Herramientas de comunicación y divulgación musical orientadas a la transferencia: entornos digitales 2.0

Este proyecto tiene como objeto la formación sobre recursos y herramientas de comunicación y divulgación musical en espacios 2.0, con el fin de utilizarlas en el aula y fomentar la transferencia y el emprendimiento en el ámbito de la musicología

Crítica, periodismo y divulgación musical en espacios digitales

Mediante el presente proyecto se ha ofrecido formación en recursos y prácticas de crítica y periodismo musical, profundizando en la importancia de la divulgación en espacios digitales. Se trata de la continuación del anterior proyecto de innovación no 21 "Herramientas de comunicación y divulgación musical orientadas a la transferencia: entornos digitales 2.0". El nuevo proyecto se ha centrado en los ámbitos de la crítica y el periodismo, concretamente en la actualidad de la prensa escrita y la radio, así como ha tenido en cuenta el uso extendido de redes sociales y plataformas online en tareas de divulgación de contenidos. Dicha formación ha querido dar respuesta a la necesidad de que el profesorado y el alumnado en Musicología actualice y refuerce su conocimiento sobre los códigos, recursos, y entornos en los que se desarrollan estos campos, ya que se trata actualmente de uno de los ámbitos principales de proyección profesional de los egresados de Musicología, a través de la demanda de publicaciones digitales que requieren especialización en música, , radios - en las cuales la interacción con el usuario de internet es crucial-, e instituciones culturales y musicales que necesitan reseñas, crónicas, y breves escritos enfocados a sus espacios de difusión y promoción en internet. Se trata de un proyecto interfacultativo e interdepartamental ya que ha implicado a profesionales, docentes, investigadores y alumnado del Departamento de Musicología, el ICCMU (ambos de la Facultad de Geografía e Historia), y el Departamento de Periodismo y Nuevos medios (Facultad de Ciencias de la Información)

Aneuploidy causes proteotoxic stress in Saccharomyces cerevisiae

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2014.Cataloged from PDF version of thesis. "June 2014."Includes bibliographical references.Gains or losses of entire chromosomes lead to aneuploidy, a condition tolerated poorly in all eukaryotes analyzed to date. How aneuploidy affects organismal and cellular physiology is only beginning to be understood. Aneuploidy also has a profound impact on human health; it is the leading cause of mental retardation and spontaneous abortions and a key characteristic of cancer, as more than 90% of all solid human tumors have aneuploid genomes. Systematic analyses of aneuploid yeast and mouse cells suggested that aneuploidy causes chromosome-specific effects elicited by the amplification of specific genes and general aneuploidy-associated phenotypes Here I describe a phenotype that is shared by most if not all aneuploid yeast cells- I find that aneuploid budding yeast cells are under proteotoxic stress. I show that aneuploid strains are prone to aggregation of endogenous proteins as well as of ectopically expressed hard to fold proteins such as polyQ stretch-containing proteins. Prion conversion rates are also increased in most aneuploid yeast strains. Protein aggregate formation in aneuploid yeast strains is likely due to limiting protein quality control systems, since I present data showing that at least one chaperone family, Hsp90, is compromised in many aneuploid strains. The link between aneuploidy and the formation and persistence of protein aggregates has important implications for diseases such as cancer and neurodegeneration.by Ana Belen Oromendia.Ph. D

Aneuploidy: implications for protein homeostasis and disease

It has long been appreciated that aneuploidy – in which cells possess a karyotype that is not a multiple of the haploid complement – has a substantial impact on human health, but its effects at the subcellular level have only recently become a focus of investigation. Here, we summarize new findings characterizing the impact of aneuploidy on protein quality control. Because aneuploidy has been associated with many diseases, foremost among them being cancer, and has also been linked to aging, we also offer our perspective on whether and how the effects of aneuploidy on protein quality control could contribute to these conditions. We argue that acquiring a deeper understanding of the relationship between aneuploidy, disease and aging could lead to the development of new anti-cancer and anti-aging treatments

Functional Genomics of Enterococcus faecalis: Multiple Novel Genetic Determinants for Biofilm Formation in the Core Genome▿ †

The ability of Enterococcus faecalis to form robust biofilms on host tissues and on abiotic surfaces such as catheters likely plays a major role in the pathogenesis of opportunistic antibiotic-resistant E. faecalis infections and in the transfer of antibiotic resistance genes. We have carried out a comprehensive analysis of genetic determinants of biofilm formation in the core genome of E. faecalis. Here we describe 68 genetic loci predicted to be involved in biofilm formation that were identified by recombinase in vivo expression technology (RIVET); most of these genes have not been studied previously. Differential expression of a number of these determinants during biofilm growth was confirmed by quantitative reverse transcription-PCR, and genetic complementation studies verified a role in biofilm formation for several candidate genes. Of particular interest was genetic locus EF1809, predicted to encode a regulatory protein of the GntR family. We isolated 14 independent nonsibling clones containing the putative promoter region for this gene in the RIVET screen; EF1809 also showed the largest increase in expression during biofilm growth of any of the genes tested. Since an in-frame deletion of EF1809 resulted in a severe biofilm defect that could be complemented by the cloned wild-type gene, we have designated EF1809 ebrA (enterococcal biofilm regulator). Most of the novel genetic loci identified in our studies are highly conserved in gram-positive bacterial pathogens and may thus constitute a pool of uncharacterized genes involved in biofilm formation that may be useful targets for drug discovery

Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series

Purpose To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC). Materials and methods We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test. Results We identified 873 patients who underwent surgery for RCC between the years 2000–2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265–1.614) and Nuclear grade (HR 2.376, 95% CI 1.734–3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343–5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001). Conclusions We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease

Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease

Abstract Idiopathic multicentric Castleman disease (iMCD) is a poorly understood hematologic disorder involving cytokine-induced polyclonal lymphoproliferation, systemic inflammation, and potentially fatal multiorgan failure. Although the etiology of iMCD is unknown, interleukin-6 (IL-6) is an established disease driver in approximately one-third of patients. Anti–IL-6 therapy, siltuximab, is the only US Food and Drug Administration–approved treatment. Few options exist for siltuximab nonresponders, and no validated tests are available to predict likelihood of response. We procured and analyzed the largest-to-date cohort of iMCD samples, which enabled classification of iMCD into disease categories, discovery of siltuximab response biomarkers, and identification of therapeutic targets for siltuximab nonresponders. Proteomic quantification of 1178 analytes was performed on serum of 88 iMCD patients, 60 patients with clinico-pathologically overlapping diseases (human herpesvirus-8–associated MCD, N = 20; Hodgkin lymphoma, N = 20; rheumatoid arthritis, N = 20), and 42 healthy controls. Unsupervised clustering revealed iMCD patients have heterogeneous serum proteomes that did not cluster with clinico-pathologically overlapping diseases. Clustering of iMCD patients identified a novel subgroup with superior response to siltuximab, which was validated using a 7-analyte panel (apolipoprotein E, amphiregulin, serum amyloid P-component, inactivated complement C3b, immunoglobulin E, IL-6, erythropoietin) in an independent cohort. Enrichment analyses and immunohistochemistry identified Janus kinase (JAK)/signal transducer and activator of transcription 3 signaling as a candidate therapeutic target that could potentially be targeted with JAK inhibitors in siltuximab nonresponders. Our discoveries demonstrate the potential for accelerating discoveries for rare diseases through multistakeholder collaboration