A5026720629- Neuroinflammation and Neurodegeneration Mechanisms
- HIV Research and Treatment
- Barrier Structure and Function Studies
- Mosquito-borne diseases and control
- Cytomegalovirus and herpesvirus research
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- Tryptophan and brain disorders
- Neurogenesis and neuroplasticity mechanisms
- Virus-based gene therapy research
- HIV/AIDS Research and Interventions
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Immune Response and Inflammation
- Influenza Virus Research Studies
- Hepatitis B Virus Studies
- Viral Infections and Immunology Research
- Nitric Oxide and Endothelin Effects
- Hepatitis C virus research
- Viral Infections and Vectors
- Extracellular vesicles in disease
- Molecular Biology Techniques and Applications
- Virology and Viral Diseases
- Neonatal and fetal brain pathology
Glasgow Royal Infirmary
2014-2025
Tulane University
2014-2024
McMaster University
2024
Edinburgh Cancer Research
2024
Tulane Medical Center
2012-2019
McGill University
2015
Western Isles Hospital
2004-2015
Matrix Research (United States)
2014
Gartnavel General Hospital
2007-2013
University of Dundee
2006-2012
Extracellular vesicles (EVs) or exosomes have been implicated in the pathophysiology of infections and cancer. The negative regulatory factor (Nef) encoded by simian immunodeficiency virus (SIV) human (HIV) plays a critical role progression to AIDS impairs endosomal trafficking. Whether HIV-1 Nef can be loaded into EVs has subject controversy, nothing is known about connection between SIV EVs. We find that both proteins are present affinity-purified derived from cultured cells, as well...
Abstract Elimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation SIV-infected macaques, well-accepted non-human primate model infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution molecules and precise cleavage removal fragments the integrated genome blood cells tissues known be viral reservoirs including lymph nodes,...
Abstract Extracellular vesicles (EVs) are secreted from all cell types and intimately involved in tissue homeostasis. They being explored as vaccine gene therapy platforms, well potential biomarkers. As their size is below the diffraction limit of light microscopy, direct visualizations have been daunting single‐particle studies under physiological conditions hampered. Here, stochastic optical reconstruction microscopy (dSTORM) was employed to visualize EVs three‐dimensions localize molecule...
Mice deficient in the inducible nitric-oxide synthase (iNOS), constructed by gene-targeting, were significantly more susceptible to herpes simplex virus (HSV)-1 infection, displayed a delayed clearance of from dorsal root ganglia (DRG) and exhibited an increase frequency reactivation DRG compared with similarly infected heterozygous mice. The iNOS-deficient mice developed enhanced Th1-type immune re- sponses their spleen cells produced higher concentrations IL-12 than This finding suggests...
The Mycobacterium tuberculosis stress response factor SigH plays a crucial role in modulating the pathogen's to heat, oxidative-stress, envelope damage and hypoxia. We hypothesized that lack of this key would alter interaction between pathogen its host cells. compared Mtb, Mtb:Δ-sigH strain where mutation had been genetically complemented (Mtb: Δ-sigH:CO) with primary rhesus macaque bone marrow derived macrophages (Rh-BMDMs). expression numerous inducible homeostatic (CCL) β-chemokines...
Globoid cell leukodystrophy is a lysosomal storage disease characterized by the loss of galactocerebrosidase. Galactocerebrosidase leads to accumulation psychosine and subsequent oligodendrocyte death, demyelination, macrophage recruitment, astroglial activation proliferation. To date, no studies have elucidated mechanism glial cytokine chemokine up-regulation release. We explored novel explanation for development pathological changes in early stages globoid associated with toll-like...
ABSTRACT Inflammatory cytokines are believed to play an important role in the pathogenesis of human immunodeficiency virus type 1-associated encephalitis. To examine this simian (SIV)-infected macaque model neuroAIDS, inflammatory cytokine gene expression was evaluated brains macaques infected with pathogenic SIV mac251 by reverse transcriptase PCR. Interleukin-1 beta readily detected all animals evaluated, regardless infection status or duration infection. Tumor necrosis factor alpha...
Brucella melitensis, a bacterial pathogen and agent of epizootic abortion causes multiple pathologies in humans as well number agriculturally important animal species. Clinical human brucellosis manifests nonspecific, chronic debilitating disease characterized by undulant fever, arthropathies, cardiomyopathies neurological sequelae. These symptoms can occur acutely for few weeks or persist months to years. Within the brain, endothelial glial cells be infected leading downstream activation...
Abstract Intestinal epithelial barrier dysfunction is a well-known sequela of HIV/SIV infection that persists despite antiretroviral therapy. Although inflammation triggering factor, the underlying molecular mechanisms remain unknown. Emerging evidence suggests function epigenetically regulated by inflammation-induced microRNAs (miRNAs). Accordingly, we profiled and characterized miRNA/mRNA expression exclusively in colonic epithelium identified 46 differentially expressed miRNAs (20...
ABSTRACT The influence of host cytokine response on viral load, disease progression, and neurologic lesions was investigated in the simian immunodeficiency virus (SIV)-infected macaque model AIDS. Cytokine gene expression (interleukin-1β [IL-1β], IL-2, IL-6, IL-10, gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α]) loads were evaluated by semiquantitative reverse transcription-PCR lymph nodes 5 control animals 28 infected with SIVmac251 at terminal stages Infected showed higher...
Abstract The foot processes of astrocytes cover over 60% the surface brain microvascular endothelial cells, regulating tight junction integrity. Retraction astrocyte has been postulated to be a key mechanism in pathology. Therefore, movement an response proinflammatory cytokine or even limited retraction would result leaky junctions between cells. Astrocytes lie at gateway CNS and are instrumental controlling leukocyte entry. Cultured typically have polygonal morphology until stimulated. We...
Abstract Background To increase the immunosurveillance in HIV infection, we used retroviral vectors expressing CD 4‐chimeric antigen receptors ( CAR s) to genetically modify autologous T cells and redirect CTL toward . The 4 extracellular domain targets envelope intracellular signaling domains activate cells. maC46 fusion inhibitor binds blocks viral replication. Methods We stimulated rhesus PBMC s with antibodies CD3/CD28 cotransduced 4‐ vectors. ‐transduced were added Env + 293T at E:T of...
We describe the burden of influenza B infections in Scotland during a 13-year study period. Influenza A and viruses cocirculated throughout period, with numbers cases approaching or exceeding those six seasons. both Victoria Yamagata lineage were detected two seasons investigated. For 2012/13 season, accounted for 44.4% all influenzas, highest incidence under age five years. virus led to fewer admissions an intensive care unit (ICU) lower mortality rate than (37 vs 81 ICU three 29 deaths)...