A Reaction-Diffusion Model of ROS-Induced ROS Release in a Mitochondrial Network

Loss of mitochondrial function is a fundamental determinant of cell injury and death. In heart cells under metabolic stress, we have previously described how the abrupt collapse or oscillation of the mitochondrial energy state is synchronized across the mitochondrial network by local interactions dependent upon reactive oxygen species (ROS). Here, we develop a mathematical model of ROS-induced ROS release (RIRR) based on reaction-diffusion (RD-RIRR) in one- and two-dimensional mitochondrial networks. The nodes of the RD-RIRR network are comprised of models of individual mitochondria that include a mechanism of ROS-dependent oscillation based on the interplay between ROS production, transport, and scavenging; and incorporating the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and Ca2+ handling. Local mitochondrial interaction is mediated by superoxide (O2.−) diffusion and the O2.−-dependent activation of an inner membrane anion channel (IMAC). In a 2D network composed of 500 mitochondria, model simulations reveal ΔΨm depolarization waves similar to those observed when isolated guinea pig cardiomyocytes are subjected to a localized laser-flash or antioxidant depletion. The sensitivity of the propagation rate of the depolarization wave to O2.− diffusion, production, and scavenging in the reaction-diffusion model is similar to that observed experimentally. In addition, we present novel experimental evidence, obtained in permeabilized cardiomyocytes, confirming that ΔΨm depolarization is mediated specifically by O2.−. The present work demonstrates that the observed emergent macroscopic properties of the mitochondrial network can be reproduced in a reaction-diffusion model of RIRR. Moreover, the findings have uncovered a novel aspect of the synchronization mechanism, which is that clusters of mitochondria that are oscillating can entrain mitochondria that would otherwise display stable dynamics. The work identifies the fundamental mechanisms leading from the failure of individual organelles to the whole cell, thus it has important implications for understanding cell death during the progression of heart disease

Extraction and purification of L-Asparaginase II from local isolate of Proteus vulgaris

Forty one isolates of genus Proteus were collected from 140 clinical specimens such as urine, stool, wound, burn, and ear swabs from patients of both sex. These isolates were identified to three Proteus spp. P. mirabilis, P. vulgaris and P. penneri .The ability of these bacteria to produce L-asparaginase II by using semi quantitative and quantitative methods was determined. P. vulgaris Pv.U.92 was distinguished for high level of L-asparaginase II production with specific activity 1.97 U/mg. Optimum conditions for enzyme production were determined; D medium with 0.3% of L-asparagine at pH 7.5 with temperature degree 35°C for incubation. Ultrasonication was used to destroy the P. vulgaris Pv.U.92 cells then ASNase II was extracted and purified throughout several purification steps including precipitation with (NH4)2SO4(60-80%), DEAE-cellulose ion exchanger chromatography followed by Sephacryl S-300 filtration. The specific activity was 155.6 U/ mg and the purification fold was 27.3 with 10.4% yield

Data Descriptor: High resolution, week-long, locomotion time series from Japanese quail in a home-box environment

Temporal and spatial patterns of locomotion reflect both resting periods and the movement from one place to another to satisfy physiological and behavioural needs. Locomotion is studied in diverse areas of biology such as chronobiology and physiology, as well as in biomathematics. Herein, the locomotion of 24 visually-isolated Japanese quails in their home-box environment was recorded continuously over a 6.5 days at a 0.5 s sampling rate. Three time series are presented for each bird: (1) locomotor activity, (2) distance ambulated, and (3) zone of the box where the bird is located. These high resolution, week-long, time series consisting of 1.07 × 10 6 data points represent, to our knowledge, a unique data set in animal behavior, and are publically available on FigShare. The data obtained can be used for analyzing dynamic changes of daily or several day locomotion patterns, or for comparison with existing or future data sets or mathematical models across different taxa.publishedVersionFil: Flesia, Ana Georgina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Flesia, Ana Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios de Matemática; Argentina.Fil: Guzmán, Diego A. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales, Cátedra de Química Biológica; Argentina.Fil: Guzmán, Diego A. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Fil: Guzmán, Diego A. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Ciencia y Tecnología de los Alimentos; Argentina.Fil: Pellegrini, Stefania. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales, Cátedra de Química Biológica; Argentina.Fil: Pellegrini, Stefania. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Fil: Pellegrini, Stefania. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Ciencia y Tecnología de los Alimentos; Argentina.Fil: Aon, Miguel A. Johns Hopkins University. School of Medicine; Estados Unidos de AméricaFil: Marin, Raúl H. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales, Cátedra de Química Biológica; Argentina.Fil: Marin, Raúl H. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Fil: Marin, Raúl H. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Ciencia y Tecnología de los Alimentos; Argentina.Fil: Kembro, Jackelyn M. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales, Cátedra de Química Biológica; Argentina.Fil: Kembro, Jackelyn M. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Fil: Kembro, Jackelyn M. Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba. Instituto de Ciencia y Tecnología de los Alimentos; Argentina.Fil: Guzmán, Diego A. Aarhus University. Department of Animal Science; Dinamarca

Cardiosphere-derived cells demonstrate metabolic flexibility that Is influenced by adhesion status

Adult stem cells demonstrate metabolic flexibility that is regulated by cell adhesion status. The authors demonstrate that adherent cells primarily utilize glycolysis, whereas suspended cells rely on oxidative phosphorylation for their ATP needs. Akt phosphorylation transduces adhesion-mediated regulation of energy metabolism, by regulating translocation of glucose transporters (GLUT1) to the cell membrane and thus, cellular glucose uptake and glycolysis. Cell dissociation, a pre-requisite for cell transplantation, leads to energetic stress, which is mediated by Akt dephosphorylation, downregulation of glucose uptake, and glycolysis. They designed hydrogels that promote rapid cell adhesion of encapsulated cells, Akt phosphorylation, restore glycolysis, and cellular ATP levels

Mitochondrial chaotic dynamics: Redox-energetic behavior at the edge of stability

Mitochondria serve multiple key cellular functions, including energy generation, redox balance, and regulation of apoptotic cell death, thus making a major impact on healthy and diseased states. Increasingly recognized is that biological network stability/instability can play critical roles in determining health and disease. We report for the first-time mitochondrial chaotic dynamics, characterizing the conditions leading from stability to chaos in this organelle. Using an experimentally validated computational model of mitochondrial function, we show that complex oscillatory dynamics in key metabolic variables, arising at the “edge” between fully functional and pathological behavior, sets the stage for chaos. Under these conditions, a mild, regular sinusoidal redox forcing perturbation triggers chaotic dynamics with main signature traits such as sensitivity to initial conditions, positive Lyapunov exponents, and strange attractors. At the “edge” mitochondrial chaos is exquisitely sensitive to the antioxidant capacity of matrix Mn superoxide dismutase as well as to the amplitude and frequency of the redox perturbation. These results have potential implications both for mitochondrial signaling determining health maintenance, and pathological transformation, including abnormal cardiac rhythms.publishedVersionKembro, Jackelyn Melissa. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Kembro, Jackelyn Melissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Cortassa, Sonia. National Institutes of Health. NIH · NIA Intramural Research Program; Estados Unidos.Lloyd, David. Cardiff University. School of Biosciences 1; Inglaterra.Sollot, Steven. Johns Hopkins University. Laboratory of Cardiovascular Science; Estados Unidos.Sollot, Steven. Johns Hopkins University. Laboratory of Cardiovascular Science; Estados Unidos