ORCID Profile
0000-0001-5853-9509
Current Organisation
University of North Carolina at Chapel Hill
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Society for Neuroscience
Date: 16-07-2008
DOI: 10.1523/JNEUROSCI.1135-08.2008
Abstract: Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior–posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that in ephrin-A −/− mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus of ephrin-A −/− mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic in ephrin-A2 −/− but disorganized in ephrin-A2/A5 −/− mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information in ephrin-A2/A5 −/− mice suggests a role for ephrin-As in integrating convergent visual inputs.
Publisher: Springer Science and Business Media LLC
Date: 02-08-2016
DOI: 10.1038/SREP30749
Abstract: Despite the extraordinary success of HIV-1 antiretroviral therapy in prolonging life, infected in iduals face lifelong therapy because of a reservoir of latently-infected cells that harbor replication competent virus. Recently, compounds have been identified that can reverse HIV-1 latency in vivo . These latency- reversing agents (LRAs) could make latently-infected cells vulnerable to clearance by immune cells, including cytolytic CD8+ T cells. We investigated the effects of two leading LRA classes on CD8+ T cell phenotype and function: the histone deacetylase inhibitors (HDACis) and protein kinase C modulators (PKCms). We observed that relative to HDACis, the PKCms induced much stronger T cell activation coupled with non-specific cytokine production and T cell proliferation. When examining antigen-specific CD8+ T cell function, all the LRAs except the HDACi Vorinostat reduced, but did not abolish, one or more measurements of CD8+ T cell function. Importantly, the extent and timing of these effects differed between LRAs. Panobinostat had detrimental effects within 10 hours of drug treatment, whereas the effects of the other LRAs were observed between 48 hours and 5 days. These observations suggest that scheduling of LRA and CD8+ T cell immunotherapy regimens may be critical for optimal clearance of the HIV-1 reservoir.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2016
DOI: 10.1161/CIRCIMAGING.115.004430
Abstract: Patients with treated HIV infection have clear survival benefits although with increased cardiac morbidity and mortality. Mechanisms of heart disease may be partly related to untreated chronic inflammation. Cardiovascular magnetic resonance imaging allows a comprehensive assessment of myocardial structure, function, and tissue characterization. We investigated, using cardiovascular magnetic resonance, subclinical inflammation and myocardial disease in asymptomatic HIV-infected in iduals. Myocardial structure and function were assessed using cardiovascular magnetic resonance at 1.5-T in treated HIV-infected in iduals without known cardiovascular disease (n=103 mean age, 45±10 years) compared with healthy controls (n=92 mean age, 44±10 years). Assessments included left ventricular volumes, ejection fraction, strain, regional systolic, diastolic function, native T1 mapping, edema, and gadolinium enhancement. Compared with controls, subjects with HIV infection had 6% lower left ventricular ejection fraction ( P .001), 7% higher myocardial mass ( P =0.02), 29% lower peak diastolic strain rate ( P .001), 4% higher short-tau inversion recovery values ( P =0.02), and higher native T1 values (969 versus 956 ms in controls P =0.01). Pericardial effusions and myocardial fibrosis were 3 and 4× more common, respectively, in subjects with HIV infection (both P .001). Treated HIV infection is associated with changes in myocardial structure and function in addition to higher rates of subclinical myocardial edema and fibrosis and frequent pericardial effusions. Chronic systemic inflammation in HIV, which involves the myocardium and pericardium, may explain the high rate of myocardial fibrosis and increased cardiac dysfunction in people living with HIV.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.JIM.2013.03.001
Abstract: The capacity of CD8+ T cells to inhibit HIV-1 replication in vitro strongly correlates with virus control in vivo. Post-hoc evaluations of HIV-1 vaccine candidates suggest that this immunological parameter is a promising benchmark of vaccine efficacy. Large-scale analysis of CD8+ T cell antiviral activity requires a rapid, robust and economical assay for accurate quantification of HIV-1 infection in primary CD4+ T cells. Detection of intracellular HIV-1 p24 antigen (p24 Ag) by flow cytometry is one such method but it is thought to be less sensitive and quantitative than p24 Ag ELISA. We report that fixation and permeabilisation of HIV-infected cells using paraformaldehyde/50% methanol/Nonidet P-40 instead of a conventional paraformaldehyde/saponin-based protocol improved their detection across multiplicities of infection (MOI) ranging from 10(-2) to 8×10(-5), and by nearly two-fold (p<0.001) at the optimal MOI tested (10(-2)). The frequency of infected cells was strongly correlated with p24 Ag release during culture, thus validating its use as a measure of productive infection. We were also able to quantify infection with a panel of HIV-1 isolates representing the major clades. The protocol described here is rapid and cost-effective compared with ELISA and thus could be a useful component of immune monitoring of HIV-1 vaccines and interventions to reduce viral reservoirs.
Location: United States of America
No related grants have been discovered for Genevieve Clutton.