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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 13 (1988), S. 1043-1048 
    ISSN: 1573-6903
    Keywords: Brain Mitochondria ; calcium ; ischemia ; protein phosphorylation ; pyruvate dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An impairment of mitochondrial functions as a result of Ca-loading may be one of the significant events that lead to neuronal death after an ischemic insult. To assess the metabolic consequences of excess Ca on brain mitochondria, pyruvate oxidation was studied in isolated cerebrocortical mitochondria loaded with Ca in vitro. The flux of pyruvate dehydrogenase complex (PDHC) ([1-14C]pyruvate decarboxylation) was inhibited as the mitochondria accumulated excess Ca under the conditions tested: the inhibition in state 3 (i.e., in the presence of added ADP) was greater than in state 4 (i.e., in the absence of added adenine nucleotides). In state 4, the inhibition of the PDHC flux was accompanied by a similar reduction of the in situ activity of PDHC, indicating a change in PDHC phosphorylation. In state 3, the inhibition of the PDHC flux was greater than the corresponding decrease of the in situ PDHC activity. Thus, mechanisms other than the phosphorylation of PDHC might also contribute to the inhibition of pyruvate oxidation. Measurement of PDHC enzymatic activity in vitro indicated that PDHC, similar to α-ketoglutarate dehydrogenase complex, was inhibited by millimolar levels of Ca. This observation suggests that PDHC may also be inhibited non-covalently in Ca-loaded mitochondria in a manner similar to that of α-ketoglutarate dehydrogenase complex.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2022-07-19
    Description: Biological tissues achieve a wide range of properties and function, however with limited components. The organization of these constituent parts is a decisive factor in the impressive properties of biological materials, with tissues often exhibiting complex arrangements of hard and soft materials. The “tessellated” cartilage of the endoskeleton of sharks and rays, for example, is a natural composite of mineralized polygonal tiles (tesserae), collagen fiber bundles, and unmineralized cartilage, resulting in a material that is both flexible and strong, with optimal stiffness. The properties of the materials and the tiling geometry are vital to the growth and mechanics of the system, but had not been investigated due to the technical challenges involved. We use high-resolution materials characterization techniques (qBEI, µCT) to show that tesserae exhibit great variability in mineral density, supporting theories of accretive growth mechanisms. We present a developmental series of tesserae and outline the development of unique structural features that appear to function in load bearing and energy dissipation, with some structural features far exceeding cortical bone’s mineral content and tissue stiffness. To examine interactions among tesserae, we developed an advanced tiling-recognition-algorithm to semi-automatically detect and isolate individual tiles in microCT scans of tesseral mats. The method allows quantification of shape variation across a wide area, allowing localization of regions of high/low reinforcement or flexibility in the skeleton. The combination of our material characterization and visualization techniques allows the first quantitative 3d description of anatomy and material properties of tesserae and the organization of tesseral networks in elasmobranch mineralized cartilage, providing insight into form-function relationships of the repeating tiled pattern. We aim to combine detailed knowledge of intra-tesseral morphology and mineralization to model the relationships of tesseral shapes and skeletal surface curvature, to understand fundamental tiling laws important for complex, mechanically loaded 3d objects.
    Language: English
    Type: poster , doc-type:Other
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  • 3
    Publication Date: 2023-03-20
    Description: Grasping, in both biological and engineered mechanisms, can be highly sensitive to the gripper and object morphology, as well as perception and motion planning. Here we circumvent the need for feedback or precise planning by using an array of fluidically-actuated slender hollow elastomeric filaments to actively entangle with objects that vary in geometric and topological complexity. The resulting stochastic interactions enable a unique soft and conformable grasping strategy across a range of target objects that vary in size, weight, and shape. We experimentally evaluate the grasping performance of our strategy, and use a computational framework for the collective mechanics of flexible filaments in contact with complex objects to explain our findings. Overall, our study highlights how active collective entanglement of a filament array via an uncontrolled, spatially distributed scheme provides new options for soft, adaptable grasping.
    Language: English
    Type: article , doc-type:article
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  • 4
    Publication Date: 2023-04-26
    Description: The remarkably complex skeletal systems of the sea stars (Echinodermata, Asteroidea), consisting of hundreds to thousands of individual elements (ossicles), have intrigued investigators for more than 150 years. While the general features and structural diversity of isolated asteroid ossicles have been well documented in the literature, the task of mapping the spatial organization of these constituent skeletal elements in a whole-animal context represents an incredibly laborious process, and as such, has remained largely unexplored. To address this unmet need, particularly in the context of understanding structure-function relationships in these complex skeletal systems, we present an integrated approach that combines micro-computed tomography, semi-automated ossicle segmentation, data visualization tools, and the production of additively manufactured tangible models to reveal biologically relevant structural data that can be rapidly analyzed in an intuitive manner. In the present study, we demonstrate this high-throughput workflow by segmenting and analyzing entire skeletal systems of the giant knobby star, Pisaster giganteus, at four different stages of growth. The in-depth analysis, presented herein, provides a fundamental understanding of the three-dimensional skeletal architecture of the sea star body wall, the process of skeletal maturation during growth, and the relationship between skeletal organization and morphological characteristics of individual ossicles. The widespread implementation of this approach for investigating other species, subspecies, and growth series has the potential to fundamentally improve our understanding of asteroid skeletal architecture and biodiversity in relation to mobility, feeding habits, and environmental specialization in this fascinating group of echinoderms.
    Language: English
    Type: article , doc-type:article
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In basic solutions, pyruvate enolizes and reacts (through its 3-carbon) with the 4-carbon of the nicotinamide ring of NAD+, yielding an NAD-pyruvate adduct in which the nicotinamide ring is in the reduced form. This adduct is a strong inhibitor of lactate dehydrogenase, presumably because it binds simultaneously to the NADH and pyruvate sites. The potency of the inhibition, however, is muted by the adduct's tendency to cyclize to a lactam. We prepared solutions of the pyruvate adduct of NAD+ and of NAD+ analogues in which the —C(O)NH2 of NAD+ was replaced with C(S)NH2, −C(O)CH3, and −C(O)H. Of the four, only the last analogue, 3-[4-(reduced 3-pyridine aldehyde-adenine dinucleotide)]-pyruvate (RAP) cannot cyclize and it was found to be the most potent inhibitor of beef heart and rat brain lactate dehydrogenases. The inhibitor binds very tightly to the NADH site (Ki∼ 1 nM for the A form). Even at high concentrations (20 μM), RAP had little or no effect on rat brain glyceraldehyde-3-phosphate, pyruvate, α-ketoglutarate, isocitrate, soluble and mitochondrial malate, and glutamate dehydrogenases. The glycolytic enzymes, hexokinase and phosphofructokinase, were similarly unaffected. RAP strongly inhibited lactate production from glucose in rat brain extracts but was less effective in inhibiting lactate production from glucose in synaptosomes.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 47 (1986), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract The substrate and cofactor requirements and some kinetic properties of the α-ketoglutarate dehydrogenase complex (KGDHC; EC 1.2.4.2, EC 2.3.1.61, and EC 1.6.4.3) in purified rat brain mitochondria were studied. Brain mitochondrial KGDHC showed absolute requirement for α-ketoglutarate, CoA and NAD, and only partial requirement for added thiamine pyrophosphate, but no requirement for Mg2+ under the assay conditions employed in this study. The pH optimum was between 7.2 and 7.4, but, at pH values below 7.0 or above 7.8, KGDHC activity decreased markedly. KGDHC activity in various brain regions followed the rank order: cerebral cortex 〉 cerebellum ≧ midbrain 〉 striatum = hippocampus 〉 hypothalamus 〉 pons and medulla 〉 olfactory bulb. Significant inhibition of brain mitochondrial KGDHC was noted at pathological concentrations of ammonia (0.2–2 mM). However, the purified bovine heart KGDHC and KGDHC activity in isolated rat heart mitochondria were much less sensitive to inhibition. At 5 mM both β-methylene-D,L-aspartate and D,L-vinylglycine (inhibitors of cerebral glucose oxidation) inhibited the purified heart but not the brain mitochondrial enzyme complex. At approximately 10 μM, calcium slightly stimulated (by 10–15%) the brain mitochondrial KGDHC.At concentrations above 100 μM, calcium (IC50= 1 mM) inhibited both brain mitochondrial and purified heart KGDHC. The present results suggest that some of the kinetic properties of the rat brain mitochondrial KGDHC differ from those of the purified bovine heart and rat heart mitochondrial enzyme complexes. They also suggest that the inhibition of KGDHC by ammonia and the consequent effect on the citric acid cycle fluxes may be of pathophysiological and/or pathogenetic importance in hyperammonemia and in diseases (e.g., hepatic encephalopathy, inborn errors of urea metabolism, Reye's syndrome) where hyperammonemia is a consistent feature. Brain accumulation of calcium occurs in a number of pathological conditions. Therefore, it is possible that such a calcium accumulation may have a deleterious effect on KGDHC activity.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The relation between the activation (phosphorylation) state of pyruvate dehydrogenase complex (PDHC;EC 1.2.4.1, EC 2.3.1.12, and EC 1.6.4.3) and the rate of pyruvate oxidation has been examined in isolated, metabolically active, and tightly coupled mitochondria from rat cerebral cortex. With pyruvate and malate as the substrates, the activation state of PDHC decreased on addition of ADP, while the rates of oxygen uptake and 14CO2 formation from [I-14C]pyruvate increased. The lack of correlation between the activation state of PDHC and rate of pyruvate oxidation was seen in media containing 5, 30, or 100 mM KCl. Both the activation state of PDHC and pyruvate oxidation increased, however, when KCl was increased from 5 to 100 mM. Although the PDHC is inactivated by an ATP-dependent kinase (EC 2.7.1.99), direct measurement of ATP and ADP failed to show a consistent relationship between the activation state of PDHC and either ATP levels or ATP/ADP ratios. Comparison of the activation state of PDHC in uncoupled or oligomycin-treated mitochondria also failed to correlate PDHC activation state to adenine nucleotides. In brain mitochondria, unlike those from other tissues, the activation state of PDHC does not seem to be related clearly to the rate of pyruvate oxidation, or to the mitochondrial adenylate energy charge.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of medicinal chemistry 28 (1985), S. 1371-1375 
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of medicinal chemistry 30 (1987), S. 716-719 
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of medicinal chemistry 32 (1989), S. 151-160 
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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