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At least 1,153 records · Page 64Linked to original sources
PubMed1999

Covariation of activity in visual and prefrontal cortex associated with subjective visual perception.

Visual areas of the occipitotemporal pathway are thought to be essential for the conscious perception of objects, but the contribution of other cortical regions and the neural mechanisms leading to the awareness of a visual stimulus remain unclear. By using functional MRI in humans exposed to bistable viewing conditions, subjective visual perception was related to covariation of activity in multiple extrastriate ventral, parietal, and prefrontal cortical areas. The coordination of activity among these regions was not linked to external sensory or motor events; rather, it reflected internal changes in perception and varied in strength with the frequency of perceptual events, suggesting that functional interactions between visual and prefrontal cortex may contribute to conscious vision. Because similar cortical systems have been implicated in short-term memory and motor planning, the results also imply that related neural processes may underlie visual awareness and the organization of voluntary behavior contingent on sensory cues.

Adult↗
PubMed2001

Plant adenosine 5'-phosphosulfate reductase is a novel iron-sulfur protein.

Adenosine 5'-phosphosulfate reductase (APR) catalyzes the two-electron reduction of adenosine 5'-phosphosulfate to sulfite and AMP, which represents the key step of sulfate assimilation in higher plants. Recombinant APRs from both Lemna minor and Arabidopsis thaliana were overexpressed in Escherichia coli and isolated as yellow-brown proteins. UV-visible spectra of these recombinant proteins indicated the presence of iron-sulfur centers, whereas flavin was absent. This result was confirmed by quantitative analysis of iron and acid-labile sulfide, suggesting a [4Fe-4S] cluster as the cofactor. EPR spectroscopy of freshly purified enzyme showed, however, only a minor signal at g = 2.01. Therefore, Mössbauer spectra of (57)Fe-enriched APR were obtained at 4.2 K in magnetic fields of up to 7 tesla, which were assigned to a diamagnetic [4Fe-4S](2+) cluster. This cluster was unusual because only three of the iron sites exhibited the same Mössbauer parameters. The fourth iron site gave, because of the bistability of the fit, a significantly smaller isomer shift or larger quadrupole splitting than the other three sites. Thus, plant assimilatory APR represents a novel type of adenosine 5'-phosphosulfate reductase with a [4Fe-4S] center as the sole cofactor, which is clearly different from the dissimilatory adenosine 5'-phosphosulfate reductases found in sulfate reducing bacteria.

Amino Acid Sequence↗
PubMed2006

Mixed analog/digital gonadotrope biosynthetic response to gonadotropin-releasing hormone.

Mammalian reproduction requires gonadotropin-releasing hormone (GnRH)-mediated signaling from brain neurons to pituitary gonadotropes. Because the pulses of released GnRH vary greatly in amplitude, we studied the biosynthetic response of the gonadotrope to varying GnRH concentrations, focusing on extracellular-regulated kinase (ERK) phosphorylation and egr1 mRNA and protein production. The overall average level of ERK activation in populations of cells increased non-cooperatively with increasing GnRH and did not show evidence of either ultrasensitivity or bistability. However, automated image analysis of single-cell responses showed that whereas individual gonadotropes exhibited two response states, inactive and active, both the probability of activation and the average response in activated cells increased with increasing GnRH concentration. These data indicate a hybrid single-cell response having both digital (switch-like) and analog (graded) features. Mathematical modeling suggests that the hybrid response can be explained by indirect thresholding of ERK activation resulting from the distributed structure of the GnRH-modulated network. The hybrid response mechanism improves the reliability of noisy reproductive signal transmission from the brain to the pituitary.

Animals↗
PubMed2003

A compartmental model of an external urethral sphincter motoneuron of Onuf's nucleus.

This article discusses a model of the electrical behavior of an external urethral sphincter motoneuron, based on morphological parameters like soma size, dendritic diameters and spatial dendritic configuration, and several electrical parameters. Because experimental data about the exact ion conductance mix of external urethral sphincter neurons is scarce, the gaps in knowledge about external urethral sphincter motoneurons were filled in with known data of alpha-motoneurons. The constructed compartmental model of motoneurons of Onuf's nucleus contains six voltage-dependent ionic conductances: a fast sodium and potassium conductance and an anomalous rectifier in the soma; a fast delayed rectifier type potassium conductance and a fast sodium conductance in the initial axon segment; an L-type calcium channel in the dendritic compartments. This paper considers the simulation of external urethral sphincter motoneuron responses to current injections that evoke bistable behavior. Simulations show self-sustained discharge following a depolarizing pulse through the microelectrode; the firing was subsequently terminated by a short hyperpolarizing pulse. This behavior is highly functional for neurons that have to exhibit prolonged activation during sphincter closure. In addition to these 'on' and 'off ' responses, we also observed a particular firing behavior in response to long-lasting triangular current pulses. When the depolarizing current was slowly increased and then decreased (triangular pulse) the firing frequency was higher during the descending phase than during the initial ascending phase.

Animals↗
PubMed1985

A model of the strain-induced B-Z transition.

The B-to-Z transition in supercoiled circular DNA is modeled as a strain-induced nonlinear excitation process. Using a model, in which DNA is regarded as a chain of units with a bistable energy function along the twisting coordinate together with a harmonic inter-unit interaction, we show that a Z region and the accompanying two B-Z junctions of finite width appear naturally as a solution of nonlinear equations, when the strain exceeds a critical value. We examine the B-Z transition behaviour as a function of twist under various situations. We also analyse available experimental results on B-Z transition in supercoiled plasmid with G-C insertions by this mechanistic model in order to estimate the magnitude of model parameters. The energy barrier of the B-Z transition is estimated to be of the order of 1 kcal/mole per base pair. The analysis shows that if the length of the insertion is less than a certain value, the entire insertion converts to Z form at a transition point, but if the insertion is much longer, the B-Z transition exhibits a different behavior, in which part of the insertion flips to Z form and the Z region expands linearly upon changing linking number.

DNA↗
PubMed2004

Ribosomal RNA kink-turn motif--a flexible molecular hinge.

Ribosomal RNA K-turn motifs are asymmetric internal loops characterized by a sharp bend in the phosphodiester backbone resulting in "V" shaped structures, recurrently observed in ribosomes and showing a high degree of sequence conservation. We have carried out extended explicit solvent molecular dynamics simulations of selected K-turns, in order to investigate their intrinsic structural and dynamical properties. The simulations reveal an unprecedented dynamical flexibility of the K-turns around their X-ray geometries. The K-turns sample, on the nanosecond timescale, different conformational substates. The overall behavior of the simulations suggests that the sampled geometries are essentially isoenergetic and separated by minimal energy barriers. The nanosecond dynamics of isolated K-turns can be qualitatively considered as motion of two rigid helix stems controlled by a very flexible internal loop which then leads to substantial hinge-like motions between the two stems. This internal dynamics of K-turns is strikingly different for example from the bacterial 5S rRNA Loop E motif or BWYV frameshifting pseudoknot which appear to be rigid in the same type of simulations. Bistability and flexibility of K-turns was also suggested by several recent biochemical studies. Although the results of MD simulations should be considered as a qualitative picture of the K-turn dynamics due to force field and sampling limitations, the main advantage of the MD technique is its ability to investigate the region close to K-turn ribosomal-like geometries. This part of the conformational space is not well characterized by the solution experiments due to large-scale conformational changes seen in the experiments. We suggest that K-turns are well suited to act as flexible structural elements of ribosomal RNA. They can for example be involved in mediation of large-scale motions or they can allow a smooth assembling of the other parts of the ribosome.

Base Sequence↗
PubMed2004

Ligand binding with continuous modification of binding sites.

Simultaneous formulation binding and structure modification of the binding site leads to binding process that can be analyzed within the framework of the non-linear theory of dynamic systems. Such an approach allows us to obtain several properties of the binding center: plurality of stationary (stable and unstable) states at binding, recognition of bistable and hysteretic binding modes. It is also shown that adsorption centre deformation leads to a S-shaped adsorption curve.

Adsorption↗
PubMed2006

Hypocretins: the timing of sleep and waking.

The appropriate time and place for sleep and waking are important factors for survival. Sleep and waking, rest and activity, flight and fight, feeding, and reproduction are all organized in relation to the day and night. A biological clock, the suprachiasmatic nucleus (SCN), synchronized by photic influences and other environmental cues, provides an endogenous timing signal that entrains circadian body rhythms and is complemented by a homeostatic sleep pressure factor. Cholinergic, catecholaminergic, serotonergic, and histaminergic nuclei control wakefulness and mutually interact with the SCN as well as sleep- and wake-promoting neurons in the hypothalamus to form a bistable switch that controls the timing of behavioral state transitions. Hypocretin neurons integrate circadian-photic and nutritional-metabolic influences and act as a conductor in the aminergic orchestra. Their loss causes narcolepsy, a disease conferring the inability to separate sleep and waking. Their role in appetitive behavior, stress, and memory functions is important to our understanding of addiction and compulsion.

Behavior↗
PubMed1995

Attentional tracking in the perception of apparent motion: evidence from sequential blanking displays.

Perception of sequential blanking displays was studied in a series of three experiments investigating factors that influence whether "shadow motion" or "item motion" is seen in a display. In addition to the duration of the blanking interval (BI) itself, three other such factors were identified: the eccentricity at which the display is viewed, the spacing of items in the display, and the type of motion that subjects are instructed to try to see. It is argued that these and other previously reported results are explicable without the need to invoke any kind of visual integration period. Instead, they are interpreted in terms of a first-order system of automatic luminance detectors and a second-order tracking system involving both voluntary and involuntary attention. The relationship of these findings to other recent work in apparent motion and visual attention and to other bistable motion displays is discussed.

Attention↗
PubMed2003

Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles: implications for spindle mechanics.

Microtubule plus ends dynamically attach to kinetochores on mitotic chromosomes. We directly imaged this dynamic interface using high resolution fluorescent speckle microscopy and direct labeling of kinetochores in Xenopus extract spindles. During metaphase, kinetochores were stationary and under tension while plus end polymerization and poleward microtubule flux (flux) occurred at velocities varying from 1.5-2.5 micro m/min. Because kinetochore microtubules polymerize at metaphase kinetochores, the primary source of kinetochore tension must be the spindle forces that produce flux and not a kinetochore-based mechanism. We infer that the kinetochore resists translocation of kinetochore microtubules through their attachment sites, and that the polymerization state of the kinetochore acts a "slip-clutch" mechanism that prevents detachment at high tension. At anaphase onset, kinetochores switched to depolymerization of microtubule plus ends, resulting in chromosome-to-pole rates transiently greater than flux. Kinetochores switched from persistent depolymerization to persistent polymerization and back again during anaphase, bistability exhibited by kinetochores in vertebrate tissue cells. These results provide the most complete description of spindle microtubule poleward flux to date, with important implications for the microtubule-kinetochore interface and for how flux regulates kinetochore function.

Anaphase↗
PubMed1982

Epitope-specific regulation. I. Carrier-specific induction of suppression for IgG anti-hapten antibody responses.

The epitope-specific regulatory system selectively controls IgG antibody production to the individual (haptenic) determinants on a complex antigen. This system can be specifically induced to suppress primary and secondary IgG antibody responses to dinitrophenyl hapten (DNP) without interfering with antibody responses to epitopes on the carrier molecule on which the DNP is presented. Furthermore, once induced, it will specifically suppress responses to DNP presented on unrelated carrier molecules. Results summarized here obtained using widely different immunization conditions, and a variety of haptens and carrier molecules indicate that this regulatory system controls antibody production in most T-dependent antibody responses. Carrier-specific suppressor T cells (CTs) that arise shortly after priming with a carrier molecule such as keyhole limpet hemocyaninin (KLH) induce the epitope-specific system to suppress in situ and adoptive antibody responses to epitopes (e.g., DNP) presented subsequently on the priming carrier. These well-known regulatory T cells are commonly believed to regulate antibody production by interfering with carrier-specific help; however, by repeating the original CTs transfer experiments with additional controls that define the specificity of the mechanism mediating suppression in CTs recipients, we show that KLH-specific CTs regulate responses by inducing typical isotope- specific suppression for anti-DNP responses when the recipients are immunized with DNP-KLH. Thus, whether KLH-primed animals are immunized directly with DNP-KLH (KLH/DNP-KLH immunization sequence) or whether T cells from these animals are challenged with DNP-KLH in (nonirradiated)recipients, anti-DNP responses are persistently suppressed while anti-carrier responses proceed normally. The aqueous KLH-priming protocols usually used to generate CTs are marginally more effective in priming for in situ suppression-induction than the alum KLH-priming protocols commonly used to generate KLH-specific helper T cells and used here in KLH/DNP-KLH immunizations. Thus, studies presented show that priming with an antigenic (carrier) molecule simultaneously prepares the animal for the production of typical secondary (anamnestic) antibody responses to epitopes on the priming antigen and for the induction of epitope-specific suppression for antibody production to determinants presented subsequently on the same antigenic molecule. We discuss the mechanism(s) responsible for this duality and its significance for antibody responses in an accompanying publication that describes the bistable regulatory capabilities of the epitope-specific system.

Animals↗
PubMed1992

Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats.

Immunization protocols that induce high levels of delayed-type hypersensitivity are often associated with low levels of antibody production, whereas alternative immunization strategies can produce the opposite effect. This reciprocal relationship appears to depend, at least in part, on the fact that T cell-derived lymphokines that are predominantly involved in one type of response inhibit the development of those T cells that promote the alternative one. Such a regulatory mechanism is likely to be bistable in that whenever one form of response is established, spontaneous development of the alternative one will be inhibited. We have applied this concept to the control of a cell-mediated autoimmune disease in rats. By covalently linking the autoantigen to anti-IgD antibody, we have targeted it to B cells for presentation to antigen-specific T cells. This form of presentation favors antibody production and may be expected to antagonize the cell-mediated disease-inducing response to the same antigen. To test this hypothesis, use was made of the fact that experimental allergic encephalomyelitis (EAE), when induced with the encephalitogenic peptide of guinea pig myelin basic protein, is purely a cell-mediated disease. The experiments show that Lewis rats, immunized with the peptide in its encephalitogenic form, were protected from disease when simultaneously injected with the peptide coupled to anti-IgD monoclonal antibodies. Control experiments showed that neither peptide nor anti-IgD alone were protective, and the peptide covalently coupled to irrelevant antibodies also failed to protect. Spleen cells from animals protected from disease by the anti-IgD-peptide conjugate, when activated in vitro with the encephalitogen, were able to transfer EAE to naive recipients. The results demonstrate that a cell-mediated immune response can be controlled by appropriate targeting of the specific antigen without inducing T cell anergy and suggest a potential strategy for preventing autoimmune diseases that are essentially cell-mediated in type.

Animals↗
PubMed1972

Voltage-dependent conductance induced in thin lipid membranes by monazomycin.

When present in micromolar amounts on one side of phospholipid bilayer membranes, monazomycin (a positively charged, polyene-like antibiotic) induces dramatic voltage-dependent conductance effects. Voltage clamp records are very similar in shape to those obtained from the potassium conductance system of the squid axon. The steady-state conductance is proportional to the 5th power of the monazomycin concentration and increases exponentially with positive voltage (monazomycin side positive); there is an e-fold change in conductance per 4-6 mv. The major current-carrying ions are univalent cations. For a lipid having no net charge, steady-state conductance increases linearly with KCl (or NaCl) concentration and is unaffected by Ca(++) or Mg(++). The current-voltage characteristic which is normally monotonic in symmetrical salt solutions is converted by a salt gradient to one with a negative slope-conductance region, although the conductance-voltage characteristic is unaffected. A membrane treated with both monazomycin and the polyene antibiotic nystatin (which alone creates anion-selective channels) displays bistability in the presence of a salt gradient. Thus monazomycin and nystatin channels can exist in parallel. We believe that many monazomycin monomers (within the membrane) cooperate to form a multimolecular conductance channel; the voltage control of conductance arises from the electric field driving monazomycin molecules at the membrane surface into the membrane and thus affecting the number of channels that are formed.

Anti-Bacterial Agents↗
PubMed1979

The contribution of a sensitizing pigment to the photosensitivity spectra of fly rhodopsin and metarhodopsin.

Most of the photoreceptors of the fly compound eye have high sensitivity in the ultraviolet (UV) as well as in the visible spectral range. This UV sensitivity arises from a photostable pigment that acts as a sensitizer for rhodopsin. Because the sensitizing pigment cannot be bleached, the classical determination of the photosensitivity spectrum from measurements of the difference spectrum of the pigment cannot be applied. We therefore used a new method to determine the photosensitivity spectra of rhodopsin and metarhodopsin in the UV spectral range. The method is based on the fact that the invertebrate visual pigment is a bistable one, in which rhodopsin and metarhodopsin are photointerconvertible. The pigment changes were measured by a fast electrical potential, called the M potential, which arises from activation of metarhodopsin. We first established the use of the M potential as a reliable measure of the visual pigment changes in the fly. We then calculated the photosensitivity spectrum of rhodopsin and metarhodopsin by using two kinds of experimentally measured spectra: the relaxation and the photoequilibrium spectra. The relaxation spectrum represents the wavelength dependence of the rate of approach of the pigment molecules to photoequilibrium. This spectrum is the weighted sum of the photosensitivity spectra of rhodopsin and metarhodopsin. The photoequilibrium spectrum measures the fraction of metarhodopsin (or rhodopsin) in photoequilibrium which is reached in the steady state for application of various wavelengths of light. By using this method we found that, although the photosensitivity spectra of rhodopsin and metarhodopsin are very different in the visible, they show strict coincidence in the UV region. This observation indicates that the photostable pigment acts as a sensitizer for both rhodopsin as well as metarhodopsin.

Animals↗
PubMed1983

Microspectrophotometry of single rhabdoms in the retina of the honeybee drone (Apis mellifera male).

The relative absorption spectra of the bistable photopigment of single rhabdoms from the dorsal region of the retina of the honeybee drone were obtained using slices of retina fixed in glutaraldehyde; less accurate measurements on unfixed tissue gave difference spectra that were similar to those for fixed retinae. The method used was based on measurements of absorbance changes during saturating adaptations of the visual pigment to different monochromatic lights. It is similar to previous methods based on measurements of difference spectra amplitudes, but is simpler to use and more accurate. The predominant pigment has states that absorb maximally at 446 (rhodopsin) and 505 nm (metarhodopsin). In addition, there is a small amount of another pigment whose two states absorb maximally at approximately 340 (UV) and 460 nm.

Animals↗
PubMed1987

The response to monochromatic light flashes of the oxygen consumption of honeybee drone photoreceptors.

Local measurements of the fall in oxygen pressure on stimulation of slices of the retina of the honeybee drone by flashes of light were made with oxygen microelectrodes and used to calculate the kinetics of the extra oxygen consumption (delta QO2) induced by each flash. The action spectrum for delta QO2 was obtained from response-intensity curves in response to brief (40 ms) monochromatic light flashes. The action spectrum of receptor potentials was obtained with the same experimental conditions. The two action spectra match closely: they deviate slightly from the photosensitivity spectrum of the drone rhodopsin (R). The deviation is thought to be due to wavelength-dependent light scattering and absorption in the preparation. In these experiments, the visual pigment was first illuminated with orange light, which is known to convert the bistable drone photopigment predominantly to the R state from the metarhodopsin (M) state. When long (300-900 ms) light flashes were used to elicit delta QO2, the responses to different wavelengths could not be matched in time course (as for the short flashes). Flashes producing large R-to-M conversions produced a prolonged delta QO2. The prolongation did not occur after double flashes, which produced both large R-to-M and M-to-R conversions. Similar changes in the length of afterpotentials in the photoreceptor cells and in a long-lasting decrease in photoreceptor intracellular K+ activity were found after long single or double flashes. The results are interpreted to show that the initial event for stimulation by light of metabolism in the drone retina is the same as that for stimulation of electrical responses (i.e., absorption of photons by R). Absorption of photons by M can produce an inhibitory effect on this stimulation.

Animals↗
PubMed2006

A probabilistic analysis of fire-induced tree-grass coexistence in savannas.

Fires play an important role in determining the composition and structure of vegetation in semiarid ecosystems. The study of the interactions between fire and vegetation requires a stochastic approach because of the random and unpredictable nature of fire occurrences. To this end, this article develops a minimalist probabilistic framework to investigate the impact of intermittent fire occurrences on the temporal dynamics of vegetation. This framework is used to analyze the emergence of statistically stable conditions favorable to tree-grass coexistence in savannas. It is found that these conditions can be induced and stabilized by the stochastic fire regime. A decrease in fire frequency leads to bush encroachment, while more frequent and intense fires favor savanna-to-grassland conversions. The positive feedback between fires and vegetation can convert states of tree-grass coexistence in semiarid savannas into bistable conditions, with both woodland and grassland as possible, though mutually exclusive, stable states of the system.

Ecosystem↗
PubMed2001

Optimization of intensity modulated radiotherapy under constraints for static and dynamic MLC delivery.

Multi-leaf collimators (MLCs) are emerging as the prevalent modality to apply intensity modulated radiotherapy (IMRT). Both the principle and the particular design of MLCs stipulate complex constraints on the practically applicable intensity modulated radiation fields. Most consequentially, the distribution of exposure times across the maximum field outline is either a piecewise constant function in the static mode or a piecewise linear function in the dynamic mode of driving an MLC. In view of clinical utility, the total leaf movement should be minimized, which requires that MLC-related constraints be considered in the dose optimization process. A method is proposed to achieve this for both static MLC fields and dynamic leaf close-in application. The method is an amendment to a generic gradient-based IMRT dose optimization algorithm and solves numerical problems related to the non-convexity of the MLC constraints, which can cause erratic behaviour of a gradient-based algorithm. It employs bistable penalty functions to select preferrable leaf configurations from the configuration space of the MLC, which is limited by specific design features. Together with an 'annealing' escape mechanism from local minima, the algorithm is capable of finding the optimum of an IMRT problem as leaf sequences with minimized leaf travel. In particular, the efficiency of static IMRT can be raised to the levels of unmodulated fields with very few field segments, thereby increasing the utility of IMRT in clinical practice.

Algorithms↗