Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349. Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma. Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.

Extrafollicular plasmablast B cells play a key role in carrying retroviral infection to peripheral organs.

B cells can either differentiate in germinal centers or in extrafollicular compartments of secondary lymphoid organs. Here we show the migration properties of B cells after differentiation in murine peripheral lymph node infected with mouse mammary tumor virus. Naive B cells become activated, infected, and carry integrated retroviral DNA sequences. After production of a retroviral superantigen, the infected B cells receive cognate T cell help and differentiate along the two main differentiation pathways analogous to classical Ag responses. The extrafollicular differentiation peaks on day 6 of mouse mammary tumor virus infection, and the follicular one becomes detectable after day 10. B cells participating in this immune response carry a retroviral DNA marker that can be detected by using semiquantitative PCR. We determined the migration patterns of B cells having taken part in the T cell-B cell interaction from the draining lymph node to different tissues. Waves of immigration and retention of infected cells in secondary lymphoid organs, mammary gland, salivary gland, skin, lung, and liver were observed correlating with the two peaks of B cell differentiation in the draining lymph node. Other organs revealed immigration of infected cells at later time points. The migration properties were correlated with a strong up-regulation of alpha(4)beta(1) integrin expression. These results show the migration properties of B cells during an immune response and demonstrate that a large proportion of extrafolliculary differentiating plasmablasts can escape local cell death and carry the retroviral infection to peripheral organs.

Further ultrastructural evidence that spirochaetes may play a role in the aetiology of Alzheimer's disease

Recently it was reported that, at autopsy, in neuropathologically confirmed cases of Alzheimer's disease spirochaetes were found in blood and cerebrospinal fluid using dark-field microscopy. Moreover, the spirochaetes were isolated and cultured from brain tissue. We now show, using scanning electron microscopy and atomic force microscopy that the helically shaped microorganisms isolated and cultured from the Alzheimer brains possess axial filaments. This indicates that these microorganisms taxonomically indeed belong to the order Spirochaetales. A morphometric analysis reinforces this notion.

Does CRP Play a Causal Role in the Development of Coronary Heart Disease: Results of a Mendelian Randomisation Experiment Involving 128,935 People

Background: C-reactive protein (CRP) is associated with risk of coronary heart disease (CHD). Whether CRP is causally associated with CHD or merely a marker of underlying atherosclerosis is uncertain. Methods: We used a Mendelian randomisation design to investigate the causal relationship of CRP with CHD. We identified three genetic variants in the CRP locus (rs7553007, rs1130864 and rs1205) which influence CRP levels. We tested the three SNPs for association with CHD amongst 28,112 CHD cases and 100,823 controls. We then compared the observed relationship between the SNPs and CHD, with that predicted from the association of SNPs with CRP levels, and of CRP levels with CHD. Results: SNPs in the CRP locus were not associated with CHD: rs7553007, OR 0.98 (95% CI, 0.94-1.01); rs1130864, OR 1.00 (95% CI, 0.86-1.15); rs1205, OR 1.03 (95% CI, 0.99-1.07); combined OR for all three SNPs, 1.00 (95% CI, 0.97-1.02), per 20% lower CRP (figure). In contrast, the predicted OR for CHD from a 20% lower CRP level is 0.94 (95% CI, 0.94- 0.95), based on meta-analysis of observational studies. Conclusions: Though CRP variants are associated with CRP levels, and CRP levels with risk of CHD, we observed that CRP variants are not associated with CHD risk. Our Mendelian randomisation experiment strongly argues against a causal association of CRP with CHD.

N-Glycosylation and conserved cysteine residues in RAMP3 play a critical role for the functional expression of CRLR/RAMP3 adrenomedullin receptor.

The calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein-3 (RAMP3) can assemble into a CRLR/RAMP3 heterodimeric receptor that exhibits the characteristics of a high affinity adrenomedullin receptor. RAMP3 participates in adrenomedullin (AM) binding via its extracellular N-terminus characterized by the presence of six highly conserved cysteine residues and four N-glycosylation consensus sites. Here, we assessed the usage of these conserved residues in cotranslational modifications of RAMP3 and addressed their role in functional expression of the CRLR/RAMP3 receptor. Using a Xenopus oocyte expression system, we show that (i) RAMP3 is assembled with CRLR as a multiple N-glycosylated species in which two, three, or four consensus sites are used; (ii) elimination of all N-glycans in RAMP3 results in a significant inhibition of receptor [(125)I]AM binding and an increase in the EC(50) value for AM; (iii) several lines of indirect evidence indicate that each of the six cysteines is involved in disulfide bond formation; (iv) when all cysteines are mutated to serines, RAMP3 is N-glycosylated at all four consensus sites, suggesting that disulfide bond formation inhibits N-gylcosylation; and (v) elimination of all cysteines abolishes adrenomedullin binding and leads to a complete loss of receptor function. Our data demonstrate that cotranslational modifications of RAMP3 play a critical role in the function of the CRLR/RAMP3 adrenomedullin receptor.

Parents - child role reversal in trilogue play: case studies of trajectories from pregnancy to toddlerhood

Role reversal, whereby a child attempts to meet her parent's adult needs for parenting, intimacy, or companionship, has been identified as a risk factor for developmental disturbances. It has been defined from diverse perspectives as a child attachment strategy, a parent - toddler relational disturbance, and a boundary disturbance between parents and child. The recently discovered infant's triangular capacity, namely the sharing of her attention and affects with both parents, allows one to analyse the infant's contribution to early family dynamics. Role reversal was detected in 4 out of 45 father - mother - infant interactions observed in trilogue play from pregnancy to toddlerhood. The developmental trajectories towards role reversal are explored by means of case analyses. Results are compared with cases of problematic triangulation encountered in the same sample. In role reversal, family interactions are rigidly organized around a "two against one" coalition, whereby the normative hierarchy between parents and child is reversed. The child's triangular capacity is overactivated, controlling the tension between her parents by provocation - animation strategies

Let's K-Map Play: Juego de aprendizaje de Karnagh Maps para móvil

En este informe se describe el trabajo de fin de máster, centrado en el estudio de la gamificación como herramienta de aprendizaje aplicada a dispositivos móviles. Se ha realizado una revisión de los artículos científicos que tratan sobre el tema de la gamificación como herramienta educativa,para terminar el trabajo desarrollando un prototipo de juego para el aprendizaje de mapas de Karnaugh. Se ha optado por un desarrollo multiplataforma y se han revisado los frameworks de desarrollo más populares para desarrollo móvil multiplataforma así como los motores de juegos aplicables a este caso. Tras la implementación, se ha probado el prototipo en dos sistemas operativos móviles libres: Android y Firefox OS.

Preguntes i respostes - Play Q&A : Programació d'aplicacions per a dispositius mòbils usant HTML5

Desenvolupament d'una aplicació per a estudiants on poden practicar els coneixements adquirits a les seves assignatures amb un joc de preguntes i respostes.

Let's K-map play : Juego de aprendizaje de Karnaugh Maps para móvil

En este informe se describe el trabajo de fin de máster, centrado en el estudio de la gamificación como herramienta de aprendizaje aplicada a dispositivos móviles. Se ha realizado una revisión de los artículos científicos que tratan sobre el tema de la gamificación como herramienta educativa, para terminar el trabajo desarrollando un prototipo de juego para el aprendizaje de mapas de Karnaugh. Se ha optado por un desarrollo multiplataforma y se han revisado los frameworks de desarrollo más populares para desarrollo móvil multiplataforma, así como los motores de juegos aplicables a este caso. Tras la implementación, se ha probado el prototipo en dos sistemas operativos móviles libres: Android y Firefox OS.

Gallery districts of Barcelona: the strategic play of art dealers

This article focuses on Barcelona"s art market to explore the underlying factors behind the clustering of art dealers in several of the city"s districts. Drawing upon quantitative and qualitative data, the article analyses how such clustering reveals a strategic action in the sense attributed to it by Crozier and Friedberg (1981). Gallery districts are not a reflection of structural factors (economic, urban development-related or social) but the result of a combination of strategic choices either individual or collective which explain the permanence of leading gallery districts or the emergence of new ones.