Genome-Wide Assessment of AU-Rich Elements by the AREScore Algorithm

In mammalian cells, AU-rich elements (AREs) are well known regulatory sequences located in the 3′ untranslated region (UTR) of many short-lived mRNAs. AREs cause mRNAs to be degraded rapidly and thereby suppress gene expression at the posttranscriptional level. Based on the number of AUUUA pentamers, their proximity, and surrounding AU-rich regions, we generated an algorithm termed AREScore that identifies AREs and provides a numerical assessment of their strength. By analyzing the AREScore distribution in the transcriptomes of 14 metazoan species, we provide evidence that AREs were selected for in several vertebrates and Drosophila melanogaster. We then measured mRNA expression levels genome-wide to address the importance of AREs in SL2 cells derived from D. melanogaster hemocytes. Tis11, a zinc finger RNA–binding protein homologous to mammalian tristetraprolin, was found to target ARE–containing reporter mRNAs for rapid degradation in SL2 cells. Drosophila mRNAs whose expression is elevated upon knock down of Tis11 were found to have higher AREScores. Moreover high AREScores correlate with reduced mRNA expression levels on a genome-wide scale. The precise measurement of degradation rates for 26 Drosophila mRNAs revealed that the AREScore is a very good predictor of short-lived mRNAs. Taken together, this study introduces AREScore as a simple tool to identify ARE–containing mRNAs and provides compelling evidence that AREs are widespread regulatory elements in Drosophila

Kommunikation zu Klimawandel und Gesundheit für spezifische Zielgruppen

Hintergrund: Der Sachstandsbericht Klima und Gesundheit hat zahlreiche Gesundheitsrisiken aufgezeigt, die durch den Klimawandel entstehen oder verstärkt werden. Eine Handlungsempfehlung ist, zielgruppenspezifisch über Risiken zu informieren. Dieser Artikel soll hierfür als Handlungsgrundlage dienen. Methode: Auf Basis von vier Erhebungen (2022/23) der pace-studie.de (N = 3.845) wird der Stand der Risikowahrnehmung aufgezeigt und eine Zielgruppenanalyse durchgeführt. Ergebnisse: Einige Gesundheitsrisiken durch die Klimakrise werden als vergleichsweise gering wahrgenommen (z. B. psychische Probleme). Personen mit einer größeren Risikowahrnehmung zeigen eine höhere Handlungsbereitschaft. Bei der Segmentierung der Zielgruppen basierend auf soziodemografischen Variablen zeigen sich jüngere, Männer, Personen mit niedrigerer Bildung und in kleineren Gemeinden als relevante Zielgruppen, da sie eine geringere Handlungsbereitschaft haben. Ca. ein Drittel gab an, sich kaum oder gar nicht gezielt zu informieren. Die Mediennutzung unterscheidet sich zwischen verschiedenen Zielgruppen; Menschen mit geringerer Handlungsbereitschaft bspw. informieren sich über alle Medientypen hinweg seltener. Schlussfolgerungen: Eine zielgruppenspezifische Kommunikation kann die Gesundheitsrisiken der Klimakrise verdeutlichen. In der Diskussion des Artikels werden ausführlich Implikationen existierender Literatur diskutiert, um Kommunikator*innen eine Handreichung zur effektiven Klimakommunikation anzubieten

Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations.

We studied here the clinical course of heterozygous carriers of X-linked Alport syndrome and a subgroup of patients with thin basement membrane disease due to heterozygous autosomal recessive Alport mutations whose prognosis may be worse than formerly thought. We analyzed 234 Alport carriers, including 29 with autosomal recessive mutations. Using Kaplan-Meier estimates and log-rank tests, autosomal and X-linked carriers were found to have similar incidences of renal replacement therapy, proteinuria, and impaired creatinine clearance. Further, age at onset of renal replacement therapy did not differ between X-chromosomal and autosomal carriers. Both groups showed an impaired life expectancy when reaching renal replacement therapy. RAAS inhibition significantly delayed the onset of end-stage renal failure. Not only carriers of X-linked Alport mutations but also heterozygous carriers of autosomal recessive mutations were found to have an increased risk for worse renal function. The risk of end-stage renal disease in both groups affected life expectancy, and this should cause a greater alertness toward patients presenting with what has been wrongly termed 'familial benign hematuria.' Timely therapy can help to delay onset of end-stage renal failure. Thus, yearly follow-up by a nephrologist is advised for X-linked Alport carriers and patients with thin basement membrane nephropathy, microalbuminuria, proteinuria, or hypertension

Outcomes of male patients with alport syndrome undergoing renal replacement therapy

Item does not contain fulltextBACKGROUND AND OBJECTIVES: Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival. RESULTS: Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls. CONCLUSIONS: These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure