Activation of Egr-1 expression in astrocytes by HIV-1 Tat: new insights into astrocyte-mediated Tat neurotoxicity

Human immunodeficiency virus type 1 (HIV-1) Tat plays an important role in HIV-associated neuropathogenesis; the underlying mechanisms are still evolving. We have recently shown that HIV-1 Tat induces expression of glial fibrillary acidic protein (GFAP), a characteristic of HIV-1 infection of the central nervous system (CNS). We have also shown that the Tat-induced GFAP expression in astrocytes is regulated by p300, and that deletion of the early growth response 1 (Egr-1) cis-transacting element within the p300 promoter abolishes Tat-induced GFAP expression. In this study, we further examined the relationship between Tat and Egr-1 in astrocytes. We found increased Egr-1 protein expression in Tat-expressing human astrocytoma cells and mouse primary astrocytes. Using the Egr-1 promoter-driven firefly luciferase reporter gene assay and the site-directed mutagenesis, we demonstrated that Tat increased Egr-1 expression by transactivating the Egr-1 promoter and involving specific serum response elements (SRE) within the promoter. Consistent with these data, we showed that Tat transactivation of the Egr-1 promoter was abrogated when astrocytes were cultured in serum-reduced media. Taken together, these results reveal that Tat directly transactivates Egr-1 expression and suggest that Tat interaction with Egr-1 is probably one of the very upstream molecular events that initiate Tat-induced astrocyte dysfunction and subsequent Tat neurotoxicity

Courtship entanglements: a first report of mating behavior and sexual dichromatism in the Southeast Asian keel-bellied whipsnake, Dryophiops rubescens

We describe the first observations of courtship behavior and sexual dichromatism in the keel-bellied whipsnake, Dryophiops rubescens, from an encounter near Sandakan, eastern Sabah, Borneo, Malaysia. During this behavior, two males and a female were longitudinally intertwined, with the males jockeying for position along the body of the female. This “mating braid” lasted for well over 1 h, with the entwined snakes moving a distance of over 10 m together. While polygynous mating is known from other snake species, direct observations of mating behaviors in Southeast Asian colubrids are extremely rare. These observations also revealed the presence of sexual dichromatism in D. rubescens, with darker head coloration present in the males

Prmt5 is a regulator of muscle stem cell expansion in adult mice.

Skeletal muscle stem cells (MuSC), also called satellite cells, are indispensable for maintenance and regeneration of adult skeletal muscles. Yet, a comprehensive picture of the regulatory events controlling the fate of MuSC is missing. Here, we determine the proteome of MuSC to design a loss-of-function screen, and identify 120 genes important for MuSC function including the arginine methyltransferase Prmt5. MuSC-specific inactivation of Prmt5 in adult mice prevents expansion of MuSC, abolishes long-term MuSC maintenance and abrogates skeletal muscle regeneration. Interestingly, Prmt5 is dispensable for proliferation and differentiation of Pax7(+) myogenic progenitor cells during mouse embryonic development, indicating significant differences between embryonic and adult myogenesis. Mechanistic studies reveal that Prmt5 controls proliferation of adult MuSC by direct epigenetic silencing of the cell cycle inhibitor p21. We reason that Prmt5 generates a poised state that keeps MuSC in a standby mode, thus allowing rapid MuSC amplification under disease conditions

Standard Testing Procedure for Quantifying Breathing Gas Carbon Dioxide Partial Pressure for Extravehicular Activity and Launch, Entry, Survival Pressure Suits

This standard test and analysis protocol establishes the procedure for determining the partial pressure of inspired carbon dioxide (PICO2) exposure level experienced by persons operating a pressurized suit. The purpose of this Standard Testing Procedure (STP) is to describe the test conditions and procedures necessary to acquire data in support of certification that manufacturer submitted Extravehicular Activity (EVA) and/or Launch, Entry, Survival (LES) suit designs maintain safe levels of carbon dioxide (CO2) in the helmet during suited operations. The STP shall be used to measure the in-suit inhaled and exhaled dry-gas partial pressure of CO2 (PCO2), followed by calculation of the water vapor saturated PICO2 during the inhalation portion of the breathing cycle, while a human test subject is performing work at levels anticipated during suited operations in ground and flight environments. The procedure is designed to test the evaluated suit on a human test subject as a dynamic system, generate repeatable results under defined laboratory conditions, and perform consistent analysis on acquired samples.This STP is used to evaluate space suits in a hyperbaric environment (above atmospheric pressure). Changes would need to be made to the test equipment/setup to accommodate a hypobaric environment. There is no specific EVA or LES suit performance requirement to meet or pass/fail criteria associated with this STP

Boundary Data Smoothness for Solutions of Nonlocal Boundary Value Problems for nth Order Differential Equations

Under certain conditions, solutions of the boundary value problem y(n)=f(x,y,y′,…,y(n−1)), y(n)=f(x,y,y′,…,y(n−1)), y(i−1)(x1)=yiy(i−1)(x1)=yi for 1≤i≤n−11≤i≤n−1, and y(x2)−∑mi=1riy(ηi)=yny(x2)−∑i=1mriy(ηi)=yn, are differentiated with respect to boundary conditions, where

Myf5-Positive Satellite Cells Contribute to Pax7-Dependent Long-Term Maintenance of Adult Muscle Stem Cells

SummarySkeletal muscle contains Pax7-expressing muscle stem or satellite cells, enabling muscle regeneration throughout most of adult life. Here, we demonstrate that induced inactivation of Pax7 in Pax7-expressing cells of adult mice leads to loss of muscle stem cells and reduced heterochromatin condensation in rare surviving satellite cells. Inactivation of Pax7 in Myf5-expressing cells revealed that the majority of adult muscle stem cells originate from myogenic lineages, which express the myogenic regulators Myf5 or MyoD. Likewise, the majority of muscle stem cells are replenished from Myf5-expressing myogenic cells during adult life, and inactivation of Pax7 in Myf5-expressing cells after muscle damage leads to a complete arrest of muscle regeneration. Finally, we demonstrate that a relatively small number of muscle stem cells are sufficient for efficient repair of skeletal muscles. We conclude that Pax7 acts at different levels in a nonhierarchical regulatory network controlling muscle-satellite-cell-mediated muscle regeneration

COMBINED GRAPE SEED EXTRACT AND L-CITRULLINE SUPPLEMENTATION IMPROVES CYCLING TIME TRIAL PERFORMANCE

Studies have shown that L-Citrulline alone improves nitric oxide (NO) production which is beneficial for vasodilation or increasing skeletal blood flow. Grape seed extract (GSE) also has been shown to increase the production of NO via activation of NO synthase, reducing peripheral resistance during exercise. PURPOSE: The aim of this study was to determine if acute administration of the combined GSE and L-Citrulline supplements had a greater effect on exercise performance compared to taking either supplement alone. METHODS: In a randomized cross-over design, 12 healthy male subjects aged between 18 to 30 years were divided into four groups: Placebo (starch), L-Citrulline, GSE, and GSE and L-Citrulline combined. They performed a timed trial (8 km) using a cycle ergometer to evaluate exercise performance after taking each supplement. RESULTS: There was no significant difference in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and ratings of perceived exertion (RPE) across supplementations. Combined GSE and L-Citrulline supplementation significantly lowered a time trial compared to other supplements (placebo: 19.9±1.0 min; GSE: 19.3±1.0 min; L-Citrulline:19.6±0.9 min; GSE+L-Citrulline; 18.9±1.0 min. CONCLUSION: our results suggest that acute supplementation with combined GSE and L-citrulline appears to be an ergogenic aid that can improve exercise performance

Solution-Focused Brief Therapy-Enhanced Fatherhood Curriculum Pilot Study: A Comparison of Delivery Methods in Response to the COVID-19 Pandemic

Many fatherhood programs provide curriculum-based peer groups, but the evidence for their effectiveness is limited and prior studies highlight challenges in recruiting and retaining participants. This pilot study aimed to test the effectiveness of a standard fatherhood curriculum enhanced with Solution Focused Brief Therapy (SFBT) using a quasi-experimental design. Study outcomes included father involvement and parenting skills measured immediately post-intervention. A sample of 92 fathers (M age = 35.2) participating in a fatherhood program were recruited to participate in the study. Due to COVID-19, the treatment groups were moved to an online format. Independent samples and paired samples t-test were used to detect group differences and Hedges’s effect sizes were also calculated to examine magnitude of treatment effects. Although the SFBT-enhanced peer group curriculum did not outperform the comparison curriculum, the online version of the SFBT-enhanced curriculum was found to be equivalent to the in-person curriculum. These novel findings suggest that online fatherhood groups may be similarly as effective as in-person groups, which may increase opportunities for access and participation in fatherhood programs