Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression

Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular mechanisms of their angiogenesis are not fully delineated. The aim of this study is to evaluate angiogenesis and expression of HIF-related molecules in a series of patients with pancreatic endocrine tumours (PETs). The expression of vascular endothelial growth factor (VEGF), HIF-1α, HIF-2α and carbonic anhydrase 9 (CA9) was examined by immunohistochemistry in 45 patients with PETs and compared to microvascular density (MVD), endothelial proliferation, tumour stage and survival. Microvascular density was very high in PETs and associated with a low endothelial index of proliferation. Microvascular density was significantly higher in benign PETs than in PETs of uncertain prognosis, well-differentiated and poorly differentiated carcinomas (mean values: 535, 436, 252 and 45 vessels mm−2, respectively, P<0.0001). Well-differentiated tumours had high cytoplasmic VEGF and HIF-1α expression. Poorly differentiated carcinomas were associated with nuclear HIF-1α and membranous CA9 expression. Low MVD (P=0.0001) and membranous CA9 expression (P=0.0004) were associated with a poorer survival. Contrary to other types of cancer, PETs are highly vascularised, but poorly angiogenic tumours. As they progress, VEGF expression is lost and MVD significantly decreases. The regulation of HIF signalling appears to be specific in pancreatic endocrine tumours

The future of biotic indices in the ecogenomic era: Integrating (e)DNA metabarcoding in biological assessment of aquatic ecosystems

The bioassessment of aquatic ecosystems is currently based on various biotic indices that use the occurrence and/or abundance of selected taxonomic groups to define ecological status. These conventional indices have some limitations, often related to difficulties in morphological identification of bioindicator taxa. Recent development of DNA barcoding and metabarcoding could potentially alleviate some of these limitations, by using DNA sequences instead of morphology to identify organisms and to characterize a given ecosystem. In this paper, we review the structure of conventional biotic indices, and we present the results of pilot metabarcoding studies using environmental DNA to infer biotic indices. We discuss the main advantages and pitfalls of metabarcoding approaches to assess parameters such as richness, abundance, taxonomic composition and species ecological values, to be used for calculation of biotic indices. We present some future developments to fully exploit the potential of metabarcoding data and improve the accuracy and precision of their analysis. We also propose some recommendations for the future integration of DNA metabarcoding to routine biomonitoring programs.info:eu-repo/semantics/publishedVersio

Ibicaba revisitada outra vez: espaço, escravidão e trabalho livre no oeste paulista

Ibicaba Farm, property of Senator Nicolau Pereira de Campos Vergueiro during the 19th century, was the subject of studies that focused on the experience with the sharecropping system. This article intends to undertake a revisit to Ibicaba through new lenses of observation. At first, it tries to insert Vergueiro's farm in the context of the changing World-economy of the first decades of the nineteenth century, and then highlight the importance of the spatial dimension of reality in this historical context. In the following two subitems, which constitute the core of the article, an analysis is made of the protocols - especially spatial - of control of the workers, used by the Vergueiros in order to extract the maximum of labor from slaves and sharecroppers, as well as the strategies that captives and immigrants used to escape from this surveillance. Finally, a brief recapitulation of the main points exposed and some considerations about the tensions that emerged in Ibicaba during the studied period are made.A Fazenda Ibicaba, propriedade do Senador Nicolau Pereira de Campos Vergueiro ao longo do século XIX, foi objeto de estudos que enfocaram a experiência com o sistema de parceria que ela abrigou. Este artigo pretende revisitar Ibicaba por meio de novas lentes de observação. Em um primeiro momento, buscar-se-á inserir a fazenda de Vergueiro no contexto de mudança pela qual a Economia-mundo passava nas primeiras décadas do Oitocentos para, em seguida, salientar a importância que a dimensão espacial da realidade cumpria nesse contexto histórico. Nos dois subitens seguintes, que constituem o núcleo do artigo, analisam-se os protocolos - sobretudo espaciais - de controle da mão de obra utilizados pelos Vergueiro, com vistas à máxima extração de trabalho de escravos e colonos, bem como as estratégias de que cativos e imigrantes lançaram mão para escapar dessa vigilância. Faz-se, ao fim, uma breve recapitulação dos principais pontos expostos e algumas considerações sobre as tensões que emergiram em Ibicaba durante o período estudado

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Assessing the potential of nematode metabarcoding for benthic monitoring of offshore oil platforms

: Environmental DNA metabarcoding is gaining momentum as a time and cost-effective tool for biomonitoring and environmental impact assessment. Yet, its use as a replacement for the conventional marine benthic monitoring based on morphological analysis of macrofauna is still challenging. Here we propose to study the meiofauna, which is much better represented in sediment DNA samples. We focus on nematodes, which are the most numerous and diverse group of meiofauna. Our aim is to assess the potential of nematode metabarcoding to monitor impacts associated with offshore oil platform activities. To achieve this goal, we used nematode-optimized marker (18S V1V2-Nema) and universal eukaryotic marker (18S V9) region to analyse 252 sediment DNA samples collected near three offshore oil platforms in the North Sea. For both markers, we analysed changes in alpha and beta diversity in relation to distance from the platforms and environmental variables. We also defined three impact classes based on selected environmental variables that are associated with oil extraction activities and used random forest classifiers to compare the predictive performance of both datasets. Our results show that alpha- and beta-diversity of nematodes varies with the increasing distance from the platforms. The variables directly related to platform activity, such as Ba and THC, strongly influence the nematode community. The nematode metabarcoding data provide more robust predictive models than eukaryotic data. Furthermore, the nematode community appears more stable in time and space, as illustrated by the overlap of nematode datasets obtained from the same platform three years apart. A significative negative correlation between distance and Shannon diversity also advocates for higher performance of the V1V2-Nema over the V9. Overall, these results suggest that the sensitivity of nematodes is higher compared to the eukaryotic community. Hence, nematode metabarcoding has the potential to become an effective tool for benthic monitoring in marine environment