A revision of the ‘coelophysoid-grade’ theropod specimen from the Lower Jurassic of the Isle of Skye (Scotland)

The broadest diversification of early predatory dinosaurs is represented by the ‘coelophysoid-grade’ neotheropods, but their Hettangian–Sinemurian (c. 191–201 Ma) record is scarce worldwide. More information is needed to shed light on the evolution of this dinosaur group after the end-Triassic mass extinction (c. 201 Ma). Here we revisit the anatomy and phylogeny of one of these earliest Jurassic neotheropod specimens, an isolated partial tibia from the lower Sinemurian of the Isle of Skye (Scotland) that was previously identified as probably closely related to Liliensternus liliensterni and coelophysids. However, we found that the Skye specimen is positioned in the branch leading to Averostra (Ceratosauria + Tetanurae), in a polytomy with Sarcosaurus woodi from the late Hettangian–lower Sinemurian of central England and a clade composed of Tachiraptor admirabilis and Averostra. The morphology of the Skye specimen is congruent with that of referred specimens of Sarcosaurus woodi, but because it probably represents a skeletally immature specimen, we assign it to cf. Sarcosaurus woodi. The Skye specimen increases the number of averostran-line neotheropod specimens recorded in the Lower Jurassic of Europe and current evidence indicates that these forms, and not coelophysoids, were relatively common in this part of the world at that time

Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25

Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10-9]

miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells

SummaryTo investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance

ESM-SnowMIP: Assessing snow models and quantifying snow-related climate feedbacks

This paper describes ESM-SnowMIP, an international coordinated modelling effort to evaluate current snow schemes, including snow schemes that are included in Earth system models, in a wide variety of settings against local and global observations. The project aims to identify crucial processes and characteristics that need to be improved in snow models in the context of local- and global-scale modelling. A further objective of ESM-SnowMIP is to better quantify snow-related feedbacks in the Earth system. Although it is not part of the sixth phase of the Coupled Model Intercomparison Project (CMIP6), ESM-SnowMIP is tightly linked to the CMIP6-endorsed Land Surface, Snow and Soil Moisture Model Intercomparison (LS3MIP)

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial

Background—Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods—This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. Findings—From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation—The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children

Statistical retrieval of thin liquid cloud microphysical properties using ground-based infrared and microwave observations

In this article, liquid water cloud microphysical properties are retrieved by a combination of microwave and infrared ground-based observations. Clouds containing liquid water are frequently occurring in most climate regimes and play a significant role in terms of interaction with radiation. Small perturbations in the amount of liquid water contained in the cloud can cause large variations in the radiative fluxes. This effect is enhanced for thin clouds (liquid water path, LWP<100 g/m(2)), which makes accurate retrieval information of the cloud properties crucial. Due to large relative errors in retrieving low LWP values from observations in the microwave domain and a high sensitivity for infrared methods when the LWP is low, a synergistic retrieval based on a neural network approach is built to estimate both LWP and cloud effective radius (r(eff)). These statistical retrievals can be applied without high computational demand but imply constraints like prior information on cloud phase and cloud layering. The neural network retrievals are able to retrieve LWP and r(eff) for thin clouds with a mean relative error of 9% and 17%, respectively. This is demonstrated using synthetic observations of a microwave radiometer (MWR) and a spectrally highly resolved infrared interferometer. The accuracy and robustness of the synergistic retrievals is confirmed by a low bias in a radiative closure study for the downwelling shortwave flux, even for marginally invalid scenes. Also, broadband infrared radiance observations, in combination with the MWR, have the potential to retrieve LWP with a higher accuracy than a MWR-only retrieval