The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering

Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex. In addition, the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands, a process known as inside-out activation. We previously showed that in Drosophila, mutating the integrin binding site in the talin head domain resulted in weakened adhesion to the ECM. Intriguingly, subsequent studies showed that canonical inside-out activation of integrin might not take place in flies. Consistent with this, a mutation in talin that specifically blocks its ability to activate mammalian integrins does not significantly impinge on talin function during fly development. Here, we describe results suggesting that the talin head domain reinforces and stabilizes the integrin adhesion complex by promoting integrin clustering distinct from its ability to support inside-out activation. Specifically, we show that an allele of talin containing a mutation that disrupts intramolecular interactions within the talin head attenuates the assembly and reinforcement of the integrin adhesion complex. Importantly, we provide evidence that this mutation blocks integrin clustering in vivo. We propose that the talin head domain is essential for regulating integrin avidity in Drosophila and that this is crucial for integrin-mediated adhesion during animal development

Influencia de un programa de ejercicios físicos adaptados para el desarrollo de la coordinación motriz en niños de 8 a 12 años del equipo de atletismo Marlins de Ciudad del Carmen, México

ejercicios físicos adaptados ejerce sobre el desarrollo de la coordinación motriz en niños que entrenan atletismo del equipo Marlin´s, lo que permitirá a futuro ser parte de un grupo de atletas, que tengan un buen nivel competitivo en esta disciplina. La investigación es de tipo longitudinal, al realizarse las mediciones a lo largo del tiempo, se enmarca en un diseño pre experimental con pre-test y post-test al mismo grupo. Se hace una comparación de muestra pareadas para eliminar el sesgo de error que tiene el pre-experimento. Los métodos utilizados para dar respuesta a la problemática detectada son diversos con énfasis en la medición como método principal que permitió realizar un análisis estadístico acorde al tipo de estudio seleccionado. La contribución se materializa en la propia concepción del programa motriz a los niños que entrenan atletismo. Las conclusiones refieren que derivado del diagnóstico se observó en la muestra seleccionada dificultades en la coordinación motriz, lo que demostró la necesidad de la elaboración de este programa. Después de aplicado, pudo comprobarse que el mismo influyó positivamente en el proceso de entrenamiento del atletismo, se logró mejorar significativamente la coordinación motriz en niños de 8 a 12 años del equipo de atletismo Marlins y con ello la ejecución de las diferentes técnicas empleadas en este deporte. Palabras clave: Coordinación motriz, entrenamiento, atletismo.   ABSTRACT The purpose of the research was to determine the influence that an adapted physical exercise program exerts on the development of motor coordination in children who train athletics for the Marlin's team, which will allow them to be part of a group of athletes in the future, who have a good competitive level in this discipline. The research is of a longitudinal type, as the measurements are made over time, it is part of a pre-experimental design with pre-test and post-test to the same group. A comparison of paired samples is made to eliminate the error bias that the pre-experiment has. The methods used to respond to the detected problems are diverse with emphasis on measurement as the main method that allowed statistical analysis according to the type of study selected. The contribution is materialized in the very conception of the motor program for children who train athletics. The conclusions refer that derived from the diagnosis, difficulties in motor coordination were observed in the selected sample, which demonstrated the need for the development of this program. After applied, it could be verified that it had a positive influence on the athletics training process, it was possible to significantly improve motor coordination in children from 8 to 12 years of age from the Marlins athletics team and with it the execution of the different techniques used in this sport. Keywords: Motor coordination, training, athletics

Plasmonic-assisted thermocyclizations in living cells using metal−organic framework based nanoreactors

We describe a microporous plasmonic nanoreactor to carry out designed near-infrared (NIR)-driven photothermal cyclizations inside living cells. As a proof of concept, we chose an intramolecular cyclization that is based on the nucleophilic attack of a pyridine onto an electrophilic carbon, a process that requires high activation energies and is typically achieved in bulk solution by heating at ∼90 °C. The core–shell nanoreactor (NR) has been designed to include a gold nanostar core, which is embedded within a metal–organic framework (MOF) based on a polymer-stabilized zeolitic imidazole framework-8 (ZIF-8). Once accumulated inside living cells, the MOF-based cloak of NRs allows an efficient diffusion of reactants into the plasmonic chamber, where they undergo the transformation upon near-IR illumination. The photothermal-driven reaction enables the intracellular generation of cyclic fluorescent products that can be tracked using fluorescence microscopy. The strategy may find different type of applications, such as for the spatio-temporal activation of prodrugsThe authors thank the financial support of the MCIN/AEI (PID2020-119206RB-I00, PID2019-108624RB-I00, CTQ2017-84767-P, RYC-2017-23457, RYC-2019-028238-I, RTI2018-093813-J-I00), the Xunta de Galicia (ED431F 2017/02, 2021-CP054, ED431C-2021/25, Centro Singular de Investigación de Galicia Accreditation 2019−2022, and ED431G 2019/03), the European Union (European Regional Development Fund − ERDF; H2020-MSCA-IF grant agreement no. 749667; H2020-MSCA-ITN grant agreement no. 860942; H2020-FET-Open grant agreement No. 899612; and INTERREG V-A Spain−Portugal, project 0624_2IQBIONEURO_6_E), and the European Research Council (starting grant no. 950421, advanced grant no. 340055). The support of the orfeo-cinqa network (CTQ2016-81797-REDC) is also kindly acknowledgedS

Influence of renal dysfunction on the differential behaviour of procalcitonin for the diagnosis of postoperative infection in cardiac surgery

Producción CientíficaBackground: procalcitonin is a valuable marker in the diagnosis of bacterial infections; however, the impairment of renal function can influence its diagnostic precision. The objective of this study is to evaluate the differential behaviour of procalcitonin, as well as its usefulness in the diagnosis of postoperative pulmonary infection after cardiac surgery, depending on the presence or absence of impaired renal function. Materials and methods: A total of 805 adult patients undergoing cardiac surgery with extracorporeal circulation (CBP) were prospectively recruited, comparing the behaviour of biomarkers between the groups with and without postoperative pneumonia and according to the presence or absence of renal dysfunction. Results: Pulmonary infection was diagnosed in 42 patients (5.21%). In total, 228 patients (28.32%) presented postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, even in the presence of renal dysfunction. The optimal procalcitonin threshold differed markedly in patients with renal dysfunction compared to patients without renal dysfunction (1 vs. 0.78 ng/mL p < 0.05). The diagnostic accuracy of procalcitonin increased significantly when the procalcitonin threshold was adapted to renal function. Conclusions: Procalcitonin is an accurate marker of postoperative infection in cardiac surgery, even in the presence of renal dysfunction. Renal function is an important determinant of procalcitonin levels and, therefore, its diagnostic thresholds must be adapted in the presence of renal dysfunction.Instituto de Salud Carlos III - (grant COV20/00491, PI18/01238, CIBERINFEC CB21/13/00051)Junta de Castilla y León - (grant VA321P18, GRS 1922/A/19, GRS 2057/A/19)Junta de Castilla y León, Consejería de Educación - (grant VA256P20)Fundación Ramón Areces - (grant CIVP19A5953)Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER)/Fondo Social Europeo - (grant CM20/00138

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation

Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant number COV20/1144 (MPY224/20) to AF-R/MJ-S). The study was also funded by CIBER - Consorcio Centro de Investigación Biomédica en Red - (CB 2021; CB21/13/00044), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea - NextGenerationEU. AF-R and MJ-S are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP14CIII/00010 to AFR and CP17CIII/00007 to MJ-S). Universidad Alfonso X el Sabio, grant number 1.013.005S

Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?

Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality. Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals. Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis. Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might "paradoxically" imply a higher risk of progression to severe disease and COVID-19-related mortality.This study was supported by grants from Instituto de Salud Carlos III [ISCIII; Grant Number COV20/1144 (MPY224/20) to AF-R/MJ-S]. AF-R, MJ-S, and MR are Miguel Servet researchers supported and funded by ISCIII (Grant Numbers: CP14CIII/00010 to AF-R, CP17CIII/00007 to MJ-S, and CP19CIII/00002 to MR).S

La Santiago es una poesía 2.0

PublishedEl libro La Santiago es una poesía 2.0 corresponde al esfuerzo hecho por estudiantes de la Universidad Santiago de Cali, centrado en mantener el espíritu vivo del arte poético. Nuestra alma mater se dio a la tarea de crear la figura de un profesor de poesía, con la premisa punzante de saber que en la educación superior, no existen asignaturas, cursos o créditos de poesía en los planes de estudio. Al comienzo se cuestionó su posibilidad o no. Consideramos que sí, y el debate inició con la siguiente pregunta: ¿qué es un profesor de poesía

Effect of sex in systemic psoriasis therapy: Differences in prescription, effectiveness and safety in the BIOBADADERM prospective cohort

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be pre-scribed biologics. There were no differences between men and women in effectiveness of therapy, measur-ed in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.The BIOBADADERM project is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which receives financial support from the Spanish Medicines and Health Products Agency (Agencia Española de Medicamentos y Productos Sanitarios) and from pharmaceutical companies (Abbott/Abbvie, Pfizer, MSD, Novartis, Lilly, Janssen and Almirall)

Study of Leading Hadrons in Gluon and Quark Fragmentation

The study of quark jets in e+e- reactions at LEP has demonstrated that the hadronisation process is reproduced well by the Lund string model. However, our understanding of gluon fragmentation is less complete. In this study enriched quark and gluon jet samples of different purities are selected in three-jet events from hadronic decays of the Z collected by the DELPHI experiment in the LEP runs during 1994 and 1995. The leading systems of the two kinds of jets are defined by requiring a rapidity gap and their sum of charges is studied. An excess of leading systems with total charge zero is found for gluon jets in all cases, when compared to Monte Carlo Simulations with JETSET (with and without Bose-Einstein correlations included) and ARIADNE. The corresponding leading systems of quark jets do not exhibit such an excess. The influence of the gap size and of the gluon purity on the effect is studied and a concentration of the excess of neutral leading systems at low invariant masses (<~ 2 GeV/c^2) is observed, indicating that gluon jets might have an additional hitherto undetected fragmentation mode via a two-gluon system. This could be an indication of a possible production of gluonic states as predicted by QCD.Comment: 19 pages, 6 figures, Accepted by Phys. Lett.

Hacia una gestión alternativa: elementos estructurantes, aproximaciones a la ciudad de Medellín y sus contextos territoriales

En la introducción se formulan los elementos conceptuales orientadores del proceso investigativo; la planeación y la participación, la planeación y la territorialidad, y la percepción de la territorialidad. El capitulo uno presenta los desarrollos del tema relativo a la planeación y el territorio en la ciudad de Medellín y el Área Metropolitana. Este capitulo contiene: El reconocimiento a la problemática; los enfoques y concepciones; sus elementos relacionantes; y la dimensión territorial para la planeación, la participación y el control. capitulo dos hace referencia a los usos, percepciones y significaciones del territorio. Partiendo de las consideraciones metodológicas del trabajo desarrollado, se aborda la problemática del territorio y la territorialidad y del crecimiento territorial urbano en Medellín. El capitulo tres inicia con algunas consideraciones metodológicas y luego desarrolla una serie de aproximaciones a la coyuntura en la ciudad de Medellín, enfatizando en el crecimiento, el presupuesto de la ciudad y la coyuntura. El capitulo cuatro contiene las conclusiones del proceso investigativo organizado según corresponda a los capítulos anteriormente mencionados. Este capítulo de conclusiones termina con la necesidad de formular una estrategia pedagógica de formación y capacitación de recursos humanos para la autogestión del hábitat urbano, particularmente en la ciudad de Medellín y el Área Metropolitana