Eleonora d'Aragona e la costruzione di un "corpo" politico al femminile (1450-1493)

La investigación se ha centrado en la biografía de Leonor de Aragón, hija del rey Ferrante de Nápoles y mujer de Hércules de Este. En una perspectiva más amplia que la tradicional cronología, se estudiará la ideología de la dinastía Trastámara de Nápoles y la historia política y cultural de la Italia renacentista. La tipología de las fuentes utilizadas – diplomáticas y epistolares – ha permitido combinar diversos niveles de análisis: biográfico, ideológico, de género, político y social. El estudio apunta a evidenciar, en primer lugar, el papel político de Leonor en el gobierno del ducado estense: un ejercicio concreto de un poder – declinado en formas diversas – que se persigue sobre todo a través del copioso e inédito intercambio epistolar entre la duquesa y Hércules, al hilo de las frecuentes ausencias del duque. En segundo lugar, gracias a la correspondencia entre Leonor y su padre, se apunta a la conformidad ideológica con una tradición familiar. Este trabajo tiende además a demostrar cómo la duquesa, en cuanto mujer de poder, fue el resultado de un proyecto formativo aragonés dirigido tanto a la descendencia masculina como a la femenina. <br /

Cardiac Bmi1(+) cells contribute to myocardial renewal in the murine adult heart

Introduction: The mammalian adult heart maintains a continuous, low cardiomyocyte turnover rate throughout life. Although many cardiac stem cell populations have been studied, the natural source for homeostatic repair has not yet been defined. The Polycomb protein BMI1 is the most representative marker of mouse adult stem cell systems. We have evaluated the relevance and role of cardiac Bmi1(+) cells in cardiac physiological homeostasis. Methods: Bmi1(CreER/+); Rosa26(YFP/+) (Bmi1-YFP) mice were used for lineage tracing strategy. After tamoxifen (TM) induction, yellow fluorescent protein (YFP) is expressed under the control of Rosa26 regulatory sequences in Bmi1(+) cells. These cells and their progeny were tracked by FACS, immunofluorescence and RT-qPCR techniques from 5 days to 1 year. Results: FACS analysis of non-cardiomyocyte compartment from TM-induced Bmi1-YFP mice showed a Bmi1 (+)-expressing cardiac progenitor cell (Bmi1-CPC: B-CPC) population, SCA-1 antigen-positive (95.9 +/- 0.4 \%) that expresses some stemness-associated genes. B-CPC were also able to differentiate in vitro to the three main cardiac lineages. Pulse-chase analysis showed that B-CPC remained quite stable for extended periods (up to 1 year), which suggests that this Bmi1(+) population contains cardiac progenitors with substantial self-maintenance potential. Specific immunostaining of Bmi1-YFP hearts serial sections 5 days post-TM induction indicated broad distribution of B-CPC, which were detected in variably sized clusters, although no YFP+ cardiomyocytes (CM) were detected at this time. Between 2 to 12 months after TM induction, YFP+ CM were clearly identified (3 +/- 0.6 \% to 6.7 +/- 1.3 \%) by immunohistochemistry of serial sections and by flow cytometry of total freshly isolated CM. B-CPC also contributed to endothelial and smooth muscle (SM) lineages in vivo. Conclusions: High Bmi1 expression identifies a non-cardiomyocyte resident cardiac population (B-CPC) that contributes to the main lineages of the heart in vitro and in vivo.We wish to thank M. Torres, J.M. Perez-Pomares and B.G. Galvez for critical discussions of the manuscript, A. M. Santos for assistance with confocal microscopy and dynamic imaging, R.M. Carmona for help with the animal colony management, F.S. Cabo for bioinformatics and statistical support, J.M Ligos for the sorting strategy, and K. McCreath and C. Mark for editorial support. This study was supported by grants to A.B. from the Ministry of Science and Innovation (SAF2012-34327; PLE2009-0147 and PSE-010000-2009-3), the Research Program of the Comunidad Autonoma de Madrid (S2010/BMD-2420), the Instituto de Salud Carlos III (RETICS-RD12/0019/0018 and RETICS-RD12/0019/0023) and the European Commission (Proposal 242038). The CNB-CSIC and CNIC are supported by the Spanish Ministry of Economy and Competitiveness.S

Immunosuppressants alter the immune response associated with Glucantime® treatment for Leishmania infantum infection in a mouse model

Background: Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. Objectives: To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Results: Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. Conclusion: The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Instituto de Salud Carlos III through ISCIII-AES projects (PI21CIII/00005 and PI22/00009). JCS was supported by a contract from CIBERINFEC (CB21/13/00018).S

Gilthead seabream (Sparus aurata) Mx proteins show positive and negative synergy in their antiviral activity

Due to their direct antiviral activity, Mx proteins play a main role in the response mediated by the type I interferon against viral infections. The study of the farmed fish gilthead seabream Mx genes is specially interesting, since this species displays an unusually high natural resistance to viral diseases, becoming a potential asymptomatic carrier and/or reservoir for several viruses pathogenic to other fish species. Gilthead seabream has three Mx proteins (Mx1, Mx2 and Mx3) that, separately, display antiviral activity against a wide range of viruses, showing interesting differences in their antiviral specificities. In this work, the possible synergy between the three Mx isoforms has been studied using in vitro systems, consisting of permanently transfected CHSE-214 cells expressing two or the three gilthead seabream Mx proteins. The antiviral activity of these Mx combinations has been tested against the infection by the Infectious Pancreatic Necrosis Virus (IPNV), the Viral Haemorrhagic Septicaemia Virus (VHSV) and the European Sheatfish Virus (ESV) in cells inoculated at 0.1 and 0.01 multiplicity of infection (MOI). The antiviral effect was evaluated by viral titration (TCID50 method). Interestingly, a positive synergistic effect in the antiviral activity against ESV was observed when Mx2 and Mx3 were combined, and this effect was intensified when the three isoforms were present in these cells. In contrast, the presence of more than one Mx isoform interfered with the antiviral activity against IPNV and VHSV showed by the Mx proteins expressed separately. Furthermore, Mx2 combined with Mx3, and the combination of the three Mx proteins exerted a negative synergistic effect against IPNV infection. Specifically, the viral titres were significantly higher in Mx expressing cells than in control cells. In the same way, in Mx1 and Mx2 expressing cells infected with VHSV the viral replication was alsoincreased. These results suggest the interaction between Mx isoforms, in which the expression level of each isoform might be an important factor, and support the idea of finely tuned mechanisms controlling the antiviral activity of Mx proteins. The authors want to thank Dr. C. P. Dopazo (University of Santiago de Compostela, Spain) and Dr. K. Way (CEFAS, Weymouth lab, UK) for supplying the viruses VHSV and ESV, respectively, used in this work.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Glucokinase (GCK) Mutations and Their Characterization in MODY2 Children of Southern Italy

Type 2 Maturity Onset Diabetes of the Young (MODY2) is a monogenic autosomal disease characterized by a primary defect in insulin secretion and hyperglycemia. It results from GCK gene mutations that impair enzyme activity. Between 2006 and 2010, we investigated GCK mutations in 66 diabetic children from southern Italy with suspected MODY2. Denaturing High Performance Liquid Chromatography (DHPLC) and sequence analysis revealed 19 GCK mutations in 28 children, six of which were novel: p.Glu40Asp, p.Val154Leu, p.Arg447Glyfs, p.Lys458_Cys461del, p.Glu395_Arg397del and c.580-2A>T. We evaluated the effect of these 19 mutations using bioinformatic tools such as Polymorphism Phenotyping (Polyphen), Sorting Intolerant From Tolerant (SIFT) and in silico modelling. We also conducted a functional study to evaluate the pathogenic significance of seven mutations that are among the most severe mutations found in our population, and have never been characterized: p.Glu70Asp, p.His137Asp, p.Phe150Tyr, p.Val154Leu, p.Gly162Asp, p.Arg303Trp and p.Arg392Ser. These seven mutations, by altering one or more kinetic parameters, reduced enzyme catalytic activity by >40%. All mutations except p.Glu70Asp displayed thermal-instability, indeed >50% of enzyme activity was lost at 50°C/30 min. Thus, these seven mutations play a pathogenic role in MODY2 insurgence. In conclusion, this report revealed six novel GCK mutations and sheds some light on the structure-function relationship of human GCK mutations and MODY2

Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.This work was supported by the Instituto de Salud Carlos III (PI17/01067) and AGAUR from the Autonomous Catalan Government (2017SGR1134). Dr. Víctor Antonio Blanco-Palmero is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Biomedical Research Institute) through a “Río Hortega” contract (CM18/0095). Dr. Sara Llamas-Velasco is supported by the Instituto de Salud Carlos III (ISCIII; Spanish Biomedical Research Institute) through a “Juan Rodés” contract (JR 18/00046).S

Guía de buenas prácticas para establecimientos lecheros : material de referencia de la Red de BPA

Con el objetivo de concentrar varios esfuerzos aislados que se han llevado a cabo en el país, INTA, la Fac. Cs. Agropecuarias de la UNC y APROCAL han tenido la iniciativa de convocar a especialistas y representantes del sector lechero nacional para trabajar en el desarrollo de una guía de buenas prácticas en el tambo consensuada entre los diferentes representantes del sector lechero. Esta guía procura ser una propuesta de fácil interpretación para ser consultada permanentemente por parte de quienes trabajan y conducen los establecimientos lecheros para apoyarse en aspectos que hacen al aseguramiento de la calidad en el tambo. A través de esta se pretende brindar recomendaciones de Buenas Prácticas para maximizar la producción y la calidad de leche en sistemas productivos sustentables.EEA PergaminoFIL: Negri Rodriguez, Livia María. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Tecnología de Alimentos; Argentina. Asociación PRO Calidad de la Leche y sus Derivados (PROCAL); ArgentinaFil: Aimar, María Verónica. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina. Asociación PRO Calidad de la Leche y sus Derivados (PROCAL); ArgentinaFil: Costamagna, Daniela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Callieri, Carlos. DeLaval Productor de Maquinaria Lechera y Agrícola; Argentina. Asociación PRO Calidad de la Leche y sus Derivados (PROCAL); ArgentinaFil: Herrero, María Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Charlón, Verónica. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Leiva, Antonio. Sancor; ArgentinaFil: Tentor, Gonzalo. Buenas Prácticas Agropecuarias (BPA); ArgentinaFil: Raciti, Julio. Manfrey Informatica; ArgentinaFil: Rampone, Alberto. Universidad Nacional de Villa María; ArgentinaFil: Chavez, Javier. Lactodiagnóstico Sur; ArgentinaFil: Gaggiotti, Mónica del Carmen. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Boffa, Susana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Paraná. Agencia de Extensión Rural La Paz. Oficina Técnica Hernandarias; ArgentinaFil: Mancuso, Walter. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Praraná; ArgentinaFil: Pautasso, Néstor. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Praraná; ArgentinaFil: Walter, Emilio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Moltoni, Luciana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Ingeniería Rural; ArgentinaFil: Serrano, Pedro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Agencia de Extensión Rural Coronel Brandsen; ArgentinaFil: Abdala, Alejandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Gonzalez Pereyra, Ana Valeria. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Lactodiagnóstico Sur; ArgentinaFil: Sardi, Graciela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Gigli, Isabel. Universidad Nacional de La Pampa; ArgentinaFil: Rodríguez, Julián. La Lacteo; ArgentinaFil: García, Karina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Brunas, Lucas. García Hermanos; ArgentinaFil: Bontá, Marcos. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Lactodiagnóstico Sur; Argentin

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research