Microtubule Regulation of Mitochondrial Bioenergetics in Cardiac and Skeletal Muscles

A novel model of mitochondrial bioenergetic regulation has been proposed whereby microtubules may directly influence the permeability of ADP into the mitochondria to stimulate the production of ATP. Specifically, tubulin, the structural unit of microtubules, physically inserts into the voltage gated dependent anion channel (VDAC) embedded in planar lipid membranes which was speculated to prevent ADP/ATP cycling. Such regulation could be profound given ADP/ATP cycling kinetics determine the rate of oxidative phosphorylation and reactive oxygen species (ROS) emission key mitochondrial functions that are critical to muscle cells. VDAC is also believed to be central to the formation of the mitochondrial permeability transition pore (mPTP) which releases pro-apoptotic factors that trigger cell death. To date, a direct measure of a tubulin-VDAC interaction has yet to be demonstrated in cardiac and skeletal muscles, particularly in relation to mitochondrial bioenergetics. The primary objective of this thesis was to explore the tubulin-VDAC model of mitochondrial bioenergetic regulation in cardiac and skeletal muscles. This was achieved by employing pharmacological and genetic models of microtubule disorganization in an attempt to alter tubulin-VDAC interactions in relation to mitochondrial dysfunction. The results demonstrate that in-vitro paclitaxel treatment in extensor digitorum longus (EDL) muscle increases both - and II-tubulin-VDAC2 interaction while impairing some mitochondrial functions in partial support of the tubulin-VDAC model. The remaining data challenges this model. Specifically, cardiac muscle demonstrated a host of bioenergetic impairments in-vitro independent of a change in tubulin-VDAC interaction, while in-vivo treatment with paclitaxel, and vinblastine resulted in creatine independent mitochondrial impairments. Second, in-vivo paclitaxel administration surprisingly increased hind-limb torque and II-tubulin-VDAC2 interaction in soleus while eliciting minor inhibitions of ADP-dependent bioenergetic functions. In contrast, in-vivo administration of vinblastine caused muscle weakness and mitochondrial dysfunction in both soleus and white gastrocnemius, but did not change tubulin-VDAC2 interactions. Lastly, EDL muscles isolated from D2.mdx mouse model of disorganized microtubules and muscle weakness did not show altered tubulin-VDAC interactions despite the presence of mitochondrial dysfunctions. Overall, this thesis is the first to identify a direct - and II-tubulin interaction with VDAC2 in cardiac and skeletal muscle. While the data presented are not always in support of this model it raises new questions that challenges the regulation of this physical interaction in ADP diffusion regulation

El proyecto lúdico pedagógico y el taller como formas de trabajo que promueven las competencias en el grado transición

Esta propuesta pretende impulsar el desarrollo de estrategias didácticas que promuevan ambientes estimulantes en educación inicial y que, además, ayude a desarrollar, no solo conocimientos, sino también valores, actitudes, competencias y habilidades, incorporando el proyecto lúdico pedagógico y el taller como herramientas fundamentales, atendiendo a un problema central: la desmotivación y actitudes negativas en la experiencia escolar ocasionada por la rigurosidad, monotonía y control de los procesos de enseñanza aprendizaje. Por lo tanto, el objetivo de esta propuesta es diseñar y ejecutar un proyecto lúdico pedagógico y el taller con el fin de promover las competencias en los niños y niñas del grado transición. Para ello, el estudio se apoya en el paradigma naturalista, que permite comprender la conducta humana a través del descubrimiento de los significados sociales, incorporando, además, los elementos de la investigación – acción como método de construcción activa de la solución. Así mismo, Se utilizó la observación, el diario de campo y formatos basado en el Núcleo Temático Integrador (NTI) y taller, como instrumentos para Planificar las actividades y recolectar los datos necesarios en el diseño. Los principales hallazgos indican que las formas de trabajo como el proyecto lúdico y el taller fomentan la participación, motivación e interés, no solo de los niños y niñas, sino también de los docentes y las familias. Finalmente, Se concluye que el proyecto lúdico y el taller son herramientas que, de manera organizada, fomenta el trabajo manual, intelectual y colaborativo que conecta la teoría con la práctica

PROMOÇÃO DA SAÚDE NA EDUCAÇÃO INFANTIL: PRÁTICAS DE EDUCADORES NA REDE PÚBLICA

This study had as general objectives comprehenda how educators promote health in a Municipal Center for Early Childhood Education (MCECE) of the municipal network in the interior of Bahia. Data collection was performed using a semi-structured interview. For data analysis, content analysis was chosen, where 3 (three) categories emerged: Health and health promotion: meanings attributed by teachers; Health promotion practices at school; The pandemic and the new health care in school contexts. In this way, it is concluded that the pedagogical practices are aimed at promoting health directly linked to child care, emphasizing the need for family participation, describing the techniques for producing this care. Health and care must be part of the routine of schools, talking about health is necessary in different contexts, it is necessary to change the idea that education is associated only with school, and health only with health services, overcoming the isolated practices through integrated work.Este estudio tuvo como objetivo comprender cómo los educadores promueven la salud en un Centro Municipal de Educación Infantil (CMEI) de la red municipal del interior de Bahía. La recolección de datos se realizó mediante una entrevista semiestructurada. Para el análisis de los datos se optó por el análisis de contenido, donde surgieron 3 (tres) categorías: Salud y promoción de la salud: significados atribuidos por los docentes; Prácticas de promoción de la salud en la escuela; La pandemia y la nueva atención a la salud en contextos escolares. Así, se concluye que las prácticas pedagógicas están dirigidas a la promoción de la salud directamente vinculada al cuidado del niño, enfatizando la necesidad de la participación de la familia, describiendo las técnicas para producir ese cuidado. La salud y el cuidado deben ser parte del cotidiano de las escuelas, hablar de salud es necesario en diferentes contextos, es necesario cambiar la idea de que la educación se asocia solo a la escuela, y la salud solo a los servicios de salud, superando las prácticas aisladas a través del trabajo integrado.Esse estudo teve como objetivo geral compreender como os educadores promovem a saúde em um Centro Municipal de Educação Infantil (CMEI) da rede municipal no interior da Bahia. A coleta de dados foi realizada a partir da entrevista semi-estruturada. Para análise de dados, optou-se pela análise de conteúdo, onde emergiram 3 (três) categorias: Saúde e promoção da saúde: significados atribuídos pelos professores; Práticas de promoção à saúde na escola; A pandemia e os novos cuidados de saúde nos contextos escolares. Desta forma, conclui-se que as práticas pedagógicas estão voltadas para promoção da saúde ligadas diretamente ao cuidado com à criança, enfatizando a necessidade de participação da família, descrevendo as técnicas para produção desse cuidado. A saúde e o cuidado devem fazer parte da rotina das escolas, falar de saúde se faz necessário em diversos contextos, precisa-se modificar a ideia de que a educação está associada apenas à escola, e a saúde somente aos serviços de saúde, superando as práticas isoladas por meio de um trabalho integrado

Extracellular matrix protein-1 as a mediator of inflammation-induced fibrosis after myocardial infarction

Irreversible fibrosis is a hallmark of myocardial infarction (MI) and heart failure. Extracellular matrix protein-1 (ECM-1) is up-regulated in these hearts, localized to fibrotic, inflammatory, and perivascular areas. ECM-1 originates predominantly from fibroblasts, macrophages, and pericytes/vascular cells in uninjured human and mouse hearts, and from M1 and M2 macrophages and myofibroblasts after MI. ECM-1 stimulates fibroblast-to-myofibroblast transition, up-regulates key fibrotic and inflammatory pathways, and inhibits cardiac fibroblast migration. ECM-1 binds HuCFb cell surface receptor LRP1, and LRP1 inhibition blocks ECM-1 from stimulating fibroblast-to-myofibroblast transition, confirming a novel ECM-1-LRP1 fibrotic signaling axis. ECM-1 may represent a novel mechanism facilitating inflammation-fibrosis crosstalk

New molecular methods to assess biodiversity. Potentials and pitfalls of DNA metabarcoding: a workshop report

This report presents the outcome of the joint work of PhD students and senior researchers working with DNA-based biodiversity assessment approaches with the goal to facilitate others the access to definitions and explanations about novel DNA-based methods. The work was performed during a PhD course (SLU PNS0169) at the Swedish University of Agricultural Sciences (SLU) in Uppsala, Sweden. The course was co-organized by the EU COST research network DNAqua-Net and the SLU Research Schools Focus on Soils and Water (FoSW) and Ecology - basics and applications. DNAqua-Net (COST Action CA15219, 2016-2020) is a network connecting researchers, water managers, politicians and other stakeholders with the aim to develop new genetic tools for bioassessment of aquatic ecosystems in Europe and beyond. The PhD course offered a comprehensive overview of the paradigm shift from traditional morphology-based species identification to novel identification approaches based on molecular markers. We covered the use of molecular tools in both basic research and applied use with a focus on aquatic ecosystem assessment, from species collection to the use of diversity in environmental legislation. The focus of the course was on DNA (meta)barcoding and aquatic organisms. The knowledge gained was shared with the general public by creating Wikipedia pages and through this collaborative Open Access publication, co-authored by all course participants

Severe malaria in children leads to a significant impairment of transitory otoacoustic emissions--a prospective multicenter cohort study.

BACKGROUND: Severe malaria may influence inner ear function, although this possibility has not been examined prospectively. In a retrospective analysis, hearing impairment was found in 9 of 23 patients with cerebral malaria. An objective method to quickly evaluate the function of the inner ear are the otoacoustic emissions. Negative transient otoacoustic emissions are associated with a threshold shift of 20 dB and above. METHODS: This prospective multicenter study analyses otoacoustic emissions in patients with severe malaria up to the age of 10 years. In three study sites (Ghana, Gabon, Kenya) 144 patients with severe malaria and 108 control children were included. All malaria patients were treated with parental artesunate. RESULTS: In the control group, 92.6 % (n = 108, 95 % confidence interval 86.19-6.2 %) passed otoacoustic emission screening. In malaria patients, 58.5 % (n = 94, malaria vs controls p < 0.001, 95 % confidence interval 48.4-67.9 %) passed otoacoustic emission screening at the baseline measurement. The value increased to 65.2 % (n = 66, p < 0.001, 95 % confidence interval 53.1-75.5 %) at follow up 14-28 days after diagnosis of malaria. The study population was divided into severe non-cerebral malaria and severe malaria with neurological symptoms (cerebral malaria). Whereas otoacoustic emissions in severe malaria improved to a passing percentage of 72.9 % (n = 48, 95 % confidence interval 59-83.4 %) at follow-up, the patients with cerebral malaria showed a drop in the passing percentage to 33 % (n = 18) 3-7 days after diagnosis. This shows a significant impairment in the cerebral malaria group (p = 0.012 at days 3-7, 95 % confidence interval 16.3-56.3 %; p = 0.031 at day 14-28, 95 % confidence interval 24.5-66.3 %). CONCLUSION: The presented data show that 40 % of children have involvement of the inner ear early in severe malaria. In children, audiological screening after severe malaria infection is not currently recommended, but is worth investigating in larger studies

Zoneamento e inchaço urbano, um comparativo da área nobre e área periférica de Belém / Zoning and urban swelling, a comparison of the noble area and the peripheral area of Belém

É evidente que nos últimos anos houve uma intensificação no processo do crescimento urbano, ligado aos processos migratórios que ocorreram na capital paraense nos anos 90, tendo em vista isso algumas das inquietações da gestão pública estão voltadas ao processo de urbanização: inchaço urbano. Levando isso em consideração, questionou-se, como será utilizado o zoneamento para a análise e formulação de auxílio aos municípios nos quais apresentaram essa problemática. A metodologia desse trabalho teve como foco de estudo dois bairros da cidade de Belém do Pará, sendo estes Umarizal e Terra Firme, um bairro de zona nobre e outra de zona periférica, respectivamente. Utilizando-se de um questionário para coleta dos dados em campo, os dados obtidos serviram de base para a elaboração e formulação de gráficos que apresentaram resultados satisfatórios mediante a problemática exposta. Tendo por conclusão a análise através de gráficos dos dados coletados 

Psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) across cross-cultural subgroups, genders, and sexual orientations: Findings from the International Sex Survey (ISS)

© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).INTRODUCTION: Despite being a widely used screening questionnaire, there is no consensus on the most appropriate measurement model for the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, there have been limited studies on its measurement invariance across cross-cultural subgroups, genders, and sexual orientations. AIMS: The present study aimed to examine the fit of different measurement models for the AUDIT and its measurement invariance across a wide range of subgroups by country, language, gender, and sexual orientation. METHODS: Responses concerning past-year alcohol use from the participants of the cross-sectional International Sex Survey were considered (N = 62,943; M age: 32.73; SD = 12.59). Confirmatory factor analysis, as well as measurement invariance tests were performed for 21 countries, 14 languages, three genders, and four sexual-orientation subgroups that met the minimum sample size requirement for inclusion in these analyses. RESULTS: A two-factor model with factors describing 'alcohol use' (items 1-3) and 'alcohol problems' (items 4-10) showed the best model fit across countries, languages, genders, and sexual orientations. For the former two, scalar and latent mean levels of invariance were reached considering different criteria. For gender and sexual orientation, a latent mean level of invariance was reached. CONCLUSIONS: In line with the two-factor model, the calculation of separate alcohol-use and alcohol-problem scores is recommended when using the AUDIT. The high levels of measurement invariance achieved for the AUDIT support its use in cross-cultural research, capable also of meaningful comparisons among genders and sexual orientations.Peer reviewe

Psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) across cross-cultural subgroups, genders, and sexual orientations: Findings from the International Sex Survey (ISS)

Introduction. Despite being a widely used screening questionnaire, there is no consensus on the most appropriate measurement model for the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, there have been limited studies on its measurement invariance across cross-cultural subgroups, genders, and sexual orientations. Aims. The present study aimed to examine the fit of different measurement models for the AUDIT and its measurement invariance across a wide range of subgroups by country, language, gender, and sexual orientation. Methods. Responses concerning past-year alcohol use from the participants of the cross-sectional International Sex Survey were considered (N = 62,943; Mage: 32.73; SD = 12.59). Confirmatory factor analysis, as well as measurement invariance tests were performed for 21 countries, 14 languages, three genders, and four sexual-orientation subgroups that met the minimum sample size requirement for inclusion in these analyses. Results. A two-factor model with factors describing ‘alcohol use’ (items 1–3) and ‘alcohol problems’ (items 4–10) showed the best model fit across countries, languages, genders, and sexual orientations. For the former two, scalar and latent mean levels of invariance were reached considering different criteria. For gender and sexual orientation, a latent mean level of invariance was reached. Conclusions. In line with the two-factor model, the calculation of separate alcohol-use and alcohol-problem scores is recommended when using the AUDIT. The high levels of measurement invariance achieved for the AUDIT support its use in cross-cultural research, capable also of meaningful comparisons among genders and sexual orientations