Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities.

Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs.

Metal-Free Aziridination of Unactivated Olefins via Transient -Pyridinium Iminoiodinanes.

We describe a metal-free aziridination of unactivated olefins to generate pyridinium aziridines. Subsequent cross-coupling affords -aryl aziridines, and reductive depyridylation affords N-H aziridines. Kinetics experiments, based on a variable time normalization analysis (VTNA), indicate that aziridination proceeds via a highly electrophilic -pyridinium iminoiodinane intermediate.

Clinical Validation of a Prenatal Cell-Free DNA Screening Test for Fetal RHD in a Large U.S. Cohort.

Objective: To present a large U.S. clinical validation of a next-generation sequencing-based, noninvasive prenatal cell-free DNA test for fetal RHD.

Poor compliance with germline testing recommendations in colorectal cancer patients undergoing molecular residual disease testing.

Background: Approximately 15% of colorectal cancers (CRCs) are associated with germline mutations. There is increasing adoption of DNA-based assays for molecular residual disease (MRD) and growing evidence supporting its clinical utility, particularly for CRC by oncologists in the U.S.

Synthesis of Secondary Amines via Self-Limiting Alkylation.

-centered nucleophilicity increases upon alkylation, and thus selective partial alkylation of ammonia and primary amines can be challenging: Poor selectivity and overalkylation are often observed. Here we introduce -aminopyridinium salts as ammonia surrogates for the synthesis of secondary amines via self-limiting alkylation chemistry. Readily available -aryl--aminopyridinium salts engage in -alkylation and depyridylation to afford secondary aryl-alkyl amines without any overalkylation products.