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PubMed1979

Regulative influence of o-aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. IV. Bistability of metabolism and the mechanism of action of aminobenzoic acids.

Using the semi-continuous cultivation technique we could establish that specifically in Streptomyces noursei JA 3890b during growth on a medium supplied with D,L-alanine, NH4+, and maize starch there are two different phenotypes of the organism and stationary states of metabolism, respectively. The expression of either the metabolic state I with an enhanced capacity to oxidative deamination of alanine via the NAD+-dependent alanaine dehydrogenase or the metabolic state 2 which may be characterized by the preferred use of ammonium ions via the NADP+-dependent glutamate dehydrogenase was shown to depend strongly on the conditions of inoculum cultivation. When the amino acid permeases were derepressed by cultivating the inoculum cells on amino acid media, probably due to the defective mechanism of negative feedback control of amino acid influx in this strain an abnormously high uptake of alanine was observed that, consequently, was correlated to the enhanced oxidation of this amino acid as well as to the intensive production of ammonia within the cell. This overproduction of cellular NH4+ seems to bring about the subsequent repression of biosynthetic glutamate dehydrogenase and so on the accumulation of ammonia autocatalytically may rise up (metabolic state I). On the other hand, if the influx of alanine was kept low and the NADH oxidation was less efficient, respectively, or when there was high cellular activity of glutamate dehydrogenase the level of ammonia never did exceed the respressory limit and, accordingly, the expression of the metabolic state 2 was observed. Switching-over of metabolic flux from the state 2 towards the state 1 can be brought about either by increasing the level of nitrogen sources in the medium or by adding buffers pH greater than 7.5. In contrast, decrease of cellular level of NH4+ was shown to induce the transition of metabolic state 1 into the state 2. This can be achieved not only by limitation of nitrogen source but also by adding different aminobenzoic acids and, alternatively, effectors of membrane function (short-chain alcohols), inhibitors of cytochrome oxidases (sodium azide, potassium cyanide), heavy metal (Fe++)-chelating agents (catechol, 2,5'-dipyridyl, o-phenanthroline), beta-alanine, and buffers pH less than 7. This suggests that these effectors are capable of preventing the abnormously high influx of amino acids as well as its wasteful catabolism within the cell of S. noursei JA 3890b. Therefore, it seems likely that by this way the aminobenzoic acids and similar effectors can diminish the catabolite repression or inhibition of secondary metabolism by cellular excess of some nitrogen compounds in good agreement with its well-known stimulatory action on the biosynthesis of the antibiotic nourseothricin in this strain.

Alanine↗
PubMedDate not supplied

Evolution in bioids: hypercompetitivity as a source of bistability and a possible role of metal complexes as prenucleoprotic mediators of molecular asymmetry.

Spontaneous production of optically active compounds can occur through kinetic instability of an asymmetric steady state in open systems, in which two enantiomeric autocatalysts compete for a common prochiral substrate in a stereoselective reaction of order n greater than 2. For the case of n=3, a proof of instability of a symmetric reacting state in the general case, and functions of reaction parameters ('Chemical Reynolds Numbers') governing the existence and stability of 7 different steady states are derived. The 'extinct state' (without autocatalyst) is stable; a finite amount of products is required to shift it into one of the reacting steady states. A mutation from one state into another in such system ('bioids') involves an amplification of different 'kinds of information', as 'stochastic' (noise into dissipative structures), 'molecular' (autocatalysts), and 'stoichimetric' information. Stereospecific third order kinetics are believed to be realizable on octahedral metal complexes with two-dentated ligands and to have played a role in the prebiological evolution of optically active compounds.

Biological Evolution↗
PubMed2000

Hopf bifurcations in multiple-parameter space of the Hodgkin-Huxley equations I. Global organization of bistable periodic solutions.

The Hodgkin-Huxley equations (HH) are parameterized by a number of parameters and shows a variety of qualitatively different behaviors depending on the parameter values. We explored the dynamics of the HH for a wide range of parameter values in the multiple-parameter space, that is, we examined the global structure of bifurcations of the HH. Results are summarized in various two-parameter bifurcation diagrams with I(ext) (externally applied DC current) as the abscissa and one of the other parameters as the ordinate. In each diagram, the parameter plane was divided into several regions according to the qualitative behavior of the equations. In particular, we focused on periodic solutions emerging via Hopf bifurcations and identified parameter regions in which either two stable periodic solutions with different amplitudes and periods and a stable equilibrium point or two stable periodic solutions coexist. Global analysis of the bifurcation structure suggested that generation of these regions is associated with degenerate Hopf bifurcations.

Axons↗
PubMed1985

Activation of NMDA receptors elicits fictive locomotion and bistable membrane properties in the lamprey spinal cord.

The motor pattern underlying locomotion in the lamprey can be elicited in the spinal cord in vitro by applying excitatory amino acids that activate NMDA receptors. When this is done oscillatory membrane potentials phase-linked with the locomotory rhythm can be recorded in different types of neurones. In some spinal neurones large amplitude oscillation continues after elimination of synaptic input with application of TTX. This oscillatory pacemaker-like activity is dependent on an activation of NMDA receptors, and is probably important in the generation of locomotion.

Animals↗
PubMed1987

Calcium ions trigger the expansion in bistable myelin.

Ultrastructural studies of nerve myelin emphasize its static aspects. However, current work indicates that the myelin multilayer is poised for a supramolecular transition from a compact to an expanded form. In teleosts, the membrane pair becomes 27 A thicker. The trigger for this expansion is physiological levels of Ca. Varying proportions of the myelin can be trapped in the expanded state by transferring an excised specimen from Ca-containing to Ca-free medium in order to prevent expansion of the remaining compact myelin. Images of the myelin multilayer show that the expansion occurs in the aqueous spaces between lipid bilayers. Previously we demonstrated the reversal of expansion by removing Ca under special conditions. These results together lead us to suggest that myelin may expand locally in normal nerve function, while wholesale expansion may be an early step in myelin breakdown in vivo.

Animals↗
PubMed2006

Bistable perception -- along the processing chain from ambiguous visual input to a stable percept.

The observation of an ambiguous figure leads to spontaneous perceptual reversals while the observed picture stays unchanged. Some ERP studies on ambiguous figures report a P300-like component correlated with perceptual reversals supporting a top-down explanation, while other studies found early visual ERP components supporting a bottom-up explanation. Based on an experimental paradigm that permits a high temporal resolution of the endogenous reversal event, we compared endogenous Necker-cube reversals with exogenously-induced reversals of unambiguous cube variants. For both reversal types, we found a chain of ERP components with the following characteristics: (1) An early occipital ERP component (130 ms) is restricted to endogenous reversals. (2) All subsequent components also appear with exogenously-induced reversals, however 40-90 ms earlier than their endogenous counterparts. (3) The latency difference between reversal types is also reflected in the timing of manual reactions, which occur 100-130 ms after P300-like components. The results suggest that the P300-like component is the same as found in other ERP studies on ambiguous figures. This component does not reflect the reversal per se, but rather its cognitive analysis, 300 ms after a change of the representation in early visual areas. The presented ERP chains integrate the different ERP results and allow to pinpoint the steps where top-down mechanisms begin to exert their influence.

Electroencephalography↗
PubMed2006

Bistable illusory rebound motion: Event-related functional magnetic resonance imaging of perceptual states and switches.

The neural correlates of a recently discovered visual illusion that we call 'illusory rebound motion' (IRM) are described. This illusion is remarkable because motion is perceived in the absence of any net motion energy in the stimulus. When viewing bars alternating between white and black on a gray background, the percept alternates between one of flashing bars (veridical) and the IRM illusion, where the bars appear to shoot back and forth rather like the opening and closing of a zipper. The event-related functional magnetic resonance imaging (fMRI) data reported here reveal that (1) the blood-oxygen-level-dependent (BOLD) signal in the human analog of macaque motion processing area MT (hMT+) increases when there is a perceptual change from "no-IRM" to "see-IRM" and decreases when there is a perceptual change from "see-IRM" to "no-IRM," although the stimulus remains constant; and (2) the BOLD signal in early retinotopic areas (V1, V2, and V3d) shows switch-related activation whenever there is a perceptual change, regardless whether from IRM to no-IRM or vice versa. We conclude that hMT+ is a neural correlate of this novel illusory motion percept because BOLD signal in hMT+ modulates with the perception of IRM.

Adolescent↗
PubMed2005

Competition in bistable vision is attribute-specific.

We employ ambiguous figures and rivalrous stimuli that have multiple ambiguous properties to show that the different attributes of an ambiguous stimulus can undergo independent switching dynamics. This suggests that competition is distributed and attribute-specific, consistent with the known functional segregation of visual processing. Conflicting evidence that binocular rivalry is an early or late visual process may be better understood as evidence for attribute-specific competition occurring at multiple stages of visual processing. Specifically, we show that whether perceptual selection during binocular rivalry is early and eye-based or late and percept-based depends on the particular ambiguous attributes of the rivalrous stimulus.

Humans↗
PubMed2004

The sonic hedgehog signaling system as a bistable genetic switch.

Sonic hedgehog (Shh) controls critical cellular decisions between distinct fates in many systems, particularly in stem cells. The Shh network functions as a genetic switch, and we have theoretically and computationally analyzed how its structure can endow it with the ability to switch fate choices at a threshold Shh concentration. The network is composed of a positive transcriptional feedback loop embedded within a negative signaling feedback loop. Specifically, positive feedback by the transcription factor Gli, which upregulates its own expression, leads to a switch that can adopt two distinct states as a function of Shh. However, Gli also upregulates the signaling repressor Patched, negative feedback that reins in the strong Gli autoregulatory loop. Mutations that have been associated with cancer are predicted to yield an irreversible switch to a high Gli state. Finally, stochastic simulation reveals the negative Patched feedback loop serves a critical function of dampening Gli fluctuations to reduce spontaneous state switching and preserve the network's robust, switch-like behavior. Tightly linked positive and negative feedback loops are present in many signaling systems, and the Shh system is therefore likely representative of a large set of gene regulation networks that control stem cell fate throughout development and into adulthood.

Animals↗