Seismic detection of the martian core

Clues to a planet's geologic history are contained in its interior structure, particularly its core. We detected reflections of seismic waves from the core-mantle boundary of Mars using InSight seismic data and inverted these together with geodetic data to constrain the radius of the liquid metal core to 1830 +/- 40 kilometers. The large core implies a martian mantle mineralogically similar to the terrestrial upper mantle and transition zone but differing from Earth by not having a bridgmanite-dominated lower mantle. We inferred a mean core density of 5.7 to 6.3 grams per cubic centimeter, which requires a substantial complement of light elements dissolved in the iron-nickel core. The seismic core shadow as seen from InSight's location covers half the surface of Mars, including the majority of potentially active regions-e.g., Tharsis-possibly limiting the number of detectable marsquakes.This is InSight contribution 200. We acknowledge NASA, CNES, and partner agencies and institutions (UKSA, SSO, ESA-PRODEX, DLR, JPL, IPGP-CNRS, ETHZ, IC, and MPS-MPG) for the development of SEIS. Numerical simulations were supported by a grant from the Swiss National Supercomputing Centre (CSCS) under project ID s922 as well as HPC resources of CINES under the allocation A0090407341, made by GENCI. We thank B. Dintrans, director of CINES, for his efficient handling of our request for computational time. Figures were created using matplotlib (83), seismic data processing was done in ObsPy (84), and numerical evaluation was done in NumPy and SciPy (85, 86). Funding: S.C.S., A.K., D.G., J.C., A.C.D., G.Z., and N.D. acknowledge support from ETHZ through the ETH+ funding scheme (ETH+2 19-1: “Planet MARS”). S.C.S. acknowledges funding from ETH research grant ETH-10 17-3. W.B.B., A.G.M., M.P.P., and S.E.S. were supported by the NASA InSight mission and funds from the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). D.A. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 724690). The French teams acknowledge support from CNES as well as Agence Nationale de la Recherche (ANR-14-CE36-0012-02 and ANR-19-CE31-0008-08). A.R. was financially supported by the Belgian PRODEX program managed by the European Space Agency in collaboration with the Belgian Federal Science Policy Office. M.S. wishes to thank SANIMS (RTI2018-095594-B-I00). M.v.D. received support from the ERC under the European Union’s Horizon 2020 program (grant no. 714069). D.S. and C.S. acknowledge funding from ETH research grant ETH-06 17-02. J.C.E.I. acknowledges support from NASA grant 80NSSC18K1633. N.S., D.K., Q.H., R.M., V.L., and A.G.M. acknowledge NASA grant 80NSSC18K1628 for support. V.L. acknowledges support from the Packard Foundation. W.T.P. and C.C. received funding from the UK Space Agency, grant ST/S001239/1. A.H. was funded by the UK Space Agency (grant ST/R002096/1). A.-C.P. acknowledges the financial support and endorsement from the DLR Management Board Young Research Group Leader Program and the Executive Board Member for Space Research and Technology. Author contributions: S.C.S., D.G., S.C., R.F.G., Q.H., D.K., V.L., M.S., N.S., D.S., É.S., C.S., and G.Z. analyzed the seismic data and made ScS arrival time picks. S.C.S., P.L., D.G., Z.X., C.C., and W.T.P. performed the statistical analysis of the observed signals. S.C.S., Q.H., N.S., R.M., and A.G.M. identified the arrivals as ScS waves based on interior models from A.K., H.S., and A.R. A.K., M.D., A.C.D., and H.S. performed the inversions. S.C.S., A.K., P.L., D.G., D.A., J.C.E.I., M.K., C.P., A.-C.P., A.R., T.G., and S.E.S. participated and contributed to the interpretation of the results. Review of the continuous data and detection of marsquakes was done by S.C.S., S.C., G.Z., C.C., N.D., J.C., M.v.D., T.K., M.P., and A.H. with operational support by É.B., C.P., and P.M.D. S.C.S. and A.K. wrote the central part of the paper with contributions from H.S., N.S., D.A., J.C.E.I., A.G.M., A.-C.P., A.R., J.C., and M.v.D. J.C.E.I., R.M., M.K., and V.L. reviewed the contributions to the supplementary materials. The InSight mission is managed by W.B.B., M.P.P., and S.E.S. The SEIS instrument development was led by P.L., D.G., W.T.P., and W.B.B. Supplementary section 1 was written by M.S., D.S., and É.S. with contributions from S.C.S., C.S., and Z.X. Supplementary section 2 was written by D.K. and V.L. with contributions from J.C.E.I. and N.S. Supplementary section 3 was written by M.S. and É.S. Supplementary section 4 was written by R.F.G. with contributions from M.D. Supplementary section 5 was written by Q.H. with contributions from N.S. Supplementary section 6 was written by S.C.S. with contributions from the authors of the other supplements. Supplementary section 7 was written by Z.X. and C.C. with contributions from P.L. and W.T.P. Supplementary section 8 was written by A.K., M.D., A.C.D., and H.S. Supplementary section 9 was written by M.D. Supplementary section 10 was written by A.C.D., A.K., and M.D. Supplementary section 11 was written by D.A. and A.R. with contributions from A.K. Competing interests: The authors declare that they have no competing interests. Data and materials availability: We thank the operators of JPL, SISMOC, MSDS, IRIS-DMC, and PDS for providing SEED SEIS data (87). Three hundred interior models derived in this study are available from MSDS (88)

The interior of Mars as seen by InSight (Invited)

InSight is the first planetary mission dedicated to exploring the whole interior of a planet using geophysical methods, specifically seismology and geodesy. To this end, we observed seismic waves of distant marsquakes and inverted for interior models using differential travel times of phases reflected at the surface (PP, SS...) or the core mantle-boundary (ScS), as well as those converted at crustal interfaces. Compared to previous orbital observations1-3, the seismic data added decisive new insights with consequences for the formation of Mars: The global average crustal thickness of 24-75 km is at the low end of pre-mission estimates5. Together with the the thick lithosphere of 450-600 km5, this requires an enrichment of heat-producing elements in the crust by a factor of 13-20, compared to the primitive mantle. The iron-rich liquid core is 1790-1870 km in radius6, which rules out the existence of an insulating bridgmanite-dominated lower mantle on Mars. The large, and therefore low-density core needs a high amount of light elements. Given the geochemical boundary conditions, Sulfur alone cannot explain the estimated density of ~6 g/cm3 and volatile elements, such as oxygen, carbon or hydrogen are needed in significant amounts. This observation is difficult to reconcile with classical models of late formation from the same material as Earth. We also give an overview of open questions after three years of InSight operation on the surface of Mars, such as the potential existence of an inner core or compositional layers above the CM

A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11Rα is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.Peer reviewe

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)