higgs boson branching fraction to $\mu\mu$bb and to $\tau\tau$bb, via a pair of $\mathrm{a}_1$s. The limits depend on the pseudoscalar mass $m_{\mathrm{a}_1}$ and are observed to be in the range (0.17-3.3) $\times$ 10$^{-4}$ and (1.7-7.7) $\times$ 10$^{2}$ in the $\mu\mu$bb and $\tau\tau$bb final states, respectively. In the framework of models with two Higgs doublets and a complex scalar singlet (2HDM+S), the results of the two final states are combined to determine model-independent upper limits on the branching fraction $\mathcal{B}$(H $\to$ $\mathrm{a}_1\mathrm{a}_1$ $\to$ $\ell\ell$bb) at 95% CL, with $\ell$ being a muon or a $\tau$ lepton. For different types of 2HDM+S, upper bounds on the branching fraction $\mathcal{B}$(H $\to$ $\mathrm{a}_1\mathrm{a}_1$) are extracted from the combination of the two channels. In most of the Type II 2HDM+S parameter space, $\mathcal{B}($H $\to$ $\mathrm{a}_1\mathrm{a}_1$) values above 0.23 are excluded at 95% CL for $m_{\mathrm{a}_1}$ values between 15 and 60 GeV

Extracting the speed of sound in the strongly interacting matter created in ultrarelativistic lead-lead collisions at the LHC

International audienceUltrarelativistic nuclear collisions create a strongly interacting state of hot and dense quark-gluon matter that exhibits a remarkable collective flow behavior with minimal viscous dissipation. To gain deeper insights into its intrinsic nature and fundamental degrees of freedom, we extracted the speed of sound in this medium created using lead-lead (PbPb) collisions at a center-of-mass energy per nucleon pair of 5.02 TeV. The data were recorded by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 0.607 nb$^{-1}$. The measurement is performed by studying the multiplicity dependence of the average transverse momentum of charged particles emitted in head-on PbPb collisions. Our findings reveal that the speed of sound in this matter is nearly half the speed of light, with a squared value of 0.241 $\pm$ 0.002 (stat) $\pm$ 0.016 (syst) in natural units. The effective medium temperature, estimated using the mean transverse momentum, is 219 $\pm$ 8 (syst) MeV. The measured squared speed of sound at this temperature aligns precisely with predictions from lattice quantum chromodynamic (QCD) calculations. This result provides a stringent constraint on the equation of state of the created medium and direct evidence for a deconfined QCD phase being attained in relativistic nuclear collisions