Bioinformatics tools for inferring immune-relatedfunctions from proteomic data

Comunicaciones a congreso

Proteomic characterization of the porcine neutrophil response to LPS from Salmonella Typhimurium by 2D-Gel electrophoresis and mass spectrometry

Comunicaciones a congreso

Gene expression pattern in swine neutrophils after lipopolysaccharide exposure: a time course comparison

Background: Experimental exposure of swine neutrophils to bacterial lipopolysaccharide (LPS) represents a model to study the innate immune response during bacterial infection. Neutrophils can effectively limit the infection by secreting lipid mediators, antimicrobial molecules and a combination of reactive oxygen species (ROS) without new synthesis of proteins. However, it is known that neutrophils can modify the gene expression after LPS exposure. We performed microarray gene expression analysis in order to elucidate the less known transcriptional response of neutrophils during infection. Methods: Blood samples were collected from four healthy Iberian pigs and neutrophils were isolated and incubated during 6, 9 and 18 hrs in presence or absence of lipopolysaccharide (LPS) from Salmonella enterica serovar Typhimurium. RNA was isolated and hybridized to Affymetrix Porcine GeneChip®. Microarray data were normalized using Robust Microarray Analysis (RMA) and then, differential expression was obtained by an analysis of variance (ANOVA). Results: ANOVA data analysis showed that the number of differentially expressed genes (DEG) after LPS treatment vary with time. The highest transcriptional response occurred at 9 hr post LPS stimulation with 1494 DEG whereas at 6 and 18 hr showed 125 and 108 DEG, respectively. Three different gene expression tendencies were observed: genes in cluster 1 showed a tendency toward up-regulation; cluster 2 genes showing a tendency for down-regulation at 9 hr; and cluster 3 genes were up-regulated at 9 hr post LPS stimulation. Ingenuity Pathway Analysis revealed a delay of neutrophil apoptosis at 9 hr. Many genes controlling biological functions were altered with time including those controlling metabolism and cell organization, ubiquitination, adhesion, movement or inflammatory response. Conclusions: LPS stimulation alters the transcriptional pattern in neutrophils and the present results show that the robust transcriptional potential of neutrophils under infection conditions, indicating that active regulation of gene expression plays a major role in the neutrophil-mediated- innate immune respons

Analysis of the Interferon Gamma (rs2430561, +874T/A) Functional Gene Variant in Relation to the Presence of Cardiovascular Events in Rheumatoid Arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. METHODS: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA. RESULTS: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not. CONCLUSION: Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients

RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and a therapeutic target in patient-derived xenografts

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor denosumab in BC patients, beyond its bone-related effects, is unclear. Here, we investigated the prognostic value of RANK expression and its functionality in human BC. We analyzed RANK and RANKL expression in more than 1500 BC cases (777 being estrogen receptor-negative (ER-)) from four independent cohorts. We confirmed that RANK is more frequently expressed in ER- tumors, but it is also found in a subset of ER+ tumors. In ER- BC, RANK expression was independently associated with poor outcome, especially in postmenopausal patients and those who received adjuvant chemotherapy. Gene expression analyses unraveled distinct biology associated with RANK in relation to ER expression and menopause, and evidenced enhanced RANK activation in ER- postmenopausal tumors, together with regulation of metabolic pathways. Functional studies and transcriptomic analyses in ER- RANK+ patients-derived orthoxenografts demonstrated that activation of RANK signaling pathway promotes tumor cell proliferation and stemness, and regulates multiple biological processes including tumor immune surveillance and metabolism. Our results demonstrate that RANK expression is an independent poor prognosis biomarker in postmenopausal ER- BC patients and support the rational of using RANK pathway inhibitors in combination with chemotherapy in ER- BC.N

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma

Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88(L265P) in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88(L265P) is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas

Música antigua para niños modernos

Con motivo de la celebración del 250 aniversario de la muerte de Mozart, se organizan una serie de actividades para dar a conocer la música clásica de una forma divertida a los niños de la etapa de Infantil. Se plantean como objetivos aproximar a los niños al mundo de la música a partir de un personaje histórico; implicar a las familias en el proceso de enseñanza-aprendizaje de sus hijos; aprovechar los recursos que ofrecen las nuevas tecnologías para enriquecer el proceso de enseñanza; y lograr que a final de curso los alumnos conozcan los instrumentos y distintos aspectos musicales. Se realizan actividades de motivación como recibir la visita de alguien caracterizado de Mozart que entrega a los niños el material que necesitan para el proyecto; actividades de educación plástica como elaborar sus propios instrumentos musicales, hacer marionetas de los personajes de La Flauta Mágica o un taller de disfraces; actividades de educación musical como la audición de música de Mozart y diferentes ejercicios; actividades de expresión oral e inglés; actividades de aproximación al lenguaje escrito; actividades de expresión corporal como aprender diferentes danzas; actividades lógico-matemáticas; y actividades de visualización de vídeos o DVD. Incluye cuadernos y material elaborado por los alumnos en el desarrollo de las actividades.Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Ordenación AcadémicaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES