A Review of Nonhuman Primate Models of Rift Valley Fever Virus Infection: Progress, Challenge Strains, and Future Directions.

Rift Valley fever (RVF) is a mosquito-borne viral disease that primarily affects animals, especially ruminants, but has the capacity to infect humans and result in outbreaks. Infection with the causative agent, RVF virus (RVFV), causes severe disease in domestic animals, especially sheep, resulting in fever, anorexia, immobility, abortion, and high morbidity and mortality rates in neonate animals. Humans become infected through exposure to infected animals and, less frequently, directly via a mosquito bite.

ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models.

Pediatric-type high-grade gliomas frequently harbor gene fusions involving receptor tyrosine kinase genes, including neurotrophic tyrosine kinase receptor (NTRK) fusions. Clinically, these tumors show high initial response rates to tyrosine kinase inhibition but ultimately recur due to the accumulation of additional resistance-conferring mutations. Here, we developed a series of genetically engineered mouse models of treatment-naïve and -experienced NTRK1/2/3 fusion-driven gliomas.

Impact of Intramolecular Hydrogen Bonding on the Reactivity of Cupric Superoxide Complexes with O-H and C-H Substrates.

The dioxygen reactivity of a series of TMPA-based copper(I) complexes (TMPA=tris(2-pyridylmethyl)amine), with and without secondary-coordination-sphere hydrogen-bonding moieties, was studied at -135 °C in 2-methyltetrahydrofuran (MeTHF). Kinetic stabilization of the H-bonded [( TMPA)Cu (O )] cupric superoxide species was achieved, and they were characterized by resonance Raman (rR) spectroscopy. The structures and physical properties of [( TMPA)Cu (N )] azido analogues were compared, and the O reactivity of ligand-Cu complexes when an H-bonding moiety is replaced by a methyl group was contrasted.

Enhanced Rates of C-H Bond Cleavage by a Hydrogen-Bonded Synthetic Heme High-Valent Iron(IV) Oxo Complex.

Secondary coordination sphere interactions are critical in facilitating the formation, stabilization, and enhanced reactivity of high-valent oxidants required for essential biochemical processes. Herein, we compare the C-H bond oxidizing capabilities of spectroscopically characterized synthetic heme iron(IV) oxo complexes, FCmpd-II (F = tetrakis(2,6-difluorophenyl)porphyrinate), and a 2,6-lutidinium triflate (LutH) Lewis acid adduct involving ferryl O-atom hydrogen-bonding, FCmpd-II(LutH). Second-order rate constants utilizing C-H and C-D substrates were obtained by UV-vis spectroscopic monitoring, while products were characterized and quantified by EPR spectroscopy and gas chromatography (GC).