A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.Seventh Framework Programme (European Commission) (Grant HEALTH-F5-2010-258236-SYSCOL)Seventh Framework Programme (European Commission) (Grant HEALTH-F2-2011-259015-COLTHERES)Cellex FoundationOlga Torres FoundationEuropean Research Council (EPINORC Project Grant Agreement 268626)Spain. Ministerio de Economia y Competividad (MINECO Project SAF2011-22803)Institute of Health Carlos III (RTICC Grant RD12/0036/0039

J-PAS: forecasts on dark energy and modified gravity theories

The next generation of galaxy surveys will allow us to test one of the most fundamental assumptions of the standard cosmology, i.e. that gravity is governed by the general theory of relativity (GR). In this paper, we investigate the ability of the Javalambre Physics of the AcceleratingUniverseAstrophysical Survey (J-PAS) to constrainGR and its extensions. Based on the J-PAS information on clustering and gravitational lensing, we perform a Fisher matrix forecast on the effective Newton constant, mu, and the gravitational slip parameter, eta, whose deviations from unity would indicate a breakdown of GR. Similar analysis is also performed for the DESI and Euclid surveys and compared to J-PAS with two configurations providing different areas, namely an initial expectation with 4000 deg(2) and the future best case scenario with 8500 deg(2). We show that J-PAS will be able to measure the parameters mu and eta at a sensitivity of 2-7 per cent, and will provide the best constraints in the interval z = 0.3-0.6, thanks to the large number of ELGs detectable in that redshift range. We also discuss the constraining power of J-PAS for dark energy models with a time-dependent equation-of-state parameter of the type w(a) = w(0) + w(a)(1 - a), obtaining Delta w(0) = 0.058 and Delta w(a) = 0.24 for the absolute errors of the dark energy parameters.© 2020 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical SocietyWe are thankful to our colleagues of J-PAS Theory Working Group for useful discussions and to Ricardo Landim for his comments. MAR and ALM acknowledge support from MINECO (Spain) project FIS2016-78859-P (AEI/FEDER, UE), Red Consolider MultiDark FPA2017-90566-REDC, and UCM pre-doctoral grant. JSA acknowledges support from FAPERJ grant no. E-26/203.024/2017; CNPq grant no. 310790/2014-0 and 400471/2014-0; and the Financiadora de Estudos e Projetos -FINEP grants REF. 1217/13-01.13.0279.00 and REF0859/10-01.10.0663.00. SC acknowledges support from CNPq grant nos 307467/2017-1 and 420641/2018-1. This paper has gone through internal review by the J-PAS collaboration. Funding for the J-PAS Project has been provided by the Governments of Espana and Aragon through the Fondo de Inversion de Teruel, European FEDER funding, the MINECO projects AYA2015-66211-C2-1- P, AYA2015-66211-C2-2, and AYA2012-30789; the Brazilian agencies FINEP, FAPESP, FAPERJ and by the National Observatory of Brazil.Peer reviewe

Facial Emotion Recognition in Psychosis and Associations With Polygenic Risk for Schizophrenia: Findings From the Multi-Center EU-GEI Case-Control Study

BACKGROUND AND HYPOTHESIS: Facial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is associated with facial emotion recognition. STUDY DESIGN: 828 First Episode Psychosis (FEP) patients and 1308 population-based controls completed assessments of the Degraded Facial Affect Recognition Task (DFAR) and a subsample of 524 FEP and 899 controls provided blood or saliva samples from which we extracted DNA, performed genotyping and computed polygenic risk scores for schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MD). STUDY RESULTS: A worse ability to globally recognize facial emotion expressions was found in patients compared with controls [B= -1.5 (0.6), 95% CI -2.7 to -0.3], with evidence for stronger effects on negative emotions (fear [B = -3.3 (1.1), 95% CI -5.3 to -1.2] and anger [B = -2.3 (1.1), 95% CI -4.6 to -0.1]) than on happiness [B = 0.3 (0.7), 95% CI -1 to 1.7]. Pooling all participants, and controlling for confounds including case/control status, facial anger recognition was associated significantly with Schizophrenia Polygenic Risk Score (SZ PRS) [B = -3.5 (1.7), 95% CI -6.9 to -0.2]. CONCLUSIONS: Psychosis is associated with impaired recognition of fear and anger, and higher SZ PRS is associated with worse facial anger recognition. Our findings provide evidence that facial emotion recognition of anger might play a role as an intermediate phenotype for psychosis

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study

Background Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. Methods Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. Results The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. Conclusions Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse

J-PLUS: Detecting and studying extragalactic globular clusters. The case of NGC 1023.

Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Context. Extragalactic globular clusters (GCs) are key objects in studies of galactic histories. The advent of wide-field surveys, such as the Javalambre Photometric Local Universe Survey (J-PLUS), offers new possibilities for the study of these systems. Aims. We performed the first study of GCs in J-PLUS to recover information on the history of NGC 1023, taking advantage of wide-field images and 12 filters. Methods. We developed the semiautomatic pipeline GCFinder for detecting GC candidates in J-PLUS images, which can also be adapted to similar surveys. We studied the stellar population properties of a sub-sample of GC candidates using spectral energy distribution (SED) fitting. Results. We found 523 GC candidates in NGC 1023, about 300 of which are new. We identified subpopulations of GC candidates, where age and metallicity distributions have multiple peaks. By comparing our results with the simulations, we report a possible broad age-metallicity relation, supporting the notion that NGC 1023 has experienced accretion events in the past. With a dominating age peak at 1010 yr, we report a correlation between masses and ages that suggests that massive GC candidates are more likely to survive the turbulent history of the host galaxy. Modeling the light of NGC 1023, we find two spiral-like arms and detect a displacement of the galaxy’s photometric center with respect to the outer isophotes and center of GC distribution (~700pc and ~1600pc, respectively), which could be the result of ongoing interactions between NGC 1023 and NGC 1023A. Conclusions. By studying the GC system of NGC 1023 with J-PLUS, we showcase the power of multi-band surveys for these kinds of studies and we find evidence to support the complex accretion history of the host galaxy. © D. de Brito Silva et al. 2022.D.B.S. also acknowledges Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2017J00204-6 for the financial support provided for the development of this project. P.C. acknowledges support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under grant 310041/2018-0 and from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2018J05392-8. A.C.S. acknowledges funding from CNPq and the Rio Grande do Sul Research Foundation (FAPERGS) through grants CNPq-403580/2016-1, CNPq-11153/2018-6, PqG/FAPERGS-17/2551-0001, FAPERGS/CAPES 19/2551-0000696-9 and L’Oréal UNESCO ABC Para Mulheres na Ciência and the Chinese Academy of Sciences (CAS) President’s International Fellowship Initiative (PIFI) through grant E085201009. G.B. acknowledges financial support from the National Autonomous University of México (UNAM) through grant DGAPA/PAPIIT IG100319 and from CONACyT through grant CB2015-252364. J.V. acknowledges the technical members of the UPAD for their invaluable work: Juan Castillo, Tamara Civera, Javier Hernández, Ángel López, Alberto Moreno, and David Muniesa. J.A.H.J. acknowledges Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), process number 2021J08920-8. A.E. acknowledges the financial support from the Spanish Ministry of Science and Innovation and the European Union – NextGenerationEU through the Recovery and Resilience Facility project ICTS-MRR-2021-03-CEFCA and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) under grant 313285/2020-9 D.A.F. thanks the ARC for financial assistance via DP170102344. Y.J.-T has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 898633. Y.J-T. also acknowledges financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). Based on observations made with the JAST80 telescope telescope/s at the Observatorio Astrofísico de Javalambre, in Teruel, owned, managed, and operated by the Centro de Estudios de Física del Cosmos de Aragón. We thank the Centro de Estudios de Física del Cosmos de Aragón for the allocation of the Director’s Discretionary Time to this program. We thank the OAJ Data Processing and Archiving Unit (UPAD) for reducing and calibrating the OAJ data used in this work. Funding for the J-PLUS Project has been provided by the Governments of Spain and Aragón through the Fondo de Inversiones de Teruel; the Aragón Government through the Research Groups E96, E103, and E16_17R; the Spanish Ministry of Science, Innovation, and Universities (MCIU/AEI/FEDER, UE) with grants PGC2018-097585-B-C21 and PGC2018-097585-B-C22; the Spanish Ministry of Economy and Competitiveness (MINECO) under AYA2015-66211-C2-1-P, AYA2015-66211-C2-2, AYA2012-30789, and ICTS-2009-14; and European FEDER funding (FCDD10-4E-867, FCDD13-4E-2685). The Brazilian agencies FINEP, FAPESP, and the National Observatory of Brazil have also contributed to this project. This work has made use of the computing facilities of the Laboratory of Astroinformatics (IAG/USP, NAT/Unicsul), whose purchase was made possible by the Brazilian agency FAPESP (grant 2009/54006-4) and the INCT-A.Peer reviewe

The miniJPAS survey: stellar atmospheric parameters from 56 optical filters

With a unique set of 54 overlapping narrow-band and two broader filters covering the entire optical range, the incoming Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS) will provide a great opportunity for stellar physics and near-field cosmology. In this work, we use the miniJPAS data in 56 J-PAS filters and 4 complementary SDSS-like filters to explore and prove the potential of the J-PAS filter system in characterizing stars and deriving their atmospheric parameters. We obtain estimates for the effective temperature with a good precision (<150 K) from spectral energy distribution fitting. We have constructed the metallicity-dependent stellar loci in 59 colours for the miniJPAS FGK dwarf stars, after correcting certain systematic errors in flat-fielding. The very blue colours, including uJAVA − r, J0378 − r, J0390 − r, uJPAS − r, show the strongest metallicity dependence, around 0.25 mag dex−1. The sensitivities decrease to about 0.1 mag dex−1 for the J0400 − r, J0410 − r, and J0420 − r colours. The locus fitting residuals show peaks at the J0390, J0430, J0510, and J0520 filters, suggesting that individual elemental abundances such as [Ca/Fe], [C/Fe], and [Mg/Fe] can also be determined from the J-PAS photometry. Via stellar loci, we have achieved a typical metallicity precision of 0.1 dex. The miniJPAS filters also demonstrate strong potential in discriminating dwarfs and giants, particularly the J0520 and J0510 filters. Our results demonstrate the power of the J-PAS filter system in stellar parameter determinations and the huge potential of the coming J-PAS survey in stellar and Galactic studies. © 2022 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society.This work is supported by the National Natural Science Foundation of China through the projects NSFC 12222301, 12173007, 11603002, National Key Basic R & D Program of China via 2019YFA0405500, and Beijing Normal University grant no. 310232102. We acknowledge the science research grants from the China Manned Space Project with NO. CMS-CSST-2021-A08 and CMS-CSST-2021-A09. This research has made use of the Spanish Virtual Observatory (https://svo.cab.inta-csic.es) project funded by MCIN/AEI/10.13039/501100011033/ through grant PID2020-112949GB-I00. PC acknowledges financial support from the Government of Comunidad Autónoma de Madrid (Spain), via postdoctoral grant ‘Atracción de Talento Investigador’2019-T2/TIC-14760. The work of VMP is supported by NOIRLab, which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. FJE acknowledges financial support by the Spanish grant MDM-2017-0737 at Centro de Astrobiología (CSIC-INTA), Unidad de Excelencia María de Maeztu. CAG acknowledges financial support from the CAPES through scholarship for developing his PhD project and any related research. Part of this work was supported by institutional research funding IUT40-2, JPUT907, and PRG1006 of the Estonian Ministry of Education and Research. We acknowledge the support by the Centre of Excellence ‘Dark side of the Universe’ (TK133) financed by the European Union through the European Regional Development Fund.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EU-GEI)

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field