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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Alfa-enolasa: a novel autoantigen in patients with premature ovarian failure
No full textAlthough controversial, the presence of circulating antiovarian antibodies (AOA) may be considered a marker of autoimmune premature ovarian failure (POF). The purpose of the present work was to evaluate the presence of AOA in POF patients, and to identify a possible autoantigen in order to develop a reliable diagnostic tool that might help to determine the real prevalence of autoimmune POF.Fil: Sundblad, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bussmann, Leonardo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Chiauzzi, Violeta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pancholy, Vijay. Ohio State University; Estados UnidosFil: Charreau, Eduardo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin
Screening of FSH receptor gene in Argentine women with premature ovarian failure (POF)
No full textFil: Sundblad, Victoria. Instituto de Biologı́a y Medicina Experimental (IBYME), Vuelta de Obligado 2490, C1428ADN Buenos Aires; Argentina.Fil: Chiauzzi, Violeta. Instituto de Biologı́a y Medicina Experimental (IBYME), Vuelta de Obligado 2490, C1428ADN Buenos Aires; Argentina.Fil: Escobar, Maria Eugenia. Centro de Investigaciones Endocrinológicas, Hospital de Niños Ricardo Gutierrez, Buenos Aires; Argentina.Fil: Dain, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Fil: Charreau, Eduardo H. Instituto de Biologı́a y Medicina Experimental (IBYME), Vuelta de Obligado 2490, C1428ADN Buenos Aires; Argentina.Diverse mutations in FSH-receptor (FSHR) gene have been described as possible cause of premature ovarian failure (POF). To investigate the presence of mutations and/or polymorphisms in FSHR gene, DNA from 20 POF, 5 of which were diagnosed as resistant ovary syndrome (ROS), and from 44 controls was isolated from peripheral lymphocytes. The complete coding sequence was analysed by PCR followed by SSCP, direct sequencing or restriction enzyme analysis. No mutations in FSHR gene were identified in the patients studied. The two already described polymorphisms in exon 10, A919G and A2039G, cosegregated in all the homozygous individuals, indicating that FSHR presents two isoforms: Ala307-Ser680 and Thr307-Asn680. OR results suggest that the 919G-2039G allelic variant or the homozygous genotype is not associated to disease risk. In addition, a heterozygous substitution T1022C (Val341Ala) was found in two control subjects. We suggest that mutations in FSHR gene are rare in women with POF in Argentine. Presence of a particular FSHR isoform does not appear to be associated with this disease
Falência ovariana prematura
Get PDFLa falla ovárica prematura (FOP) es un sindrome caracterizado por amenorrea hipergonadotrófica antes de los 40 años. Las causas del desarrollo de FOP pueden ser autoinmunes, genéticas, cromosómicas e idiopáticas. Es importante identificar marcadores para predecir la cesación prematura de los ciclos y planear una concepción temprana.Premature ovarian failure (POF) is defined as hyper-gonadotropic amenorrhea before the age of 40. The causes of POF development could be autoimmune, genetic, chromosomic and idiopathic. It is important to identify markers that can predict the premature cessation of menses and enable early conception planningA falência ovariana prematura (FOP) é uma síndrome caracterizada por amenorreia hipergonadotrófica antes dos 40 anos. As causas do desenvolvimento de FOP podem ser autoimunes, genéticas, cromossômicas e idiopáticas. É importante identificar marcadores para predizer a cessação prematura dos ciclos e planificar uma concepção precoce.Fil: Chiauzzi, Violeta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Sundblad, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Ferder, Ianina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Dain, Liliana Beatriz. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud; ArgentinaFil: Charreau, Eduardo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin
Regulatory circuits mediated by galectin-12 in the interaction between adipose tissue and vascularization programs
Get PDFLa obesidad es una enfermedad de alta relevancia en salud pública, particularmente en el mundo occidental. Es definida como una condición patológica en la cual se acumula grasa de modo anormal o en exceso en el tejido adiposo (TA), producto de una desregulación metabólica e inflamatoria, promoviendo un deterioro progresivo de la salud del individuo. Esta patología es considerada factor de riesgo mayoritario para el desarrollo de enfermedades tales como diabetes, desórdenes músculo-esqueléticos, enfermedades cardiovasculares y algunos tipos de cáncer. El TA es un órgano inmunoendócrino involucrado en la regulación del metabolismo de energía y de la respuesta inflamatoria, a través de mecanismos que incluyen la secreción de adipoquinas, hormonas y citoquinas. Entre las poblaciones celulares que constituyen el TA, los más representativos son los adipocitos, células especializadas en el almacenamiento de lípidos neutros en el interior de gotas de lípidos (GL), organelas celulares conformadas por una monocapa de fosfolípidos y proteínas. A lo largo de la vida adulta, el TA se halla constantemente sometido a procesos de remodelación, de expansión y reducción, lo cual requiere cambios concomitantes en la microvasculatura adyacente. Sin embargo, a pesar de un gran número de estudios realizados en esta dirección, los mediadores que vinculan el tejido adiposo con programas vasculares e inflamatorios es aún un terreno fértil para explorar. Las lectinas, moléculas encargadas de decodificar la información biológica encriptada en glicanos, participan en un amplio espectro de eventos biológicos como inflamación, diferenciación celular y angiogénesis. Entre las tres familias de lectinas más conocidas, las galectinas son proteínas solubles y, a diferencia de las siglecs o lectinas de tipo C, no se encuentran como receptores de membrana plasmática. De acuerdo a su estructura, las galectinas se clasifican en tres subfamilias: prototipo, quimera y de repeticiones en tándem. La mayoría poseen dominios de reconocimiento de carbohidratos (DRC) con alta afinidad por residuos N-acetilactosamina (LacNAc) y diferentes derivados de este disacárido. Galectina-12 (Gal-12) es un miembro de la subfamilia repeticiones en tándem (tandem-repeat), y a diferencia de otras galectinas de distribución ubicua, presenta un patrón de expresión preferencialmente restringido al TA. Estudios previos sugieren un papel importante de Gal-12 en la activación de macrófagos, como así también en el metabolismo lipídico y en la sensibilidad a insulina. En este contexto, Gal-12 surge como un posible mediador clave en el diálogo entre el tejido adiposo y la respuesta inflamatoria. Debido a ello, en el presente trabajo se propone que Gal-12 actuaría como nexo entre la expansión del TA y la generación de programas vasculares e inflamatorios. En primer lugar, se estudió esta proteína a nivel bioquímico y se buscó identificar sus posibles ligandos. Para ello, luego de su expresión recombinante y purificación, se desarrollaron ensayos de competencia y afinidad, a partir de los cuales se encontró una marcada afinidad de esta lectina por glicanos 3-fucosilados. Modelos computacionales generados por homología de cada uno de sus DRCs permitieron comprender e interpretar los determinantes atomísticos que favorecían esta predilección. En ensayos in vitro de adipocitos diferenciados a partir de células 3T3-L1, se observó la presencia de Gal-12 en GL y un aumento de la expresión de esta lectina en respuesta a hipoxia. A su vez, Gal-12 recombinante indujo un aumento en la migración y en la formación de túbulos en células endoteliales humanas (HUVEC), ambos procesos inhibidos por la presencia de ligandos oligosacarídicos 3-fucosilados. Asimismo, en condiciones de hipoxia, las HUVEC presentaron un aumento de un glicofenotipo permisivo para la unión de Gal-12. In vivo, el TA de ratones deficientes en Gal-12 (Lgals12-/- o Gal12KO) reveló menor área vascular total, menor densidad microvascular, vasos más delgados y con menor ramificación en comparación con sus contrapartes de genotipo salvaje (WT). Estos resultados sugieren que Gal-12 contribuye no solo a la formación de vasos sanguíneos sino también a la remodelación de los mismos; y aquellas interacciones reguladas por hipoxia entre Gal-12 y sus ligandos fucosilados pueden influir en la vascularización del TA. Por otra parte, con el fin de evaluar el impacto de Gal-12 sobre el efecto de la dieta de alto contenido graso (DAG) en la homeostasis del TA desafiamos ratones Gal12KO y WT a DAG o dieta normal (DN). Siguiendo diariamente el peso de los ratones observamos un marcado aumento de peso en los ratones WT respecto de los Gal12KO sometidos a DAG. Además, los ratones Gal12KO presentaron una mejor tolerancia a la depuración de glucosa en comparación a los WT, sugiriendo que Gal-12 podría estar involucrada en el desarrollo del síndrome metabólico. Actualmente nos encontramos explorando la relevancia de Gal-12 en el desarrollo de procesos inflamatorios y autoinmunes. Hemos observado que ratones Gal12KO presentan menores manifestaciones clínicas de encefalomielitis autoinmune experimental (EAE) respecto de ratones WT, y en cuanto a los modelos de colitis inducida por el hapteno TNBS, los ratones deficientes en Gal-12 requieren de una sensibilización previa para iniciar los procesos inflamatorios que conlleva a la pérdida de peso corporal. El presente trabajo demuestra que Gal-12 es un mediador clave del tejido adiposo capaz de modular programas vasculares e inflamatorios, revelando una función extracelular novedosa para esta lectina, y sugiriendo su participación en el metabolismo de glucosa en condiciones de sobrecarga de ingesta lipídica.Obesity has emerged as an important problem for public health, particularly in the western world. It is defined as a condition where fat accumulates abnormally or excessively in adipose tissue (AT), as a result of metabolic or inflammatory process, contributing to progressive deterioration of human health. This pathology is considered a major risk factor for the development of diseases such as diabetes, skeletal muscle disorders, cardiovascular diseases, and some types of cancer. AT is an immunoendocrine organ involved in the regulation of energy metabolism and inflammatory response, through mechanisms that include the secretion of adipokines, hormones and cytokines. Among the cell populations that constitute AT, the most representative are adipocytes, cells specialized in the storage of neutral lipids inside lipid drops, cellular organelles formed by a monolayer of phospholipids and proteins. Throughout adulthood, AT is constantly undergoing remodeling processes, characterized by repeated expansions and reductions processes, which requires concomitant changes in the microvasculature. However, in spite of considerable progress, little is known about key mediators that link AT growth, vascular signaling programs and inflammation. In this regard, lectins, have emerged as major regulators of inflammation, cell differentiation and angiogenesis responsible of deciphering the biological information encrypted in the the glycome (the repertoire of glycans expressed on the surface of individual cells). Galectins, a soluble family of glycan-binding proteins, are characterized by the presence of at least one carbohydrate recognition domain (CRD). According to their structure, they are classified into prototype galectins, chimera-type galectins and tandem-repeat galectins with two CRDs in tandem connected by a linker peptide. Most galectins display affinity for N-acetylactosamine (LacNAc) residues and different derivatives of this disaccharide. Galectin-12 (Gal-12) is a member of tandem repeat subfamily, and unlike other ubiquitously distributed galectins, Gal-12 has a preferential expression pattern mostly restricted to TA. Previous studies suggest an important role of this lectin in the activation of macrophages, as well as in lipid metabolism and insulin sensitivity. In this context, Gal-12 emerges as a possible key mediator in the dialogue between adipose tissue, vascular programs and inflammatory responses. In the present work we investigated whether Gal-12 might act as a link between AT expansion, vascularization and inflammation. First, this protein was studied at the biochemical level and analyzed for glycan specificity. Following its recombinant expression and purification we developed competence and affinity tests, which revealed fine specificity for 3-fucosylated glycans. Computational modeling generated by homology of each of its CRDs allowed us to understand and interpret the atomistic determinants that favored this glycan-binding preference. Differentiated 3T3-L1 adipocytes showed the presence of Gal-12 mainly in lipid droplets, and its expression was markedly up-regulated in response to hypoxia. In in vitro assays, recombinant Gal-12 induced migration and tube formation in HUVEC, an effect that was inhibited by the presence of specific 3-fucosylated ligands. Similarly, under hypoxic conditions, HUVEC showed a highly permissive glycophenotype, required for Gal-12 binding and angiogenesis. In vivo, AT isolated from mice lacking Gal-12 (Lgals12-/- or Gal12KO) revealed reduced total vascular area, lower microvascular density, thinner vessels and less branching compared to their wild-type (WT) counterpart. These results suggested that Gal-12 contributes not only to AT vascularization but also to vessel remodeling; and hypoxia-regulated interactions between Gal-12 and its fucosylated ligands can influence AT vascularization. On the other hand, in order to evaluate the relevance of Gal-12 in the effects of high-fat diet (HFD) on AT homeostasis, we challenged Gal12KO and WT mice with HFD or normal diet (ND). A daily follow-up revealed a marked increase in body weight of WT compared to Gal12KO mice subjected to HFD. In addition, Gal12KO mice exhibit greater tolerance to glucose clearance compared to WT, suggesting that Gal-12 could be involved in development of metabolic syndrome. The impact of Gal-12 on the development of inflammatory and autoimmune processes is currently being explored. In preliminary studies, Gal12KO mice with experimental autoimmune encephalomyelitis (EAE) showed lower clinical severity compared to WT mice. Moreover, in models of TNBS-induced colitis, Gal12KO mice required a primary sensitization to initiate the intestinal inflammatory process and body weight loss. Collectively, the present work reveals novel biochemical and functional properties of Gal-12, highlighting its major role in vascularization within AT. In addition, these studies suggest involvement of this endogenous lectin in inflammation and glucose metabolism under conditions of increased lipid intake.Fil: Maller, Sebastián Matías. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Variations on the Author
Get PDF“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
Get PDFWe 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
Inmunological and molecular aspects of premature ovarian failure
No full textLa falla ovárica prematura (FOP), caracterizada por amenorrea hipergonadotrófica antes de los 40 años, afecta al 1% de las mujeres en edad fértil. Por su parte, el síndrome de ovario resistente (SOR) es propuesto como una forma folicular de FOP, caracterizado por la presencia de numerosos folículos primordiales en los ovarios. La FOP puede ser de origen autoinmune, iatrogénico, infeccioso, genético/cromosómico o metabólico, entre otros. Cuando no es posible identificar una causa para su desarrollo, la FOP es clasificada como idiopática. Nuestro estudio consistió en abordar el análisis de posibles causas inmunológicas y moleculares de la FOP. En trabajos previos detectamos mediante Western-blot la presencia de anticuerpos dirigidos hacia un antígeno ovárico de ~50 kDa en el 19,1% de un total de 110 pacientes FOP. En esta parte del estudio, trabajamos en la purificación e identificación de esta proteína. Mediante espectrometría de masa identificamos a la enolasa-α como el antígeno específico hacia el cual estarían dirigidos estos anticuerpos anti-ovario en pacientes FOP. Estos resultados fueron confirmados mediante Western-blots en los que se utilizó a la proteína recombinante como antígeno. Concluímos que la determinación de anticuerpos anti-enolasa-α podría significar un aporte importante para el diagnóstico de FOP autoinmune, y su utilización como marcador de autoinmunidad ovárica permitiría brindar a las pacientes un tratamiento acorde a la naturaleza autoinmune del síndrome. Asimismo, realizamos un estudio retrospectivo sobre el análisis de 247 pacientes FOP que habían sido derivadas a nuestro laboratorio para la determinación de la presencia de inmunoglobulinas dirigidas hacia el R-FSH (Ig-R-FSH). Encontramos que sólo las 23 mujeres que habían sido previamente diagnosticadas como SOR presentaban estos anticuerpos. Además, confirmamos que la actividad inhibitoria de las Ig-R-FSH puede ser clasificada en dos grupos: uno con efecto inhibitorio “irreversible”, cuya Ki aparente es 2,94 x 1012 M-1, mil veces mayor que la constante de afinidad de la FSH por su receptor, y el otro con un mecanismo inhibitorio “reversible”, con una Ki aparente similar a la constante de afinidad de la FSH por su receptor. Concluímos que la determinación de estos anticuerpos sería un instrumento importante para el diagnóstico del SOR, permitiendo realizar el diagnóstico principalmente sobre la base de estudios serológicos. Con respecto a las posibles causas genéticas de la FOP, el gen del R-FSH ha sido uno de los genes candidatos más estudiados. Hasta el presente se han descripto 9 mutaciones inactivantes en este gen. En nuestro laboratorio investigamos la presencia de mutaciones en el gen del R-FSH en 20 pacientes FOP, 5 de las cuales habían sido diagnosticadas como SOR, y 44 mujeres controles. Estudiamos la secuencia codificante completa del gen del R-FSH mediante PCR-SSCP, digestión con enzimas de restricción y/o secuenciación directa. No detectamos mutaciones en los exones 1 al 10 en ninguno de los individuos analizados. Además, observamos que los polimorfismos A919G y A2039G del exón 10 se presentan en dos posibles combinaciones, avalando la existencia dos isoformas del R-FSH: Ala307-Ser680 y Thr307-Asn680. Nuestros resultados sugieren que la variante alélica 919G-2039G (OR G vs A= 1,20; IC 95%= 0.53-2.71) o el genotipo homocigota (OR GG vs AG = 1,00; IC 95%= 0.22-4.46; OR GG vs AA = 1,40; IC 95%= 0.25-7.87) no estarían asociados al riesgo de desarrollo de FOP. Además, en dos individuos controles detectamos la presencia de la sustitución C1022T, en heterocigosis. En conclusión, sugerimos que las mutaciones en el gen del R-FSH son poco frecuentes en las pacientes FOP de Argentina. La presencia de una isoforma particular del R-FSH no estaría asociada a la enfermedad. Por su parte, el gen de la inhibina α (INHα) ha sido propuesto como otro gen candidato para el desarrollo de FOP, debido al rol de las inhibinas en la regulación de la FSH. En dos trabajos previos se sugiere que el polimorfismo C129T y la sustitución G769A estarían involucrados en la etiología de la FOP. En este trabajo analizamos 52 pacientes FOP; 14 presentaban FOP asociada a enfermedad/es autoinmune/s (FOP-EA) y las 38 restantes fueron consideradas idiopáticas (FOP-I). Además, estudiamos 136 mujeres controles, separadas en dos grupos: a) menores de 40 años (C40). No encontramos diferencias significativas en el riesgo de desarrollo de FOP para el alelo T del polimorfismo C129T, cuando comparamos FOP-I con C40 (OR T vs C; I-POF vs C40 = 1.07; IC 95% = 0.53-2.16). Obtuvimos resultados similares al comparar los genotipos (OR CC vs (CT+TT) ; I-POF vs C40 = 1.05; IC 95% = 0.43-2.56). La posible implicancia del polimorfismo C129T en los niveles serológicos de inhibinas fue analizada en un grupo de 42 mujeres controles. No hallamos diferencias significativas (p>0,05) entre los grupos CC y CT+TT al comparar los valores de los péptidos de inhibina de la fase folicular media (Pro-αC e Inhibina B), o los valores de la fase lútea media (Pro-αC e Inhibina A). Con respecto a la mutación G769A, hallamos 8/135 controles y 1/52 pacientes FOP (una FOP-EA) heterocigotas para dicha sustitución. La presencia de la variante G769A en un número relevante de individuos controles se describe en este trabajo por primera vez. Nuestros resultados indicarían que las variantes C129T y G769A no estarían asociadas al desarrollo de FOP. En conclusión: i) la proteína enolasa-α sería el el antígeno específico de ~50 kDa hacia el cual estarían dirigidos los anticuerpos anti-ovario en pacientes FOP; ii) las Ig-R-FSH se encontrarían presentes exclusivamente en las pacientes con diagnóstico de SOR; iii) el gen del R-FSH y las variantes C129T y G769A del gen INHα no estarían involucrados en la etiopatología de la FOP en pacientes argentinas.Premature ovarian failure (POF) is characterized by amenorrhea before the age of 40. POF is usually classified as “follicular” or “afollicular” form. Resistant ovary syndrome (SOR) is proposed as a follicular form of POF, with ovaries in which numerous primordial follicles are present. POF involves almost 1% of the western female population. It is a very heterogeneous syndrome, with a multicausal pathogenesis, and any of the following: chromosomal, enzymatic, iatrogenic, autoimmune or infectious aberration, may be the cause of the disease. In our laboratory, we focused our POF research on some immunological and genetic etiological factors. In previous studies, by Western-blot using ovarian cytosolic fraction antigens, we found that 19.1% of 110 POF patients showed specific reactivity with a ~ 50 kDa antigen. In the present work, we focused on the purification and identification of this protein. NanoLC-ESI-MS/MS identificated α-enolase as the specific antigen to which anti-ovarian antibodies are directed in these POF patients. These results were confirmed by Western-blot using recombinant human α-enolase. In conclusion, detection of anti- α-enolase antibodies by Western-blot could be a suitable marker for diagnosis of autoimmune POF. Its implementation as marker of ovarian autoimmunity may allow treatment of patients according to the immunological nature of their pathology. We also evaluated the presence of circulating immunoglobulins that inhibit FSH binding to its receptor (Ig-FSHR) by FSH-binding inhibition assay, in 247 patients with POF and 60 normally menstruating women (controls). We found that only those 23 patients that had been previously diagnosed as ROS presented Ig-FSHR. The remaining 224 POF patients and 60 control subjects proved negative. In addittion, our results clearly demonstrated that immunoglobulin fractions can be classified into two groups: one, with an “irreversible” nature of inhibitory effect, which Ki was 2.94 x 1012 M-1, a thousand times higher than the affinity constant for FSH-receptor (FSHR) binding interaction, and the other group with a “reversible” mechanism of inhibition, with an apparent Ki similar to the affinity constant for FSHR binding interaction. We concluded that determination of Ig-FSHR could be instrumental in diagnosing ROS, mainly upon the basis of serological findings. Regarding genetic factors, the FSHR gene has long be considered a strong candidate gene for POF. Nine mutations have been described in this gene to date. We investigated the presence of mutations and/or polymorphisms in FSHR gene, in 20 patients with POF, 5 of which were diagnosed as ROS, and 44 controls. The complete coding sequence was analyzed by PCR followed by SSCP, direct sequencing or restriction enzyme analysis. No mutations in FSHR gene were identified in the subjects studied. Polymorphisms A919G and A2039G of exon 10, cosegregated in all the homozygous individuals, indicating that FSHR presents two isoforms: Ala307-Ser680 and Thr307-Asn680. OR results suggested that the 919G-2039G allelic variant (OR G vs A= 1,20; IC 95%= 0.53-2.71) or the homozygous genotype (OR GG vs AG = 1,00; IC 95%= 0.22- 4.46; OR GG vs AA = 1,40; IC 95%= 0.25-7.87) is not associated to disease risk. In addition, a heterozygous substitution C1022T (Val341Ala) was found in two control subjects. We suggest that mutations in FSHR gene are rare in women with POF in Argentine. Presence of a particular FSHR isoform does not appear to be associated with this disease. On the other hand, inhibin-α gene is also proposed as a candidate gene for POF, due to its role in negative feedback control of hypophyseal FSH. In two previous studies, polymorphism C129T and substitution G769A of this gene were suggested to be involved in the etiology of POF. We studied 52 POF patients; 14 presented POF in association with autoimmune/s disease/s (AAD-POF), and the remaining 38 wereconsidered idiopathic (I-POF). As controls, 136 normal women were also studied, divided into two groups: a) controls below the age of 40 years (C40). We found no significant differences in risk of POF development for the T allele of polymorphism C129T when we compared I-POF either with C40 (OR T vs C; I-POF vs C40 = 1.07; IC 95% = 0.53-2.16). Similar results were found when genotypes were compared (OR CC vs (CT+TT); I-POF vs C40 = 1.05; IC 95% = 0.43-2.56). The implication of this polymorphism in serum inhibin levels was analyzed in 42 control women, and found no significant differences (p>0.05) between CC and CT+TT groups either when we compared mid-follicular phase inhibin peptide values (Pro-αC and Inhibin B) or when we compared mid-luteal phase values (Pro-αC and Inhibin A). Heterozygocity for the substitution G769A was found in 8/135 controls and only in 1/52 POF women (an AAD-POF). Presence of this substitution in a relevant number of control subjects is herein described for the first time. Our results might indicate that C129T and G769A variants in INH-α gene may not be associated to POF disease. In conclusion: i) α-enolase would be the specific antigen of ~50 kDa to which anti-ovarian antibodies are directed in POF patients; ii) Ig-FSHR would be present only in those patients diagnosed as ROS; c) neither FSHR gene nor C129T and G769A variants in INHα gene would be involved in the etiology of POF.Fil: Sundblad, Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
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