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排序方式: 共有1626条查询结果,搜索用时 218 毫秒
51.
Christoph S. Clemen Harald Herrmann Sergei V. Strelkov Rolf Schröder 《Acta neuropathologica》2013,125(1):47-75
The intermediate filament protein desmin is an essential component of the extra-sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous framework exerts central roles in the structural and functional alignment and anchorage of myofibrils, the positioning of cell organelles and signaling events. Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked phenotypic variability. The disease onset ranges from childhood to late adulthood. The clinical course is progressive and no specific treatment is currently available for this severely disabling disease. The muscle pathology is characterized by desmin-positive protein aggregates and degenerative changes of the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a complex, multilevel issue. In addition to direct effects on the formation and maintenance of the extra-sarcomeric intermediate filament network, mutant desmin affects essential protein interactions, cell signaling cascades, mitochondrial functions, and protein quality control mechanisms. This review summarizes the currently available data on the epidemiology, clinical phenotypes, myopathology, and genetics of desminopathies. In addition, this work provides an overview on the expression, filament formation processes, biomechanical properties, post-translational modifications, interaction partners, subcellular localization, and functions of wild-type and mutant desmin as well as desmin-related cell and animal models. 相似文献
52.
Tatyana G. Pekun Valeriya V. Lemeshchenko Tamara I. Lyskova Tatyana V. Waseem Sergei V. Fedorovich 《Journal of molecular neuroscience : MN》2013,49(1):211-222
Brain ischemia is accompanied by lowering of intra- and extracellular pH. Stroke often leads to irreversible damage of synaptic transmission by unknown mechanism. We investigated an influence of lowering of pHi and pHo on free radical formation in synaptosomes. Three models of acidosis were used: (1) pHo 6.0 corresponding to pHi decrease down to 6.04; (2) pHo 7.0 corresponding to the lowering of pHi down to 6.92: (3) 1 mM amiloride corresponding to pHi decrease down to 6.65. We have shown that both types of extracellular acidification, but not intracellular acidification, increase 2′,7′-dichlorodihydrofluorescein diacetate fluorescence that reflects free radical formation. These three treatments induce the rise of the dihydroethidium fluorescence that reports synthesis of superoxide anion. However, the impact of amiloride on superoxide anion synthesis was less than that induced by moderate extracellular acidification. Superoxide anion synthesis at pHo 7.0 was almost completely eliminated by mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone. Furthermore, using fluorescent dyes JC-1 and rhodamine-123, we confirmed that pHo lowering, but not intracellular acidification, led to depolarization of intrasynaptosomal mitochondria. We have shown that pHo but not pHi lowering led to oxidative stress in neuronal presynaptic endings that might underlie the long-term irreversible changing in synaptic transmission. 相似文献
53.
Mureev S Kushnir S Kolesnikov AA Breitling R Alexandrov K 《Molecular and biochemical parasitology》2007,155(2):71-83
The trypanosomatid protozoan Leishmania tarentolae has been extensively used as a model system for studying causative agents of several tropical diseases and more recently as a host for recombinant protein production. Here we analyze the rates of partial or complete deletions of expression cassettes integrated into small ribosomal RNA and tubulin gene clusters as well as into ornithine decarboxylase gene of L. tarentolae. In approximately 60% of cases gene conversion was responsible for the deletion while in the rest of the cases deletion occurred within the expression cassette. We used this observation to design constitutive and inducible expression vectors that could be stably integrated into the genome and subsequently depleted of the antibiotic resistance genes using thymidine kinase or bleomycin resistance genes as negative selection markers. This enabled us to obtain L. tarentolae strains containing constitutive or inducible markerless expression cassettes. Analysis of the markerless strains demonstrated that although stability varied among clones some were stable for as many as 200 generations. We expect that this approach will be useful for the construction of strains carrying multiple expression cassettes for analysis of trypanosomatid pathogenicity mechanisms and overexpression of multi-subunit protein complexes for biochemical and structural studies. 相似文献
54.
Interferon-alpha and ribavirin resistance of Huh7 cells transfected with HCV subgenomic replicon 总被引:1,自引:0,他引:1
Aus dem Siepen M Oniangue-Ndza C Wiese M Ross S Roggendorf M Viazov S 《Virus research》2007,125(1):109-113
To model HCV resistance to a treatment with interferon-alpha (IFN-alpha) and ribavirin, Huh7 cells, bearing HCV subgenomic replicons, were treated with these compounds for several weeks. Analysis of the cell clones, which were able to support replication of HCV RNA in the presence of high concentrations of these antivirals, demonstrated that the observed resistance was due to changes in the host cell phenotype but not to the emergence of resistant variants of the replicon. No changes in the type I IFN receptor mRNA levels or sequences were found in IFN-treated cells suggesting that the observed resistance of replicon-containing cells to IFN-alpha was caused by modifications of some other cellular factors. The resistance of cells to high concentrations of ribavirin was due to a single point mutation in the NS5A gene of the HCV replicon, and was not associated with a defect in a ribavirin uptake. This mutation, however, did not change the sensitivity of the replicon itself to this antiviral. 相似文献
55.
Posner MR Hershock DM Blajman CR Mickiewicz E Winquist E Gorbounova V Tjulandin S Shin DM Cullen K Ervin TJ Murphy BA Raez LE Cohen RB Spaulding M Tishler RB Roth B Viroglio Rdel C Venkatesan V Romanov I Agarwala S Harter KW Dugan M Cmelak A Markoe AM Read PW Steinbrenner L Colevas AD Norris CM Haddad RI;TAX Study Group 《The New England journal of medicine》2007,357(17):1705-1715
56.
Xiang Y John P Yakushin SB Kunin M Raphan T Cohen B 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,177(4):551-572
We characterized the three-dimensional kinematics and dynamics of quadrupedal gait of young adult rhesus and cynomolgus monkeys
while they walked with diagonal and lateral gaits at 0.4–1.0 m/s on a treadmill. Rigid bodies on the wrist, ankle, and back
were monitored by an optical motion detection system (Optotrak). Kinematic data could be normalized using characteristic stride
length, reducing variance due to different gait styles, to emphasize common characteristics of swing and stance parameters
among animals. Mean swing phase durations fell as walking speed increased, but the swing phase durations increased at each
walking velocity as a linear function of increases in amplitude, thereby following a main sequence relationship. The phase
plane trajectories of the swing phases, i.e., plots of the relation of the rising and falling limb velocity to limb position
in the sagittal (X–Z) plane, had unique dynamic characteristics. Trajectories were separable at each walking velocity and increases in swing amplitude
were linearly related to peak swing velocities, thus comprising main sequences. We infer that the swing phase dynamics are
set by central neural mechanisms at the onset of the swing phases according to the intended amplitude, which in turn is based
on the walking velocity in the stance phases. From the many dynamic similarities between swing phases and rapid eye movements,
we further suggest that the swing phases may be generated by neural mechanisms similar to those that produce saccades and
quick phases of nystagmus from a signal related to sensed or desired walking velocity.
Grants: This work was supported by National Institute of Health Grants EY11812, EY04148, DC05204, and EY01867. 相似文献
57.
Messier J Adamovich S Jack D Hening W Sage J Poizner H 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,179(3):457-474
Successful adaptation to novel sensorimotor contexts critically depends on efficient sensory processing and integration mechanisms, particularly those required to combine visual and proprioceptive inputs. If the basal ganglia are a critical part of specialized circuits that adapt motor behavior to new sensorimotor contexts, then patients who are suffering from basal ganglia dysfunction, as in Parkinson's disease should show sensorimotor learning impairments. However, this issue has been under-explored. We tested the ability of 8 patients with Parkinson's disease (PD), off medication, ten healthy elderly subjects and ten healthy young adults to reach to a remembered 3D location presented in an immersive virtual environment. A multi-phase learning paradigm was used having four conditions: baseline, initial learning, reversal learning and aftereffect. In initial learning, the computer altered the position of a simulated arm endpoint used for movement feedback by shifting its apparent location diagonally, requiring thereby both horizontal and vertical compensations. This visual distortion forced subjects to learn new coordinations between what they saw in the virtual environment and the actual position of their limbs, which they had to derive from proprioceptive information (or efference copy). In reversal learning, the sign of the distortion was reversed. Both elderly subjects and PD patients showed learning phase-dependent difficulties. First, elderly controls were slower than young subjects when learning both dimensions of the initial biaxial discordance. However, their performance improved during reversal learning and as a result elderly and young controls showed similar adaptation rates during reversal learning. Second, in striking contrast to healthy elderly subjects, PD patients were more profoundly impaired during the reversal phase of learning. PD patients were able to learn the initial biaxial discordance but were on average slower than age-matched controls in adapting to the horizontal component of the biaxial discordance. More importantly, when the biaxial discordance was reversed, PD patients were unable to make appropriate movement corrections. Therefore, they showed significantly degraded learning indices relative to age-matched controls for both dimensions of the biaxial discordance. Together, these results suggest that the ability to adapt to a sudden biaxial visuomotor discordance applied in three-dimensional space declines in normal aging and Parkinson disease. Furthermore, the presence of learning rate differences in the PD patients relative to age-matched controls supports an important contribution of basal ganglia-related circuits in learning novel visuomotor coordinations, particularly those in which subjects must learn to adapt to sensorimotor contingencies that were reversed from those just learned. 相似文献
58.
Akao T Saito H Fukushima J Kurkin S Fukushima K 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,177(3):400-410
The smooth pursuit system and the vestibular system interact to keep the retinal target image on the fovea by matching the eye velocity in space to target velocity during head and/or whole body movement. The caudal part of the frontal eye fields (FEF) in the fundus of the arcuate sulcus contains pursuit-related neurons and the majority of them respond to vestibular stimulation induced by whole body movement. To understand the role of FEF pursuit neurons in the interaction of vestibular and pursuit signals, we examined the latency and time course of discharge modulation to horizontal whole body rotation during different vestibular task conditions in head-stabilized monkeys. Pursuit neurons with horizontal preferred directions were selected, and they were classified either as gaze-velocity neurons or eye/head-velocity neurons based on the previous criteria. Responses of these neurons to whole body step-rotation at 20 degrees/s were examined during cancellation of the vestibulo-ocular reflex (VOR), VOR x1, and during chair steps in complete darkness without a target (VORd). The majority of pursuit neurons tested (approximately 70%) responded during VORd with latencies <80 ms. These initial responses were basically similar in the three vestibular task conditions. The shortest latency was 20 ms and the modal value was 24 ms. These responses were also similar between gaze-velocity neurons and eye/head-velocity neurons, indicating that the initial responses (<80 ms) were vestibular responses induced by semicircular canal inputs. During VOR cancellation and x1, discharge of the two groups of neurons diverged at approximately 90 ms following the onset of chair rotation, consistent with the latencies associated with smooth pursuit. The shortest latency to the onset of target motion during smooth pursuit was 80 ms and the modal value was 95 ms. The time course of discharge rate difference of the two groups of neurons between VOR cancellation and x1 was predicted by the discharge modulation associated with smooth pursuit. These results provide further support for the involvement of the caudal FEF in integration of vestibular inputs and pursuit signals. 相似文献
59.
Sergei V. Jargin 《Dose-response》2014,12(3):404-414
The reported incidence of thyroid cancer in children and adolescents in Soviet Union before the Chernobyl accident was lower than in other developed countries. This is not clearly recognizable from the literature because comparisons of the high incidence figures 4 years after the accident and later have been made with those from the first years after the accident, when the registered incidence had already started to increase. Considering the low pre-accident registered incidence, there was an accumulated pool of undiagnosed thyroid tumors before the accident. The percentage of more advanced cancers, larger in size and less differentiated, was higher after the accident, when the pool of neglected cancers was diagnosed due to the screening and improved diagnostics. Some of these advanced tumors found by screening were interpreted as aggressive radiogenic cancers. The same tendency might be true also for other cancers, e.g. renal cell carcinoma. Furthermore, the screening-effect, false-positivity and registration of non-exposed patients as Chernobyl victims has obviously contributed to the registered incidence increase of malignancy. 相似文献
60.
Sergei V. Raik Tatiana V. Mashel Albert R. Muslimov Olga S. Epifanovskaya Mikhail A. Trofimov Daria N. Poshina Kirill V. Lepik Yury A. Skorik 《Materials》2021,14(9)
Polyplex-based gene delivery systems are promising substitutes for viral vectors because of their high versatility and lack of disadvantages commonly encountered with viruses. In this work, we studied the DNA polyplexes with N-[4-(N,N,N-trimethylammonium)benzyl]chitosan chloride (TMAB-CS) of various compositions in different cell types. Investigations of the interaction of TMAB-CS with DNA by different physical methods revealed that the molecular weight and the degree of substitution do not dramatically influence the hydrodynamic properties of polyplexes. Highly substituted TMAB-CS samples had a high affinity for DNA. The transfection protocol was optimized in HEK293T cells and achieved the highest efficiency of 30–35%. TMAB-CS was dramatically less effective in nonadherent K562 cells (around 1% transfected cells), but it was more effective and less toxic than polyarginine. 相似文献