Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia

A Radial Velocity Study of the Planetary System of pi Mensae: Improved Planet Parameters for pi Mensae c and a Third Planet on a 125 Day Orbit

π Men hosts a transiting planet detected by the Transiting Exoplanet Survey Satellite space mission and an outer planet in a 5.7 yr orbit discovered by radial velocity (RV) surveys. We studied this system using new RV measurements taken with the HARPS spectrograph on ESO's 3.6 m telescope, as well as archival data. We constrain the stellar RV semiamplitude due to the transiting planet, π Men c, as Kc = 1.21 ± 0.12 m s^{−1}, resulting in a planet mass of M_{c} = 3.63 ± 0.38 M_{⊕}. A planet radius of R_{c} = 2.145 ± 0.015 R_{⊕} yields a bulk density of ρc = 2.03 ± 0.22 g cm^{−3}. The precisely determined density of this planet and the brightness of the host star make π Men c an excellent laboratory for internal structure and atmospheric characterization studies. Our HARPS RV measurements also reveal compelling evidence for a third body, π Men d, with a minimum mass M_{d} sin i_{d} = 13.38 ± 1.35 M_{⊕} orbiting with a period of Porb,d = 125 days on an eccentric orbit (e_{d} = 0.22). A simple dynamical analysis indicates that the orbit of π Men d is stable on timescales of at least 20 Myr. Given the mutual inclination between the outer gaseous giant and the inner rocky planet and the presence of a third body at 125 days, π Men is an important planetary system for dynamical and formation studies

TOI-132 b: A short-period planet in the Neptune desert transiting a V=11.3 G-type star

The Neptune desert is a feature seen in the radius-period plane, whereby a notable dearth of short period, Neptune-like planets is found. Here, we report the Transiting Exoplanet Survey Satellite (TESS) discovery of a new short-period planet in the Neptune desert, orbiting the G-type dwarf TYC 8003-1117-1 (TOI-132). TESS photometry shows transit-like dips at the level of similar to 1400 ppm occurring every similar to 2.11 d. High-precision radial velocity follow-up with High Accuracy Radial Velocity Planet Searcher confirmed the planetary nature of the transit signal and provided a semi-amplitude radial velocity variation of 11.38(-0.85)(+0.84) m s(-1), which, when combined with the stellar mass of 0.97 +/- 0.06 M-circle dot, provides a planetary mass of 22.40(-1.92)(+1.90) M-circle plus. Modelling the TESS light curve returns a planet radius of 3.42(-0.14)(+0.13) R-circle plus , and therefore the planet bulk density is found to be 3.08(-0.46)(+0.44) g cm(-3). Planet structure models suggest that the bulk of the planet mass is in the form of a rocky core, with an atmospheric mass fraction of 4.3(-2.3)(+1.2) percent. TOI-132 b is a TESS Level 1 Science Requirement candidate, and therefore priority follow-up will allow the search for additional planets in the system, whilst helping to constrain low-mass planet formation and evolution models, particularly valuable for better understanding of the Neptune desert

Greening of the brown-dwarf desert EPIC 212036875b: a 51 M-J object in a 5-day orbit around an F7V star

Context. Although more than 2000 brown dwarfs have been detected to date, mainly from direct imaging, their characterisation is difficult due to their faintness and model-dependent results. In the case of transiting brown dwarfs, however, it is possible to make direct high-precision observations. Aims. Our aim is to investigate the nature and formation of brown dwarfs by adding a new well-characterised object, in terms of its mass, radius and bulk density, to the currently small sample of less than 20 transiting brown dwarfs. Methods. One brown dwarf candidate was found by the KESPRINT consortium when searching for exoplanets in the K2 space mission Campaign 16 field. We combined the K2 photometric data with a series of multicolour photometric observations, imaging, and radial velocity measurements to rule out false positive scenarios and to determine the fundamental properties of the system. Results. We report the discovery and characterisation of a transiting brown dwarf in a 5.17-day eccentric orbit around the slightly evolved F7V star EPIC 212036875. We find a stellar mass of 1.15 +/- 0.08 M-circle dot, a stellar radius of 1.41 +/- 0.05 R-circle dot, and an age of 5.1 +/- 0.9 Gyr. The mass and radius of the companion brown dwarf are 51 +/- 2 M-J and 0.83 +/- 0.03 R-J, respectively, corresponding to a mean density of 108(-13)(+15) g cm(-3). Conclusions. EPIC 212036875 b is a rare object that resides in the brown-dwarf desert. In the mass-density diagram for planets, brown dwarfs, and stars, we find that all giant planets and brown dwarfs follow the same trend from similar to 0.3 M-J to the turn-over to hydrogen burning stars at similar to 73 M-J. EPIC 212036875 b falls close to the theoretical model for mature H/He dominated objects in this diagram as determined by interior structure models. We argue that EPIC 212036875 b formed via gravitational disc instabilities in the outer part of the disc, followed by a quick migration. Orbital tidal circularisation may have started early in its history for a brief period when the brown dwarf\u27s radius was larger. The lack of spin-orbit synchronisation points to a weak stellar dissipation parameter (Q(star)\u27 greater than or similar to 10(8)), which implies a circularisation timescale of greater than or similar to 23 Gyr, or suggests an interaction between the magnetic and tidal forces of the star and the brown dwarf

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Solar-like oscillations and ellipsoidal variations in TESS observations of the binary 12 Bootis

Binary stars in which oscillations can be studied in either or both components can provide powerful constraints on our understanding of stellar physics. The bright binary 12 Bootis (12 Boo) is a particularly promising system because the primary is roughly 60 per cent brighter than the secondary despite being only a few per cent more massive. Both stars have substantial surface convection zones and are therefore, presumably, solar-like oscillators. We report here the first detection of solar-like oscillations and ellipsoidal variations in the TESS light curve of 12 Boo. Though the solar-like oscillations are not clear enough to unambiguously measure individual mode frequencies, we combine global asteroseismic parameters and a precise fit to the spectral energy distribution (SED) to provide new constraints on the properties of the system that are several times more precise than values in the literature. The SED fit alone provides new effective temperatures, luminosities, and radii of 6115 +/- 45 K, 7.531 +/- 0.110 L-circle dot, and 2.450 +/- 0.045 R-circle dot for 12 Boo A and 6200 +/- 60 K, 4.692 +/- 0.095 L-circle dot, and 1.901 +/- 0.045 R-circle dot for 12 Boo B. When combined with our asteroseismic constraints on 12 Boo A, we obtain an age of 2.67(-0.16)(+0.12) Gyr, which is consistent with that of 12 Boo B.UK Science and Technology Facilities Council (STFC) [ST/R0023297/1]; ERC Consolidator Grant funding scheme (project ASTEROCHRONOMETRY) [772293]; PLATO grant; GOLF CNES grant; grant FPI-SO from the Spanish Ministry of Economy and Competitiveness (MINECO) [SEV-2015-0548-17-2, BES-2017-082610]; Spanish Ministry of Science and Innovation (MICINN) [RYC-2015-17697, PID2019-107187GB-I00]; AEI under the Severo Ochoa Centres of Excellence Programme 2020-2023 [CEX2019000920-S]; TESS GI Program under NASA [80NSSC18K1585, 80NSSC19K0385]; Max Planck Society; Erciyes University Scientific Research Coordination Unit [DOSAP MAP-2020-9749]; NASA Explorer ProgramWHB and WJC thank the UK Science and Technology Facilities Council (STFC) for support under grant ST/R0023297/1. AM acknowledges support from the ERC Consolidator Grant funding scheme (project ASTEROCHRONOMETRY, https://www.asteroch ronometry.eu, G.A. n. 772293). RAG acknowledges the support from PLATO and GOLF CNES grants. LGC thanks the support from grant FPI-SO from the Spanish Ministry of Economy and Competitiveness (MINECO) (research project SEV-2015-0548-17-2 and predoctoral contract BES-2017-082610). SM acknowledges support from the Spanish Ministry of Science and Innovation (MICINN) with the Ram ' on y Cajal fellowship no. RYC-2015-17697 and grant no. PID2019-107187GB-I00, and through AEI under the Severo Ochoa Centres of Excellence Programme 2020-2023 (CEX2019000920-S). DLB acknowledges support from the TESS GI Program under NASA awards 80NSSC18K1585 and 80NSSC19K0385. JC is supported by a grant from the Max Planck Society to prepare for the scientific exploitation of the PLATO mission. CK is supported by Erciyes University Scientific Research Coordination Unit under grant number DOSAP MAP-2020-9749.; This paper includes data collected by the TESS mission, which are publicly available from the Mikulski Archive for Space Telescopes (MAST). Funding for the TESS mission is provided by the NASA Explorer Program.; This work has used data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement

Robust asteroseismic properties of the bright planet host HD 38529

Deal, Morgan/0000-0001-6774-3587; Celik Orhan, Zeynep/0000-0002-9424-2339; Santos, Angela/0000-0001-7195-6542; Ball, Warrick/0000-0002-4773-1017; Lysgaard Rorsted, Jakob/0000-0001-9234-430X; Cunha, Margarida/0000-0001-8237-7343; Huber, Daniel/0000-0001-8832-4488; Stokholm, Amalie/0000-0002-5496-365X; Basu, Sarbani/0000-0002-6163-3472; Ong, Joel/0000-0001-7664-648XWOS:000599131700104The Transiting Exoplanet Survey Satellite (TESS) is recording short-cadence, high duty-cycle timeseries across most of the sky, which presents the opportunity to detect and study oscillations in interesting stars, in particular planet hosts. We have detected and analysed solar-like oscillations in the bright G4 subgiant HD 38529, which hosts an inner, roughly Jupiter-mass planet on a 14.3d orbit and an outer, low-mass brown dwarf on a 2136 d orbit. We combine results frommultiple stellarmodelling teams to produce robust asteroseismic estimates of the star's properties, including its mass M = 1.48 +/- 0.04 M-circle dot, radius R = 2.68 +/- 0.03 R-circle dot, and age t = 3.07 +/- 0.39 Gyr. Our results confirm that HD 38529 has a mass near the higher end of the range that can be found in the literature and also demonstrate that precise stellar properties can be measured given shorter timeseries than produced by CoRoT, Kepler, or K2.UK Science and Technology Facilities Council (STFC)UK Research & Innovation (UKRI)Science & Technology Facilities Council (STFC) [ST/R0023297/1]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF106]; grant FPI-SO from the Spanish Ministry of Economy and Competitiveness (MINECO) [SEV-2015-0548-17-2, BES-2017-082610]; Spanish Ministry with the Ramon y Cajal fellowship [RYC-2015-17697]; NASANational Aeronautics & Space Administration (NASA) [NNX17AF27G, NNX16AI09G, 80NSSC19K0374]; TESS GI Program under NASA [80NSSC18K1585, 80NSSC19K0385]; Carlsberg FoundationCarlsberg Foundation [CF19-0649]; Independent Research Fund Denmark [7027-00096B]; Alexander von Humboldt Foundation at the Max-Planck-Institut fur Astrophysik; national funds through Fundacao para a Ciencia e Tecnologia (FCT); FCT/MCTES through national funds (PIDDAC) [UIDB/04434/2020, UIDP/04434/2020, PTDC/FIS-AST/30389/2017]; Fundo Europeu de Desenvolvimento Regional (FEDER) through COMPETE2020: Programa Operacional Competitividade e Internacionalizacao [POCI01-0145-FEDER-030389]; European Union's Horizon 2020 research and innovation programme under the H2020 Marie Sklodowska-Curie Actions grant [792848]; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK:118F352]; NASA Explorer ProgramNational Aeronautics & Space Administration (NASA); PLATO-CNES grantWHB, WJC, and MBN thank the UK Science and Technology Facilities Council (STFC) for support under grant ST/R0023297/1. Funding for the Stellar Astrophysics Centre is provided by The Danish National Research Foundation (grant DNRF106). LGC thanks the support from grant FPI-SO from the Spanish Ministry of Economy and Competitiveness (MINECO; research project SEV-2015-0548-17-2 and predoctoral contract BES-2017-082610). SM acknowledges support from the Spanish Ministry with the Ramon y Cajal fellowship number RYC-2015-17697. ARGS acknowledges the support from NASA under grant NNX17AF27G. RAG acknowledges the support of the PLATO-CNES grant. DLB acknowledges support from the TESS GI Program under NASA awards 80NSSC18K1585 and 80NSSC19K0385. JRM acknowledges support from the Carlsberg Foundation (grant CF19-0649). VSA acknowledges support from the Independent Research Fund Denmark (Research grant 7027-00096B). BN acknowledges postdoctoral funding from the Alexander von Humboldt Foundation taken at the Max-Planck-Institut fur Astrophysik. MSC and MD are supported in the form of work contracts funded by national funds through Fundacao para a Ciencia e Tecnologia (FCT). MSC and MD acknowledge support by FCT/MCTES through national funds (PIDDAC) by grants UIDB/04434/2020, UIDP/04434/2020, and PTDC/FIS-AST/30389/2017 and by Fundo Europeu de Desenvolvimento Regional (FEDER) through COMPETE2020: Programa Operacional Competitividade e Internacionalizacao by grant POCI01-0145-FEDER-030389. TC acknowledges support from the European Union's Horizon 2020 research and innovation programme under the H2020 Marie Sklodowska-Curie Actions grant 792848 (PULSATION). SB acknowledges NASA grants NNX16AI09G and 80NSSC19K0374. ZCO, MY, and SO acknowledge the Scientific and Technological Research Council of Turkey (TUBITAK:118F352) This paper includes data collected by the TESS mission, which are publicly available from the Mikulski Archive for Space Telescopes (MAST). Funding for the TESS mission is provided by the NASA Explorer Program. Calculations in this paper had used the University of Birmingham's BlueBEAR High-Performance Computing service.1</SUP

Study of the dynamics of in vitro infection with bovine gammaherpesvirus type 4 and apoptosis markers in susceptible cells

Bovine gammaherpesvirus type 4 (BoHV-4) shows tropism for the endometrium, in which it causes the death of epithelial and stroma cells. Despite having anti-apoptotic genes in its genome, experiments based on immortalized cell lines have shown that BoHV-4 induces cell death by apoptosis. In the present study, we evaluated BoHV-4 replication, pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) mitochondrial genes expression and chromatin condensation in bovine endometrium primary culture cells (BEC) and in the Madin Darby bovine kidney (MDBK) cell line. Results showed that BoHV-4 has a preference for replication in BEC cells over the MDBK cell line, demonstrated by the high viral titer that is consistent with the tropism of the virus. In BEC cells, chromatin condensation was consistent with the values of viral kinetics at the late stage of infection, accompanied with a balance in the mRNA levels of apoptotic mitochondrial proteins. As a consequence, in those cells viral transmission would be enhanced by inhibiting apoptosis in the early stage of virus proliferation, allowing the complete production of viral progeny, and then, the induction of apoptosis in late stages would allow neighboring cells infection. In MDBK cells replication kinetics was coincident with the up-regulation of Bcl-2, which suggests that the productive infection in MDBK is associated with a lytic phase of the virus or another cell death pathway (probably autophagy mechanism) at the late stage of infection. The results agree with the study of nuclear morphology, where a constant chromatin condensation was observed over time. It is clear that the documented BoHV-4 apoptotic responses observed in the cell lines studied above are not valid in cells from primary cultures. The data presented in this study suggest that BoHV-4 could induce apoptosis in BEC cells without a leading role of the mitochondria pathway. Further studies will be necessary to characterize in detail the programmed cell death pathways involved in BoHV-4 infection in the primary cell cultures evaluated.EEA BalcarceFil: Romeo, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Romeo, Florencia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Delgado, Santiago. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Louge Uriarte, Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina.Fil: Storani, Leonardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina.Fil: Storani, Leonardo. Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación; Argentina.Fil: Martínez Cuesta, Lucia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Martínez Cuesta, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Morán, Pedro. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina.Fil: González Altamiranda, Erika. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina.Fil: Odeón, Anselmo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Pérez, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Centro de Investigación Veterinaria de Tandil; Argentina.Fil: Verna, Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina