In vitro-generated neural precursors participate in mammalian brain development

During embryogenesis, pluripotent stem cells segregate into daughter lineages of progressively restricted developmental potential. In vitro, this process has been mimicked by the controlled differentiation of embryonic stem cells into neural precursors. To explore the developmental potential of these cell-culture-derived precursors in vivo, we have implanted them into the ventricles of embryonic rats. The transplanted cells formed intraventricular neuroepithelial structures and migrated in large numbers into the brain tissue. Embryonic-stem-cell-derived neurons, astrocytes, and oligodendrocytes incorporated into telencephalic, diencephalic, and mesencephalic regions and assumed phenotypes indistinguishable from neighboring host cells. These observations indicate that entirely in vitro-generated neural precursors are able to respond to environmental signals guiding cell migration and differentiation and have the potential to reconstitute neuronal and glial lineages in the central nervous system.     

Spike protein fusion peptide and feline coronavirus virulence

Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically.     

Air pollution and DNA methylation: interaction by psychological factors in the VA Normative Aging Study

DNA methylation is a potential pathway linking air pollution to disease. Studies indicate that psychological functioning modifies the association between pollution and morbidity. The authors estimated the association of DNA methylation with ambient particulate matter less than 2.5 μm in diameter (PM(2.5)) and black carbon, using mixed models. DNA methylation of the inducible nitric oxide synthase gene, iNOS, and the glucocorticoid receptor gene, GCR, was measured by quantitative polymerase chain reaction pyrosequencing of 1,377 blood samples from 699 elderly male participants in the VA Normative Aging Study (1999-2009). The authors also investigated whether this association was modified by psychological factors including optimism or pessimism, anxiety, and depression. iNOS methylation was decreased after acute exposure to both black carbon and PM(2.5). A 1-μg/m(3) increase in exposure to black carbon in the 4 hours preceding the clinical examination was associated with a 0.9% decrease in 5-methylcytosine (95% CI: 0.4, 1.4) in iNOS, and a 10-μg/m(3) increase in exposure to PM(2.5) was associated with a 0.6% decrease in 5-methylcytosine (95% CI: 0.03, 1.1) in iNOS. Participants with low optimism and high anxiety had associations that were 3-4 times larger than those with high optimism or low anxiety. GCR methylation was not associated with particulate air pollution exposure.     

Personality, family history, and alcohol use among older men: the VA Normative Aging Study

BACKGROUND: We examined personality traits (Sociability, Impulsivity, Neuroticism) as mediators of the effects of family history on alcohol outcomes. METHODS: A sample of 485 men reported on family history of alcohol problems in 1973, completed the Eysenck Personality Inventory in 1976, and responded to a survey on alcohol use in 1982. RESULTS: Using structural equation modeling, family history was found to have direct effects on number of drinks per day and on the number of alcohol problems, as well as indirect effects mediated through Neuroticism. There were no effects of Sociability or Impulsivity on either alcohol outcome. CONCLUSIONS: In this sample of older men, family history had both direct and indirect effects, and personality traits found to affect alcohol outcomes were different from those that have been found in younger men.     

Is DSM‐IV criterion A2 associated with PTSD diagnosis and symptom severity?

The diagnostic criteria for posttraumatic stress disorder (PTSD) have received significant scrutiny. Several studies have investigated the utility of Criterion A2, the subjective emotional response to a traumatic event. The American Psychiatric Association (APA) has proposed elimination of A2 from the PTSD diagnostic criteria for DSM-5; however, there is mixed support for this recommendation and few studies have examined A2 in samples at high risk for PTSD such as veterans. In the current study of 908 veterans who screened positive for a traumatic event, A2 was not significantly associated with having been told by a doctor that the veteran had PTSD. Those who endorsed A2, however, reported greater PTSD symptom severity in the 3 DSM-IV symptom clusters of reexperiencing (d = 0.45), avoidance (d = 0.61), and hyperarousal (d = 0.44), and A2 was significantly associated with PTSD symptom severity for all 3 clusters (R(2) = .25, .25, and .27, respectively) even with trauma exposure in the model. Thus, although A2 may not be a necessary criterion for PTSD diagnosis, its association with PTSD symptom severity warrants further exploration of its utility.