HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are ...synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γ and NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3′ untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3′UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.
AbstractSeveral factors influence adolescents’ life satisfaction. At school, peer relatedness and school supportiveness, as well as individual self-perceptions such as academic self-efficacy, promote ...life satisfaction. Yet school is a context within which risks such as victimization can occur. The aim of this study was to test a model of relations of school factors predicting life satisfaction. We tested the mediator effects of victimization and academic self-efficacy between school supportiveness and peer belonging and life satisfaction. Participants were 2200 6th and 7th grades children attending middle school in Southern Switzerland. Data have been collected with the Middle Years Development Instrument questionnaire. Results showed that the sense of peer belonging and a supportive school environment have a positive effect on children academic self-efficacy and life satisfaction, and reduce the probability of victimization. Victimization, in turn, negatively affects life satisfaction and academic self-efficacy, while academic self-efficacy has a positive effect on life satisfaction.
Leukocyte immunoglobulin (Ig)‐like receptors (LILR) LILRB1 and LILRB2 may play a pivotal role in maintaining self‐tolerance and modulating the immune response through interaction with classical and ...nonclassical HLA molecules. Although both diversity and natural selection patterns over HLA genes have been extensively evaluated, little information is available concerning the genetic diversity and selection signatures on the LILRB1/2 regions. Therefore, we identified the LILRB1/2 genetic diversity using next‐generation sequencing in a population sample from São Paulo State, Brazil. We identified 58 LILRB1 Single Nucleotide Variants (SNVs), which gave rise to 13 haplotypes, and 41 LILRB2 SNVs arranged into 11 haplotypes. Although we may not exclude as a possible effect of population structure, we found evidence of either positive or purifying selection on LILRB1/2 coding regions. Some residues in both proteins showed to be under the effect of positive selection, suggesting that amino acid replacements in these proteins resulted in beneficial functional changes. Finally, we have revealed that allelic variation (six and five amino acid exchanges in LILRB1 and LILRB2, respectively) affects the structure and/or stability of both molecules. Nonetheless, LILRB2 has shown higher average stability, with no D1/D2 residue affecting protein structure. Overall, our findings demonstrate that LILRB1 and LILRB2 are as polymorphic as HLA class Ib genes and provide strong evidence supporting the directional selection regime hypothesis.
Recent theoretical and empirical research outlined the role of organizational identification in the stress process. We provide an empirical test of the social identity model of stress by testing a ...two-step mediation model of the identification-burnout link. We hypothesize that strongly identified teachers will receive more support from colleagues which, in turn, relates to perceptions of reduced workload, which finally leads to both lower work- and student-related burnout. We tested our model in a large cross-sectional sample of 2685 Swiss teachers representing half of the teacher population of Ticino Canton. Hypotheses were supported. Implications for theory and practice are discussed.
•A mediational model with two mediator in series is proposed.•The relation between school identification and teachers well-being is explored.•Identification is positively related to support and negatively related with teachers burnout.
HLA-G molecule plays an important role on immune response regulation and has been implicated on the inhibition of T and natural killer cell cytolytic function and inhibition of allogeneic T-cell ...proliferation. Due to its immune-modulator properties, the HLA-G gene expression has been associated with the outcome of allograft and of autoimmune, infectious, and malignant disorders. Several lines of evidence indicate that HLA-G polymorphisms at the 5′-upstream regulatory region (5′ URR) and 3′-untranslated region (3′ UTR) may influence the HLA-G expression levels. Because Brazilians represent one of the most heterogeneous populations in the world with the widest HLA-G coding region variability already detected among the studied populations, a high level of variability and haplotype diversity would be expected in Brazilians. On this basis, the 5′ URR, coding, and 3′ UTR variability were evaluated in a Brazilian series consisting of 100 healthy bone marrow donors, as well as the linkage disequilibrium pattern along the gene and the extended haplotypes encompassing several gene segment variations. The HLA-G locus seems to present six different HLA-G lineages showing functional variations mainly in nucleotides of the regulatory regions. Differences were observed at the 5′ URR in positions that either coincide with or are close to transcription factor-binding sites and at the 3′ UTR mainly in positions that have already been reported to influence HLA-G mRNA availability. We report several lines of evidence for balancing selection acting on the regulatory regions, which may indicate that these HLA-G lineages may be related to the differential HLA-G expression profiles.
Work stress and burnout affect teachers to a significant extent. The objective of this study is to evaluate and compare the impact of relational and organizational factors on teacher burnout in two ...samples of primary school teachers, one Italian (Naples) and the other Swiss (Cantone Ticino). The hypothesis is that, given the socio-cultural and economic differences of the two contexts, the variables under investigation impact teacher burnout differently. We collected data through a self-reported questionnaire containing the following scales: Copenhagen Burnout Inventory, Satisfaction with Life Scale, Life Orientation test, organizational identification, colleague support, and workload. The Swiss sample consists of 964 teachers (26% kindergarten and 73.7% primary school teachers); the Italian sample consists of 104 teachers (20% kindergarten and 80% primary schools teachers). Descriptive analyses, mean comparison (
test), correlational analyses, and multiple linear regression analyses were conducted. There are no significant differences between the two samples with respect to burnout, colleague support, and workload. Correlations between burnout and the variables under investigation are significant in both samples, except for optimism in the Italian sample. Regression analysis shows that optimism and colleague support have an impact on burnout only in the Swiss sample; organizational identification has a stronger impact on burnout in the Italian sample.
Human leukocyte antigen‐C (HLA‐C) is a classical HLA class I molecule that binds and presents peptides to cytotoxic T lymphocytes in the cell surface. HLA‐C has a dual function because it also ...interacts with Killer‐cell immunoglobulin‐like receptors (KIR) receptors expressed in natural killer and T cells, modulating their activity. The structure and diversity of the HLA‐C regulatory regions, as well as the relationship among variants along the HLA‐C locus, are poorly addressed, and few population‐based studies explored the HLA‐C variability in the entire gene in different population samples. Here we present a molecular and bioinformatics method to evaluate the entire HLA‐C diversity, including regulatory sequences. Then, we applied this method to survey the HLA‐C diversity in two population samples with different demographic histories, one highly admixed from Brazil with major European contribution, and one from Benin with major African contribution. The HLA‐C promoter and 3′UTR were very polymorphic with the presence of few, but highly divergent haplotypes. These segments also present conserved sequences that are shared among different primate species. Nucleotide diversity was higher in other segments rather than exons 2 and 3, particularly around exon 5 and the second half of the 3′UTR region. We detected evidence of balancing selection on the entire HLA‐C locus and positive selection in the HLA‐C leader peptide, for both populations. HLA‐C motifs previously associated with KIR interaction and expression regulation are similar between both populations. Each allele group is associated with specific regulatory sequences, reflecting the high linkage disequilibrium along the entire HLA‐C locus in both populations.
•We propose an NGS approach to detect full HLA-E variability and haplotypes.•Variability was surveyed in a very admixed population sample from Brazil.•The bioinformatics proposed was able to detect ...the HLA-E variability and haplotypes.•The HLA-E coding alleles encode mainly two different HLA-E molecules.•The distal promoter is the most variable HLA-E segment.
The HLA-E gene is characterized by low but wide expression on different tissues. HLA-E is considered a conserved gene, being one of the least polymorphic class I HLA genes. The HLA-E molecule interacts with Natural Killer cell receptors and T lymphocytes receptors, and might activate or inhibit immune responses depending on the peptide associated with HLA-E and with which receptors HLA-E interacts to. Variable sites within the HLA-E regulatory and coding segments may influence the gene function by modifying its expression pattern or encoded molecule, thus, influencing its interaction with receptors and the peptide. Here we propose an approach to evaluate the gene structure, haplotype pattern and the complete HLA-E variability, including regulatory (promoter and 3′UTR) and coding segments (with introns), by using massively parallel sequencing. We investigated the variability of 420 samples from a very admixed population such as Brazilians by using this approach. Considering a segment of about 7kb, 63 variable sites were detected, arranged into 75 extended haplotypes. We detected 37 different promoter sequences (but few frequent ones), 27 different coding sequences (15 representing new HLA-E alleles) and 12 haplotypes at the 3′UTR segment, two of them presenting a summed frequency of 90%. Despite the number of coding alleles, they encode mainly two different full-length molecules, known as E*01:01 and E*01:03, which corresponds to about 90% of all. In addition, differently from what has been previously observed for other non classical HLA genes, the relationship among the HLA-E promoter, coding and 3′UTR haplotypes is not straightforward because the same promoter and 3′UTR haplotypes were many times associated with different HLA-E coding haplotypes. This data reinforces the presence of only two main full-length HLA-E molecules encoded by the many HLA-E alleles detected in our population sample. In addition, this data does indicate that the distal HLA-E promoter is by far the most variable segment. Further analyses involving the binding of transcription factors and non-coding RNAs, as well as the HLA-E expression in different tissues, are necessary to evaluate whether these variable sites at regulatory segments (or even at the coding sequence) may influence the gene expression profile.
Over the past thirty years, the sense of school belonging received increasing attention in the educational field because of the many developmental and educational advantages associated with it. ...Previous research suggested that small schools are in a better position to create a strong sense of belonging among students. The aim of our study was to test the effect of school size on students’ sense of school belonging and to test whether this effect holds after considering the effect of the classroom after controlling for individual differences. The study was conducted on a sample of 1698 sixth- and seventh-grade students distributed among 20 school institutes in Switzerland. Multilevel analyses have been conducted. While first results showed an effect of the school size on the sense of school belonging, a comparison of the two-level and three-level hierarchical linear models showed that this effect is no longer significant when considering the intermediate level of the classroom in the analysis, indicating that previous research may have overestimated the effect of school size on the sense of school belonging. These evidence raises the question of which levels of the school environment are more relevant to better understanding individual differences in the sense of school belonging.
•An NGS approach to detect HLA-G variability and haplotypes is proposed.•Variability was surveyed in two geographically and demographically distinct samples.•The bioinformatics proposed was able to ...detect the HLA-G variability and haplotypes.•Both samples shared most of the haplotypes, which may be old and found worldwide.•HLA-G variability might have arisen in Africa before human dispersion.
The HLA-G molecule presents immunomodulatory properties that might inhibit immune responses when interacting with specific Natural Killer and T cell receptors, such as KIR2DL4, ILT2 and ILT4. Thus, HLA-G might influence the outcome of situations in which fine immune system modulation is required, such as autoimmune diseases, transplants, cancer and pregnancy. The majority of the studies regarding the HLA-G gene variability so far was restricted to a specific gene segment (i.e., promoter, coding or 3′ untranslated region), and was performed by using Sanger sequencing and probabilistic models to infer haplotypes. Here we propose a massively parallel sequencing (NGS) with a bioinformatics strategy to evaluate the entire HLA-G regulatory and coding segments, with haplotypes inferred relying more on the straightforward haplotyping capabilities of NGS, and less on probabilistic models. Then, HLA-G variability was surveyed in two admixed population samples of distinct geographical regions and demographic backgrounds, Cyprus and Brazil. Most haplotypes (promoters, coding, 3′UTR and extended ones) were detected both in Brazil and Cyprus and were identical to the ones already described by probabilistic models, indicating that these haplotypes are quite old and may be present worldwide.
PDF
