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1.
It has been established that in healthy persons functional brain asymmetry positively influences the effective performance of sensomotor function of oral cavity organs. Individual brain asymmetry is of considerable importance, the higher it is, the quicker the final results of sensomotor function are achieved. The character of brain asymmetry (right hand or left hand) does not practically influence the performance of sensomotor functions. 相似文献
2.
Lesia Dmytrenko Michal Cicanic Miroslava Anderova Ivan Vorisek Ole Petter Ottersen Eva Sykova Lydia Vargova 《PloS one》2013,8(7)
Aquaporin-4 (AQP4) is the primary cellular water channel in the brain and is abundantly expressed by astrocytes along the blood-brain barrier and brain-cerebrospinal fluid interfaces. Water transport via AQP4 contributes to the activity-dependent volume changes of the extracellular space (ECS), which affect extracellular solute concentrations and neuronal excitability. AQP4 is anchored by α-syntrophin (α-syn), the deletion of which leads to reduced AQP4 levels in perivascular and subpial membranes. We used the real-time iontophoretic method and/or diffusion-weighted magnetic resonance imaging to clarify the impact of α-syn deletion on astrocyte morphology and changes in extracellular diffusion associated with cell swelling in vitro and in vivo. In mice lacking α-syn, we found higher resting values of the apparent diffusion coefficient of water (ADCW) and the extracellular volume fraction (α). No significant differences in tortuosity (λ) or non-specific uptake (k′), were found between α-syn-negative (α-syn −/−) and α-syn-positive (α-syn +/+) mice. The deletion of α-syn resulted in a significantly smaller relative decrease in α observed during elevated K+ (10 mM) and severe hypotonic stress (−100 mOsmol/l), but not during mild hypotonic stress (−50 mOsmol/l). After the induction of terminal ischemia/anoxia, the final values of ADCW as well as of the ECS volume fraction α indicate milder cell swelling in α-syn −/− in comparison with α-syn +/+ mice. Shortly after terminal ischemia/anoxia induction, the onset of a steep rise in the extracellular potassium concentration and an increase in λ was faster in α-syn −/− mice, but the final values did not differ between α-syn −/− and α-syn +/+ mice. This study reveals that water transport through AQP4 channels enhances and accelerates astrocyte swelling. The substantially altered ECS diffusion parameters will likely affect the movement of neuroactive substances and/or trophic factors, which in turn may modulate the extent of tissue damage and/or drug distribution. 相似文献
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Andrea Ganna Fernando Rivadeneira Albert Hofman André G. Uitterlinden Patrik K. E. Magnusson Nancy L. Pedersen Erik Ingelsson Henning Tiemeier 《Human genetics》2013,132(5):553-561
Twin studies have estimated the heritability of longevity to be approximately 20–30 %. Genome-wide association studies (GWAS) have revealed a large number of determinants of morbidity, but so far, no new polymorphisms have been discovered to be associated with longevity per se in GWAS. We aim to determine whether the genetic architecture of mortality can be explained by single nucleotide polymorphisms (SNPs) associated with common traits and diseases related to mortality. By extensive quality control of published GWAS we created a genetic score from 707 common SNPs associated with 125 diseases or risk factors related with overall mortality. We prospectively studied the association of the genetic score with: (1) time-to-death; (2) incidence of the first of nine major diseases (coronary heart disease, stroke, heart failure, diabetes, dementia, lung, breast, colon and prostate cancers) in two population-based cohorts of Dutch and Swedish individuals (N = 15,039; age range 47–99 years). During a median follow-up of 6.3 years (max 22.2 years), we observed 4,318 deaths and 2,132 incident disease events. The genetic score was significantly associated with time-to-death [hazard ratio (HR) per added risk allele = 1.003, P value = 0.006; HR 4th vs. 1st quartile = 1.103]. The association between the genetic score and incidence of major diseases was stronger (HR per added risk allele = 1.004, P value = 0.002; HR 4th vs. 1st quartile = 1.160). Associations were stronger for individuals dying at older ages. Our findings are compatible with the view of mortality as a complex and highly polygenetic trait, not easily explainable by common genetic variants related to diseases and physiological traits. 相似文献
5.
Yi-Juan Hu Sonja?I. Berndt Stefan Gustafsson Andrea Ganna Genetic Investigation of ANthropometric Traits Consortium Joel Hirschhorn Kari E. North Erik Ingelsson Dan-Yu Lin 《American journal of human genetics》2013,93(2):236-248
Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying “causal” rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available. 相似文献
6.
Zhyvoloup A Nemazanyy I Panasyuk G Valovka T Fenton T Rebholz H Wang ML Foxon R Lyzogubov V Usenko V Kyyamova R Gorbenko O Matsuka G Filonenko V Gout IT 《The Journal of biological chemistry》2003,278(50):50316-50321
CoA synthase mediates the last two steps in the sequence of enzymatic reactions, leading to CoA biosynthesis. We have recently identified cDNA for CoA synthase and demonstrated that it encodes a bifunctional enzyme possessing 4'-phosphopantetheine adenylyltransferase and dephospho-CoA kinase activities. Molecular cloning of CoA synthase provided us with necessary tools to study subcellular localization and the regulation of this bifunctional enzyme. Transient expression studies and confocal microscopy allowed us to demonstrate that full-length CoA synthase is associated with the mitochondria, whereas the removal of the N-terminal region relocates the enzyme to the cytosol. In addition, we showed that the N-terminal sequence of CoA synthase (amino acids 1-29) exhibits a hydrophobic profile and targets green fluorescent protein exclusively to mitochondria. Further analysis, involving subcellular fractionation and limited proteolysis, indicated that CoA synthase is localized on the mitochondrial outer membrane. Moreover, we demonstrate for the first time that phosphatidylcholine and phosphatidylethanolamine, which are the main components of the mitochondrial outer membrane, are potent activators of both enzymatic activities of CoA synthase in vitro. Taken together, these data provide the evidence that the final stages of CoA biosynthesis take place on mitochondria and the activity of CoA synthase is regulated by phospholipids. 相似文献
7.
Hryshchenko NV Bychkova AM Pichkur NA Skyban HV Dmytrenko VV Livshyts' LA 《T?Sitologii?a i genetika》2003,37(6):55-59
Charcot-Marie-Tooth neuropathy (CMT) is one of the most common hereditary disorders, affecting 1:2500 individuals. CMT is a heterogeneous group of disorders characterized by chronic peripheral motor and sensory neuropathy. We have performed the detection of 1.5 Mb CMT1A tandem duplication in 17p11.2-12 chromosome region for autosome-dominant CMT1 patients and their relatives using the analysis of two (CA)n polymorphic microsatellite loci: 17S921 and 17S1358 localised in the duplication region. CMT1A duplication was found in three of five autosome-dominant CMT1 families. It has been shown that CMT1A duplication analysis is important for early differential diagnosis of CMT including prenatal diagnosis and genetic consulting in high risk families. 相似文献
8.
Somogyi GT Zernova GV Yoshiyama M Rocha JN Smith CP de Groat WC 《Neurochemistry international》2003,43(1):73-77
Muscarinic facilitation of 14C-ACh release from post-ganglionic parasympathetic nerve terminals was studied in bladder strips prepared from spinal intact (SI) and spinal cord transected (SCT) rats. The spinal cord was transected at the lower thoracic spinal segments 3 weeks prior to the experiments. Using non-facilitatory stimulation (2 Hz) the release of ACh in spinal intact rats did not change in the presence of a non-specific muscarinic antagonist, atropine (100 nM), an M(1) specific antagonist (pirenzepine, 50 nM) or an M(1)-M(3) specific antagonist (4-DAMP, 5 nM). However, during a facilitatory stimulation paradigm (10 Hz or 40 Hz, 100 shocks) atropine and pirenzepine, but not 4-DAMP inhibited the release of ACh in bladders from spinal intact rats, indicating an M(1) receptor-mediated facilitation. In spinal cord transected rats, 2 Hz stimulation-induced release was significantly inhibited by atropine or 4-DAMP but not by pirenzepine indicating that a pre-junctional facilitatory mechanism mediated via M(3) muscarinic receptors could be induced by a non-facilitatory stimulation paradigm after spinal injury. In bladders of spinal cord transected rats, 10 Hz stimulation-evoked release of ACh was also inhibited by atropine and 4-DAMP (5 nM) but not by pirenzepine (50 nM). These results indicate that pre-junctional muscarinic receptors at cholinergic nerve endings in the bladder change after chronic spinal cord injury. It appears that low affinity M(1) muscarinic receptors are replaced by high affinity M(3) receptors. This change in modulation of ACh release may partly explain the bladder hyperactivity after chronic spinal cord injury. 相似文献
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L. N. Shapoval O. V. Dmytrenko L. S. Pobegailo L. G. Stepanenko V. F. Sagach 《Neurophysiology》2007,39(3):201-212
In acute experiments on normotensive rats and those with genetically determined hypertension (urethane anesthesia), we studied
hemodynamic effects resulting from modulation of the activities of neuronal NO synthase (NOS-1), arginase II, and superoxide
dismutase, and also of the mitochondrial permeability in medullary cardiovascular neurons. Unilateral microinjections of either
a nitric oxide (NO) donor, sodium nitroprusside, or a substrate for endogenous NO synthesis, L-arginine, into the medullary
cardiovascular nuclei (nucl. tractus solitarius, NTS, nucl. ambiguous, AMB, paramedian nucleus, PMn, and lateral reticular nucleus LRN) were shown to induce hemodynamic responses with rather similar dynamics in both normotensive and spontaneously hypertensive
rats, although in the latter the reactions were more intense. Injections of an antagonist of NOS-1, NG nitro-L-arginine (L-NNA), into the medullary nuclei under study in spontaneously hypertensive rats resulted in shifts of
the systemic arterial pressure (SAP), which did not differ dramatically from those observed in normotensive animals. The data
obtained serve as the background for the suggestion that the functional activity of NOS-1 is not fundamentally impaired under
hypertension conditions, but, probably, the amount of the substrate for adequate synthesis of NO via the NO-synthase pathway
of metabolism of L-arginine is insufficient. Considering this, we examined the functional activity of arginase, an enzyme
that also, similarly to NOS, uses L-arginine for metabolic transformation. Injections of antagonists of arginase, norvaline
or α-difluoromethylornithine hydrochloride (DFMO), into populations of the medullary neurons under study induced similar shifts
of the SAP in normotensive and spontaneously hypertensive rats, and those responses did not differ significantly from the
effects of inhibition of the NOS-1 activity. Thus, both the above-mentioned enzymes are potentially active in normotensive
and spontaneously hypertensive rats; so, a possibility for their competition for L-arginine in certain situations does exist.
Modulation of the mitochondrial permeability in medullary cardiovascular neurons in normotensive and spontaneously hypertensive
rats induced significant hemodynamic effects. In particular, an increase in the mitochondrial permeability in the medullary
cardiovascular nuclei by injections of an inductor of mitochondrial permeability transition pore (mPTP) opening, phenylarsine
oxide (PAO), was accompanied by SAP drops in both normotensive and spontaneously hypertensive rats; the effects were dose-dependent
and, in some cases, irreversible. A decrease in the mitochondrial permeability in the neurons under study by injections of
an inhibitor of mPTP, melatonin, induced mostly hypertensive responses, although in some experiments we observed hypotensive
and two-phase responses.
Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 232–244, May–June, 2007. 相似文献
10.
Kalayda GV Fakih S Bertram H Ludwig T Oberleithner H Krebs B Reedijk J 《Journal of inorganic biochemistry》2006,100(8):1332-1338
Nine structurally distinct dinuclear platinum complexes have been evaluated in a novel model system for the investigation of renal epithelial toxicity of platinum drugs. The results showed that these compounds are toxic when applied at the basolateral side of renal epithelia, whereas their toxic effects on the apical side are negligible. Such a difference in toxicity of the complexes has been found to result from their poor uptake through the apical membrane, as compared to the basolateral membrane. Toxicity of the compounds on the basolateral side varies depending on their structure. Structure-toxicity relationships for the group of complexes with rigid ligands and for the group of complexes with flexible ligands are discussed. Among the dinuclear complexes with rigid ligands, sterically hindered complexes are less toxic, due to their poor uptake and low reactivity towards glutathione. Within the group of complexes with flexible ligands, cis-configured isomers are more toxic than their trans-counterparts. 相似文献