Amyotrophic lateral sclerosis (ALS) is a heterogeneous degenerative motor neuron disease linked to numerous genetic mutations in apparently unrelated proteins. These proteins, including SOD1, TDP-43, and FUS, are highly aggregation-prone and form a variety of intracellular inclusion bodies that are characteristic of different neuropathological subtypes of the disease. Contained within these inclusions are a variety of proteins that do not share obvious characteristics other than coaggregation. However, recent evidence from other neurodegenerative disorders suggests that diseaseaffected biochemical pathways can be characterized by the presence of proteins that are supersaturated, with cellular concentrations significantly greater than their solubilities. Here, we show that the proteins that form inclusions of mutant SOD1, TDP-43, and FUS are not merely a subset of the native interaction partners of these three proteins, which are themselves supersaturated. To explain the presence of coaggregating proteins in inclusions in the brain and spinal cord, we observe that they have an average supersaturation even greater than the average supersaturation of the native interaction partners in motor neurons, but not when scores are generated from an average of other human tissues. These results suggest that inclusion bodies in various forms of ALS result from a set of proteins that are metastable in motor neurons, and thus prone to aggregation upon a disease-related progressive collapse of protein homeostasis in this specific setting.protein aggregation | protein misfolding | protein homeostasis | supersaturation | motor neuron disease

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Protein aggregation is a pathological feature of neurodegenerative disorders. We previously demonstrated that protein inclusions in the brain are composed of supersaturated proteins, which are abundant and aggregation-prone, and form a metastable subproteome. It is not yet clear, however, whether this phenomenon is also associated with non-neuronal protein conformational disorders. To respond to this question, we analyzed proteomic datasets from biopsies of patients with genetic and acquired protein aggregate myopathy (PAM) by quantifying the changes in composition, concentration and aggregation propensity of proteins in the fibers containing inclusions and those surrounding them. We found that a metastable subproteome is present in skeletal muscle from healthy patients. The expression of this subproteome escalate as proteomic samples are taken more proximal to the pathologic inclusion, eventually exceeding its solubility limits and aggregating. While most supersaturated proteins decrease or maintain steady abundance across healthy fibers and inclusion-containing fibers, proteins within the metastable subproteome rise in abundance, suggesting that they escape regulation. Taken together, our results show in the context of a human conformational disorder that the supersaturation of a metastable subproteome underlies widespread aggregation and correlates with the histopathological state of the tissue.

Introducción: En Chile el primer caso de COVID-19 fue diagnosticado el tres de marzo del 2020 y el día dieciocho del mismo mes el presidente decreto estado de catástrofe, por lo que las clases a nivel escolar y universitario pasaron de la presencialidad a la virtualidad. El presente estudio tiene como objetivo conocer el nivel de satisfacción de las clases virtuales de los estudiantes de Educación Física. Metodología: Cuantitativa, no experimental, transversal. La muestra estuvo constituida por 542 alumnos de Educación Física de diferentes casas de estudio de Chile. Se adaptó y validó la escala Satisfacción clases online. Resultados: existen diferencias significativas comparando las asignaturas teóricas y prácticas, siendo mejor valoradas las cátedras teóricas. También se encontraron diferencias por sexo, donde los varones poseen una percepción más negativa sobre las clases virtuales y al comparar por curso, los alumnos de primer año poseen una percepción más positiva sobre las clases virtuales en relación con los cursos superiores. Conclusiones: existe una resistencia por parte de los alumnos a las clases virtuales en la Educación Física, pues, si bien se encontraron diferencias significativas entre las asignaturas teóricas y prácticas, los valores siempre estuvieron alrededor de 3 en una escala de 1 a 5. Se hacen necesarias futuras investigaciones con otras variables como actividad física, niveles de estrés y estrategias para la enseñanza de la Educación Física virtual. Abstract. Introduction: In Chile the first case of COVID-19 was diagnosed on March 3, 2020 and on the eighteenth of the same month the president decreed state of catastrophe, so that classes at school and university level went from the presence to the virtuality. The present study aims to know the level of satisfaction of the virtual classes of the students of Physical Education. Methodology: Quantitative, non experimental, transversal. The sample consisted of 542 students of Physical Education from different study houses in Chile. The Satisfaction scale online classes was adapted and validated. Results: there are significant differences comparing theoretical and practical subjects, with theoretical chairs being better valued. Differences were also found by sex, where males have a more negative perception about virtual classes and when comparing by course, freshmen have a more positive perception about virtual classes in relation to higher courses. Conclusions: there is a resistance on the part of students to virtual classes in Physical Education, because, although significant differences were found between the theoretical and practical subjects, values were always around 3 on a scale of 1 to 5. Future research with other variables such as physical activity, stress levels and strategies for the teaching of Virtual Physical Education are necessary.

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