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排序方式: 共有158条查询结果,搜索用时 31 毫秒
1.
Dimitry M. Gorinevsky 《Biological cybernetics》1993,69(3):219-228
We propose and simulate a new paradigm for organization of motor control in fast and accurate human arm motions. We call the paradigm direct motor program learning since the control programs are learned directly without knowing or learning the dynamics of a controlled system.The idea is to approximate the dependence of the motor control programs on the vector of the task parameters rather than to use a model of the system dynamics. We apply iterative learning control and scattered data multivariate approximation techniques to achieve the goal. The advantage of the paradigm is that the control complexity depends neither on the order nor on the nonlinearity of the system dynamics.We simulate the direct motor program learning paradigm in the task of point-to-point control of fast planar human arm motions. Simulation takes into account nonlinear arm dynamics, muscle force dynamics, delay in low-level reflex feedback, time dependence of the feedback gains and coactivation of antagonist muscles. Despite highly nonlinear time-variant dynamics of the controlled system, reasonably good motion precision is obtained over a wide range of the task parameters (initial and final positions of the arm). The simulation results demonstrate that the paradigm is indeed viable and could be considered as a possible explanation for the organization of motor control of fast motions. 相似文献
2.
Justin M. Bradley Dimitry A. Svistunenko Michael T. Wilson Andrew M. Hemmings Geoffrey R. Moore Nick E. Le Brun 《The Journal of biological chemistry》2020,295(51):17602
Iron is an essential micronutrient, and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable “free” iron be tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exist, but overaccumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species. To avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage, and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review, we seek to highlight the similarities of iron homeostasis between different bacteria, while acknowledging important variations. In this way, we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron. 相似文献
3.
Dimitry N. Krementsov Tina M. Thornton Cory Teuscher Mercedes Rincon 《Molecular and cellular biology》2013,33(19):3728-3734
Multiple sclerosis (MS), the most common disabling neurologic disease of young adults, is considered a classical T cell-mediated disease and is characterized by demyelination, axonal damage, and progressive neurological dysfunction. The currently available disease-modifying therapies are limited in their efficacy, and improved understanding of new pathways contributing to disease pathogenesis could reveal additional novel therapeutic targets. The p38 mitogen-activated protein kinase (MAPK) signaling pathway is known to be triggered by stress stimuli and to contribute to inflammatory responses. Importantly, a number of recent studies have identified this signaling pathway as a central player in MS and its principal animal model, experimental allergic encephalomyelitis. Here, we review the evidence from mouse and human studies supporting the role of p38 MAPK in regulating key immunopathogenic mechanisms underlying autoimmune inflammatory disease of the central nervous system and the potential of targeting this pathway as a disease-modifying therapy in MS. 相似文献
4.
Russian Journal of Genetics - In this article, we summarize the basic concepts and techniques widely used in microsatellite studies. We describe briefly the main stages of the work and provide... 相似文献
5.
Hoffmann S Spitkovsky D Radicella JP Epe B Wiesner RJ 《Free radical biology & medicine》2004,36(6):765-773
The mitochondrial electron transport chain (ETC) is the most important source of reactive oxygen species (ROS) in mammalian cells. To assess its relevance to the endogenous generation of oxidative DNA damage in the nucleus, we have compared the background (steady-state) levels of oxidative DNA base modifications sensitive to the repair glycosylase Fpg (mostly 7,8-dihydro-8-oxoguanine) in wild-type HeLa cells and HeLa rho0 cells. The latter are depleted of mitochondrial DNA and therefore are unable to produce ROS in the ETC. Although the levels of ROS measured by flow cytometry and redox-sensitive probes in rho0 cells were only 10-15% those of wild-type cells, steady-state levels of oxidative DNA base modifications were the same as in wild-type cells. Mitochondrial generation of ROS was then stimulated in HeLa wild-type cells using inhibitors interfering with the ETC. Although mitochondrial ROS production was raised up to 6-fold, none of the substances nor their combinations induced additional oxidative base modifications in the nuclear DNA. This was also true for glutathione-depleted cells. The results indicate that the contribution of mitochondria to the endogenously generated background levels of oxidative damage in the nuclear DNA is negligible. 相似文献
6.
Yang A Sonin D Jones L Barry WH Liang BT 《American journal of physiology. Heart and circulatory physiology》2004,287(3):H1096-H1103
The P2X4 purinergic receptor (P2X4R) is a ligand-gated ion channel. Its activation by extracellular ATP results in Ca2+ influx. Transgenic cardiac overexpression of the human P2X4 receptor showed an in vitro phenotype of enhanced basal contractility. The objective here was to determine the in vivo cardiac physiological role of this receptor. Specifically, we tested the hypothesis that this receptor plays an important role in modulating heart failure progression. Transgenic cardiac overexpression of canine calsequestrin (CSQ) showed hypertrophy, heart failure, and premature death. Crossing the P2X4R mouse with the CSQ mouse more than doubled the lifespan (182 +/- 91 days for the binary CSQ/P2X4R mouse, n = 35) of the CSQ mouse (71.3 +/- 25.4 days, n = 50, P < 0.0001). The prolonged survival in the binary CSQ/P2X4R mouse was associated with an improved left ventricular weight-to-body weight ratio and a restored beta-adrenergic responsiveness. The beneficial phenotype of the binary mouse was not associated with any downregulation of the CSQ level but correlated with improved left ventricular developed pressure and +/-dP/dt. The enhanced cardiac performance was manifested in young binary animals and persisted in older animals. The increased contractility likely underlies the survival benefit from P2X4 receptor overexpression. An increased expression or activation of this receptor may represent a new approach in the therapy of heart failure. 相似文献
7.
Diversity, activity, and abundance of sulfate-reducing bacteria in saline and hypersaline soda lakes
Foti M Sorokin DY Lomans B Mussman M Zacharova EE Pimenov NV Kuenen JG Muyzer G 《Applied and environmental microbiology》2007,73(7):2093-2100
Soda lakes are naturally occurring highly alkaline and saline environments. Although the sulfur cycle is one of the most active element cycles in these lakes, little is known about the sulfate-reducing bacteria (SRB). In this study we investigated the diversity, activity, and abundance of SRB in sediment samples and enrichment cultures from a range of (hyper)saline soda lakes of the Kulunda Steppe in southeastern Siberia in Russia. For this purpose, a polyphasic approach was used, including denaturing gradient gel electrophoresis of dsr gene fragments, sulfate reduction rate measurements, serial dilutions, and quantitative real-time PCR (qPCR). Comparative sequence analysis revealed the presence of several novel clusters of SRB, mostly affiliated with members of the order Desulfovibrionales and family Desulfobacteraceae. We detected sulfate reducers and observed substantial sulfate reducing rates (between 12 and 423 micromol/dm(3) day(-1)) for most lakes, even at a salinity of 475 g/liter. Enrichments were obtained at salt saturating conditions (4 M Na(+)), using H(2) or volatile fatty acids as electron donors, and an extremely halophilic SRB, strain ASO3-1, was isolated. Furthermore, a high dsr gene copy number of 10(8) cells per ml was detected in a hypersaline lake by qPCR. Our results indicate the presence of diverse and active SRB communities in these extreme ecosystems. 相似文献
8.
9.
Human aggression/impulsivity-related traits have a complex background that is greatly influenced by genetic and non-genetic
factors. The relationship between aggression and anxiety is regulated by highly conserved brain regions including amygdala,
which controls neural circuits triggering defensive, aggressive, or avoidant behavioral models. The dysfunction of neural
circuits responsible for emotional control was shown to represent an etiological factor of violent behavior. In addition to
the amygdala, these circuits also involve the anterior cingulated cortex and regions of the prefrontal cortex. Excessive reactivity
in the amygdala coupled with inadequate prefrontal regulation serves to increase the likelihood of aggressive behavior. Developmental
alterations in prefrontal-subcortical circuitry as well as neuromodulatory and hormonal abnormality appear to play a role.
Imbalance in testosterone/serotonin and testosterone/cortisol ratios (e.g., increased testosterone levels and reduced cortisol
levels) increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control
and self-regulation. Serotonin facilitates prefrontal inhibition, and thus insufficient serotonergic activity can enhance
aggression. Genetic predisposition to aggression appears to be deeply affected by the polymorphic genetic variants of the
serotoninergic system that influences serotonin levels in the central and peripheral nervous system, biological effects of
this hormone, and rate of serotonin production, synaptic release and degradation. Among these variants, functional polymorphisms
in the monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) may be of particular importance due to the relationship
between these polymorphic variants and anatomical changes in the limbic system of aggressive people. Furthermore, functional
variants of MAOA and 5-HTT are capable of mediating the influence of environmental factors on aggression-related traits. In
this review, we consider genetic determinants of human aggression, with special emphasis on genes involved in serotonin and
dopamine metabolism and function. 相似文献
10.
Pfannkuche K Wunderlich FT Doss MX Spitkovsky D Reppel M Sachinidis A Hescheler J 《Nature protocols》2008,3(9):1510-1526
Here we describe the generation of a double-fluorescent Cre/loxP indicator system. This protocol involves (i) all cloning steps to generate the plasmid vector (3-5 months); (ii) a guide to prepare high-efficiency transformation competent E. coli; (iii) generation of double-fluorescent reporter cell lines (3-4 weeks); and (iv) the functional testing of the indicator cell lines by application of cell-permeable Cre recombinase. The indicator is designed to monitor recombination events by switching the fluorescence light from red to green. The red fluorescence, indicating the nonrecombined state, is accompanied by the expression of a resistance gene against the antibiotic blasticidin. Appearance of green fluorescence concomitantly with the activation of puromycin-acetyltransferase monitors the recombination of the indicator construct by the Cre recombinase. In summary, we have developed a plasmid vector allowing a fast, stable and straightforward generation of transgenic clones. The expression of red fluorescent protein enables the selection of positive clones upon transfection and significantly shortens the time for identification of stable clones. This feature and the option to select for recombined cells by puromycin application are advantages compared with other alternative methods. Moreover, we developed a method utilizing cell-permeable Cre protein to validate the transgenic clones. Ultimately, this powerful methodology facilitates Cre/loxP-based applications such as cell lineage tracking or monitoring of cell fusion. 相似文献