Localized Populations of CD8low/− MHC Class I Tetramer+ SIV-Specific T Cells in Lymphoid Follicles and Genital Epithelium

CD8 T cells play an important role in controlling viral infections. We investigated the in situ localization of simian immunodeficiency virus (SIV)-specific T cells in lymph and genital tissues from SIV-infected macaques using MHC-class I tetramers. The majority of tetramer-binding cells localized in T cell zones and were CD8+. Curiously, small subpopulations of tetramer-binding cells that had little to no surface CD8 were detected in situ both early and late post-infection, and in both vaginally and rectally inoculated macaques. These tetramer+CD8low/− cells were more often localized in apparent B cell follicles relative to T cell zones and more often found near or within the genital epithelium than the submucosa. Cells analyzed by flow cytometry showed similar populations of cells. Further immunohistological characterization revealed small populations of tetramer+CD20− cells inside B cell follicles and that tetramer+ cells did not stain with γδ-TCR nor CD4 antibodies. Negative control tetramer staining indicated that tetramer+CD8low/− cells were not likely NK cells non-specifically binding to MHC tetramers. These findings have important implications for SIV-specific and other antigen-specific T cell function in these specific tissue locations, and suggest a model in which antigen-specific CD8+ T cells down modulate CD8 upon entering B cell follicles or the epithelial layer of tissues, or alternatively a model in which only antigen-specific CD8 T cells that down-modulate CD8 can enter B cell follicles or the epithelium

Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency

OBJECTIVE: Alpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the 'Pi*Z' variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous 'Pi*Z' carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common 'Pi*S' variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD. DESIGN: Baseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption. RESULTS: Among UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8-53.7)) and primary liver cancer (aOR=44.5 (10.8-183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2-2.2)) and cholelithiasis (aOR=1.3 (1.2-1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1-8.2)) and primary liver cancer (aOR=6.6 (1.6-26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis. CONCLUSION: Our study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance

Entrepreneurial intentions and entrepreneurship education to University students in Portugal

[EN] This article analyzes entrepreneurial intentions and motivations that encourage university students of Tourism to create their own company. Methodology is based on an empirical study, using a questionnaire adapted from a model of Veciana and Urbano (Actitudes de los estudiantes universitarios hacia la creación de empresas: un estudio empírico comparativo entre Catalunya y Puerto Rico. El emprendedor innovador y la creación de empresas de I + D + I, University of Valencia, pp 35 58, 2004), including the desirability and viability concepts. One hundred and sixty students answered the questionnaire from a total study population of 243 official Tourism degree students of the Superior Institute of Accounting and Management of Porto. This research finds out that the university students have a very positive perception about the desire to create their own company; a 90 % of students express their desire to do it, and 83.5 % express their intention. Moreover, a 57.5 % think that within actual crisis it is more difficult to do than before it. This research lets us get an in-depth study of a student of Tourism degree, finding out his entrepreneurial attitudes. It can be the first step to wake up and encourage students interest for starting up their own business.Del Rio-Rama, MDLC.; Peris-Ortiz, M.; Álvarez García, J.; Rueda Armengot, C. (2016). Entrepreneurial intentions and entrepreneurship education to University students in Portugal. Technology, Innovation and Education. 2(7):1-11. doi:10.1186/s40660-016-0013-5S11127Ajzen I (1991) The theory of plannes behavior. Organ Behav Hum Decis Process 50:179–211Aponte M (2002) Factores condicionantes de la creación de empresas en Puerto Rico: un enfoque institucional. Doctoral dissertation, Autonomous University of BarcelonaAponte M, Urbano D, Veciana JM (2006) Actitudes hacia la creación de empresas: un estudio comparativo entre Catalunya y Puerto Rico. 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Entrep Reg Dev 7(1):41–62De Jorge-Moreno J, Castillo LL, Triguero MS (2012) The effect of business and economics education programs on students’ entrepreneurial intention. Eur J Train Dev 36(4):409–425Díaz JC, Hernández RM, Barata ML (2007) Estudiantes universitarios y creación de empresas. Un análisis comparativo entre España y Portugal. In Ayala, J.C. (coord.) Conocimiento, innovación y emprendedores: camino al futuro. Grupo FEDRA, MadridDo Paço AMF, Ferreira JM, Raposo M, Rodrigues RG, Dinis A (2011) Behaviours and entrepreneurial intention: empirical findings about secondary students. J Int Entrep 9(1):20–38Dohse D, Walter SG (2010) The role of entrepreneurship education and regional context in forming entrepreneurial intentions (No. 2010, 18). Document de treball de l’IEBEuropean Commission (2006). 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Afr J Econ Manag Stud 3(2):258–277Gorman G, Hanlon D, King W (1997) Some research perspectives on entrepreneurship education and education for small business management: a ten-year literature review. Int Small Bus J 15(3):56–77Guerrero M, Rialp J, Urbano D (2008) The impact of desirability and feasibility on entrepreneurial intentions: a structural equation model. Int Entrep Manag J 4(1):35–50Haynie JM, Shepherd DA, McMullen JS (2009) An opportunity for me? The role of resources in opportunity evaluation decisions. J Manage Stud 46(3):337–361Hernangomez J, Martín N, Rodriguez AI, Saboia F (2005) El emprendedor nace o se hace? Un análisis de los determinantes del espíritu emprendedor. XVI Spanish-Portuguese Meeting of Scientic Management. Sevilla:33–44Hmieleski KM, Corbett AC (2006) Proclivity for improvisation as a predictor of entrepreneurial intentions. J Small Bus Manage 44(1):45–63Honjo Y (2004) Growth of new start-up firms: evidence from the Japanese manufacturing industry. Appl Econ Lett 11(1):21–32Hyde GC (1989) The relationship between policy and research. In Rosa, P.; Birley, S. Cannon, T. and O´Neill, K. The Role and Contribution of Small Business Research, Chap. 3:55–77, Institute ReportKolvereid L (1996) Prediction of employment status choice intentions. Entrep Theory Pract 21(1):47–57Kourilsky ML, Walstad WB (1998) Entrepreneurship and female youth: knowledge, attitude, gender differences, and educational practices. J Bus Ventur 13(1):77–88Krueger N, Brazeal D (1994) Entrepreneurial Potencial and Potencial Entrepreneurs. Entrep Theory Pract 18(3):91–104Krueger NF, Carsrud AL (1993) Entrepreneurial intentions: applying the theory of planned behaviour. Entrep Reg Dev 5(4):315–330Lanero A, Vázquez JL, Gutiérrez P, García MP (2011) The impact of entrepreneurship education in European universities: an intention-based approach analyzed in the Spanish area. Int Rev Public Nonprofit Marketin 8(2):111–130Miller BK, Bell JD, Palmer M, González A (2009) Predictors of entrepreneurial intentions: a quasi-experiment comparing students enrolled in introductory management and entrepreneurship classes. J Bus Entrep 21(2):39–62Neck HM, Zacharakis AL, Bygrave WD, Reynolds PD (2003) Global entrepreneurship monitor: 2002 executive report. Babson College, Babson, MANorth DC (1990) Institutions, Institutional Change and Economic Performance. Cambridge University Press, Cambridge (UK)North D (1993) Instituciones, cambio institucional y desempeño económico. Fondo de Cultura Económica, MéxicoNorth DC (2005) Understanding the Process of Economic Change. Academic Foundation. University Press, PrincentonGEM Portugal (2012) Estudo sobre o Empreendedorismo. Global Entrepreneruship Monitor (GEM). Instituto Universitário de Lisboa (ISCTEIUL) http://web.spi.pt/GEMportugal2012/files/GEM_PORTUGAL_2012.pdfRaposo M, do Paço A, Ferreira J (2008a) Entrepreneur’s profile: a taxonomy of attribu tes and motivations of university students. J Small Bus Enterp Dev 15(2):405–420Raposo MLB, Ferreira JJM, do Paço AMF, Rodrigues RJG (2008b) Propensity to firm creation: empirical research using structural equations. Int Entrep Manag J 4(4):485–504Robinson PB, Stimpson DV, Huefner JC, Hunt HK (1991) An attitude approach to the prediction of entrepreneurship. Entrep Theory Pract 15(4):13–31Samad Aghayi J (2008) Entrepreneurship organization. Public Administration Training Center Publications, TehranScherer RF, Adams JS, Carley S, Wiebe FA (1989) Role model performance effects on development of entrepreneurial career preference. Entrep Theory and Pract, spring:53–71Scherer RF, Brodzinski JD, Wiebe F (1991) Examining the relationship between personality and entrepreneurial career preference. 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Complexity of Bidirectional Transcription and Alternative Splicing at Human RCAN3 Locus

Human RCAN3 (regulator of calcineurin 3) belongs to the human RCAN gene family

Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET)

Background and aims Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. Methods Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. Results Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. Conclusions Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF

Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET)

Background and aims: Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. Methods: Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. Results: Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. Conclusions: Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF

A keratin K5Cre transgenic line appropriate for tissue-specific or generalized Cre-mediated recombination

We describe here a mouse line bearing a bovine keratin K5Cre recombinase transgene. These mice showed a dual pattern of Cre-mediated recombination, depending on the parent transmitting the transgene. In paternal transmission, recombination occurred specifically in the skin and stratified epithelia-as expected according to the expression of endogenous keratin K5. However, constitutive recombination between loxP sites transmitted by the sperm took place when the mother possessed the K5Cre transgene, even when the transgene was absent in the progeny. Cre expression in late-stage oocytes, with the Cre protein persisting into the developing embryo, leads to the constitutive recombination observed. Thus, this transgenic line allows for both tissue-specific and generalized recombination, depending on the breeding scheme. (C) 2004 Wiley-Liss, Inc