Social isolation can exacerbate the negative consequences of stress and increase the risk of developing psychopathology. However, the influence of living alone on experiences generally considered to be beneficial to the brain, such as physical exercise, remains unknown. We report here that individual housing precludes the positive influence of short-term running on adult neurogenesis in the hippocampus of rats and, in the presence of additional stress, suppresses the generation of new neurons. Individual housing also influenced corticosterone levels--runners in both housing conditions had elevated corticosterone during the active phase, but individually housed runners had higher levels of this hormone in response to stress. Moreover, lowering corticosterone levels converted the influence of short-term running on neurogenesis in individually housed rats from negative to positive. These results suggest that, in the absence of social interaction, a normally beneficial experience can exert a potentially deleterious influence on the brain.

Physical activity enhances hippocampal function but its effects on neuronal structure remain relatively unexplored outside of the dentate gyrus. Using Golgi impregnation and the lipophilic tracer DiI, we show that long-term voluntary running increases the density of dendritic spines in the entorhinal cortex and hippocampus of adult rats. Exercise was associated with increased dendritic spine density not only in granule neurons of the dentate gyrus, but also in CA1 pyramidal neurons, and in layer III pyramidal neurons of the entorhinal cortex. In the CA1 region, changes in dendritic spine density are accompanied by changes in dendritic arborization and alterations in the morphology of individual spines. These findings suggest that physical activity exerts pervasive effects on neuronal morphology in the hippocampus and one of its afferent populations. These structural changes may contribute to running-induced changes in cognitive function.

Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-1 27–35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for “classical” cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8 + T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency.

The lateral occipital cortex (LOC), a visual area known to be involved in object recognition, was dynamically coupled with each of two distributed patterns of neural activity depending upon the percept (default or alternative) elicited by a bistable figure. The two distributed patterns included core nodes of the default-mode and frontoparietal networks (FPN), and they were most highly coupled to each other during the alternative percept, whereas they were less coupled during the default percept. Surprisingly, the regions associated with the nonengaged percept exhibited the highest connectivity to the LOC. Together, these findings reveal a dynamic organization between the default mode and the FPNs, and the incoming bottom-up visual stream during perceptual binding of visual images.

The authors report a case of a verrucous carcinoma (VC) of the buttocks clinically simulating a giant (6.5 cm in length and 5.4 cm in greatest diameter) fibroepithelial polyp (FEP) capped by a large cutaneous horn. The growth had been present for 15 years and had never been biopsied despite numerous physical exams. VC typically presents distinctly as a large cauliflower-like growth with histological features of acanthosis, parakeratosis, minimal cytological atypia, and deep pushing epithelial borders. It is considered a low-grade, well-differentiated variant of squamous cell cancer and is commonly associated with human papillomavirus (HPV). Anogenital VC has been associated more with "low-risk" (type 6 and 11) than "high-risk" (16 and 18) HPV types. Presentation of VC as a FEP is unusual and demonstrates the necessity of maintaining a high level of clinical suspicion of anogenital growths, particularly those involving atypical features such as ulceration or the presence of a cutaneous horn.