Evidence for seasonal cycles in deep-sea fish abundances: A great migration in the deep SE Atlantic?

Animal migrations are of global ecological significance, providing mechanisms for the transport of nutrients and energy between distant locations. In much of the deep sea (>200 m water depth), the export of nutrients from the surface ocean provides a crucial but seasonally variable energy source to seafloor ecosystems. Seasonal faunal migrations have been hypothesized to occur on the deep seafloor as a result, but have not been documented. Here, we analyse a 7.5‐year record of photographic data from the Deep‐ocean Environmental Long‐term Observatory Systems seafloor observatories to determine whether there was evidence of seasonal (intra‐annual) migratory behaviours in a deep‐sea fish assemblage on the West African margin and, if so, identify potential cues for the behaviour. Our findings demonstrate a correlation between intra‐annual changes in demersal fish abundance at 1,400 m depth and satellite‐derived estimates of primary production off the coast of Angola. Highest fish abundances were observed in late November with a smaller peak in June, occurring approximately 4 months after corresponding peaks in primary production. Observed changes in fish abundance occurred too rapidly to be explained by recruitment or mortality, and must therefore have a behavioural driver. Given the recurrent patterns observed, and the established importance of bottom‐up trophic structuring in deep‐sea ecosystems, we hypothesize that a large fraction of the fish assemblage may conduct seasonal migrations in this region, and propose seasonal variability in surface ocean primary production as a plausible cause. Such trophic control could lead to changes in the abundance of fishes across the seafloor by affecting secondary production of prey species and/or carrion availability for example. In summary, we present the first evidence for seasonally recurring patterns in deep‐sea demersal fish abundances over a 7‐year period, and demonstrate a previously unobserved level of dynamism in the deep sea, potentially mirroring the great migrations so well characterized in terrestrial systems

The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease

Expression of Human Beta-Defensins in Children with Chronic Inflammatory Bowel Disease

Background: Human beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children. Methods: Intestinal biopsies were obtained from the duodenum (n = 88), terminal ileum (n = 90) and ascending colon (n = 105) of children with Crohn’s disease (n = 26), ulcerative colitis (n = 11) and healthy controls (n = 16). Quantitative realtime (RT) PCR was performed and absolute mRNA copy numbers analyzed for hBD1-3 as well as inflammatory cytokines IL-8 and TNF-alpha. Results: Significant induction of hBD2 and hBD3 was observed in the inflamed terminal ileum and ascending colon of IBD children. In the ascending colon induction of hBD2 was found to be significantly lower in children with Crohn’s disease compared to ulcerative colitis. A strong correlation was found between inducible defensins hBD2 and 3 and the inflammatory cytokines IL-8 and TNF-alpha, both in the terminal ileum and ascending colon. Conclusion: Our study demonstrates distinct changes in hBD expression throughout the intestinal tract of children with IBD

HNF4A and GATA6 loss reveals therapeutically actionable subtypes in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC

Do público e do privado: uma perspectiva de género sobre uma dicotomia moderna

Neste texto propomos uma interpretação crítica da dicotomia histórica entre público e privado como dinâmica fundamental da modernidade. A partir de uma perspectiva de género, discutimos as fronteiras construídas entre espaço coletivo de cidadania e de sociabilidade e espaço individual de intimidade e desigualdade. Argumentamos a favor de uma relação de cumplicidade, ainda que tensa, entre as duas esferas, observando que a vida privada foi, em grande medida, moldada pelas mudanças operadas na vida pública. Recorrendo a diferentes definições de "público", notamos que, à medida que as sociabilidades tradicionais, essencialmente masculinas, estudadas entre outros por Ariès ou Sennett, sofriam uma erosão, crescia o sentimento de intimidade, aumentando igualmente a inclusão do privado no público através do alargamento da cidadania, em consequência das lutas travadas na esfera pública por vários movimentos de emancipação, como o operário ou o feminista. À medida que a pessoa era retirada da comunidade, do clã, do grupo de parentesco, em que eram "naturais" as desigualdades, no sentido aristotélico do termo, ia-se reencontrando progressivamente como indivíduo portador de cidadania. Se o espaço privado se tornou central na definição de uma identidade, ele é também crescentemente atravessado por mecanismos públicos de regulação. Nesse sentido, o movimento de ascensão do privado, que nas últimas décadas tem ocupado espaço de debate, deve ser cuidadosamente reinterpretado

Clinical Experience in Adults and Children Treated with Intravenous Peramivir for 2009 Influenza A (H1N1) Under an Emergency IND Program in the United States

Peramivir, an investigational intravenous neuraminidase inhibitor, was given to 31 hospitalized patients with severe viral pneumonia during the 2009 H1N1 influenza pandemic under the Emergency IND regulations. The drug was generally well tolerated and associated with recovery in most patientes

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy