I260Q DNA polymerase β highlights precatalytic conformational rearrangements critical for fidelity.

DNA polymerase β (pol β) fills single nucleotide gaps in DNA during base excision repair and non-homologous end-joining. Pol β must select the correct nucleotide from among a pool of four nucleotides with similar structures and properties in order to maintain genomic stability during DNA repair. Here, we use a combination of X-ray crystallography, fluorescence resonance energy transfer and nuclear magnetic resonance to show that pol β's ability to access the appropriate conformations both before and upon binding to nucleotide substrates is integral to its fidelity.

Movement and specificity in a modular DNA binding protein.

The single-stranded DNA (ssDNA) binding protein RPA binds to and protects ssDNA while simultaneously recruiting numerous replication and repair proteins essential for genome integrity. In this issue of Structure, Brosey et al. (2015) show that the flexibility and interactions of the modular domains of RPA are altered by ssDNA binding and suggest that these changes in configurational freedom are important for the many functions of RPA.

Tag and Capture Flow Hydrogen Exchange Mass Spectrometry with a Fluorous-Immobilized Probe.

Analysis of complex mixtures of proteins by hydrogen exchange (HX) mass spectrometry (MS) is limited by one's ability to resolve the protein(s) of interest from the proteins that are not of interest. One strategy for overcoming this problem is to tag the target protein(s) to allow for rapid removal from the mixture for subsequent analysis. Here we illustrate a new solution involving fluorous conjugation of a retrievable probe.

Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women.

Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF.

A multiplex immunoassay gives different results than singleplex immunoassays which may bias epidemiologic associations.

Objectives: Multiplex immunoassays are increasingly used in epidemiologic studies to measure inflammatory factors, however there are few published evaluations of this technology. Our objective was to compare a common multiplex immunoassay to singleplex immunoassays for measuring inflammatory factors, and to examine how combining data from each affects an epidemiologic association.

Design And Methods: Plasma IL-1 beta, IFN-gamma, IL-6, and TNF-alpha were measured in 100 samples using a multiplex kit from Mesoscale Discovery (MSD) and singleplex ELISAs from R&D Systems.