Evolution of Th2 responses : Characterization of IL-4/13 in sea bass (Dicentrarchus labrax L.) and studies of expression and biological activity

Acknowledgements This research was funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). T.W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference number HR09011) and contributing institutions.Peer reviewedPublisher PD

Inhibition of activin/nodal signalling is necessary for pancreatic differentiation of human pluripotent stem cells

Peer reviewedPublisher PD

The 4D Nucleome Project [preprint]

The spatial organization of the genome and its dynamics contribute to gene expression and cellular function in normal development as well as in disease. Although we are increasingly well equipped to determine a genome\u27s sequence and linear chromatin composition, studying the three-dimensional organization of the genome with high spatial and temporal resolution remains challenging. The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the long term goal of gaining deeper mechanistic understanding of how the nucleus is organized. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Further efforts will be directed at applying validated experimental approaches combined with biophysical modeling to generate integrated maps and quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells

Achievement motives and emotional processes in children during problem-solving: Two experimental studies of their relation to performance in different achievement goal conditions

In two studies, the influence of key emotional and motivational factors on performance in different achievement goal-type situations is examined. In study 1, based on 314 sixth-graders, two types of goal situations were induced; performance and mastery. The goals were examined with respect to important antecedents (e.g., motive dispositions) and several consequences (e.g., performance, satisfaction, pleasant affect, worry, and emotionality). The results showed that the motive to achieve success (Ms) produced positive affects, satisfaction, and increased performance, whereas the motive to avoid failure (Mf) produced worries and performance reduction. In study 2, based on 331 sixth-graders, three types of goal situations were induced; performance–approach, performance–avoidance, and mastery goals. The findings revealed that the most important single factors positively related to performance were Ms and mastery–goal situation. In addition, high Ms pupils performed better under mastery condition than under performance condition. Finally, avoidance-goal situation accentuate the negative effects of high Mf on performance

Cross-Cultural Validation of the Inventory of School Motivation (ISM) in the Asian Setting: Hong Kong and the Philippines

Students’ achievement goals in school have received increasing research attention because they have been shown to be important in predicting important outcomes. As such, there has been a growing interest in measuring and comparing them across different cultural groups. However, these comparisons cannot be made until validity evidence has been attained to support the use of an instrument in the new cultural setting. In this study, we investigated the cross-cultural applicability of the Inventory of School Motivation (ISM, McInerney et al. American Educational Research Journal 34:207-236, 1997) in the Hong Kong Chinese and Philippine contexts using both within-network and between-network approaches to construct validation. The ISM measures four types of achievement goals: mastery, performance, social, and extrinsic goals. 1,406 high school students from Hong Kong (n = 697) and the Philippines (n = 709) participated. Results of the within-network test showed that the ISM had good internal consistency reliability and the confirmatory factor analysis provided support for the hypothesized four-factor model. Multigroup confirmatory factor analyses supported invariance of factor loadings across the two samples. The between-network test also indicated that these achievement goals correlated systematically with different aspects of students’ self-concepts. These findings support the applicability of the ISM among Hong Kong Chinese and Filipino students

Regulation of Cathepsin G Reduces the Activation of Proinsulin-Reactive T Cells from Type 1 Diabetes Patients

Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major histocompatibility complex (MHC) class II molecules for CD4+ T cell inspection. However, the processing and presentation of proinsulin by antigen-presenting cells (APC) in humans is only partially understood. Here we demonstrate that the processing of proinsulin by B cell or myeloid dendritic cell (mDC1)-derived lysosomal cathepsins resulted in several proinsulin-derived intermediates. These intermediates were similar to those obtained using purified CatG and, to a lesser extent, CatD, S, and V in vitro. Some of these intermediates polarized T cell activation in peripheral blood mononuclear cells (PBMC) from T1D patients indicative for naturally processed T cell epitopes. Furthermore, CatG activity was found to be elevated in PBMC from T1D patients and abrogation of CatG activity resulted in functional inhibition of proinsulin-reactive T cells. Our data suggested the notion that CatG plays a critical role in proinsulin processing and is important in the activation process of diabetogenic T cells

Cystatin E/M suppresses legumain activity and invasion of human melanoma

<p>Abstract</p> <p>Background</p> <p>High activity of cysteine proteases such as legumain and the cathepsins have been shown to facilitate growth and invasion of a variety of tumor types. In breast cancer, several recent studies have indicated that loss of the cysteine protease inhibitor cystatin E/M leads to increased growth and metastasis. Although cystatin E/M is normally expressed in the skin, its role in cysteine protease regulation and progression of malignant melanoma has not been studied.</p> <p>Methods</p> <p>A panel of various non-melanoma and melanoma cell lines was used. Cystatin E/M and C were analyzed in cell media by immunoblotting and ELISA. Legumain, cathepsin B and L were analyzed in cell lysates by immunoblotting and their enzymatic activities were analyzed by peptide substrates. Two melanoma cell lines lacking detectable secretion of cystatin E/M were transfected with a cystatin E/M expression plasmid (pCST6), and migration and invasiveness were studied by a Matrigel invasion assay.</p> <p>Results</p> <p>Cystatin E/M was undetectable in media from all established melanoma cell lines examined, whereas strong immunobands were detected in two of five primary melanoma lines and in two of six lines derived from patients with metastatic disease. Among the four melanoma lines secreting cystatin E/M, the glycosylated form (17 kD) was predominant compared to the non-glycosylated form (14 kD). Legumain, cathepsin B and L were expressed and active in most of the cell lines, although at low levels in the melanomas expressing cystatin E/M. In the melanoma lines where cystatin E/M was secreted, cystatin C was generally absent or expressed at a very low level. When melanoma cells lacking secretion of cystatin E/M were transfected with pCST6, their intracellular legumain activity was significantly inhibited. In contrast, cathepsin B activity was not affected. Furthermore, invasion was suppressed in cystatin E/M over-expressing melanoma cell lines as measured by the transwell Matrigel assay.</p> <p>Conclusions</p> <p>These results suggest that the level of cystatin E/M regulates legumain activity and hence the invasive potential of human melanoma cells.</p

Islet-Like Cell Aggregates Generated from Human Adipose Tissue Derived Stem Cells Ameliorate Experimental Diabetes in Mice

BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs) to differentiate into functional islet like cell aggregates (ICAs). Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17) and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes

AIDS knowledge and sexual activity among Flemish secondary school students: a multilevel analysis of the effects of type of education

<p>Abstract</p> <p>Background</p> <p>The behavior of adolescents puts them at an increased risk for HIV and other STIs, and their knowledge about HIV/AIDS is often inadequate. An understanding of how AIDS knowledge and sexual activity co-vary among Flemish secondary school students and of how education type, specifically, affects these students is limited. This study addresses the question of whether the effects of education type on HIV/AIDS knowledge and sexual activity are independent of the socio-demographic characteristics of the students.</p> <p>Methods</p> <p>Data from the Flemish Educational Assessment survey, which collected data from a large representative sample of third- and fifth-grade high school students (<it>N </it>= 11,872), were used. Data were analyzed using multilevel logistic and Poisson regression techniques.</p> <p>Results</p> <p>There is an indication that type of education affects both an adolescent's sexual activity and his/her AIDS knowledge; these effects prove robust for differences in socio-economic backgrounds. Students in lower status education types are more likely to be sexually active and to have poorer AIDS knowledge. The relationship between AIDS knowledge and sexual activity is, however, more complex. Although students in education types with poorer AIDS knowledge are more sexually active, within each of these groups the sexually active have better AIDS knowledge than the non-sexually active. There is also evidence of active information seeking by sexually active students, which leads to improved AIDS knowledge.</p> <p>Conclusion</p> <p>These findings are consistent with the literature on the role of the educational system in the reproduction of social inequalities. Students from lower status education types are at increased sexual risk compared to those from higher status types. There is also evidence of active information seeking by sexually active students, which leads to improved AIDS knowledge.</p