Multiple Determinants of Whole and Regional Brain Volume among Terrestrial Carnivorans

Mammalian brain volumes vary considerably, even after controlling for body size. Although several hypotheses have been proposed to explain this variation, most research in mammals on the evolution of encephalization has focused on primates, leaving the generality of these explanations uncertain. Furthermore, much research still addresses only one hypothesis at a time, despite the demonstrated importance of considering multiple factors simultaneously. We used phylogenetic comparative methods to investigate simultaneously the importance of several factors previously hypothesized to be important in neural evolution among mammalian carnivores, including social complexity, forelimb use, home range size, diet, life history, phylogeny, and recent evolutionary changes in body size. We also tested hypotheses suggesting roles for these variables in determining the relative volume of four brain regions measured using computed tomography. Our data suggest that, in contrast to brain size in primates, carnivoran brain size may lag behind body size over evolutionary time. Moreover, carnivore species that primarily consume vertebrates have the largest brains. Although we found no support for a role of social complexity in overall encephalization, relative cerebrum volume correlated positively with sociality. Finally, our results support negative relationships among different brain regions after accounting for overall endocranial volume, suggesting that increased size of one brain regions is often accompanied by reduced size in other regions rather than overall brain expansion

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Federal Lands and Endangered Species: The Role of Military and Other Federal Lands in Sustaining Biodiversity

The US government has multiple responsibilities for the protection of endangered species, many of them stemming from its role as the nation\u27s largest landowner. To explore how endangered and imperiled species are distributed across the federal estate, we carried out a geographic information system (GIS)-based analysis using natural heritage species occurrence data. In this 10-year update of a previous analysis, we found that the Department of Defense and the USDA Forest Service harbor more species with formal status under the Endangered Species Act (ESA) than other US agencies. The densities of ESA status species and imperiled species are at least three times higher on military lands—2.92 and 3.77, respectively, per 100,000 hectares—than on any other agency\u27s lands. Defense installations in Hawaii are especially significant; more than one-third of all ESA status species on military lands are Hawaiian. These findings highlight the continued importance of public lands for the survival of America\u27s plant and animal species