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PubMed2003

The insulator binding protein CTCF associates with the nuclear matrix.

Nuclear DNA is organized into chromatin loop domains. At the base of these loops, matrix-associated regions (MARs) of the DNA interact with nuclear matrix proteins. MARs act as structural boundaries within chromatin, and MAR binding proteins may recruit multiprotein complexes that remodel chromatin. The potential tumor suppressor protein CTCF binds to vertebrate insulators and is required for insulator activity. We demonstrate that CTCF is associated with the nuclear matrix and can be cross-linked to DNA by cisplatin, an agent that preferentially cross-links nuclear matrix proteins to DNA in situ. These results suggest that CTCF anchors chromatin to the nuclear matrix, suggesting that there is a functional connection between insulators and the nuclear matrix. We also show that the chromatin-modifying enzymes HDAC1 and HDAC2, which are intrinsic nuclear matrix components and thought to function as corepressors of CTCF, are incapable of associating with CTCF. Hence, the insulator activity of CTCF apparently involves an HDAC-independent association with the nuclear matrix. We propose that CTCF may demarcate nuclear matrix-dependent points of transition in chromatin, thereby forming topologically independent chromatin loops that may support gene silencing.

Amino Acid Sequence↗
PubMed2005

Exploring functional relationships between components of the gene expression machinery.

Eukaryotic gene expression requires the coordinated activity of many macromolecular machines including transcription factors and RNA polymerase, the spliceosome, mRNA export factors, the nuclear pore, the ribosome and decay machineries. Yeast carrying mutations in genes encoding components of these machineries were examined using microarrays to measure changes in both pre-mRNA and mRNA levels. We used these measurements as a quantitative phenotype to ask how steps in the gene expression pathway are functionally connected. A multiclass support vector machine was trained to recognize the gene expression phenotypes caused by these mutations. In several cases, unexpected phenotype assignments by the computer revealed functional roles for specific factors at multiple steps in the gene expression pathway. The ability to resolve gene expression pathway phenotypes provides insight into how the major machineries of gene expression communicate with each other.

Adenosine Triphosphatases↗
PubMed2001

Coevolutionary networks: a novel approach to understanding the relationships of humans with the infectious agents.

Human organism is interpenetrated by the world of microorganisms, from the conception until the death. This interpenetration involves different levels of interactions between the partners including trophic exchanges, bi-directional cell signaling and gene activation, besides genetic and epigenetic phenomena, and tends towards mutual adaptation and coevolution. Since these processes are critical for the survival of individuals and species, they rely on the existence of a complex organization of adaptive systems aiming at two apparently conflicting purposes: the maintenance of the internal coherence of each partner, and a mutually advantageous coexistence and progressive adaptation between them. Humans possess three adaptive systems: the nervous, the endocrine and the immune system, each internally organized into subsystems functionally connected by intraconnections, to maintain the internal coherence of the system. The three adaptive systems aim at the maintenance of the internal coherence of the organism and are functionally linked by interconnections, in such way that what happens to one is immediately sensed by the others. The different communities of infectious agents that live within the organism are also organized into functional networks. The members of each community are linked by intraconnections, represented by the mutual trophic, metabolic and other influences, while the different infectious communities affect each other through interconnections. Furthermore, by means of its adaptive systems, the organism influences and is influenced by the microbial communities through the existence of transconnections. It is proposed that these highly complex and dynamic networks, involving gene exchange and epigenetic phenomena, represent major coevolutionary forces for humans and microorganisms.

Adaptation, Physiological↗
PubMed1982

[Blood volume in aorto-femoral bypass operation. Effects of continuous thoracic epidural-, halothane- or neuroleptanesthesia].

49 patients with obliterative arteriosclerotic disease of aortic or iliac artery were tested with three different types of anaesthesia, epidural, halothane, and neuroleptanaesthesia. A normal blood volume was found preoperatively in these patients, i.e. of 75.8 +/- 14.9 ml/kg weight. Connections between blood volume and age or factors of risk were not traced. A patient with a-v fistula showed an obvious increased blood volume (120.2 ml/kg). Intraoperatively the blood volume varied widely during the different types of anaesthesia: while the blood volume increased in epidural anaesthesia (+17%) and remained unchanged by halothane (+1%), it decreased at the same volume load during neuroleptanaesthesia (-17%). A clear connection between changes of cardiac output and changes of the filling potential of the heart (cvp x bv) was found during epidural anaesthesia (r = 0.93). There was no functional connection in the neurolept group (r = -0.08). With halothane changes of filling potential correlated negatively with changes in cardiac output (r = 0.72). A connection between changes of the blood volume and the central venous pressure is evident only in the epidural group (r = 0.59). At the same time these reactions are dependent on the extent of the individual alterations of the vegetative tonus by the epidural block. Those individual changes are even more evident under halothane (r = 0.32) and especially neuroleptanaesthesia (r = 0.28). Therefore we question the control of blood volume by measurement of the central venous pressure for these patients.

Anesthesia, Epidural↗
PubMed1977

[Organization of the hypothalamo-amygdalar system in rats].

In acute experiments on rabbits, the ascending influences of phylogenetically different parts of hypothalamus on different nuclei of amygdala were studied with the aid of EP method. In mammals a certain type of organization of hypothalamic ascending connections with amygdala was found. It was shown that phylogenetically ancient--anterior--parts of hypothalamus are projected mainly onto the oldest (cortico--medial) division of amygdala, which is the olfactory center of the forebrain. On the other hand, phylogenetically younger nuclei of hypothalamus are functionally connected with young parts of amygdala (basolateral division) which are the important regulatory component of limbic system. The properties of functional organization of hypothalamic--amygdaloid system of integration in rabbits are discussed.

Amygdala↗
PubMed1980

Peptide-containing neurones connect the two ganglionated plexuses of the enteric nervous system.

The enteric nervous system (ENS) of the mammalian gut consists principally of two ganglionated plexuses, the myenteric and submucous, which are embedded in the gut wall. Little is known about the anatomical and functional connections between the two plexuses and further clarification of their relationship is of central importance for the understanding of the ENS. In the present study we have approached this problem in a new way, using methods we have previously developed for maintaining the myenteric and submucous plexuses separately in vitro for several weeks. In an immunohistochemical study of these preparations and also of sections from normal and extrinsically denervated gut wall, we have found evidence for reciprocal projections between the myenteric and submucous plexuses, by nerve fibres containing two putative neurotransmitters, vasoactive intestinal polypeptide (VIP) and substance P (ref. 5) (see Fig. 1). Our observations were supported by radioimmunoassay of tissue extracts. These results suggest that one of the roles of these peptides in the gut is to coordinate the function of the two enteric plexuses.

Animals↗
PubMed1983

Vasoactive peptides and regulation of hemodynamics in different functional states of the organism.

It is important to emphasize that the biochemical systems participating in humoral hemodynamic regulation may function at any level of the circulatory homeostasis: in the blood as a biological fluid constantly circulating along the vessels, at the microcirculatory bed where the exchange with tissues is realized, on the tonic activity of the resistive and capacitance vessels, defining the systemic blood pressure rate and organ redistribution, or, finally, on the main motive force of the blood, the heart. The interrelations of some molecular factors form the biochemical basis for the interaction of the main humoral systems. These factors are kallikrein for kinins and converting enzyme for the renin-angiotensin system, 9-ketoreductase and phospholipase for kinin and prostaglandin systems, and Hageman factors for coagulation, fibrinolysis, and kininogenesis systems. This main scheme includes "functional" connections, which are defined by a physiological interaction, and those between the central and peripheral nervous systems. We may, evidently, postulate an important biological regularity of a multi-functional participation of the same physiologically active factors in maintaining circulatory homeostasis. On the other hand, we have to emphasize the functional unity and joint correlating actions of different biochemical blood systems.

Animals↗
PubMed1986

Functional relations of the rodent claustral-entorhinal-hippocampal system.

Electrophysiological studies of the claustrum of rat demonstrate functional connections with the limbic system (dentate gyrus, hippocampus) via the entorhinal cortex. The pathways show reciprocal connectivity, a degree of topological organization and the capacity for a long-term response potentiation in the claustral projection to entorhinal cortex. The hypothesis that claustrum acts to functionally link neocortical regions with components of the limbic system is considered.

Animals↗
PubMed2003

Electroencephalographic signatures of attentional and cognitive default modes in spontaneous brain activity fluctuations at rest.

We assessed the relation between hemodynamic and electrical indices of brain function by performing simultaneous functional MRI (fMRI) and electroencephalography (EEG) in awake subjects at rest with eyes closed. Spontaneous power fluctuations of electrical rhythms were determined for multiple discrete frequency bands, and associated fMRI signal modulations were mapped on a voxel-by-voxel basis. There was little positive correlation of localized brain activity with alpha power (8-12 Hz), but strong and widespread negative correlation in lateral frontal and parietal cortices that are known to support attentional processes. Power in a 17-23 Hz range of beta activity was positively correlated with activity in retrosplenial, temporo-parietal, and dorsomedial prefrontal cortices. This set of areas has previously been characterized by high but coupled metabolism and blood flow at rest that decrease whenever subjects engage in explicit perception or action. The distributed patterns of fMRI activity that were correlated with power in different EEG bands overlapped strongly with those of functional connectivity, i.e., intrinsic covariations of regional activity at rest. This result indicates that, during resting wakefulness, and hence the absence of a task, these areas constitute separable and dynamic functional networks, and that activity in these networks is associated with distinct EEG signatures. Taken together with studies that have explicitly characterized the response properties of these distributed cortical systems, our findings may suggest that alpha oscillations signal a neural baseline with "inattention" whereas beta rhythms index spontaneous cognitive operations during conscious rest.

Attention↗
PubMed2000

Reciprocal information flow between prefrontal cortex and ventral tegmental area in an animal model of schizophrenia.

The medial prefrontal cortex (PFC) is anatomically and functionally connected with the ventral tegmental area (VTA), the neuronal source of mesocorticolimbic system that is pathophysiologically related to schizophrenia-like symptoms. Methamphetamine (MAP) was applied to examine the functional relationship between PFC and VTA in an animal model of schizophrenia. Hyperactivity and stereotyped behavior were observed accompanied by a distinctive direction of information flow. In hyperactivity, information flow in the direction from PFC to VTA was dominant. Contrarily, dominant information flow from VTA to PFC was found in stereotyped behavior. These results indicate that dysfunctional interaction between PFC and VTA is the neuronal basis of MAP-induced schizophrenia-like psychosis. The information flow and its direction can be useful tool to explain the neurogenesis of these abnormal behaviors.

Animals↗
PubMed2002

Basic mechanisms of TMS.

Transcranial magnetic stimulation (TMS) is now established as an important noninvasive measure for neurophysiologic investigation of the central and peripheral nervous systems in humans. Magnetic stimulation can be used for stimulating peripheral nerves with a similar mechanism of activation as for electrical stimulation. When TMS is applied to the cerebral cortex, however, some features emerge that distinguish it from transcranial electrical stimulation. One of the most important features is designated the D and I wave hypothesis, which is now widely accepted as a mechanism of TMS of the motor cortex. Transcranial electrical stimulation excites the pyramidal tract axons directly, either at the initial segment of the neuron or at proximal internodes in the subcortical white matter, giving rise to D (direct) waves, whereas TMS excites the pyramidal neurons transsynaptically, giving rise to I (indirect) waves. There are still other phenomena with mechanisms that remain to be elucidated. First, not only excitatory effects but also inhibitory effects can be elicited by TMS of the cerebral cortex (e.g., the silent period and intracortical inhibition). The inhibitory effect may also be used to investigate cerebral functions other than the motor cortex, such as the visual, sensory cortices, and the frontal eye field, from which no overt response like the motor evoked potential can be elicited. Second, there is an abundance of intraregional functional connectivities among different cortical areas that can also be revealed by TMS, or TMS in combination with neuroimaging techniques. Last, repetitive transcranial stimulation exerts a lasting effect on brain function even after the stimulation has ceased. With further investigation of the neural mechanisms of TMS, these techniques will open up new possibilities for investigating the physiologic function of the brain as well as opportunities for clinical application.

Brain↗
PubMed1977

Quantitive studies of the reactions to horizontal angular accelerations in axolotls. II. head-turning reflexes in animals with a supernumerary pair of labyrinths.

In axolotls (Ambystoma mexicanun) the labyrinths and the associated parts of the medulla were doubled artificially. In these so-called tandem-heads the vestibular afferent fibres from both labyrinths on one side united within the medulla to form common bundles. The head-turning reflexes following impulse acceleration and during long-lasting acceleration were measured quantitatively and compared with those for normal animals. The form and the time-course of the reactions were almost identical in both groups. Tandem-heads showed a linear relationship between stimulus intensity and reaction strength, parallel to that in normal animals but with a greater reaction for a given stimulus. Consequent to this shift in the relationship, there was a significant decrease in the reaction threshold. The removal of one horizontal semicircular canal in tandem-heads proved that both pairs of labyrinths were functionally connected with the brain. It was suggested that during ontogenesis there exists a kind of specificity in the connexion of vestibular fibres. From the parallel shift of the intensity functions it was concluded that the input from both pairs of labyrinths in tandem-heads is not simply accumulate but compared with a reference parameter, which is also double in tandem-heads.

Ambystoma↗
PubMed1983

[Neuropsychological repercussions of chronic alcoholism.].

Although there is no evidence of general intellectual deterioration in chronic alcoholics, several specific deficits have been identified in them during neuropsychological tests used to evaluate their cognitive, mnemonic, visual-motor and spatial capacities. The neurological interpre-ation of this data allows one to suppose that diffuse cerebral damage exists, involving in particular the frontal lobes and their functional connections with the limbic and diencephalic structure. Although a substantial recuperation is effected during the 2 or 3 weeks following the termination of alcohol consumption, the restoration of the functions remains generally incomplete; thus the necessity for treatment programs adapted to the needs and capacities of this population and the elaboration of techniques aimed at the maximum recuperation of these deficits.

English Abstract↗
PubMed1991

The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography.

We have studied regional cerebral blood flow changes in 6 patients after their recovery from a first hemiplegic stroke. All had a single well-defined hemispheric lesion and at least a brachial monoparesis that subsequently recovered. Each patient had 6 measurements of cerebral blood flow by positron tomography with 2 scans at rest, 2 during movement of fingers of the recovered hand, and 2 during movement of fingers of the normal hand. When the normal fingers were moved, regional cerebral blood flow increased significantly in contralateral primary sensorimotor cortex and in the ipsilateral cerebellar hemisphere. When the fingers of the recovered hand were moved, significant regional cerebral blood flow increases were observed in both contralateral and ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres. Other regions, namely, insula, inferior parietal, and premotor cortex, were also bilaterally activated with movement of the recovered hand. We have also demonstrated, by using a new technique of image analysis, different functional connections between the thalamic nuclei and specific cortical and cerebellar regions during these movements. Our results suggest that ipsilateral motor pathways may play a role in the recovery of motor function after ischemic stroke.

Adult↗
PubMed2004

The circadian clock in the brain: a structural and functional comparison between mammals and insects.

The circadian master clocks in the brains of mammals and insects are compared in respect to location, organization and function. They show astonishing similarities. Both clocks are anatomically and functionally connected to the optic system and possess multiple output pathways allowing synchronization with the environmental light-dark cycles as well as the control of diverse endocrine, autonomic and behavioral functions. Both circadian master clocks are composed of multiple neurons, which are organized in populations with different morphology, physiology and neurotransmitter content and appear to subserve different functions. In the hamster and in the cockroach, the master clock consists of a core region that gets input from the eyes, and a shell region from which the majority of output projections originate. Communication between core and shell, between all other populations of clock neurons as well as between the master clocks of both brain hemispheres is a prerequisite of normal rhythmic function. Phenomena like rhythm splitting and internal desynchronization can be observed under constant light conditions and are caused by the "uncoupling" of the master clocks of both brain hemispheres.

Animals↗
PubMed1998

[Intraepidermal free nerve fiber endings and their importance for cutaneous pain].

INTRODUCTION: Former studies performed by means of supravital methylene blue (MB) staining could demonstrate intraepidermal free nerve fiber endings (FNE). Unfortunately, these publications were only illustrated by drawings. Furthermore, the practical details of the method were only insufficiently handed down to posterity. Therefore, a modification of the staining procedure should be worked out for this purpose. Subsequently, the possible advantages of the method compared with common histochemical techniques should be clarified. Regarding the possible nociceptive functions of the FNE, the corresponding conclusions should be drawn from the results. METHODS: The dye was injected subepidermally into the hairless skin of the palmar- and plantar sites of rat paws followed by light microscopy. RESULTS: 2 different morphological types of FNE could be detected within the epidermis. The thick FNE, which occurred less frequently than the thin ones (approximately 20/mm(2) in relation to 1000/mm(2)), represented nerve fiber branches ascending up to the granular layer where they formed superficial plexus (Figs. 1 and 3b). In contrast to the thick FNE, the thin ones were varicose and unbranched (Figs. 2 and 3a). CONCLUSIONS: Regarding the demonstration of morphological details, especially the branching pattern and the thickness of FNE, MB-staining achieves interesting results. The visualization of 2 different types of FNE within the epidermis extends the validity of the concept of punctate sensibility into this skin layer. Both types of FNE have to be functionally connected with different sensoric tasks. Possibly, a subpopulation of the thin FNE might be identical to the substance P-immunoreactive one which is wellknown to possess primarily a nociceptive function.

English Abstract↗
PubMed2004

Brain differences in newborn rats predisposed to helpless and depressive behavior.

Inborn brain differences in metabolic capacity were mapped in congenitally helpless rats, a genetically selected strain predisposed to show helpless and depressive behavior. There are a number of brain regions showing abnormal metabolism in adult congenitally helpless rats. Some of these alterations may be innate while others may be due to environmental factors, such as maternal care and postnatal stress. To identify which brain structures show innate differences, brains of newborn rats from congenitally helpless and non-helpless strains were compared using cytochrome oxidase histochemistry, an endogenous marker of regional metabolic capacity. A smaller subset of regions affected in adults showed significantly less metabolic activity in the newborn brains, including paraventricular hypothalamus, habenula, hippocampus, subiculum, lateral septal nucleus, anterior cingulate cortex, infralimbic cortex, and medial orbitofrontal cortex. A covariance analysis further revealed a striking reduction of functional connectivity in the congenitally helpless brain, including a complete decoupling of limbic forebrain regions from midbrain/diencephalic regions. This pattern of brain metabolism suggests that helplessness vulnerability is linked to altered functioning of limbic networks that are key to controlling the hypothalamic-pituitary-adrenal axis. This implies that vulnerable animals have innate deficits in brain systems that would normally allow them to cope with stress, predisposing them in this manner to more readily develop helpless and depressive behaviors.

Analysis of Variance↗
PubMed2000

Genes, themes and microarrays: using information retrieval for large-scale gene analysis.

The immense volume of data resulting from DNA microarray experiments, accompanied by an increase in the number of publications discussing gene-related discoveries, presents a major data analysis challenge. Current methods for genome-wide analysis of expression data typically rely on cluster analysis of gene expression patterns. Clustering indeed reveals potentially meaningful relationships among genes, but can not explain the underlying biological mechanisms. In an attempt to address this problem, we have developed a new approach for utilizing the literature in order to establish functional relationships among genes on a genome-wide scale. Our method is based on revealing coherent themes within the literature, using a similarity-based search in document space. Content-based relationships among abstracts are then translated into functional connections among genes. We describe preliminary experiments applying our algorithm to a database of documents discussing yeast genes. A comparison of the produced results with well-established yeast gene functions demonstrates the effectiveness of our approach.

Animals↗