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1.
The central mechanisms of regulation of certain types of motivation at different respiration modes were investigated. Brain activity was studied by the safest and sufficiently informative method of electroencephalography. In total, 24 apparently healthy young subjects were examined. The subjects were relatively homogeneous according to the results of the following tests: motivation to success of primarily moderate and high level, moderate readiness to risk, and low motivation to approval. The realization of motivation as the most important component of the functional system of purposeful behavior caused changes in the level of activation of brain structures. A significant increase in the θ-rhythm power in response to forced hyperventilation with room-temperature air and in almost all frequency ranges during forced isocapnic hyperventilation with cold air was detected in virtually all brain regions. Multiple correlations between the studied types of motivation and the electrical activity of the brain at different loading modes were found. An expressed motivation to success is associated with a reduced power of pathological rhythms, whereas a decreased motivation of public approval is associated with the activation of deep structures of the brain at rest and under the influence of cold. At rest and during hyperventilation, an inverse correlation between the readiness to risk and slow brain activity was observed. In the case of cold air inhalation, the lower the individual readiness to take risks, the higher the β-rhythm power in all cortical areas. Regardless of the stable level of certain types of motivation, brain responses to various provocative factors changed the correlation patterns: some correlations became negligible, some were enhanced, and others changed their direction. 相似文献
2.
《Comptes rendus biologies》2014,337(12):661-678
Target identification aims at identifying biomolecules whose function should be therapeutically altered to cure the considered pathology. An algorithm for in silico target identification using Boolean network attractors is proposed. It assumes that attractors correspond to phenotypes produced by the modeled biological network. It identifies target combinations which allow disturbed networks to avoid attractors associated with pathological phenotypes. The algorithm is tested on a Boolean model of the mammalian cell cycle and its applications are illustrated on a Boolean model of Fanconi anemia. Results show that the algorithm returns target combinations able to remove attractors associated with pathological phenotypes and then succeeds in performing the proposed in silico target identification. However, as with any in silico evidence, there is a bridge to cross between theory and practice. Nevertheless, it is expected that the algorithm is of interest for target identification. 相似文献
3.
Gukovsky I Lugea A Shahsahebi M Cheng JH Hong PP Jung YJ Deng QG French BA Lungo W French SW Tsukamoto H Pandol SJ 《American journal of physiology. Gastrointestinal and liver physiology》2008,294(1):G68-G79
Although alcohol abuse is the major cause of chronic pancreatitis, the pathogenesis of alcoholic chronic pancreatitis (ACP) remains obscure. A critical obstacle to understanding the mechanism of ACP is lack of animal models. Our objective was to develop one such model. Rats were pair-fed for 8 wk ethanol or control Lieber-DeCarli liquid diet. For the last 2 wk, they received cyclosporin A (CsA; 20 mg/kg once daily) or vehicle. After 1 wk on CsA, one episode of acute pancreatitis was induced by four 20 microg/kg injections of cerulein (Cer); controls received saline. Pancreas was analyzed 1 wk after the acute pancreatitis. CsA or Cer treatments alone did not result in pancreatic injury in either control (C)- or ethanol (E)-fed rats. We found, however, that alcohol dramatically aggravated pathological effect of the combined CsA+Cer treatment on pancreas, resulting in massive loss of acinar cells, persistent inflammatory infiltration, and fibrosis. Macrophages were prominent in the inflammatory infiltrate. Compared with control-fed C+CsA+Cer rats, their ethanol-fed E+CsA+Cer counterparts showed marked increases in pancreatic NF-kappaB activation and cytokine/chemokine mRNA expression, collagen and fibronectin, the expression and activities of matrix metalloproteinase-2 and -9, and activation of pancreatic stellate cells. Thus we have developed a model of alcohol-mediated postacute pancreatitis that reproduces three key responses of human ACP: loss of parenchyma, sustained inflammation, and fibrosis. The results indicate that alcohol impairs recovery from acute pancreatitis, suggesting a mechanism by which alcohol sensitizes pancreas to chronic injury. 相似文献
4.
Few ecologists today doubt that competition is an important structuring factor in plant communities, but researchers disagree on the circumstances where it is most intense, and on which traits can be considered to contribute to competitive ability in different species. The distinction between a species' effect on resources and its response to reduced resource levels might help to solve these questions. Whereas classical competition theory predicts competitive exclusion of species with similar requirements, recent ideas stress that species diversity may be explained by a multitude of processes acting at different scales, and that similarities in competitive abilities often may facilitate coexistence. 相似文献
5.
Chereshnev VA Gusev EIu Zotova NV 《Rossi?skii fiziologicheski? zhurnal imeni I.M. Sechenova / Rossi?skaia akademiia nauk》2010,96(7):696-707
The concept of systemic inflammatory response syndrome (SIRS) by sepsis as well as quality of SIRS criteria, classification, and PIRO system has been a subject to analytical criticism in terms of theory of physiologic and typical pathological process. It has been disclosed SIRS can be considered only as the syndrome, that solves particular clinical tasks, but not as a basic model of pathogenesis of critical states. In authors' opinion it is more correctly to discuss systemic inflammation as a typical pathologic process that appears as a complex of one or another "resuscitation" syndrome in a clinical course. 相似文献
6.
Chen X Ghribi O Geiger JD 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,294(3):R829-R835
Sporadic inclusion body myositis (IBM) is the most common age-related muscle disease in humans; however, its etiology is unknown, there are few animal models for this disease, and effective treatments have not been identified. Similarities between pathological findings in Alzheimer's disease brain and IBM skeletal muscle include increased levels of amyloid precursor protein (APP) and amyloid beta-protein (Abeta). Moreover, there have been suggestions that elevated levels of free cholesterol might participate in the pathogenesis of Alzheimer's disease and IBM due, in part, to its role in Abeta generation. Here, we tested the hypothesis that rabbits fed cholesterol-enriched diets might faithfully exhibit human-like IBM pathological features. In skeletal muscle of one-third of the female rabbits fed cholesterol-enriched diet but not control diet, we found features of IBM, including vacuolated muscle fibers, increased numbers of mononuclear inflammatory cells, increased intramuscular deposition of Abeta, hyperphosphorylated tau, and increased numbers of muscle fibers immunopositive for ubiquitin. The cholesterol-enriched diet increased mRNA and protein levels of APP, increased the protein levels of betaAPP cleaving enzyme, and shifted APP processing in favor of Abeta production. Our study has demonstrated that increased ingestion of high levels of dietary cholesterol can result in pathological features that resemble IBM closely and thus may serve as an important new model with which to study this debilitating disorder. 相似文献
7.
Many theoretical and field studies have emphasized the impact of disturbance in the dynamics and diversity of sessile organism communities. This view is best reflected by the Intermediate Disturbance Hypothesis (IDH), which states that a maximum of diversity is found in ecosystems or communities experiencing intermediate disturbance regimes or at an intermediate stage of development since the last major disturbance event. Although theoretical models based on competitive interactions tend to validate this hypothesis, a recent meta-analysis of field experiments revealed that the mono-modal relationship between disturbance and diversity might not be a general pattern. In this article, we investigate the relationship between disturbance and diversity through the study of patch models, combining two types of competitive interactions: with or without competitive hierarchy, with two mechanisms influencing colonization: negative frequency dependence in colonization rates and immigration. These combinations led to various disturbance-diversity patterns. In the model without competitive hierarchy (founder effect model), a decreasing relationship appeared to be the rule as mentioned in previous studies. In the model with competitive hierarchy, the IDH pattern was obtained for low frequency dependence and low immigration. Nevertheless, high negative frequency dependence in colonization rates led to a decreasing relationship between disturbance and diversity. In contrast, high immigration led to an increasing relationship. The coexistence window (the range of disturbance intensity allowing coexistence) was the widest for intermediate immigration rates. For random species assemblages, patterns with multiple peaks were also possible. These results highlight the fact that the mono-modal IDH pattern should not be considered a rule. Competition and colonization mechanisms have a profound impact on the relationship between disturbance and diversity. 相似文献
8.
Tatiana Kameneva Tianlin Ying Ben Guo Dean R. Freestone 《Journal of computational neuroscience》2017,42(2):203-215
Epilepsy is one of the most common neurological disorders and is characterized by recurrent seizures. We use theoretical neuroscience tools to study brain dynamics during seizures. We derive and simulate a computational model of a network of hippocampal neuronal populations. Each population within the network is based on a model that has been shown to replicate the electrophysiological dynamics observed during seizures. The results provide insights into possible mechanisms for seizure spread. We observe that epileptiform activity remains localized to a pathological region when a global connectivity parameter is less than a critical value. After establishing the critical value for seizure spread, we explored how to correct the effect by altering particular synaptic gains. The spreading of seizures is quantified using numerical methods for seizure detection. The results from this study provide a new avenue of exploration for seizure control. 相似文献
9.
In rats with alcohol motivation on the model of water deprivation with substitution of water for 20% ethanol solution, motivatiogenic "drinking centres" of the hypothalamus initiate in response to electro- and chemostimulation (acetylcholine) behavioural reactions of search and taking of alcohol and not of water. Electrolytic ablation of "thirst centres" of the perifornical hypothalamus area in rats with a formed attraction to alcohol is accompanied by a decrease of its taking during 3-5 days of observation. Microinjections of dipsogenic peptide angiotensin II, unlike acetylcholine administration, do not initiate taking of water or alcohol, but elicit only appearance of orienting-investigating, alimentary, sexual and other behavioural reactions. It is suggested that formation of alcohol motivation in these conditions is connected with a change of neurophysiological and neurochemical properties of the hypothalamus "thirst centres" initiating an active search and taking of alcohol and not of the water in rats with experimental alcoholism. 相似文献
10.
The NAD+ analogue, 3-aldoxime pyridine adenine dinucleotide, is prepared by transglycosidation. Contrary to the published data, this analogue shows no activity as coenzyme with alcohol dehydrogenase from horse liver or from yeast. This is demonstrated by three methods: no increase of absorption at 331 nm by the enzymic oxidation of ethanol; no increase at 290 nm with cinnamic alcohol; and no exchange reaction. The inhibition by this analogue of the oxidation of ethanol by NAD+ is competitive at pH 7.6 and 9.5 with yeast alcohol dehydrogenase; with liver alcohol dehydrogenase, it is of the mixed type at pH 7.6 and non-competitive at pH 9.5. The lack of activity of the analogue and inhibition of the competitive or mixed type may be explained by the fact that the binary complex does not bind the substrate or that in the ternary complex the hydride shift does not occur. The non-competitive inhibition at pH 9.5 with the horse liver alcohol dehydrogenase may be explained by the existence of binding sites specific for this analogue. 相似文献
11.
Kuner R 《Nature medicine》2010,16(11):1258-1266
Chronic pain is a major challenge to clinical practice and basic science. The peripheral and central neural networks that mediate nociception show extensive plasticity in pathological disease states. Disease-induced plasticity can occur at both structural and functional levels and is manifest as changes in individual molecules, synapses, cellular function and network activity. Recent work has yielded a better understanding of communication within the neural matrix of physiological pain and has also brought important advances in concepts of injury-induced hyperalgesia and tactile allodynia and how these might contribute to the complex, multidimensional state of chronic pain. This review focuses on the molecular determinants of network plasticity in the central nervous system (CNS) and discusses their relevance to the development of new therapeutic approaches. 相似文献
12.
Ethanol elimination from the blood of rats with different psychophysiological features was studied using gas chromatographic head-space analysis in the general complex of tests aimed at determination of ethanol consumption. The selection of animals with different levels of the initial alcohol motivation was performed according to modified Porsolt's method. It was shown that the initial level of predisposition to depression-like states is in a dose-dependent correlation with the high rate of ethanol elimination. This is suggested to be one of the genetic indications which promotes the formation of the initial alcohol motivation and the development of experimental alcoholism. 相似文献
13.
Kinetics of inhibition of ethanol metabolism in rats and the rate-limiting role of alcohol dehydrogenase 总被引:1,自引:0,他引:1
If liver alcohol dehydrogenase were rate-limiting in ethanol metabolism, inhibitors of the enzyme should inhibit the metabolism with the same type of kinetics and the same kinetic constants in vitro and in vivo. Against varied concentrations of ethanol, 4-methylpyrazole is a competitive inhibitor of purified rat liver alcohol dehydrogenase (Kis = 0.11 microM, in 83 mM potassium phosphate and 40 mM KCl buffer, pH 7.3, 37 degrees C) and is competitive in rats (with Kis = 1.4 mumol/kg). Isobutyramide is essentially an uncompetitive inhibitor of purified enzyme (Kii = 0.33 mM) and of metabolism in vivo (Kii = 1.0 mmol/kg). Low concentrations of both inhibitors decreased the rate of metabolism as a direct function of their concentrations. Qualitatively, therefore, alcohol dehydrogenase activity appears to be a major rate-limiting factor in ethanol metabolism. Quantitatively, however, the constants may not agree because of distribution in the animal or metabolism of the inhibitors. At saturating concentrations of inhibitors, ethanol is eliminated by inhibitor-insensitive pathways, at about 10% of the total rate at a dose of ethanol of 10 mmol/kg. Uncompetitive inhibitors of alcohol dehydrogenase should be especially useful for inhibiting the metabolism of alcohols since they are effective even at saturating levels of alcohol, in contrast to competitive inhibitors, whose action is overcome by saturation with alcohol. 相似文献
14.
The study of alcohol dependence mechanisms has been aided by work in rodents, where regimens of intermittent chronic administration
with repeated episodes of intoxication and withdrawal can be coupled with controlled timing of in vitro studies and the possibility of relating them to behavior. The chronic intermittent ethanol (CIE) model in the rat has been
found to be a good model of human alcohol dependence, showing persistent signs of withdrawal and self-administration. Studies
in CIE rats suggest that plastic changes in GABA-mediated inhibition involving the GABAA receptor system may be responsible for the behavioral alterations. Here we summarize a combination of evidence that the alcoholic
rat CIE model demonstrates changes in GABAA receptor subunit levels, in receptor localization, and in physiology and pharmacology, leading to alterations in behavior
that contribute to the hyperexcitable alcohol withdrawal state (anxiety, insomnia, seizure susceptibility) and alcohol dependence.
Special Issue dedicated to Dr. Simo S. Oja 相似文献
15.
Dias-Peixoto MF Ferreira AJ Almeida PW Braga VB Coutinho DC Melo DS Gomes Filho A Melo MB Greco L Campagnole-Santos MJ Lima RF Santos RA Guatimosim S 《Peptides》2012,35(2):196-201
The Mas protooncogene encodes a G protein-coupled receptor that has been described as a functional receptor for the cardioprotective fragment of the renin-angiotensin system (RAS), Angiotensin (Ang)-(1-7). The aim of this current study was to evaluate the responsiveness of Mas expression in hearts during different physiological and pathological conditions in rats. Physical training was considered a physiological condition, while isoproterenol-induced hypertrophy, myocardial infarction and DOCA-salt model of hypertension were used as pathological models of heart injury. The expression of Mas was analyzed by western blotting. Although swim-trained rats presented significant cardiac hypertrophy, our physical training protocol was unable to induce changes in the expression of Mas. On the other hand, cardiac hypertrophy and damage elicited by isoproterenol treatment led to a reduction in Mas expression. Myocardial infarction also significantly decreased the expression of Mas after 21 days of myocardial ischemia. Additionally, Mas expression levels were increased in hearts of DOCA-salt rats. Our present data indicate that Mas expression is responsive to different pathological stimuli, thereby suggesting that Mas receptor is involved in the homeostasis of the heart, as well as in the establishment and progression of cardiac diseases. 相似文献
16.
Sagar Kania Alparslan Oztekin Xuanhong Cheng X. Frank Zhang Edmund Webb 《Biophysical journal》2021,120(10):1903-1915
The globular-to-unraveled conformation transition of von Willebrand factor (vWF), a large polymeric glycoprotein in human blood plasma, is a crucial step in the process of clotting at sites of vascular injury. However, unraveling of vWF multimers in uninjured vasculature can lead to pathology (i.e., thrombus formation or degradation of vWF proteins by enzyme ADAMTS13, making them nonfunctional). To identify blood flow conditions that might induce pathological unraveling of vWF multimers, here we have computed the globular-to-unraveled transition rate of vWF multimers subjected to varying strain rate elongational flow by employing an enhanced sampling technique, the weighted ensemble method. Weighted ensemble sampling was employed instead of standard brute-force simulations because pathological blood flow conditions can induce undesired vWF unraveling on timescales potentially inaccessible to standard simulation methods. Results here indicate that brief but periodic exposure of vWF to the elongational flow of strain rate greater than or equal to 2500 s−1 represents a source of possible pathology caused by the undesired unraveling of vWF multimers. 相似文献
17.
M A Abdallah J F Biellmann J P Samama A D Wrixon 《European journal of biochemistry》1976,64(2):351-360
The preparation of model compounds 1-(2',6'-dichlorobenzyl)-3-halogenopyridinium and the study of their properties were achieved. Their chemical reduction to the corresponding 1,4-dihydropyridines is proved by spectroscopic analysis. 3-Iodopyridine--adenine dinucleotide was prepared by enzymic transglycosidation while the 3-chloro, 3-bromo and 3-iodo pyridine--adenine dinucleotides were synthesized from 3-amino-pyridine--adenine dinucleotide. The 3-halogenopyridine--adenine dinucleotides were proved to be active as hydrogen acceptors with alcohol as a substrate. The absorption band at 290 nm of cinnamaldehyde appeared to be a very sensitive tool for studying the enzymic reaction. With the alcohol dehydrogenase from yeast, only slight activity was detected. 3-Halogenopyridine--adenine dinucleotides are competitive inhibitors with respect to nicotinamide--adenine dinucleotide with alcohol dehydrogenase from yeast, lactate dehydrogenase and malate dehydrogenase. The use of 3-iodopyridine--adenine dinucleotide as a heavy-atom derivative for X-ray structure determination is proposed. 相似文献
18.
The development of methods to assess the impact of amino acid mutations on human health has become an important goal in biomedical research, due to the growing number of nonsynonymous SNPs identified. Within this context, computational methods constitute a valuable tool, because they can easily process large amounts of mutations and give useful, almost cost-free, information on their pathological character. In this paper we present a computational approach to the prediction of disease-associated amino acid mutations, using only sequence-based information (amino acid properties, evolutionary information, secondary structure and accessibility predictions, and database annotations) and neural networks, as a model building tool. Mutations are predicted to be either pathological or neutral. Our results show that the method has a good overall success rate, 83%, that can reach 95% when trained for specific proteins. The methodology is fast and flexible enough to provide good estimates of the pathological character of large sets of nonsynonymous SNPs, but can also be easily adapted to give more precise predictions for proteins of special biomedical interest. 相似文献
19.
Moira L. Steyn-Ross D. Alistair Steyn-Ross Jamie W. Sleigh 《Cognitive neurodynamics》2012,6(3):215-225
During slow-wave sleep, general anesthesia, and generalized seizures, there is an absence of consciousness. These states are
characterized by low-frequency large-amplitude traveling waves in scalp electroencephalogram. Therefore the oscillatory state
might be an indication of failure to form coherent neuronal assemblies necessary for consciousness. A generalized seizure
event is a pathological brain state that is the clearest manifestation of waves of synchronized neuronal activity. Since gap
junctions provide a direct electrical connection between adjoining neurons, thus enhancing synchronous behavior, reducing
gap-junction conductance should suppress seizures; however there is no clear experimental evidence for this. Here we report
theoretical predictions for a physiologically-based cortical model that describes the general anesthetic phase transition
from consciousness to coma, and includes both chemical synaptic and direct electrotonic synapses. The model dynamics exhibits
both Hopf (temporal) and Turing (spatial) instabilities; the Hopf instability corresponds to the slow (≲8 Hz) oscillatory
states similar to those seen in slow-wave sleep, general anesthesia, and seizures. We argue that a delicately balanced interplay
between Hopf and Turing modes provides a canonical mechanism for the default non-cognitive rest state of the brain. We show
that the Turing mode, set by gap-junction diffusion, is generally protective against entering oscillatory modes; and that
weakening the Turing mode by reducing gap conduction can release an uncontrolled Hopf oscillation and hence an increased propensity
for seizure and simultaneously an increased sensitivity to GABAergic anesthesia. 相似文献
20.
Erik D. Fagerholm Chayanin Tangwiriyasakul Karl J. Friston Inês R. Violante Steven Williams David W. Carmichael Suejen Perani Federico E. Turkheimer Rosalyn J. Moran Robert Leech Mark P. Richardson 《PLoS computational biology》2020,16(12)
The propagation of epileptic seizure activity in the brain is a widespread pathophysiology that, in principle, should yield to intervention techniques guided by mathematical models of neuronal ensemble dynamics. During a seizure, neural activity will deviate from its current dynamical regime to one in which there are significant signal fluctuations. In silico treatments of neural activity are an important tool for the understanding of how the healthy brain can maintain stability, as well as of how pathology can lead to seizures. The hope is that, contained within the mathematical foundations of such treatments, there lie potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the dynamic causal modelling neuronal state equation generalises to a Fokker-Planck formalism if one extends the framework to model the ways in which activity propagates along the structural connections of neural systems. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity–i.e., by lowering the rate at which neuronal fluctuations disperse to neighbouring regions. We show, for neural systems prone to epileptic seizures, that such a reduction in diffusivity can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror the activity profile of a pathological region in its functionally connected areas. This counter-intuitive method is intended to be used pre-emptively–i.e., in order to mitigate the effects of the seizure, or ideally even prevent it from occurring in the first place. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network prior to seizure onset. Our hope is that this technique can form the basis for future real-time monitoring and intervention devices that are capable of treating epilepsy in a non-invasive manner. 相似文献