A5052525811- PI3K/AKT/mTOR signaling in cancer
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- HIV/AIDS drug development and treatment
- Cardiac Ischemia and Reperfusion
- Polyamine Metabolism and Applications
- Cancer Genomics and Diagnostics
- Protein Kinase Regulation and GTPase Signaling
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Mast cells and histamine
- Advanced biosensing and bioanalysis techniques
- SARS-CoV-2 detection and testing
- Bioactive Compounds and Antitumor Agents
- Cytomegalovirus and herpesvirus research
- Bacillus and Francisella bacterial research
- Microbial Inactivation Methods
- Foot and Ankle Surgery
- Clostridium difficile and Clostridium perfringens research
- Genetics, Bioinformatics, and Biomedical Research
- Fungal and yeast genetics research
- Neuroscience and Neuropharmacology Research
Aintree University Hospital
2023
University of Liverpool
2023
Clark Art Institute
2022
Frederick National Laboratory for Cancer Research
2016-2021
Leidos (United States)
2016-2019
East Lancashire Hospitals NHS Trust
2019
Courtagen Life Sciences (United States)
2014
Houston Methodist
2012
Methodist Hospital
2012
Qiagen (United States)
2011
The removal of extracellular amino acids or leucine alone inhibits the ability mammalian target rapamycin (mTOR) to signal raptor-dependent substrates, p70 S6 kinase and 4E-BP. This inhibition can be overcome by overexpression Rheb GTPase. binds directly amino-terminal lobe mTOR catalytic domain, activates in a GTP-dependent manner. Herein we show that binding endogenous recombinant is reversibly inhibited withdrawal all just leucine. effect acid not attributable changes Rheb-GTP charging;...
The transition from compensated hypertrophy to failure in spontaneously hypertensive rats (SHR) of advanced age is associated with a marked increase collagen, reduction myocyte mass, and maximum Ca(2+)-activated myofibrillar force. We hypothesized that the mass functional loss may be due increased cell death by apoptosis. To test this hypothesis, we studied hearts failing (SHR-F) nonfailing SHR (SHR-NF) age-matched Wistar-Kyoto (WKY). In addition, SHR-F had been treated an...
The small GTPase Rheb is a positive upstream regulator of the target rapamycin (TOR) complex 1 in mammalian cells and can bind directly to TOR 1. To identify regions surface most critical for signaling 1, we created set 26 mutants wherein clusters 1-5 putative solvent-exposed residues were changed alanine, ultimately changing 65 distributed over entire surface. function these was assessed by their ability, comparison wild type Rheb, restore phosphorylation S6K1(Thr389) when expressed...
The major obstacle to more-definitive treatment for HIV infection is the early establishment of virus that persists despite long-term combination antiretroviral therapy (cART) and can cause recrudescent viremia if cART interrupted. Previous studies DNA indicated only a small fraction persistent viral sequences was intact. Experimental simian immunodeficiency (SIV) infections nonhuman primates (NHPs) are essential models testing interventions designed reduce reservoir. We studied genomic...
Human embryonic stem cell (hESC) lines derived from poor quality embryos usually have either normal or abnormal karyotypes. However, it is still unclear whether their biological characteristics are similar. Seven new hESC were established using discarded embryos. Five had karyotype, one was with an unbalanced Robertsonian translocation and a triploid karyotype. Their characteristics, short tandem repeat loci, HLA typing, differentiation capability imprinted gene, DNA methylation X chromosome...
Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course SIV infection SMs are absence chronic immune activation and low CD4(+) central memory (TCM) stem cell (TSCM) T cells. To better understand role replication determining main features SMs, we treated 12 with a potent antiretroviral therapy (ART) regimen for 2 to months. We observed that ART suppressed viremia <60 copies/ml plasma 10...
Highly sensitive detection of HIV-1 nucleic acids is critical importance for evaluating treatment interventions superimposed on combination antiretroviral therapy (cART) in infected individuals. SIV infection rhesus macaques models many key aspects human and plays a role evaluation approaches prevention, attempted eradication HIV infection. Here we describe two droplet digital PCR (ddPCR) assays, ddPCR DNA assay an RT-ddPCR RNA detecting simian immunodeficiency virus (SIV) the RainDance...
Screening of patients for cancer-driving mutations is now used cancer prognosis, remission scoring and treatment selection. Although recently emerged targeted next-generation sequencing-based approaches offer promising diagnostic capabilities, there are still limitations. There a pressing clinical need well-validated, rapid, cost-effective mutation profiling system in patient specimens. Given their speed cost-effectiveness, quantitative PCR detection techniques well suited the environment....
Abstract Background Simian immunodeficiency virus (SIV)-infected rhesus macaques constitute an excellent model of human HIV infection. Sensitive detection SIV RNA in cell and tissue samples from infected animals subjected to treatment regimens becomes especially critical determining which therapeutic attempts are successful, consequently, interventions should be prioritized cure research. Results In this report, we describe the design testing a Raindance ddPCR platform-based, sensitive...
Accurate and sensitive quantification of rebound competent HIV that persists despite combination antiretroviral treatment (cART), including in latently infected cells (i.e., viral reservoir), is critical for evaluating cure strategies decreasing or eliminating this reservoir. Simian immunodeficiency virus (SIV)-infected Rhesus macaques are an important non-human primate (NHP) system studying potential as they model many key aspects human HIV-infection the persistence a latent reservoir...