Thylakoid localized bestrophin-like proteins are essential for the CO2 concentrating mechanism of Chlamydomonas reinhardtii

The green alga Chlamydomonas reinhardtii possesses a CO2 concentratingmechanism (CCM) which helps in successful acclimationto low CO2 conditions. Current models of the CCM postulate that aseries of ion transporters bring HCO3- from outside the cell to thethylakoid lumen, where the carbonic anhydrase CAH3 dehydratesaccumulated HCO3- to CO2, raising the CO2 concentration forRubisco. Previously, HCO3- transporters have been identified atboth the plasma membrane and the chloroplast envelope, butthe transporter thought to be on the thylakoid membrane hasnot been identified. Three paralogous genes (BST1, BST2, BST3)belonging to the bestrophin family have been found to be upregulatedin low CO2 conditions, and their expression is controlledby CIA5, a transcription factor that controls many CCM genes.YFP fusions demonstrate that all three proteins are located onthe thylakoid membrane, and interactome studies indicate thatthey might associate with chloroplast CCM components. A singlemutant defective in BST3 still grows nearly normally on low CO2,indicating that the three bestrophin-like proteins may have redundantfunctions. Therefore, an RNAi approach was adopted to reducethe expression of all three genes at once. RNAi mutants withreduced expression of BST1-3 were unable to grow at low CO2concentrations, exhibited a reduced affinity to inorganic carboncompared to the wild type cells, and showed reduced inorganiccarbon uptake. We propose that these bestrophin-like proteins areessential components of the CCM that deliver HCO3- accumulatedin the chloroplast stroma to CAH3 inside the thylakoid lumen

Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort study.

BACKGROUND: Chronic liver disease is a major cause of premature death in sub-Saharan Africa. Efficacy of antiviral therapy among patients with hepatitis B virus (HBV)-related cirrhosis is not well established in Africa. We described the clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia and assessed the impact of tenofovir disoproxil fumarate (TDF) on survival of HBV-infected patients with cirrhosis. METHODS: In this prospective cohort study, we followed up adults who were consecutively diagnosed with cirrhosis or hepatocellular carcinoma between 2012 and 2015 in The Gambia, west Africa. Patients with chronic HBV infection and cirrhosis, without hepatocellular carcinoma, were offered TDF. Primary outcome was overall survival. To determine the effect of TDF on survival, we performed a Cox proportional hazard regression model with inverse probability of treatment weighting (IPTW) based on propensity score. FINDINGS: Of 529 patients enrolled in this study, 336 patients (252 with hepatocellular carcinoma and 84 with cirrhosis) were analysed. Patients were predominantly male (253 [75%] men and 83 [25%] women), with a median age of 42 years (IQR 33-55). 276 (84%) of 327 of patients with data were positive for HBV biomarkers, 31 (10%) of 311 were positive for hepatitis C virus antibodies, and 22 (10%) of 223 were positive for hepatitis D virus antibodies. 64% of patients with hepatocellular carcinoma had multifocal tumour, with a median size of 7·5 cm (IQR 5·4-10·8). 173 patients with hepatocellular carcinoma and 70 patients with cirrhosis were included in the survival analysis. Median survival was 1·5 months (95% CI 1·1-2·0) in patients with hepatocellular carcinoma and 17·1 months (11·2-24·0) in patients with cirrhosis (log-rank p<0·0001). In patients with hepatocellular carcinoma, ascites (hazard ratio [HR] 1·78, 95% CI 1·21-2·60), partial or complete portal thrombosis (HR 2·61, 1·58-4·30), and platelet count (HR 1·80, 1·19-2·70) were independent predictive factors of mortality at baseline. In HBV-infected patients with cirrhosis, median turnaround time between cirrhosis diagnosis and TDF initiation was 4·9 months (IQR 3·2-7·3). In IPTW analysis, TDF treatment was associated with improved survival in patients with HBV-related cirrhosis (adjusted HR 0·14, 0·06-0·34; p<0·0001). INTERPRETATION: These results highlight poor survival of patients with cirrhosis or hepatocellular carcinoma as well as the effectiveness of TDF in reducing the premature mortality of patients with cirrhosis and HBV infection. Interventions for early diagnosis and treatment of cirrhosis as well as screening programmes for hepatocellular carcinoma are urgently required in Africa. FUNDING: European Commission and Medical Research Council UK. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Political leaders' identity leadership and civic citizenship behavior:The mediating role of trust in fellow citizens and the moderating role of economic inequality

Identity leadership captures leaders efforts to create and promote a sense of shared group membership (i.e., a sense of “we” and of “us”) among followers. The present research report tests this claim by drawing on data from 26 countries that are part of the Global Identity Leadership Development (GILD) project to examine the relationship between political leaders' identity leadership and civic citizenship behavior (N = 6787). It also examines the contributions of trust and economic inequality to this relationship. Political leaders' identity leadership (PLIL) was positively associated with respondents' people-oriented civic citizenship behaviors (CCB-P) in 20 of 26 countries and civic citizenship behaviors aimed at one's country (CCB-C) in 23 of 26 countries. Mediational analyses also confirmed the indirect effects of PLIL via trust in fellow citizens on both CCB-P (in 25 out of 26 countries) and CCB-C (in all 26 countries). Economic inequality moderated these effects such that the main and indirect effects of trust in one's fellow citizens on CCB-C were stronger in countries with higher economic inequality. This interaction effect was not observed for CCB-P. The study highlights the importance of identity leadership and trust in fellow citizens in promoting civic citizenship behavior, especially in the context of economic inequality.</p

Political leaders' identity leadership and civic citizenship behavior:The mediating role of trust in fellow citizens and the moderating role of economic inequality

Identity leadership captures leaders efforts to create and promote a sense of shared group membership (i.e., a sense of “we” and of “us”) among followers. The present research report tests this claim by drawing on data from 26 countries that are part of the Global Identity Leadership Development (GILD) project to examine the relationship between political leaders' identity leadership and civic citizenship behavior (N = 6787). It also examines the contributions of trust and economic inequality to this relationship. Political leaders' identity leadership (PLIL) was positively associated with respondents' people-oriented civic citizenship behaviors (CCB-P) in 20 of 26 countries and civic citizenship behaviors aimed at one's country (CCB-C) in 23 of 26 countries. Mediational analyses also confirmed the indirect effects of PLIL via trust in fellow citizens on both CCB-P (in 25 out of 26 countries) and CCB-C (in all 26 countries). Economic inequality moderated these effects such that the main and indirect effects of trust in one's fellow citizens on CCB-C were stronger in countries with higher economic inequality. This interaction effect was not observed for CCB-P. The study highlights the importance of identity leadership and trust in fellow citizens in promoting civic citizenship behavior, especially in the context of economic inequality.</p

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Les amphores du Cécube et du Falerne. Prospections, typologie, analyses

Antoinette Hesnard et Charlotte Lemoine, Les amphores du Cécube et du Falerne. Prospections, typologie, analyses, p. 243-295. Des prospections de surface menées dans le sud du Latium et le nord de la Campanie ont permis de localiser des ateliers d'amphores à vin dans ces deux régions. Ces prospections sont complétées par l'étude des tessons ramassés sur les différents sites : analyse typologique et caractérisation chimique. Les avantages et les limites de chacune des méthodes sont exposés, les résultats obtenus comparés. On peut déjà conclure que les ateliers découverts dans la plaine de Fondi et sur le territoire de Sinuessa ont produit des amphores gréco-italiques, Dr. 1 et Dr. 2-4.Hesnard Antoinette, Lemoine Charlotte. Les amphores du Cécube et du Falerne. Prospections, typologie, analyses. In: Mélanges de l'École française de Rome. Antiquité, tome 93, n°1. 1981. pp. 243-295

Membrane estrogen receptor alpha rapidly regulates male mice sexual behavior

Introduction/Aim: The activation of male sexual behavior depends on brain aromatization of testosterone into an estrogen. Estrogens exert slow genomic effects (hours/days) by binding to nuclear estrogen receptors but also rapid effects (seconds/minutes) by acting on membrane-associated receptors (including G-protein coupled estrogens receptor 1 [GPER1] or the nuclear receptors themselves following palmitoylation) to activate intracellular signaling pathways. Rapid effects of estrogens have been described on reproductive behavior of rodents but the identity of the receptor involved is not known. In mice, estrogen receptor alpha (ERα) plays a major role in the control of male sexual behavior but whether these effects involve membrane triggered-actions remains unclear. In this study, we used a mouse model carrying a mutation at the palmitoylation site of ERα making it unable to traffic to and signal from the membrane (C451A-ERα) to investigate the role of membrane estrogen receptor alpha (mERα) in the motivational and copulatory aspects of male sexual behavior. Methods/Results: Sexually experienced and gonadally intact C451A-ERα and wild-type male mice were tested for sexual motivation using the partner preference test and for sexual performance by measuring the frequencies and latencies of mounts, intromissions and ejaculations observed during a 30 minutes interaction with a receptive female. Both aspects of behavior were tested 10 minutes after single subcutaneous injections of estetrol (E4), a natural estrogen acting as an antagonist of mER or the aromatase inhibitor 1,4,6-Androstatriene-3,17-dione (ATD). In both genotypes, ATD acutely decreased both sexual performance and the time spent by males near the female, confirming the key role of aromatization in the rapid control of male sexual performance and extended this conclusion to sexual motivation. On the other hand, E4 rapidly decreased sexual performance in wild-type males, but it had no effect on the sexual performance of C451A-ERα males. Moreover, E4 did not affect time spent near the female in both genotypes. Conclusions : These data indicate that E4 rapidly inhibits sexual performance, but not sexual motivation. Since this rapid effect of E4 is prevented in mice invalidated for mERα, this demonstrates the role of mERα in the regulation of rapid effects of neuroestrogens on sexual performance in mice. Finally, the persistence of the effect of ATD on behavior in C451A-ERα mice suggests that another estrogen receptor, such as ERβ or GPER1, could also regulate both aspects of male sexual behavior