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At least 1,081 records · Page 60Linked to original sources
PubMed2003

Plastic control of striatal glutamatergic transmission by ensemble actions of several neurotransmitters and targets for drugs of abuse.

Long-lasting alterations in the efficacy of glutamatergic synapses, such as long-term potentiation (LTP) and long-term depression (LTD), are prominent models for mechanisms of information storage in the brain. It has been suggested that exposure to drugs of abuse produces synaptic plasticity at glutamatergic synapses that shares many features with LTP and LTD, and that these synaptic changes may play roles in addiction. We have examined the involvement of particular neurotransmitters in synaptic plasticity at glutamatergic synapses within the striatum, a brain region with prominent roles in initiation and sequencing of actions, as well as habit formation. Our studies indicate that multiple neurotransmitters interact to produce striatal synaptic plasticity, and that the relative strength and patterning of the afferent inputs that release the various neurotransmitters determines whether LTP or LTD is activated. Drugs of abuse interact with glutamatergic synaptic plasticity in multiple ways, including alterations in dopamine release and more direct effects on glutamate release and glutamate receptors. We hypothesize that these effects contribute to addiction by facilitating the formation of new, drug-centered habits, and by disruption of more adaptive behaviors.

Animals↗
PubMed2004

Noninvasive optical imaging by speckle ensemble.

We propose a new method imaging through scattering media. An object hidden between two biological tissues (chicken breast) is reconstructed from any speckled images obtained from the output of a multichannel optical imaging system. The effect of multiple imaging is achieved with a microlens array. Each lens is the array projects a different speckled image onto a digital camera. The set of speckled images from the entire array is first shifted to a common center and then accumulated into a single average picture.

Animals↗
PubMed2005

Molecular mechanism for stabilizing a short helical peptide studied by generalized-ensemble simulations with explicit solvent.

We study the folding mechanism of an analog of the C-peptide of ribonuclease A in explicit water by a replica-exchange multicanonical molecular dynamics simulation based on all-atom models. The multicanonical weight factor was determined by the combined use of the multicanonical replica-exchange method and the replica-exchange multicanonical algorithm. Using statistically reliable data thus obtained, we have examined the free-energy landscape of the peptide system. The global-minimum free-energy state in the landscape at room temperature has an alpha-helix structure with a distortion near the N-terminus. The state also has a salt bridge between Glu(-)-2 and Arg(+)-10 and an aromatic-aromatic interaction between Phe-8 and His(+)-12, both of which have been observed in x-ray and other experimental measurements. Principal component analysis clearly shows the different roles of these side-chain interactions in the peptide folding. The side-chain interaction between Phe-8 and His(+)-12 greatly enhances the stability of helical structure toward the C-terminal end, whereas the salt bridge between Glu(-)-2 and Arg(+)-10 mainly works as a restraint to prevent the alpha-helix structure from extending to the N-terminus. The free-energy landscape of C-peptide reveals a funnel-like shape where all of these interactions consistently exist only in the global-minimum state. This is the major reason why the native structure of the short helical peptide shows significant stability at low temperatures.

Algorithms↗
PubMed2006

Ensemble-based convergence analysis of biomolecular trajectories.

Assessing the convergence of a biomolecular simulation is an essential part of any careful computational investigation, because many fundamental aspects of molecular behavior depend on the relative populations of different conformers. Here we present a physically intuitive method to self-consistently assess the convergence of trajectories generated by molecular dynamics and related methods. Our approach reports directly and systematically on the structural diversity of a simulation trajectory. Straightforward clustering and classification steps are the key ingredients, allowing the approach to be trivially applied to systems of any size. Our initial study on met-enkephalin strongly suggests that even fairly long trajectories (approximately 50 ns) may not be converged for this small--but highly flexible--system.

Biopolymers↗
PubMed2006

Spectral signatures of heterogeneous protein ensembles revealed by MD Simulations of 2DIR spectra.

A model for the calculation of amide I FTIR and 2DIR spectra taking into account fluctuations in hydrogen bonding and structure from molecular dynamics (MD) simulations is tested on three systems. It is found that although the homogeneous lineshape approximation yields satisfactory FTIR spectra, 2DIR spectra are sensitive to the inhomogeneity naturally present in any solvated protein and the common approximations of a static structure and averaged-effect solvent are invalid. By building on the local amide Hamiltonian and incorporating site energy variation with electrostatic-based models and disorder from MD trajectories, good agreement is obtained between calculated and measured 2DIR spectra. The largest contribution to the observed inhomogeneity is found to be the fluctuating site energies, which in turn are most sensitive to the water solvent. With the ability to accurately predict 2DIR spectra from atomistic simulations, new opportunities to test force fields and mechanistic predictions from MD are revealed.

Computer Simulation↗
PubMed1981

The structure of EEG arousal as a dynamic ensemble of neuronal activities in cat motor cortex.

1. Intracellular potentials were recorded from 164 cells in cat precruciate cortex, and their responses were examined during the phasic and tonic phases of EEG arousal. 2. According to the initial responses corresponding to phasic EEG arousal, these cells were classified into 71 E (excitation), 49 I (inhibition), 38 DF (disfacilitation), and 6 DI (disinhibition) cells. 3. The late responses corresponding to tonic EEG arousal varied among these cells. Thirty-two of the 164 cells were unresponsive. Of the remaining cells, 102 showed excitation, 16 inhibition, 12 disfacilitation, and 2 disinhibition. These cells were retermed +E, +I, +DF, and +DI cells, respectively. 4. +E cells were located at all depths through laminae I to VI, but the majority were found in laminae IIIb-VI. +I cells were between lamina I and the lower half of lamina III (IIIb), and +DF and +DI cells were between lamina I and the upper half of lamina III (IIIa). From these characteristic layer distributions it is postulated that an upward cascade transmission from deep to superficial layers occurs during tonic EEG arousal. 5. Nine types of combinations of the initial and late responses were found: E, I, DF or DI with +E, E or I with +I, E or I with +DF, and I with +DI. To explain these various activity patterns, an 'arousal' circuit model was proposed by combining the downward and upward cascade transmission patterns. The elementary structure of cortical arousal was thus formulated, and discussed from the development aspect of behavior.

Action Potentials↗
PubMed2006

Macromolecular ensembles of internal and external fibrinolysis: the resources for enhancement of thrombolysis efficacy.

The results of the search for new plasminogen activators for thrombolytic therapy have been reviewed with analysis of slowdown in this process. The reserves of increasing the effectiveness of thrombolysis are considered and the mechanisms underlying the interactions between plasminogen and its activators with fibrin are described. The domain composition of the fibrinolytic agents and the functional role of their structural elements in fibrinolytic interactions are discussed. The action of fibrin-specific and fibrin-nonspecific plasminogen activators in fibrinolysis has been evaluated. The necessity of the investigation of the regularities of internal and external fibrinolysis has been substantiated. The internal fibrinolysis became the resource for enhancement of thrombolysis efficacy. The approaches to the use of internal fibrinolysis to increase the effectiveness of enzyme therapy (monotherapy with plasminogen or new-made plasminogen activator as well as polytherapy with combination of different plasminogen activators /thrombolysis trigger plus third-generation plasminogen activator of prolonged action/) have been outlined and the relationship between this research and the current tendencies in the improvement of clinical thrombolysis (dose reduction, adjacent therapy, etc.) has been discussed.

Antifibrinolytic Agents↗
PubMed2004

Evolutionary origins of lymphocytes: ensembles of T cell and B cell transcriptional regulators in a cartilaginous fish.

The evolutionary origins of lymphocytes can be traced by phylogenetic comparisons of key features. Homologs of rearranging TCR and Ig (B cell receptor) genes are present in jawed vertebrates, but have not been identified in other animal groups. In contrast, most of the transcription factors that are essential for the development of mammalian T and B lymphocytes belong to multigene families that are represented by members in the majority of the metazoans, providing a potential bridge to prevertebrate ancestral roles. This work investigates the structure and regulation of homologs of specific transcription factors known to regulate mammalian T and B cell development in a representative of the earliest diverging jawed vertebrates, the clearnose skate (Raja eglanteria). Skate orthologs of mammalian GATA-3, GATA-1, EBF-1, Pax-5, Pax-6, Runx2, and Runx3 have been characterized. GATA-3, Pax-5, Runx3, EBF-1, Spi-C, and most members of the Ikaros family are shown throughout ontogeny to be 1) coregulated with TCR or Ig expression, and 2) coexpressed with each other in combinations that for the most part correspond to known mouse T and B cell patterns, supporting conservation of function. These results indicate that multiple components of the gene regulatory networks that operate in mammalian T cell and B cell development were present in the common ancestor of the mammals and the cartilaginous fish. However, certain factors relevant to the B lineage differ in their tissue-specific expression patterns from their mouse counterparts, suggesting expanded or divergent B lineage characteristics or tissue specificity in these animals.

Amino Acid Sequence↗
PubMed1999

The effect of a chemical protective ensemble on intravenous line insertion by emergency medical technicians.

Protective gear is mandatory for medical personnel treating casualties in a contaminated environment. In the present study, we assessed the ability of emergency medical technicians to insert an intravenous line in this situation. Sixty emergency medical technicians were randomized to a control group, wearing fatigues, and a study group, wearing full protective gear. The ability to insert an intravenous line in healthy volunteers was assessed 1, 2, 4, and 8 hours after randomization. We found no effect of protective gear (p = 0.543) or time in protective gear (p = 0.8869) on success rate or on time needed for successful task completion (p = 0.4005 and p = 0.9021, respectively). The overall success rate was 58.6%, 65% in the unprotected state and 56% in the protected state, and the time was 303 +/- 115 and 351 +/- 113 seconds, respectively. These findings suggest that introduction of an intravenous line is possible but time consuming even after a prolonged stay in full protective gear. Alternative methods for antidotal treatment, such as the use of automatic autoinjectors for intramuscular administration, might be suggested.

Adolescent↗
PubMed2002

[Sequential rearrangements of ensemble activity of the putamen neurons of monkeys as a correlate to continuous behavior].

Simultaneous recording of unit activity of 6-8 putamen neurons in two monkeys (M. nemestrina and M. mulatta) during performance of the task of alternative spatial choice, was carried out. The extent of rearrangements of the activity in the groups of neurons with the transition from every step of the behavioral program to the next one and the degree of difference in mosaics of reactivity, forming at every step with a different variants of performance, were evaluated using discriminative analysis. The rearrangements of the impulse activity were recorded in all steps of the program. The dynamics of rearrangements with the choice of right or left feeder was different, which resulted in appearance of significant differences in mosaics of reactivity at the stage of decision making and receiving reward. The rearrangements preceding the task-oriented movement of one hand were more pronounced in the contralateral hemisphere. The volume of rearrangements may increase with the performance of movement but the differences of mosaics formed during the movement of right and left hand are decreasing. At the stage of reception of the reward, the rearrangements were greater in case the animal chose the certain (left) feeder irrespective of the side of recording the unit activity.

Action Potentials↗