- Genomics, phytochemicals, and oxidative stress
- Astro and Planetary Science
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Isotope Analysis in Ecology
- Glutathione Transferases and Polymorphisms
- Alzheimer's disease research and treatments
- Nuclear Physics and Applications
- Twentieth Century Scientific Developments
- Planetary Science and Exploration
- Neuroinflammation and Neurodegeneration Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Tryptophan and brain disorders
- Historical Medical Research and Treatments
- SARS-CoV-2 and COVID-19 Research
- Coenzyme Q10 studies and effects
- Molecular Biology Techniques and Applications
- History and advancements in chemistry
- SARS-CoV-2 detection and testing
- Parkinson's Disease Mechanisms and Treatments
- Space Exploration and Technology
- Astronomical Observations and Instrumentation
- Vitamin C and Antioxidants Research
- Virus-based gene therapy research
University of Alberta
2025
University of Wisconsin–Madison
2012-2024
Centers for Disease Control and Prevention
2013-2024
National Center for HIV/AIDS Viral Hepatitis STD and TB Prevention
2008-2024
University of California, Los Angeles
2023
Lawrence Berkeley National Laboratory
2021
Atlas Copco (United States)
2020
Hyattsville Community Development Corporation
2019
Villanova University
1996-2018
William S. Middleton Memorial Veterans Hospital
2014
Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex men; however, efficacy heterosexuals is uncertain.
The antioxidant responsive element (ARE) mediates transcriptional regulation of phase II detoxification enzymes and proteins such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases, glutamate-cysteine ligase. In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in activation ARE-driven genes identify Nrf2-dependent by oligonucleotide microarray analysis using primary cortical astrocytes from Nrf2(+/+) Nrf2(-/-) mice. had decreased basal NQO1...
Astrocytes have a higher antioxidant potential in comparison to neurons. Pathways associated with this selective advantage include the transcriptional regulation of enzymes via action Cap'n'Collar transcription factor Nrf2 at response element (ARE). Here we show that overexpression can reengineer neurons express glial pathway and enhance gene expression. However, Nrf2-mediated protection from oxidative stress is conferred primarily by glia mixed cultures. The properties Nrf2-overexpressing...
Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence in affected communities. Large-scale seroprevalence studies provide better estimates proportion population previously infected.
Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model PD. It is known that under conditions oxidative stress, transcription factor NF-E2-related (Nrf2) binds to antioxidant response element (ARE) induce phase II detoxification enzymes. To investigate role Nrf2 process MPTP-induced toxicity, mice expressing human placental alkaline phosphatase (hPAP) gene driven by a promoter containing core ARE...
Binding of the transcription factor nuclear E2-related 2 (Nrf2) to antioxidant response element (ARE) in neural cells results induction a battery genes that can coordinate protective against variety oxidative stressors. In this study, tert -butylhydroquinone (tBHQ) and sulforaphane were used as activators pathway. Consistent with previous studies, treatment primary cortical cultures from ARE reporter mice revealed selective promoter activity astrocytes. This activation protected neurons...
NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcription that binds to the promoter sequence "antioxidant responsive element (ARE)" leading coordinated up-regulation of ARE-driven detoxification and antioxidant genes. Since expression wide array genes are positively regulated by ARE sequence, Nrf2 may serve as master regulator cellular defense system against oxidative stress. In support this, numerous studies have shown protects many cell types organ systems from broad spectrum...
Activation of the transcription factor Nrf2 in astrocytes coordinates upregulation antioxidant defenses and confers protection to neighboring neurons. Dominant mutations Cu/Zn-superoxide dismutase (SOD1) cause familial forms amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by progressive loss motor Non-neuronal cells, including astrocytes, shape neuron survival ALS are potential target prevent degeneration. The protective effect activation has never been examined chronic...
Transmitted HIV-1 drug resistance can compromise initial antiretroviral therapy (ART); therefore, its detection is important for patient management. The absence of drug-associated selection pressure in treatment-naïve persons cause drug-resistant viruses to decline levels undetectable by conventional bulk sequencing (minority variants). We used sensitive and simple tests investigate evidence transmitted drug-naïve assess the clinical implications minority variants.We performed a...
In the absence of an effective vaccine, HIV continues to spread globally, emphasizing need for novel strategies limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove be intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily intermittent regimens increasing antiviral activity in a macaque model that closely resembles human
Zika virus is a single-stranded RNA in the genus Flavivirus and closely related to dengue, West Nile, Japanese encephalitis, yellow fever viruses (1,2). Among flaviviruses, dengue share similar symptoms of infection, transmission cycles, geographic distribution. Diagnostic testing for infection can be accomplished using both molecular serologic methods. For persons with suspected disease, positive real-time reverse transcription-polymerase chain reaction (rRT-PCR) result confirms but...
Compared with the volume of data on coronavirus disease 2019 (COVID-19) outbreaks among older adults, relatively few are available concerning COVID-19 in younger, healthy persons United States (1,2). In late March 2020, aircraft carrier USS Theodore Roosevelt arrived at port Guam after numerous U.S. service members onboard developed COVID-19. April, Navy and CDC investigated this outbreak, demographic, epidemiologic, laboratory findings a convenience sample 382 serving aboard reported study....
Abstract Alzheimer’s disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis astrocytes in APP/PS1 ß-amyloidopathy MAPT P301S tauopathy mice revealed that only influenced expression AD risk genes, both pathologies precociously induced age-dependent changes, had distinct overlapping signatures found human post-mortem astrocytes. Both an astrocyte signature involving repression bioenergetic translation machinery, induction...
Abstract Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes mature myelin-forming oligodendrocytes a determinant remyelination. Using vivo/ ex vitro rodent models, unbiased RNA sequencing, functional manipulation, human brain lesion analyses, discover...
NF-E2-related factor-2 (Nrf2) regulates the gene expression of phase II detoxification enzymes and antioxidant proteins through an enhancer sequence referred to as antioxidant-responsive element (ARE). In this study, we demonstrate that Nrf2 protects neurons in mixed primary neuronal cultures containing both astrocytes (∼10%) (∼90%) coordinate up-regulation ARE-driven genes. Nrf2-/- culture system were more sensitive mitochondrial toxin (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine or...
Tg2576 mice overexpress a mutant form of human amyloid precursor protein with the Swedish mutation (APP(Sw)), resulting in high beta-amyloid (Abeta) levels brain. Despite this, plaques do not develop until 12 months age, and there is no neuronal loss as old 16 months. Gene expression profiles hippocampus cerebellum 6-month-old APP(Sw) were compared age-matched controls. The transthyretin, shown to sequester Abeta prevent fibril formation vitro, several genes insulin-signaling pathway, e.g.,...
Abstract Synthetic triterpenoids have been developed, which are potent inducers of cytoprotective enzymes and inhibitors inflammation, greatly improving on the weak activity naturally occurring triterpenoids. An imidazolide triterpenoid derivative, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im or TP235), has previously shown to potently protect against hepatic tumorigenesis, acting in part by inducing genes through Keap1-Nrf2-antioxidant response element (ARE) signaling....
Alzheimer's disease (AD) may be caused by the abnormal processing of amyloid precursor protein (APP) and accumulation β-amyloid (Aβ). The can proteolytically cleaved into multiple fragments, many which have distinct biological actions. Although a high level Aβ toxic, α-secretase APP (sAPPα) is neuroprotective. However, mechanism sAPPα protection unknown. Here, we show that increases expression levels several neuroprotective genes protects organotypic hippocampal cultures from Aβ-induced tau...