A Preliminary Assessment of Silver Nanoparticle Inhibition of Monkeypox Virus Plaque Formation

The use of nanotechnology and nanomaterials in medical research is growing. Silver-containing nanoparticles have previously demonstrated antimicrobial efficacy against bacteria and viral particles. This preliminary study utilized an in vitro approach to evaluate the ability of silver-based nanoparticles to inhibit infectivity of the biological select agent, monkeypox virus (MPV). Nanoparticles (10–80 nm, with or without polysaccharide coating), or silver nitrate (AgNO3) at concentrations of 100, 50, 25, and 12.5 μg/mL were evaluated for efficacy using a plaque reduction assay. Both Ag-PS-25 (polysaccharide-coated, 25 nm) and Ag-NP-55 (non-coated, 55 nm) exhibited a significant (P ≤ 0.05) dose-dependent effect of test compound concentration on the mean number of plaque-forming units (PFU). All concentrations of silver nitrate (except 100 μg/mL) and Ag-PS-10 promoted significant (P ≤ 0.05) decreases in the number of observed PFU compared to untreated controls. Some nanoparticle treatments led to increased MPV PFU ranging from 1.04- to 1.8-fold above controls. No cytotoxicity (Vero cell monolayer sloughing) was caused by any test compound, except 100 μg/mL AgNO3. These results demonstrate that silver-based nanoparticles of approximately 10 nm inhibit MPV infection in vitro, supporting their potential use as an anti-viral therapeutic

A resonant-term-based model including a nascent disk, precession, and oblateness: application to GJ 876

Investigations of two resonant planets orbiting a star or two resonant satellites orbiting a planet often rely on a few resonant and secular terms in order to obtain a representative quantitative description of the system's dynamical evolution. We present a semianalytic model which traces the orbital evolution of any two resonant bodies in a first- through fourth-order eccentricity or inclination-based resonance dominated by the resonant and secular arguments of the user's choosing. By considering the variation of libration width with different orbital parameters, we identify regions of phase space which give rise to different resonant ''depths,'' and propose methods to model libration profiles. We apply the model to the GJ 876 extrasolar planetary system, quantify the relative importance of the relevant resonant and secular contributions, and thereby assess the goodness of the common approximation of representing the system by just the presumably dominant terms. We highlight the danger in using ''order'' as the metric for accuracy in the orbital solution by revealing the unnatural libration centers produced by the second-order, but not first-order, solution, and by demonstrating that the true orbital solution lies somewhere ''in-between'' the third- and fourth-order solutions. We also present formulas used to incorporate perturbations from central-body oblateness and precession, and a protoplanetary or protosatellite thin disk with gaps, into a resonant system. We quantify these contributions to the GJ 876 system, and thereby highlight the conditions which must exist for multi-planet exosystems to be significantly influenced by such factors. We find that massive enough disks may convert resonant libration into circulation; such disk-induced signatures may provide constraints for future studies of exoplanet systems.Comment: 39 pages of body text, 21 figures, 5 tables, 1 appendix, accepted for publication in Celestial Mechanics and Dynamical Astronom

Cohesin complex-associated holoprosencephaly

Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80–90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly