Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction

Human myxovirus resistance 2 (MX2/MXB) is an interferon-induced post-entry inhibitor of human immunodeficiency virus type-1 (HIV-1) infection. While the precise mechanism of viral inhibition remains unclear, MX2 is localized to the nuclear envelope, and blocks the nuclear import of viral cDNAs. The amino-terminus of MX2 (N-MX2) is essential for anti-viral function, and mutation of a triple arginine motif at residues 11 to 13 abrogates anti-HIV-1 activity. In this study, we sought to investigate the role of N-MX2 in anti-viral activity by identifying functionally relevant host-encoded interaction partners through yeast-two-hybrid screening. Remarkably, five out of seven primary candidate interactors were nucleoporins or nucleoporin-like proteins, though none of these candidates were identified when screening with a mutant RRR11-13A N-MX2 fragment. Interactions were confirmed by co-immunoprecipitation, and RNA silencing experiments in cell lines and primary CD4+ T cells demonstrated that multiple components of the nuclear pore complex and nuclear import machinery can impact MX2 anti-viral activity. In particular, the phenylalanine-glycine (FG) repeat containing cytoplasmic filament nucleoporin NUP214, and transport receptor transportin-1 (TNPO1) were consistently required for full MX2, and interferon-mediated, anti-viral function. Both proteins were shown to interact with the triple arginine motif, and confocal fluorescence microscopy revealed that their simultaneous depletion resulted in diminished MX2 accumulation at the nuclear envelope. We therefore propose a model whereby multiple components of the nuclear import machinery and nuclear pore complex help position MX2 at the nuclear envelope to promote MX2-mediated restriction of HIV-1

Maternal activity level in patients with preterm premature rupture of membranes: A Prospective Observational Cohort Study

Objective: To evaluate the level of maternal physical activity effect on the perinatal outcomes of women with preterm premature rupture of membranes (PPROM) Study Design: This is a pilot, prospective, observational multicenter cohort study. We approached patients admitted between 23 0/7 weeks to 32 0/7 weeks gestation with confirmed PPROM between January of 2014 and June of 2017 All patients received corticosteroids and latency antibiotics. Enrollment was done on third day of admission. Delivery occurred at 34 weeks per protocol via induction of labor or cesarean section as obstetrically indicated; or sooner if chorioamnionitis was diagnosed or spontaneous preterm labor occurred. Patients were provided a pedometer to wear for the duration of their antepartum course and they have maternal activity at lib and were encouraged to go to the physical therapy gymnasium. Results: We enrolled 32 women. We stratified them in two groups: low activity as less than 500 step a day and higher maternal activity more than 500 steps a day, There were no significant differences in the demographics. Latency from PPROM to delivery were significantly prolonged in women with maternal activity \u3e 500 steps a day: 11.0 ± 8.42 vs 21.18 ± 4.26 days p = 0.004. No maternal or fetal adverse outcomes were identified. Conclusion: Maternal activity more than 500 steps a day showed a significant association with prolongation of latencyhttps://jdc.jefferson.edu/obgynposters/1001/thumbnail.jp

Caractérisation hydrologique de l'interface Sol-Végétation-Atmosphère - Groupe de travail sur l'hydrologie du Plateau de Saclay

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Caractérisation hydrologique de l'interface Sol-Végétation-Atmosphère Groupe de travail sur l'hydrologie du Plateau de Saclay

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