CXCR4(+)-targeted protein nanoparticles produced in the food-grade bacterium Lactococcus lactis

Lactococcus lactis is a Gram-positive (endotoxin-free) food-grade bacteria exploited as alternative to Escherichia coli for recombinant protein production. We have explored here for the first time the ability of this platform as producer of complex, self-assembling protein materials. Materials & methods: Biophysical properties, cell penetrability and in vivo biodistribution upon systemic administration of tumor-targeted protein nanoparticles produced in L. lactis have been compared with the equivalent material produced in E. coli. Results: Protein nanoparticles have been efficiently produced in L. lactis, showing the desired size, internalization properties and biodistribution. Conclusion: In vitro and in vivo data confirm the potential and robustness of the production platform, pointing out L. lactis as a fascinating cell factory for the biofabrication of protein materials intended for therapeutic applications.Award-winningPostprint (published version

Biosensor para la detección de anticuerpos anti-VIH

Biosensor para la detección de anticuerpos anti-VIH. En la presente invención se provee un biosensor capaz de detectar anticuerpos anti-VIH en una muestra biológica, basado en la utilización combinada de una enzima alostérica, modificada genéticamente, y una matriz con redes de microelectrodos.Consejo Superior de Investigaciones Científicas (España), Universidad Autónoma de BarcelonaA1 Solicitud de patente con informe sobre el estado de la técnic

sRNAbench and sRNAtoolbox 2022 update: accurate miRNA and sncRNA profiling for model and non-model organisms

European Union [765492 to M.H.]; Spanish Government [AGL2017-88702-C2-2-R to M.H.]; Chair 'Doctors Galera-Requena in cancer stem cell research' (to J.A.M.); Tromsoforskningsstiftelse (TFS) [20 SG BF 'MIRevolution' to B.F.]; Stichting Cancer Center Amsterdam [CCA2021-9-77 to C.G]; TKI-Health Holland ['AQrate' project to C.G. and M.P.]. This publication is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 765492.The NCBI Sequence Read Archive currently hosts microRNA sequencing data for over 800 different species, evidencing the existence of a broad taxonomic distribution in the field of small RNA research. Simultaneously, the number of samples per miRNA-seq study continues to increase resulting in a vast amount of data that requires accurate, fast and user-friendly analysis methods. Since the previous release of sRNAtoolbox in 2019, 55 000 sRNAbench jobs have been submitted which has motivated many improvements in its usability and the scope of the underlying annotation database. With this update, users can upload an unlimited number of samples or import them from Google Drive, Dropbox or URLs. Micro- and small RNA profiling can now be carried out using high-confidence Metazoan and plant specific databases, MirGeneDB and PmiREN respectively, together with genome assemblies and libraries from 441 Ensembl species. The new results page includes straightforward sample annotation to allow downstream differential expression analysis with sRNAde. Unassigned reads can also be explored by means of a new tool that performsmapping to microbial references, which can reveal contamination events or biologically meaningful findings as we describe in the example. sRNAtoolbox is available at: https://arn.ugr.es/srnatoolbox/.European Commission 765492Spanish GovernmentEuropean Commission AGL2017-88702-C2-2-RChair 'Doctors Galera-Requena in cancer stem cell research'Stichting Cancer Center Amsterdam CCA2021-9-77Tromsoforskningsstiftelse (TFS) ['MIRevolution'] 20 SG BFTKI-Health Holland ['AQrate' project

Análisis de la percepción del profesorado sobre la conciencia del aprendizaje del alumnado en las actividades participativas

We find ourselves in a society in which learning has changed dramatically, due to various factors such as the improvement of educational technology, the pandemic caused by COVID-19 or the advancement of the knowledge society. That is why it is not only important to train students in the contents of the official curricula of each of the Autonomous Communities, but it is also necessary to seek for students to acquire a set of key skills, acquired in formal or non-formal contexts, that allows them to develop as people and can efficiently access the labor market. For this reason, a participatory didactic proposal was planned and designed to help acquire these key competencies. We ask ourselves the research question: Are the students aware of their learning when carrying out participatory activities? as a concern of our research group when developing the didactic proposal with a group of 1st year Secondary Education from the Vía Dalmacia Institute in the town of Torrejoncillo. Semi-structured interviews wereconducted with fourkeyinformants, who wereteachers who participated in the planning and development of the experience. A qualitative methodology was used with a phenomenological dilemma, based on content analysis. Among the results obtained, it stands out that the teachers preferentially think that the students are aware of their learning bycarrying out theactivities. In addition, the factors that improve this perception are having an active role, collaboration, interest and curiosity. On the other hand, among the factors that hinder students’ awareness of learning are immaturity and lack of self-perception. The didactic proposal carried out has helped to verify which are the factors in which the teaching staff should focus so that the students can be aware of the key competences they acquire.Nos encontramos en una sociedad en la que el aprendizaje ha cambiado vertiginosamente, debido a diversos factores como la mejora de la tecnología educativa, la pandemia provocada por el COVID-19 o el avance de la sociedad del conocimiento. Es por ello, que no solo es importante formar al alumnado en los contenidos de los currículos oficiales de cada una de las Comunidades Autónomas, sino que hay que buscar que el alumnado adquiera un conjunto de competencias clave, adquiridas en contextos formales o no formales, que les permita desarrollarse como personas y puedan acceder de forma eficiente al mercado laboral. Por ello, se planificó y diseñó una propuesta didáctica participativa, que ayude a la adquisición de estas competencias clave. Nos planteamos la pregunta de investigación: ¿El alumnado es consciente de su aprendizaje al realizar actividades participativas? como inquietud de nuestro grupo de investigación al desarrollar la propuesta didáctica con un grupo de 1º de Educación Secundaria del Instituto Vía Dalmacia de la población de Torrejoncillo. Se realizaron entrevistas semiestructuradas a cuatro informantes clave, que fueron docentes que participaron en la planificación y desarrollo de la experiencia. Se utilizó una metodología cualitativa con un díselo fenomenológico, basado en el análisis de contenido. Entre los resultados obtenidos, se destaca que el profesorado piensa preferentemente que el alumnado es consciente de su aprendizaje con la realización de las actividades. Además, los factores que mejoran esta percepción son el tener un papel activo, la colaboración, el interés y la curiosidad. En cambio, entre los factores que dificultan la consciencia del aprendizaje en el alumnado son la inmadurez y la falta de auto-percepción. La propuesta didáctica realizada, ha ayudado a comprobar cuáles son los factores en los que el profesorado se debe focalizar para que el alumnado pueda ser consciente de las competencias clave que adquiere.

GENYOi005-A: An induced pluripotent stem cells (iPSCs) line generated from a patient with Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) carrying a p.Thr196Ala variant

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) is a rare platelet disorder caused by mutations in RUNX1. We generated an iPSC line (GENYOi005-A) from a FPDMM patient with a non-previously reported variant p.Thr196Ala. Non-integrative Sendai viruses expressing the Yamanaka reprogramming factors were used to reprogram peripheral blood mononuclear cells from this FPDMM patient. Characterization of GENYOi005-A included genetic analysis of RUNX1 locus, Short Tandem Repeats profiling, alkaline phosphatase enzymatic activity, expression of pluripotency-associated factors and differentiation studies in vitro and in vivo. This iPSC line will provide a powerful tool to study developmental alterations of FPDMM patientsThis work was supported by the Ramon y Cajal (RYC-2015-18382) to PJR founded by the Ministry of Economy and Competitiveness; the Instituto de Salud Carlos III-FEDER (CP12/03175 and CPII17/00032) to V.R-M., (PI17/01311) to M.L.L and J.R., (PI17/01966; Fundación Mutua Madrileña AP172142019; Premio Lopez Borrasca SETH 2019; GRS2061/A/19) to J.M.B. and (CPII15/00018 and PI16/01340) to PJR; by the Chair "Doctors Galera-Requena in cancer stem cell research" (CMC-CTS963) to J.A.M. and C.G-L

Experiencia vivencial: Elaboración de documental “Torres de San Borja” en el marco del Proyecto Uniones

Resumen El presente documento describe los detalles de la realización del documental “Torres de San Borja”, cuya finalidad es crear conciencia sobre las dificultades que enfrenta el asentamiento humano del mismo nombre y alentar al apoyo de esta comunidad mediante la Responsabilidad Social. Para ello se realizaron visitas a la zona de intervención buscando familias dispuestas a ser entrevistadas, estas entrevistas fueron grabadas y editadas en formato documental con la intención de que sea proyectada públicamente y frente a los protagonistas del documental. Estas actividades se llevaron a cabo exitosamente congregando a 59 personas en total.Abstract This document describes the details of the documentary film "Torres de San Borja", whose purpose is to raise awareness of the difficulties faced by the human settlement with the same name and to encourage the support of this community through social responsibility. To do this, we have to visit the intervention area, looking for families who wants to support us with the interviews, these interviews were recorded and edited in a documentary format with the intention of being projected openly and in front of the protagonists of the documentary. These activities were successfully carried out with 59 participants

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

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

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

n/