Emerging technologies for food and drug safety.

Emerging technologies are playing a major role in the generation of new approaches to assess the safety of both foods and drugs. However, the integration of emerging technologies in the regulatory decision-making process requires rigorous assessment and consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) in partnership with the Brazilian Health Surveillance Agency (ANVISA) hosted the seventh Global Summit on Regulatory Science (GSRS17) in Brasilia, Brazil on September 18-20, 2017 to discuss the role of new approaches in regulatory science with a specific emphasis on applications in food and medical product safety.

Cell-intrinsic functional effects of the α-cardiac myosin Arg-403-Gln mutation in familial hypertrophic cardiomyopathy.

Human familial hypertrophic cardiomyopathy is the most common Mendelian cardiovascular disease worldwide. Among the most severe presentations of the disease are those in families heterozygous for the mutation R403Q in β-cardiac myosin. Mice heterozygous for this mutation in the α-cardiac myosin isoform display typical familial hypertrophic cardiomyopathy pathology.

Robust mechanosensing and tension generation by myosin VI.

Myosin VI is a molecular motor that is thought to function both as a transporter and as a cytoskeletal anchor in vivo. Here we use optical tweezers to examine force generation by single molecules of myosin VI under physiological nucleotide concentrations. We find that myosin VI is an efficient transporter at loads of up to ∼2 pN but acts as a cytoskeletal anchor at higher loads.

Contribution of the myosin VI tail domain to processive stepping and intramolecular tension sensing.

Myosin VI is proposed to act as both a molecular transporter and as an anchor in vivo. A portion of the molecule C-terminal to the canonical lever arm, termed the medial tail (MT), has been proposed to act as either a lever arm extension or as a dimerization motif. We describe constructs in which the MT is interrupted by a glycine-rich molecular swivel.

Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells.

The growth and differentiation of mesenchymal stem cells (MSCs) is controlled by various growth factors, the activities of which can be modulated by heparan sulfates (HSs). We have previously noted the necessity of sulfated glycosaminoglycans for the fibroblast growth factor type 2 (FGF-2)-stimulated differentiation of osteoprogenitor cells. Here we show that exogenous application of HS to cultures of primary rat MSCs stimulates their proliferation, leading to increased expression of osteogenic markers and enhanced bone nodule formation.

Regional determinants of arterial endothelial phenotype dominate the impact of gender or short-term exposure to a high-fat diet.

Regional arterial hemodynamics correlates with distinct endothelial phenotypes that may be modified by risk factors to influence focal and regional susceptibility to atherosclerosis. We compared endothelial transcript profiles from hemodynamically distinct arterial regions in 15 mature pigs: males and females fed a normal diet, and males fed a high-fat diet (15% lard, 1.5% cholesterol) for two weeks.