Energy efficient walking with central pattern generators: from passive dynamic walking to biologically inspired control

Like human walking, passive dynamic walking—i.e. walking down a slope with no actuation except gravity—is energy efficient by exploiting the natural dynamics. In the animal world, neural oscillators termed central pattern generators (CPGs) provide the basic rhythm for muscular activity in locomotion. We present a CPG model, which automatically tunes into the resonance frequency of the passive dynamics of a bipedal walker, i.e. the CPG model exhibits resonance tuning behavior. Each leg is coupled to its own CPG, controlling the hip moment of force. Resonance tuning above the endogenous frequency of the CPG—i.e. the CPG’s eigenfrequency—is achieved by feedback of both limb angles to their corresponding CPG, while integration of the limb angles provides resonance tuning at and below the endogenous frequency of the CPG. Feedback of the angular velocity of both limbs to their corresponding CPG compensates for the time delay in the loop coupling each limb to its CPG. The resonance tuning behavior of the CPG model allows the gait velocity to be controlled by a single parameter, while retaining the energy efficiency of passive dynamic walking.     

Molecular basis of protective effect by crocetin on survival and liver tissue damage following hemorrhagic shock

Hemorrhagic shock (HS) causes reduction of cellular energy stores, as measured by levels of ATP and ADP. Furthermore, energy depletion may cause mitochondrial damage, which in turn leads to cell death by apoptosis. The hypothesis of the present study is that by enhancing the recovery of cellular ATP and ADP and mitochondrial damage can be reduced, and the extent of apoptosis minimized. Crocetin, a carotenoid compound, appears to enhance the diffusion of oxygen in aqueous solution, and hence may improve energy stores both to the cell and within it. HS was produced in Sprague–Dawley rats by withdrawing blood from the carotid cannula until a mean arterial pressure of 35–40 mm Hg was reached, and then maintained by further withdrawals of blood for 30 and 60 min. Crocetin was administered 2–4 mg/kg in resuscitation fluid through venus cannula and the animals survived for 24–48 h after HS. Experiments designed to promote tissue reconstitution of ATP using crocetin indicate that these approaches are successful in increasing ATP post-hemorrhage and survival. Crocetin treatment also inhibited cellular damage as indicated by increase of Bcl-2 following decrease in cytosolic cytochrome c and caspase-3 after resuscitation. The prolonged energy deficit seen after hemorrhagic shock can produce late damage and rapid restoration of ATP levels to baseline can reduce apoptosis. In conclusions, crocetin can minimize the cellular damage as evidenced by apoptosis and increased the survival of rats. (Mol Cell Biochem 278: 139–146, 2005)     

Coenzyme Q10 and its putative role in the ageing process

Summary A phenomenon associated with the aging process is a general age-dependent decline in cellular bioenergetic capacity that varies from tissue to tissue and even from cell to cell within the same tissue. This variation eventually forms a tissue bioenergy mosaic. Recent evidence by our group suggests that the accumulation of mitochondrial DNA mutations, in conjunction with a concurrent decrease in full-length mtDNA in tissues such as skeletal and cardiac muscle, strongly correlates with decreased mitochondrial function and accounts for the bioenergy mosaic. Evidence is also presented suggesting that amelioration with coenzyme Q₁₀ may restore some of the age-associated decline in bioenergy function, in effect providing the potential for a “redox therapy”. Coenzyme Q is a naturally occurring material that is present in the membranes of all animal cells. Its primary function is to act as an electron carrier in the mitochondrial electron transport chain enabling the energy from substrates such as fats and sugars (in the form of reducing equivalents) to be ultimately captured in the form of ATP, which in turn may be utilised as a source of cellular bioenergy. Coenzyme Q₁₀ has no known toxic effects and has been used in a limited number of animal studies and human clinical trials; however, the mechanism of action of coenzyme Q₁₀ remains unclear. A series of experiments by this group aimed at determining the efficacy of coenzyme Q₁₀ treatment on ameliorating the bioenergy capacity at the organ and cellular level will also be reviewed.     

Multifactorial nature of high frequency of mitochondrial DNA mutations in somatic mammalian cells

The high frequency of mitochondrial DNA (mtDNA) mutations in somatic mammalian cells, which is more than two orders of magnitude higher than the mutation frequency of nuclear DNA (nDNA), significantly correlates with development of a variety of mitochondrial diseases (neurodegenerative diseases, cardiomyopathies, type II diabetes mellitus, cancer, etc.). A direct cause—consequence relationship has been established between mtDNA mutations and aging phenotypes in mammals. However, the unclear nature of the high frequency of mtDNA mutations requires a comprehensive consideration of factors that contribute to this phenomenon: oxidative stress, features of structural organization and repair of the mitochondrial genome, ribonucleotide reductase activity, replication errors, mutations of nuclear genes encoding mitochondrial proteins.     

Glutamate and Parkinson’s disease

Altered glutamatergic neurotransmission and neuronal metabolic dysfunction appear to be central to the pathophysiology of Parkinson’s disease (PD). The substantia nigra pars compacta—the area where the primary pathological lesion is located—is particularly exposed to oxidative stress and toxic and metabolic insults. A reduced capacity to cope with metabolic demands, possibly related to impaired mitochondrial function, may render nigral neurons highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism. In this way, glutamate may participate in the pathogenesis of PD. Degeneration of dopamine nigral neurons is followed by striatal dopaminergic denervation, which causes a cascade of functional modifications in the activity of basal ganglia nuclei. As an excitatory neurotransmitter, glutamate plays a pivotal role in normal basal ganglia circuitry. With nigrostriatal dopaminergic depletion, the glutamatergic projections from subthalamic nucleus to the basal ganglia output nuclei become overactive and there are regulatory changes in glutamate receptors in these regions. There is also evidence of increased glutamatergic activity in the striatum. In animal models, blockade of glutamate receptors ameliorates the motor manifestations of PD. Therefore, it appears that abnormal patterns of glutamatergic neurotransmission are important in the symptoms of PD. The involvement of the glutamatergic system in the pathogenesis and symptomatology of PD provides potential new targets for therapeutic intervention in this neuro-degenerative disorder.     

线粒体功能障碍与孤独症

孤独症谱系障碍（ASDs）患儿中约有5%伴有线粒体功能紊乱.线粒体功能紊乱会损害对能量高度依赖的生理进程,如神经发育和神经可塑性,从而导致孤独症.本文综述了孤独症个体中线粒体过量的活性氧（reactive oxygen species,ROS）产生及其抗氧化系统减弱、呼吸链复合物异常、线粒体基因突变及与线粒体功能相关的基因组DNA编码的蛋白质异常等方面的研究,旨在阐述线粒体系统多方面的紊乱在孤独症个体中均有所体现,希望能够对孤独症的发病机制和治疗提供帮助.     

Mitochondrial haplogroups associated with Japanese Alzheimer’s patients

The relationships between Japanese Alzheimer’s disease (AD) patients and their mitochondrial single nucleotide polymorphism (mtSNP) frequencies at individual mtDNA positions of the entire mitochondrial genome are described using the radial basis function (RBF) network and the modified method. Japanese AD patients are associated with the haplogroups G2a, B4c1, and N9b1. In addition, to compare mitochondrial haplogroups of the AD patients with those of other classes of Japanese people, the relationships between four classes of Japanese people (i.e., Japanese centenarians, Parkinson’s disease (PD) patients, type 2 diabetic (T2D) patients, and non-obese young males) and their mtSNPs are also described. The four classes of people are associated with following haplogroups: Japanese centenarians—M7b2, D4b2a, and B5b; Japanese PD patients—M7b2, B4e, and B5b; Japanese T2D patients—B5b, M8a1, G, D4, and F1; and Japanese healthy non-obese young males—D4g and D4b1b. The haplogroups of the AD patients are therefore different from those of the other four classes of Japanese people. As the analysis method described in this article can predict a person’s mtSNP constitution and the probabilities of becoming an AD patient, centenarian, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.     

Electrophysiological and Structural Aspects in the Frontal Cortex After the Bee (<Emphasis Type="Italic">Apis mellifera</Emphasis>) Venom Experimental Treatment

The aim of this study is to evaluate the bioelectrical and structural–functional changes in frontal cortex after the bee venom (BV) experimental treatments simulating both an acute envenomation and a subchronic BV therapy. Wistar rats were subcutaneously injected once with three different BV doses: 700 μg/kg (T₁ group), 2100 μg/kg (T₃ group), and 62 mg/kg (sublethal dose—in T_SL group), and repeated for 30 days with the lowest dose (700 μg/kg—in T_S group). BV effects were assessed by electrophysiological, histological, histochemical, and ultrastructural methods. Single BV doses produced discharges of negative and biphasic sharp waves, and epileptiform spike-wave complexes. The increasing frequency of these elements suggested a dose-dependent neuronal hyperexcitation or irritation. As compared to the lower doses, the sublethal dose was responsible for a pronounced toxic effect, confirmed by ultrastructural data in both neurons and glial cells that underwent extensive, irreversible changes, triggering the cellular death. Subchronic BV treatment in T_S group resulted in a slower frequency and increased amplitude of cortical activity suggesting neuronal loss. However, neurons were still stimulated by the last BV dose. Structural–functional data showed a reduced cellular density in frontal cortex of animals in this group, while the remaining neurons displayed both specific (stimulation of neuronal activity) and unspecific modifications (moderate alterations to necrotic phenomena). Molecular mechanisms involved in BV interactions with the nervous tissue are also discussed. We consider all these data very important for clinicians who manage patients with multiple bee stings, or who intend to set an appropriate BV therapy.     

Amino acid and energy requirements for rat hepatocytes in primary culture

Summary The amino acid and energy requirements of rat hepatocytes in suspension and early culture were investigated. Among a number of potential energy substrates tested, pyruvate (20 mM) was found to be most effective in stimulating hepatocytic protein synthesis. Amino acids stimulated protein synthesis both as energy substrates and as protein precursors. An amino acid mixture was designed to provide maximal inhibition of protein degradation as well as maximal stimulation of protein synthesis. In a defined medium containing amino acids at these concentrations, and supplemented with glucocorticoid hormone and insulin, hepatocytes could be maintained—on a collagen substratum—for at least a week without any significant net loss of cells or cellular protein. The work was supported by grants from The Norwegian Cancer Society and from The Norwegian Council for Science and the Humanities. An erratum to this article is available at .     

Consciousness is Cheap, Even if Symbols are Expensive; Metabolism and the Brain’s Dark Energy

Use of symbols, the key to the biosemiotics field as to many others, required bigger brains which implied a promissory note for greater energy consumption; symbols are obviously expensive. A score years before the current estimate of 18–20% for the human brain’s metabolic demand on the organism, it was known that neural tissue is metabolically dear. This paper first discusses two evolutionary responses to this demand, on both of which there is some consensus. The first, assigning care of altricial infants with burgeoning brains (and in human infants the metabolic demand peaks at 65% of the total) to “allomothers” is not unique to humans. The second, using relatively small neurons as primates do, risks misfires past a certain minimal value. Moreover, in apparent paradox, there is an increasing consensus that large “Von Economo” neurons are critical for communication. This paper’s main contribution is the discussion of two further evolutionary tricks. The first is the use of self-similarity in the cortex, both in structure and process, to allow the cortex readily—and in energetic terms, parsimoniously—to shift between states in a high-dimensional space. This leads to discussion of the kind of formalism appropriate to model these shifts, a formalism which—it is tentatively suggested—may do double duty for the modeling of symbolic thought. The second trick is the superimposition on the background “white noise” of neural firing of EEG-detected waves like gamma. The paper describes a method, using the Hilbert transform, of calculating the dips in energy consumption as the brain is transitioned by gamma waves. It is hypothesized that consciousness may be a spandrel, the incidental result of a neurodynamic imperative that the brain enter a maximally sensitive (in sensory terms) “zero power” state a few times a second. If that is the case, then there are obvious benefits for health in meditation, which can be viewed as a state of consciousness extended over time by limiting afferent stimuli.     

High-sensitivity express immunochromatographic method for detection of plant infection by tobacco mosaic virus

A highly sensitive express immunochromatography method for molecular diagnosis of plant virus infections was elaborated on the example of a model object — tobacco mosaic virus (TMV). The analysis time does not exceed 5 min, and the lower limit of TMV detection in non-clarified leaf extract (2–4 ng/ml) is comparable with the sensitivity of the enzyme-linked immunosorbent assay of the virus. A single measurement requires 0.1–0.2 ml tested solution (extract from 10–20 mg of leaf material). The sensitivity of TMV determination in the leaf tissue extract was increased by more than one order of magnitude using signal enhancement by silver and is 0.1 ng/ml. In this case, analysis time did not exceed 25 min. The simplicity of this method makes it especially convenient in express diagnosis of numerous analyzed specimens. The prototype of a diagnostic kit for serial analyses of plant viral infections both in laboratory and field conditions was elaborated.     

Tumor necrosis factor alpha inhibits oxidative phosphorylation through tyrosine phosphorylation at subunit I of cytochrome c oxidase

Mitochondrial oxidative phosphorylation provides most cellular energy. As part of this process, cytochrome c oxidase (CcO) pumps protons across the inner mitochondrial membrane, contributing to the generation of the mitochondrial membrane potential, which is used by ATP synthase to produce ATP. During acute inflammation, as in sepsis, aerobic metabolism appears to malfunction and switches to glycolytic energy production. The pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) has been shown to play a central role in inflammation. We hypothesized that TNFalpha-triggered cell signaling targets CcO, which is a central enzyme of the aerobic energy metabolism and can be regulated through phosphorylation. Using total bovine and murine hepatocyte homogenates TNFalpha treatment led to an approximately 60% reduction in CcO activity. In contrast, there was no direct effect of TNFalpha on CcO activity using isolated mitochondria and purified CcO, indicating that a TNFalpha-triggered intracellular signaling cascade mediates CcO inhibition. CcO isolated after TNFalpha treatment showed tyrosine phosphorylation on CcO catalytic subunit I and was approximately 50 and 70% inhibited at high cytochrome c concentrations in the presence of allosteric activator ADP and inhibitor ATP, respectively. CcO phosphorylation occurs on tyrosine 304 as demonstrated with a phosphoepitope-specific antibody. Furthermore, the mitochondrial membrane potential was decreased in H2.35 cells in response to TNFalpha. Concomitantly, cellular ATP was more than 35 and 64% reduced in murine hepatocytes and H2.35 cells. We postulate that an important contributor in TNFalpha-mediated pathologies, such as sepsis, is energy paucity, which parallels the poor tissue oxygen extraction and utilization found in such patients.     

Influence of periodic field with constant and slowly changing frequency on movement of DNA kink

The movement of a kink in homogeneous polynucleotide chains of DNA under the influence of three kinds of external periodic field—with constant, growing, and decreasing frequencies is investigated in the work. Dependences of speed and coordinate of the kink on time have been found with the help of McLaughlin and Scott energy method. Phase trajectories of the kink have been constructed. It has been shown that in the case of external action with constant frequency, the kink aspires to a limit cycle; in the case of an external field with increasing frequency it tends to a stationary state corresponding to a special point of stable focus type; in the case of an external field with decreasing frequency, the kink transfers from one stationary state (unstable focus) to another (stable focus). The obtained results show the possibility of governing the kink movement by slowly changing the frequency.     

Importance of ROS and antioxidant system during the beneficial interactions of mitochondrial metabolism with photosynthetic carbon assimilation

The present study suggests the importance of reactive oxygen species (ROS) and antioxidant metabolites as biochemical signals during the beneficial interactions of mitochondrial metabolism with photosynthetic carbon assimilation at saturating light and optimal CO₂. Changes in steady-state photosynthesis of pea mesophyll protoplasts monitored in the presence of antimycin A [AA, inhibitor of cytochrome oxidase (COX) pathway] and salicylhydroxamic acid [SHAM, inhibitor of alternative oxidase (AOX) pathway] were correlated with total cellular ROS and its scavenging system. Along with superoxide dismutase (SOD) and catalase (CAT), responses of enzymatic components—ascorbate peroxidase (APX), monodehydroascorbate reductase (MDAR), glutathione reductase (GR) and non-enzymatic redox components of ascorbate–glutathione (Asc–GSH) cycle, which play a significant role in scavenging cellular ROS, were examined in the presence of mitochondrial inhibitors. Both AA and SHAM caused marked reduction in photosynthetic carbon assimilation with concomitant rise in total cellular ROS. Restriction of electron transport through COX or AOX pathway had differential effect on ROS generating (SOD), ROS scavenging (CAT and APX) and antioxidant (Asc and GSH) regenerating (MDAR and GR) enzymes. Further, restriction of mitochondrial electron transport decreased redox ratios of both Asc and GSH. However, while decrease in redox ratio of Asc was more prominent in the presence of SHAM in light compared with dark, decrease in redox ratio of GSH was similar in both dark and light. These results suggest that the maintenance of cellular ROS at optimal levels is a prerequisite to sustain high photosynthetic rates which in turn is regulated by respiratory capacities of COX and AOX pathways.     

Erythropoietin ameliorates the reduced migration of human fibroblasts during in vitro hypoxia

Erythropoietin promotes the formation of granulation tissue when administered to soft tissue wounds and it was shown to be most effective under tissue hypoxia. However, the action of erythropoietin on the cellular level is not well understood. In order to get a better insight into these processes, an in vitro wound healing assay was applied. Two main players of soft tissue healing—fibroblasts and microvascular endothelial cells—were used as mono- and co-cultures, subsequently inflicting in vitro wounds. Cell migration, proliferation, the differentiation of fibroblasts to myofibroblasts, and the release of vascular endothelial cell growth factor A and angiogenin were quantified in response to hypoxia and erythropoietin (5 IU/ml). Erythropoietin supplementation did neither affect proliferation nor migration of endothelial cells and fibroblasts under normoxia. Under hypoxia, the reduced fibroblast migration was ameliorated by erythropoietin. This effect coincided with an attenuated release of vascular endothelial growth factor A, whereas angiogenin release was unaffected by erythropoietin. The in vitro model applied in this study may represent an adequate approximation to certain aspects of the in vivo status of soft tissue regeneration and the results might serve to interpret the in vivo efficiency of erythropoietin at the cellular level: Erythropoietin has different impacts on the cells in normoxia and hypoxia. Its positive influence on fibroblast migration during hypoxia seems to support the strategies of applying erythropoietin in those chronic wounds, which exhibit fibroblastic dysfunction although good vascularisation is present.     

Genetic analysis of short term callus culture and morphogenesis in pearl millet,Pennisetum glaucum

Genetic analysis of five in vitro characters was made through a 5 × 5 diallel analysis using callus derived from immature inflorescence segments of pearl millet (Pennisetum glaucum). The characters studied were: — volume of total callus, — frequency of embryogenic calli, — embryogenic callus volume, — growth rate in terms of increase in fresh weight, and — frequency of regeneration. High heritability values and heterosis were noticed for all these characters except for E callus frequency. Additive gene action was predominant for callus growth rate and frequency of regeneration. Of the five inbreds, IP 1346 (= P5) was found to be the best genetic background for embryogenic callus volume, embryogenic growth rate and frequency of regeneration. This revised version was published online in June 2006 with corrections to the Cover Date.     

Ultrastructure of spermatozoa and spermiogenesis inSpirula spirula (L.): systematic importance and comparison with other cephalopods

Spermatozoa and spermiogenesis in the deep-water cephalopodSpirula sprirula (L.) are examined using transmission electron microscopy. Mature spermatozoa (taken from spermatophores) are elongate cells 115–120 μm long, composed of a conical acrosomal vesicle, cylindrical nucleus (6.8–7 μm long), flagellum and a loose mitochondrial sleeve — the latter concealing the proximal 6–8 μm of the flagellum. The acrosomal vesicle is 2.8 μm long with fibro-granular contents and an electron-lucent apical zone. Subacrosomal material, organized as closely packed granules, fills a basal invagination of the acrosomal vesicle. In early spermatids the flagellum is derived from a triplet substructure centriole positioned close to the developing nuclear invagination. As flagellum formation proceeds, the acrosomal vesicle (produced evidently through Golgi secretion) attaches to the condensing nucleus. Spermatids are connected by cytoplasmic bridges throughout their development, and exhibit a perinuclear sheath of microtubules from the onset of the fibrous stage of nuclear condensation (mid-, late spermatids). In mid-spermatids, mitochondria collect posterior to the nucleus and subsequently are packed into a cylindrical extension of the plasma membrane to form the periflagellar mitochondrial sleeve. These features of spermiogenesis and mature spermatozoa ofSpirula clearly associate the Spirulidae with the Sepiida, Teuthida and Sepiolida — particularly with the latter order. However, pending results of a thorough review of coleoid sperm morphology, the Spirulidae are here included in their own order — Spirulida (of Reitner & Engeser, 1982) — rather than in either the Sepiida or Sepiolida.     

Population size at the time of mitochondrial eve

This study takes a fresh but simple approach to a controversial subject. A computer simulation is used to investigate the relation between the age of our most recent mitochondrial DNA ancestor (often called “mitochondrial Eve”) and the number of her contemporaries. The simulation follows a female population through 16,000 generations, allowing it to fluctuate at random, although guided by a growth rate of .02% per generation. At each generation an account is kept of the number of viable female lineages, that is, the number of original females who retain at least one female descendent. Simple statistical methods are applied to the results of thousands of such runs, and a correspondence is suggested — in tabular, functional, and graphical form — between the various ages commonly proposed for “mitochondrial Eve” and the likely size of the population at these times. In addition, several specific assertions are made about maximum and minimum populations in the past hundreds of thousands of years. This simulation does not presume to solve the age problem, nor to remove it from the ultimate authority of genetic research. Rather it provides a different tool with which to investigate the matter.     

Influence of mitochondrial DNA level on cellular energy metabolism: implications for mitochondrial diseases

The total amount of cellular mitochondrial DNA (mtDNA) varies widely and seems to be related to the nature and metabolic state of tissues and cells in culture. It is not known, however, whether this variation has any significance in vivo, and to which extent it regulates energy production. To better understand the importance of the cellular mtDNA level, we studied the influence of a gradual reduction of mtDNA copy number on oxidative phosphorylation in two models: (a) a control human cell line treated with different concentrations of 2′, 3′-dideoxycytidine, a nucleoside analogue that inhibits mtDNA replication by interfering with mitochondrial DNA polymerase γ, and (b) a cell line derived from a patient presenting mtDNA depletion. The two models were used to construct biochemical and phenotypic threshold curves. Our results show that oxidative phosphorylation activities are under a tight control by the amount of mtDNA in the cell, and that the full complement of mtDNA molecules are necessary to maintain a normal energy production level.     

Down-regulated energy metabolism genes associated with mitochondria oxidative phosphorylation and fatty acid metabolism in viral cardiomyopathy mouse heart

The majority of experimental and clinical studies indicates that the hypertrophied and failing myocardium are characterized by changes in energy and substrate metabolism that attributed to failing heart changes at the genomic level, in fact, heart failure is caused by various diseases, their energy metabolism and substrate are in different genetic variations, then the potential significance of the molecular mechanisms for the aetiology of heart failure is necessary to be evaluated. Persistent viral infection (especially coxsackievirus group B3) of the myocardium in viral myocarditis and viral dilated cardiomyopathy has never been neglected by experts. This study aimed to explore the role and regulatory mechanism of the altered gene expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism in viral dilated cardiomyopathy. cDNA Microarray technology was used to evaluate the expression of >35,852 genes in a mice model of viral dilated cardiomyopathy. In total 1385 highly different genes expression, we analyzed 33 altered genes expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism and further selected real-time-PCR for quantity one of regulatory mechanisms for energy including fatty acid metabolism—the UCP2 and assayed cytochrome C oxidase activity by Spectrophotometer to explore mitochondrial oxidative phosphorylation function. We found obviously different expression of 33 energy metabolism genes associated with mitochondria oxidative phosphorylation, fatty acid metabolism in cardiomyopathy mouse heart, the regulatory gene for energy metabolism: UCP2 was down-regulated and cytochrome C oxidase activity was decreased. Genes involved in both fatty acid metabolism and mitochondrial oxidative phosphorylation were down-regulated, mitochondrial uncoupling proteins (UCP2) expression did not increase but decrease which might be a kind of adaptive protection response to regulate energy metabolism for ATP produce.