CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer

Background: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation. The aim was to analyze CDH1 somatic alterations in Mexican patients with diffuse and mixed gastric cancer. Methods: We searched for mutations in the CDH1 gene in tumor DNA from DGC (n = 13) and MGC (n = 7) patients by next generation sequencing (NGS). Validation of findings was performed using Sanger sequencing. LOH was analyzed using dinucleotide repeat markers surrounding the CDH1 gene, and methylation was investigated by DNA bisulfite conversion and sequencing. E-cadherin protein deficiency was analyzed by immunohistochemistry. Results: Seventeen point variants were identified by NGS, 13 of them were validated by Sanger sequencing. Only 1/13 had not been previously reported (c.-137C > A), and 12/13 were already reported as polymorphisms. Two DGC cases presented LOH at the locus 16q22.1 (13.3%). CDH1 promoter methylation was positive in (7/11) 63.6% and (4/6) 66.6% of the cases with DGC and MGC, respectively. E-cadherin protein deficiency was observed in 58.3% of DGC cases while 100% in MGC cases. Conclusions: While no pathogenic somatic mutations were found that could explain the diffuse histology of gastric cancer in DGC and MGC, methylation was the most common somatic inactivation event of the CDH1 gene, and LOH was rare. The previously unreported c.-137C > A variant modify the CDH1 gene expression since it alters the binding sites for transcription factors.This work was supported by the “Consejo Nacional de Ciencia y Tecnología (CONACYT)” (grant Ciencia Básica 2013–1-222972) and by the “Fondo de Investigación en Salud (FIS), Instituto Mexicano del Seguro Social (IMSS)” (grant FIS/IMSS/PROT/G13/1189), that contributed to the design of the study, collection, analysis, interpretation of data and writing the manuscript. We thank the following institutions: 1) Coordinación de Investigación en Salud (CIS), Instituto Mexicano del Seguro Social (IMSS) for the support given to ARBC, through the Professional Development in the International Research of Graduate Students (PRODESI) program; 2) Fundación IMSS, A.C. for the research grant awarded to JYSL and MTMT; 3) FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274); 4) The project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); 5) FCT fellowships (SFRH/BPD/86543/2012 to JC; SFRH/BPD/89764/2012 to PO; PD/ BD/128007/2016 to AS). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology

Non-L\'evy mobility patterns of Mexican Me'Phaa peasants searching for fuelwood

We measured mobility patterns that describe walking trajectories of individual Me'Phaa peasants searching and collecting fuelwood in the forests of "La Monta\~na de Guerrero" in Mexico. These one-day excursions typically follow a mixed pattern of nearly-constant steps when individuals displace from their homes towards potential collecting sites and a mixed pattern of steps of different lengths when actually searching for fallen wood in the forest. Displacements in the searching phase seem not to be compatible with L\'evy flights described by power-laws with optimal scaling exponents. These findings however can be interpreted in the light of deterministic searching on heavily degraded landscapes where the interaction of the individuals with their scarce environment produces alternative searching strategies than the expected L\'evy flights. These results have important implications for future management and restoration of degraded forests and the improvement of the ecological services they may provide to their inhabitants.Comment: 15 pages, 4 figures. First version submitted to Human Ecology. The final publication will be available at http://www.springerlink.co

Targeted glutamate supply boosts insulin concentrations, ovarian activity, and ovulation rate in yearling goats during the anestrous season

The neuroendocrine regulation of the seasonal reproductive axis requires the integration of internal and external signals to ensure synchronized physiological and behavioral responses. Seasonal reproductive changes contribute to intermittent production, which poses challenges for optimizing goat product yields. Consequently, a significant objective in seasonal reproduction research is to attain continuous reproduction and enhance profitability in goat farming. Glutamate plays a crucial role as a modulator in several reproductive and metabolic processes. Hence, the aim of this study was to evaluate the potential impact of exogenous glutamate administration on serum insulin concentration and ovarian function during the out-of-season period in yearling goats. During the anestrous season, animals were randomly located in individual pens to form two experimental groups: (1) glutamate (n = 10, live weight (LW) = 29.1 ± 1.02 kg, body condition score (BCS) = 3.4 ± 0.2 units) and (2) control (n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2), with no differences (p < 0.05) regarding LW and BCS. Then, goats were estrus-synchronized, and blood sampling was carried out for insulin quantification. Ovaries were ultrasonographically scanned to assess ovulation rate (OR), number of antral follicles (AFs), and total ovarian activity (TOA = OR + AF). The research outcomes support our working hypothesis. Certainly, our study confirms that those yearling goats treated with exogenous glutamate displayed the largest (p < 0.05) insulin concentrations across time as well as an augmented (p < 0.05) out-of-season ovarian activity

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

Culture, method, and the content of self-concepts : testing trait, individual–self-primacy, and cultural psychology perspectives

Three theoretical perspectives on cultural universals and differences in the content of self-concepts were tested in individualistic (United States, n = 178; Australia, n = 112) and collectivistic (Mexico, n = 157; Philippines, n = 138) cultures, using three methods of self-concept assessment. Support was found for both trait perspectives and the individual–self-primacy hypothesis. In contrast, support for cultural psychology hypotheses was limited because traits and other personal attributes were not more salient, or social attributes less salient, in individualistic cultures than collectivistic cultures. The salience of some aspects of self-concept depended on the method of assessment, calling into question conclusions based on monomethod studies

Implicit theories and self-perceptions of traitedness across cultures: Toward integration of cultural and trait psychology perspectives

From the trait perspective, traitedness, or consistency of behavior, is expected in all cultures. However, cultural psychologists argue that behavior may be more determined by traits in individualistic than collectivistic cultures. The authors investigated implicit theories and self-perceptions of traitedness in two individualistic cultures, the United States (n = 342) and Australia (n = 172), and four collectivistic cultures, Mexico (n = 400), Philippines (n = 363), Malaysia (n = 251), and Japan (n = 192). Although implicit trait beliefs were endorsed in all cultural groups, they were stronger in individualistic than collectivistic cultures. Cultural differences in self-perceptions of one\u27s own traitedness, as operationalized by self-monitoring, were also found, and comparisons involving the United States and most collectivistic cultures were consistent with cultural psychology perspectives. The ability of self-construals to predict implicit beliefs and self-perceptions of traitedness was also investigated. Overall, the results supported efforts to integrate trait and cultural psychology perspectives. © 2006 Sage Publications

Genotyping of high-risk anal human papillomavirus (HPV): ion torrent-next generation sequencing vs. linear array

Abstract Background Our next generation sequencing (NGS)-based human papillomavirus (HPV) genotyping assay showed a high degree of concordance with the Roche Linear Array (LA) with as little as 1.25 ng formalin-fixed paraffin-embedded-derived genomic DNA in head and neck and cervical cancer samples. This sensitive genotyping assay uses barcoded HPV PCR broad-spectrum general primers 5+/6+ (BSGP)5+/6+ applicable to population studies, but it’s diagnostic performance has not been tested in cases with multiple concurrent HPV infections. Methods We conducted a cross-sectional study to compare the positive and negative predictive value (PPV and NPV), sensitivity and specificity of the NGS assay to detect HPV genotype infections as compared to the LA. DNA was previously extracted from ten anal swab samples from men who have sex with men in Nigeria enrolled on the TRUST/RV368 cohort study. Two-sample tests of proportions were used to examine differences in the diagnostic performance of the NGS assay to detect high vs. low-risk HPV type-specific infections. Results In total there were 94 type-specific infections detected in 10 samples with a median of 9.5, range (9 to 10) per sample. Using the LA as the gold standard, 84.4% (95% CI: 75.2–91.2) of the same anal type-specific infections detected on the NGS assay had been detected by LA. The PPV and sensitivity differed significantly for high risk (PPV: 90%, 95% CI: 79.5–96.2; sensitivity: 93.1%, 95% CI: 83.3–98.1) as compared to low risk HPV (PPV: 73%, 95% CI: 54.1–87.7; sensitivity: 61.1, 95% CI: 43.5–76.9) (all p < 0.05). The NPV for all types was 92.5% (95% CI: 88.4–95.4). The NPV and specificity were similar for high and low risk HPVs (all p > 0.05). The NGS assay detected 10 HPV genotypes that were not among the 37 genotypes found on LA (30, 32, 43, 44, 74, 86, 87, 90, 91, 114). Conclusions The NGS assay accurately detects multiple HPV infections in individual clinical specimens with limited sample volume and has extended coverage compared to LA