Addressing the Intracellular Vestibule of the Plasmodial Lactate Transporter PfFNT by p-Substituted Inhibitors Amplifies In Vitro Activity.

Inhibition of the lactate transporter PfFNT is a valid novel mode of action against malaria parasites. Current pyridine-substituted pentafluoro-3-hydroxy-pent-2-en-1-ones act as substrate analogs with submicromolar EC in vitro, and >99.7% activity in mice.

Pediatric reference values for myocardial contraction fraction and global function index of the left ventricle: A cardiovascular magnetic resonance study.

Background: Cardiovascular magnetic resonance (CMR) derived global function index (GFI) and myocardial contraction fraction (MCF) were identified as useful imaging markers to assess left ventricular (LV) cardiac performance and can provide prognostic information for several cardiac diseases. As pediatric reference values are lacking, the aim of this retrospective study was to establish these values.

Methods: 154 CMR examinations of healthy children and adolescents (4-18 years) were included.

Human cardiovascular disease model predicts xanthine oxidase inhibitor cardiovascular risk.

Some health concerns are often not identified until late into clinical development of drugs, which can place participants and patients at significant risk. For example, the United States Food and Drug Administration (FDA) labeled the xanthine oxidase inhibitor febuxostat with a"boxed" warning regarding an increased risk of cardiovascular death, and this safety risk was only identified during Phase 3b clinical trials after its approval. Thus, better preclinical assessment of drug efficacy and safety are needed to accurately evaluate candidate drug risk earlier in discovery and development.

Fluorescence Cross-Correlation Spectroscopy Yields True Affinity and Binding Kinetics of Lactate Transport Inhibitors.

Blocking lactate export in the parasitic protozoan is a novel strategy to combat malaria. We discovered small drug-like molecules that inhibit the sole plasmodial lactate transporter, PfFNT, and kill parasites in culture. The pentafluoro-3-hydroxy-pent-2-en-1-one BH296 blocks PfFNT with nanomolar efficiency but an in vitro selected PfFNT G107S mutation confers resistance against the drug.

UCYN-A/haptophyte symbioses dominate N fixation in the Southern California Current System.

The availability of fixed nitrogen (N) is an important factor limiting biological productivity in the oceans. In coastal waters, high dissolved inorganic N concentrations were historically thought to inhibit dinitrogen (N) fixation, however, recent N fixation measurements and the presence of the N-fixing UCYN-A/haptophyte symbiosis in nearshore waters challenge this paradigm. We characterized the contribution of UCYN-A symbioses to nearshore N fixation in the Southern California Current System (SCCS) by measuring bulk community and single-cell N fixation rates, as well as diazotroph community composition and abundance.