Defective FoxP3+ Treg cell differentiation in the gut of Type 1 Diabetic patients

Environmental factors that act at the intestinal level such as diet, drugs, and microflora have a high impact on the pathogenesis of autoimmune Type 1 Diabetes (T1D), but it is still unclear how the gut milieu affects autoimmunity outside the intestine. Here we show that peripheral FoxP3+ Treg cell differentiation, a mechanism that takes place in the gut and is crucial to maintain systemic immune tolerance, is impaired in T1D patients. These results provide the first evidence that gut mucosa alteration could predispose to autoimmune T1D by affecting systemic immune regulation

THE ASMATIC CHILD IN THE FAMILY: A STUDY ON A REPRESENTATION

The aim of this work, based on the Theory of Social Representations, commected to the Psychoanalytical Theory, was to apprehend the social representation of the family concerning asthmatic children. Five families collaborated. The study matenal was obtained ffirough semistructured home interviews and amalysed ffirough the content amalysis method. Questions were raised regarding the knowledge about ffie disease and the impact that its diagnosis produces on the family relations. Other emerging points were analysed, such as ffie questions of heredity amd blame, negation and fear, feelmgs of ambivaience amd impotence ffiat pervade ffie moffier-child relationship, besides using the disease as a mask to hide a conflicting family structure.O presente trabalho, que teve por fio condutor a Teoria das Representações Sociais, articulada à Teoria Psicanalítica, buscou apreender a representação social da família acerca da criança asmática. Para tanto, contou-se com a colaboração de cinco famílias. O material de estudo foi obtido por meio de entrevistas domiciliares, semi-estruturadas, sendo utilizado o método de análise de conteúdo. Foram levantadas questões concernentes ao conhecimento da doença e ao impacto que o seu diagnóstico produz no ambito das relações familiares. Foram analisados alguns pontos emergentes, como a questão da hereditariedade e da culpabilidade, a negação e o medo, os sentimentos de ambivalência e impotência que permeiam as relações mães-filhos, além do uso da doença como máscara para ocultar uma possível estrutura familiar conflituosa

A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction.

Acquired mutations in the juxtamembrane region of MPL (W515K or W515L), the receptor for thrombopoietin, have been described in patients with primary myelofibrosis or essential thrombocythemia, which are chronic myeloproliferative disorders. We have developed a real-time polymerase chain reaction assay for the detection and quantification of MPL mutations that is based on locked nucleic acid fluorescent probes. Mutational analysis was performed using DNA from granulocytes. Reference curves were obtained using cloned fragments of MPL containing either the wild-type or mutated sequence; the predicted sensitivity level was at least 0.1% mutant allele in a wild-type background. None of the 60 control subjects presented with a MPLW515L/K mutation. Of 217 patients with myelofibrosis, 19 (8.7%) harbored the MPLW515 mutation, 10 (52.6%) with the W515L allele. In one case, both the W515L and W515K alleles were detected by real-time polymerase chain reaction. By comparing results obtained with conventional sequencing, no erroneous genotype attribution using real-time polymerase chain reaction was found, whereas one patient considered wild type according to sequence analysis actually harbored a low W515L allele burden. This is a simple, sensitive, and cost-effective procedure for large-scale screening of the MPLW515L/K mutation in patients suspected to have a myeloproliferative disorder. It can also provide a quantitative estimate of mutant allele burden that might be useful for both patient prognosis and monitoring response to therapy

Assessing the effects of Bt maize on the non-target pest Rhopalosiphum maidis by demographic and life-history measurement endpoints.

AbstractThe most commercialized Bt maize plants in Europe were transformed with genes which express a truncated form of the insecticidal delta-endotoxin (Cry1Ab) from the soil bacterium Bacillus thuringiensis (Bt) specifically against Lepidoptera. Studies on the effect of transgenic maize on non-target arthropods have mainly converged on beneficial insects. However, considering the worldwide extensive cultivation of Bt maize, an increased availability of information on their possible impact on non-target pests is also required. In this study, the impact of Bt-maize on the non-target corn leaf aphid, Rhopalosiphum maidis, was examined by comparing biological traits and demographic parameters of two generations of aphids reared on transgenic maize with those on untransformed near-isogenic plants. Furthermore, free and bound phenolics content on transgenic and near-isogenic plants were measured. Here we show an increased performance of the second generation of R. maidis on Bt-maize that could be attributable to indirect effects, such as the reduction of defense against pests due to unintended changes in plant characteristics caused by the insertion of the transgene. Indeed, the comparison of Bt-maize with its corresponding near-isogenic line strongly suggests that the transformation could have induced adverse effects on the biosynthesis and accumulation of free phenolic compounds. In conclusion, even though there is adequate evidence that aphids performed better on Bt-maize than on non-Bt plants, aphid economic damage has not been reported in commercial Bt corn fields in comparison to non-Bt corn fields. Nevertheless, Bt-maize plants can be more easily exploited by R. maidis, possibly due to a lower level of secondary metabolites present in their leaves. The recognition of this mechanism increases our knowledge concerning how insect-resistant genetically modified plants impact on non-target arthropods communities, including tritrophic web interactions, and can help support a sustainable use of genetically modified crops

The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils of polycythemia vera.

BACKGROUND: The JAK2V617F mutation has been associated with constitutive and enhanced activation of neutrophils, while no information is available concerning other leukocyte subtypes. DESIGN AND METHODS: We evaluated correlations between JAK2V617F mutation and the count of circulating basophils, the number of activated CD63(+) basophils, their response in vitro to agonists as well as the effects of a JAK2 inhibitor. RESULTS: We found that basophil count was increased in patients with JAK2V617F -positive myeloproliferative neoplasms, particularly in those with polycythemia vera, and was correlated with the V617F burden. The burden of V617F allele was similar in neutrophils and basophils from patients with polycythemia vera, while total JAK2 mRNA content was remarkably greater in the basophils; however, the content of JAK2 protein in basophils was not increased. The number of CD63(+) basophils was higher in patients with polycythemia vera than in healthy subjects or patients with essential thrombocythemia or primary myelofibrosis and was correlated with the V617F burden. Ultrastructurally, basophils from patients with polycythemia vera contained an increased number of granules, most of which were empty suggesting cell degranulation in vivo. Ex vivo experiments revealed that basophils from patients with polycythemia vera were hypersensitive to the priming effect of interleukin-3 and to f-MLP-induced activation; pre-treatment with a JAK2 inhibitor reduced polycythemia vera basophil activation. Finally, we found that the number of circulating CD63(+) basophils was significantly greater in patients suffering from aquagenic pruritus, who also showed a higher V617F allele burden. CONCLUSIONS: These data indicate that the number of constitutively activated and hypersensitive circulating basophils is increased in polycythemia vera, underscoring a role of JAK2V617F in these cells’ abnormal function and, putatively, in the pathogenesis of pruritus