Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Sembène Ousmane's Xala: The Use of Film and Novel as Revolutionary Weapon

Sembène Ousmane's Xala was written as a novel and made into a film in 1974. It is a biting attack upon the newly risen bourgeois class that has ascended to power and wealth in Senegal since independence. The ideological framework of Xala rests upon Marxist assumptions adapted to and modified by the circumstances in Africa. The distinctively Senegalese features which mark Sembène's portrayal include Muslim and traditional religious beliefs which form the basis of the class oppression and the sexism depicted in Xala . They also supply the title to the work since xala means impotency in Wolof, and it is described with great humor by Sembène, as the result of a marabout's curse. Sembène's treatment of the theme of class oppression focuses upon the great disparities that exist between the wealthy, elite classes and the impoverished masses, especially the beggars and cripples who live on the streets of Dakar. By focusing upon the issue of acculturation in the film, and by emphasizing the importance of imagery related to sight and the act of seeing, Sembène effectively overcomes the deficiencies of the novel in creating the film version of Xala

Sembène Ousmane\u27s Xala: The Use of Film and Novel as Revolutionary Weapon

Sembène Ousmane\u27s Xala was written as a novel and made into a film in 1974. It is a biting attack upon the newly risen bourgeois class that has ascended to power and wealth in Senegal since independence. The ideological framework of Xala rests upon Marxist assumptions adapted to and modified by the circumstances in Africa. The distinctively Senegalese features which mark Sembène\u27s portrayal include Muslim and traditional religious beliefs which form the basis of the class oppression and the sexism depicted in Xala. They also supply the title to the work since xala means impotency in Wolof, and it is described with great humor by Sembène, as the result of a marabout\u27s curse. Sembène\u27s treatment of the theme of class oppression focuses upon the great disparities that exist between the wealthy, elite classes and the impoverished masses, especially the beggars and cripples who live on the streets of Dakar. By focusing upon the issue of acculturation in the film, and by emphasizing the importance of imagery related to sight and the act of seeing, Sembène effectively overcomes the deficiencies of the novel in creating the film version of Xala

Faat Kine and the Feminism of the Old Man

Faat Kine (2000), c’est l’anti-Xala (1974) : ce film tardif semble complètement renverser les structures et la pensée à l’oeuvre dans la production antérieure, et l’on peut se demander pourquoi Sembène rompt ainsi avec sa critique du capitalisme. Dans Faat Kine, l’auteur aborde en effet les impératifs féministes dans le cadre d’une économie libérale qui limite la libération à une égalité consentie dans un imaginaire phallocentrique : en somme, « un féminisme à l’ancienne ». De façon plus générale, Faat Kine comprend un élément mélodramatique, et dans ce cadre, une opposition binaire et manichéenne entre le bien et le mal qui ne fait pas dans le détail mais verse plutôt dans le déterminisme : nous sommes exposés au tableau misérabiliste d’un ordre injuste, mais cela permet en dernier ressort de prendre conscience de notre opposition à la patriarchie : ce sont là tout à la fois la finalité et les limites de l’idéologie du film