The gene PTPN22 is located on chromosome 1p13 and encodes a protein tyrosine phosphatase called the lymphoid-specific phosphatase (Lyp). Lyp is expressed in lymphocytes, where it physically ...associates through its proline-rich motif (called P1) with the SH3 domain of the protein tyrosine kinase Csk, an important suppressor of the Src family of kinases Lck and Fyn, which mediate TCR signaling. Therefore, it is said that interaction between Lyp and Csk enables these effectors to inhibit T-cell activation synergistically. It was reported that a missense single nucleotide polymorphism , R620W (rs2476601), 1858C->T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals. PTPN22 gene polymorphisms were genotyped in 571 Swedish SLE patients and 1042 healthy controls using TaqMan SNP Genotyping Assay. Differences were observed between cases and control subjects at both the allele (chi(2)=11.2895;P=0.0007,1df) and genotype (chi(2)=10.2243;P=0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(2)=9.5660;P=0.0019). We then analyzed if in patients with renal disorder associations with PDCD1 and PTPN22 were independent. Our data suggest that this appears to be the case although we observed some degree of interaction.
The feeding preference by
Thaumastocoris peregrinus
, Carpintero and Dellapé (Heteroptera: Thaumastocoridae) on different
Eucalyptus
species was evaluated through choice tests in a paired comparisons ...design. Twenty individuals per combination were tested over a 48 h period, and each one was offered leaves of two species at a time, in all possible combinations. Preference was determined by counting the number of insect excrements on each plant as a proxy for effective feeding, and then ranked through a paired comparison matrix. A linearity index was calculated to test for hierarchy preferences and, after that, a cardinal index (David’s score) was calculated to assign a preference value for each species. The essential oils were extracted from leaves of each
Eucalyptus
species, and their chemical composition determined through GC-MS. The results show a significant and strictly linear feeding preference ranking between the species tested. The order of preference between species was
E. viminalis
>
E. grandis
>
E. tereticornis
>
E. dunnii
>
E. maidenii
>
E. globulus
. The qualitative and quantitative chemical compositions of the essential oils of these
Eucalyptus
species differed. A significant correlation was found between the feeding preferences and the concentrations of 1,8-cineole as a repellent and
p
-cymene as a feeding stimulant. These results underline the importance of selecting the right
Eucalyptus
species in areas infested by
T. peregrinus
.
Cognitive biases are unreasonable ways of making decisions, often in a one-sided way. The objective of this research was to describe the level of representativeness and confirmation biases in Chilean ...psychology students, in order to know how this phenomenon occurs. The participants were 198 psychology students from three universities in southern Chile. The instrument was based on two cognitive tasks derived from Kanheman and Tversky. The data were analyzed through descriptive statistics and mean differences. The results indicate a high level of biases in the groups of students, in the two tasks evaluated; the representativeness bias presents differences among universities only in sub-task 1, as well as in task 2, related to confirmation bias. Likewise, there are differences in representation bias according to age and sex. The need to strengthen reasoning skills in the initial training of future psychologists, in order to improve skills related to decision making in the professional field is concluded.
PurposeIn this work we analyzed the therapeutic potential of a natural compound, Patemine A (PatA) to treat SLE. Pat A is an inhibitor of the eIF4 complex, involved in the translation initiation ...process, with immunosuppressive properties that has been tested successfully in cancer mouse models.MethodsTo evaluate Pat A efficiency in SLE we used the BXSB.Yaa lupus model. In this strain the presence of Yaa in males results in autoimmune disease manifestations, renal failure, and a mortality rate of 60% by 20 weeks of age. BXSB.Yaa males were treated with PatA administered intraperitoneally 3 times per week for 8 weeks starting at the initial stage of disease (12 weeks). Sera was collected every three weeks to follow disease progression and at final point (20 weeks) we performed serological analysis (cytokines and autoantibodies), flow cytometry on spleen, kidney histological and functional assays and behavioral tests to evaluate neurological signs of the disease.ResultsPat A treatment increased survival rates and reduced circulating levels of proinflammatory cytokines and autoantibodies in the BXSB.Yaa lupus model. Kidney function was also improved in the animal that received Pat A with no major changes at the histological level. Treated mice also showed an improvement on cognitive function (learning/memory, and depression) together with a reduction of proinflammatory cytokines locally in the hippocampus.ConclusionsThese data suggest that translation inhibition improves disease signs at the immunological and neurological level opening a new line of research based on translation inhibition to treat lupus and other autoimmune diseases.
T-cell activation results from productive T-cell receptor (TCR) engagement by a cognate peptide-MHC (pMHC) complex on the antigen presenting cell (APC) surface, a process leading to the polarization ...of the T-cell secretory machinery toward the APC interface. We have previously shown that the half-life of the TCR/pMHC interaction and the density of pMHC on the APC are two parameters determining T-cell activation. However, whether the half-life of the TCR/pMHC interaction can modulate the efficiency of T-cell secretory machinery polarization toward an APC still remains unclear. Here, by using altered peptide ligands conferring different half-lives to the TCR/pMHC interaction, we have tested how this parameter can control T-cell polarization. We observed that only TCR/pMHC interactions with intermediate half-lives can promote the assembly of synapses that lead to T-cell activation. Strikingly, intermediate half-life interactions can be competed out by short half-life interactions, which can efficiently promote T-cell polarization and antagonize T-cell activation that was induced by activating intermediate half-life interactions. However, short TCR/pMHC interactions fail at promoting phosphorylation of signaling molecules at the T-cell-APC contact interface, which are needed for T-cell activation. Our data suggest that although intermediate half-life pMHC ligands promote assembly of activating synapses, this process can be inhibited by short half-life antagonistic pMHC ligands, which promote the assembly of non activating synapses.
The research projects of the European Forum on Antiphospholipid Antibodies are representative of how dynamic is this area of investigation. The present review is focused on the most recent projects ...of the Forum on the aetiopathogenic aspects of the antiphospholipid syndrome (APS). Studies on the genetic background of the APS are ongoing in order to better define the proximity between APS and full-blown systemic lupus erythematosus. However, the analysis of the polymorphisms of genes coding for inflammatory mediators may offer new information on the role of inflammatory processes in triggering thrombotic events as well as the whole susceptibility for developing the vascular manifestations. A systematic and wide detection of serological markers of infectious processes will give new insight on the role of infectious agents in favouring autoimmunity in APS. Owing to the well-known role of vitamin D3 defect in autoimmune disease, the detection of vitamin plasma levels in APS patients will offer the rationale for a possible therapeutic supplementation. Additional projects are aimed to better characterize the diagnostic/prognostic value of antiphospholipid antibodies (aPL) by defining their epitope specificity and binding avidity. Pregnancy complications represent the obstetric side of APS. Research projects are focussed on the role of complement activation in placenta damage and on the potential ability of aPL to affect the fertility. Finally, a study has been planned in order to draw definitive conclusions on the associations between aPL and atherosclerosis.
Los sesgos cognitivos son formas no razonadas de tomar decisiones, a menudo de manera parcializada. El objetivo de esta investigación fue describir el nivel de sesgos de representatividad y ...confirmación en estudiantes de psicología chilenos, para conocer cómo se presenta este fenómeno. Los participantes fueron 198 estudiantes de psicología, de tres universidades del sur de Chile. El instrumento se basó en dos tareas cognitivas derivadas de Kanheman y Tversky; se analizaron los datos con estadística descriptiva y diferencias de medias. Los resultados indican alto nivel de sesgos en los grupos de estudiantes, en las dos tareas evaluadas; el sesgo de representatividad presenta diferencias entre universidades, solo en la subtarea 1, así como en la tarea 2, relacionada con sesgo de confirmación; así mismo se observan diferencias en sesgo de representación según edad y sexo. Se concluye la necesidad de fortalecer habilidades de razonamiento en la formación inicial de los futuros psicólogos y psicólogas, con la finalidad de mejorar las habilidades relacionadas con la toma de decisiones en el campo profesional.
The aim of this study was to analyze in families with SLE for the presence of linkage and the structure and transmission of haplotypes containing alleles for the low-affinity Fcγ receptors. The Fcγ ...receptor polymorphisms FcγRIIA-131R/H, FcγRIIIA-176F/V and FcγRIIIB-NA1/2 and a polymorphism in the FcγRIIB gene were genotyped with RFLP, allele-specific PCR or pyrosequencing. Individual SNPs and haplotypes were tested for linkage in multicase families and for association using contingency tables, transmission disequilibrium test and affected family-based control groups in Swedish and Mexican single-case families. No linkage or association could be detected using the FcγR polymorphisms in the multicase families. However, an association was found for both FcγRIIA-131R and IIIA-176F alleles in the single-case families, but not for IIIB or IIB. Allelic association to SLE was found for a haplotype that included both risk alleles, but not in haplotypes where only one or the other was present. We propose that FcγRIIA-131R and FcγRIIIA-176F are both risk alleles for SLE transmitted primarily, but not exclusively on a single major haplotype that behaves functionally in a situation similar to that of compound heterozygozity.
We have developed a “Molecular Toolkit” comprising interchangeable promoters and marker genes to facilitate transformation of homobasidiomycete mushrooms. We describe the evaluation of a range of ...promoters in the homobasidiomycetes
Agaricus bisporus and
Coprinus cinereus using green fluorescent protein (GFP) as a reporter gene; the
C. cinereus trp1 promoter and
A. bisporus trp2 and
gpdII promoters proving successful in driving expression in
C. cinereus, with the
gpdII promoter also functioning in
A. bisporus. Our investigations demonstrate that a prerequisite for GFP expression in
C. cinereus and
A. bisporus is the presence of an intron. This is the first reported expression of GFP in either
C. cinereus or
A. bisporus.
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