A functional PTPN22 polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population

BACKGROUND: The 1858C/T SNP of the PTPN22 gene has been associated with many autoimmune diseases, suggesting the existence of an inflammatory process common to all of them. We studied the association of that polymorphism with immunoglobulin A deficiency (IgAD) following a double approach: a case-control and a TDT study. METHODS: A total of 259 IgAD patients and 455 unrelated matched controls, and 128 families were used for each approach. Comparisons were performed using Chi-Square tests or Fisher's exact test when necessary. RESULTS: No association between the PTPN22 1858C/T SNP and IgA deficiency was found in any case (allelic frequencies 8% vs. 6% in patients and controls, respectively, OR= 1.14 (0.72–1.79), p= 0.56; TDT p = 0.08). CONCLUSION: The result obtained seems to reinforce the consideration of IgA deficiency as a primary immunodeficiency rather than an autoimmune disease

Visual ecology of aphids – a critical review on the role of colours in host finding

We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms. Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region. We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours that are not likely to hold. Finally we also discuss the implications for developing and optimising strategies of aphid control and monitoring

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Interleukin-10 polymorphisms in Spanish IgA deficiency patients: a case-control and family study

BACKGROUND: IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. Genetic and environmental factors are suspected to be involved in the development of the disease. Interleukin-10 (IL-10) is a cytokine with stimulatory activity on immunoglobulin production and it may be an important regulator in IgAD pathogenesis. The IL-10 gene contains several single nucleotide polymorphisms (SNPs) and two polymorphic microsatellites located in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers are associated or linked to IgAD in Spanish patients. METHODS: We genotyped 278 patients with IgAD and 573 ethnically matched controls for the microsatellites IL-10R and IL-10G and for three single nucleotide polymorphisms at positions -1082, -819 and -592 in the proximal promoter of the gene. We also included in this study the parents of 194 patients in order to study the IL-10 haplotypes transmitted and not transmitted to the affected offspring. RESULTS: The only allele where a significant difference was observed in the comparison between IgA deficiency patients and controls was the IL-10G12 allele (OR = 1.58 and p = 0.021). However, this p value could not withstand a Bonferroni correction. None of the IL-10R or promoter SNP alleles was found at a different frequency when patients were compared with controls. CONCLUSION: Our data do not show any significant difference in IL-10 polymorphism frequencies between control and IgAD patient samples. Their haplotype distribution among patients and controls was also equivalent and therefore these microsatellites and SNPs do not seem to influence IgAD susceptibility

Plastic and Heritable Components of Phenotypic Variation in Nucella lapillus: An Assessment Using Reciprocal Transplant and Common Garden Experiments

Assessment of plastic and heritable components of phenotypic variation is crucial for understanding the evolution of adaptive character traits in heterogeneous environments. We assessed the above in relation to adaptive shell morphology of the rocky intertidal snail Nucella lapillus by reciprocal transplantation of snails between two shores differing in wave action and rearing snails of the same provenance in a common garden. Results were compared with those reported for similar experiments conducted elsewhere. Microsatellite variation indicated limited gene flow between the populations. Intrinsic growth rate was greater in exposed-site than sheltered-site snails, but the reverse was true of absolute growth rate, suggesting heritable compensation for reduced foraging opportunity at the exposed site. Shell morphology of reciprocal transplants partially converged through plasticity toward that of native snails. Shell morphology of F2s in the common garden partially retained characteristics of the P-generation, suggesting genetic control. A maternal effect was revealed by greater resemblance of F1s than F2s to the P-generation. The observed synergistic effects of plastic, maternal and genetic control of shell-shape may be expected to maximise fitness when environmental characteristics become unpredictable through dispersal

High-Density SNP Mapping of the HLA Region Identifies Multiple Independent Susceptibility Loci Associated with Selective IgA Deficiency

Selective IgA deficiency (IgAD; serum IgA<0.07 g/l) is the most common form of human primary immune deficiency, affecting approximately 1∶600 individuals in populations of Northern European ancestry. The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a genome-wide association study. Among the characterized susceptibility loci, the association with specific HLA haplotypes represents the major genetic risk factor for IgAD. Despite the robust association, the nature and location of the causal variants in the HLA region remains unknown. To better characterize the association signal in this region, we performed a high-density SNP mapping of the HLA locus and imputed the genotypes of common HLA-B, -DRB1, and -DQB1 alleles in a combined sample of 772 IgAD patients and 1,976 matched controls from 3 independent European populations. We confirmed the complex nature of the association with the HLA locus, which is the result of multiple effects spanning the entire HLA region. The primary association signal mapped to the HLA-DQB1*02 allele in the HLA Class II region (combined P = 7.69×10−57; OR = 2.80) resulting from the combined independent effects of the HLA-B*0801-DRB1*0301-DQB1*02 and -DRB1*0701-DQB1*02 haplotypes, while additional secondary signals were associated with the DRB1*0102 (combined P = 5.86×10−17; OR = 4.28) and the DRB1*1501 (combined P = 2.24×10−35; OR = 0.13) alleles. Despite the strong population-specific frequencies of HLA alleles, we found a remarkable conservation of these effects regardless of the ethnic background, which supports the use of large multi-ethnic populations to characterize shared genetic association signals in the HLA region. We also provide evidence for the location of association signals within the specific extended haplotypes, which will guide future sequencing studies aimed at characterizing the precise functional variants contributing to disease pathogenesis

Simple methodology for the quantitative analysis of fatty acids in human red blood cells

In the last years, there has been an increasing interest in evaluating possible relations between fatty acid (FA) patterns and the risk for chronic diseases. Due to the long life span (120 days) of red blood cells (RBCs), their FA profile reflects a longer term dietary intake and was recently suggested to be used as an appropriate biomarker to investigate correlations between FA metabolism and diseases. Therefore, the aim of this work was to develop and validate a simple and fast methodology for the quantification of a broad range of FAs in RBCs using gas chromatography with flame ionization detector, as a more common and affordable equipment suitable for biomedical and nutritional studies including a large number of samples. For this purpose, different sample preparation protocols were tested and compared, including a classic two-step method (Folch method) with modifications and different one-step methods, in which lipid extraction and derivatization were performed simultaneously. For the one-step methods, different methylation periods and the inclusion of a saponification reaction were evaluated. Differences in absolute FA concentrations were observed among the tested methods, in particular for some metabolically relevant FAs such as trans elaidic acid and eicosapentaenoic acid. The one-step method with saponification and 60 min of methylation time was selected since it allowed the identification of a higher number of FAs, and was further submitted to in-house validation. The proposed methodology provides a simple, fast and accurate tool to quantitatively analyse FAs in human RBCs, useful for clinical and nutritional studies.This work received financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project PTDC/SAU-ENB/116929/2010 and EXPL/EMS-SIS/2215/2013. ROR acknowledges PhD scholarship SFRH/BD/97658/2013 attributed by FCT (Fundação para a Ciência e Tecnologia).info:eu-repo/semantics/publishedVersio

Association of temporal factors and suicides in the United States, 2000–2004

The purpose of the study was to examine the association of temporal factors, in particular days of the week and seasons of the year and death from suicide in the United States. Data were pooled from the Multiple Cause of Death Files. Hierarchical logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. The incidence of suicide was significantly higher on Wednesdays, compared to Sunday. Specifically, individuals were 99% more likely to kill themselves on Wednesday than on Sunday. Suicides were more prevalent in the summer months, and they were less likely to occur in winter. The state suicide rate significantly elevated individual suicide risk. The results held even after controlling for the potentially confounding effects of socio-economic and demographic variables at both the individual and state levels. It was concluded that the observed association between seasonality and suicide cannot be discounted as a mere coincidence. Future research ought to focus on integrating individual level data and contextual variables when testing for seasonality effects

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.)