237 research outputs found
Overeducation across British regions
This paper analyses levels of over-education and wage returns to education for males across
eleven regions of the UK using Labour Force Survey data. Significant differences are found
in the probability of being over-educated across regions; also, differences are found in the
return to the âcorrectâ level of education in each region, in each case associated with
flexibility of movement between and into particular regions, which determines the ease of job
matching. Furthermore, evidence is found that, after controlling for the level of education
acquired, there exists a premium to the âcorrectâ level of education, which varies across UK
regions
Circulating beta cell-specific CD8(+) T cells restricted by high-risk HLA class I molecules show antigen experience in children with and at risk of type 1 diabetes
In type 1 diabetes (T1D), autoreactive cytotoxic CD8(+) T cells are implicated in the destruction of insulin-producing beta cells. The HLA-B*3906 and HLA-A*2402 class I genes confer increased risk and promote early disease onset, suggesting that CD8(+) T cells that recognize peptides presented by these class I molecules on pancreatic beta cells play a pivotal role in the autoimmune response. We examined the frequency and phenotype of circulating preproinsulin (PPI)-specific and insulin B (InsB)-specific CD8(+) T cells in HLA-B*3906(+) children newly diagnosed with T1D and in high-risk HLA-A*2402(+) children before the appearance of disease-specific autoantibodies and before diagnosis of T1D. Antigen-specific CD8(+) T cells were detected using human leucocyte antigen (HLA) class I tetramers and flow cytometry was used to assess memory status. In HLA-B*3906(+) children with T1D, we observed an increase in PPI5-12-specific transitional memory CD8(+) T cells compared to non-diabetic, age- and HLA-matched subjects. Furthermore, PPI5-12-specific CD8(+) T cells in HLA-B*3906(+) children with T1D showed a significantly more antigen-experienced phenotype compared to polyclonal CD8(+) T cells. In longitudinal samples from high-risk HLA-A*2402(+) children, the percentage of terminal effector cells within the InsB(15-24)-specific CD8(+) T cells was increased before diagnosis relative to samples taken before the appearance of autoantibodies. This is the first study, to our knowledge, to report HLA-B*3906-restricted autoreactive CD8(+) T cells in T1D. Collectively, our results provide evidence that beta cell-reactive CD8(+) T cells restricted by disease-associated HLA class I molecules display an antigen-experienced phenotype and acquire enhanced effector function during the period leading to clinical diagnosis, implicating these cells in driving disease.Peer reviewe
Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination
Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCRâCD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCRâCD3 complexes. We found that only TCRâCD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCRâpMHC affinity determined the density of TCRâCD3 clusters, which scaled with overall phosphorylation levels. Thus, TCRâCD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination
Assessing the Incidence and Wage Effects of Overeducation Among Italian Graduates Using a New Measure for Educational Requirements
Five characteristics of youth unemployment in Europe
Current levels of youth unemployment need to be understood in the context of increased labor market flexibility, an expansion of higher education, youth migration, and family legacies of long-term unemployment. Compared with previous recessions, European-wide policies and investments have significantly increased with attempts to support national policies. By mapping these developments and debates, we illustrate the different factors shaping the future of European labor markets. We argue that understanding youth unemployment requires a holistic approach that combines an analysis of changes in the economic sphere around labor market flexibility, skills attainment, and employer demand, as well as understanding the impact of family legacies affecting increasingly polarized trajectories for young people today. The success of EU policy initiatives and investments will be shaped by the ability of national actors to implement these effectively
Circulating ÎČ cell-specific CD8+ T cells restricted by high-risk HLA class I molecules show antigen experience in children with and at risk of type 1 diabetes
In type 1 diabetes (T1D), autoreactive cytotoxic CD8+ T cells are implicated in the destruction of insulinâproducing ÎČ cells. The HLAâB*3906 and HLAâA*2402 class I genes confer increased risk and promote early disease onset, suggesting that CD8+ T cells that recognize peptides presented by these class I molecules on pancreatic ÎČ cells play a pivotal role in the autoimmune response. We examined the frequency and phenotype of circulating preproinsulin (PPI)âspecific and insulin B (InsB)âspecific CD8+ T cells in HLAâB*3906+ children newly diagnosed with T1D and in highârisk HLAâA*2402+ children before the appearance of diseaseâspecific autoantibodies and before diagnosis of T1D. Antigenâspecific CD8+ T cells were detected using human leucocyte antigen (HLA) class I tetramers and flow cytometry was used to assess memory status. In HLAâB*3906+ children with T1D, we observed an increase in PPI5â12âspecific transitional memory CD8+ T cells compared to nonâdiabetic, ageâ and HLAâmatched subjects. Furthermore, PPI5â12âspecific CD8+ T cells in HLAâB*3906+ children with T1D showed a significantly more antigenâexperienced phenotype compared to polyclonal CD8+ T cells. In longitudinal samples from highârisk HLAâA*2402+ children, the percentage of terminal effector cells within the InsB15â24âspecific CD8+ T cells was increased before diagnosis relative to samples taken before the appearance of autoantibodies. This is the first study, to our knowledge, to report HLAâB*3906ârestricted autoreactive CD8+ T cells in T1D. Collectively, our results provide evidence that ÎČ cellâreactive CD8+ T cells restricted by diseaseâassociated HLA class I molecules display an antigenâexperienced phenotype and acquire enhanced effector function during the period leading to clinical diagnosis, implicating these cells in driving disease.</p
Risk, balanced skills and entrepreneurship
This paper proposes that risk aversion encourages individuals to invest in balanced skill profiles, making them more likely to become entrepreneurs. By not taking this possible linkage into account, previous research has underestimated the impacts of both risk aversion and balanced skills on the likelihood individuals choose entrepreneurship. Data on Dutch university graduates provide an illustration supporting our contention. We raise the possibility that even risk-averse people might be suited to entrepreneurship; and it may also help explain why prior research has generated somewhat mixed evidence about the effects of risk aversion on selection into entrepreneurship
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