University of Pittsburgh

About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.

Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies

Abstract: Background Late-life depression may increase the risk of incident dementia, in particular of Alzheimer’s disease and vascular dementia. Aims To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer’s disease and vascular dementia in individuals with late-life depression in population-based prospective studies. Method A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer’s disease and vascular dementia in older adults with late-life depression. Results Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P <0.001), Alzheimer’s disease (1.65, 95% CI 1.42-1.92, P <0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P <0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer’s disease ( P = 0.03). Conclusions Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer’s disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer’s disease.

DNA-based immunization by in vivo transfection of dendritic cells

Abstract: Delivery of antigen in a manner that induces effective, antigen-specific immunity is a critical challenge in vaccine design. Optimal antigen presentation is mediated by professional antigen-presenting cells (APCs) capable of taking up, processing and presenting antigen to T cells in the context of costimulatory signals required for T-cell activation. Developing immunization strategies to optimize antigen presentation by dendritic cells, the most potent APCs, is a rational approach to vaccine design. Here we show that cutaneous genetic immunization with naked DNA results in potent, antigen-specific, cytotoxic T lymphocyte-mediated protective tumor immunity. This method of immunization results in the transfection of skin-derived dendritic cells, which localize in the draining lymph nodes. These observations provide a basis for further development of DNA-based vaccines and demonstrate the feasibility of genetically engineering dendritic cells in vivo.

Evidence for reionization at z ∼ 6: Detection of a gunn-peterson trough in a z = 6.28 quasar

Abstract: We present moderate-resolution Keck spectroscopy of quasars at z = 5.82, 5.99, and 6.28, discovered by the Sloan Digital Sky Survey (SDSS). We find that the Ly? absorption in the spectra of these quasars evolves strongly with redshift. To z ~ 5.7, the Ly? absorption evolves as expected from an extrapolation from lower redshifts. However, in the highest-redshift object, SDSSp J103027.10+052455.0 (z = 6.28), the average transmitted flux is 0.0038 ? 0.0026 times that of the continuum level over 8450 ? 20, on the optical depth to Ly? absorption at z = 6. This is a clear detection of a complete Gunn-Peterson trough, caused by neutral hydrogen in the intergalactic medium. Even a small neutral hydrogen fraction in the intergalactic medium would result in an undetectable flux in the Ly? forest region. Therefore, the existence of the Gunn-Peterson trough by itself does not indicate that the quasar is observed prior to the reionization epoch. However, the fast evolution of the mean absorption in these high-redshift quasars suggests that the mean ionizing background along the line of sight to this quasar has declined significantly from z ~ 5 to 6, and the universe is approaching the reionization epoch at z ~ 6.

Neuronal Activity–Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis

Abstract: The mammalian brain exhibits diverse types of neural plasticity, including activity-dependent neurogenesis in the adult hippocampus. How transient activation of mature neurons leads to long-lasting modulation of adult neurogenesis is unknown. Here we identify Gadd45b as a neural activity-induced immediate early gene in mature hippocampal neurons. Mice with Gadd45b deletion exhibit specific deficits in neural activity-induced proliferation of neural progenitors and dendritic growth of newborn neurons in the adult hippocampus. Mechanistically, Gadd45b is required for activity-induced DNA demethylation of specific promoters and expression of corresponding genes critical for adult neurogenesis, including brain-derived neurotrophic factor and fibroblast growth factor. Thus, Gadd45b links neuronal circuit activity to epigenetic DNA modification and expression of secreted factors in mature neurons for extrinsic modulation of neurogenesis in the adult brain.

Time Discounting for Primary Rewards

Abstract: Previous research, involving monetary rewards, found that limbic reward-related areas show greater activity when an intertemporal choice includes an immediate reward than when the options include only delayed rewards. In contrast, the lateral prefrontal and parietal cortex (areas commonly associated with deliberative cognitive processes, including future planning) respond to intertemporal choices in general but do not exhibit sensitivity to immediacy (McClure et al., 2004). The current experiments extend these findings to primary rewards (fruit juice or water) and time delays of minutes instead of weeks. Thirsty subjects choose between small volumes of drinks delivered at precise times during the experiment (e.g., 2 ml now vs 3 ml in 5 min). Consistent with previous findings, limbic activation was greater for choices between an immediate reward and a delayed reward than for choices between two delayed rewards, whereas the lateral prefrontal cortex and posterior parietal cortex responded similarly whether choices were between an immediate and a delayed reward or between two delayed rewards. Moreover, relative activation of the two sets of brain regions predicts actual choice behavior. A second experiment finds that when the delivery of all rewards is offset by 10 min (so that the earliest available juice reward in any choice is 10 min), no differential activity is observed in limbic reward-related areas for choices involving the earliest versus only more delayed rewards. We discuss implications of this finding for differences between primary and secondary rewards.