A new algorithm for particle weighted subtraction to decrease signals from unwanted components in single particle analysis

Single particle analysis (SPA) in cryo-electron microscopy (cryo-EM) is highly used to obtain the near-atomic structure of biological macromolecules. The current methods allow users to produce high-resolution maps from many samples. However, there are still challenging cases that require extra processing to obtain high resolution. This is the case when the macromolecule of the sample is composed of different components and we want to focus just on one of them. For example, if the macromolecule is composed of several flexible subunits and we are interested in a specific one, if it is embedded in a viral capsid environment, or if it has additional components to stabilize it, such as nanodiscs. The signal from these components, which in principle we are not interested in, can be removed from the particles using a projection subtraction method. Currently, there are two projection subtraction methods used in practice and both have some limitations. In fact, after evaluating their results, we consider that the problem is still open to new solutions, as they do not fully remove the signal of the components that are not of interest. Our aim is to develop a new and more precise projection subtraction method, improving the performance of state-of-the-art methods. We tested our algorithm with data from public databases and an in–house data set. In this work, we show that the performance of our algorithm improves the results obtained by others, including the localization of small ligands, such as drugs, whose binding location is unknown a prioriThe authors acknowledge the economic support from MICIN to the Instruct Image Processing Center (I2PC) as part of the Spanish participation in Instruct-ERIC, the European Strategic Infrastructure Project (ESFRI) in Structural Biology. Grant PID2019-104757RB-I00 is funded by MCIN/AEI/ 10.13039/ 501100011033 and “ERDF A way of making Europe”, by the European Union. The “Comunidad Autónoma de Madrid” through Grant S2022/BMD-7232, the European Union (EU) and Horizon 2020 through grant HighResCells (ERC-2018-SyG, Proposal: 810057). The authors also acknowledge grant PID2019-104098 GB-I00/AEI/10.13039/501100011033, cofunded by the Spanish State Research Agency and the European Regional Development and grant 2023AEP082 by Agencia Estatal CSIC. Ruben Sanchez-Garcia is funded by an Astex Pharmaceuticals Sustaining Innovation Post-Doctoral Awar

Clinical factors associated with a Candida albicans Germ Tube Antibody positive test in Intensive Care Unit patients

Background: Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting. Methods: A prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was >= 1: 160 in at least one sample and no other microbiological evidence of invasive candidiasis was found. Results: Fifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients. Conclusions: This study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.This study has been supported by a Pfizer research gran

The Sant Pau Initiative on Neurodegeneration (SPIN) cohort : A data set for biomarker discovery and validation in neurodegenerative disorders

Altres ajuts: The SPIN cohort has received funding from CIBERNED; Instituto de Salud Carlos III; jointly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa"; Generalitat de Catalunya; Fundació "La Marató TV3" Fundació Bancària Obra Social La Caixa; Fundación BBVA; Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica (FUNDELA); Global Brain Health Institute; Fundació Catalana Síndrome de Down; and Fundació Víctor Grífols i Lucas. These funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.The SPIN (Sant Pau Initiative on Neurodegeneration) cohort is a multimodal biomarker platform designed for neurodegenerative disease research following an integrative approach. Participants of the SPIN cohort provide informed consent to donate blood and cerebrospinal fluid samples, receive detailed neurological and neuropsychological evaluations, and undergo a structural 3T brain MRI scan. A subset also undergoes other functional or imaging studies (video-polysomnogram, 18 F-fluorodeoxyglucose PET, amyloid PET, Tau PET). Participants are followed annually for a minimum of 4 years, with repeated cerebrospinal fluid collection and imaging studies performed every other year, and brain donation is encouraged. The integration of clinical, neuropsychological, genetic, biochemical, imaging, and neuropathological information and the harmonization of protocols under the same umbrella allows the discovery and validation of key biomarkers across several neurodegenerative diseases. We describe our particular 10-year experience and how different research projects were unified under an umbrella biomarker program, which might be of help to other research teams pursuing similar approaches

Advances in Xmipp for cryo-electron microscopy: from Xmipp to Scipion

Xmipp is an open-source software package consisting of multiple programs for processing data originating from electron microscopy and electron tomography, designed and managed by the Biocomputing Unit of the Spanish National Center for Biotechnology, although with contributions from many other developers over the world. During its 25 years of existence, Xmipp underwent multiple changes and updates. While there were many publications related to new programs and functionality added to Xmipp, there is no single publication on the Xmipp as a package since 2013. In this article, we give an overview of the changes and new work since 2013, describe technologies and techniques used during the development, and take a peek at the future of the package

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Presentació

Dada-Surrealismo: precursores, marginales y heterodoxos

Presentar las actas del coloquio «Dada-Surrealismo: precursores, marginales y heterodoxos» celebrado en Cádiz del 19 al 22 de noviembre pasado, constituye para este Departamento de Lengua y Literatura Francesas un motivo de satisfacción y una incitación a la confianza. Confianza en las posibilidades de difusión y audiencia que la literatura francesa (francófona en general) presenta hoy en nuestro país, y confianza, igualmente, en el futuro de unas más estrechas relaciones culturales, tanto nacionales como internacionales

Clinical factors associated with a <it>Candida albicans </it>Germ Tube Antibody positive test in Intensive Care Unit patients

Abstract Background Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting. Methods A prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was ≥ 1:160 in at least one sample and no other microbiological evidence of invasive candidiasis was found. Results Fifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients. Conclusions This study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.</p

Optimisation et application des améliorations dans l'évaluation des compétences transversales conçues à partir de la vision multidisciplinaire d'ApreRED

The specific competences are acquired by the students and certified by passing the different subjects of the study plans. However, soft skills are not systematically worked on and are not evaluated, which means that their acquisition cannot be guaranteed. However, these skills are a fundamental basis in higher education and in the future employment of university graduates. The current methodological paradigm of Higher Education shows the importance of authentic and alternative evaluation of learning, based on relevant activities or execution tasks. AprenRED's work in recent years has focused on the field of soft skills. In this case, the objective of this study is to optimize and improve the strategies and instruments for evaluating soft skills, based on the results obtained in recent years, from our multidisciplinary perspective.Las competencias específicas son adquiridas por los estudiantes y certificadas mediante la superación de las diferentes materias de los planes de estudio. Sin embargo, las competencias transversales no se trabajan sistemáticamente y no se evalúan, lo que implica que no pueda garantizarse su adquisición. Sin embargo, dichas competencias son base fundamental en la formación superior y en la futura inserción laboral de los graduados universitarios. El actual paradigma metodológico de la Educación Superior muestra la importancia de la evaluación auténtica y alternativa de los aprendizajes, a partir de actividades o tareas de ejecución relevantes. El trabajo de AprenRED durante los últimos años se ha centrado en el campo de las competencias transversales. En este caso, el objetivo de este trabajo es optimizar y mejorar las estrategias e instrumentos de evaluación de las competencias transversales, en base a los resultados obtenidos en los últimos años, desde nuestra visión multidisciplinar.Des compétences spécifiques sont acquises par les étudiants et certifiées par la réussite des différentes matières des plans d'études. Cependant, les compétences transversales ne sont pas systématiquement travaillées et ne sont pas évaluées, ce qui ne permet pas de garantir leur acquisition. Or, ces compétences constituent une base fondamentale dans l'enseignement supérieur et dans l'emploi futur des diplômés universitaires. Le paradigme méthodologique actuel de l'enseignement supérieur montre l'importance d'une évaluation authentique et alternative des apprentissages, basée sur des activités ou des tâches d'exécution pertinentes. Le travail d'ApreRED ces dernières années s'est concentré sur le domaine des compétences transversales. Dans ce cas, l'objectif de ce travail est d'optimiser et d'améliorer les stratégies et les instruments d'évaluation des compétences transversales, sur la base des résultats obtenus ces dernières années, à partir de notre vision multidisciplinaire