In Vivo Tracking of Human Neural Stem Cells with 19F Magnetic Resonance Imaging

(c)The Author

Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart

<p>Abstract</p> <p>Background</p> <p>The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate.</p> <p>Results</p> <p>The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (Δ<it>G</it>_ATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of Δ<it>G</it>_ATPasein the beating heart.</p> <p>Conclusion</p> <p>The CK system stabilizes Δ<it>G</it>_ATPaseby both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.</p

NO Dioxygenase Activity in Hemoglobins Is Ubiquitous In Vitro, but Limited by Reduction In Vivo

Genomics has produced hundreds of new hemoglobin sequences with examples in nearly every living organism. Structural and biochemical characterizations of many recombinant proteins reveal reactions, like oxygen binding and NO dioxygenation, that appear general to the hemoglobin superfamily regardless of whether they are related to physiological function. Despite considerable attention to “hexacoordinate” hemoglobins, which are found in nearly every plant and animal, no clear physiological role(s) has been assigned to them in any species. One popular and relevant hypothesis for their function is protection against NO. Here we have tested a comprehensive representation of hexacoordinate hemoglobins from plants (rice hemoglobin), animals (neuroglobin and cytoglobin), and bacteria (Synechocystis hemoglobin) for their abilities to scavenge NO compared to myoglobin. Our experiments include in vitro comparisons of NO dioxygenation, ferric NO binding, NO-induced reduction, NO scavenging with an artificial reduction system, and the ability to substitute for a known NO scavenger (flavohemoglobin) in E. coli. We conclude that none of these tests reveal any distinguishing predisposition toward a role in NO scavenging for the hxHbs, but that any hemoglobin could likely serve this role in the presence of a mechanism for heme iron re-reduction. Hence, future research to test the role of Hbs in NO scavenging would benefit more from the identification of cognate reductases than from in vitro analysis of NO and O2 binding

Special issue on fluorine-19 magnetic resonance: technical solutions, research promises and frontier applications

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Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex

The cerebral cortex has the ability to adapt to altered sensory inputs. In the visual cortex, a small lesion to the retina causes the deprived cortical region to become responsive to adjacent parts of the visual field. This extensive topographic remapping is assumed to be mediated by the rewiring of intracortical connections, but the dynamics of this reorganization process remain unknown. We used repeated intrinsic signal and two-photon imaging to monitor functional and structural alterations in adult mouse visual cortex over a period of months following a retinal lesion. The rate at which dendritic spines were lost and gained increased threefold after a small retinal lesion, leading to an almost complete replacement of spines in the deafferented cortex within 2 months. Because this massive remodeling of synaptic structures did not occur when all visual input was removed, it likely reflects the activity-dependent establishment of new cortical circuits that serve the recovery of visual responses