HLA Class I or Class II and Disease Association: Catch the Difference if You Can

The association of autoimmune diseases with HLA has been known for many decades. To date, however, the underlying mechanisms have not been fully understood. The recently introduced genome-wide association studies (GWAS) have suggested that several genes converging in common pathways contribute to the genetic susceptibility in such disorders. Nevertheless, for most autoimmune/autoinflammatory diseases, the HLA genes are by far the strongest risk factors. The basis of some associations has now been elucidated, particularly in those cases in which exogenous factors are involved

Detecting the traders' strategies in Minority-Majority games and real stock-prices

Price dynamics is analyzed in terms of a model which includes the possibility of effective forces due to trend followers or trend adverse strategies. The method is tested on the data of a minority-majority model and indeed it is capable of reconstructing the prevailing traders' strategies in a given time interval. Then we also analyze real (NYSE) stock-prices dynamics and it is possible to derive an indication for the the ``sentiment'' of the market for time intervals of at least one day.Comment: 13 pages, 10 figure

Ankylosing Spondylitis: a trade Off of HLA-B27, ERAP, and pathogen interconnections? Focus on Sardinia

The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the native population genome affecting the relative allele frequency of relevant genes. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum Amino Peptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria

Diversidade de insetos coletados com armadilha luminosa em plantio de mogno no interior de São Paulo.

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Dinâmica populacional da broca-do-mogno, Hypsipyla grandella (Lepidoptera: Pyralidae) em Garça, SP.

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An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes

The Endoplasmatic Reticulum Aminopeptidases ERAP1 and ERAP2 are implicated in a variety of immune and non-immune functions. Most studies however have focused on their role in shaping the HLA class I peptidome by trimming peptides to the optimal size. Genome Wide Association Studies highlighted non-synonymous polymorphisms in their coding regions as associated with several immune mediated diseases. The two genes lie contiguous and oppositely oriented on the 5q15 chromosomal region. Very little is known about the transcriptional regulation and the quantitative variations of these enzymes. Here, we correlated the level of transcripts and proteins of the two aminopeptidases in B-lymphoblastoid cell lines from 44 donors harbouring allelic variants in the intergenic region between ERAP1 and ERAP2. We found that the presence of a G instead of an A at SNP rs75862629 in the ERAP2 gene promoter strongly influences the expression of the two ERAPs with a down-modulation of ERAP2 coupled with a significant higher expression of ERAP1. We therefore show here for the first time a coordinated quantitative regulation of the two ERAP genes, which can be relevant for the setting of specific therapeutic approaches

Study of the impact of breeding seasons in the dynamics of dairy goat herds.

Abstract: The competitiveness in the animal production field has forced the smaller activities to be more efficient when compared to big business of the agro-industries. The dairy goat production is one of those market niches that need a better understand of its sector. For those reasons it has been proposed that by changing the number of reproduction seasons would increase income of the producers. The objectives of this study were to evaluate the impact of 1 or 2 annual reproductive cycles on production and economical health of dairy goats and to identify differences of production costs and revenues associated with changes in the herd dynamics as predicted by a mathematical model. A previously developed goat model using the System Dynamics approach to study long-term changes in the dynamics of the herd was used in these simulations. The model simulations used feeds, labor, and fixed costs as inputs and the outputs were revenues from milk production sales and sales of animals from all categories of the herd. The simulation time unit was ?month? and a long-term horizon of 10 years was considered for these simulations. The model was set up to simulate a freestall facility of a herd in equilibrium with 100 does in lactation. All parameters considered in this model assumed average values reported in production systems in the Southeast region of Brazil. The simulations results indicated that improvements of 10% in the fertility rate would increase the number animals in the herd up to 185% and 35% for one and two breeding season, respectively. Establishing a milk price as US$0.68 the break even for one and two breeding seasons was respectively US$0.62, and US$0.50, giving the systems with two breeding a capacity to support reductions on milk price up to 26% against 9% with one breeding season. When comparing the models with 1 or 2 breeding seasons was found that models with 2 breeding seasons was considerably more profitable and had a higher turnover than the model with 1 breeding season. The results indicate that the use of a second (artificial) breeding season might be an important management strategy to improve the efficiency of the dairy goat production systems. [Estudio del impacto de la estación reproductiva sobre la dinâmica de los rebaños lecheros]

A dairy goat model to study the impacts on herd dynamics.

The understanding of a dairy goat production system is crucial to establish a more competitive activity. Therefore, a simulation model was built to evaluate the dynamics of dairy goat herd under different scenarios of production. A System Dynamics approach was used to identify management policies that affect the behavior of the herd. All parameters considered in this model assumed average values reported in production systems in the Southeast region of Brazil. To simulate a herd in dynamic equilibrium, the culling and retention rates were used. Thereafter, simulations were performed based on changes in reproductive and mortality rates. All the simulations were planned to take the variation in herd development based on simple management strategies over 10 years of simulation. The dynamic equilibrium of 50 lactating does was obtained when fixed culling and retention rates of 20 and 70%, respectively, were assigned to the does after 36 months of simulation. A sensitivity analysis was made and indicated that an increase of 20% in the reproduction rates increased the number of animals in the herd in 56%. A decrease in the reproduction rate of 20% reduced the number of animals in 43%. A third simulation indicated that increasing mortality rate from 4 to 10% of the female kids decreased the number of lactating does by 36%. These results indicated that small changes in reproduction and mortality rates can considerably affect the dynamics of the herd, even though the herd may not be immediately affected because of the intrinsic delays in the system. This result is extremely important to justify the need of activity planning to consider the gap between a measurement taken and the consequences, preparing the producers to potential delays in the system. The use of mathematical models is important to understand the relationships between variables and the dynamic of the system and to assist in applying best management strategies to enhance productivity of dairy goats. [Modelo de cabras lecheras para evaluar el impacto de las estrategias de manejo en la dinámica del rebaño]

Relative impact of diagnosis and clinical stage on response to electroconvulsive therapy: a retrospective cohort

OBJECTIVES: Electroconvulsive therapy (ECT) is commonly indicated for refractory psychiatric disorders. However, little research has compared response across diagnoses. Here, we aimed to evaluate the relative impact of diagnosis and clinical staging as response predictors in a cross-diagnostic sample. METHODS: In a retrospective cohort of adult inpatients (n=287) who underwent at least six sessions of ECT, we investigated predictors of complete response (a clinical global impression of 1) to ECT. We use adjusted regression models to estimate the impact of clinical diagnosis and staging on complete response and dominance analysis to assess the relative importance of these predictors. RESULTS: Those for whom a depressive episode was a primary indication for treatment were the most likely to have complete improvement, while those with psychosis were the least likely; clinical stage had a significant influence on outcome in all diagnoses. A diagnosis of psychosis was the strongest predictor of non-response. CONCLUSIONS: A diagnosis of psychosis (mainly schizophrenia) was the strongest predictor of non-response. We also found that clinical staging can aggregate information on ECT response that is independent of clinical diagnosis