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At least 613 records · Page 34Linked to original sources
PubMed1978

Internal organization of membranes at end bulbs of Held in the anteroventral cochlear nucleus.

The end of bulb of Held in the rostral ventral cochlear nucleus of the chinchilla and guinea pig was studied with the freeze-fracture technique. The end bulb has multiple, small active zones which are uniformly distributed within the calyceal portion of this terminal. Single or small groups of active zones are surrounded by enlarged channels of extracellular space often containing processes of astrocytes. Small plasmalemmal deformations occur at these active zones. The number of these deformations is thought to be indicative of exocytotic transmitter release because they are more frequent in animals fixed in a noisy environment compared to animals fixed in a quiet environment. Thus, our study provides a basis for the quantitative study of changes in transmitter secretion at a central nervous system synapse driven by a controllable natural stimulus. The postsynaptic active zone at end bulbs resembles other excitatory synapses in the central nervous system in having an aggregate of large particles on the external membrane leaflet. This junctional aggregate of particles is coextensive with the presynaptic active zone and with the postsynaptic density seen in thin sections. Several perisynaptic aggregates of particles are deployed around each active zone on the external membrane leaflet. These irregularly-shaped aggregates occur preferentially opposite the channels of enlarged extracellular space and along the edge of the end bulb and are not components of intercellular junctions or plasmalemmal contacts with cytoplasmic organelles. Although the function of the different particle aggregates on the postsynaptic membrane is not clear, our findings provide a basis for studying the factors controlling and maintaining their structure as well as more evidence that a consistent relationship exists between types of synaptic action and structure of the postsynaptic membrane.

Acoustic Stimulation↗
PubMedDate not supplied

[Uterotonic action of sigetin and its effect on the Mg2+, ATP-dependent transport and stationary metabolism of Ca2+ through the myometrial sarcolemma].

The effect of sigetin (dipotassium salt, meso-3, 4-di-(n-sulfophenyl)- hexane) on the electrical and mechanical activity, Ca2+, Mg2+-ATPase activity and Mg2+, ATP-dependent Ca2+ transport in uterine smooth muscle have been investigated. Sigetin caused depolarization of the cell membrane, leading to Ca2+ dependent spike discharge and development of mechanical response. Sigetin also produced deceleration of the relaxation of carbachol contracture controlled mostly by the sarcolemmal ATP driven Ca2+ pump. The drug produced strong inhibition of Mg2+, ATP-dependent Ca2+ transport in sarcolemmal vesicles as well as the enzyme and transport activity of the solubilized Ca2+, Mg(2+)-ATPase reconstructed in liposomes. Under the experimental conditions close to the physiological (i.e. in the presence of an outwardly directed Ca2+ gradient) Ca2+ pump normally compensates passive release of this cation. Sigetin was found to shift this calcium equilibrium towards a non-compensated slow diffusion of the cation in the extravesicular space. Addition of sigetin to the incubation medium during the existence of the stationary transmembrane Ca2+ equilibrium stimulates transition of the stationary concentration of the cation in vesicles from high to lower level. The results suggest that the excitatory action of sigetin on myometrial smooth muscle may involve not only indirect stimulation of Ca2+ influx via the voltage operated Ca2+ channels but also through the inhibition of the ATP driven Ca2+ pump of the cell membrane.

Adenosine Triphosphate↗
PubMed2004

Extracellular mass transport considerations for space flight research concerning suspended and adherent in vitro cell cultures.

Conducting biological research in space requires consideration be given to isolating appropriate control parameters. For in vitro cell cultures, numerous environmental factors can adversely affect data interpretation. A biological response attributed to microgravity can, in theory, be explicitly correlated to a specific lack of weight or gravity-driven motion occurring to, within or around a cell. Weight can be broken down to include the formation of hydrostatic gradients, structural load (stress) or physical deformation (strain). Gravitationally induced motion within or near individual cells in a fluid includes sedimentation (or buoyancy) of the cell and associated shear forces, displacement of cytoskeleton or organelles, and factors associated with intra- or extracellular mass transport. Finally, and of particular importance for cell culture experiments, the collective effects of gravity must be considered for the overall system consisting of the cells, their environment and the device in which they are contained. This does not, however, rule out other confounding variables such as launch acceleration, on orbit vibration, transient acceleration impulses or radiation, which can be isolated using onboard centrifuges or vibration isolation techniques. A framework is offered for characterizing specific cause-and-effect relationships for gravity-dependent responses as a function of the above parameters.

Biophysical Phenomena↗
PubMed2003

Determinants of the exclusion zone in dopaminergic amacrine cell mosaics.

A fundamental organizing feature of the retina is the presence of regularly spaced distributions of neurons, yet we have little knowledge of how this patterning emerges during development. Among these retinal mosaics, the spatial organization of the dopaminergic amacrine cells is unique: using nearest-neighbor and Vornoi domain analysis, we found that the dopaminergic amacrine cells were neither randomly distributed, nor did they achieve the regularity documented for other retinal cell types. Autocorrelation analysis revealed the presence of an exclusion zone surrounding individual dopaminergic amacrine cells and modeling studies confirmed this organization, as the mosaic could be simulated by a minimal distance spacing rule defined by a broad set of parameters. Experimental studies determined the relative contributions of tangential dispersion, fate determination, and cell death in the establishment of this exclusion zone. Clonal boundary analysis and simulations of proximity-driven movement discount tangential dispersion, while data from bcl-2 overexpressing mice rule out feedback-inhibitory fate-deterministic accounts. Cell death, by contrast, appears to eliminate dopaminergic amacrine cells that are within close proximity, thereby establishing the exclusion zone surrounding individual cells and in turn creating their mosaic regularity.

Amacrine Cells↗
PubMed1999

Modelling action potentials and membrane currents of mammalian skeletal muscle fibres in coherence with potassium concentration changes in the T-tubular system.

During prolonged activity the action potentials of skeletal muscle fibres change their shape. A model study was made as to whether potassium accumulation and removal in the tubular space is important with respect to those variations. Classical Hodgkin-Huxley type sodium and (potassium) delayed rectifier currents were used to determine the sarcolemmal and tubular action potentials. The resting membrane potential was described with a chloride conductance, a potassium conductance (inward rather than outward rectifier) and a sodium conductance (minor influence) in both sarcolemmal and tubular membranes. The two potassium conductances, the Na-K pump and the potassium diffusion between tubular compartments and to the external medium contributed to the settlement of the potassium concentration in the tubular space. This space was divided into 20 coupled concentric compartments. In the longitudinal direction the fibre was a cable series of 56 short segments. All the results are concerned with one of the middle segments. During action potentials, potassium accumulates in the tubular space by outward current through both the delayed and inward rectifier potassium conductances. In between the action potentials the potassium concentration decreases in all compartments owing to potassium removal processes. In the outer tubular compartment the diffusion-driven potassium export to the bathing solution is the main process. In the inner tubular compartment, potassium removal is mainly effected by re-uptake into the sarcoplasm by means of the inward rectifier and the Na-K pump. This inward transport of potassium strongly reduces the positive shift of the tubular resting membrane potential and the consequent decrease of the action potential amplitude caused by inactivation of the sodium channels. Therefore, both potassium removal processes maintain excitability of the tubular membrane in the centre of the fibre, promote excitation-contraction coupling and contribute to the prevention of fatigue.

Action Potentials↗
PubMed2001

The relevance of stereopsis for motorists: a pilot study.

PURPOSE: To study the influence of stereoscopic depth perception on automobile driving performance. METHODS: Ten patients with strabismus and defective stereopsis were compared with ten healthy controls with respect to their performance in a series of automobile driving manoeuvres. The two groups were individually matched as to age, annual miles driven, years of licence holding and type of vehicle owned. After an ophthalmologic examination the subjects in each group performed the following series of driving tests: (1) stopping in front of an obstacle, (2) reversing into a parking space, (3) driving through a slalom course, (4) estimating the relative positions of two cars. All tests were performed binocularly and monocularly (with the non-dominant eye covered). RESULTS: Only in the slalom test did the normal subjects perform significantly better than the stereo-deficient subjects (odds ratio 10.5; P<0.01). In estimating position, normal subjects actually performed significantly worse (odds ratio 0.091; P<0.01). A significant distance ratio of 2.5 (95% CI 1.1-5.5; P=0.033) of the monocular with respect to the binocular performance of the normal subjects was found for the stopping task only, while the subjects with defective stereopsis showed no difference between their monocular and binocular performance. CONCLUSION: In this study, stereopsis had a positive effect on driving performance only in dynamic situations at intermediate distances.

Adult↗
PubMed2006

Limited contribution of claudin-5-dependent tight junction strands to endothelial barrier function.

Members of the claudin family are involved in formation of barriers that control access to the paracellular space of epithelia. Likewise, endothelium-specific claudin-5 is involved in the function of the blood-brain barrier (BBB). Here, we assessed the role of claudin-5 in non-BBB endothelial barriers using lentiviral-driven overexpression and silencing of claudin-5 in its native environment of primary vascular endothelial cells. Effects were monitored using macromolecular tracers between 342Da and 40kDa. Measurements were made both in absence and presence of transmigrating leukocytes. Freeze-fracture preparations were analyzed for effects at the ultrastructural level. We show that overexpression of claudin-5 leads to formation of elaborate networks of junction strands, which are absent in untransduced endothelial cells. Concomitantly, a modest, non-size-selective enhancement of the barrier function was observed. In contrast, silencing of endogenous claudin-5 does not influence barrier function. The efficient sealing of the endothelium during diapedesis of monocytes or granulocytes is also claudin-5 independent. Collectively, these data provide evidence for a limited contribution of claudin-5 to the barrier function of human umbilical vein endothelial cells (HUVEC), implying that, unlike selective barriers in epithelia, the barrier of non-BBB endothelium seems largely independent of claudin-directed tight junction structures.

Cell Membrane Permeability↗
PubMed1998

Supramolecular organization of immature and mature murine leukemia virus revealed by electron cryo-microscopy: implications for retroviral assembly mechanisms.

We have used electron cryo-microscopy and image analysis to examine the native structure of immature, protease-deficient (PR-) and mature, wild-type (WT) Moloney murine leukemia virus (MuLV). Maturational cleavage of the Gag polyprotein by the viral protease is associated with striking morphological changes. The PR- MuLV particles exhibit a rounded central core, which has a characteristic track-like shell on its surface, whereas the WT MuLV cores display a polygonal surface with loss of the track-like feature. The pleomorphic shape and inability to refine unique orientation angles suggest that neither the PR- nor the WT MuLV adheres to strict icosahedral symmetry. Nevertheless, the PR- MuLV particles do exhibit paracrystalline order with a spacing between Gag molecules of approximately 45 A and a length of approximately 200 A. Because of the pleomorphic shape and paracrystalline packing of the Gag-RNA complexes, we raise the possibility that assembly of MuLV is driven by protein-RNA, as well as protein-protein, interactions. The maturation process involves a dramatic reorganization of the packing arrangements within the ribonucleoprotein core with disordering and loosening of the individual protein components.

Animals↗
PubMed2002

Dynamics of coupled light waves and electron-acoustic waves.

The nonlinear interaction between coherent light waves and electron-acoustic waves in a two-electron plasma is considered. The interaction is governed by a pair of equations comprising a Schrödinger-like equation for the light wave envelope and a driven (by the light pressure) electron-acoustic wave equation. The newly derived nonlinear equations are used to study the formation and dynamics of envelope light wave solitons and light wave collapse. The implications of our investigation to space and laser-produced plasmas are pointed out.

Journal Article↗
PubMed2006

Fluctuation relations for a driven Brownian particle.

We consider a driven Brownian particle, subject to both conservative and nonconservative applied forces, whose probability evolves according to the Kramers equation. We derive a general fluctuation relation, expressing the ratio of the probability of a given Brownian path in phase space with that of the time-reversed path, in terms of the entropy flux to the heat reservoir. This fluctuation relation implies those of Seifert, Jarzynski, and Gallavotti-Cohen in different special cases.

Journal Article↗
PubMed2006

Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism.

The AcrA/AcrB/TolC complex spans the inner and outer membranes of Escherichia coli and serves as its major drug-resistance pump. Driven by the proton motive force, it mediates the efflux of bile salts, detergents, organic solvents, and many structurally unrelated antibiotics. Here, we report a crystallographic structure of trimeric AcrB determined at 2.9 and 3.0 angstrom resolution in space groups that allow asymmetry of the monomers. This structure reveals three different monomer conformations representing consecutive states in a transport cycle. The structural data imply an alternating access mechanism and a novel peristaltic mode of drug transport by this type of transporter.

Biological Transport↗
PubMed1991

Positive autoregulation of c-myb expression via Myb binding sites in the 5' flanking region of the human c-myb gene.

The nuclear proto-oncogene c-myb is preferentially expressed in lymphohematopoietic cells, in which it plays an important role in the processes of differentiation and proliferation. The mechanism(s) that regulates c-myb expression is not fully understood, although in mouse cells a regulatory mechanism involves a transcriptional block in the first intron. To analyze the contribution of the 5' flanking sequences in regulating the expression of the human c-myb gene, we isolated a genomic clone containing extensive 5' flanking sequences, the first exon, and a large portion of the first intron. Sequence analysis of a subcloned 1.3-kb BamHI insert corresponding to 687 nucleotides of the 5' flanking sequence, the entire first exon, and 300 nucleotides of the first intron revealed the presence of closely spaced putative Myb binding sites within a segment extending from nucleotides -616 to -575 upstream from the cap site. A 165-bp segment containing these putative Myb binding sites was linked to a human thymidine kinase (TK) cDNA driven by a low-activity proliferating cell nuclear antigen promoter and cotransfected into TK- ts13 cells with a plasmid in which a full-length human c-myb cDNA is driven by the early simian virus 40 promoter; Myb inducibility of TK mRNA expression was observed both in transient expression assays and in stable transformants. The highest level of inducibility was detected when the 165-bp fragment was placed 138 bp upstream of the proliferating cell nuclear antigen promoter-TK cDNA reporter unit or 3' of the TK cDNA. Mutation of the putative Myb binding sites greatly reduced c-myb transactivation of TK mRNA expression and specifically reduced the binding of in vitro-translated Myb protein at those sites. Finally, c-myb transactivated TK mRNA expression driven by a segment of the authentic c-myb 5' flanking region containing the Myb binding sites. These data suggest that human c-myb maintains high levels of Myb protein in cells that require this gene product for proliferation and/or differentiation by an autoregulatory mechanism involving Myb binding sites in the 5' flanking region.

Base Sequence↗
PubMed1998

The thyroid hormone receptor variant alpha2 is a weak antagonist because it is deficient in interactions with nuclear receptor corepressors.

The thyroid hormone receptor splice variant, alpha2, is unable to bind thyroid hormone (T3) and has been proposed to function as an endogenous inhibitor of T3 action. In this report, we examined further the DNA sequence requirements for alpha2 binding to thyroid hormone response elements (TREs) in an attempt to identify response elements that mediate potent inhibition by alpha2. Heterodimers of alpha2 and retinoid X receptor were found to bind to a subset of TREs (DR4, direct repeats spaced by 4 bp) in which selected flanking and spacer sequences enhanced interactions with the AGGTCA core binding sequence. Despite the optimization of the TRE-binding sites, alpha2 remained a weak dominant negative inhibitor of TRE-driven transcription. A promoter interference assay was also developed for testing inhibition by alpha2. In these studies, alpha2 blocked gene transcription, but it required cotransfected retinoid X receptor, and it was not as potent as unliganded thyroid hormone receptors. These results led to the hypothesis that alpha2 might be deficient in interactions with nuclear receptor corepressors. Consistent with this view, alpha2 did not silence basal transcription in its native form or when linked to Gal4. Alpha2 also failed to interact with corepressors (NCoR and SMRT) in both gel shift assays and mammalian two-hybrid assays. We conclude that alpha2 is a weak antagonist of thyroid hormone action because it binds weakly to a limited repertoire of response elements, and it does not interact with corepressors. Thus, alpha2 may be able to compete with thyroid hormone receptors for binding to a limited group of target sites, but it is not able to actively inhibit transcription.

Binding Sites↗
PubMedDate not supplied

The Windkesselventricle with guiding balloon as a new approach for assisted circulation.

A simple method was developed to aid the patient with low cardiac output syndrome following cardiac surgery. The concept was shown to be feasible in electric circulatory analog studies and verified in 20 dog experiments. A Dacron graft (end-to-side) through the right second intercostal space connects the ascending aorta to the subcutaneously implanted, ellipsoidal-shaped artifical ventricle. A spherical polyurethane balloon is positioned in the aorta distal to the Dacron graft via the femoral artery. The ventricle and balloon are pneumatically driven synchronously with the ECG. In natural systole the balloon is inflated, occluding the aorta, and the artificial ventricle sucks the entire stroke volume. In natural diastole the balloon deflates and the artificial ventricle ejects the blood into the peripheral arteries. With this system it is possible to maintain a normal systemic pressure and have high hemodynamic efficiency. The left ventricular systolic pressure is 85 percent unloaded. The systolic wave is turned 180 degrees to the natural. After treatment, the device can be removed without thoracotomy.

Animals↗
PubMed1990

Functional organization of the cortical 17/18 border region in the cat.

The representation of the visual field in the 17/18 border region of the cat's visual cortex, and the layout of orientation and ocular dominance columns, were studied by making many closely spaced electrode penetrations into the superficial layers of the flattened dorsal region of the marginal gyrus and recording response properties at each location. The 17/18 border region was defined by measuring the change in the horizontal component of receptive field position within the gyrus: as the position of the recording electrode moved from medial to lateral, the receptive fields moved towards the vertical midline, indicating that the electrode was in area 17; as penetrations were made in increasingly lateral positions, the trend reversed, and receptive field positions moved away from the midline, indicating that the electrode was in area 18. The receptive fields of cells close to the border straddled, or lay within 2 degrees-3 degrees on either side of the vertical midline. In addition, patches of cortex were sometimes encountered in which cells had receptive field centers located up to 7 degrees in the ipsilateral visual field. Experiments in which maps were made in the left and right hemispheres of a single animal showed that these patches had a complementary distribution in the two hemispheres. Cells within the patches behaved as though driven by Y-cell inputs: they usually had large receptive fields and responded to rapidly-moving stimuli. They were broadly tuned for orientation and strongly dominated by the contralateral eye. Fourier spectral analysis of orientation selectivity maps showed that iso-orientation bands had an average spacing of 1.14 +/- 0.1 mm and tended to be elongated in a direction orthogonal to the 17/18 border. Individual bands crossed the border without obvious interruption, although singularities (points of discontinuity in the layout of orientations) were more frequently observed in the border region than in adjacent areas. Two dominant periodicities could be measured in the maps of ocular dominance, one at around 0.8 +/- 0.2 mm and a second at 2.0 +/- 0.3 mm. No constant direction of elongation was noted. These are close to the periods present within areas 17 and 18 respectively.

Animals↗
PubMed2003

Partial nectar loads as a cause of multiple nectar transfer in the honey bee (Apis mellifera): a simulation model.

Honey bee foragers transfer their nectar loads to receiver bees within the nest. Surprisingly, they often transfer to more than one receiver (published values range from 1.9 to 2.7). Several adaptive hypotheses have been proposed to explain why multiple transfer occurs. One hypothesis, information improvement, states that multiple transfer arises as an adaptive forager-driven process. Foragers use the delay in finding a receiver to assess the relative work capacities of foragers and receivers, performing recruitment dances when appropriate. Multiple transferring improves their delay information. We used a stochastic simulation model to investigate the non-adaptive partial loads hypothesis. We determined the extent to which partial crop loads and receiver filling and emptying rules (i.e. how much nectar to accept before leaving the transfer area) can cause multiple transfer. As many as 1.9 nectar transfers per returning forager were generated within biologically realistic parameter space. We suggest that much multiple transfer arises as a non-adaptive consequence of partitioning nectar foraging between foragers and receivers, but that this will also result in foragers having better information about the relative work capacities of foragers and receivers as a useful consequence. We suggest that the number of transfers caused by partial loads could also be increased by an adaptive forager-driven effort to improve their information concerning the balance of foragers and receivers and we outline a framework wherein the information improvement hypothesis can be directly tested.

Adaptation, Psychological↗
PubMed2000

Interactive fast spin-echo imaging.

It is shown that a spin-echo sequence may be used to acquire T(2)-weighted, high-resolution, high-SNR sections at quasi-real-time frame rates for interactive, diagnostic imaging. A single-shot fast spin-echo sequence was designed which employs driven equilibrium to realign transverse magnetization remaining at the final spin echo. Driven equilibrium is shown to improve T(2) contrast at a given TR, or conversely to reduce TR by approximately 1000 msec and thus increase temporal resolution while maintaining a given level of contrast. Wiener demodulation of k-space data prior to reconstruction is shown to reduce blurring caused by T(2)-decay while constraining noise often associated with other inverse filters. Images are continuously acquired, reconstructed, and displayed at rates of one image every one to two seconds, while section position and contrast may be altered interactively. The clinical utility of this method is demonstrated with applications to dynamic pelvic floor imaging and interactive obstetric imaging.

Computer Systems↗