Ecological segregation inferred using chemical tracers and contamination assessment of five toothed whales in the Northwest Iberian Peninsula

Tese de doutoramento em Ciências (ramo de conhecimento em Biologia)The first objective of this PhD was to determine the degree of ecological segregation between five sympatric species of toothed whales (i.e. common dolphin Delphinus delphis, harbour porpoise Phocoena phocoena, bottlenose dolphin Tursiops truncatus, striped dolphin Stenella coeruleoalba and long finned pilot whale Globicephala melas) inhabiting a restricted and highly productive area, the North West Iberian Peninsula (NWIP). To this end, chemical parameters analyses were used as an “alternative method” of assessing diet and habitat of these animals over different periods of integration, complementing the information given by traditional methods of investigation such as stomach contents, faeces analyses and field observations. The second objective was to evaluate the contamination status of these species in order to estimate the toxicological risk these populations face and to complete the existing database. In this context, trace elements, carbon and nitrogen stable isotopes, as well as persistent organic pollutants (POPs) were selected as chemical parameters for our investigations. Firstly, the chemical parameters were used as ecological tracers of populations (or parts of populations) by drawing an image of the diet and habitat of the species at different time scales. We estimated that the food web has five trophic levels, with toothed whales occupying the top positions, with no significant difference in trophic positions among them, ranging from 4.3 to 5.3. While the analysis of a single chemical parameter did not completely segregate between the five species, the information gained by combining the analyses of several long-term ecological tracers (i.e. nitrogen and carbon stable isotopes in teeth and renal cadmium concentrations) revealed ecological niche segregation in two dimensions of this niche (the trophic and the spatial dimensions). However, year-to-year or seasonal variations could not be investigated, except for in common dolphin, and thus temporary overlap cannot be excluded. Additionally, we showed that polychlorinated biphenyls (PCBs) profiles could be a relevant tracer of the foraging ecology of taxonomically close species, allowing a fine separation of the species as result of their different patterns. This was particularly clear for the harbour porpoise and striped dolphin. Secondly, the contamination status of the species in this area was evaluated, with concentrations interpreted in the light of biological and ecological factors. But the bioaccumulation of trace elements appeared to be less predictable than that of POPs. Bottlenose dolphins and harbour porpoises were found to have higher PCBs concentrations than the rest of the analysed NWIP toothed whales, as well as those of adjacent NE Atlantic waters. The main results of this PhD highlight the relevance of exploiting these chemical parameters as ecological tracers, as well as their usefulness in the comprehensive study of structure and function of ecosystems through the role of top predators. Combined with the information on anthropogenic activities, this work can also contribute to the development and implementation of management plans and mitigation measures for these five species of toothed whales in the NWIP.O primeiro objetivo desta tese foi determinar qual grau de segregação ecológica existente entre cinco espécies simpráticas de cetáceos odontocetes (i.e. golfinho-comum Delphinus delphis, bôto Phocoena phocoena, roaz-corvineiro Tursiops truncatus, golfinho-riscado Stenella coeruleoalba e baleia-piloto Globicephala melas) que habitam numa área restrita e altamente produtiva, o Noroeste da Península Ibérica (NOPI). Para este fim, foram analisados parâmetros químicos como um "método alternativo" que pode refletir a dieta e habitat em diferentes períodos de integração destes animais, complementando a informação obtida através de métodos tradicionais tais como as análises de conteúdos estomacais, as análises de fezes e a observação de campo levadas a cabo no NOPI. O segundo objetivo foi avaliar o estado de contaminação destas espécies, obtendo dados de base de contaminantes nestas populações e estimar o risco toxicológico. Os elementos traço, os isótopos estáveis de carbono e nitrogênio e os poluentes orgânicos persistentes (POPs) foram seleccionados como parâmetros químicos para responder aos nossos objectivos. Em primeiro lugar, os parâmetros químicos foram utilizados como traçadores ecológicos de populações (ou partes das populações) pondo em evidência a dieta e habitat das espécies em estudo ao longo de diferentes escalas temporais. Estimou-se que a cadeia trófica possui um total de cinco niveis tróficos onde os cetáceos odontocetes estudados ocupam as posições mais elevadas sem apresentar diferenças significativas entre elas, variando desde 4.3 para 5.3. Embora a análise de um único parâmetro químico não tenha permitido segregar completamente as cinco espécies, a informação obtida combinando as análises de vários traçadores ecológicos a longo prazo (i.e. isótopos estáveis de carbono e nitrogênio em dentes e concentrações de cádmio nos rins) revela uma segregação do nicho ecológico entre as cinco espécies em duas dimensões do nicho (a dimensão trófica e a dimensão espacial). Porém, não pode ser excluída uma sobreposição temporal, uma vez que não foi possível investigar variações sazonais ou interanuais, excepto no caso do golfinho-comum. Adicionalmente, mostramos que perfis de policloro bifenis (PCBs) podem ser un traçador pertinente da ecologia alimentar de espécies taxonomicamente próximas permitindo uma boa separação das espécies bôto e golfinho-riscado de acordo com os seus diferentes padrões. Em segundo lugar, foi avaliado o estado de contaminação das espécies nesta área. As concentrações foram interpretadas tendo em conta factores biológicos e ecológicos. No entanto, a bio-acumulação dos elementos traço mostrou-se menos previsível que a bio-acumulação dos POPs. O roaz-corvineiro e o bôto exibiram as concentrações mais elevadas de PCBs com respeito dos outros cetáceos odontocetes do NOPI e com respeito aos outros indivíduos de águas vizinhas do Oceano Atlântico Nordeste. Os principais resultados desta tese mostram a relevância destes parâmetros químicos como os traçadores ecológicos e a sua utilidade no estudo da estrutura e funcionamento dos ecossistemas através do papel dos predadores de topo. Combinando estes dados com a informação sobre as atividades antropogénicas, este trabalho pode contribuir ao desenvolvimento e implementação de planos de gestão e mitigação para estas cinco espécies de cetáceos odontocetes no NOPI.Le premier objectif de ce travail de thèse était de déterminer quel est le degré de ségrégation écologique entre cinq espèces sympatriques de cétacés odontocètes (i.e. le dauphin commun Delphinus delphis, le marsouin commun Phocoena phocoena, le grand dauphin tursiops truncatus, le dauphin bleu et blanc Stenella coeruleoalba et le globicéphale noir Globicephala melas) fréquentant l’aire marine restreinte et très productive du Nord-Ouest de la Péninsule Ibérique (NOPI). Pour cela, des paramètres chimiques ont été analysés dans les tissus biologiques, en tant que “ méthode alternative ” pouvant refléter de façon précise le régime alimentaire et l’habitat de ces animaux à différents échelles de temps d’intégration, et ainsi compléter les informations apportées par des méthodes plus traditionnelles tels que l’analyse des contenus stomacaux ou des fèces, ou encore les données d’observations en mer. Le second objectif de ce travail était d’évaluer l’état de contamination de ces espèces, pour acquérir une base de données de référence complète les concernant et estimer le risque toxicologique auquel elles peuvent faire face. Dans ce contexte, les éléments traces, les isotopes stables du carbone et de l’azote, et les polluants organiques persistants (POPs) sont les paramètres chimiques qui ont été sélectionnés pour répondre aux objectifs fixés. Dans un premier temps, les paramètres chimiques ont été utilisés comme traceurs écologiques des populations (ou de segments de population), procurant une image du régime alimentaire et de l’habitat des espèces à différentes échelles de temps. Nous avons calculé que le réseau trophique du NOPI avait cinq niveaux trophiques, au sein duquel les espèces étudiées occupaient les plus hautes positions, comprises entre 4,3 à 5,3, et sans qu’il y ait de différence significative de position trophiques entre les espèces. Alors que l’analyse d’un seul paramètre chimique ne permettait pas ségréger les cinq espèces, les informations apportées par l’analyse de plusieurs traceurs de long terme (i.e. rapport des isotopes stables du carbone et de l’azote dans les dents et concentrations de cadmium dans les reins) ont révélé une ségrégation de leur niche écologique dans deux des dimensions possibles (les dimensions trophique et spatiale). Cependant, les variations pouvant survenir d’une année sur l’autre ou saisonnières n’ont pas pu être étudiées, excepté pour le dauphin commun, et un chevauchement temporaire des niches ne peut donc pas être totalement exclu. De plus, nous avons montré que les profils de polychlorobiphényles (PCBs) pouvaient être un traceur pertinent de l’écologie trophique d’espèces taxinomiquement proches, en permettant une séparation fine des espèces telles que le marsouin commun et le dauphin bleu et blanc, d’après les différents profiles d’accumulation de ces deux espèces. Dans un second temps, l’état de contamination des espèces dans la zone d’étude a été évalué. Les concentrations ont été interprétées à la lumière des facteurs biologiques et écologiques pouvant influencer ces concentrations, et la bioaccumulation des éléments traces s’est révélée moins prévisible que celle des POPs. Le grand dauphin et le marsouin commun présentaient les concentrations de PCBs les plus élevées par rapport aux autres cétacés odontocètes du NOPI et par rapport à d’autres individus des eaux adjacentes de l’Atlantique Nord-Est. Les résultats principaux de ce travail de thèse ont mis en évidence la pertinence d’utiliser ces paramètres chimiques comme traceurs écologiques, et leur utilité dans la compréhension de la structure et le fonctionnement des écosystèmes à travers le rôle des prédateurs supérieurs. En combinant ces résultats à des informations concernant les activités anthropiques, ce travail peut contribuer au développement et à l’implémentation de mesures de gestion pour ces cinq espèces de cétacés odontocètes du NOPI.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/36766/200

IL-6 Trans-Signaling in the Brain Influences the Metabolic Phenotype of the 3xTg-AD Mouse Model of Alzheimer's Disease

Altres ajuts: Fundació La Marató de TV3 (20142210)Alzheimer's disease (AD) is a neurodegenerative disorder that causes the most prevalent dementia in the elderly people. Obesity and insulin resistance, which may cause major health problems per se, are risk factors for AD, and cytokines such as interleukin-6 (IL-6) have a role in these conditions. IL-6 can signal either through a membrane receptor or by trans-signaling, which can be inhibited by the soluble form of the co-receptor gp130 (sgp130). We have addressed the possibility that blocking IL-6 trans-signaling in the brain could have an effect in the triple transgenic 3xTg-AD mouse model of AD and/or in obesity progression, by crossing 3xTg-AD mice with GFAP-sgp130Fc mice. To serve as control groups, GFAP-sgp130Fc mice were also crossed with C57BL/6JOlaHsd mice. Seventeen-month-old mice were fed a control diet (18% kcal from fat) and a high-fat diet (HFD; 58.4% kcal from fat). In our experimental conditions, the 3xTg-AD model showed a mild amyloid phenotype, which nevertheless altered the control of body weight and related endocrine and metabolic factors, suggestive of a hypermetabolic state. The inhibition of IL-6 trans-signaling modulated some of these traits in both 3xTg-AD and control mice, particularly during HFD, and in a sex-dependent manner. These experiments provide evidence of IL-6 trans-signaling playing a role in the CNS of a mouse model of AD

Factors associated with adherence to immunomodulator treatment in people with multiple sclerosis

Abstract To determine the association between factors and adherence to immunomodulator treatment in people with multiple sclerosis treated in reference centers. Cross-sectional study conducted with 188 people who used immunomodulators in three reference centers in Ceará from March to July 2012. Adherence was assessed using the Moriskscale and factors were assessed using a questionnaire addressing socioeconomic and personal characteristics, the disease, the use of immunomodulator and educational activities. The determination of the association was expressed in crude and adjusted odds ratio with a 95% confidence interval. Adherence rate was 46% and after the logistic regression model the adherence to immunomodulator treatment was positively associated with the following factors: age 18-38 years, time of diagnosis and treatment between 6 and 24 months, 0-3.5 score in the Expanded Disability Status Scale, perception of treatment benefits, intrinsic and extrinsic motivation, phone contact with the doctor and not missing the return visit. This study is important because it allowed to determine the association between factors and adherence to immunomodulator treatment in multiple sclerosis, contributing to prevention and control actions

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19

Background. COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods. A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results. The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). Conclusions. SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.This work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 – 170357), Research Nova Scotia (DJK), Atlantic Genome/Genome Canada (DJK), Li-Ka Shing Foundation (DJK), Dalhousie Medical Research Foundation (DJK), the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO–COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and fnally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la fnanciación de proyectos de investigación en enfermedad COVID-19” (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Infammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript

The Eighteenth Data Release of the Sloan Digital Sky Surveys: Targeting and First Spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Comment: Accepted to ApJ

The eighteenth data release of the Sloan Digital Sky Surveys : targeting and first spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Publisher PDFPeer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Contamination en DDT chez les mammifères marins. Région marine Manche-Atlantique

La présente fiche indicateur candidat concerne l’évaluation de la contamination en DDT chez les mammifères marins du plateau continental au-delà de l’emprise des masses d’eaux côtières des Sous-Régions Marines Manche – Mer du Nord (MMN), Mers Celtiques (MC) et Golfe de Gascogne (GdG). Du fait de leur persistance, bioaccumulation dans les réseaux trophiques et de leur toxicité, les dichlorodiphényltrichloroéthane (DDT) sont listés « Polluants Organiques Persistants » (POP) par la convention de Stockholm. Le DDT et ses métabolites majoritaires (notamment le pp’DDE) sont utilisés comme indicateurs communs par OSPAR et font également partie de la liste des substances prioritaires de la directive cadre sur l’eau (DCE 2013/39/UE). Leurs concentrations sont mesurées dans la graisse sous-cutanée des deux espèces de mammifères (le dauphin commun en MC et GdG et le marsouin en MMN, MC et GdG) échantillonnés entre 2001 et 2019 lors des échouages aléatoires de carcasses sur le littoral, et dans le cadre du suivi « Contaminants chez les cétacés des côtes françaises ». Les concentrations en DDT dans les dauphins communs et dans les marsouins communs analysés ne présentent pas de tendance temporelle significative (p-value > 0,05) sur les trois SRM de la façade Manche-Atlantique