Trade-offs between risk of predation and starvation in larvae make the shelf break an optimal spawning location for Atlantic Bluefin tuna

Atlantic bluefin tuna (ABT) (Thunnus thynnus) travel long distances to spawn in oligotrophic regions of the Gulf of Mexico (GoM) which suggests these regions offer some unique benefit to offspring survival. To better understand how larval survival varies within the GoM a spatially explicit, Lagrangian, individual-based model was developed that simulates dispersal and mortality of ABT early life stages within realistic predator and prey fields during the spawning periods from 1993 to 2012. The model estimates that starvation is the largest cumulative source of mortality associated with an early critical period. However, elevated predation on older larvae is identified as the main factor limiting survival to late postflexion. As a result, first-feeding larvae have higher survival on the shelf where food is abundant, whereas older larvae have higher survival in the open ocean with fewer predators, making the shelf break an optimal spawning area. The modeling framework developed in this study explicitly simulates both physical and biological factors that impact larval survival and hence could be used to support ecosystem based management efforts for ABT under current and future climate conditions.Postprin

Targeting the Ataxia Telangiectasia Mutated-null Phenotype in Chronic Lymphocytic Leukemia with Pro-oxidants

Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting. We found that in comparison to Ataxia Telangiectasia Mutated-wild type chronic lymphocytic leukemia, pro-oxidant treatment of Ataxia Telangiectasia Mutated-null cells led to reduced binding of NF-E2 p45-related factor-2 to antioxidant response elements and thus decreased expression of target genes. Furthermore, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia cells contained lower levels of antioxidants and elevated mitochondrial reactive oxygen species. Consequently, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia, but not tumours with 11q deletion or TP53 mutations, exhibited differentially increased sensitivity to pro-oxidants both in vitro and in vivo. We found that cell death was mediated by a p53- and caspase-independent mechanism associated with apoptosis inducing factor activity. Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia

Reconstructing the Cosmic Expansion History up to Redshift z=6.29 with the Calibrated Gamma-Ray Bursts

Recently, Gamma-Ray Bursts (GRBs) were proposed to be a complementary cosmological probe to type Ia supernovae (SNIa). GRBs have been advocated to be standard candles since several empirical GRB luminosity relations were proposed as distance indicators. However, there is a so-called circularity problem in the direct use of GRBs. Recently, a new idea to calibrate GRBs in a completely cosmology independent manner has been proposed, and the circularity problem can be solved. In the present work, following the method proposed by Liang {\it et al.}, we calibrate 70 GRBs with the Amati relation using 307 SNIa. Then, following the method proposed by Shafieloo {\it et al.}, we smoothly reconstruct the cosmic expansion history up to redshift $z=6.29$ with the calibrated GRBs. We find some new features in the reconstructed results.Comment: 12 pages, 4 figures, 1 table, revtex4; v2: title changed, accepted by Eur. Phys. J. C; v3: published versio

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Resistência anti-helmíntica em rebanhos caprinos no Estado do Ceará Anthelmintic resistance in goat herds in the State of Ceará

Um levantamento em nível de campo sobre resistência anti-helmíntica em nematódeos gastrintestinais de caprinos foi realizado em 34 rebanhos no Estado do Ceará. Em cada rebanho foram separados 30 cabritos, de ambos os sexos, com idade variando de 1 a 6 meses, os quais foram individualmente pesados, identificados e distribuídos em três tratamentos: 1) Oxfendazole na dose de 4,75mg/kg; 2) Levamisole na dose de 7,5 mg/kg e 3) Controle (não medicado). Os anti-helmínticos foram administrados de acordo com o peso individual de cada animal e, a dosagem utilizada para cada produto foi a recomendada pelo laboratório fabricante. Foram colhidas fezes dos animais de todos os tratamentos, para OPG e coprocultura, no dia da medicação e 7 dias após. Dos 34 rebanhos avaliados, 7 (20,6%) apresentaram resistência aos imidazóis, 6 (17,6%) aos benzimidazóis e 12 (35,3%) revelaram resistência múltipla. Apenas em 9 rebanhos (26,5%), os nematódeos foram sensíveis aos anti-helmínticos avaliados. Através do questionário aplicado detectou-se que 52,9% dos caprinocultores entrevistados usavam anti-helmínticos de amplo espectro. Os resultados das coproculturas mostraram que os gêneros sobreviventes à medicação com oxfendazole foram principalmente Haemonchus sp, seguido em menor frequência por Oesophagostomum sp, enquanto que ao cloridrato de levamisole sobreviveram Haemonchus sp, Oesophagostomum sp e Trichostrongylus sp.<br>Goats of 45 farms in the State of Ceará, Brazil, were treated with anthelmintics for gastrointestinal nematodes, and their resistance to the anthelmintics was evaluated. On each farm 30 kids were weighed, ear-tagged and divided into three groups of ten. The first group received oxfendazole at 4.75mg/kg, the second levamisole at 7.5mg/kg, and the third group remained untreated as control. All goats were drenched according to their individual body weight. Fecal samples were collected from all animals (treated and control) on the day of treatment and 7 days later, to provide material for egg counts and larval cultures. Among 34 surveyed herds 20.6% showed levamisole resistance, 17.6% showed resistance to benzimidazole, and 35.3% had multiple resistance. At the time of the assessment 52.9% of the farmers were using broad spectrum anthelmintics. Only 26.5% of the surveyed herds had nematode populations susceptible to the anthelmintics assessed. The results of larval cultures showed that larvae surviving the treatment with oxfendazole were mainly Haemonchus sp and, to a lesser extent, Oesophagostomum sp; those surviving levamisole treatment were Haemonchus sp, Oesophagostomum sp and Trichostrongylus sp