Isolated effective coherence (iCoh): causal information flow excluding indirect paths

A problem of great interest in real world systems, where multiple time series measurements are available, is the estimation of the intra-system causal relations. For instance, electric cortical signals are used for studying functional connectivity between brain areas, their directionality, the direct or indirect nature of the connections, and the spectral characteristics (e.g. which oscillations are preferentially transmitted). The earliest spectral measure of causality was Akaike's (1968) seminal work on the noise contribution ratio, reflecting direct and indirect connections. Later, a major breakthrough was the partial directed coherence of Baccala and Sameshima (2001) for direct connections. The simple aim of this study consists of two parts: (1) To expose a major problem with the partial directed coherence, where it is shown that it is affected by irrelevant connections to such an extent that it can misrepresent the frequency response, thus defeating the main purpose for which the measure was developed, and (2) To provide a solution to this problem, namely the "isolated effective coherence", which consists of estimating the partial coherence under a multivariate auto-regressive model, followed by setting all irrelevant associations to zero, other than the particular directional association of interest. Simple, realistic, toy examples illustrate the severity of the problem with the partial directed coherence, and the solution achieved by the isolated effective coherence. For the sake of reproducible research, the software code implementing the methods discussed here (using lazarus free-pascal "www.lazarus.freepascal.org"), including the test data as text files, are freely available at: https://sites.google.com/site/pascualmarqui/home/icoh-isolated-effective-coherenceComment: 2014-02-21 pre-print, technical report, KEY Institute for Brain-Mind Research, University of Zurich, et a

35 años de análisis de isótopos estables en la arqueología Argentina: conceptos, fundamentos, metodología y aplicaciones

El objetivo de este trabajo es celebrar más de tres décadas de la integración de los análisis de isótopos estables en investigaciones arqueológicas en nuestro país. Se presenta una síntesis sobre los conceptos,fundamentos teóricos y metodológicos y las aplicaciones, principalmente en tres grandes temas: paleodieta, paleomovilidad y paleoambiente. A su vez, brindamos ejemplos de abordajes isotópicos sobre problemáticas de paleodietas en sociedades cazadoras recolectoras y agricultoras; movilidad de grupos humanos; estrategias de pastoreo; preparación y cocción de alimentos; estudios paleoambientales y paleoclimáticos. Este compendio puede resultar una referencia útil para estudiantes e investigadores que decidan adentrarse en este campo de investigación. Los casos mencionados no agotan el estado de la cuestión, ni abarcan todas las regiones donde fueron desarrollados estos estudios, sino que el propósito es mostrar la diversidad temática y el modo en que los isótopos estables permiten ampliar el conocimiento sobre las sociedades en el pasado.The main goal of this work is to celebrate more than three decades of the application of stable isotope analyses in Argentinian archaeology. We present a synthesis of the concepts, theoretical and methodological aspects and applications covering three main topics: paleodiet, paleomobility and paleoenvironment. At the same time, we provide examples of isotopic approaches to study problems such as paleodiets in hunter-gatherer and agricultural societies, human mobility, herding strategies, food preparation and cooking, and paleoenvironmental and paleoclimatic studies. This compendium will be a useful reference for students and researchers inclined to enter this field of research. However, the cases mentioned here do not represent the state of art nor do they cover all the Argentinian regions where these studies were carried out, but rather show the thematic diversity and the way in which stable isotope analyses allow to broaden our knowledge about societies in the past.Introducción - Conceptos básicos, fundamentación y notación de los análisis de isótopos estables - Espectrometría de masas - Relaciones isotópicas mayormente utilizadas en arqueología -- Isótopos estables del carbono -- Isótopos estables del nitrógeno -- Isótopos estables del oxígeno e hidrógeno -- Otras relaciones isotópicas de interés: azufre y estroncio - Tejidos y materiales -- Tejidos biológicos -- Residuos orgánicos -- Carbonatos biogénicos -- Sedimentos - Conservación, contaminación y diagénesis -- Fracción orgánica o colágeno -- Fracción Mineral o Bioapatita - Discriminación y fraccionamiento isotópico - Interpretación paleodietaria y ecología isotópica - Abordajes isotópicos de problemáticas en arqueología argentina - Consideraciones finales y perspectivas futura

Myelin Basic Protein as a Novel Genetic Risk Factor in Rheumatoid Arthritis—A Genome-Wide Study Combined with Immunological Analyses

Rheumatoid arthritis (RA) is a major cause of adult chronic inflammatory arthritis and a typical complex trait. Although several genetic determinants have been identified, they account for only a part of the genetic susceptibility. We conducted a genome-wide association study of RA in Japanese using 225,079 SNPs genotyped in 990 cases and 1,236 controls from two independent collections (658 cases and 934 controls in collection1; 332 cases and 302 controls in collection2), followed by replication studies in two additional collections (874 cases and 855 controls in collection3; 1,264 cases and 948 controls in collection4). SNPs showing p<0.005 in the first two collections and p<10−4 by meta-analysis were further genotyped in the latter two collections. A novel risk variant, rs2000811, in intron2 of the myelin basic protein (MBP) at chromosome 18q23 showed strong association with RA (p = 2.7×10−8, OR 1.23, 95% CI: 1.14–1.32). The transcription of MBP was significantly elevated with the risk allele compared to the alternative allele (p<0.001). We also established by immunohistochemistry that MBP was expressed in the synovial lining layer of RA patients, the main target of inflammation in the disease. Circulating autoantibody against MBP derived from human brain was quantified by ELISA between patients with RA, other connective tissue diseases and healthy controls. As a result, the titer of anti-MBP antibody was markedly higher in plasma of RA patients compared to healthy controls (p<0.001) and patients with other connective tissue disorders (p<0.001). ELISA experiment using citrullinated recombinant MBP revealed that a large fraction of anti-MBP antibody in RA patients recognized citrullinated MBP. This is the first report of a genetic study in RA implicating MBP as a potential autoantigen and its involvement in pathogenesis of the disease

Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice

<p>Abstract</p> <p>Background</p> <p>Obesity and related metabolic abnormalities, including inflammation and lipid accumulation in the liver, play a role in liver carcinogenesis. Adipocytokine imbalances, such as decreased serum adiponectin levels, are also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-<it>db/db </it>(<it>db/db</it>) obese mice.</p> <p>Methods</p> <p>Male <it>db/db </it>mice were administered tap water containing 40 ppm DEN for 2 weeks and were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 14 weeks.</p> <p>Results</p> <p>At sacrifice, feeding with 10 ppm pitavastatin significantly inhibited the development of hepatic premalignant lesions, foci of cellular alteration, as compared to that in the untreated group by inducing apoptosis, but inhibiting cell proliferation. Pitavastatin improved liver steatosis and activated the AMPK-α protein in the liver. It also decreased free fatty acid and aminotransferases levels, while increasing adiponectin levels in the serum. The serum levels of tumor necrosis factor (TNF)-α and the expression of <it>TNF-α </it>and <it>interleukin-6 </it>mRNAs in the liver were decreased by pitavastatin treatment, suggesting attenuation of the chronic inflammation induced by excess fat deposition.</p> <p>Conclusions</p> <p>Pitavastatin is effective in inhibiting the early phase of obesity-related liver tumorigenesis and, therefore, may be useful in the chemoprevention of liver cancer in obese individuals.</p

Defining strawberry shape uniformity using 3D imaging and genetic mapping

Strawberry shape uniformity is a complex trait, influenced by multiple genetic and environmental components. To complicate matters further, the phenotypic assessment of strawberry uniformity is confounded by the difficulty of quantifying geometric parameters ‘by eye’ and variation between assessors. An in-depth genetic analysis of strawberry uniformity has not been undertaken to date, due to the lack of accurate and objective data. Nonetheless, uniformity remains one of the most important fruit quality selection criteria for the development of a new variety. In this study, a 3D-imaging approach was developed to characterise berry shape uniformity. We show that circularity of the maximum circumference had the closest predictive relationship with the manual uniformity score. Combining five or six automated metrics provided the best predictive model, indicating that human assessment of uniformity is highly complex. Furthermore, visual assessment of strawberry fruit quality in a multi-parental QTL mapping population has allowed the identification of genetic components controlling uniformity. A “regular shape” QTL was identified and found to be associated with three uniformity metrics. The QTL was present across a wide array of germplasm, indicating a potential candidate for marker-assisted breeding, while the potential to implement genomic selection is explored. A greater understanding of berry uniformity has been achieved through the study of the relative impact of automated metrics on human perceived uniformity. Furthermore, the comprehensive definition of strawberry shape uniformity using 3D imaging tools has allowed precision phenotyping, which has improved the accuracy of trait quantification and unlocked the ability to accurately select for uniform berries

IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

[Background] IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. [Methods and Results] Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. [Conclusions] These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases.Financial support for the study was provided by the Ministerio de Educación y Ciencia (grants PN-SAF2006-02023 and TIN2007-67418-C03-03) and Junta de Andalucía (P07-CVI-02551) to A. Alcina and Servicio Andaluz de Salud de la Junta de Andalucía (grant PI0168/2007) to F. Matesanz. María Fedetz is a holder of a fellowship from Fundación IMABIS. Dorothy Ndagire is a holder of AECI-Ministerio de Asuntos Exteriores fellowship

Memórias da Infância e da Educação: abordagens eliasianas sobre as mulheres

Relações sociais entre indivíduos estão pautadas pela experiência de educação e formação que cada um traz consigo ao longo da vida, pelo modo como se constituem individual e coletivamente. A partir de Elias e da metodologia da história oral, o objetivo foi buscar nas memórias de infância de sete mulheres, professoras de crianças, nascidas entre 1950 e 1970, a formação e a educação que se constituiu na infância em espaços privados e domésticos. Apreendeu-se que a escolha profissional tem vínculos com a educação feminina, normatizada por regras de controle e civilidade

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset