1,720,976 research outputs found
El transportador de zinc: repercusiones de su polimorfismo en la diabetes tipo 2, y en las variantes tipo 1/LADA
No full textLa diabetes autoinmune resulta de una pérdida progresiva de células del islote pancreático, en donde los linfocitos T adquieren fundamental protagonismo. Es una enfermedad tejido-específica, en la cual la autoinmunidad se limita a una serie de moléculas expresadas en las células β pancreáticas. La identificación de esas moléculas, blanco del sistema inmune, proporciona información relevante acerca del mecanismo patogénico y abre el panorama para el desarrollo de futuros agentes terapéuticos. El principal autoantígeno descubierto en los últimos diez años es el transportador de zinc 8 (ZnT8). Es una proteína de 369 aminoácidos codificada por el gen SLC30A8 localizado en el cromosoma 8 en la posición q24.11. Presenta seis dominios de transmembrana y un dominio rico en histidina entre la cuarta y la quinta hélice (importante esta mención ya que es uno de los sitios conocidos a los que se une la molécula de zinc). Su principal función es la de transportar zinc desde el citoplasma de la célula beta al interior del gránulo de secreción. La ausencia experimentalmente provocada del ZnT8 en ratones knock out produce disminución de las concentraciones del catión en la célula β, generando gránulos de almacenamiento atípicos, vacíos e inmaduros y un aumento de la relación plasmática proinsulina/insulina. En efecto, el ZnT8 es la principal herramienta con la que cuenta la célula β pancreática para proveer el zinc destinado al procesamiento, maduración y almacenamiento de la insulina, y en consecuencia, presenta un rol activo en la regulación de la homeostasis de la glucosa.Fil: Figueredo, Carolina Paola. Provincia del Chaco. Clínica San Ramón; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Provincia del Chaco. Clínica San Ramón; Argentin
Autoimmune Diabetes Mellitus: The Importance of Autoantibodies for Disease Prediction and Diagnostic Support
Full text linkMore than three decades ago, screening for autoantibodies associated with immune mediated type 1A diabetes was limited to measuring antibodies to cytoplasmic antigens of islet cells (ICAs). After a period of identification and sequencing of the major autoantigens involved (insulin, glutamic acid decarboxylase and tyrosine phosphatase IA-2) the recombinant technology allowed the quasi-quantitative assessment of the respective specific autoantibodies (IAA, GADA and IA-2A). In addition, the beta-cell-specific zinc transporter isoform 8 (ZnT8) has recently emerged as another major autoantigenic target of type 1 diabetes. The first useful assay for measuring islet autoantibodies was an indirect immunofluorescence assay with frozen sections of human pancreas as substrate. Other methods for the determination of islet autoantibodies (markers) are the radioligand binding assay (RBA) and ELISA. The current fluid phase RBA utilizes low levels of tracers, usually labeled with 125I, 35S-methionine or 35S-cysteine. After a series of international workshops and proficiency programs starting in 1985, the first Diabetes Antibody Standardization Program (DASP) was run in 2000. The predictive value of markers assays was shown in several series of prospectively followed first-degree relatives of type 1 diabetes patients. On the other hand, islet autoimmunity is frequent in adult patients considered to have type 2 diabetes (Latent Autoimmune Diabetes of Adults, LADA). The presence of autoantibodies in such patients may forecast the need of insulin administration, thus sparing these patients from months of inadequate metabolic control. Signals above a cutoff value were usually employed as the criterion for marker positivity, whereas in other studies determination of titer, epitope specificity, and IgG subclass were included to improve diabetes prediction. Recently it was suggested that combining affinity and titer of specific antibodies significantly improves the sensitivity, specificity, and concordance of markers measurement between laboratories. These new contributions on stratification of type 1 diabetes risk on the basis of markers characteristics will be invaluable in the design, implementation and interpretation of multicenter intervention trials. Moreover, marker testing is likely to be increasingly used in clinical practice, and may need to be performed in nonspecialized laboratories.Fil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Common variants in SOCS7 gene predict obesity, disturbances in lipid metabolism and insulin resistance
Full text linkBackground and Aims: Specific Suppressor Of Cytokine Signaling (SOCS) members, such as SOCS7, may play a role in the development of insulin resistance (IR) owing to their ability to inhibit insulin signaling pathways. The objective was to explore the association between common variants and related haplotypes in SOCS7 gene and metabolic traits related to obesity, lipid metabolism and IR. Methods and Results: 780 unrelated men were included in a cross-sectional study. We selected three tagged SNPs that capture 100% of SNPs with minor allele frequency ≥ 0.10. Analyses were done separately for each SNP and followed up by haplotype analysis. rs8074124C was associated with both obesity (P = 0.005) and abdominal obesity (P = 0.002) and allele C carriers showed, in comparison with TT-carriers, lower BMI (P = 0.001) and waist circumference (P = 0.001). rs8074124CC- carriers showed lower fasting insulin (P = 0.017) and HOMA-IR (P = 0.018) than allele T carriers. rs12051836C was associated with hypertriglyceridemia (P = 0.009) and hypertriglyceridemic waist (P = 0.006). rs12051836CC- carriers showed lower fasting insulin (P = 0.043) and HOMA-IR (P = 0.042). Haplotype-based association analysis (rs8074124 and rs12051836 in that order) showed associations with lipid and obesity -related phenotypes, consistent with single locus analysis. Haplotype analysis also revealed association between haplotype CT and both decreased HDL-C (P = 0.026) and HDL-C (P = 0.014) as a continuous variable. Conclusion: We found, for the first time, significant associations between SOCS7 common variants and related haplotypes and obesity, IR and lipid metabolism disorders.Fil: Tellechea, Mariana Lorena. Consejo Nacional de Investigaciones Cientiâficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Penas Steinhardt, Alberto. Consejo Nacional de Investigaciones Cientiâficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Rodriguez, G.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Taverna, Mariano Javier. Consejo Nacional de Investigaciones Cientiâficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Cientiâficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Frechtel, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin
X-ray structure of the mature ectodomain of phogrin
Full text linkPhogrin/IA-2 and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet -cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and -cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure?function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-Å resolution, respectively. Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel -strands packed against two -helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes.Fil: Noguera, Martín Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Primo, Maria Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Jakoncic, Jean. Brookhaven National Laboratory; Estados UnidosFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Solimena, Michele. Technische Universität Dresden.; Alemania. Max Planck Institute of Molecular Cell Biology and Genetics; AlemaniaFil: Ermacora, Mario Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentin
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