Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

Prótesis unicompartimental lateral de rodilla. Indicaciones, técnica y resultados a mediocorto plazo

Objectives: In patients with lateral osteoarthritis of the knee, use of external unicompartmental knee arthroplasty it is a well known surgical alternative, used by the minor trauma involved, short hospital stay and rapid recovery. The purpose of this study is to show the clinical outcomes to short-medium term of patients undergoing this procedure. Methods: we describe the technique used and the peculiarities of the prosthesis (A Mobile-bearing lateral unicompartmental knee replacement, Oxford Domed ®). This is an observational retrospective longitudinal study, of 15 arthroplasties performed in 13 women and 2 men, between 2010 and 2013, with a mean age of 60’7 years, with a diagnosis of lateral osteoarthritis of the knee, without involvement of the medial or patellofemoral compartment and cruciate ligaments functionally intact, with a mean follow up of 25 months. All patients complete the Oxford Knee Score and Visual Analog Scale (VAS) during the study. Results: The results are favorable, with an improvement of 6.60 points on the EVA, 3.73 for 1 in the postoperatory funcionality, the OKS very satisfactory with an average of 38 points over 50 and without any postoperative function surgical revision. Anserine tendinitis was observed in 20% of cases. Conclusions: The benefits of this surgery against their alternatives are assessed, and their potential drawbacks. External unicompartmental knee arthroplasty is an effective alternative in cases of knee osteoarthritis of the lateral compartment with no other associated injuries.

Adaptively weighted maximum likelihood estimation of discrete distributions

SummaryDiscrete data arise in various research fields, typically when the observations are count data.I propose a robust and efficient parametric procedure for estimation of discrete distributions. The estimation is done in two phases. First, a very robust, but possibly inefficient, estimate of the model parameters is computed and used to indentify outliers. Then the outliers are either removed from the sample or given low weights, and a weighted maximum likelihood estimate (WML) is computed.The weights are determined via an adaptive process such that if the data follow the model, then asymptotically no observation is downweighted.I prove that the final estimator inherits the breakdown point of the initial one, and that its influence function at the model is the same as the influence function of the maximum likelihood estimator, which strongly suggests that it is asymptotically fully efficient.The initial estimator is a minimum disparity estimator (MDE). MDEs can be shown to have full asymptotic efficiency, and some MDEs have very high breakdown points and very low bias under contamination. Several initial estimators are considered, and the performances of the WMLs based on each of them are studied.It results that in a great variety of situations the WML substantially improves the initial estimator, both in terms of finite sample mean square error and in terms of bias under contamination. Besides, the performances of the WML are rather stable under a change of the MDE even if the MDEs have very different behaviors.Two examples of application of the WML to real data are considered. In both of them, the necessity for a robust estimator is clear: the maximum likelihood estimator is badly corrupted by the presence of a few outliers.This procedure is particularly natural in the discrete distribution setting, but could be extended to the continuous case, for which a possible procedure is sketched.RésuméLes données discrètes sont présentes dans différents domaines de recherche, en particulier lorsque les observations sont des comptages.Je propose une méthode paramétrique robuste et efficace pour l'estimation de distributions discrètes. L'estimation est faite en deux phases. Tout d'abord, un estimateur très robuste des paramètres du modèle est calculé, et utilisé pour la détection des données aberrantes (outliers). Cet estimateur n'est pas nécessairement efficace. Ensuite, soit les outliers sont retirés de l'échantillon, soit des faibles poids leur sont attribués, et un estimateur du maximum de vraisemblance pondéré (WML) est calculé.Les poids sont déterminés via un processus adaptif, tel qu'asymptotiquement, si les données suivent le modèle, aucune observation n'est dépondérée.Je prouve que le point de rupture de l'estimateur final est au moins aussi élevé que celui de l'estimateur initial, et que sa fonction d'influence au modèle est la même que celle du maximum de vraisemblance, ce qui suggère que cet estimateur est pleinement efficace asymptotiquement.L'estimateur initial est un estimateur de disparité minimale (MDE). Les MDE sont asymptotiquement pleinement efficaces, et certains d'entre eux ont un point de rupture très élevé et un très faible biais sous contamination. J'étudie les performances du WML basé sur différents MDEs.Le résultat est que dans une grande variété de situations le WML améliore largement les performances de l'estimateur initial, autant en terme du carré moyen de l'erreur que du biais sous contamination. De plus, les performances du WML restent assez stables lorsqu'on change l'estimateur initial, même si les différents MDEs ont des comportements très différents.Je considère deux exemples d'application du WML à des données réelles, où la nécessité d'un estimateur robuste est manifeste : l'estimateur du maximum de vraisemblance est fortement corrompu par la présence de quelques outliers.La méthode proposée est particulièrement naturelle dans le cadre des distributions discrètes, mais pourrait être étendue au cas continu.

Unraveling the complex metabolic nature of astrocytes.

Since the initial description of astrocytes by neuroanatomists of the nineteenth century, a critical metabolic role for these cells has been suggested in the central nervous system. Nonetheless, it took several technological and conceptual advances over many years before we could start to understand how they fulfill such a role. One of the important and early recognized metabolic function of astrocytes concerns the reuptake and recycling of the neurotransmitter glutamate. But the description of this initial property will be followed by several others including an implication in the supply of energetic substrates to neurons. Indeed, despite the fact that like most eukaryotic non-proliferative cells, astrocytes rely on oxidative metabolism for energy production, they exhibit a prominent aerobic glycolysis capacity. Moreover, this unusual metabolic feature was found to be modulated by glutamatergic activity constituting the initial step of the neurometabolic coupling mechanism. Several approaches, including biochemical measurements in cultured cells, genetic screening, dynamic cell imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have provided further insights into the intrinsic characteristics giving rise to these key features of astrocytes. This review will provide an account of the different results obtained over several decades that contributed to unravel the complex metabolic nature of astrocytes that make this cell type unique.

Questioni di pulizia: rappresentazioni e valori

In the framework of social representation, this research explores how the concept of cleanness does not refer solely to individual hygienic praxes and thoughts, but it is also linked to social and cultural aspects. In this way, the definitions of what is dirty and what is clean, what is pure and what is impure, are linked to social discrimination attitudes, based for example on the fear for contamination. Our general hypothesis is that the representations of dirt/cleanness and purity/impurity define ideas and praxes linked to personal hygiene, but refer also to the way people interact with the world and the others. Hence, we hypothesize that the representations of dirt/cleanness and purity/impurity are linked to values and political and religious orientations. A questionnaire with closed-answer questions and a free association task were distributed to 450 subjects. Results show how, in effects, the concepts of dirt/cleanness, purity/ impurity skip from their daily praxis connotations and assume a symbolic function for discriminating between individuals and social groups.

Connectivity differences in brain networks.

The scenario considered here is one where brain connectivity is represented as a network and an experimenter wishes to assess the evidence for an experimental effect at each of the typically thousands of connections comprising the network. To do this, a univariate model is independently fitted to each connection. It would be unwise to declare significance based on an uncorrected threshold of α=0.05, since the expected number of false positives for a network comprising N=90 nodes and N(N-1)/2=4005 connections would be 200. Control of Type I errors over all connections is therefore necessary. The network-based statistic (NBS) and spatial pairwise clustering (SPC) are two distinct methods that have been used to control family-wise errors when assessing the evidence for an experimental effect with mass univariate testing. The basic principle of the NBS and SPC is the same as supra-threshold voxel clustering. Unlike voxel clustering, where the definition of a voxel cluster is unambiguous, 'clusters' formed among supra-threshold connections can be defined in different ways. The NBS defines clusters using the graph theoretical concept of connected components. SPC on the other hand uses a more stringent pairwise clustering concept. The purpose of this article is to compare the pros and cons of the NBS and SPC, provide some guidelines on their practical use and demonstrate their utility using a case study involving neuroimaging data.

Association with coregulators is the major determinant governing peroxisome proliferator-activated receptor mobility in living cells.

The nucleus is an extremely dynamic compartment, and protein mobility represents a key factor in transcriptional regulation. We showed in a previous study that the diffusion of peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptors regulating major cellular and metabolic functions, is modulated by ligand binding. In this study, we combine fluorescence correlation spectroscopy, dual color fluorescence cross-correlation microscopy, and fluorescence resonance energy transfer to dissect the molecular mechanisms controlling PPAR mobility and transcriptional activity in living cells. First, we bring new evidence that in vivo a high percentage of PPARs and retinoid X receptors is associated even in the absence of ligand. Second, we demonstrate that coregulator recruitment (and not DNA binding) plays a crucial role in receptor mobility, suggesting that transcriptional complexes are formed prior to promoter binding. In addition, association with coactivators in the absence of a ligand in living cells, both through the N-terminal AB domain and the AF-2 function of the ligand binding domain, provides a molecular basis to explain PPAR constitutive activity.

Antiretroviral activity of ancestral TRIM5alpha.

The antiretroviral protein TRIM5alpha is known to have evolved different restriction capacities against various retroviruses, driven by positive Darwinian selection. However, how these different specificities have evolved in the primate lineages is not fully understood. Here we used ancestral protein resurrection to estimate the evolution of antiviral restriction specificities of TRIM5alpha on the primate lineage leading to humans. We used TRIM5alpha coding sequences from 24 primates for the reconstruction of ancestral TRIM5alpha sequences using maximum-likelihood and Bayesian approaches. Ancestral sequences were transduced into HeLa and CRFK cells. Stable cell lines were generated and used to test restriction of a panel of extant retroviruses (human immunodeficiency virus type 1 [HIV-1] and HIV-2, simian immunodeficiency virus [SIV] variants SIV(mac) and SIV(agm), and murine leukemia virus [MLV] variants N-MLV and B-MLV). The resurrected TRIM5alpha variant from the common ancestor of Old World primates (Old World monkeys and apes, approximately 25 million years before present) was effective against present day HIV-1. In contrast to the HIV-1 restriction pattern, we show that the restriction efficacy against other retroviruses, such as a murine oncoretrovirus (N-MLV), is higher for more recent resurrected hominoid variants. Ancestral TRIM5alpha variants have generally limited efficacy against HIV-2, SIV(agm), and SIV(mac). Our study sheds new light on the evolution of the intrinsic antiviral defense machinery and illustrates the utility of functional evolutionary reconstruction for characterizing recently emerged protein differences.

Diagnosis of muscular dystrophies at the nanometer scale

The diagnosis of muscular dystrophies or the assessment of the functional benefit of gene or cell therapies can be difficult, especially for poorly accessible muscles, and it often lacks a singlefiber resolution. In the present study, we evaluated whether muscle diseases can be diagnosed from small biopsies using atomic force microscopy (AFM). AFM was shown to provide a sensitive and quantitative description of the resistance of normal and dystrophic myofibers within live muscle tissues explanted from Duchenne mdx mice. The rescue of dystrophin expression by gene therapy approaches led to the functional recovery of treated dystrophic muscle fibers, as probed using AFM and by in situ wholemuscle strength measurements. Comparison of muscles treated with viral or non-viral vectors indicated that the efficacy of the gene transfer approaches could be distinguished with a single myofiber resolution. This indicated full correction of the resistance to deformation in nearly all of the muscle fibers treated with an adeno-associated viral vector that mediates exon-skipping on the dystrophin mRNA. Having shown that AFM can provide a quantitative assessment of the expression of muscle proteins and of the muscular function in animal models, we assessed myofiber resistance in the context of human muscular dystrophies and myopathies. Thus, various forms of human Becker syndrome can also be detected using AFM in blind studies of small frozen biopsies from human patients. Interestingly, it also allowed the detection of anomalies in a fraction of the muscle fibers from patients showing a muscle weakness that could not be attributed to a known molecular or genetic defect. Overall, we conclude that AFM may provide a useful method to complement current diagnosis tools of known and unknown muscular diseases, in research and in a clinical context.

Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence.

Fungal infections represent a serious threat, particularly in immunocompromised patients. Interleukin-1beta (IL-1beta) is a key pro-inflammatory factor in innate antifungal immunity. The mechanism by which the mammalian immune system regulates IL-1beta production after fungal recognition is unclear. Two signals are generally required for IL-1beta production: an NF-kappaB-dependent signal that induces the synthesis of pro-IL-1beta (p35), and a second signal that triggers proteolytic pro-IL-1beta processing to produce bioactive IL-1beta (p17) via Caspase-1-containing multiprotein complexes called inflammasomes. Here we demonstrate that the tyrosine kinase Syk, operating downstream of several immunoreceptor tyrosine-based activation motif (ITAM)-coupled fungal pattern recognition receptors, controls both pro-IL-1beta synthesis and inflammasome activation after cell stimulation with Candida albicans. Whereas Syk signalling for pro-IL-1beta synthesis selectively uses the Card9 pathway, inflammasome activation by the fungus involves reactive oxygen species production and potassium efflux. Genetic deletion or pharmalogical inhibition of Syk selectively abrogated inflammasome activation by C. albicans but not by inflammasome activators such as Salmonella typhimurium or the bacterial toxin nigericin. Nlrp3 (also known as NALP3) was identified as the critical NOD-like receptor family member that transduces the fungal recognition signal to the inflammasome adaptor Asc (Pycard) for Caspase-1 (Casp1) activation and pro-IL-1beta processing. Consistent with an essential role for Nlrp3 inflammasomes in antifungal immunity, we show that Nlrp3-deficient mice are hypersusceptible to Candida albicans infection. Thus, our results demonstrate the molecular basis for IL-1beta production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo.

Analysis of LEDGF/p75 expression regulation

Background To replicate, retroviruses must insert DNA copies of their RNA genomes into the host genome. This integration process is catalyzed by the viral integrase protein. The site of viral integration has been shown to be non-random and retrovirus-specific. LEDGF/p75, a splice variant encoded by PSIP1 gene and described as a general transcription coactivator, was identified as a tethering factor binding both to chromatin and to lentiviral integrases, thereby affecting integration efficiency as well as integration site selection. LEDGF/p75 is still a poorly characterized protein, and its cellular endogenous function has yet to be fully determined. In order to start unveiling the roles of LEDGF/p75 in the cell, we started to investigate the mechanisms involved in the regulation of LEDGF/p75. Materials and methods To identify PSIP1 minimal promoter and associated regulatory elements, we cloned a region starting 5 kb upstream the transcription start site (TSS, +1 reference position) to the ATG start codon (+816), as well as systematic truncations, in a plasmid containing the firefly luciferase reporter gene. These constructs were co-transfected into HEK293 cells with a plasmid encoding the Renilla luciferase under the pTK promoter as an internal control for transfection efficiency. Both luciferase activities were assessed by luminescence as an indicator of promoter activity. Results Luciferase assays identified regions -76 to +1 and +1 to +94 as two independent minimal promoters showing respectively a 3.7x and 2.3x increase in luciferase activity. These two independent minimal promoters worked synergistically increasing luciferase activity up to 16.3x as compared to background. Moreover, we identified five regulatory blocks which modulated luciferase activity depending on the DNA region tested, three enhancers (- 2007 to -1159, -284 to -171 and +94 to +644) and two silencers (-171 to -76 and +796 to +816). However, the silencing effect of the region -171 to -76 is dependent on the presence of the +94 to +644 region, ruling out the enhancer activity of the latter. Computational analysis of PSIP1 promoter revealed the absence of TATA box and initiator (INR) sequences, classifying this promoter as nonconventional. TATA-less and INR-less promoters are characterized by multiple Sp1 binding sites, involved in the recruitment of the RNA pol II complex. Consistent with this, PSIP1 promoter contains multiple putative Sp1 binding sequences in regions -76 to +1 and +1 to +94.

Assigning proctors to exams with scatter search

In this paper we present an algorithm to assign proctors toexams. This NP-hard problem is related to the generalized assignmentproblem with multiple objectives. The problem consists of assigningteaching assistants to proctor final exams at a university. We formulatethis problem as a multiobjective integer program (IP) with a preferencefunction and a workload-fairness function. We then consider also a weightedobjective that combines both functions. We develop a scatter searchprocedure and compare its outcome with solutions found by solving theIP model with CPLEX 6.5. Our test problems are real instances from aUniversity in Spain.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

Precursors of functional MHC class I- or class II-restricted CD8alphaalpha(+) T cells are positively selected in the thymus by agonist self-peptides.

The origin and specificity of alphabeta TCR(+) T cells that express CD8alphaalpha have been controversial issues. Here we provide direct evidence that precursors of functional CD8alphaalpha T cells are positively selected in the thymus in the presence of agonist self-peptides. Like conventional positive selection, this agonist selection process requires functional TCR alpha-CPM, whereas it is independent of CD8beta expression. Furthermore, CD8alphaalpha expression on mature, agonist-selected T cells does not imply selection by MHC class I, and CD8alphaalpha(+) T cells can be either class I or class II restricted. Our data define a distinct agonist-dependent, positive selection process in the thymus, and they suggest a function for CD8alphaalpha distinct from the conventional TCR coreceptor function of CD8alphabeta or CD4.