The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms

Objectives: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown. Methods: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1−/−) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues. Results: Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1−/− mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1−/− mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1−/− mice. Conclusions: Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity

Linkages between rapid climate variability and deep‐sea benthic foraminifera in the deep Subantarctic South Atlantic during the last 95 kyr

We present a high-resolution record of benthic foraminifera fauna from a sediment core retrieved from the South Cape Basin (Subantarctic South Atlantic) spanning the last glacial cycle (95 kyr). Information provided by benthic foraminiferal assemblages together with paleoclimate proxies from the same core allow us to interpret changes in the style of primary production (episodic vs sustained) in relation to abrupt climate oscillations. Our results indicate that fluctuations in the abundance of the phytodetritus- related species, Epistominella exigua, are concomitant with millennial scale high latitude climate perturbations. Episodic phytoplankton blooms increased during a negative mode of the bipolar seesaw, irrespective of the magnitude of the perturbation (i.e., HS versus non-H stadial events). We provide a hypothesis linking the frequency and intensity of these events to atmospheric perturbations, interhemispheric climate variability and millennial scale changes in atmospheric CO2. A notable exception to the overall pattern is the generally high abundance of E. exigua across the globally synchronous onset of glacial MIS 4, a period generally characterized by increased dustiness and low quality organic carbon as inferred by the percentage of the non-phytodetritus species. This highlights the special characteristics governing the onset of MIS 4 in the Subantarctic

Eficiência da iluminação pública - lâmpadas vapor de sódio de alta pressão v.s. tecnologia LED

O trabalho teve como principal objetivo a análise da comparação dos gastos entre duas variantes para a substituição das luminárias, da iluminação pública em fim de vida, tendo como referência a cidade de Macedo de Cavaleiros. Não se pretende elaborar qualquer comparação com as características técnicas nem com a repartição de benefícios entre autarquias e concessionários das redes de iluminação pública. Na escolha da melhor opção teve-se por base o critério CAL – Custo Atual Líquido uma vez que apenas foram comparados os gastos com as duas variantes. Pelo critério utilizado verifica-se que a opção mais favorável, em termos económicos, é a tecnologia LED. Dado que foram estimadas duas variáveis, a variação da tarifa e o preço das luminárias, foi elaborada uma análise de sensibilidade a qual indica que a instalação de tecnologia LED torna-se ainda mais favorável com as alterações das variáveis utilizadas na análise de sensibilidade.info:eu-repo/semantics/publishedVersio

Climate fluctuations during the Holocene in NW Iberia: high and low latitude linkages

International audienceHigh resolution benthic foraminiferal oxygen and carbon stable isotopes (?18O, ?13C) from core EUGC-3B are used here to infer rapid climatic changes for the last 8500 yr in the Ría de Muros (NW Iberian Margin). Benthic foraminiferal ?18O and ?13C potentially register migrations in the position of the hydrographic front formed between two different intermediate water masses: Eastern North Atlantic Central Water of subpolar origin (ENACWsp), and subtropical origin (ENACWsp). The isotopic records have been compared with two well established North Atlantic marine Holocene paleoceanographic records from low (Sea Surface Temperatures anomalies off Cape Blanc, NW Africa) and high latitudes (Hematite Stained Grains percentage, subpolar North Atlantic). This comparison clearly demonstrates that there is a strong link between high- and low-latitude climatic perturbations at centennial-millennial time scales during the Holocene. Spectral analyses also points at a pole-to-equator propagation of the so-called 1500 yr cycles. Our results demonstrate that during the Holocene, the NW Iberian Margin has undergone a series of cold episodes which are likely triggered at high latitudes in the North Atlantic and are rapidly propagated towards lower latitudes. Conceivably, the propagation of these rapid climatic changes involves a shift of atmospheric and oceanic circulatory systems and so a migration of the hydrographical fronts and water masses all along the North Atlantic area

A perceção do Assistente Social sobre o impacto da pandemia COVID-19 no processo de intervenção/acompanhamento no utente internado em UCCI

Ao longo do último ano, com o surgimento da doença SARS-COV 2 assistimos a grandes alterações ao nível económico, social e sanitário. O setor social e da saúde foram afetados com as consequências da pandemia e as instituições e os seus profissionais foram obrigados a adaptar-se e a reinventar os seus modos de trabalho. Também em contexto de Unidade de Cuidados Continuados Integrados (UCCI) houve necessidade de adaptação. OBJETIVO: Conhecer de que forma o Assistente Social (AS) que trabalha em UCCI perceciona o impacto da COVID-19 no processo de intervenção e acompanhamento dos utentes. METODOLOGIA: Grupo focal, estudo qualitativo. Elaboração de guião: foram definidas as dimensões a abordar através de indicadores que resultam em perguntas-tipo. Entrevista orientada via Zoom a 5 AS a trabalhar em UCCI, que aceitaram participar, selecionados aleatoriamente, por contatos telefónicos. A análise de conteúdo foi efetuada através do MAXQDA. CONCLUSÕES: Os efeitos da pandemia COVID-19 permitiram manter as atividades com as devidas adaptações de segurança impostas. O teletrabalho não constituiu uma opção viável dada a presença constante deste profissional na unidade. Os efeitos da pandemia nas relações, apesar dos constrangimentos apresentados pela impossibilidade de contactar presencialmente com utentes e seus familiares, o trabalho presencial foi determinante para o estabelecimento de laços e ligações. Ao nível institucional a articulação com outras instituições e a comunidade teve efeitos decisivos para que a Rede e os seus utentes continuem a beneficiar da qualidade na continuidade dos cuidados.info:eu-repo/semantics/publishedVersio

Morphologic and morphometric study of the musculus obliquus dorsalis of the dog

In the present investigation, the dorsal oblique muscle of the right ocular globe was removed from six adult dogs weighing 40-50 kg and analyzed by light microscopy. Muscle samples were taken from the central portion of the muscle belly, subsequently ultrafrozen, cut and stained with m-ATPase at pH 4.6. Fibers were classified as type I or type II according to their reaction to the m-ATPase and detailed morphologic and morphometric studies were made. The muscles showed two clearly distinct layers, a central layer and a peripheral layer, mainly composed of type II fibers. The fibers in the central layer were larger in size than those in the peripheral layer. The peculiar stratigraphy of the dorsal oblique muscle should be taken into account when performing analyses of this muscle and investigating the significance of the fiber types it contains.En el presente trabajo se han extraído, de los globos oculares derechos, de seis perros adultos de 40-50 kilogramos de peso, los músculos oblicuos dorsales y analizados con microscopia de luz. Las muestras musculares para su análisis se tomaron de la porción central del vientre muscular y fueron ultracongeladas, cortadas y teñidas por la técnica de m-ATPasa a pH 4,6. Las fibras se clasificaron en tipo I y tipo II en virtud a su reacción frente a la m-ATPasa, realizándose un detallado estudio morfológico y morfométrico. Los músculos presentaron dos estratos netamente diferenciados, uno central y otro periférico, compuestos mayoritariamente por fibras tipo II. Las fibras del estrato central presentaron un mayor tamaño que las correspondientes del estrato periférico. La peculiar estratigrafía del músculo oblicuo dorsal debería tenerse en consideración al analizar este músculo e investigar el significado de los tipos fibrilares que contien

MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex

The MYC axis is disrupted in cancer, predominantly through activation of the MYC family oncogenes but also through inactivation of the MYC partner MAX or of the MAX partner MGA. MGA and MAX are also members of the polycomb repressive complex, ncPRC1.6. Here, we use genetically modified MAX-deficient small-cell lung cancer (SCLC) cells and carry out genome-wide and proteomics analyses to study the tumor suppressor function of MAX. We find that MAX mutant SCLCs have ASCL1 or NEUROD1 or combined ASCL1/NEUROD1 characteristics and lack MYC transcriptional activity. MAX restitution triggers prodifferentiation expression profiles that shift when MAX and oncogenic MYC are coexpressed. Although ncPRC1.6 can be formed, the lack of MAX restricts global MGA occupancy, selectively driving its recruitment toward E2F6-binding motifs. Conversely, MAX restitution enhances MGA occupancy to repress genes involved in different functions, including stem cell and DNA repair/replication. Collectively, these findings reveal that MAX mutant SCLCs have either ASCL1 or NEUROD1 or combined characteristics and are MYC independent and exhibit deficient ncPRC1.6-mediated gene repression.We thank Isabel Bartolessis for technical assistance, the confocal facility (Carmen Casals) and the RNA-sequencing genomic facility (Anna Esteve) for important services. Funding: This work was supported by Spanish grant SAF2017-82186-RAEI/FEDER (UE) (to MSC) from the MINECO and a grant from the Fundación Científica Asociación Española Contra el Cancer- GCB14142170MONT (to MSC). M Torres-Diz was supported by the FPI-fellowship: BES- 2012-054579, P Llabata by the FPI-fellowship: BES-2015-072204 and by the European Association for Cancer Research Travel fellowship and L Tomas-Daza by the FPI-fellowship (number PRE2019-088005). BMJ is funded by Spanish Ministry of Science, Innovation, and Universities (MICINN) project number RTI2018-094788-A-I00 and by La Caixa Banking Foundation Junior Leader project (LCF/BQ/PI19/11690001). The proteomics analyses were performed in the IJC Proteomics Unit. The IJC Proteomics Unit is part of the Spanish Platform of Molecular and Bioinformatics Resources (ProteoRed), Instituto de Salud Carlos III (PT13/0001). Competing Interests: All authors declare no competing financial interests.Peer Reviewed"Article signat per 12 autors/es: Paula Llabata, Manuel Torres-Diz, Antonio Gomez, Laureano Tomas-Daza, Octavio A. Romero, Joaquim Grego-Bessa, Pere Llinas-Arias, Alfonso Valencia, Manel Esteller, Biola M. Javierre, Xiaoyang Zhang, and Montse Sanchez-Cespedes"Postprint (author's final draft

Steering cell migration by alternating blebs and actin-rich protrusions

Background High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. Results Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. Conclusions Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times

Optimization of ultrasound-assisted extraction to obtain mycosterols from Agaricus bisporus L. by response surface methodology and comparison with conventional Soxhlet extraction

Ergosterol, a molecule with high commercial value, is the most abundant mycosterol in Agaricus bisporus L. To replace common conventional extraction techniques (e.g. Soxhlet), the present study reports the optimal ultrasound-assisted extraction conditions for ergosterol. After preliminary tests, the results showed that solvents, time and ultrasound power altered the extraction efficiency. Using response surface methodology, models were developed to investigate the favourable experimental conditions that maximize the extraction efficiency. All statistical criteria demonstrated the validity of the proposed models. Overall, ultrasound-assisted extraction with ethanol at 375 W during 15 min proved to be as efficient as the Soxhlet extraction, yielding 671.5 ± 0.5mg ergosterol/100 g dw. However, with n-hexane extracts with higher purity (mg ergosterol/g extract) were obtained. Finally, it was proposed for the removal of the saponification step, which simplifies the extraction process and makes it more feasible for its industrial transference.The authors acknowledge FCT (Portugal) for financial support to CIMO (PEst-OE/AGUI0690/2014), Sandrina A. Heleno (SFRH/BPD/101413/2014) and L. Barros research contract, to FCT/MEC and FEDER under Programme PT2020 for financial support to LSRE (Project UID/EQU/50020/2013), and to QREN, ON2 and FEDER (Projects NORTE-07-0124-FEDER-000014 and NORTE-07-0162-FEDER-000050). Xunta de Galicia for financial support for the post-doctoral researcher of M.A. Prieto

Salud y enfermedad desde la perspectiva de los jóvenes. Un estudio en jóvenes escolarizados de la Ciudad de Buenos Aires

Se presentan los datos recogidos a través de la realización de una encuesta a jóvenes escolarizados de la Ciudad de Buenos Aires, acerca de sus conocimientos, actitudes y conductas en relación con la salud. El trabajo forma parte de un estudio más amplio que se enmarca en el Modelo de Escuelas Promotoras de Salud pro-puesto por la Organización Mundial de la Salud