Programmed cell senescence during mammalian embryonic development

Cellular senescence disables proliferation in damaged cells, and it is relevant for cancer and aging. Here, we show that senescence occurs during mammalian embryonic development at multiple locations, including the mesonephros and the endolymphatic sac of the inner ear, which we have analyzed in detail. Mechanistically, senescence in both structures is strictly dependent on p21, but independent of DNA damage, p53, or other cell-cycle inhibitors, and it is regulated by the TGF-beta/SMAD and PI3K/FOXO pathways. Developmentally programmed senescence is followed by macrophage infiltration, clearance of senescent cells, and tissue remodeling. Loss of senescence due to the absence of p21 is partially compensated by apoptosis but still results in detectable developmental abnormalities. Importantly, the mesonephros and endolymphatic sac of human embryos also show evidence of senescence. We conclude that the role of developmentally programmed senescence is to promote tissue remodeling and propose that this is the evolutionary origin of damage-induced senescence

Long-term immune response accompanies clinical outcomes in severe asthmatics treated with anti-IL-5/IL-5R biologics

This work was supported by ISCIII - Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria - Spanish Health Research Fund) grants PI21/00896 and FI19/00067; Ciber de Enfermedades Respiratorias (CIBERES); SEAIC grants 22A07; BASEAS STUDY (Basophils in EosinophilicAsthma) Study Code ESR-20-20764 AstraZeneca International; Comunidad de Madrid grant PEJ2021-AI_BMD-22320 and FEDER funds (Fondo Europeo de Desarrollo Regiona

Phenotypic, molecular characterization, antimicrobial susceptibility and draft genome sequence of Corynebacterium argentoratense strains isolated from clinical samples

During a 12-year period we isolated five Corynebacterium argentoratense strains identified by phenotypic methods, including the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and 16S rRNA gene sequencing. In addition, antimicrobial susceptibility was determined, and genome sequencing for the detection of antibiotic resistance genes was performed. The organisms were isolated from blood and throat cultures and could be identified by all methods used. All strains were resistant to cotrimoxazole, and resistance to β-lactams was partly present. Two strains were resistant to erythromycin and clindamycin. The draft genome sequences of theses isolates revealed the presence of the erm(X) resistance gene that is embedded in the genetic structure of the transposable element Tn5423. Although rarely reported as a human pathogen, C. argentoratense can be involved in bacteraemia and probably in other infections. Our results also show that horizontal transfer of genes responsible for antibiotic resistance is occurring in this species.Supported in part by the Gerencia Regional de Salud, Junta de Castilla y León, Spain (research project GRS 698/A/2011

Serum micrornas as tool to predict early response to benralizumab in severe eosinophilic asthma

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.This manuscript was funded by Fondo de Investigación Sanitaria–FIS and FEDER (Fondo Europeo de Desarrollo Regional) [PI15/00803, PI18/00044, and FI16/00036], CIBER de Enfermedades Respiratorias (CIBERES), Merck Health Foundation funds, and Ministerio de Ciencia, Innovación y Universidades (RTC-2017-6501-1

Similarities and differences in RANTES and (AOP)-RANTES-triggered signals : implications for chemotaxis

11 páginas, 8 figuras.Chemokines are a family of proinflammatory cytokines that attract and activate specific types of leukocytes. Chemokines mediate their effects via interaction with seven transmembrane G proteinÐcoupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)-RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylation,and Gai as well as JAK/STAT association to the receptor. In contrast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measured by the association of focal adhesion kinase (FAK) to the chemokine receptor complex, impaired cell polarization required for migration, or chemotaxis. The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals.Peer reviewe

Analysis of the Yield of Radish (Raphanus Sativus L.) Fertilized with Compost Based on Organic Waste from Markets and its Relationship with its Stomatal Density

For higher yields in vegetable cultivation, the availability of soil nutrients must be improved. Therefore, the aim of this research was to establish the relationship between stomatal density and the yield of the radish crop fertilized with compost made from organic market waste. A completely randomized block design was used, which consisted of 3 blocks and 5 treatments, which were T1, T2, T3, T4 and T5 with 00, 10, 15, 15, 20 and 25 g compost/plant respectively. The physical characteristics of the plants were evaluated from sowing to harvest and the data obtained were processed by analysis of variance and Duncan's test. Chemical analysis of the compost and soil was carried out, as well as a foliar analysis to determine the nutrient concentration by treatment. The results determined that the treatment (T4) stood out in plant length with 28.96 cm, plant weight with 43.33 g, yield of 10.82 t/ha and bulb diameter of 3.92 cm; likewise, in the concentration of nutrients in the leaves, the treatment (T5) highlighted in N with 5.94%, Ca 4.84%, Mg 1.29%, Zn 64.58 ppm and a stomatal density of 642 stomas/mm2. It is concluded that, at an adequate dose of compost, the concentration of nutrients increases, as well as the stomatal density, resulting in higher yields

MANAGEMENT PROPERTIES AND PROCEDURES IN THE INFORMATION MODEL OF THE HISTORIC BUILDING HBIM ON BUILDING FACADES

Historic Building Information Modelling (HBIM) has become the ideal tool for professionals studying building conservation and restoration. The BIM model allows one to identify structural deformations following three-dimensionally resolved models. In addition, this methodology is specifically designed to register parametric construction models, as an information manager by adding semantic components to the model, including information on the different transformations of the historical artefact, and allowing continuous progress in the building's life cycle. In this work, graphic information and data related to conservation projects are compiled that allow a management of all the documentation integrated in the same Project, from all the disciplinary fields related to the heritage conservation and rehabilitation process. Specifically, from the geometric identification and the restoration documents, it is intended to develop an experimental application where both terrestrial laser scanning records and the use of image processing routines can allow automatic operations to monitor alterations in façades, in order to subsequent control by conservation experts. For this, a building with certain characteristics has been chosen, such as the Miguel de Mañara palace in the city of Seville. A building that has a main façade of 43.30 metres in length by 6.75 metres in height and, in which its façade rotates in an angled guideline to adapt to the urban planning of the time. The analysis is based on the applicability of two segmentation algorithms and the construction of the multilayer enclosure model where the different stratigraphies of the results obtained are exposed

Ibero-American Society of Interventionism (SIDI) and the Spanish Society of Vascular and Interventional Radiology (SERVEI) Standard of Practice (SOP) for the management of inferior Vena Cava filters in the treatment of acute venous Thromboembolism

Objectives: to present an interventional radiology standard of practice on the use of inferior vena cava filters (IVCFs) in patients with or at risk to develop venous thromboembolism (VTE) from the Iberoamerican Interventional Society (SIDI) and Spanish Vascular and Interventional Radiology Society (SERVEI). Methods: a group of twenty-two interventional radiologist experts, from the SIDI and SERVEI societies, attended online meetings to develop a current clinical practice guideline on the proper indication for the placement and retrieval of IVCFs. A broad review was undertaken to determine the participation of interventional radiologists in the current guidelines and a consensus on inferior vena cava filters. Twenty-two experts from both societies worked on a common draft and received a questionnaire where they had to assess, for IVCF placement, the absolute, relative, and prophylactic indications. The experts voted on the different indications and reasoned their decision. Results: a total of two-hundred-thirty-three articles were reviewed. Interventional radiologists participated in the development of just two of the eight guidelines. The threshold for inclusion was 100% agreement. Three absolute and four relative indications for the IVCF placement were identified. No indications for the prophylactic filter placement reached the threshold. Conclusion: interventional radiologists are highly involved in the management of IVCFs but have limited participation in the development of multidisciplinary clinical practice guidelines

Fodder, Nitrogen, and Energy Balances in Grasslands with Algarroba Trees (Prosopis juliflora (S.W.) DC.) under Dairy Cow Grazing

The purpose of this study was to evaluate the effect of algarroba (Prosopis juliflora (S.W.) DC.) on fodder, nitrogen and energy contents in Ecuadoran dairy farm grasslands. The study was made at ESPAM bovine facility, 15 meters above sea level, in Manabí, 00º49’23’’, south latitude, and 80º11’01” west longitude, with 962.4 mm of annual precipitation, between September 2011 and December 2014. The stocking rate was 1.09 LU/ha. The areas were populated with 1-4 algarroba trees/ha by 2011, and 8-35 trees/ha, in 2014. Fodder, nitrogen, and energy balances depended on the arborization degree. As a result, 52 t of DM were estimated in 2014, in comparison to the 21 t produced in 2011. Nitrogen was higher with increased arborization between 2011 (60.9 kg/ha), greater nutrient intake from external sources, and 2014 (39.3 kg/ha), with less use of supplements and mineral fertilizers, and greater N2 contribution by arborization. The energy values were higher in 2014, with an increase in algarroba population/ha. The rise in trees/ha in 2014 favored forage yields, with improved N2 and energy efficiency, which was linked to the benefits acquired by the grassland, the contribution of nitrogen to the ecosystem, and the reduction in feed and fertilizer consumption, which led to energy savings