Learning and CRF-Induced Indecision during Escape and Submission in Rainbow Trout during Socially Aggressive Interactions in the Stress-Alternatives Model

Socially stressful environments induce a phenotypic dichotomy of coping measures for populations in response to a dominant aggressor and given a route of egress. This submission- (Stay) or escape-oriented (Escape) dichotomy represents individual decision-making under the stressful influence of hostile social environments. We utilized the Stress-Alternatives Model (SAM) to explore behavioral factors which might predict behavioral phenotype in rainbow trout. The SAM is a compartmentalized tank, with smaller and larger trout separated by an opaque divider until social interaction, and another divider occluding a safety zone, accessible by way of an escape route only large enough for the smaller fish. We hypothesized that distinctive behavioral responses during the first social interaction would indicate a predisposition for one of the behavioral phenotypes in the subsequent interactions. Surprisingly, increased amount or intensity of aggression received had no significant effect on promoting escape in test fish. In fact, during the first day of interaction, fish that turned toward their larger opponent during attack eventually learned to escape. Escaping fish also learn to monitor the patrolling behavior of aggressors, and eventually escape primarily when they are not being observed. Escape per se, was also predicted in trout exhibiting increased movements directed toward the escape route. By contrast, fish that consistently remained in the tank with the aggressor (Stay) showed significantly higher frequency of swimming in subordinate positions, at the top or the bottom of the water column, as well as sitting at the bottom. In addition, a corticotropin-releasing factor (CRF)-induced behavior, snap-shake, was also displayed in untreated fish during aggressive social interaction, and blocked by a CRF1 receptor antagonist. Especially prevalent among the Stay phenotype, snap-shake indicates indecision regarding escape-related behaviors. Snap-shake was also exhibited by fish of the Escape phenotype, showing a positive correlation with latency to escape. These results demonstrate adaptive responses to stress that reflect evolutionarily conserved stress neurocircuitry which may translate to psychological disorders and decision-making across vertebrate taxa

Pressure balance in the multiphase ISM of cosmologically simulated disc galaxies

Pressure balance plays a central role in models of the interstellar medium (ISM), but whether and how pressure balance is realized in a realistic multiphase ISM is not yet well understood. We address this question by using a set of FIRE-2 cosmological zoom-in simulations of Milky Way-mass disc galaxies, in which a multiphase ISM is self-consistently shaped by gravity, cooling, and stellar feedback. We analyse how gravity determines the vertical pressure profile as well as how the total ISM pressure is partitioned between different phases and components (thermal, dispersion/turbulence, and bulk flows). We show that, on average and consistent with previous more idealized simulations, the total ISM pressure balances the weight of the overlying gas. Deviations from vertical pressure balance increase with increasing galactocentric radius and with decreasing averaging scale. The different phases are in rough total pressure equilibrium with one another, but with large deviations from thermal pressure equilibrium owing to kinetic support in the cold and warm phases, which dominate the total pressure near the mid-plane. Bulk flows (e.g. inflows and fountains) are important at a few disc scale heights, while thermal pressure from hot gas dominates at larger heights. Overall, the total mid-plane pressure is well-predicted by the weight of the disc gas and we show that it also scales linearly with the star formation rate surface density (ΣSFR). These results support the notion that the Kennicutt-Schmidt relation arises because ΣSFR and the gas surface density (Σg) are connected via the ISM mid-plane pressure

Pressure balance in the multiphase ISM of cosmologically simulated disc galaxies

Pressure balance plays a central role in models of the interstellar medium (ISM), but whether and how pressure balance is realized in a realistic multiphase ISM is not yet well understood. We address this question by using a set of FIRE-2 cosmological zoom-in simulations of Milky Way-mass disc galaxies, in which a multiphase ISM is self-consistently shaped by gravity, cooling, and stellar feedback. We analyse how gravity determines the vertical pressure profile as well as how the total ISM pressure is partitioned between different phases and components (thermal, dispersion/turbulence, and bulk flows). We show that, on average and consistent with previous more idealized simulations, the total ISM pressure balances the weight of the overlying gas. Deviations from vertical pressure balance increase with increasing galactocentric radius and with decreasing averaging scale. The different phases are in rough total pressure equilibrium with one another, but with large deviations from thermal pressure equilibrium owing to kinetic support in the cold and warm phases, which dominate the total pressure near the mid-plane. Bulk flows (e.g. inflows and fountains) are important at a few disc scale heights, while thermal pressure from hot gas dominates at larger heights. Overall, the total mid-plane pressure is well-predicted by the weight of the disc gas and we show that it also scales linearly with the star formation rate surface density (Σ_(SFR)). These results support the notion that the Kennicutt–Schmidt relation arises because Σ_(SFR) and the gas surface density (Σ_g) are connected via the ISM mid-plane pressure

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Elements Fall 2011 Issue

PDF of Elements' Fall 2011 journa

IL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii

Summary: Interleukin-18 (IL-18) promotes natural killer (NK) and T cell production of interferon (IFN)-γ, a key factor in resistance to Toxoplasma gondii, but previous work has shown a limited role for endogenous IL-18 in control of this parasite. Although infection with T. gondii results in release of IL-18, the production of IFN-γ induces high levels of the IL-18 binding protein (IL-18BP). Antagonism of IL-18BP with a “decoy-to-the-decoy” (D2D) IL-18 construct that does not signal but rather binds IL-18BP results in enhanced innate lymphoid cell (ILC) and T cell responses and improved parasite control. In addition, the use of IL-18 resistant to IL-18BP (“decoy-resistant” IL-18 [DR-18]) is more effective than exogenous IL-18 at promoting innate resistance to infection. DR-18 enhances CD4+ T cell production of IFN-γ but results in CD4+ T cell-mediated pathology. Thus, endogenous IL-18BP restrains aberrant immune pathology, and this study highlights strategies that can be used to tune this regulatory pathway for optimal anti-pathogen responses

Endothelial histamine H1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Disruption of the blood–brain barrier (BBB) underlies the development of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Environmental factors, such as Bordetella pertussis, are thought to sensitize central endothelium to biogenic amines like histamine, thereby leading to increased BBB permeability. B. pertussis-induced histamine sensitization (Bphs) is a monogenic intermediate phenotype of EAE controlled by histamine H1 receptor (Hrh1/H1R). Here, we transgenically overexpressed H1R in endothelial cells of Hrh1-KO (H1RKO) mice to test the role of endothelial H1R directly in Bphs and EAE. Unexpectedly, transgenic H1RKO mice expressing endothelial H1R under control of the von Willebrand factor promoter (H1RKO-vWFH1R Tg) were Bphs-resistant. Moreover, H1RKO-vWFH1R Tg mice exhibited decreased BBB permeability and enhanced protection from EAE compared with H1RKO mice. Thus, contrary to prevailing assumptions, our results show that endothelial H1R expression reduces BBB permeability, suggesting that endothelial H1R signaling may be important in the maintenance of cerebrovascular integrity