Sleeve gastrectomy reveals the plasticity of the human gastric epithelium.

Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs).

Single-plate kinome screening in live-cells to enable highly cost-efficient kinase inhibitor profiling.

Cancer research, cancer treatment, and the field of chemical biology are examples which heavily rely on the discovery of selective kinase inhibitors. While determining on-target potency is often feasible for most laboratories, the equally critical but frequently neglected selectivity screening remains less accessible to the broader scientific community. This limitation can stem from various factors, such as the unavailability of a large number of purified kinases or the costs associated with commercial screening systems.

DARPin-induced reactivation of p53 in HPV-positive cells.

Infection of cells with high-risk strains of the human papillomavirus (HPV) causes cancer in various types of epithelial tissue. HPV infections are responsible for ~4.5% of all cancers worldwide.

Alternative splicing in the DBD linker region of p63 modulates binding to DNA and iASPP in vitro.

The transcription factor p63 is expressed in many different isoforms as a result of differential promoter use and splicing. Some of these isoforms have very specific physiological functions in the development and maintenance of epithelial tissues and surveillance of genetic integrity in oocytes. The ASPP family of proteins is involved in modulating the transcriptional activity of the p53 protein family members, including p63.

Molecular basis of JAK kinase regulation guiding therapeutic approaches: Evaluating the JAK3 pseudokinase domain as a drug target.

Janus kinases (JAK1-3, TYK2) are critical mediators of cytokine signaling and their role in hematological and inflammatory and autoimmune diseases has sparked widespread interest in their therapeutic targeting. JAKs have unique tandem kinase structure consisting of an active tyrosine kinase domain adjacent to a pseudokinase domain that is a hotspot for pathogenic mutations. The development of JAK inhibitors has focused on the active kinase domain and the developed drugs have demonstrated good clinical efficacy but due to off-target inhibition cause also side-effects and carry a black box warning limiting their use.