Glucocortiocoid Treatment of MCMV Infected Newborn Mice Attenuates CNS Inflammation and Limits Deficits in Cerebellar Development

Infection of the developing fetus with human cytomegalovirus (HCMV) is a major cause of central nervous system disease in infants and children; however, mechanism(s) of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV) results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC) proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ) in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV

Novel route to synthesize complex metal sulfides: Hydrothermal coupled dissolution-reprecipitation replacement reactions

A novel route for the synthesis of complex metal sulfides using hydrothermal coupled dissolutionreprecipitation reactions is reported. Two thiospinels, (Ni,Fe)₃S₄ (violarite) and Co₃S₄ (linnaeite), were synthesized using (Fe,Ni)₉S₈ (pentlandite) and Co₉S₈ (cobaltpentlandite) as precursors. The Fe/Ni ratio of (Ni,Fe)₃S₄ can be adjusted by varying the reaction conditions, for example, temperature (125–145 °C), pH (2.90, 3.90, 5.00), and precursor stoichiometry ((FexNi1-x)₉S₈, x = 0.4, 0.5, 0.55, 0.6). Pure (Ni,Fe)₃S₄ can be synthesized by utilizing a flow-through hydrothermal cell rather than a static hydrothermal cell as the fluid flow improves mass transfer and flushes away the Fe₂O₃ byproduct from the reaction front. Synthesis times range from 10 to 20 days, compared to the traditional dry synthesis route for (Ni,Fe)₃S₄ that requires 3 months annealing to obtain a product of only 72 ± 3 wt % purity. This synthesis route is ideal for preparing compounds with low thermal stabilities (<500 °C)