O linguado do Senegal (Solea senegalensis) apresenta um elevado valor comercial, sendo bastante procurado, não só nos mercados da Península Ibérica, mas também amplamente na Europa. Nos últimos 30 ...anos, atraiu importantes pesquisas e desenvolvimentos na metodologia de produção, bem como consideráveis investimentos, sendo uma das espécies que tem sido identificada com maior potencial e interesse comercial na aquacultura marinha.O presente estudo teve como objectivo geral a optimização de um protocolo de produção de S. senegalensis em regime semi-intensivo e em policultura com Sparus aurata (dourada) e/ou Dicentrarchus labrax (robalo), mantendo padrões de bem-estar animal elevados e avaliando a sua viabilidade. Foi ainda associado a este objectivo a utilização e rentabilização de lotes de alevins “cauda” (que em regime intensivo seriam eliminados) e a avaliação da possibilidade de obter um produto de elevada qualidade e valor comercial acrescido. Como objectivos específicos, o estudo pretendeu: identificar a melhor estratégia de policultura em termos de combinação de espécies; definir as densidades óptimas de linguado e da espécie de cultivo (robalo e/ou dourada); definir as épocas do ano ideais para a introdução do linguado; elucidar sobre o tipo de sedimento ideal para o crescimento de linguado e perceber a eventual influência da latitude da unidade de produção.Foram seleccionadas 4 pisciculturas - Riáqua (Aveiro), Nasharyba (Figueira da Foz), Aqualvor (Lavos) e Tideland 2000 (Aiamonte – sul de Espanha) - de acordo com uma distribuição geográfica (abarcando uma grande amplitude de condições ambientais) e representando contextos de produção diversos. O estudo abrangeu um período médio de 12 meses. De um modo geral, todos os tanques de todas as pisciculturas apresentaram crescimentos positivos (à excepção do tanque 9.1 da Tideland 2000), traduzindo uma boa adaptabilidade do linguado às condições impostas. Destacaram-se as pisciculturas Nasharyba e Aqualvor, que apresentaram os maiores valores médios de peso ganho (103 e 128g), taxa de crescimento específica (0,25 %/dia e 0,32 %/dia), factor de condição (1,54 e 1,56), e produtividade (0,127 g/m2 /dia e 0,178 g/m2 /dia), respectivamente.As análises comparativas intra- e inter-piscicultura permitiram apontar como vantajosa a presença de sedimento do tipo vasoso e a adopção de baixas densidades de linguado, embora todas as densidades testadas (0,01 - 0,04 kg/m3 ) se tenham mostrado viáveis.Foi possível perceber a ampla elasticidade do linguado relativamente às diferentes densidades utilizadas para a espécie em co-cultura (0,06 - 1,83 kg/m3 ), assim como a sua adaptabilidade a diferentes latitudes com as inerentes diferenças de parâmetros ambientais (ex. temperatura).Não foi encontrada uma estratégia explícita de policultura em termos de combinação de espécies. Contudo, foi possível verificar que quando uma piscicultura apresenta uma produção apenas ou maioritariamente de robalo, é de extrema importância optar por combinar uma percentagem adequada de dourada, pois impede o crescimento excessivo de macroalgas.Os resultados sugerem ainda como prática ideal a introdução de linguado em Novembro, usando alevins com peso médio inicial de 80 a 90 g.Independentemente dos condicionalismos encontrados, globalmente, os resultados obtidos contribuíram para construir as linhas gerais de um protocolo de produção de linguado do Senegal em regime semi-intensivo e em policultura com dourada e/ou robalo, demonstrando a sua viabilidade.
Microglia play a critical role in maintaining neural function. While microglial activity follows a circadian rhythm, it is not clear how this intrinsic clock relates to their function, especially in ...stimulated conditions such as in the control of systemic energy homeostasis or memory formation. In this study, we found that microglia-specific knock-down of the core clock gene, Bmal1, resulted in increased microglial phagocytosis in mice subjected to high-fat diet (HFD)-induced metabolic stress and likewise among mice engaged in critical cognitive processes. Enhanced microglial phagocytosis was associated with significant retention of pro-opiomelanocortin (POMC)-immunoreactivity in the mediobasal hypothalamus in mice on a HFD as well as the formation of mature spines in the hippocampus during the learning process. This response ultimately protected mice from HFD-induced obesity and resulted in improved performance on memory tests. We conclude that loss of the rigorous control implemented by the intrinsic clock machinery increases the extent to which microglial phagocytosis can be triggered by neighboring neurons under metabolic stress or during memory formation. Taken together, microglial responses associated with loss of Bmal1 serve to ensure a healthier microenvironment for neighboring neurons in the setting of an adaptive response. Thus, microglial Bmal1 may be an important therapeutic target for metabolic and cognitive disorders with relevance to psychiatric disease.
Tissue-resident macrophages can self-maintain without contribution of adult hematopoiesis. Herein we show that tissue-resident interstitial macrophages (Res-TAMs) in mouse lungs contribute to the ...pool of tumor-associated macrophages (TAMs) together with CCR2-dependent recruited macrophages (MoD-TAMs). Res-TAMs largely correlated with tumor cell growth in vivo, while MoD-TAMs accumulation was associated with enhanced tumor spreading. Both cell subsets were depleted after chemotherapy, but MoD-TAMs rapidly recovered and performed phagocytosis-mediated tumor clearance. Interestingly, anti-VEGF treatment combined with chemotherapy inhibited both Res and Mod-TAM reconstitution without affecting monocyte infiltration and improved its efficacy. Our results reveal that the developmental origin of TAMs dictates their relative distribution, function, and response to cancer therapies in lung tumors.
A low allele burden (i.e., <20%) of the CALR driver mutation is found in 10.8% of CALR‐mutated MPNs, mostly in essential thrombocythemia, and correlates with a milder phenotype and a more indolent ...evolution compared to patients with an allele burden ≥20%.
Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such ...as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies.
Objectives
Impairment of type I interferon (IFN‐I) immunity has been reported in critically ill COVID‐19 patients. This defect can be explained in a subset of patients by the presence of circulating ...autoantibodies (auto‐Abs) against IFN‐I. We set out to improve the detection and the quantification of IFN‐I auto‐Abs in a cohort of critically ill COVID‐19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease.
Methods
The concentration of anti‐IFN‐α2 Abs was determined in the serum of 84 critically ill COVID‐19 patients who were admitted to ICU in Hospices Civils de Lyon, France, using a commercially available kit (Thermo Fisher, Catalog #BMS217).
Results
A total of 21 of 84 (25%) critically ill COVID‐19 patients had circulating anti‐IFN‐α2 Abs above cut‐off (> 34 ng mL−1). Among them, 15 of 21 had Abs with neutralising activity against IFN‐α2, that is 15 of 84 (18%) critically ill patients. In addition, we noticed an impairment of the IFN‐I response in the majority of patients with neutralising anti‐IFN‐α2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralising anti‐IFN‐α2 auto‐Abs. We detected anti‐IFN‐α2 auto‐Abs in COVID‐19 patients' sera throughout their ICU stay. Finally, we also found auto‐Abs against multiple subtypes of IFN‐I including IFN‐ω.
Conclusions
We reported that 18% of critically ill COVID‐19 patients were positive for IFN‐I auto‐Abs, whereas all mild COVID‐19 patients were negative, confirming that the presence of these antibodies is associated with a higher risk of developing a critical COVID‐19 form.
We report here that 18% of severe COVID‐19 patients were positive for autoantibodies able to neutralize type I interferon (IFN). This finding further confirms the deleterious role of IFN‐I auto‐Abs in the antiviral immune response supporting the use of recombinant type I IFNs not targeted by the auto‐Abs (e.g. IFN‐β) in COVID‐19 patients with an impairment of the IFN‐I response.
Cancer progression is driven in part by genomic alterations
. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations
, leading to the concept that ...generation of genomic profiling in patients with cancer could allow the selection of effective therapies
. Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462 patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment
with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as level I/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)
(adjusted hazards ratio (HR): 0.41, 90% confidence interval (CI): 0.27-0.61, P < 0.001), but not when alterations are unselected using ESCAT (adjusted HR: 0.77, 95% CI: 0.56-1.06, P = 0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR: 1.15, 95% CI: 0.76-1.75) for patients presenting with ESCAT alteration beyond level I/II. Patients with germline BRCA1/2 mutations (n = 49) derived high benefit from olaparib (gBRCA1: HR = 0.36, 90% CI: 0.14-0.89; gBRCA2: HR = 0.37, 90% CI: 0.17-0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer.
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