What is the neural substrate of our capability to properly react to changes in the environment? It can be hypothesized that the anterior cingulate cortex (ACC) manages repetitive stimuli in routine conditions and alerts the dorsolateral prefrontal cortex (PFC) when stimulation unexpectedly changes. To provide evidence in favor of this hypothesis, intracerebral stereoelectroencephalographic (SEEG) data were recorded from the anterior cingulate and dorsolateral PFC of eight epileptic patients in a standard visual oddball task during presurgical monitoring. Two types of stimuli (200 ms duration) such as the letters O (frequent stimuli; 80% of probability) and X (rare stimuli) were presented in random order, with an interstimulus interval between 2 and 5 s. Subjects had to mentally count the rare (target) stimuli and to press a button with their dominant hand as quickly and accurately as possible. EEG frequency bands of interest were theta (4-8 Hz), alpha (8-12 Hz), beta (14-30 Hz), and gamma (30-45 Hz). The directionality of the information flux within the EEG rhythms was indexed by a directed transfer function (DTF). The results showed that compared with the frequent stimuli, the target stimuli induced a statistically significant increase of DTF values from the anterior cingulate to the dorsolateral PFC at the theta rhythms (P < 0.01). These results provide support to the hypothesis that ACC directly or indirectly affects the oscillatory activity of dorsolateral PFC by a selective frequency code under typical oddball conditions. (c) 2007 Wiley-Liss, Inc.

• MeSH
• akční potenciály fyziologie   MeSH
• biologické hodiny fyziologie   MeSH
• cingulární gyrus anatomie a histologie   fyziologie   MeSH
• dospělí MeSH
• duševní procesy fyziologie   MeSH
• elektroencefalografie metody   MeSH
• evokované potenciály fyziologie   MeSH
• financování organizované MeSH
• interpretace statistických dat MeSH
• kognice fyziologie   MeSH
• lidé MeSH
• mapování mozku MeSH
• mladý dospělý MeSH
• nervové dráhy anatomie a histologie   fyziologie   MeSH
• neurony fyziologie   MeSH
• neuropsychologické testy MeSH
• počítačové zpracování signálu MeSH
• prefrontální mozková kůra anatomie a histologie   fyziologie   MeSH
• světelná stimulace MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Alterations in the default mode network (DMN) are associated with aging. We assessed age-dependent changes of DMN interactions and correlations with a battery of neuropsychological tests, to understand the differences of DMN directed connectivity between young and older subjects. Using a novel multivariate analysis method on resting-state functional MRI data from fifty young and thirty-one healthy older subjects, we calculated intra- and inter-DMN 4-nodes directed pathways. For the old subject group, we calculated the partial correlations of inter-DMN pathways with: psychomotor speed and working memory, executive function, language, long-term memory and visuospatial function. Pathways connecting the DMN with visual and limbic regions in older subjects engaged at BOLD low frequency and involved the dorsal posterior cingulate cortex (PCC), whereas in young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) cortex and the DMN, were SM efferent in the young subjects and SM afferent in the older subjects. Most DMN efferent pathways correlated with reduced speed and working memory. We suggest that the reduced sensorimotor efferent and the increased need to control such activities, cause a higher dependency on external versus internal cues thus suggesting how physical activity might slow aging.

• MeSH
• krátkodobá paměť MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mapování mozku * metody   MeSH
• mozek * diagnostické zobrazování   MeSH
• nervové dráhy MeSH
• senioři MeSH
• stárnutí MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Studies in the sensorimotor system of older versus young individuals have shown alterations in functional connectivity and organization. Our objective was to explore the implications of these differences in terms of local organizations, and to identify processes that correlate with neuropsychological parameters. METHODS: Using a novel multivariate analysis method on resting-state functional MRI data obtained from 50 young and 31 older healthy individuals, we identified directed 4-node functional pathways within the sensorimotor system and examined their correlations with neuropsychological assessments. RESULTS: In young individuals, the functional pathways were unidirectional, flowing from the primary motor and sensory cortices to higher motor and visual regions. In older individuals, the functional pathways were more complex. They originated either from the calcarine sulcus or the insula and passed through mutually coupled high-order motor areas before reaching the primary sensory and motor cortices. Additionally, the pathways in older individuals that resembled those found in young individuals exhibited a positive correlation with years of education. DISCUSSION: The flow pattern of young individuals suggests efficient and fast information transfer. In contrast, the mutual coupling of high-order motor regions in older individuals suggests an inefficient and slow transfer, a less segregated and a more integrated organization. The differences in the number of sensorimotor pathways and of their directionality suggests reduced efferent degenerated pathways and increased afferent compensated pathways. Furthermore, the positive effect of years of education may be associated with the Cognitive Reserve Hypothesis, implying that cognitive reserve could be maintained through specific information transfer pathways.

• Publikační typ
• časopisecké články MeSH

Understanding the molecular mechanism of HIV-1 integrase (IN) activity is critical to find functional inhibitors for an effective AIDS therapy. A robust, fast, and sensitive method for studying IN activity is required. In this work, an assay for real-time label-free monitoring of the IN activity based on surface plasmon resonance was developed. This assay enabled direct monitoring of the integration of a viral doubled-stranded (ds) DNA into the host genome. The strand transfer reaction was detected by using two different DNA targets: supercoiled plasmid (pUC 19) and short palindrome oligonucleotide. The effect of the length of the DNA target on the possibility to monitor the actual process of the strand transfer reaction is discussed. The surface density of integrated ds-DNA was determined. IN binding to the oligonucleotide complexes and model DNA triplexes in the presence of various divalent ions as metal cofactors was investigated as well. The assay developed can serve as an important analytical tool to search for potential strand transfer reaction inhibitors as well as for the study of compounds interfering with the binding of ds long terminal repeats-IN complexes with the host DNA.

• MeSH
• DNA primery MeSH
• financování organizované MeSH
• HIV-integrasa chemie   MeSH
• povrchová plasmonová rezonance metody   MeSH
• sekvence nukleotidů MeSH

Dopamine depletion in the axons of Parkinson's disease (PD) patients precedes depletion in cell bodies thus proposing that macroscopic connectivity can be used to understand disease mechanism. A novel multivariate functional connectivity analysis, based on high order coherence among four fMRI BOLD signals was applied on resting-state fMRI data of controls and PD patients (OFF and ON medication states) and unidirectional multiple-region pathways in the sensorimotor system were identified. Pathways were classified as "preserved" (unaffected by the disease), "damaged" (not observed in patients) and "corrected" (observed in controls and in PD-ON state). The majority of all pathways were feedforward, most of them with the pattern "S1→M1→SMA." Of these pathways, 67% were "damaged," 28% "preserved," and 5% "corrected." Prefrontal cortex (PFC) afferent and efferent pathways that corresponded to goal directed and habitual activities corresponded to recurrent circuits. Eighty-one percent of habitual afferent had internal cue (i.e., M1→S1→), of them 79% were "damaged" and the rest "preserved." All goal-directed afferent had external cue (i.e., S1→M1→) with third "damaged," third "preserved," and third "corrected." Corrected pathways were initiated in the dorsolateral PFC. Reduced connectivity of the SMA and PFC resulted from reduced sensorimotor afferent to these regions. Reduced sensorimotor internal cues to the PFC resulted with reduced habitual processes. Levodopa effects were for pathways that started in region reach with dopamine receptors. This methodology can enrich understudying of PD mechanisms in other (e.g., the default mode network) systems.

• MeSH
• levodopa MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• nervové dráhy MeSH
• odpočinek MeSH
• Parkinsonova nemoc * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• buněčná membrána enzymologie   MeSH
• kvasinky MeSH
• kyselina asparagová MeSH
• kyselina glutamová MeSH
• mutageneze cílená MeSH
• přenos energie MeSH

INTRODUCTION: Propofol causes a profound inhibition of fatty acid oxidation and reduces spare electron transfer chain capacity in a range of human and rodent cells and tissues-a feature that might be related to the pathogenesis of Propofol Infusion Syndrome. We aimed to explore the mechanism of propofol-induced alteration of bioenergetic pathways by describing its kinetic characteristics. METHODS: We obtained samples of skeletal and cardiac muscle from Wistar rat (n = 3) and human subjects: vastus lateralis from hip surgery patients (n = 11) and myocardium from brain-dead organ donors (n = 10). We assessed mitochondrial functional indices using standard SUIT protocol and high resolution respirometry in fresh tissue homogenates with or without short-term exposure to a range of propofol concentration (2.5-100 μg/ml). After finding concentrations of propofol causing partial inhibition of a particular pathways, we used that concentration to construct kinetic curves by plotting oxygen flux against substrate concentration during its stepwise titration in the presence or absence of propofol. By spectrophotometry we also measured the influence of the same propofol concentrations on the activity of isolated respiratory complexes. RESULTS: We found that human muscle and cardiac tissues are more sensitive to propofol-mediated inhibition of bioenergetic pathways than rat's tissue. In human homogenates, palmitoyl carnitine-driven respiration was inhibited at much lower concentrations of propofol than that required for a reduction of electron transfer chain capacity, suggesting FAO inhibition mechanism different from downstream limitation or carnitine-palmitoyl transferase-1 inhibition. Inhibition of Complex I was characterised by more marked reduction of Vmax, in keeping with non-competitive nature of the inhibition and the pattern was similar to the inhibition of Complex II or electron transfer chain capacity. There was neither inhibition of Complex IV nor increased leak through inner mitochondrial membrane with up to 100 μg/ml of propofol. If measured in isolation by spectrophotometry, propofol 10 μg/ml did not affect the activity of any respiratory complexes. CONCLUSION: In human skeletal and heart muscle homogenates, propofol in concentrations that are achieved in propofol-anaesthetized patients, causes a direct inhibition of fatty acid oxidation, in addition to inhibiting flux of electrons through inner mitochondrial membrane. The inhibition is more marked in human as compared to rodent tissues.

• MeSH
• druhová specificita MeSH
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• oxidace-redukce účinky léků   MeSH
• potkani Wistar MeSH
• propofol farmakologie   MeSH
• respirační komplex I metabolismus   MeSH
• respirační komplex IV metabolismus   MeSH
• senioři MeSH
• srdeční mitochondrie metabolismus   MeSH
• svalové mitochondrie metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• fyziologické jevy MeSH
• fyziologie MeSH
• lidské tělo MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• fyziologie
• NLK Publikační typ
• kolektivní monografie

OBJECT: The authors present the long-term results of nerve grafting and neurotization procedures in their group of patients with brachial plexus injuries and compare the results of "classic" methods of nerve repair with those of end-to-side neurorrhaphy. METHODS: Between 1994 and 2006, direct repair (nerve grafting), neurotization, and end-to-side neurorrhaphy were performed in 168 patients, 95 of whom were followed up for at least 2 years after surgery. Successful results were achieved in 79% of cases after direct repair and in 56% of cases after end-to-end neurotization. The results of neurotization depended on the type of the donor nerve used. In patients who underwent neurotization of the axillary and the musculocutaneous nerves, the use of intraplexal nerves (motor branches of the brachial plexus) as donors of motor fibers was associated with a significantly higher success rate than the use of extraplexal nerves (81% compared with 49%, respectively, p = 0.003). Because of poor functional results of axillary nerve neurotization using extraplexal nerves (success rate 47.4%), the authors used end-to-side neurorrhaphy in 14 cases of incomplete avulsion. The success rate for end-to-side neurorrhaphy using the axillary nerve as a recipient was 64.3%, similar to that for neurotization using intraplexal nerves (68.4%) and better than that achieved using extraplexal nerves (47.4%, p = 0.19). CONCLUSIONS: End-to-side neurorrhaphy offers an advantage over classic neurotization in not requiring sacrifice of any of the surrounding nerves or the fascicles of the ulnar nerve. Typical synkinesis of muscle contraction innervated by the recipient nerve with contraction of muscles innervated by the donor was observed in patients after end-to-side neurorrhaphy.

• MeSH
• anastomóza chirurgická metody   MeSH
• dospělí MeSH
• financování organizované MeSH
• lidé středního věku MeSH
• lidé MeSH
• míšní nervy transplantace   MeSH
• mladiství MeSH
• následné studie MeSH
• nervový transfer MeSH
• obnova funkce MeSH
• plexus brachialis chirurgie   zranění   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

The wide variety of protein structures and functions results from the diverse properties of the 20 canonical amino acids. The generally accepted hypothesis is that early protein evolution was associated with enrichment of a primordial alphabet, thereby enabling increased protein catalytic efficiencies and functional diversification. Aromatic amino acids were likely among the last additions to genetic code. The main objective of this study was to test whether enzyme catalysis can occur without the aromatic residues (aromatics) by studying the structure and function of dephospho-CoA kinase (DPCK) following aromatic residue depletion. We designed two variants of a putative DPCK from Aquifex aeolicus by substituting (a) Tyr, Phe and Trp or (b) all aromatics (including His). Their structural characterization indicates that substituting the aromatics does not markedly alter their secondary structures but does significantly loosen their side chain packing and increase their sizes. Both variants still possess ATPase activity, although with 150-300 times lower efficiency in comparison with the wild-type phosphotransferase activity. The transfer of the phosphate group to the dephospho-CoA substrate becomes heavily uncoupled and only the His-containing variant is still able to perform the phosphotransferase reaction. These data support the hypothesis that proteins in the early stages of life could support catalytic activities, albeit with low efficiencies. An observed significant contraction upon ligand binding is likely important for appropriate organization of the active site. Formation of firm hydrophobic cores, which enable the assembly of stably structured active sites, is suggested to provide a selective advantage for adding the aromatic residues.

• MeSH
• Aquifex enzymologie   genetika   MeSH
• bakteriální proteiny chemie   genetika   MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem chemie   genetika   MeSH
• katalytická doména MeSH
• katalýza MeSH
• mutageneze cílená MeSH
• sekundární struktura proteinů MeSH
• substituce aminokyselin MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH