The Synaptotagmin-1 C2B Domain Is a Key Regulator in the Stabilization of the Fusion Pore

Fusion pores serve as an effective mechanism to connect intracellular organelles and release vesicle contents during exocytosis. A complex lipid rearrangement takes place as membranes approximate, bend, fuse, and establish a traversing water channel to define the fusion pore, linking initially isolated chambers. Thermodynamically, the process is unfavorable and thought to be mediated by specialized proteins. In this work, we have developed a reaction coordinate to induce fusion pores from initially flat and parallel lipid bilayers and we have used it to describe the effects of the synaptotagmin-1 C2B domain during the process. We have obtained free-energy profiles of the whole lipid reorganization in biologically realistic membranes, going from planar and parallel bilayers through stalk hemifusion to water channel formation. Our results point to a lysine-rich polybasic region on synaptotagmin-1 C2B as the key to lipid reorganization control through the formation of phosphatidylinositol bisphosphate clusters that stabilize the fusion pore.Fil: Caparotta, Marcelo Rubén. Universidad Nacional de Cuyo; ArgentinaFil: Tomes, Claudia Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Producción musical de un himno para la Institución Educativa Rufino Cuervo del municipio de Chocontá.

El presente proyecto de grado se centra en la realización de una producción musical, donde se realizó un himno para la Institución Educativa Departamental Rufino Cuervo ubicada en el municipio de Chocontá departamento de Cundinamarca Colombia. Para la realización de la producción del himno se tuvo en cuenta los diferentes mecanismos de ordenamiento y planificación los cuales sirvieron de base para tener una idea clara de lo que se deseaba lograr y así implementar los conocimientos tecnológicos de producción de audio en las diferentes etapas de una producción musical. Debimos conocer el objetivo principal del proyecto, como la problemática que presentaba la institución educativa Rufino cuervo, pues en pocas palabras, esta institución no contaba con un himno sonoro, pues el himno estaba en partitura y requería la utilización con un grupo orquestal o interpretes para realizar la grabación del mismo y así aplicar los procesos que intervienen en una producción musical. (Edición, mezcla y masterización). Ahora bien, para la producción musical del himno, se hizo una pertinente investigación de las tres etapas más importantes que influyen en una producción musical como lo es: la pre producción, producción y post producción; Por consiguiente, se necesitó de la utilización de aplicaciones tecnológicas (Software) o estaciones de trabajo DAW. Además, de fijar ciertos conceptos básicos que se utilizan cuando se trabaja en un entorno de audio digital. Adicionalmente, se hizo necesario la utilización de los equipos que se requieren en un estudio para llevar a cabo los procesos antes mencionados. Finalmente, una vez realizadas las etapas de la producción musical se consiguió un producto sonoro de calidad que resolvió la problemática que se presentaba en la Institución Educativa Departamental Rufino Cuervo. Pues una vez se obtuvo el himno se dio a conocer por la audiencia como insignia para la institución y que además el proyecto servirá para investigaciones futuras.The present project of degree centers in the accomplishment of a musical production, where a hymn was realized for the Rufino Cuervo Departmental Educational Institution located in the municipality of Chocontá department of Cundinamarca Colombia. To carry out the production of the anthem, the different ordering and planning mechanisms were taken into account, which served as a basis to have a clear idea of ​​what was wanted to be achieved and thus implement the technological knowledge of audio production in the different stages of a musical production We should know the main objective of the project, as the problem presented by the Rufino Cuervo educational institution, because in a few words, this institution did not have a sound anthem, because the anthem was in score and required the use with an orchestral group or interpreters to perform the recording of it and thus apply the processes involved in a musical production. (Editing, mixing and mastering). Now, for the musical production of the anthem, a pertinent investigation was made of the three most important stages that influence a musical production as it is: pre production, production and post production; Consequently, it was necessary to use technological applications (Software) or DAW workstations. Also, to fix certain basic concepts that are used when working in a digital audio environment. Additionally, it became necessary to use the equipment that is required in a study to carry out the aforementioned processes. Finally, once the stages of the musical production were completed, a quality sound product was obtained that solved the problem that was presented in the Rufino Cuervo Departmental Educational Institution. For once the anthem was obtained, it was announced by the audience as a badge for the institution and that the project will also serve for future research

Efecto del calentamiento sobre el rendimiento motor en escolares. Una revisión sistemática.

Comunicación oralIntroducción. El impacto de los diferentes tipos de protocolo de calentamiento en el rendimiento de los niños es claramente una cuestión sin resolver que aún no se ha investigado satisfactoriamente. En consecuencia, el propósito de esta revisión fue analizar la literatura actual sobre el tema. Material y métodos. El primer paso fue realizar una búsqueda en PROSPERO con la palabra clave warm up. Posteriormente, se realizaron búsquedas en cinco bases de datos bibliográficas electrónicas hasta el 10 de abril de 2021: Web of Science (todas las bases de datos), Scopus, SportDiscus, PubMed y Google Scholar. Resultados. Se incluyeron en los análisis finales seis estudios con un total de 138 participantes. En cuanto a las cualidades físicas que se evaluaron, 4 de los estudios evaluaron la fuerza a través del salto vertical, 3 evaluaron la velocidad de carrera, uno evaluó la resistencia anaeróbica (30 segundos) con un cicloergómetro y otro evaluó la flexibilidad mediante el Sit & Reach. Conclusiones. La práctica de un calentamiento dinámico o específico antes del entrenamiento parece mejorar el rendimiento de velocidad y fuerza en comparación con la ausencia de calentamiento en niños en edad escolar. Sin embargo, es necesario seguir investigando los efectos del calentamiento en la resistencia y la flexibilidad en niños en edad escolar.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Usefulness of myeloid dendritic cells in cellular in vitro assays for evaluating immediate hypersensitivity reactions to betalactams.

Introduction Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) with an important role detecting, processing, and presenting antigens to T cells. The analysis of maturation after in vitro stimulation with the culprit drug, and their ability to trigger the proliferation of specific T cell populations in patients with immediate drug hypersensitivity reactions (IDHRs) could serve to prove the sensitization to a drug. Most approaches used monocyte-derived DCs (moDCs), although their sensitivity is not optimal. The different nature of moDCs and myeloid DCs (mDCs), main DC population involved during the in vivo development of IDHRs, could influence the sensitivity of these in vitro tests. Therefore, we evaluated the effect of two betalactams (BLs), amoxicillin (AX) and clavulanic acid (CLV) in moDCs and mDCs from selective-allergic patients (AP) to each BL, as well as to assess their capacity to stimulate different T cell populations. Methods mDCs and moDCs were obtained from 14 AX-AP, 14 CLV-AP and 10 Healthy controls (HC). After stimulating with the culprit BL, maturation and their capacity to stimulate different T cell populations was assessed by flow cytometry. Results Higher maturation was observed in both AX- and CLV-AP compared with HC when using BL-stimulated-mDCs, whereas with moDCs, only higher was observed in AX-AP, but not in CLV-AP. The % of positive maturation cases was higher with mDCs than moDCs, with higher % with AX compared to CLV. The most relevant T cell population proliferative response was obtained in CD4+Th2 cells, reaching to 67% of positivity when using mDCs, followed by 50% with the traditional LTT, and only of 22% with moDCs from AX-AP. The specificity was higher than 80% in all cases. Conclusions mDCs from selective AP efficiently recognised the culprit drug and triggered the proliferation of T-cells, mainly those with a Th2 cytokine pattern, although these responses depended on the drug.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Las actividades lúdicas y el estado emocional en estudiantes de educación básica superior

Within physical activity, an effective tool in pedagogy is the use of recreational activities, being a didactic strategy that generates great benefits for the development of the physical culture subject; focusing on three fundamental aspects in students such as: physical, social, and psychological capacities. Objective: In the present investigation the association of the variable’s recreational activities and the emotional state of the students is analyzed. Methodology: A quantitative approach was used, with a basic purpose of non-experimental design, with a descriptive scope with a method of the hypothetical-deductive theoretical level. In the data collection, the DASS 21 and the survey were used to evaluate each variable in a study sample of 59 students. Results: They were determined using the chi-square statistical test with bilateral asymptotic differentiation at a level of P ≤ 0.05, resulting in a significant statistical value in the level of association between the use of recreational activities and the emotional state of the students. Conclusion: It is concluded that the use of playful activities acts as a protective factor to prevent negative moods from developing in students.Dentro de la actividad física una herramienta eficaz en la pedagogía es el uso de actividades lúdicas, siendo una estrategia didáctica que genera grandes beneficios al desarrollo de la asignatura de cultura física; incidiendo en tres aspectos fundamentales en los estudiantes como son: las capacidades físicas, sociales y psicológicas. Objetivo: En la presente investigación se analizo la asociación de las variables actividades lúdicas y el estado emocional de los estudiantes. Metodología: Se utilizo un enfoque cuantitativo, con una finalidad básica de diseño no experimental, con un alcance descriptivo con un método del nivel teórico hipotético-deductivo. En la recolección de datos se utilizo el DASS 21 y la encuesta para evaluar cada variable en una muestra de estudio de 59 estudiantes. Resultados: Fueron determinados mediante la prueba estadística chi cuadrado con diferenciación asintótica bilateral en un nivel de P ≤ 0.05 dando como consecuencia un valor estadístico significativo en el nivel de asociación del uso de actividades lúdicas y el estado emocional de los estudiantes. Conclusión: Se concluye que el uso de actividades lúdicas actúa como factor protector para evitar que se desarrollen estados de ánimo negativos en los estudiantes

Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers CD63 and CD203c in a prospective study

Amoxicillin (AX) combined or not with clavulanic acid (CLV) is frequently involved in IgE-mediated reactions. Drug provocation test (DPT) is considered as the gold standard for diagnosis, although contraindicated in high-risk patients. Basophil activation test (BAT) can help diagnose immediate reactions to beta-lactams, although controversy exists regarding the best activation marker. We have performed a real-life study in a prospective cohort to analyze the real value of BAT as diagnostic tool and the best activation marker, CD63 and CD203c, for the evaluation of immediate reactions to these drugs.We thank Claudia Corazza for her invaluable English language support; Verónica Prados and Ana Molina for their help in technical support in flow cytometry methods. This work has been supported by Institute of Health “Carlos III” (ISCIII) of the Ministry of Economy and Competitiveness (MINECO; grants co-funded by European Regional Development Fund: PI15/01206, PI17/01237, PI18/00095, PI20/01734, RETICS ARADYAL RD16/0006/0001, and RICORS REI (RD21/0002/0008); Andalusian Regional Ministry of Health (grants PI-0241-2016, PE-0172-2018, and PI-0127-2020); Spanish Ministerio de Ciencia e Innovación Proyectos de I + D + I «Programación Conjunta Internacional», EuroNanoMed 2019 (PCI2019-111825-2)). AA holds a Senior Postdoctoral Contract (RH-0099-2020) with the Andalusian Regional Ministry of Health (cofunded by European Social Fund (ESF): "Andalucía se mueve con Europa". GB holds a “Juan Rodes” contract (JR18/00054) by ISCIII of MINECO (cofounded by ESF). ID holds a clinical research stabilization contract by Andalusian Regional Ministry of Health (RB-0001-2022). ML holds a “Rio Hortega” contract (CM20/00210) by ISCIII of MINECO (cofounded by ESF). CF holds a Marie Skłodowska-Curie Individual Fellowship by the European Union's Horizon 2020 research and innovation program (agreement n° PI-0241-2016101027955). CM holds a “Nicolas Monardes” research contract by Andalusian Regional Ministry of Health (RC-0004-2021). // Funding for open access charge: Universidad de Málaga / CBUA

El Dominio C2B de la Sinaptotagmina-1 es un Regulador Clave de la Estabilización de los Poros de Fusión

Los poros de fusión sirven como un efectivo mecanismo para conectar organelas intracelulares y liberar contenido vesicular durante la exocitosis. Un complejo reordenamiento lipídico tiene lugar a medida que las membranas se aproximan, curvan, fusionan, y establecen un canal de agua para definir el poro de fusión, vinculando compartimentos inicialmente aislados. En este trabajo, hemos desarrollado una coordenada de reacción para inducir poros de fusión a partir de bicapas lipídicas inicialmente planas y paralelas y la hemos usado para describir los efectos del dominio C2B de la sinaptotagmina-1 durante este proceso. Hemos obtenido perfiles de energía libre del proceso completo. Nuestros resultados señalan a la región polibásica rica en lisina del dominio C2B de la sinaptotagmina-1 como la clave para controlar la reorganización lipídica a partir de la formación de grupos de fosfatidilinositol bifosfato, los cuales estabilizan el poro de fusión.Fil: Caparotta, Marcelo Rubén. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Tomes, Claudia Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ingeniería; ArgentinaVIII Congreso de Matemática Aplicada, Computacional e IndustrialLa PlataArgentinaUniversidad Nacional de La PlataAsociación Argentina de Matemática Aplicada Computacional e Industria

Previsão para auditoria interna baseada em risco

The internal audit in essence is a control of the controls established by the organization, which must be essentially preventive, which implies that the organization has clearly identified the risks that may affect the fulfillment of the objectives. In order to carry out their work, the internal auditor must fully know the entity that audits, in order to be able to foresee the risks that may arise, determine if the controls counteract said risks, to carry out their evaluation, that is, they must look prospectively at the company, plan your work, apply the international framework for the practice of internal auditing and perform high quality work.La auditoría interna realiza un control a los controles establecidos por la organización, los cuales deben ser en esencia preventivos, lo que implica que se tengan claramente identificados los riesgos que pueden afectar el cumplimiento de los objetivos. Para la realización de su trabajo el auditor interno debe conocer ampliamente la entidad que audita, para poder prever los riesgos que se puedan presentar, determinar si los controles si contrarrestan dichos riesgos, para realizar su evaluación, es decir, debe mirar prospectivamente a la empresa, planear su trabajo, aplicar el marco internacional para la práctica de la auditoría interna y realizar un trabajo de alta calidad.A auditoria interna monitora os controles estabelecidos pela organização, os quais devem ser essencialmente preventivos, o que significa que os riscos que podem afetar a realização dos objetivos devem ser claramente identificados. Para realizar seu trabalho, o auditor interno deve ter um amplo conhecimento da entidade que está auditando, para poder prever os riscos que possam surgir, para determinar se os controles neutralizam esses riscos, para realizar sua avaliação, ou seja, deve olhar prospectivamente para a empresa, planejar seu trabalho, aplicar a estrutura internacional para a prática da auditoria interna e realizar um trabalho de alta qualidade

Latin America and the Caribbean code against cancer: Developing evidence-based recommendations to reduce the risk of cancer in Latin America and the Caribbean

Latin America and the Caribbean (LAC) has a population of more than 650 million inhabitants (8.5% of the world population),1 with a cancer incidence of more than 1.4 million new patients and more than 670,000 deaths in 2018. These figures will increase by 78% by 2040 to more than 2.5 million people diagnosed with cancer each year, and these patients will require medical attention, care, and support. However, many of these new cancer diagnoses can be prevented through public policies, supportive environments, and lifestyles that promote health and prevent cancer (Fig 1).2 In the LAC region, there are many organizations and institutions providing information on cancer prevention, including national cancer institutes, cancer societies and foundations, and public health agencies. Nevertheless, the information is frequently confusing, overwhelming, or even contradictory. The scientific source and credibility, as well as the primary message, differ according to the type of organization that provides the information (eg, patient organization, scientific or governmental institution).For the LAC region, a coalition of institutions and international organizations has joined forces to adapt the European Code to the cancer risks and situation in the LAC region. This involves collecting, analyzing, and evaluating the scientific evidence to support suitable cancer prevention recommendations to the LAC context. A multistakeholder participation in the project is a key approach to ensure that all players will be owners of the Code and true promoters. The coalition is composed of the Pan-American Health Organization (PAHO; also part of the WHO) and the IARC as leading international organizations; a Scientific Committee of senior researchers and distinguished leaders in cancer prevention from LAC; and an Advocacy Group representing important organizations in LAC, including the Latin American and Caribbean Society of Medical Oncology, the Network of Latin-American Cancer Institutes, the Healthy Caribbean Coalition, and the Association of Latin American Leagues Against Cancer.Fil: Cazap, Eduardo. Sociedad Latinoamericana y del Caribe de Oncología Médica; ArgentinaFil: de Almeida, Liz Maria. Instituto Nacional de Câncer Brasil Jose Alencar Gomes da Silva; BrasilFil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Patricia J.. Universidad Cayetano Heredia; PerúFil: Garmendia, María Luisa. Universidad de Chile; ChileFil: Gil, Enrique. South America Pan-American Health Organization; PerúFil: Hassel, Trevor. Healthy Caribbean Coalition; BarbadosFil: Mayorga, Rubén. South America Pan-American Health Organization; PerúFil: Mohar, Alejandro. Universidad Nacional Autónoma de México; MéxicoFil: Murillo, Raúl. Centro Javeriano de Oncología; ColombiaFil: Owen, Gabriel O.. Healthy Caribbean Coalition; BarbadosFil: Paonessa, Diego. Liga Argentina de Lucha contra el Cancer; ArgentinaFil: Santamaría, Julio. Centro Hemato Oncológico Panamá; PanamáFil: Tortolero Luna, Guillermo. Universidad de Puerto Rico; Puerto RicoFil: Zoss, Walter. Red de Institutos e Instituciones Nacionales de Cancer; BrasilFil: Herrero, Rolando. Agencia Internacional para la Investigación del Cáncer; FranciaFil: Luciani, Silvana. Pan-American Health Organization; Estados UnidosFil: Schüz, Joachim. Agencia Internacional para la Investigación del Cáncer; FranciaFil: Espina, Carolina. Agencia Internacional para la Investigación del Cáncer; Franci

Operative Mechanism of Hole-Assisted Negative Charge Motion in Ground States of Radical-Anion Molecular Wires

Charge transfer/transport in molecular wires over varying distances is a subject of great interest. The feasible transport mechanisms have been generally accounted for on the basis of tunneling or superexchange charge transfer operating over small distances which progressively gives way to hopping transport over larger distances. The underlying molecular sequential steps that likely take place during hopping and the operative mechanism occurring at inter mediate distances have received much less attention given the difficulty in assessing detailed molecular-level information. We describe here the operating mechanisms for unimolecular electron transfer/transport in the ground state of radical-anion mixed-valence derivatives occurring between their terminal perchlorotriphenylmethyl/ide groups through thiophene−vinylene oligomers that act as conjugated wires of increasing length up to 53 Å. The unique finding here is that the net transport of the electron in the larger molecular wires is initiated by an electron− hole dissociation intermediated by hole delocalization (conformationally assisted and thermally dependent) forming transient mobile polaronic states in the bridge that terminate by an electron−hole recombination at the other wire extreme. On the contrary, for the shorter radical-anions our results suggest that a flickering resonance mechanism which is intermediate between hopping and superexchange is the operative one. We support these mechanistic interpretations by applying the pertinent biased kinetic models of the charge/spin exchange rates determined by electron paramagnetic resonance and by molecular structural level information obtained from UV−vis and Raman spectroscopies and by quantum chemical modeling