Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity

Background Interferon (IFN) signalling pathways, a key element of the innate immune response, contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy, and are often deregulated in cancer. The deubiquitylating enzyme USP18 is a major negative regulator of the IFN signalling cascade and is the predominant human protease that cleaves ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo.Methods In this study, using advanced proteomic techniques, we have significantly expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line. USP18-dependent effects were explored further in CML and colorectal carcinoma cellular models.Results Novel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation.Conclusions Our results provide strong evidence for USP18 in regulating antigenicity and radiosensitivity, highlighting its potential as a cancer target.Subject terms: Cancer immunotherapy, Ubiquitylation, RIG-I-like receptors, Radiotherapy, Mechanisms of disease     

Operation duration and adrenal gland size,but not BMI,are correlated with complication rate for posterior retroperitoneoscopic adrenalectomy for benign diseases

Background

We sought to determine whether obesity is correlated with complications after posterior retroperitoneoscopic adrenalectomy for benign diseases and to develop surrogate markers of abdominal fat in preoperative computed tomography.

Same-Sex Sexual Attraction Does Not Spread in Adolescent Social Networks

Peers have a powerful effect on adolescents’ beliefs, attitudes, and behaviors. Here, we examine the role of social networks in the spread of attitudes towards sexuality using data from the National Longitudinal Study of Adolescent Health (Add Health). Although we found evidence that both sexual activity (OR = 1.79) and desire to have a romantic relationship (OR = 2.69) may spread from person to person, attraction to same sex partners did not spread (OR = 0.96). Analyses of comparable power to those that suggest positive and significant peer-to-peer influence in sexual behavior fail to demonstrate a significant relationship on sexual attraction between friends or siblings. These results suggest that peer influence has little or no effect on the tendency toward heterosexual or homosexual attraction in teens, and that sexual orientation is not transmitted via social networks.     

Aspirin use and cardiovascular events in social networks

We tested whether friends' and family members' cardiovascular health events and also their own aspirin use are associated with the likelihood that an individual takes aspirin regularly. Analyses were based on longitudinal data on 2724 members of the Framingham Heart Study (based in Massachusetts, U.S.A.) who were linked to friends and family members who were also participants in the same study. Men were more likely to take aspirin if a male friend had recently been taking aspirin, and women were more likely to take aspirin if a brother had recently been taking aspirin. Men were also more likely to take aspirin if a brother recently had a cardiovascular event, and women were more likely to take aspirin if a female friend recently experienced a cardiovascular event. Aspirin use is correlated with the health and behavior of friends and family. These findings add to a growing body of evidence which suggests that behavioral changes that promote cardiovascular health may spread through social networks.     

Physical activity and beverages in home- and center-based child care programs

ObjectiveTo describe and compare obesity prevention practices related to physical activity and beverages in home- and center-based child care programs.MethodsA telephone survey of licensed home- and center-based child care programs in Florida, Massachusetts, Michigan, and Washington between October and December 2008.ResultsMost programs reported almost universal access to outdoor play areas and staff who frequently engage in and lead physical activities. About half of the programs reported ≤ 60 minutes of outdoor play time per day for preschoolers. Fewer home-based programs offered a variety of fixed and portable play equipment. Over a third of the programs did not have adequate indoor space for all physical activities. Over two thirds of programs offered juice 3 or 4 times per week or more.Conclusions and ImplicationsMany child care programs could increase active opportunities (by increasing outdoor time and providing better spaces for indoor physical activity) and decrease juice provision.