Proteomic study on gender differences in aging kidney of mice

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: This study aims to analyze sex differences in mice aging kidney. We applied a proteomic technique based on subfractionation, and liquid chromatography coupled with 2-DE. Samples from male and female CD1-Swiss outbred mice from 28 weeks, 52 weeks, and 76 weeks were analysed by 2-DE, and selected proteins were identified by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Results: This proteomic analysis detected age-related changes in protein expression in 55 proteinspots, corresponding to 22 spots in males and 33 spots in females. We found a protein expression signature (PES) of aging composed by 8 spots, common for both genders. The identified proteins indicated increases in oxidative and proteolytic proteins and decreases in glycolytic proteins, and antioxidant enzymes. Conclusion: Our results provide insights into the gender differences associated to the decline of kidney function in aging. Thus, we show that proteomics can provide valuable information on agerelated changes in expression levels of proteins and related modifications. This pilot study is stil

Age-related subproteomic analysis of mouse liver and kidney peroxisomes

<p>Abstract</p> <p>Background</p> <p>Despite major recent advances in the understanding of peroxisomal functions and how peroxisomes arise, only scant information is available regarding this organelle in cellular aging. The aim of this study was to characterize the changes in the protein expression profile of aged versus young liver and kidney peroxisome-enriched fractions from mouse and to suggest possible mechanisms underlying peroxisomal aging. Peroxisome-enriched fractions from 10 weeks, 18 months and 24 months C57bl/6J mice were analyzed by quantitative proteomics.</p> <p>Results</p> <p>Peroxisomal proteins were enriched by differential and density gradient centrifugation and proteins were separated by two-dimensional electrophoresis (2-DE), quantified and identified by mass spectrometry (MS). In total, sixty-five proteins were identified in both tissues. Among them, 14 proteins were differentially expressed in liver and 21 proteins in kidney. The eight proteins differentially expressed in both tissues were involved in β-oxidation, α-oxidation, isoprenoid biosynthesis, amino acid metabolism, and stress response. Quantitative proteomics, clustering methods, and prediction of transcription factors, all indicated that there is a decline in protein expression at 18 months and a recovery at 24 months.</p> <p>Conclusion</p> <p>These results indicate that some peroxisomal proteins show a tissue-specific functional response to aging. This response is probably dependent on their differential regeneration capacity. The differentially expressed proteins could lead several cellular effects: such as alteration of fatty acid metabolism that could alert membrane protein functions, increase of the oxidative stress and contribute to decline in bile salt synthesis. The ability to detect age-related variations in the peroxisomal proteome can help in the search for reliable and valid aging biomarkers.</p

A study of quality measures for protein threading models

BACKGROUND: Prediction of protein structures is one of the fundamental challenges in biology today. To fully understand how well different prediction methods perform, it is necessary to use measures that evaluate their performance. Every two years, starting in 1994, the CASP (Critical Assessment of protein Structure Prediction) process has been organized to evaluate the ability of different predictors to blindly predict the structure of proteins. To capture different features of the models, several measures have been developed during the CASP processes. However, these measures have not been examined in detail before. In an attempt to develop fully automatic measures that can be used in CASP, as well as in other type of benchmarking experiments, we have compared twenty-one measures. These measures include the measures used in CASP3 and CASP2 as well as have measures introduced later. We have studied their ability to distinguish between the better and worse models submitted to CASP3 and the correlation between them. RESULTS: Using a small set of 1340 models for 23 different targets we show that most methods correlate with each other. Most pairs of measures show a correlation coefficient of about 0.5. The correlation is slightly higher for measures of similar types. We found that a significant problem when developing automatic measures is how to deal with proteins of different length. Also the comparisons between different measures is complicated as many measures are dependent on the size of the target. We show that the manual assessment can be reproduced to about 70% using automatic measures. Alignment independent measures, detects slightly more of the models with the correct fold, while alignment dependent measures agree better when selecting the best models for each target. Finally we show that using automatic measures would, to a large extent, reproduce the assessors ranking of the predictors at CASP3. CONCLUSIONS: We show that given a sufficient number of targets the manual and automatic measures would have given almost identical results at CASP3. If the intent is to reproduce the type of scoring done by the manual assessor in in CASP3, the best approach might be to use a combination of alignment independent and alignment dependent measures, as used in several recent studies

A progressive hedging approach to solve harvest scheduling problem under climate change

Due to the long time horizon typically characterizing forest planning, uncertainty plays an important role when developing forest management plans. Especially important is the uncertainty related to recently human-induced global warming since it has a clear impact on forest capacity to contribute to biogenic and anthropogenic ecosystem services. If the forest manager ignores uncertainty, the resulting forest management plan may be sub-optimal, in the best case. This paper presents a methodology to incorporate uncertainty due to climate change into forest management planning. Specifically, this paper addresses the problem of harvest planning, i.e., defining which stands are to be cut in each planning period in order to maximize expected net revenues, considering several climate change scenarios. This study develops a solution approach for a planning problem for a eucalyptus forest with 1000 stands located in central Portugal where expected future conditions are anticipated by considering a set of climate scenarios. The model including all the constraints that link all the scenarios and spatial adjacency constraints leads to a very large problem that can only be solved by decomposing it into scenarios. For this purpose, we solve the problem using Progressive Hedging (PH) algorithm, which decomposes the problem into scenario sub-problems easier to solve. To analyze the performance of PH versus the use of the extensive form (EF), we solve several instances of the original problem using both approaches. Results show that PH outperforms the EF in both solving time and final optimality gap. In addition, the use of PH allows to solve the most di cult problems while the commercial solvers are not able to solve the EF. The approach presented allows the planner to develop more robust management plans that incorporate the uncertainty due to climate change in their plansinfo:eu-repo/semantics/publishedVersio

Evaluation of knowledge in the subjects of civil procedure and comercial law through mock trial

[ES] Los cambios a los que nos enfrentamos en el Espacio Europeo de Educación Superior, unido a la reforma legal para el acceso a la profesión de abogado, por Ley 34/2006 de 30 de noviembre, hacen necesario que las universidades en las que se imparte el grado en Derecho, realicen una tarea de innovación docente para incorporar las metodologías que, dependiendo del tipo de asignatura,  permitan  lograr procesos de aprendizaje que se puedan adaptar a los constantes cambios sociales y legales, para lo cual es imprescindible adquirir competencias y no solo conocimientos.Ahora bien, para conseguir el anterior objetivo con efectividad, es esencial el feed-back constante del profesor para perfeccionar o corregir el aprendizaje del alumno, orientando su esfuerzo personal.[EN] The changes that we face in the European Higher Education Area, together with legal reform for access to the legal profession, by Law 34/2006 of 30 November, make it necessary for universities that teach the law degree, made a task to incorporate innovative teaching methodologies, depending on the type of course, provide the learning processes that can adapt to constantly changing social and legal, to which it is essential not only to acquire skills and knowledge.    However, to achieve the above objective effectively, it is essential to constant feedback to improve or correct teacher student learning, focusing its effort.[FR] Les changements auxquels nous sommes confrontés dans l'Espace européen de l'enseignement supérieur, ainsi que la réforme juridique de l'accès à la profession juridique, par la loi 34/2006 du 30 Novembre, rendent nécessaire pour les universités qui enseignent la diplôme en droit, a fait une tâche à intégrer les méthodes d'enseignement innovatrices, selon le type de cours, de fournir les processus d'apprentissage qui peuvent s'adapter aux changements constants sociale et juridique, à laquelle il est essentiel non seulement d'acquérir des compétences et des connaissances. Toutefois, pour atteindre l'objectif ci‐dessus efficacement, il est essentiel de feedback constant d'améliorer ou de corriger l'apprentissage d'élèves par enseignant, en concentrant ses efforts.Zúñiga Durán, O.; San Cristobal Reales, S. (2011). Evaluación de conocimientos en las asignaturas de derecho procesal civil y derecho mercantil a través del juicio simulado. REDU. Revista de Docencia Universitaria. 8(2):197-206. https://doi.org/10.4995/redu.2010.6203OJS19720682BAIN K (2008) Lo que hacen los mejores profesores de Universidad. Universitat de Valencia, Valencia.BONSÓN AVENTÍN M. (2009) "Desarrollo de competencias en Educación Superior", en Desarrollo y Evaluación de Competencias en Educación Superior, Blanco A. (coord..), NarceaBARBER M. (2008) "A formula for great teaching", Times Educational Supplement; vol. 48BENITOA. et.al. (2006) "Análisis de la enseñanza de la Física en Europa: el fomento de competencias generales en estudiantes universitarios". Revista Iberoamericana de Educación, nº 38GONZALEZ MAURA V. y, GONZÁLEZ TIRADOS, R.M. (2008), "Competencias genéricas y formación profesional: un análisis desde la docencia universitaria", Revista Iberoamericana de Educación Número 47PUSZTAL G. y SZABÓ P.C. (2008), "The Bologna process as a Trojan horse", European Education, Vol. 40, nº

Microstructure and properties of Fe3O4/BaTiO3/epoxy composites

Con el objetivo de estudiar nuevos materiales multipropósito, en este trabajo se analizó la influencia de las partículas de Fe3O4 y BaTiO3 sobre las propiedades magnéticas y dieléctricas de los sistemas Fe3O4/BaTiO3/epoxi. A tal efecto se analizaron los sistemas bifásicos Fe3O4/epoxi y BaTiO3/epoxi y a partir del análisis de los resultados se conformaron los compuestos Fe3O4/BaTiO3/epoxi. En todos los casos los valores de permitividad y pérdidas dieléctricas fueron altamente influenciados por el contenido de carga. En este sentido, los materiales procesados con Fe3O4 presentaron muy elevadas pérdidas dieléctricas para altas concentraciones de carga debido a efectos de percolación y a las propiedades semiconductoras del Fe3O4.The influence of Fe3O4 and BaTiO3 on dielectric and magnetic properties of Fe3O4/BaTiO3/epoxy composites was studied. Initially, biphasic Fe3O4/epoxy and BaTiO3/epoxy composites were analyzed, and based on these results Fe3O4/BaTiO3/epoxy composite were conformed. In all the cases, dielectric properties were influenced by the frequency and filler concentration. In this way, Fe3O4/epoxy composites with high filler concentration showed high dielectric loss due to percolation effects and semiconducting properties of Fe3O4.Fil: Ramajo, Leandro Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Cristobal, Adrian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Porto Lopez, Jose Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Botta, Pablo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Reboredo, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Castro, Miriam Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

Upregulation of NKG2D ligands impairs hematopoietic stem cell function in Fanconi anemia

Cellular immune response; Immunology; Stem cellsRespuesta inmune celular; Inmunología; Células madreResposta immune cel·lular; Immunologia; Cèl·lules mareFanconi anemia (FA) is the most prevalent inherited bone marrow failure (BMF) syndrome. Nevertheless, the pathophysiological mechanisms of BMF in FA have not been fully elucidated. Since FA cells are defective in DNA repair, we hypothesized that FA hematopoietic stem and progenitor cells (HSPCs) might express DNA damage–associated stress molecules such as natural killer group 2 member D ligands (NKG2D-Ls). These ligands could then interact with the activating NKG2D receptor expressed in cytotoxic NK or CD8+ T cells, which may result in progressive HSPC depletion. Our results indeed demonstrated upregulated levels of NKG2D-Ls in cultured FA fibroblasts and T cells, and these levels were further exacerbated by mitomycin C or formaldehyde. Notably, a high proportion of BM CD34+ HSPCs from patients with FA also expressed increased levels of NKG2D-Ls, which correlated inversely with the percentage of CD34+ cells in BM. Remarkably, the reduced clonogenic potential characteristic of FA HSPCs was improved by blocking NKG2D–NKG2D-L interactions. Moreover, the in vivo blockage of these interactions in a BMF FA mouse model ameliorated the anemia in these animals. Our study demonstrates the involvement of NKG2D–NKG2D-L interactions in FA HSPC functionality, suggesting an unexpected role of the immune system in the progressive BMF that is characteristic of FA.This work was supported by the “Ministerio de Ciencia e Innovación y Competitividad y Fondo Europeo de Desarrollo Regional (FEDER)” (SAF2015-68073-R, SAF2015-64152-R, and RTI2018-097125-B-I00); Next Generation EU; Plan de Recuperación Transformación y Resilencia (Instituto de Salud Carlos III; TERAV) (RD12/0019/0023); Programs of the European Commission (HEALTHF5-2012-305421 and EUROFANCOLEN); the “Ministerio de Sanidad, Servicios Sociales e Igualdad” (EC11/060 and EC11/550 “Comunidad de Madrid” (AvanCell, B2017/BMD-3692); and the ICREA-Academia program

Geographic and breeding distribution extension of the Striped owl (Asio clamator) in buenos aires province, Argentina

Se extiende el área de distribución geográfica conocida en la Argentina para el Lechuzón Orejudo (Asio clamator) hasta el partido de Bahía Blanca, en el sudoeste de la provincia de Buenos Aires, donde también se confirmó su reproducción exitosa.We extended the known geographic distribution range of the Eared Owl (Asio clamator) in Argentina to the Bahía Blanca Department, in the southwest of the Buenos Aires province. We also confirmed its successful reproduction in the area.Fil: Petracci, Pablo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Spagnuolo, Jorge Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Geología; ArgentinaFil: Tartaglia, Susana. Universidad Nacional del Sur; ArgentinaFil: Doyni Cabré, Cristobal. Universidad Nacional del Sur; ArgentinaFil: Carrizo, Martín. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Proteinen desnaturalizazio termalaren bidezko analisia konposatu bioeraginkor berriak aurkitzeko

Bioactive compounds are either natural or synthetic chemicals that can affect both the cellular and/or physiological activity in living organisms. Included among these are, for example, drugs that can have beneficial effects on health, through the modulation of biological processes. The development of new strategies to search new bioactive compounds and their new biological targets is a high impact challenge. In order to find target proteins and mechanisms of action, several different methodologies have been developed, including the method discussed in this paper. It is based on the analysis of the modifications caused by bioactive compounds on the protein thermal denaturation process. This work describes the basics of this methodology suitable in the search of bioactive compounds as well as the criteria for its implementation.; Konposatu bioeraginkorrak bizidunetan jarduera zelularraren edota fisiologikoaren gain eragin dezaketen substantzia kimiko naturalak zein sintetikoak dira. Horien artean daude, adibidez, farmakoak, prozesu biologikoen modulazioaren bitartez osasunaren gain efektu onuragarriak bideratu ditzaketenak. Konposatu bioeraginkor berrien eta horien itu biologikoak bilatzeko estrategia berrien garapena inpaktu handiko erronka da. Itu proteinak edota ekintza mekanismoak aurkitzeko metodologia ezberdinak garatu dira. Itu proteinak aurkitzeko metodoen artean, lan honetan jorratzen dena daukagu: konposatu bioeraginkorrek proteinen desnaturalizazio termalean eragindako aldaketen azterketan oinarritutako metodoa. Lan honetan, konposatu bioeraginkorrak bilatzeko metodologia horren oinarriak eta haren inplementaziorako irizpideak azaltzen dira

Machine learning-based model for prediction of clinical deterioration in hospitalized patients by COVID 19

[EN] Despite the publication of great number of tools to aid decisions in COVID-19 patients, there is a lack of good instruments to predict clinical deterioration. COVID19-Osakidetza is a prospective cohort study recruiting COVID-19 patients. We collected information from baseline to discharge on: sociodemographic characteristics, comorbidities and associated medications, vital signs, treatment received and lab test results. Outcome was need for intensive ventilatory support (with at least standard high-flow oxygen face mask with a reservoir bag for at least 6 h and need for more intensive therapy afterwards or Optiflow high-flow nasal cannula or noninvasive or invasive mechanical ventilation) and/or admission to a critical care unit and/or death during hospitalization. We developed a Catboost model summarizing the findings using Shapley Additive Explanations. Performance of the model was assessed using area under the receiver operating characteristic and prediction recall curves (AUROC and AUPRC respectively) and calibrated using the Hosmer-Lemeshow test. Overall, 1568 patients were included in the derivation cohort and 956 in the (external) validation cohort. The percentages of patients who reached the composite endpoint were 23.3% vs 20% respectively. The strongest predictors of clinical deterioration were arterial blood oxygen pressure, followed by age, levels of several markers of inflammation (procalcitonin, LDH, CRP) and alterations in blood count and coagulation. Some medications, namely, ATC AO2 (antiacids) and N05 (neuroleptics) were also among the group of main predictors, together with C03 (diuretics). In the validation set, the CatBoost AUROC was 0.79, AUPRC 0.21 and Hosmer-Lemeshow test statistic 0.36. We present a machine learning-based prediction model with excellent performance properties to implement in EHRs. Our main goal was to predict progression to a score of 5 or higher on the WHO Clinical Progression Scale before patients required mechanical ventilation. Future steps are to externally validate the model in other settings and in a cohort from a different period and to apply the algorithm in clinical practice. Registration: ClinicalTrials.gov Identifier: NCT04463706.This work was supported in part by grants from the Instituto de Salud Carlos III and the European Regional Development Fund COVID20/00459; the health outcomes group from Galdakao-Barrualde Health Organization; the Kronikgune Institute for Health Service Research; and the thematic network–REDISSEC (Red de Investigación en Servicios de Salud en Enfermedades Crónicas)–of the Instituto de Salud Carlos III. The funder of the study had no role in study design, data collection, analysis, management or interpretation, or writing of the report