Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Suicide prevention for youth - a mental health awareness program: lessons learned from the Saving and Empowering Young Lives in Europe (SEYLE) intervention study.

ABSTRACT: BACKGROUND: The Awareness program was designed as a part of the EU-funded Saving and Empowering Young Lives in Europe (SEYLE) intervention study to promote mental health of adolescents in 11 European countries by helping them to develop problem-solving skills and encouraging them to self-recognize the need for help as well as how to help peers in need. METHODS: For this descriptive study all coordinators of the SEYLE Awareness program answered an open-ended evaluation questionnaire at the end of the project implementation. Their answers were synthesized and analyzed and are presented here. RESULTS: The results show that the program cultivated peer understanding and support. Adolescents not only learned about mental health by participating in the Awareness program, but the majority of them also greatly enjoyed the experience. CONCLUSIONS: Recommendations for enhancing the successes of mental health awareness programs are presented. Help and cooperation from schools, teachers, local politicians and other stakeholders will lead to more efficacious future programs

Prevalence of pathological internet use among adolescents in Europe: demographic and social factors.

AIMS: To investigate the prevalence of pathological internet use (PIU) and maladaptive internet use (MIU) among adolescents in 11 European countries in relation to demographic, social factors and internet accessibility. DESIGN: Cross-sectional survey. SETTING: The 7th Framework European Union (EU) funded project, Saving and Empowering Young Lives in Europe (SEYLE), is a randomized controlled trial (RCT) evaluating interventions for risk behaviours among adolescents in Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain, with Sweden serving as the coordinating centre. PARTICIPANTS: A total of 11 956 adolescents (female/male: 6731/5225; mean age: 14.9 ± 0.89) recruited from randomly selected schools within the 11 study sites. MEASUREMENTS: Internet users were classified by gender into three categories: adaptive, maladaptive and pathological, based on their score in the Young Diagnostic Questionnaire for Internet Addiction (YDQ). FINDINGS: The overall prevalence of PIU was 4.4%; it was higher among males than females (5.2% versus 3.8%) and differed between countries (χ(2)  = 309.98; d.f. = 20; P < 0.001). PIU correlated significantly with mean hours online and male gender. The highest-ranked online activities were watching videos, frequenting chatrooms and social networking; significantly higher rates of playing single-user games were found in males and social networking in females. Living in metropolitan areas was associated with PIU. Students not living with a biological parent, low parental involvement and parental unemployment showed the highest relative risks of both MIU and PIU. CONCLUSIONS: Across a range of countries in Europe, using the Young Diagnostic Questionnaire for Internet Addiction yields a prevalence of 'pathological internet use' of 4.4% among adolescents, but varies by country and gender; adolescents lacking emotional and psychological support are at highest risk

Electrical-thermal analytical modeling of monopolar RF thermal ablation of biological tissues: determining the circumstances under which tissue temperature reaches a steady state

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in MATHEMATICAL BIOSCIENCES doi:10.3934/mbe.2015003 AND ENGINEERING following peer review. The definitive publisher-authenticated version Mathematical Biosciences and Engineering (MBE) Pages: 281 - 301, Volume 13, Issue 2, April 2016 is available online at http://www.aimsciences.org/journals/displayArticlesnew.jsp?paperID=11998[EN] It has been suggested that during RF thermal ablation of biological tissue the thermal lesion could reach an equilibrium size after 1-2 minutes. Our objective was to determine under which circumstances of electrode geometry (needle-like vs. ball-tip), electrode type (dry vs. cooled) and blood perfusion the temperature will reach a steady state at any point in the tissue. We solved the bioheat equation analytically both in cylindrical and spherical coordinates and the resultant limit temperatures were compared. Our results demonstrate mathematically that tissue temperature reaches a steady value in all cases except for cylindrical coordinates without the blood perfusion term, both for dry and cooled electrodes, where temperature increases infinitely. This result is only true when the boundary condition far from the active electrode is considered to be at infinitum. In contrast, when a finite and sufficiently large domain is considered, temperature reaches always a steady state.This work received financial support from the Spanish "Plan Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad" under Grant TEC2014-52383-C3-R (TEC2014-52383-C3-1-R).López Molina, JA.; Rivera Ortun, MJ.; Berjano, E. (2016). Electrical-thermal analytical modeling of monopolar RF thermal ablation of biological tissues: determining the circumstances under which tissue temperature reaches a steady state. Mathematical Biosciences and Engineering. 13(2):281-301. https://doi.org/10.3934/mbe.2015003S28130113