Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection

Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection. Accelerated mortality was not due to expanded viral tropism or increased replication. Rather, viral entry increased specifically in the hindbrain of IFNAR-deficient mice, suggesting that IFNAR signaling critically regulates BBB permeability in this brain region. Pattern recognition receptors and IFN-stimulated genes had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes than did cerebral cortical astrocytes, suggesting that IFNAR signaling has brain region–specific roles in CNS immune responses. Taken together, our data identify cerebellar astrocytes as key responders to viral infection and highlight the existence of distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS

Coinductive subtyping for abstract compilation of object-oriented languages into Horn formulas

In recent work we have shown how it is possible to define very precise type systems for object-oriented languages by abstractly compiling a program into a Horn formula f. Then type inference amounts to resolving a certain goal w.r.t. the coinductive (that is, the greatest) Herbrand model of f. Type systems defined in this way are idealized, since in the most interesting instantiations both the terms of the coinductive Herbrand universe and goal derivations cannot be finitely represented. However, sound and quite expressive approximations can be implemented by considering only regular terms and derivations. In doing so, it is essential to introduce a proper subtyping relation formalizing the notion of approximation between types. In this paper we study a subtyping relation on coinductive terms built on union and object type constructors. We define an interpretation of types as set of values induced by a quite intuitive relation of membership of values to types, and prove that the definition of subtyping is sound w.r.t. subset inclusion between type interpretations. The proof of soundness has allowed us to simplify the notion of contractive derivation and to discover that the previously given definition of subtyping did not cover all possible representations of the empty type

Investigating corroboration of self-perceived posttraumatic growth among Sri Lankan Tamil survivors of ethnopolitical warfare through trait, domain, and profile agreement approaches.

Though research on assessing posttraumatic growth has been severely critiqued, some evidence suggests close others can observe and report changes in individuals following traumatic life events and are sensitive to idiosyncratic ways in which changes manifest. We extended these findings by investigating corroboration of self-perceived posttraumatic growth (PTG) and depreciation (PTD) as measured by the Posttraumatic Growth Inventory–42 (PTGI-42) among Sri Lankan Tamil war survivors (n = 200). Informants slightly corroborated overall levels of PTG and PTD, while a more nuanced profile analysis procedure revealed overall—but not distinctive—profile agreement. This suggests self–other agreement is modest and may partly reflect shared narratives and collective cultural understandings about how people change after trauma. Results demonstrate further that informants were not sensitive to idiosyncratic ways in which target individuals had changed. Together, the lack of validity evidence suggests that the PTGI-42 may be inadequate in some cross-cultural contexts as a measure of nuanced posttraumatic change (i.e., as a measure of specific changes in the five theorized domains of growth and depreciation). Future work should emphasize culture- and context-sensitive measurement of posttraumatic change, particularly focusing on methods other than retrospective self-reports, such as prospective longitudinal designs