Members of the MOAG/SERF protein family have been attributed a neuropathologic significance because of their ability to enhance the proteotoxic polymerization of amyloidogenic proteins such as alpha-Synuclein (aSyn). However, the cellular function remains unknown. Here, we identify SERF1a as an RNA-organizing protein i) with no structural homology to canonical RNA-binding proteins, ii) with an RNA-chaperoning activity which favours the incorporation of RNA into nucleoli and liquid-like artificial RNAorganelles, and iii) with a high degree of conformational disorder in the RNA-bound state. We demonstrate that this type of structural fuzziness determines an undifferentiated interaction of SERF1a with aSyn and RNA. Both molecules bind to one identical, positively charged site of SERF1a by an analogous electrostatic binding mode, with similar binding affinities, and without any observable disorder-to-order transition. The absence of primary or secondary structure discriminants results in SERF1a being unable to distinguish between nucleic acid and amyloidogenic protein, leading the pro-amyloid aSyn:SERF1a interaction to prevail under conditions of cellular stress. We suggest that structural fuzziness of SERF1a accounts for an adverse gain-of-interaction which favours toxic binding to aSyn at the expense of non-toxic RNA binding, therefore promoting a functionally distorted and pathogenic process. Our results provide a direct link between structural disorder, amyloid aggregation and the malfunctioning of RNA-associated cellular processes, three hallmarks of neurodegenerative diseases.Similarly, the probe Cy5-R21(+) failed to target isolated nucleoli as a monomer (Fig. 5D) or
Introduction: Non-cardiac chest pain (NCCP) is mainly related to oesophageal disease, and in spite of being a common condition in Mexico, information regarding it is scarce. Aim: To assess the clinical characteristics and health-related quality of life of patients with NCCP of presumed oesophageal origin. Material and methods: Patients with NCCP of presumed oesophageal origin with no previous treatment were included in the study. Associated symptoms were assessed and upper gastrointestinal endoscopy and 24-hour oesophageal pH monitoring were performed to diagnose gastroesophageal reflux disease, while oesophageal manometry was used to determine oesophageal motility disorders. The SF-36 Health-Related Quality of Life (HR-QoL) questionnaire was completed and its results compared to a control group without oesophageal symptoms. Results: The study included 33 patients, of which 61% were women, and the mean age was 46.1 (± 11.6) years. Causes of NCCP were gastroesophageal reflux disease in 48%, achalasia in 34%, and functional chest pain in 18%. The average progression time for chest pain was 24 (2-240) months, with ≤3 events/week in 52% of the patients. The most frequent accompanying symptoms were: regurgitation (81%), dysphagia (72%) and heartburn (66%). Patients with NCCP show deterioration in HR-QoL compared to the control group (P = .01), regardless of chest pain aetiology. The most affected areas were general perception of health, emotional issues, and mental health sub-scale (P > 0.05). ଝ Please cite this article as: Ortiz-Garrido O, Ortiz-Olvera NX, González-Martínez M, Morán-Villota S, Vargas-López G, Dehesa-Violante M, et al. Evaluación clínica y de la calidad de vida relacionada con la salud en pacientes con dolor torácico no cardiaco. Revista de Gastroenterología de México. 2015;80:121---129. -Olvera). 2255-534X/Published by Masson Doyma México S.A. on behalf of Asociación Mexicana de Gastroenterología. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 122 O. Ortiz-Garrido et al. Conclusions: In our population, patients with NCCP show deterioration in HR-QoL regardless of the aetiology, frequency, and accompanying symptoms. Published by Masson Doyma México S.A. on behalf of Asociación Mexicana de Gastroenterología. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
PALABRAS CLAVEAcalasia; Dolor torácico funcional; Enfermedad por reflujo gastroesofágico; Dolor torácico no cardiaco; Calidad de vida Evaluación clínica y de la calidad de vida relacionada con la salud en pacientes con dolor torácico no cardiaco Resumen Introducción: El dolor torácico no cardiaco (DTNC) se relaciona principalmente con enfermedades del esófago, y aunque se considera una condición común, en México la información aún es escasa. Objetivo: Evaluar las características clínicas y la calidad de vida relacionada con salud en pacientes con DTNC de presunto origen esofágico. Material y métodos: Se incluyeron en el...
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