Cross-reactive memory T cells induced by primary infection with one of the four serotypes of dengue virus (DENV) are hypothesized to have an immunopathological function in secondary heterologous DENV infection. To define the T-cell response to heterologous serotypes, we isolated HLA-A*1101-restricted epitope-specific CD8 + T-cell lines from primary DENV-immune donors. Cell lines exhibited marked cross-reactivity toward peptide variants representing the four DENV serotypes in tetramer binding and functional assays. Many clones responded similarly to homologous and heterologous serotypes with striking crossreactivity between the DENV-1 and DENV-3 epitope variants. In vitro-stimulated T-cell lines consistently revealed a hierarchical induction of MIP-1b4degranulation4tumor necrosis factor a (TNFa)4interferon-c (IFNc), which depended on the concentration of agonistic peptide. Phosphoflow assays showed peptide dose-dependent phosphorylation of ERK1/2, which correlated with cytolysis, degranulation, and induction of TNFa and IFNc, but not MIP-1b production. This is the first study to show significant DENV serotype-cross-reactivity of CD8 + T cells after naturally acquired primary infection. We also show qualitatively different T-cell receptor signaling after stimulation with homologous and heterologous peptides. Our data support a model whereby the order of sequential DENV infections influences the immune response to secondary heterologous DENV infection, contributing to varying disease outcomes. The World Health Organization estimates that 50 million dengue virus (DENV) infections occur each year within the nearly two-fifths of the world population living in areas at risk for dengue transmission. 1 With increasing urbanization, as well as international travel, the range of the principal mosquito vector of DENV, Aedes agypti, is expanding. 2 Co-circulation of the four serotypes of DENV, DENV 1-4, along with the increased risk for severe disease during secondary DENV infections 3-5 represents a serious global health problem. With no reliable immunocompetent animal model available to mimic sequential human DENV infections, ex vivo studies on human samples are necessary to investigate the mechanisms for increased disease severity during heterologous secondary DENV infections.Immunologic memory established by a primary DENV infection influences the response to a secondary heterologous DENV infection because of the significant (B70%) amino-acid homology between the four DENV serotypes. 6 In particular, DENV-specific memory T and B cells can be reactivated during secondary heterologous DENV infection resulting in a more vigorous and cross-reactive secondary immune response. A number of studies have found increased markers of immune cell activation in patients with dengue hemorrhagic fever compared with patients with the less severe form of disease, dengue fever. These markers include interferon-g (IFNg), tumor necrosis factor a (TNFa), soluble CD8, soluble IL-2 receptor, soluble TNF receptor, and CD69, 7-10 which support a ...

Characterizing movement dynamics and spatial aspects of gene flow within a species permits inference on population structuring. As patterns of structuring are products of historical and current demographics and gene flow, assessment of structure through time can yield an understanding of evolutionary dynamics acting on populations that are necessary to inform management. Recent dramatic population declines in hibernating bats in eastern North America from white-nose syndrome have prompted the need for information on movement dynamics for multiple bat species. We characterized population genetic structure of the little brown bat, Myotis lucifugus, at swarming sites in southeastern Canada using 9 nuclear microsatellites and a 292-bp region of the mitochondrial genome. Analyses of FST, ΦST, and Bayesian clustering (STRUCTURE) found weak levels of genetic structure among swarming sites for the nuclear and mitochondrial genome (Global FST = 0.001, P < 0.05, Global ΦST = 0.045, P < 0.01, STRUCTURE K = 1) suggesting high contemporary gene flow. Hierarchical AMOVA also suggests little structuring at a regional (provincial) level. Metrics of nuclear genetic structure were not found to differ between males and females suggesting weak asymmetries in gene flow between the sexes. However, a greater degree of mitochondrial structuring does support male-biased dispersal long term. Demographic analyses were consistent with past population growth and suggest a population expansion occurred from approximately 1250 to 12,500 BP, following Pleistocene deglaciation in the region. Our study suggests high gene flow and thus a high degree of connectivity among bats that visit swarming sites whereby mainland areas of the region may be best considered as one large gene pool for management and conservation.

Women experiencing severe perinatal mental illness during pregnancy or postpartum have unique needs when psychiatric hospitalization is indicated. Although many countries have established mother-baby psychiatric units, similar facilities have not been available in the US. In 2011, the University of North Carolina at Chapel Hill inaugurated the first Perinatal Psychiatry Inpatient Unit (PPIU) in the US. We describe the unique characteristics of the patient population and report clinical outcomes guiding development and refinement of treatment protocols. Ninety-two perinatal patients were admitted between September 2011 and September 2012, and 91 completed self-report measures at admission and discharge. Perinatal unipolar mood disorder was the most frequent primary diagnosis (60.43%), and eleven patients (12%) were admitted with psychosis. The data document clinically and statistically significant improvements in symptoms of depression, anxiety and active suicidal ideation between admission and discharge (p < .0001), as assessed by the Edinburgh Postnatal Depression Scale, Patient Health Questionnaire, and Generalized Anxiety Disorder Scale. Overall functioning was also improved, demonstrated by a significant mean difference of −10.96 in total scores of the Work and Social Adjustment Scale (p < 0.0001). Data suggest that delivering specialized and targeted interventions for severe maternal mental illness in a safe and supportive setting produces positive patient outcomes.

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