A photo-SAR study of photoswitchable azobenzene tubulin-inhibiting antimitotics identifying a general method for near-quantitative photocontrol.

Azobenzene analogues of the tubulin polymerisation inhibitor combretastatin A4 (PSTs) were previously developed to optically control microtubule dynamics in living systems, with subsecond response time and single-cell spatial precision, by reversible photoswitching of their bioactivity with near-UV/visible light. First-generation PSTs were sufficiently potent and photoswitchable for use in live cells and embryos. However, the link between their seconds-scale and hours-scale bioactivity remained untested.

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs.

Increasing the chemical space of proteins in living cells via genetic code expansion.

In recent years it has become possible to genetically encode an expanded set of designer amino acids with tailored chemical and physical properties (dubbed unnatural amino acids, UAAs) into proteins in living cells by expanding the genetic code. Together with developments in chemistries that are amenable to and selective within physiological settings, these strategies have started to have a big impact on biological studies, as they enable exciting in cellulo applications. Here we highlight recent advances to covalently stabilize transient protein-protein interactions and capture enzyme substrate-complexes in living cells using proximity-triggered and residue-selective photo-induced crosslinking approaches.

Hepatitis C care cascade among persons born 1945-1965: 3 medical centers.

Objectives: Effective screening, diagnosis, and treatment are needed to reduce chronic hepatitis C virus (HCV) infection-associated morbidity and mortality. In order to successfully increase HCV treatment, it is necessary to identify and understand gaps in linkage of antibody-positive patients with newly identified HCV to subsequent HCV RNA testing, clinical evaluation, and treatment.

Study Design: To estimate attainment of HCV care cascade steps among antibody-positive patients with newly identified HCV, we conducted chart reviews of patients with a new positive HCV antibody test at 3 academic medical centers participating in the Birth-Cohort Evaluation to Advance Screening and Testing of Hepatitis C (BEST-C) study.

Regulation of the Activity in the p53 Family Depends on the Organization of the Transactivation Domain.

Despite high sequence homology among the p53 family members, the regulation of their transactivation potential is based on strikingly different mechanisms. Previous studies revealed that the activity of TAp63α is regulated via an autoinhibitory mechanism that keeps inactive TAp63α in a dimeric conformation. While all p73 isoforms are constitutive tetramers, their basal activity is much lower compared with tetrameric TAp63.