In vitro modeling of CD8 T cell exhaustion enables CRISPR screening to reveal a role for BHLHE40.

Identifying molecular mechanisms of exhausted CD8 T cells (T) is a key goal of improving immunotherapy of cancer and other diseases. However, high-throughput interrogation of in vivo T can be costly and inefficient. In vitro models of T are easily customizable and quickly generate high cellular yield, enabling CRISPR screening and other high-throughput assays.

Modeling of CD8 T Cell Exhaustion Enables CRISPR Screening to Reveal a Role for BHLHE40.

Identifying novel molecular mechanisms of exhausted CD8 T cells (T ) is a key goal of improving immunotherapy of cancer and other diseases. However, high-throughput interrogation of T can be costly and inefficient. models of T are easily customizable and quickly generate high cellular yield, offering an opportunity to perform CRISPR screening and other high-throughput assays.

Obesity Management in Kidney Transplant Candidates: Current Paradigms and Gaps in Knowledge.

In this review, we discuss the increasing prevalence of obesity among people with chronic and end-stage kidney disease (ESKD) and implications for kidney transplant (KT) candidate selection and management. Although people with obesity and ESKD receive survival and quality-of-life benefits from KT, most KT programs maintain strict body mass index (BMI) cutoffs to determine transplant eligibility. However, BMI does not distinguish between visceral adiposity, which confers higher cardiovascular risks and risks of perioperative and adverse posttransplant outcomes, and muscle mass, which is protective in ESKD.

Cdk2 catalytic activity is essential for meiotic cell division in vivo.

Cyclin-dependent kinases (Cdks) control the eukaryotic cell cycle by phosphorylating serine and threonine residues in key regulatory proteins, but some Cdk family members may exert kinase-independent functions that cannot easily be assessed using gene knockout approaches. While Cdk2-deficient mice display near-normal mitotic cell proliferation due to the compensatory activities of Cdk1 and Cdk4, they are unable to undergo meiotic generation of gametes and are consequently sterile. To investigate whether Cdk2 regulates meiosis via protein phosphorylation or by alternative kinase-independent mechanisms, we generated two different knockin mouse strains in which Cdk2 point mutations ablated enzyme activity without altering protein expression levels.