Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness.To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat. RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors. CONCLUSION: Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions

Mitochondrial polymorphisms in rat genetic models of hypertension

Hypertension is a complex trait that has been studied extensively for genetic contributions of the nuclear genome. We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variations in mtDNA were observed between the comparisons S versus LEW, S versus MNS, S versus SHR, S versus AS, and SHR versus AS, respectively. Among the 13 genes coding for proteins of the electron transport chain, 8 genes had nonsynonymous variations between S, LEW, MNS, SHR, and AS. The lack of any sequence variants between the mitochondrial genomes of S and R rats provides conclusive evidence that divergence in blood pressure between these two inbred strains is exclusively programmed through their nuclear genomes. The variations detected among the various hypertensive strains provides the basis to construct conplastic strains and further evaluate the effects of these variants on hypertension and associated phenotypes

Toward High Performance Computing Education

High Performance Computing (HPC) is the ability to process data and perform complex calculations at extremely high speeds. Current HPC platforms can achieve calculations on the order of quadrillions of calculations per second with quintillions on the horizon. The past three decades witnessed a vast increase in the use of HPC across different scientific, engineering and business communities, for example, sequencing the genome, predicting climate changes, designing modern aerodynamics, or establishing customer preferences. Although HPC has been well incorporated into science curricula such as bioinformatics, the same cannot be said for most computing programs. This working group will explore how HPC can make inroads into computer science education, from the undergraduate to postgraduate levels. The group will address research questions designed to investigate topics such as identifying and handling barriers that inhibit the adoption of HPC in educational environments, how to incorporate HPC into various curricula, and how HPC can be leveraged to enhance applied critical thinking and problem solving skills. Four deliverables include: (1) a catalog of core HPC educational concepts, (2) HPC curricula for contemporary computing needs, such as in artificial intelligence, cyberanalytics, data science and engineering, or internet of things, (3) possible infrastructures for implementing HPC coursework, and (4) HPC-related feedback to the CC2020 project