The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by pausing POL II at pro-differentiation genes

In pluripotent cells, a delicate activation-repression balance maintains pro-differentiation genes ready for rapid activation. The identity of transcription factors (TFs) that specifically repress pro-differentiation genes remains obscure. By targeting ~1,700 TFs with CRISPR loss-of-function screen, we found that ZBTB11 and ZFP131 are required for embryonic stem cell (ESC) pluripotency. ZBTB11 and ZFP131 maintain promoter-proximally paused Polymerase II at pro-differentiation genes in ESCs. ZBTB11 or ZFP131 loss leads to NELF pausing factor release, an increase in H3K4me3, and transcriptional upregulation of genes associated with all three germ layers. Together, our results suggest that ZBTB11 and ZFP131 maintain pluripotency by preventing premature expression of pro-differentiation genes and present a generalizable framework to maintain cellular potency

The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by repressing pro-differentiation genes

In pluripotent cells, a delicate activation-repression balance maintains pro-differentiation genes ready for rapid activation. The identity of transcription factors (TFs) that specifically repress pro-differentiation genes remains obscure. By targeting ∼1,700 TFs with CRISPR loss-of-function screen, we found that ZBTB11 and ZFP131 are required for embryonic stem cell (ESC) pluripotency. ESCs without ZBTB11 or ZFP131 lose colony morphology, reduce proliferation rate, and upregulate transcription of genes associated with three germ layers. ZBTB11 and ZFP131 bind proximally to pro-differentiation genes. ZBTB11 or ZFP131 loss leads to an increase in H3K4me3, negative elongation factor (NELF) complex release, and concomitant transcription at associated genes. Together, our results suggest that ZBTB11 and ZFP131 maintain pluripotency by preventing premature expression of pro-differentiation genes and present a generalizable framework to maintain cellular potency

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Behandlung des Typ-1-Diabetes im Frühstadium: eine Kasuistik.

Durch Studien zur Früherkennung werden Kinder mit Typ-1-Diabetes in einem Stadium diagnostiziert, in dem sie noch keine oder allenfalls wenige Symptome aufweisen. Für diese Patienten existieren bisher keine einheitlichen Therapiestandards. Anhand der folgenden Kasuistik werden Ersteinstellung und Verlauf im ersten Behandlungsjahr bei einer Patientin mit früh diagnostiziertem Typ-1-Diabetes dargestellt

Früherkennung und Primärprävention des Typ-1-Diabetes: „Global Platform for the Prevention of Autoimmune Diabetes“ (GPPAD).

Background: Betacell autoimmunity, which leads to type 1 diabetes, starts in early childhood with a peak in incidence at 12 months and insulin is its primary target. GPPAD (Global Platform for the Prevention of Autoimmune Diabetes): This network of collaborating European scientists aims to realize the early detection of an elevated risk to develop type 1 diabetes and primary prevention of betacell autoimmunity and type 1 diabetes in Europe. A new genetic risk score can identify newborns with 25-fold increased risk of type 1 diabetes. These children can participate in a primary prevention trial called POInT (Primary Oral Insulin Trial). POInT study: This is a randomized, placebo-controlled, double-blind clinical trial that will test the efficacy of oral insulin to prevent autoimmunity and type 1 diabetes