Impacts of climate change on the biogeography of three amnesic shellfish toxin producing diatom species

Harmful algal blooms (HABs) are considered one of the main risks for marine ecosystems and human health worldwide. Climate change is projected to induce significant changes in species geographic distribution, and, in this sense, it is paramount to accurately predict how it will affect toxin-producing microalgae. In this context, the present study was intended to project the potential biogeographical changes in habitat suitability and occurrence distribution of three key amnesic shellfish toxin (AST)-producing diatom species (i.e., Pseudo-nitzschia australis, P. seriata, and P. fraudulenta) under four different climate change scenarios (i.e., RCP-2.6, 4.5, 6.0, and 8.5) up to 2050 and 2100. For this purpose, we applied species distribution models (SDMs) using four abiotic predictors (i.e., sea surface temperature, salinity, current velocity, and bathymetry) in a MaxEnt framework. Overall, considerable contraction and potential extirpation were projected for all species at lower latitudes together with projected poleward expansions into higher latitudes, mainly in the northern hemisphere. The present study aims to contribute to the knowledge on the impacts of climate change on the biogeography of toxin-producing miinfo:eu-repo/semantics/publishedVersio

Projecting future climate change-mediated impacts in Three Paralytic Shellfish Toxins-Producing dinoflagellate species

Simple Summary Harmful algal blooms present a particular risk for marine ecosystems and human health alike. In this sense, it is important to accurately predict how toxin-producing microalgae could be affected by future climate change. The present study applied species distribution models (SDMs) to project the potential changes in the habitat suitability and distribution of three key paralytic shellfish toxin (PST)-producing dinoflagellate species (i.e., Alexandrium catenella, A. minutum, and Gymnodinium catenatum), up to 2040/50 and 2090/2100, across four different greenhouse gas emission scenarios, and using four abiotic predictors (i.e., sea surface temperature, salinity, current velocity, and bathymetry). In general, considerable contractions were observed for all three species in the lower latitudes of their distribution, together with projected expansions into higher latitudes, particularly in the Northern Hemisphere. This study aims to entice further research on the future biogeographical impacts of climate change in toxin-producing microalgae species while, at the same time, helping to advise the correct environmental management of coastal habitats and ecosystems. Toxin-producing microalgae present a significant environmental risk for ecosystems and human societies when they reach concentrations that affect other aquatic organisms or human health. Harmful algal blooms (HAB) have been linked to mass wildlife die-offs and human food poisoning episodes, and climate change has the potential to alter the frequency, magnitude, and geographical extent of such events. Thus, a framework of species distribution models (SDMs), employing MaxEnt modeling, was used to project changes in habitat suitability and distribution of three key paralytic shellfish toxin (PST)-producing dinoflagellate species (i.e., Alexandrium catenella, A. minutum, and Gymnodinium catenatum), up to 2050 and 2100, across four representative concentration pathway scenarios (RCP-2.6, 4.5, 6.0, and 8.5; CMIP5). Despite slightly different responses at the regional level, the global habitat suitability has decreased for all the species, leading to an overall contraction in their tropical and sub-tropical ranges, while considerable expansions are projected in higher latitudes, particularly in the Northern Hemisphere, suggesting poleward distributional shifts. Such trends were exacerbated with increasing RCP severity. Yet, further research is required, with a greater assemblage of environmental predictors and improved occurrence datasets, to gain a more holistic understanding of the potential impacts of climate change on PST-producing species.info:eu-repo/semantics/publishedVersio

Behavioral patterns that increase or decrease risk of abdominal adiposity in adults

The identification of risk or protective behavioral patterns associated with abdominal adiposity may aid in prevention and health promotion measures. To identify and to associate behavioral patterns of risk and protection to abdominal adiposity in adults in a Brazilian city. Material and methods: A population-based cross-sectional study was carried out in Viçosa, Brazil, with 1,226 adults of both sexes. Information on social-demographic characteristics, food intake, level of physical activity, alcohol consumption and smoking were collected by using a questionnaire. The anthropometric measurement of waist circumference and anthropometric indices waist/hip ratio and waist/height ratio were indicators of abdominal adiposity. To identify behavioral patterns, exploratory factor analysis was applied for the variables considered as risk or protective factors. The association of the identified patterns with abdominal adiposity was estimated by multiple linear regression, adjusted for gender, age and social economical class. Two patterns were obtained, “healthy” and “risk”. The “healthy” pattern, comprised of the clustering of the variables food consumption, fruits, fresh fruit juices, raw and cooked vegetables and the appropriate level of physical activity, was negatively associated with abdominal adiposity identified by waist circumference (p = 0.048), waist/hip (p = 0.013) and waist/height (p = 0.018) indices. The “risk” pattern, composed of smoking, alcohol beverage abuse and habit of consuming visible fat in fat-rich red meat or poultry skin, was positively associated with abdominal adiposity identified by waist circumference (p = 0.002) and waist/hip (p = 0.007) and waist/height indices (p = 0.006). Two behavioral patterns were identified, a risk pattern and a protective pattern for abdominal adiposity in the assessed population. The study shows the importance of conducting clustering of multiple risk and protective factors to better explain the health conditions of a group.la identificación de los riesgos o los patrones de comportamiento de protección asociados con la adiposidad abdominal puede ayudar en las medidas de prevención y promoción de la salud. identificar y establecer la asociación entre los patrones de comportamiento de riesgo y de protección y la adiposidad abdominal en adultos en una ciudad brasileña. Material y métodos: se llevó a cabo un estudio transversal basado en la población en Viçosa, Brasil, con 1.226 adultos de ambos sexos. Se recogió información sobre las características sociodemográficas, la ingesta de alimentos, el nivel de actividad física, el consumo de bebidas alcohólicas y el hábito tabáquico mediante un cuestionario. La medición antropométrica de la circunferencia de la cintura y de los índices antropométricos cintura/cadera y cintura/altura fueron los indicadores de adiposidad abdominal. Para identificar los patrones de comportamiento, se aplicó un análisis factorial exploratorio de las variables de riesgo o factores de protección considerados. La asociación de los patrones identificados con la adiposidad abdominal se estimó por regresión lineal múltiple, ajustada por género, edad y nivel socioeconómico. Se establecieron dos patrones, “sano” y “riesgo”. El patrón “sano”, compuesto por la agrupación de las variables consumo de alimentos, frutas, zumos de fruta fresca, verdura cruda y cocida y el nivel apropiado de actividad física, se asoció negativamente con la adiposidad abdominal identificada por la circunferencia de la cintura (p = 0,048) y los índices cintura/cadera (p = 0,013) y cintura/altura (p = 0,018). El patrón de “riesgo”, compuesto por hábito tabáquico, abuso de alcohol y consumo de grasa visible en carnes rojas ricas en grasa o piel de las aves, se asoció positivamente con la adiposidad abdominal identificada por la circunferencia de la cintura (p = 0,002) y las ratios intura/cadera (p = 0,007) y cintura/altura (p = 0,006). Fueron identificados dos patrones de comportamiento, el patrón de riesgo y el patrón de protección, relacionados con la adiposidad abdominal en la población estudiada. El estudio muestra la importancia de agrupar múltiples factores de riesgo y de protección para explicar mejor las condiciones de salud de un grupo

Gymnodinium catenatum paralytic Shellfish toxin production and photobiological responses under marine heat waves

Marine heatwaves (MHWs) have doubled in frequency since the 1980s and are projected to be exacerbated during this century. MHWs have been shown to trigger harmful algal blooms (HABs), with severe consequences to marine life and human populations. Within this context, this study aims to understand, for the first time, how MHWs impact key biological and toxicological parameters of the paralytic shellfish toxin (PST) producer Gymnodinium catenatum, a dinoflagellate inhabiting temperate and tropical coastal waters. Two MHW were simulated—category I (i.e., peak: 19.9 ◦C) and category IV (i.e., peak: 24.1 ◦C)—relative to the estimated baseline in the western coast of Portugal (18.5 ◦C). No significant changes in abundance, size, and photosynthetic efficiency were observed among treatments. On the other hand, chain-formation was significantly reduced under category IV MHW, as was PSP toxicity and production of some PST compounds. Overall, this suggests that G. catenatum may have a high tolerance to MHWs. Nevertheless, some sublethal effects may have occurred since chain-formation was affected, suggesting that these growth conditions may be sub-optimal for this population. Our study suggests that the increase in frequency, intensity, and duration of MHWs may lead to reduced severity of G. catenatum blooms.info:eu-repo/semantics/publishedVersio

Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

R.F. and acknowledge the funding from the Fundação para a Ciência e Tecnologia (FCT), Portugal. S.B. was supported by CDG & Allies—PAIN funding. M.A. acknowledges PhD program at the DISTABIF, Università degli Studi della Campania “Luigi Vanvitelli”, PhD fellowship POR Campania FSE 2014/2020 “Dottorati di Ricerca Con Caratterizzazione Industriale”.Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders' views on AI for therapy discovery in CDG.publishersversionpublishe

UMA RELAÇÃO ENTRE DESIGN E PERCEPÇÃO DE DESCONFORTO EM CARROS DE COMPETIÇÃO BAJA SAE

Design, Vehicles' Ergonomics, Comfort The present paper analyses the relationship between design and comfort among pilots of Baja SAE competitionvehicles. The results indicate that differences between the two models under evaluation, affected the room available to use the control-panel, the driver's posture, and consequently;  the comfort in the cockpit. The paper ends by recommending changes in the design to improve its ergonomic aspects.Design, Ergonomia de transporte, Conforto O presente artigo analisa a influência do design na percepção de conforto em pilotos do veículo de competição BAJA SAE. Os resultados indicam que diferenças nos designs de dois modelos, afetaram o espaço livre de manuseio dos controles, a postura, e consequentemente a sensação de conforto. O artigo encerra recomendando ajustes para um design mais ergonômico

Receptor-Induced Dilatation in the Systemic and Intrarenal Adaptation to Pregnancy in Rats

Normal pregnancy is associated with systemic and intrarenal vasodilatation resulting in an increased glomerular filtration rate. This adaptive response occurs in spite of elevated circulating levels of angiotensin II (Ang II). In the present study, we evaluated the potential mechanisms responsible for this adaptation. The reactivity of the mesangial cells (MCs) cultured from 14-day-pregnant rats to Ang II was measured through changes in the intracellular calcium concentration ([Cai]). The expression levels of inducible nitric oxide synthase (iNOS), the Ang II-induced vasodilatation receptor AT2, and the relaxin (LGR7) receptor were evaluated in cultured MCs and in the aorta, renal artery and kidney cortex by real time-PCR. The intrarenal distribution of LGR7 was further analyzed by immunohistochemistry. The MCs displayed a relative insensitivity to Ang II, which was paralleled by an impressive increase in the expression level of iNOS, AT2 and LGR7. These results suggest that the MCs also adapt to the pregnancy, thereby contributing to the maintenance of the glomerular surface area even in the presence of high levels of Ang II. The mRNA expression levels of AT2 and LGR7 also increased in the aorta, renal artery and kidney of the pregnant animals, whereas the expression of the AT1 did not significantly change. This further suggests a role of these vasodilatation-induced receptors in the systemic and intrarenal adaptation during pregnancy. LGR7 was localized in the glomeruli and on the apical membrane of the tubular cells, with stronger labeling in the kidneys of pregnant rats. These results suggest a role of iNOS, AT2, and LGR7 in the systemic vasodilatation and intrarenal adaptation to pregnancy and also suggest a pivotal role for relaxin in the tubular function during gestation

Invariant Natural Killer T Cell Agonist Modulates Experimental Focal and Segmental Glomerulosclerosis

A growing body of evidence demonstrates a correlation between Th2 cytokines and the development of focal and segmental glomerulosclerosis (FSGS). Therefore, we hypothesized that GSL-1, a monoglycosylceramide from Sphingomonas ssp. with pro-Th1 activity on invariant Natural Killer T (iNKT) lymphocytes, could counterbalance the Th2 profile and modulate glomerulosclerosis. Using an adriamycin(ADM)-based model of FSGS, we found that BALB/c mice presented albuminuria and glomerular degeneration in association with a Th2-like pro-fibrogenic profile; these mice also expressed a combination of inflammatory cytokines, such as IL-4, IL-1α, IL-1β, IL-17, TNF-α, and chemokines, such as RANTES and eotaxin. In addition, we observed a decrease in the mRNA levels of GD3 synthase, the enzyme responsible for GD3 metabolism, a glycolipid associated with podocyte physiology. GSL-1 treatment inhibited ADM-induced renal dysfunction and preserved kidney architecture, a phenomenon associated with the induction of a Th1-like response, increased levels of GD3 synthase transcripts and inhibition of pro-fibrotic transcripts and inflammatory cytokines. TGF-β analysis revealed increased levels of circulating protein and tissue transcripts in both ADM- and GSL-1-treated mice, suggesting that TGF-β could be associated with both FSGS pathology and iNKT-mediated immunosuppression; therefore, we analyzed the kidney expression of phosphorylated SMAD2/3 and SMAD7 proteins, molecules associated with the deleterious and protective effects of TGF-β, respectively. We found high levels of phosphoSMAD2/3 in ADM mice in contrast to the GSL-1 treated group in which SMAD7 expression increased. These data suggest that GSL-1 treatment modulates the downstream signaling of TGF-β through a renoprotective pathway. Finally, GSL-1 treatment at day 4, a period when proteinuria was already established, was still able to improve renal function, preserve renal structure and inhibit fibrogenic transcripts. In conclusion, our work demonstrates that the iNKT agonist GSL-1 modulates the pathogenesis of ADM-induced glomerulosclerosis and may provide an alternative approach to disease management

Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Mutational analysis of the <it>KRAS </it>gene has recently been established as a complementary <it>in vitro </it>diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of <it>KRAS </it>might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although <it>KRAS </it>is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of <it>KRAS </it>in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.</p> <p>Methods</p> <p>Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. <it>KRAS </it>mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type <it>KRAS </it>or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.</p> <p>Results</p> <p>We found no evidence of <it>KRAS </it>oncogenic mutations in all analyzed tumors.</p> <p>Conclusions</p> <p>This study indicates that <it>KRAS </it>mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.</p