Alteration of platelet GPVI signaling in ST-elevation myocardial infarction patients demonstrated by a combination of proteomic, biochemical, and functional approaches

The platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide). STEMI and SCAD samples were compared by a phosphoproteomics approach. Validations were by immunoblotting in systemic and intracoronary blood from independent cohorts of patients. Twenty-six differentially regulated proteins were identified when comparing CRP-activated systemic platelets from STEMI and SCAD patients, 4 of which were selected for validation studies: PLCɣ2, G6f, SLP-76, and Dok-2. Immunoblot analyses showed these four proteins had higher tyrosine phosphorylation levels in response to CRP in platelets from STEMI patients, being these levels more pronounced at the culprit site of coronary artery occlusion. Moreover, platelet aggregation studies showed a higher response to GPVI agonists in STEMI patients compared to SCAD controls. In conclusion, we show an altered activation state of GPVI signaling in STEMI patients, confirming this receptor as a promising anti-thrombotic target for myocardial infarctionhis work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) [grant No. SAF2013-45014-R, co-funded by the European regional development fund (ERDF)]. AG acknowledges support from the Sociedad Española de Trombosis y Hemostasia – Fundación Española de Trombosis y Hemostasia (SETH-FETH). PV is a predoctoral fellow from the Instituto de Investigación Sanitaria de Santiago (IDIS)S

Actitudes del personal de la planta de Esval S.A., sobre algunos programas que recursos humanos les brinda

Tesis (Licenciado en Psicología)A continuación presentaremos una investigación de tipo exploratorio, de caso, descriptiva, donde se busca precisar las actitudes de los funcionarios de ESVAL S. A frente a ciertos servicios que presta el área de Recursos Humanos (como Descripción de Cargo, Capacitación y Entrenamiento y Evaluación de Desempeño), describir dichas actitudes y establecer las posibles diferencias entre diversos grupos humanos que se pueden distinguir al interior de la empresa. El estudio se puede dividir en tres grandes partes: En la primera parte se contextualizan las temáticas del estudio en las áreas de la psicología social, la psicología organizacional, las actitudes y gestión de Recursos Humanos, donde se incluyen los programas de Capacitación y Entrenamiento, Evaluación de Desempeño y Descripción de Cargo, intentando definir un marco conceptual para nuestro estudio. En la segunda parte se realiza una descripción detallada de la metodología empleada en éste estudio, y se explica, entre otras cosas, el procedimiento utilizado para la recolección de datos (que básicamente consiste en la elaboración y aplicación de una encuesta de actitudes a los funcionarios de ESVAL S. A) y el procesamiento y la tabulación de datos así como de los criterios que nos permiten hacer una distinción entre una actitud favorable, desfavorable o intermedia. Por último, en la tercera parte, se presenta un análisis de los resultados obtenidos separado según los distintos grupos demográficos existentes al interior de la empresa, además de un análisis general, que muestra -por parte de los funcionarios de ESVAL S. A- una actitud más bien favorable hacia los programas de Recursos Humanos anteriormente mencionados

Expression of SOCS1, SOCS2, and SOCS3 in growth hormone-stimulated skin fibroblasts from children with idiopathic short stature

Background/aim: Possible etiologies of idiopathic short stature (ISS) include a range of conditions, some of which may be caused by defects in the modulation of the growth hormone (GH)-signaling pathway. The Janus kinase/signal transducer and activator of transcription pathway is regulated by several mechanisms, including negative feedback regulation by the suppressors of cytokine signaling (SOCS). However, the specific induction of SOCS transcript levels in fibroblasts from ISS patients has not been studied. Methods: We determined the transcript levels of the SOCS1-3 genes under basal conditions, and in the presence or absence of stimulation with rhGH for 24 h in skin fibroblast cultures obtained from patients with ISS and children with normal height. Results: Under basal conditions, ISS patients express higher SOCS2-3 transcript levels than control children. After incubation with recombinant human GH (rhGH), the transcript levels of SOCS2 increased significantly in ISS patients comp

Molecular divergence between Iridaea cordata (Turner) Bory de Saint-Vincent from the Antarctic Peninsula and the Magellan Region

The distribution of the Southern Ocean (SO) biota is the result of major geological, oceanographic, and climate changes during the last 50 million years (Ma). Several groups of marine benthic organisms exhibit marked taxonomic similarities between the Antarctic Peninsula and southern South America, where families, genera, and even species are currently co-distributed in these continents. Several species of macroalgae including Gigartina skottsbergii, Plocamium cartilagineum, and Iridaea cordata are currently found on both sides of the Drake Passage. Advances in molecular techniques have allowed estimating phylogenetic relationships, levels of differentiation and divergence time estimates between populations from these continents in order to determine whether they constitute separate evolutionary units. In this study, we determine whether Iridaea cordata represents the same evolutionary unit in southern South America and the Antarctic Peninsula or if populations on the two sides of the Drake Passage represent different genetic lineages. According to our results, I. cordata populations from the Antarctic Peninsula and South America are clearly distinguishable evolutionary units with 8.31% and 3.17% mtDNA and cpDNA molecular divergence, respectively. The separation between Antarctic and South American populations of I. cordata occurred at the end of the Miocene, between 5 Ma (rbcL) and 9 Ma (COI-5P). These results are similar to those reported in G. skottsbergii on both sides of the Drake Passage. Thus, I. cordata populations on the two sides of the Drake Passage should be considered two sister species. Cryptic speciation plays an important role in the evolution of the Southern Ocean; thus, the systematics, biogeography, and biodiversity of the region require major revisions

Phosphotyrosine phosphatases in GH-stimulated skin fibroblasts from children with idiopathic short stature

Artículo de publicación ISIAim: Some cases of idiopathic short stature (ISS) may be caused by defects in the modulation of the negative feedback regulation of the growth hormone receptor (GHR)/ Janus kinase (JAK)2/signal transducers and activators of transcription (STAT)5 signaling pathway. The cytosolic tyrosine phosphatases, protein tyrosine phosphatase 1B (PTP1B) and Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase-1 (SHP-1), the later which translocates to the nucleus after activation, interact with JAK2 in a GH-dependent manner. The possible contribution of PTP1B and SHP-1 to GH signaling in fibroblasts from ISS patients has not been studied. Methods: We determined the basal protein content of PTP1B and SHP-1 in the presence of recombinant human GH (rhGH) for 24 h in skin fibroblast cultures, obtained from patients with ISS, and were compared with a normal height control children group. JAK2 activation was determined in both groups. Results: JAK2 activation was delayed in fibroblasts from ISS patients compared to controls. Under basal conditions, the protein content of SHP-1 was lower in ISS, and after incubation with rhGH, it decreased in the non-nuclear and nuclear fraction of controls, but not in ISS patients. The protein content of PTP1B, however, increased in a similar fashion in fibroblasts from both ISS and control children. Conclusion: The delayed activation of JAK2 and the lack of response of SHP-1 after incubation with GH in fibroblasts from ISS patients, suggests that the growth retardation observed in some of these children may be mediated in part by this phosphotyrosine phosphatase

Estradiol and testosterone potentiate the effect of GH on JAK2/STAT5 activation and IGF-I gene expression in HEPG2 cells

SOCHED 2016-0

Intrauterine Twin Discordancy and Partial Postnatal Catch-up Growth in a Girl with a Pathogenic IGF1R Mutation

Objective: Insulin like growth factors-1 (IGF-1) is essential for normal in utero and postnatal human growth. It mediates its effects through the IGF-1 receptor (IGF1R), a widely expressed cell surface tyrosine kinase receptor. The aim of the study was to analyze pre- and post-natal growth, clinical features and laboratory findings in a small for gestational age (SGA) girl in whom discordant postnatal growth persisted and her appropriate for gestational age (AGA) brother. Methods: A girl born with a low weight and length [-2.3 and -2.4 standard deviation (SD) score (SDS), respectively] but borderline low head circumference (-1.6 SD) presented with a height of -1.7 SDS, in contrast to a normal height twin brother (0.0 SDS). IGF-1 resistance was suspected because of elevated serum IGF-1 levels. Results: Sequencing revealed the presence of a previously described pathogenic heterozygous mutation (p.Glu1050Lys) in the SGA girl which was not present in the parents nor in the AGA twin brothe

Gene therapy reduces ethanol intake in an animal model of alcohol dependence

Background: Some gene polymorphisms strongly protect against the development of alcoholism. A large proportion of East Asians carry a protective inactivating mutation in aldehyde dehydrogenase (ALDH2*2). These subjects display high levels of blood acetaldehyde when consuming alcohol, a condition that exerts a 66 to 99% protection against alcohol abuse and alcoholism. Present knowledge allows the incorporation of therapeutic genes that can modify the expression of disease predisposing genes, an effect that can last from months to years. In line with the above, we have tested if inhibiting the expression of the aldehyde dehydrogenase gene (ALDH2) by an anti-Aldh2 antisense gene can curtail the drive of alcohol-dependent animals to consume alcohol. Methods: Wistar-derived rats bred as high alcohol drinkers (UChB; Universidad de Chile Bibulous) were rendered alcohol dependent by a 2-month period of voluntary ethanol (10%) intake, subjected to a 3-day withdrawal period and further allowed