Low aerobic capacity in McArdle disease: A role for mitochondrial network impairment?

[Background]: McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO2peak)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. [Methods]: We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO2peak in patients (both sexes, N = 145) and healthy controls (N = 133). [Results]: Besides corroborating very poor VO2peak values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. [Conclusions]: In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses.The present study was funded by grants received from the Fondo de Investigaciones Sanitarias (FIS, PI17/02052, PI18/00139, PI19/01313, and PI20/00645) and cofunded by ‘Fondos FEDER’. Gisela Nogales-Gadea and Carmen Fiuza-Luces are supported by the Miguel Servet research contracts (ISCIII CD14/00032 and CP18/00034, respectively and cofounded by Fondos FEDER′). Research by Pedro L. Valenzuela is funded by a postdoctoral contract granted by Instituto de Salud Carlos III (Sara Borrell, CD21/00138). Monica Villarreal Salazar is supported by the Mexican National Council for Science and Technology (CONACYT)

Low aerobic capacity in McArdle disease : A role for mitochondrial network impairment?

McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO in patients (both sexes, N = 145) and healthy controls (N = 133). Besides corroborating very poor VO values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses

Near- And Sub-barrier Fusion Of The Be7+ Ni58 System

Evaporation proton yields were measured for the fusion of the radioactive proton-rich nucleus Be-7 onto a Ni-58 target at six near-barrier energies. Total fusion cross sections were deduced by using calculated proton multiplicities. The resulting fusion excitation function shows a considerable enhancement with respect to calculations for a bare potential, even for energies above the Coulomb barrier. Inelastic couplings can account for the enhancement at the highest energy. Total fusion channels nearly saturate the total reaction cross section in the measured energy region. Comparison with previous results scaled appropriately for Be-7 + (Al-27, U-238) shows good agreement

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Virtualización del Título Propio en Olivicultura y Elaiotecnia. Elaboración de Materiales

Es conocido que España es primer país productor de aceite de oliva del mundo, con un 40 % de la producción mundial y el 50 % de la producción de la Unión Europea, siendo la provincia de Jaén, con el 38,4 % de la producción española, la mayor zona productora del mundo en aceite de oliva. Sin embargo, se trata de un sector en el que la escasa profesionalización es, tal vez, su mayor debilidad.La Universidad de Jaén, consciente del importante papel que ha de jugar como Institución dinamizadora del desarrollo de su entorno, en el que el sector del olivar y del aceite de oliva tiene una enorme importancia, considera que es urgente formar titulados universitarios de grado superior que posean conocimientos integrales y solventes en olivicultura y elaiotecnia de modo que incorporados a las empresas del sector del olivar y el aceite de oliva o creando las suyas propias, lo modernicen y desarrollen, contribuyendo a dotarlo de cultura empresarial y al desarrollo socioeconómico y, por ende, al bienestar de los ciudadanos de la provincia

Stress modulation as a means to improve yeasts for lignocellulose bioconversion

The second-generation (2G) fermentation environment for lignocellulose conversion presents unique challenges to the fermentative organism that do not necessarily exist in other industrial fermentations. While extreme osmotic, heat, and nutrient starvation stresses are observed in sugar- and starch-based fermentation environments, additional pre-treatment-derived inhibitor stress, potentially exacerbated by stresses such as pH and product tolerance, exist in the 2G environment. Furthermore, in a consolidated bioprocessing (CBP) context, the organism is also challenged to secrete enzymes that may themselves lead to unfolded protein response and other stresses. This review will discuss responses of the yeast Saccharomyces cerevisiae to 2G-specific stresses and stress modulation strategies that can be followed to improve yeasts for this application. We also explore published –omics data and discuss relevant rational engineering, reverse engineering, and adaptation strategies, with the view of identifying genes or alleles that will make positive contributions to the overall robustness of 2G industrial strains

La casa en crisis: dina\u301micas financieras, concentracio\u301n del capital y el mercado inmobiliario

L'articolo introduce il numero monografico della rivista dedicato al tema della casa. L\u2019obiettivo \ue8 quello di indagare quale impatto hanno avuto dinamiche finanziarie, speculazione immobiliare e mancanza di politi- che urbane sulla citta\u300 e sulla qualita\u300 della vita della popolazione, e quali possono essere le politiche di intervento capaci di contenere gli effetti della crisi attuale

Casa e crisi : dinamiche finanziarie, concentrazione di capitali e mercato immobiliare

L\u2019obiettivo del numero monografico e\u300 quello di analizzare quale impatto hanno avuto le dinamiche finanziarie, la speculazione immobiliare e la mancanza di politiche urbane sulla citta\u300 e sulla qualita\u300 della vita della popolazione a livello mondiale, ma anche quali possono essere le politiche di intervento mirate e capaci di contenere gli effetti della crisi. Il mercato immobiliare ha avuto un ruolo centrale nella crisi economica manifestatati a partire dall\u2019autunno del 2007 negli Stati Uniti e per questo si \ue8 voluto da un lato indagare il rapporto tra i processi economici e finanziari globali ed il loro impatto sul valore del patrimonio edilizio nelle citta\u300, dall'altro provare ad identificare come le dinamiche finanziarie hanno impattato sul territorio e quali manifestazioni territoriali, urbanistiche e sociali hanno avuto