BUSCADOR RECOLECTA

Additional file 6: Movie S3. Time-lapse movie of the system showing oscillations. Time-lapse movie of the system showing periodic assembly and disassembly of the actomyosin cortex (G-actin labeled in green, ACs labeled in red, Myosin labeled in red)., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 7 Figure S4. Oscillations for different levels of Myosin. Oscillations in the number of G-actin in the cortex for conditions of (A) low and (B) high concentration of Myosin in the system. The corresponding Fourier transform for each oscillation is also shown., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 8: Movie S4. Oscillations in D. Melanogaster basal follicle cells. Control conditions. Cells are stained with Lifeact-GFP., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Additional file 12 Figure S7. Scheme of the effect of Myosin over F-actin. (1), Myosin movement in parallel f-Actin. (2) F-actin sliding. (3) Tension building in the filaments. (4) Release from cortex after threshold tension is reached. After release, tension (illustrated in red) is redistributed to other F-actin in the network., Ministerio de Ciencia, Innovación y Universidades, Peer reviewed

Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed

Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency., Peer reviewed

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency., Peer reviewed

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency., Peer reviewed

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency., Peer reviewed