Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

Temps de l'Histoire et temps du destin ((Julien Gracq, Ernst Jünger, Mircea Eliade)

Les situations historiques du XXe siècle ont conduit Julien Gracq, Ernst Jünger et Mircea Eliade à mener une vaste réflexion sur l'Histoire, qui passe par la critique de la Raison historique et de ses fondements : temps linéaire et continu, vecteur du progrès constant. Pour ces trois écrivains, le refus de l'Histoire n'est autre que le refus de tous les historicismes prétendant réduire l'homme à sa seule dimension historique. Si tous les trois se tournent vers le mythe, qui constitue la grande découverte historico-scientifique du XXe siècle, ce n'est absolument pas le fait d'un désintérêt pour l'Histoire. Bien au contraire, leur approche du mythe, qui va de pair avec l'exploration des dimensions du temps autres que linéaire, renouvelle et dépasse l'opposition traditionnelle entre mythe et Histoire. Ceci n'est pas sans conséquences sur le conception que Gracq, Jünger et Eliade se font de la littérature.STRASBOURG-B.N.U.S. (674821001) / SudocSudocFranceF

The Breaking News Effect and Its Impact on the Credibility and Trust in Information Posted on Social Media

The development of social media has triggered important changes in our society and in the way consumers read and trust online information. The presence of consumers in the online environment exposes them to a greater extent to various instances of fake news, which are spread more or less intentionally. Sensational and breaking-news-style information are one of the ways in which consumers’ attention is attracted, by posting exaggerated or distorted information. The objective of our research is to determine the impact of sensational and breaking news headlines on content credibility. In a mediation model, we show that the perception of sensationalism mediates the relation between the presence of breaking news headlines and trust in the content of the information. Based on our proposed model, the existence of breaking news headlines increases the consumers’ perception of sensationalism and reduces trust in news content. These results have important implications for patterns of news consumption. If a piece of information is presented in a sensational way, it might attract more consumers’ attention in the short term, but in the long run it will reduce the credibility of its content. Based on our research, we recommend using sensational headlines with caution to maintain credibility

Circulating Biomarkers for Laboratory Diagnostics of Atherosclerosis—Literature Review

Atherosclerosis is still considered a disease burden with long-term damaging processes towards the cardiovascular system. Evaluation of atherosclerotic stages requires the use of independent markers such as those already considered traditional, that remain the main therapeutic target for patients with atherosclerosis, together with emerging biomarkers. The challenge is finding models of predictive markers that are particularly tailored to detect and evaluate the evolution of incipient vascular lesions. Important advances have been made in this field, resulting in a more comprehensible and stronger linkage between the lipidic profile and the continuous inflammatory process. In this paper, we analysed the most recent data from the literature studying the molecular mechanisms of biomarkers and their involvement in the cascade of events that occur in the pathophysiology of atherosclerosis

PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis.

International audienceBackground - PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. Study design - Case series, January 2010 to March 2016. Settings & participants - Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. Outcomes - Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. Results - The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. Limitations - Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers. Conclusions - Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out