Chemokine Transfer by Liver Sinusoidal Endothelial Cells Contributes to the Recruitment of CD4+ T Cells into the Murine Liver

Leukocyte adhesion and transmigration are central features governing immune surveillance and inflammatory reactions in body tissues. Within the liver sinusoids, chemokines initiate the first crucial step of T-cell migration into the hepatic tissue. We studied molecular mechanisms involved in endothelial chemokine supply during hepatic immune surveillance and liver inflammation and their impact on the recruitment of CD4+ T cells into the liver. In the murine model of Concanavalin A-induced T cell-mediated hepatitis, we showed that hepatic expression of the inflammatory CXC chemokine ligands (CXCL)9 and CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased. Consistently, CD4+ T cells expressing the CXC chemokine receptor (CXCR)3 accumulated within the inflamed liver tissue. In histology, CXCL9 was associated with liver sinusoidal endothelial cells (LSEC) which represent the first contact site for T-cell immigration into the liver. LSEC actively transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin- coated vesicles to CD4+ T cells leading to enhanced transmigration of CXCR4+ total CD4+ T cells and CXCR3+ effector/memory CD4+ T cells, respectively in vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of endothelial CXCR4 inhibited CXCL12-dependent CD4+ T-cell transmigration. In contrast, CXCR3 was not involved in the endothelial transport of its ligands CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked endothelial chemokine internalization and CD4+ T-cell transmigration in vitro as well as migration of CD4+ T cells into the inflamed liver in vivo. Moreover, hepatic accumulation of CXCR3+ CD4+ T cells during T cell-mediated hepatitis was strongly reduced after administration of chlorpromazine. These data demonstrate that LSEC actively provide perivascularly expressed homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent intracellular transport mechanisms thereby contributing to the hepatic recruitment of CD4+ T-cell populations during immune surveillance and liver inflammation

Early Adolescent Depressive Symptoms: Prediction from Clique Isolation, Loneliness, and Perceived Social Acceptance

This study examined whether clique isolation predicted an increase in depressive symptoms and whether this association was mediated by loneliness and perceived social acceptance in 310 children followed from age 11–14 years. Clique isolation was identified through social network analysis, whereas depressive symptoms, loneliness, and perceived social acceptance were assessed using self ratings. While accounting for initial levels of depressive symptoms, peer rejection, and friendlessness at age 11 years, a high probability of being isolated from cliques from age 11 to 13 years predicted depressive symptoms at age 14 years. The link between clique isolation and depressive symptoms was mediated by loneliness, but not by perceived social acceptance. No sex differences were found in the associations between clique isolation and depressive symptoms. These results suggest that clique isolation is a social risk factor for the escalation of depressive symptoms in early adolescence. Implications for research and prevention are discussed

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Predictors of Recovery in Activities of Daily Living Among Disabled Older Persons Living in the Community

OBJECTIVE: To identify the factors that predict recovery in activities of daily living (ADLs) among disabled older persons living in the community. DESIGN: Prospective cohort study with 2-year follow-up. SETTING: General community. PARTICIPANTS: 213 men and women 72 years or older, who reported dependence in one or more ADLs. MEASUREMENTS AND MAIN RESULTS: All participants underwent a comprehensive home assessment and were followed for recovery of ADL function, defined as requiring no personal assistance in any of the ADLs within 2 years. Fifty-nine participants (28%) recovered independent ADL function. Compared with those older than 85 years, participants aged 85 years or younger were more than 8 times as likely to recover their ADL function (relative risk [RR] 8.4; 95% confidence interval [CI] 2.7, 26). Several factors besides age were associated with ADL recovery in bivariate analysis, including disability in only one ADL, self-efficacy score greater than 75, Folstein Mini-Mental State Examination (MMSE) score of 28 or better, high mobility, score in the best third of timed physical performance, fewer than five medications, and good nutritional status. In multivariable analysis, four factors were independently associated with ADL recovery—age 85 years or younger (adjusted RR 4.1; 95% CI 1.3, 13), MMSE score of 28 or better (RR 1.7; 95% CI 1.2, 2.3), high mobility (RR 1.7; 95% CI 1.0, 2.9), and good nutritional status (RR 1.6; 95% CI 1.0, 2.5). CONCLUSIONS: Once disabled, few persons older than 85 years recover independent ADL function. Intact cognitive function, high mobility, and good nutritional status each improve the likelihood of ADL recovery and may serve as markers of resiliency in this population

'Our desires are ungovernable' - writing graffiti in urban space

C1 - Refereed Journal ArticleOur aim in this article is to contribute to the body of research on graffiti by considering some of the hitherto hidden aspects of graffiti culture. Drawing on detailed interviews with graffiti writers, we examine four main themes: motivations for graffiti writing; thresholds dividing ‘art’ from ‘vandalism’; writers’ reactions to ‘blank’ surfaces; and graffiti’s relation to other types of crime. We orient our discussion towards the affective dimensions of the activity in the hope that the words of writers become a visible and productive presence in urban (and academic) space

Mating behaviour by the haddock (Melanogrammus aeglefinus)

This study examines the full repertoire of haddock reproductive behaviour, monitored in an aquarium for 3 months over each of two successive spawning seasons. Observations showed that male haddock were territorial and that visits to their territories by females triggered courtship behaviour, leading to spawning. Entry of females to the territories was induced by an acoustic and visual self-advertisement of displaying males, termed patrolling behaviour, exhibited for many hours each night for several months. The existence of sneaking behaviour by non-territorial males was observed for the first time for haddock and was supported by genetic data. Overall our observations are consistent with the behaviour expected from lekking species, as in the cod, a closely related species. Lekking is said to occur when non-resource-based aggregations of males are visited by females for the purpose of mating. Implications for the management of fish stocks are discussed