Outflows, envelopes, and disks as evolutionary indicators in Lupus YSOs

By studying 7 objects in the Lupus clouds we aim to test if a coherence exists between commonly used evolutionary tracers. We present ALMA observations of the continuum and molecular line emission that probe the dense gas and dust of cores and their associated molecular outflows. Our source selection in a common environment allows for a consistent comparison across different evolutionary stages. The quality of the ALMA molecular data allows us to reveal the nature of the molecular outflows by studying their morphology and kinematics. The images in IRAS15398-3359 appear to show that it drives a precessing episodic jet-driven outflow with at least 4 ejections separated by periods of time between 50 and 80 years, while data in IRAS16059-3857 show similarities with a wide-angle wind model also showing signs of being episodic. The outflow of J160115-41523 could be better explain with the wide-angle wind model as well, but new observations are needed to explore its nature. We find that the most common evolutionary tracers are useful for broad evolutionary classifications, but are not consistent with each other to provide enough granularity to disentangle different evolutionary stage of sources that belong to the same Class. Outflow properties used as protostellar age tracers (mass, momentum, energy, opening angle) may suffer from differences in the nature of each outflow, thus detailed observations are needed to refine evolutionary classifications. We found both AzTEC-lup1-2 and AzTEC-lup3-5 to be in the pre-stellar stage, although the latter could be more evolved. IRAS15398-3359, IRAS16059-3857 and J160115-41523, which have clearly detected outflows, are Class 0 sources, although we are not able to determine which is younger and which is older. Sz102 and Merin28 are the most evolved sources and show signs of having associated flows, not as well traced by CO as for the younger sources.Fil: Vazzano, María Mercedes. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Fernandez Lopez, Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Plunkett, Adele. National Radio Astronomy Observatory; Estados UnidosFil: de Gregorio Monsalvo, Itziar. European Southern Observatory Chile.; ChileFil: Santamaría Miranda, Alejandro. European Southern Observatory Chile.; ChileFil: Takahashi, Satoko. Joint Alma Observatory; ChileFil: Lopez, Cristian. Joint Alma Observatory; Chil

Non-destructive production of exosomes loaded with ultrathin Palladium nanosheets for targeted bioorthogonal catalysis

The use of exosomes as selective delivery vehicles of therapeutic agents, such as drugs or hyperthermia-capable nanoparticles, is being intensely investigated on account of their preferential tropism toward their parental cells. However, the methods used to introduce a therapeutic load inside exosomes often involve disruption of their membrane, which may jeopardize their targeting capabilities, attributed to their surface integrins. On the other hand, in recent years bio-orthogonal catalysis has emerged as a new tool with a myriad of potential applications in medicine. These bio-orthogonal processes, often based on Pd-catalyzed chemistry, would benefit from systems capable of delivering the catalyst to target cells. It is therefore highly attractive to combine the targeting capabilities of exosomes and the bio-orthogonal potential of Pd nanoparticles to create new therapeutic vectors. In this protocol, we provide detailed information on an efficient procedure to achieve a high load of catalytically active Pd nanosheets inside exosomes, without disrupting their membranes. The protocol involves a multistage process in which exosomes are first harvested, subjected to impregnation with a Pd salt precursor followed by a mild reduction process using gas-phase CO, which acts as both a reducing and growth-directing agent to produce the desired nanosheets. The technology is scalable, and the protocol can be conducted by any researcher having basic biology and chemistry skills in ~3 d.We gratefully acknowledge financial support from the ERC Advanced Grant CADENCE (grant no. ERC-2016-ADG-742684) and the EPSRC (Healthcare Technology Challenge award no. EP/N021134/1). M.S.-A. thanks the Spanish Government for an FPU PhD research fellowship. B.R.-R. thanks the EC (grant no. H2020-MSCA-IF-2014–658833). V.S. acknowledges the financial support of Ministerio de Ciencia, Innovación y Universidades, Programa Retos Investigación, Proyecto REF: RTI2018-099019-A-I00. M.A. acknowledges the financial support of the ERC Consolidator Grant programme (grant no. ERC-2013-CoG-614715). P.M.-D. also thanks Instituto de Salud Carlos III (PI19/01007). We also thank CIBER-BBN, an initiative funded by the VI National R&D&i Plan 2008–2011 financed by the Instituto de Salud Carlos III and by Fondo Europeo de Desarrollo Regional (Feder) ‘Una manera de hacer Europa’, with the assistance of the European Regional Development Fund. This study is also partially funded by the Aragon Government (T57_17R p) cofounded by Feder 2014–2020 ‘Building Europe from Aragon’.Peer reviewe

In Cellulo Bioorthogonal Catalysis by Encapsulated AuPd Nanoalloys. Overcoming Intracellular Deactivation

Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed AuPd nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media. We also show that the intracellular catalytic performance of these nanoalloys is significantly enhanced by protecting them following two different encapsulation methods. Encapsulation in mesoporous silica nanorods resulted in augmented catalyst reactivity, whereas the use of a biodegradable PLGA matrix increased nanoalloy delivery across the cell membrane. The functional potential of encapsulated AuPd was demonstrated by releasing the potent chemotherapy drug paclitaxel inside cancer cells. Nanoalloy encapsulation provides a novel methodology to develop nanoreactors capable of mediating new-to-life reactions in cell

Application of Copper-Based NPs for Cancer Therapy in 3D Microfluidic-Based Cell Culture Model

En este trabajo se ha utilizado un modelo de cultivo celular 3D basado en microfluídica para crecer esferoides tumorales de glioblastoma y realizar un estudio del efecto de NPs basadas en cobre como posible terapia antitumoral. Se han obtenido resultados satisfactorios sobre el crecimiento, la viabilidad y la capacidad metastásica

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

Dementia in Latin America : paving the way towards a regional action plan

Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF

Use of Biofuels in the Aeronautical Industry:: Colombian Air Force Case

The present work makes a panorama of the uses of biofuels in the aeronautical industry, considering military aviation. The state of the art contemplates researches for the production and characterization of the different alternatives that can partially or totally replace fossil fuels of aviation, aiming to reduce the emissions of greenhouse gases. In the local case, through the development of a research project, the use of biofuels for aircraft engines has been evaluated. In the first phase, ground tests were carried out to justify and present the results of the options considered. In this way, an outline is made of the production of biokerosene and FAME produced at laboratory level, as well as the inherent challenges to incorporate these two biofuels in mixtures with Jet Fuel in a commercial level for the national scope.El presente trabajo realiza un panorama de los usos de los biocombustibles en la industria aeronáutica, considerando la aviación militar. El estado del arte contempla las investigaciones para la producción y caracterización de las diferentes alternativas que pueden reemplazar parcial o totalmente los combustibles fósiles de aviación con el ánimo de reducir las emisiones de gases de efecto invernadero. En el caso local, mediante el desarrollo de un proyecto de investigación, se ha evaluado el uso de biocombustibles para motores de aeronaves. En una primera fase, se realizaron ensayos en tierra, para justificar y presentar los resultados de las opciones consideradas. De esta manera, se hace un esbozo de la producción de bioqueroseno y FAME a nivel de laboratorio, así como de los desafíos inherentes para incorporar estos dos biocombustibles en mezclas con Jet Fuel a nivel comercial en el ámbito nacional

Delayed introduction of sirolimus in paediatric intestinal transplant recipients: indications and long-term benefits

To review our experience using sirolimus in a single centre paediatric intestinal transplantation cohort. Intestinal transplant patients with more than 3 months follow-up were divided into two groups according to their immunosuppression regimen: tacrolimus, (TAC group, n = 45 grafts) or sirolimus (SRL group, n = 38 grafts), which included those partially or completely converted from tacrolimus to sirolimus. The indications to switch were tacrolimus side effects and immunological complications. Survival and complications were retrospectively analysed comparing both groups. SRL was introduced 9 months (0 months–16.9 years) after transplant. The main cause for conversion was worsening renal function (45%), followed by haemolytic anaemia (21%) and graft-versus-host-disease (16%). Both groups showed a similar overall patient/graft survival (P = 0.76/0.08) and occurrence of rejection (24%/17%, P = 0.36). Immunological complications did not recur after conversion. Renal function significantly improved in most SRL patients. After a median follow-up of 65.17 months, 28/46 survivors were on SRL, 26 with monotherapy, with good graft function. Over one-third of our patients eventually required SRL conversion that allowed to improve their kidney function and immunological events, without entailing additional complications or survival impairment. Further trials are warranted to clarify the potential improvement of the standard tacrolimus maintenance by sirolimus conversion or addition.Fil: Andres, Ane M.. Hospital Universitario la Paz; EspañaFil: Talayero, Paloma. Hospital Universitario 12 de Octubre; EspañaFil: Alcolea Sanchez, Alida. No especifíca;Fil: Sanchez Galán, Alba. Hospital Universitario la Paz; EspañaFil: Serradilla Rodríguez, Javier. Hospital Universitario la Paz; EspañaFil: Bueno Jimenez, Alba. Hospital Universitario la Paz; EspañaFil: Gonzalez Sacristan, Rocío. No especifíca;Fil: Stringa, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Papa Gobbi, Rodrigo. Hospital Universitario la Paz; EspañaFil: Lasa Lazaro, Maria. Hospital Universitario 12 de Octubre; EspañaFil: Díaz Almirón, Mariana. Hospital Universitario la Paz; EspañaFil: Ramos Boluda, Esther. No especifíca;Fil: Lopez Santamaría, Manuel. Hospital Universitario la Paz; EspañaFil: Hernández Oliveros, Francisco. Hospital Universitario la Paz; Españ

A multicentric study to evaluate the use of relative retention times in targeted proteomics

Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. BIOLOGICAL SIGNIFICANCE: From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.All laboratories from Spain are members of ProteoRed (Plataforma de Recursos Biomoleculares y Bioinformáticos) and are supported by grant PT13/0001 funded by Instituto de Salud Carlos III (ISCIII) and FEDER.S

A multicentric study to evaluate the use of relative retention times in targeted proteomics

Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. [Biological significance]: From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.All laboratories from Spain are members of ProteoRed (Plataforma de Recursos Biomoleculares y Bioinformáticos) and are supported bygrant PT13/0001 funded by Instituto de Salud Carlos III (ISCIII) andFEDERPeer Reviewe