6 research outputs found

    Inhibition of MLC Phosphorylation Restricts Replication of Influenza Virus—A Mechanism of Action for Anti-Influenza Agents

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    Influenza A viruses are a severe threat worldwide, causing large epidemics that kill thousands every year. Prevention of influenza infection is complicated by continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK and protein kinase C inhibitors; however, the downstream effectors of these pathways have not been determined. In this study, we identified a common mechanism for the inhibitory effects of a significant group of anti-influenza agents. Our studies showed that influenza infection activates a series of signaling pathways that converge to induce myosin light chain (MLC) phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C, and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation leads to the inhibition of influenza proliferation. In contrast, the induction of MLC phosphorylation enhances influenza proliferation, as does activation of the HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC phosphorylation. Additionally, in intracellular trafficking studies, we found that the nuclear export of influenza ribonucleoprotein depends on MLC phosphorylation. Our studies provide evidence that modulation of MLC phosphorylation is an underlying mechanism for the inhibitory effects of many anti-influenza compounds

    Family first: Evidence of consistency and variation in the value of family versus personal happiness across 49 different cultures

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    People care about their own well-being, but also about the well-being of their families. It is currently however unknown how much people tend to value their own and their family’s well-being. A recent study documented that people value family happiness over personal happiness across four cultures. In this study, we sought to replicate this finding across a larger sample size (N = 12,819) and a greater number of countries (N = 49), We found that the strength of the idealization of family over personal happiness preference was small (average Cohen’s ds = .20 with country levels varying from -.02 to almost .48), but ubiquitous, i.e., direction presented in 98% of the studied countries, 73-75% with statistical significance and .40 and .30). Importantly, we did not find strong support for traditional theories in cross-cultural psychology that associate collectivism with greater prioritization of the family versus the individual; country level individualism-collectivism was not associated with variation in the idealization of family versus individual happiness. Our findings indicate that no matter how much various populists abuse the argument of “protecting family life” to disrupt emancipation, family happiness seems to be a pan-culturally phenomenon. Family well-being is a key ingredient of social fabric across the world, and should be acknowledged by psychology and well-being researchers, and by progressive movements too

    Phosphorylation Site Dynamics of Early T-cell Receptor Signaling

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    The value of open-source clinical science in pandemic response: lessons from ISARIC

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