Fisiología de la nutrición y del estrés en las primeras fases de vida del pulpo común (Octopus vulgaris). Resultados del proyecto OCTOPHYS

El cultivo del pulpo común (Oclopus vulgaris) está severamente limitado por las altas mortalidades que se producen durante su cultivo larvano, aunque en la actualidad, las causas especfficas de tan alta mortalidad siguen siendo desconocidas. Este proyecto pretende adquirir conocimientos básicos sobre la biología y fisiologia de las paralarvas a través de un enfoque multidisciplinarque incluye aspectos innovadores relacionados con la fisiologia de la nutrición y el estrés. Los objetivos propuestos están basados en un fuerte input zootécnico y prevén el uso de herramientas biométricas, bioquímicas, enzimáticas, moleculares y proteómicas, con el fin último de optimizar la condición y supervivencia de las paralarvas. Incluyen asimismo la búsqueda y selección de biomarcadores capaces de detectar y cuantíñcar el estrés nutricional.The culture oflhe common octopus (Octopus vulgaris) is hindered by high mortalities encountered during its paralarval rearing, allhough at present, Ihe specific causes forlhe high mortalities observed remain unidentified. This project aims at galhering a beller understanding of Ihe basic biology and physiology ofthe paralarvae, through a multidisciplinary and integrated approach, which includes Ihe study oflhe physiology 01 nutrition and!he evaluation 01Ihe stress condition. The objectives proposed are basad on a strong zootechnical input and foresee Ihe use of biometric, biochemical, enzymatic, molecular biology and proteomic tools, pointing towards the ultimate optimisation of Ihe paralarval condition and survival. They also include Ihe study ofthe nutritionally-derived stress and Ihe selection ofbiomarkers capable of its detection and quantification

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Epigenetic variability in the human oxytocin receptor (OXTR) gene : A possible pathway from early life experiences to psychopathologies

The human oxytocin (OXT) system is implicated in the regulation of complex social behaviors, as well as in psychopathologies characterized by social deficits. Emerging evidence suggests that variation in epigenetic regulation of the oxytocin receptor gene (OXTR) provides the oxytocin system with flexibility in response to environmental events, especially those occurring during early childhood. Changes in DNA methylation patterns of OXTR associated with these events may reflect biological alterations of social sensitivity. This is often related to an increased risk of developing mental disorders later in life. Here, we systematically reviewed all human studies (n = 30) discussing OXTR methylation in relation to socio-behavioral phenotypes. As such, we provide a complete and up-to-date overview of the literature that will aid future research in the interdisciplinary field of epigenetics and socio-behavioral sciences

Integrating technical and political views for a sustainable European Distributed Infrastructure on Population Health.

BACKGROUND: Non-Communicable diseases (NCD) are the main contributors to mortality and burden of disease. There is no infrastructure in Europe that could provide health information (HI) on Public Health monitoring and Health Systems Performance (HSP) for research and evidence-informed decision-making. Moreover, there was no EU and European Economic Area Member States (EU/EEA MSs) general consensus, on developing this initiative and guarantee its sustainability. The aim of this study is to analyze the integration of technical and political views made by the Joint Action on Health Information (InfAct; Information for Action) and the results obtained from those activities, in terms of advice and national and institutional support to develop an integrated and sustainable European Distributed Infrastructure on Population Health (DIPoH) for research and evidence-informed&nbsp;policy-making. METHODS: InfAct established two main boards, the Technical Dialogues (TDs) and the Assembly of Members (AoM), to provide a platform for discussion with EU/EEA MSs to establish a sustainable infrastructure for HI: 1) The TDs were composed by national technical experts (NTE) with the aim to discuss and provide feedback about scientific aspects, feasibility and EU-added value of the infrastructure proposed by InfAct. 2) The AoM gathered country representatives from Ministries of Health and Research at the highest political level, with the aim of providing policy-oriented advice for the future political acceptance, support, implementation, and development of InfAct&#8217;s outcomes including DIPoH. The documentation provided for the meetings consisted in Fact-Sheets, where the main results, new methods and proposals were clearly exposed for discussion and assessment; altogether with more extended information of the DIPoH. The documentation was provided to national representatives within one more before each TD and AoM meeting. The Agenda and methodological approaches for each TD and AoM meeting consisted in the presentations of the InfAct outcomes extending the information provided in the Fact-Sheets; followed by a non-structured interaction, exchange of information, discussion and suggestions by the MSs representatives. The outcomes of the non-structured discussions were collected in Minutes of the TD and AoM meetings, and the final version was obtained with the consensus of all participants. Additionally, structured letters of political support were provided to the AoM representatives, for them to consider providing their MS written support for DIPoH. RESULTS: NTE, within the TDs, considered that DIPoH was useful for technical mutual learning and cooperation among and within countries; although they considered that the technical feasibility to uptake InfAct deliverables at the national and EU level was complex. The AoM focused on political support, resources, and expected MSs returns. The AoM representatives agreed in the interest of setting up an integrated and sustainable HI infrastructure and they considered DIPoH to be well-articulated and defined; although, some of them, expressed some barriers for providing DIPoH political support. The AoM representatives stated that the AoM is the most suitable way to inform EU MSs/ACs about future advances of DIPoH. Both boards provided valuable feedback to develop this infrastructure. Eleven countries and sixteen institutions supported the proposal, either by letters of political support or by signing the Memorandum of Understandings (MoU) and three countries, additionally, provided expression of financial commitment, for DIPoH to be added to the ESFRI 2021&nbsp;roadmap. CONCLUSIONS: TDs and AoM were key forums to develop, advise, advocate and provide support for a sustainable European research infrastructure for Population&nbsp;Health.</p

The InfAct proposal for a sustainable European health information infrastructure on population health: the Distributed Infrastructure on Population Health (DIPoH).

BACKGROUND: In Europe, data on population health is fragmented, difficult to access, project-based and prone to health information inequalities in terms of availability, accessibility and especially in quality between and within countries. This situation is further exacerbated and exposed by the recent COVID-19 pandemic. The Joint Action on Health Information (InfAct) that builds on previous works of the BRIDGE Health project, carried out collaborative action to set up a sustainable infrastructure for health information in the European Union (EU). The aim of this paper is to present InfAct&#8217;s proposal for a sustainable research infrastructure, the Distributed Infrastructure on Population Health (DIPoH), which includes the setup of a Health Information Portal on population health to be maintained beyond InfAct&#8217;s time&nbsp;span. METHODS: The strategy for the proposal was based on three components: scientific initiatives and proposals to improve Health Information Systems (HIS), exploration of technical acceptability and feasibility, and finally obtaining high-level political support.. The technical exploration (Technical Dialogues-TD) was assumed by technical experts proposed by the countries, and political guidance was provided by the Assembly of Members (AoM), which gathered representatives from Ministries of Health and Science of EU/EEA countries. The results from the AoM and the TD were integrated in the sustainability plan compiling all the major outputs of&nbsp;InfAct. RESULTS: The InfAct sustainability plan was organized in three main sections: a proposal of a new research infrastructure on population health (the DIPoH), new health information tools and innovative proposals for HIS, and a comprehensive capacity building programme. These activities were carried out in InfAct and are being further developed in the Population Health Information Research Infrastructure (PHIRI). PHIRI is a practical rollout of DIPoH facilitating and generating the best available evidence for research on health and wellbeing of populations as impacted by COVID-19. CONCLUSIONS: The sustainability plan received wide support from Member States and was recognized to have an added value at EU level. Nevertheless, there were several aspects which still need to be considered for the near future such as: (i) a commitment of stable financial and political support by Member States (MSs), (ii) the availability of resources at regional, national and European level to deal with innovations, and (iii) a more direct involvement from EU and international institutions such as the European Centre for Disease Prevention and Control (ECDC), the World Health Organization (WHO) and the Organisation for Economic Cooperation and Development OECD for providing support and sustainable&nbsp;contributions.</p