TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

Role of Ep2 and Ep4 receptors in airway microvascular leak induced by prostaglandin E2

Background and Purpose Airway microvascular leak (MVL) involves the extravasation of proteins from post-capillary venules into surrounding tissue. MVL is a cardinal sign of inflammation and an important feature of airway inflammatory diseases such as asthma. Prostaglandin E2 (PGE2), a product of cyclooxygenase mediated metabolism of arachidonic acid, binds to 4 receptors, termed EP1-4. PGE2 has a wide variety of effects within the airway, including modulation of inflammation, sensory nerve activation and airway tone. However, the effect of PGE2 on airway MVL and the receptor/s that mediate this have not been described. Experimental Approach Evans Blue dye was used as a marker of airway MVL and selective EP receptor agonists and antagonists were used alongside EP receptor deficient mice to define the receptor subtype involved. Key Results PGE2 induced significant airway MVL in mice and guinea pigs. A significant reduction in PGE2-induced MVL was demonstrated in Ptger2-/- and Ptger4-/- mice and in wild type mice pre-treated simultaneously with EP2 (PF-04418948) and the EP4 (ER-819762) receptor antagonists. In a model of allergic asthma, an increase in airway levels of PGE2 was associated with a rise in MVL; this change was absent in Ptger2-/- and Ptger4-/- mice. Conclusions and Implications PGE2 is a key mediator produced by the lung and has widespread effects according to the EP receptor activated. Airway MVL represents a response to injury and under ‘disease’ conditions is a prominent feature of airway inflammation. The data presented highlight a key role for EP2 and EP4 receptors in MVL induced by PGE2. This article is protected by copyright. All rights reserved

Glutathione-Related Antioxidant Defense System in Elderly Patients Treated for Hypertension

The purpose of this study was to analyze glutathione antioxidant defense system in elderly patients treated for hypertension. Studies were carried out in the blood collected from 18 hypertensive and 15 age- and sex-matched controls, all subjects age over 60. Hypertensives were on their usual antihypertensive treatment at the time of blood collection. The concentration of glutathione (GSH) in whole blood and activities of glutathione peroxidase (GPx-1), glutathione transferase (GST), and glutathione reductase (GR) in erythrocytes were measured. The data from patients and controls were compared using independent-samples t test. P value of 0.05 and less was considered statistically significant. We observed increased glutathione-related antioxidant defense in treated hypertensive elderly patients (HT) when compared with healthy controls (C). Mean GSH concentration was significantly higher in HT when compared with C: 3.1 ± 0.29 and 2.6 ± 0.25 mmol/L, respectively, P < 0.001. Mean activity of GR was significantly higher in HT group if compared with C: 83.4 ± 15.25 U/g Hb versus 64.2 ± 8.26 U/g Hb, respectively, P < 0.001. Mean activity of GST was significantly higher in HT group compared with C: 3.0 ± 0.60 mmol CDNB-GSH/mgHb/min and 2.6 ± 0.36 mmol CDNB-GSH/mgHb/min, respectively, P < 0.05. No difference in GPx activity was observed between two groups. These results show that glutathione-related antioxidant defense system was enhanced in elderly hypertensive patients treated for their conditions. This suggests important role of glutathione system in blood pressure regulation. Alterations in concentration and activity of antioxidants observed during antihypertensive medication are likely to be related to the effect of the treatment on NO bioavailability

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

Background and purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P&lt;0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P&lt;0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT

The mammals of Angola

Scientific investigations on the mammals of Angola started over 150 years ago, but information remains scarce and scattered, with only one recent published account. Here we provide a synthesis of the mammals of Angola based on a thorough survey of primary and grey literature, as well as recent unpublished records. We present a short history of mammal research, and provide brief information on each species known to occur in the country. Particular attention is given to endemic and near endemic species. We also provide a zoogeographic outline and information on the conservation of Angolan mammals. We found confirmed records for 291 native species, most of which from the orders Rodentia (85), Chiroptera (73), Carnivora (39), and Cetartiodactyla (33). There is a large number of endemic and near endemic species, most of which are rodents or bats. The large diversity of species is favoured by the wide range of habitats with contrasting environmental conditions, while endemism tends to be associated with unique physiographic settings such as the Angolan Escarpment. The mammal fauna of Angola includes 2 Critically Endangered, 2 Endangered, 11 Vulnerable, and 14 Near-Threatened species at the global scale. There are also 12 data deficient species, most of which are endemics or near endemics to the countryinfo:eu-repo/semantics/publishedVersio

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality.

BACKGROUND AND PURPOSE: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. METHODS: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). RESULTS: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. CONCLUSIONS: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT