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Role of PTPN22 in type 1 diabetes
Full text linkIl polimorfismo missense C1858T del gene PTPN22 e’ associato con
diverse malattie autoimmuni umane, incluso il diabete autoimmune tipo 1,
l’artrite reumatoide, il lupus eritematoso sistemico, la malattia di Graves,
l’artrite giovanile idiopatica, e la vitiligine generalizzata. Diversi studi hanno
mostrato che la associazione del polimorfismo PTPN22 C1858T con
l’autoimmunita’ e’ primaria e presente in diverse popolazioni. Il gene
PTPN22 codifica per la tirosin fosfatasi linfoide LYP, che e’ espressa solo in
cellule emopoietiche, ed e’ un importante regolatore negativo della
attivazione dei linfociti T. Il meccanismo molecolare utilizzato da LYP per
ridurre la segnazione attraverso il recettore delle cellule T (TCR) include la
formazione di un complesso fra LYP e la chinasi Csk, anche essa un
inibitore della attivazione del TCR. L’allele 1858T di PTPN22 codifica per la
variante LYP-W620 della fosfatasi, che non puo’ legare Csk. Questo studio
e’ stato condotto per elucidare il meccanismo di azione della variante LYPW620
nella trasduzione del segnale del TCR. Abbiamo trovato che cellule T
di soggetti portatori della variante LYP-W620 producono meno IL-2 dopo
stimolazione del TCR, e che la fosfatasi –W620 ha una incrementata
attivita’ enzimatica. I nostri dati suggeriscono che la variante di LYP
associata alla autoimmunita’ umana possiede incrementata funzione ed e’
un piu’ potente inibitore della attivazione dei linfociti T.A missense single-nucleotide polymorphism, C1858T in the PTPN22 gene,
is associated with several human autoimmune diseases, including type 1
diabetes, rheumatoid arthritis, systemic lupus erythematosus, Graves’
disease, juvenile idiopathic arthritis, generalized vitiligo, and others. Genetic
studies have shown that the PTPN22 C1858T polymorphism is primarily
associated with autoimmunity in different populations. The PTPN22 gene
encodes the lymphoid tyrosine phosphatase LYP, which is expressed only
in white blood cells and acts as a gatekeeper for T lymphocyte activation.
The molecular mechanism by which LYP tempers T lymphocyte activation
through the T cell receptor (TCR) involves the formation of a complex
between LYP and the negative regulatory kinase Csk. The autoimmunepredisposing
PTPN22 T1858 allele encodes the phosphatase variant LYPW620,
which cannot bind Csk. This study was undertaken in order to
elucidate the mechanism of action of LYP-W620 in TCR signaling. We
found that T cells from carriers of the predisposing allele produce less
interleukin-2 upon TCR stimulation, and the encoded phosphatase has
higher catalytic activity and is a more potent negative regulator of T
lymphocyte activation. We conclude that the autoimmune-predisposing
allele is a gain-of-function mutant
Modified carbon nanotubes: from nanomedicine to nanotoxicology
No full textNanomedicine is the science of fabricating smart devices able to diagnose and treat diseases more efficiently than conventional medicine while minimizing costs, complexity and adverse effects. Carbon nanotubes (CNTs) are receiving considerable attention for biomedical applications due to their extraordinary properties. In particular, their chemical nature and high aspect ratio (ratio between the length and the diameter) make them ideal carriers to achieve delivery of high doses of therapeutic and imaging cargo to a specific site of interest. A major obstacle to the use of pristine (unmodified) CNTs in biological systems is their complete aqueous insolubility and low biocompatibility and toxicity profiles. To endow CNTs with solubility in a biological milieu, several non-covalent and covalent modification methods have been explored. Suitably modified CNTs have shown increased solubility under physiological conditions, improved biocompatibility profiles and lack of toxicity after injection in living animals. Additionally, after being loaded with cargo (small molecules, proteins, peptides or nucleic acids) they have been successfully evaluated as pharmaceutical, therapeutic and diagnostic tools
Association between PTPN22 and endometriosis
No full textPTPN22 is currently one of the few known shared-autoimmunity genes and is therefore a candidate marker for endometriosis. Our data show that female carriers of the PTPN22( *)T variant are significantly more susceptible to endometriosis than controls
Role of PTPN22 in type 1 diabetes and other autoimmune diseases
No full textWe recently discovered that a single-nucleotide polymorphism (SNP) in the lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene on chromosome lp13, correlates strongly with the incidence of type 1 diabetes (T1D) in two independent populations. This findings has now been verified by numerous studies and it has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, generalized vitiligo and other autoimmune disease. Here we review the genetics of the SNP and its association with autoimmunity, discuss the function of the phosphatase in signaling, the biochemistry of the disease-predisposing allele, and the possible mechanisms by which PTPN22 contributes to the development of human disease. (C) 2006 Elsevier Ltd. All rights reserved
Cyclic seasonal variation of G-6-PD deficiency in newborn infants from Sardinia
No full textGlucose-6-Phosphate Dehydrogenase has been studied in 5267 consecutive newborn infants from Sardinian population during a four years period. The proportion of G-6-PD deficient female infants is much higher in those conceived in the winter-spring than among those conceived in summer-autumn, resulting in a lower sex ratio among G-6-PD deficient infants conceived in winter-spring as compared to G-6-PD deficient infants conceived in the summer-autumn. The overall frequency of the gene for G-6-PD deficiency is much lower in infants conceived in the summer period than in infants conceived in the other seasons. A greater reproductive efficiency of G-6-PD deficient males in the winter-spring season and/or some effect at post zygotic level favouring the survival of heterozygous G-6-PD deficient females conceived in the winter-spring period could contribute to the pattern described. Fresh vegetables containing oxidative substances are more abundant in the spring time. These substances may interact with seasonal reproductive cycles influencing reproduction efficiency of G-6-PD deficient males and/or the relative survival rate of heterozygous female embryos
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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