Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment

<p>Abstract</p> <p>Background</p> <p>Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus.</p> <p>Results</p> <p>Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor.</p> <p>Conclusions</p> <p>We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.</p

Comparison between the Short Story Task and the Reading the Mind in the Eyes Test for evaluating Theory of Mind: A replication report

Introduction The ability to attribute emotional states, beliefs, and intentions to others has been termed Theory of Mind (ToM), mentalizing, and mind reading. The purpose of this study was to find an instrument to measure ToM in the Mexican population, that would yield similar results to those obtained in other cultures, and could discriminate between individuals. To achieve this objective, we replicated a study which compared two measures of ToM in a sample of English-speaking, neurologically intact adults. Methods A sample of young Mexican adults (n = 118) was evaluated on the Reading the Mind in the Eyes Test (RMET) and a test that uses naturalistic narrative stimuli, the Short Story Task (SST), and on tests of general cognitive ability, executive functions, and empathy. Results We found a significant correlation between the ToM tests, and both tests correlated with verbal ability, general cognitive ability, and empathy, similar to what was seen in a previous study. Both tests discriminated between individuals and were challenging enough that we found no perfect scores. Conclusions These results show that both the RMET, which taps into emotion recognition and its categorization with language, and the SST, which relies on narrative fiction to test the ability to interpret mental states, show concurrent validity in a sample of neurologically intact young adults from a Latin-American culture; these tests may be useful in the clinical setting and for basic research into ToM

TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation

IF 2.264International audiencePierpont syndrome is a rare and sporadic syndrome, including developmental delay, facial characteristics, and abnormal extremities. Recently, a recurrent de novo TBL1XR1 variant (c.1337A > G; p.Tyr446Cys) has been identified in eight patients by whole‐exome sequencing. A dominant‐negative effect of this mutation is strongly suspected, since patients with TBL1XR1 deletion and other variants predicting loss of function do not share the same phenotype. We report two patients with typical Pierpont‐like syndrome features. Exome sequencing allowed identifying a de novo heterozygous missense TBL1XR1 variant in both patients, different from those already reported: p.Cys325Tyr and p.Tyr446His. The localization of these mutations and clinical features of Pierpont‐like syndrome suggest that their functional consequences are comparable with the recurrent mutation previously described, and provided additional data to understand molecular mechanisms of TBL1XR1 anomalies

Towards an European consensus on possible causes of MCCI ablation anisotropy in an oxidic pool

International audienceOne of the most disputed issues raised by molten corium concrete interaction (MCCI) is how the 2D cavity ablation in an oxidic pool evolves why is the ablation anisotropic with siliceous concretes and isotropic with carbonaceous concretes. The work performed in the frame of the SARNET2 WP6 group during the last 4 years has enabled significant progress on this topic. This paper summarizes this progress using the analysis of recent 2D real material experiments in an oxidic pool and from analytical simulant experiments on 2D heat convection in a bubbling pool, including calculations and recalculations with MCCI codes available in Europe. Firstly, the effective heat transfer coefficients from the bulk pool to the bottom and lateral pool interfaces deduced from MCCI experiments lead to a range of a few 100 W/m2/K. By contrast, a detailed review of possible 2D convection mechanisms shows that the individual heat convection mechanisms (without taking a crust into account) such as gas bubbling convection and solutal convection overestimates the overall heat transfer coefficient, and does not account for the main trends of 2D ablation deduced from MCCI tests, which are very dependent on the composition of concrete components and aggregates. This fact, in turn, points to the effect of more complex pool/concrete interface structures. On the basis of a thorough interpretation of the experimental database and of a detailed comparison of MCCI code predictions, a set of the most realistic and consistent assumptions are identified and major remaining uncertainties are listed. © 2014 Elsevier Ltd