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PubMed1983

[Structure of the palisade nerve fibers of the sinuous hair after cutting the infraorbital nerve].

The state of the palisade neural fibers (PNF) in the connective tissue of the internal follicle of the cat sinuous hair has been studied after the infraorbital nerve had been cut. Denervation of the sinuous hair is demonstrated to result in certain destructive changes in the PNF. Two days after the operation, cytoplasm becomes more dense, mitochondria undergo destruction, large vacuoles appear in the neural terminals. In the receptory specialized cells, as well as in the neural fiber lemmocytes, the number of the large vacuoles increases, electron opaque bodies appear. On the 7th day after the operation maximal destructive changes are noted. In 30 days after cutting the nerve, regeneration of the neural fibers, the PNF including, begins. In this connection the fate of the specialized cells after destruction of the receptor and their participation in the regenerative process is discussed. The data obtained demonstrate that there are some important functional connections between the axons and the specialized PNF cells. This is necessary to maintain the differentiated state of the receptor in question.

Animals↗
PubMed1995

Characterization of synaptic connections between cortex and deep nuclei of the rat cerebellum in vitro.

Intracellular recordings were used to characterize the inhibitory synapses formed by Purkinje cells on neurons in the deep cerebellar nuclei of the rat. This work was performed on organotypic cerebellar cultures where functional connections between Purkinje cells and deep cerebellar neurons are formed de novo. After blocking ionotropic excitatory amino acid, and GABAA receptors with 6-cyano-7-nitro-quinoxaline-2,3-dione,D-2-amino-5-phosphonovalerate and bicuculline, respectively, the majority of deep cerebellar neurons fired spontaneously without accommodation. This tonic firing was linearly dependent on membrane potential and was abolished with hyperpolarization. Bath application of muscimol and baclofen reversibly hyperpolarized deep cerebellar nuclei cells. In the presence of excitatory amino acid receptor antagonists, field stimulation within the Purkinje cell layer induced monosynaptic inhibitory potentials in deep cerebellar neurons that were graded and completely blocked by bicuculline. Inhibitory potential amplitudes were not markedly reduced during fast repetitive stimulation of Purkinje cells, and the resulting hyperpolarization was not affected by the competitive GABAB receptor antagonist CGP 35348. A single inhibitory potential temporarily interrupted trains of action potentials induced in deep cerebellar cells by short depolarizing pulses. Trains of five inhibitory postsynaptic potentials, evoked at 20 Hz, induced a hyperpolarization which transiently blocked the spontaneous firing of deep cerebellar cells. The efficiency to block action potential discharges depended on the frequency of evoked inhibitory potentials. Bath application of bicuculline induced burst discharges in the control solution. When the excitatory amino acid receptors were pharmacologically blocked, bicuculline depolarized deep cerebellar neurons inducing sustained action potential discharges. In the presence of tetrodotoxin, bicuculline abolished miniature inhibitory postsynaptic potentials and resulted in a membrane depolarization of deep cerebellar cells. We conclude that deep cerebellar neurons isolated from synaptic inputs display a pacemaker-like activity. Although these neurons possess GABAA and GABAB receptors, we confirm that only GABAA receptors were involved in the generation of inhibitory postsynaptic potentials, even with high frequency stimulation. The amplitude of evoked inhibitory potentials was weakly frequency-dependent, thus allowing a powerful inhibition of the pacemaker-like activity by trains of evoked inhibitory postsynaptic potentials. Additionally, spontaneous and miniature inhibitory potentials control the excitability of deep cerebellar neurons by exerting a continuous hyperpolarizing tone.

2-Amino-5-phosphonovalerate↗
PubMed2004

PASSCLAIM--body weight regulation, insulin sensitivity and diabetes risk.

BACKGROUND: Insulin sensitivity is a key function in human metabolism because it has a crucial role in the development of disease that are increasingly common in modern society. Impaired insulin sensitivity is an important determinant of type 2 diabetes; moreover, it has been proposed as an independent risk factor for cardiovascular disease. Thus, reduced insulin sensitivity is strongly associated with the metabolic syndrome, which represents a cluster of metabolic abnormalities and cardiovascular risk factor. Insulin sensitivity can be modulated by different environmental factors, including dietary habits. Obesity, especially if associated with abdominal adiposity, impairs insulin-sensitivity while physical activity can improve it; however, the composition of the habitual diet is clearly an important regulator of this function. AIM: To evaluate methodologies and markers that can be used to substantiate existing and potential claims of beneficial effects of foods on relevant functions connected with body fat deposition, insulin sensitivity and blood glucose regulation. RESULTS: We have reviewed the scientific basis for existing and potential claims, based not only on modifications of the target functions (body fat deposition, insulin sensitivity and blood glucose regulation) but also on modifications of other relevant associated functions (energy intake, energy expenditure, fat storage and oxidation, lipotoxicity, body fat composition, inflammation, oxidative stress, vascular function, glucose production and utilization). In this context we have identified a number of markers and evaluated appropriate method to measure and validate them. CONCLUSIONS: Relevant functions contributing to overweight, the metabolic syndrome and diabetes have been identified. The evidence reviewed indicates that in this field the link between nutrition, biological responses and diseases is clearly established. Therefore, there is a strong potential to develop functional food science. The major gap in the evidence continues to be the lack of diet based intervention trials of sufficient duration to be relevant for affecting the natural history of these conditions.

Absorptiometry, Photon↗
PubMed2005

MEG and TMS combined with EEG for mapping alcohol effects.

Magnetoencephalography (MEG) is a noninvasive method of studying magnetic fields from outside the skull that are generated by at least partially synchronized neuronal populations in the brain. The advantage of MEG over electroencephalography (EEG) is the transparency of the skull, scalp, and brain tissue to the magnetic fields, which facilitates easy localization of the cortical activity. In MEG, alcohol increased the relative power of the alpha rhythm and reduced the relative power of beta activity in parieto-occipital regions. In contrast, no changes were observed in EEG, indicating that these methods differently detect alcohol's action on the cortex. Furthermore, MEG and EEG also differently detected the effects of alcohol on cognition. Alcohol reduced magnetic and electric auditory N1 and mismatch negativity amplitudes. P3a amplitudes were also reduced in EEG but not in MEG, suggesting that different cortical areas are responsible for alcohol's action on involuntary attention. Transcranial magnetic stimulation (TMS) provides new possibilities for studying localized changes in the electrical properties of the human cortex, especially when combined with EEG. Different cortical areas can be stimulated and the subsequent brain activity can be measured, yielding information about cortical excitability and connectivity. Alcohol modulates EEG responses evoked by motor-cortex TMS, the effects being largest at the right prefrontal cortex (assessed by minimum-norm estimation), meaning that alcohol changed the functional connectivity between motor and prefrontal cortices. Furthermore, alcohol decreases amplitudes of EEG responses after the left prefrontal stimulation of anterior parts of the cortex, which may be associated with the decrease of prefrontal cortical excitability. Taken together, MEG and TMS combined with EEG provide new insight into the focal actions of alcohol on the cortex with a temporal resolution of milliseconds, giving information different from that given by other brain imaging modalities.

Alcohol Drinking↗
PubMed2003

A new approach to spike sorting for multi-neuronal activities recorded with a tetrode--how ICA can be practical.

Multi-neuronal recording with a tetrode is a powerful technique to reveal neuronal interactions in local circuits. However, it is difficult to detect precise spike timings among closely neighboring neurons because the spike waveforms of individual neurons overlap on the electrode when more than two neurons fire simultaneously. In addition, the spike waveforms of single neurons, especially in the presence of complex spikes, are often non-stationary. These problems limit the ability of ordinary spike sorting to sort multi-neuronal activities recorded using tetrodes into their single-neuron components. Though sorting with independent component analysis (ICA) can solve these problems, it has one serious limitation that the number of separated neurons must be less than the number of electrodes. Using a combination of ICA and the efficiency of ordinary spike sorting technique (k-means clustering), we developed an automatic procedure to solve the spike-overlapping and the non-stationarity problems with no limitation on the number of separated neurons. The results for the procedure applied to real multi-neuronal data demonstrated that some outliers which may be assigned to distinct clusters if ordinary spike-sorting methods were used can be identified as overlapping spikes, and that there are functional connections between a putative pyramidal neuron and its putative dendrite. These findings suggest that the combination of ICA and k-means clustering can provide insights into the precise nature of functional circuits among neurons, i.e. cell assemblies.

Action Potentials↗
PubMed2004

A dynamic shift of neural network activity before and after learning-set formation.

Learning-set (LS) is a property of insight and hypothesis testing characterized by the ability to solve novel problems based on previous experiences with problem solving. However, the neural organization and mechanisms underlying LS remain unclear. To further characterize this process, positron emission tomography (PET) studies with [15O]H2O were performed to measure regional cerebral blood flow (rCBF) during the learning phase of the two-choice visual discrimination task under the LS paradigm in rhesus monkeys. When comparing studies before and after LS formation, the orbitofrontal and lateral prefrontal cortices were differentially activated, and functional connections between these structures and the striatum, which contributes to habit learning, were altered. We conclude that changes in the lateral prefrontal cortex during problem solving may contribute to the executive function of working memory and also inhibit control of a primitive learning system, thereby promoting LS formation.

Animals↗
PubMed2001

The neural substrate of orientation working memory.

We have used positron emission tomography (PET) to identify the neural substrate of two major cognitive components of working memory (WM), maintenance and manipulation of a single elementary visual attribute, i.e., the orientation of a grating presented in central vision. This approach allowed us to equate difficulty across tasks and prevented subjects from using verbal strategies or vestibular cues. Maintenance of orientations involved a distributed fronto-parietal network, that is, left and right lateral superior frontal sulcus (SFSl), bilateral ventrolateral prefrontal cortex (VLPFC), bilateral precuneus, and right superior parietal lobe (SPL). A more medial superior frontal sulcus region (SFSm) was identified as being instrumental in the manipulative operation of updating orientations retained in the WM. Functional connectivity analysis revealed that orientation WM relies on a coordinated interaction between frontal and parietal regions. In general, the current findings confirm the distinction between maintenance and manipulative processes, highlight the functional heterogeneity in the prefrontal cortex (PFC), and suggest a more dynamic view of WM as a process requiring the coordinated interaction of anatomically distinct brain areas.

Adult↗
PubMed1999

[Testosterone and atherosclerosis in males during andropause].

Nowadays besides the commonly accepted atherogenic risk factors a special emphasis is laid on the significance of testosterone in atherogenesis in men which physiologic deficit during "andropause" is able to promote this pathology. An elevated estradiol:testosterone ratio seems to be an independent risk factor of atheromatous heart complications. There is a proved positive correlation between free testosterone, total testosterone, dihydrotestosterone and HDL-cholesterol, apoA1 apolipoprotein. The relationship between LDL-cholesterol, VLDL-cholesterol, total cholesterol and total and free testosterone seems to be unanimous, but in certain studies the beneficial influence of testosterone on the mentioned lipids has been observed. The discussed hormone is also functionally connected with coagulation and fibrynolisis; a positive correlation was found between endogenous testosterone and tPA-Fx and a negative correlation between testosterone and PAI-1, fibrinogen, D-dimers, alpha 2-antiplasmin. Testosterone is a functional regulator of the vascular tonus and influences on reological properties of microcirculation (the application of testosterone infusion into canine coronary arteries causes the dilatation of main and the small vessels, through NO syntetase induction and ATP-dependent K(+)- channel activation). A statistically significant positive correlation between testosterone and insulin has been stated (an elevated oestradiol:testosterone ratio is connected with the insulin resistance). Additionally a negative relationship between testosterone and android obesity has been observed. Although nowadays there are more and more facts proving the benefits of the retaining the proper testosterone levels in aging men, the final influence of the testosterone supplementary therapy on atherogenesis is not solved.

Adult↗
PubMed2004

Contralateral voluntary hand movement inhibits human parkinsonian tremor and variably influences essential tremor.

While voluntary movement blocks Parkinsonian rest tremor (PT), essential tremor (ET) is enforced by postural and/or kinetic action. We studied the effect of contralateral externally- and internally triggered hand movement on PT and ET to investigate the transhemispheric influences on tremor genesis. We measured the changes of tremor peak frequency power after flash signal (F), flash triggered (FM) and self-paced (SPM) movement of the contralateral hand in nine PT and seven ET patients using accelerometer. PT significantly decreased both during FM and SPM tasks, suggesting that it is generated by a constant subcortico-cortical network, which includes higher order motor areas. Intensity of ET showed a remarkable intra- and interindividual variability both during FM and SPM reflecting a different generator circuitry with variable functional connections.

Aged↗
PubMed2005

Neuropsychological deficits, syndromes, and cognitive competency in schizophrenia.

INTRODUCTION: Neuropsychological functioning connects neuropathology and symptoms in schizophrenia. Previous work suggests that deficient initiation and inhibition underlie the psychomotor poverty and disorganisation syndromes, respectively. Furthermore, although the syndromes are associated with impairments in everyday functioning, cognitive competency (CC; cognitive skills for independent living) has been neglected as an outcome. This study tested a three-level model of schizophrenia pathology (Neuropsychological dysfunction --> Syndromes --> CC), using unstructured neuropsychological tasks to measure initiation and inhibition. METHODS: Participants were 40 adults with schizophrenia. A verbal picture description and the Tinkertoy test yielded initiation and inhibition measures with good interrater reliability. Symptoms were rated using the SANS and SAPS, and an insight scale was administered. The Cognitive Competency Test utilised simulated situations to assess CC. RESULTS: Initiation failed to predict psychomotor poverty, but affected CC directly. Only one indicator of disinhibition (intermingling of personal material into speech) predicted disorganisation, which, through mediation, led to CC deficits. Insight correlated with disorganisation and contributed to CC. Unique effects of initiation, disorganisation, and insight, combined, explained 58% of CC variance. CONCLUSIONS: Partial support for the three-level model was obtained. Specific neuropsychological abilities and symptoms explain a substantial proportion of the variance in cognitive competency.

Journal Article↗
PubMed2005

The RSC chromatin remodeling complex bears an essential fungal-specific protein module with broad functional roles.

RSC is an essential and abundant ATP-dependent chromatin remodeling complex from Saccharomyces cerevisiae. Here we show that the RSC components Rsc7/Npl6 and Rsc14/Ldb7 interact physically and/or functionally with Rsc3, Rsc30, and Htl1 to form a module important for a broad range of RSC functions. A strain lacking Rsc7 fails to properly assemble RSC, which confers sensitivity to temperature and to agents that cause DNA damage, microtubule depolymerization, or cell wall stress (likely via transcriptional misregulation). Cells lacking Rsc14 display sensitivity to cell wall stress and are deficient in the assembly of Rsc3 and Rsc30. Interestingly, certain rsc7delta and rsc14delta phenotypes are suppressed by an increased dosage of Rsc3, an essential RSC member with roles in cell wall integrity and spindle checkpoint pathways. Thus, Rsc7 and Rsc14 have different roles in the module as well as sharing physical and functional connections to Rsc3. Using a genetic array of nonessential null mutations (SGA) we identified mutations that are sick/lethal in combination with the rsc7delta mutation, which revealed connections to a surprisingly large number of chromatin remodeling complexes and cellular processes. Taken together, we define a protein module on the RSC complex with links to a broad spectrum of cellular functions.

Chromatin Assembly and Disassembly↗
PubMedDate not supplied

[The reflection of compensation processes in the structure of the EEG spatial-temporal relationships in patients with disordered brain regulatory mechanisms].

Studies of intercentral relations of electrical activity in the cerebral cortex of the patients with hypophysis tumours under the conditions of chronic (before operation) and acute (after tumour ablation, early post-operative period) influence of the focus on the regulatory brain systems allowed to reveal definite changes of spectral-coherent EEG characteristics, reflecting the functional state of the cerebral adaptive-compensatory apparatus. It has been shown that reciprocal character of changes of various forms of the brain electrical activity and their intercentral relations is one of manifestations of development of the processes of cerebral compensation. At the same time, global fall of the EEG intercentral relations indicating the disintegration of the cerebral functional connections, reflects a loss of CNS compensatory mechanisms. The revealed EEG-characteristics at the present time are applied in Burdenko Institute of Neurosurgery for diagnostic-prognostic estimation of the brain functional state in patients during pre- and post-operative period.

Adaptation, Physiological↗
PubMed1989

Kinetics of p-mercuribenzoate binding to sulfhydryl groups on the isolated cytoplasmic fragment of band 3 protein. Effect of hemoglobin binding on the conformation.

Hemoglobin binds to the cytoplasmic domain of band 3 protein (CDB3) at physiologic pH and ionic strength in an oxygen-linked fashion, with deoxyhemoglobin having the higher affinity. The evidence in the literature suggests functional communication between the hemoglobin-binding site on CDB3 and the anion transport sites within the membrane-bound domain of band 3. Since the hemoglobin-binding site is estimated to be over 200 A from the transport domain, the functional communication hypothesis would require the existence of long-range, global changes in the CDB3 dimeric quaternary structure consequent to hemoglobin binding. In this report sulfhydryl reactivity toward p-mercuribenzoate is studied in an attempt to identify such long-range conformational changes. Formation of stoichiometric hemoglobin/CDB3 complexes is shown to produce major changes in sulfhydryl reactivity. Since the sulfhydryl pocket of CDB3 is known to lie at the dimeric interface over 100 A from the hemoglobin-binding site, the observed changes in reactivity suggest that hemoglobin complexation induces a global change in quaternary structure of the CDB3 dimer. This change offers a mechanism to explain functional connections between CDB3-binding sites and the anion transport sites on band 3. The existence of such long-range conformational changes would imply that the CDB3 dimer is poised to function as a cytosolic arm or lever in order to modulate the global structure of the porter.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1987

Cross-correlation analysis of neuronal activities.

Nerve impulses are generally regarded as spike train and analyzed by use of various kinds of so-called time series analyses. Cross-correlation analysis is used to reveal temporal and/or spatial relationships between more than two spike trains in the neuronal circuit, in which two neurons are synaptically connected or two neurons are independent but receive a common input. Three main characteristics of discharge dependency between two neurons become clear from the cross-correlation histogram: 1) the direction of dependency; 2) the latency of interaction; and 3) the type of functional connections between the neurons. We reviewed the cross-correlation analysis from these points of view: 1) what is cross-correlation analysis; 2) what are primary and secondary effects; 3) what kinds of functional information can be obtained from the shape of the primary effect; 4) how sensitively cross-correlation can detect neuronal interaction; 5) how to express quantitatively the primary effect; 6) what kinds of extension technique are available from cross-correlation; and 7) research trends using cross-correlation analysis.

Animals↗
PubMed2001

Physiological concentrations of melatonin and corticosterone affect phagocytosis and oxidative metabolism of ring dove heterophils.

A functional connection between the neuroendocrine and the immune systems has been established. Of particular interest is the finding that hormones such as melatonin and corticosterone are able to exert modulating effects on the immune function. Therefore, after determining the circadian rhythms of melatonin and corticosterone, we evaluated the in vitro effect of physiological concentrations of melatonin and corticosterone, separately and together, on the phagocytic function and superoxide anion levels of heterophils in ring dove (Streptopelia risoria). Trials were performed with concentrations corresponding to the nocturnal and diurnal levels reached by each of the hormones (50:300 pg/mL and 100:10 ng/mL for melatonin and corticosterone, diurnal:nocturnal, respectively). The phagocytes were incubated with the hormones both alone and concurrently. At the highest (nocturnal) concentration, melatonin augmented phagocytic function and at the same time inducing a fall in superoxide anion levels. At the highest (diurnal) concentration, corticosterone also enhanced phagocytic function, but without modifying the phagocyte oxidative metabolism. In the presence of both hormones, however, whether with nocturnal or diurnal concentrations, there was a greater increase in phagocytic function and a decrease in superoxide anion levels than was produced by either of the hormones alone. In conclusion, our findings suggest that melatonin and corticosterone may have an additive effect in the modulation of phagocytic function.

Animals↗
PubMed2003

Transcriptional activities of the zinc finger protein Zac are differentially controlled by DNA binding.

Zac encodes a zinc finger protein that promotes apoptosis and cell cycle arrest and is maternally imprinted. Here, we show that Zac contains transactivation and repressor activities and that these transcriptional activities are differentially controlled by DNA binding. Zac transactivation mapped to two distinct domains. One of these contained multiple repeats of the peptide PLE, which behaved as an autonomous activation unit. More importantly, we identified two related high-affinity DNA-binding sites which were differentially bound by seven Zac C(2)H(2) zinc fingers. Zac bound as a monomer through zinc fingers 6 and 7 to the palindromic DNA element to confer transactivation. In contrast, binding as a monomer to one half-site of the repeat element turned Zac into a repressor. Conversely, Zac dimerization at properly spaced direct and reverse repeat elements enabled transactivation, which strictly correlated with DNA-dependent and -independent contacts of key residues within the recognition helix of zinc finger 7. The later ones support specific functional connections between Zac DNA binding and transcriptional-regulatory surfaces. Both classes of DNA elements were identified in a new Zac target gene and confirmed that the zinc fingers communicate with the transactivation function. Together, our data demonstrate a role for Zac as a transcription factor in addition to its role as coactivator for nuclear receptors and p53.

Amino Acid Sequence↗
PubMed2005

Large brains in autism: the challenge of pervasive abnormality.

The most replicated finding in autism neuroanatomy-a tendency to unusually large brains-has seemed paradoxical in relation to the specificity of the abnormalities in three behavioral domains that define autism. We now know a range of things about this phenomenon, including that brains in autism have a growth spurt shortly after birth and then slow in growth a few short years afterward, that only younger but not older brains are larger in autism than in controls, that white matter contributes disproportionately to this volume increase and in a nonuniform pattern suggesting postnatal pathology, that functional connectivity among regions of autistic brains is diminished, and that neuroinflammation (including microgliosis and astrogliosis) appears to be present in autistic brain tissue from childhood through adulthood. Alongside these pervasive brain tissue and functional abnormalities, there have arisen theories of pervasive or widespread neural information processing or signal coordination abnormalities (such as weak central coherence, impaired complex processing, and underconnectivity), which are argued to underlie the specific observable behavioral features of autism. This convergence of findings and models suggests that a systems- and chronic disease-based reformulation of function and pathophysiology in autism needs to be considered, and it opens the possibility for new treatment targets.

Animals↗
PubMed2003

Human von Willebrand factor (factor VIII-related antigen) in glial neoplastic cells of brain gliomas.

In order to determine whether the glial neoplastic cells within the brain gliomas show human von Willebrand factor (factor VIII-related antigen [FVIII-rA]) expression, and the possible distribution of FVIII-rA positive glial cells within the neoplasm, morphological examination and computerised morphometric analysis were conducted in 35 brain neoplasms, divided into 2 groups: glioblastoma multiforme (15 cases) and astrocytoma II (20 cases). Only in glioblastomas was the expression of FVIII-rA within the glial neoplastic cells found to be significantly higher than in background. The groups of FVIII-rA positive glial cells were usually found near the vascular glomeruloid structures. On the basis of the examination, the following conclusions were drawn: at least a part of the glial neoplastic cells within the glioblastoma multiforme may present expression of FVIII-rA; lack of FVIII-rA expression in the glial cells of astrocytomas II suggests that the activity of FVIII-rA within these cells is connected with the malignancy of gliomas; the role of FVIII-rA positive glial cells remains unknown, but the tendency to location near the vascular glomeruloid structures of glioblastomas might suggest their potential functional connection with endothelial cells.

Adult↗