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At least 613 records · Page 34Linked to original sources

Pattern formation in discrete cell lattices.

In recent years, models for lattices of discrete cells have been attracting increased attention due to their greater flexibility to represent signalling and contact-dependent cell-cell interaction than conventional reaction-diffusion models. Using the almost forgotten method of Othmer and Scriven (1971) to calculate eigenvalues and eigenvectors for the Jacobian of the homogeneous state, a Turing-like linear stability analysis is carried out for diffusion-driven (DD) and signalling-driven (SD) discrete models. The method is a generalisation of the original method of Turing (1952). For two-species models it is found that there are profound differences between the two types of model when the size of the lattice increases. For DD models, the homogeneous state is typically either always stable, always unstable, or becomes unstable when the lattice gets suffficiently large. For SD models, the homogeneous state is typically unstable independent of lattice size, and stable only in a minor part of parameter space. Thus, SD models seem in general more pattern-prone than DD models. The conjecture that the linear analysis predicts the final pattern is investigated for a DD system with Thomas internal dynamics. Commonly the final pattern resembles the pattern of the initial perturbation of the homogeneous state, but this is by no means a general feature. When applied to a recent model for Delta-Notch lateral inhibition, linear analysis must be supplemented by various non-linear techniques to get a deeper insight into the patterning mechanisms. The overall conclusion is that a linear Turing analysis may be useful for predicting pattern, but when it comes to explaining patterns, non-linear analysis cannot be ignored.

Animals↗

Stability of the saccadic oculomotor system.

A variety of different types of instability has been found in the saccadic system of humans. Some of the instabilities correspond to clinical conditions, whereas others are inherent in the normal saccadic system. How can these instabilities arise within the mechanism of normal saccadic eye movements? A physiologically-based model of the saccadic system predicts that horizontal saccadic oscillations will occur with excessive mutual inhibition between the left and right burst cells and with underaction of the pause cells. The amplitudes and frequencies of the oscillations had ranges of 0-6 degrees and 6-20 cycles per second, respectively. Application of stability analysis techniques to the model reveals that development of the oscillations can be explained by the Hopf bifurcation mechanism. Future development of this approach will involve classifying pathological instabilities of the saccadic system according to the bifurcation involved in their generation.

Action Potentials↗

A developmental model of ocular dominance column formation on a growing cortex.

We derive an activity-based developmental model of ocular dominance column formation in primary visual cortex that takes into account cortical growth. The resulting evolution equation for the densities of feedforward afferents from the two eyes exhibits a sequence of pattern forming instabilities as the size of the cortex increases. We use linear stability analysis to investigate the nature of the transitions between successive patterns in the sequence. We show that these transitions involve the splitting of existing ocular dominance (OD) columns, such that the mean width of an OD column is approximately preserved during the course of development. This is consistent with recent experimental observations of postnatal growth in cat.

Algorithms↗

Transition state of the glycolytic pathway under FDP saturating conditions: experimental studies and a theoretical model.

1. The transition state of the glycolytic pathway, under FDP saturating conditions, from no ADP to ADP-saturating levels, is studied in a metabolic model in vitro obtained from rat skeletal muscle. 2. When ADP is absent from the reaction mixture a steady state for NADH concentration is observed. After ADP addition, a new steady state is reached. The transition state from the first steady state to the second one shows a pulse of NADH. Both the profile and the size of this pulse depend on the enzyme concentration. 3. A kinetic model of the lower part of glycolysis (after PFK reaction) is proposed, and this is described by a set of first order coupled nonlinear differential equations. The results obtained through stability analysis and numerical integration of these equations agree with the experimental ones. 4. The possible role of the above mentioned transition state on the transmitter mechanism of glycolytic oscillations from PFK to the lower part of the glycolysis is discussed.

Adenosine Diphosphate↗

Effects of walking velocity on relative phase dynamics in the trunk in human walking.

The nature of coordination changes and stability features in the relative phase dynamics of the trunk were examined in seven healthy subjects, while walking velocity on a treadmill was gradually increased and decreased. Predictions from Schöner et al (J. Theor. Biol. 142, 359-391, 1990) regarding transition mechanisms in quadrupedal walking generalized to pelvis-thorax phase relations in bipedal walking, in that more continuous transitions with and without loss of stability were observed when walking velocity was manipulated as a control parameter. Relative phase changed from more in-phase (about 25 degrees) at lower velocities to more out-of-phase (about 110 degrees) at higher velocities. Stability analysis of relative phase demonstrated the existence of more than one stable coordination pattern ('multistability'). Total ranges of motion in pelvis, thorax, and trunk, as well as stride length were larger at the decreasing velocity range was compared to the increasing velocity range, showing dependence on direction of control parameter manipulation ('hysteresis effect'). The nature of these transitions identifies phase relations in the trunk in human walking as lower symmetry dynamics, a finding consistent with the proposed dynamics of the quadrupedal walking mode. These results suggest the existence of different coordination patterns (multistability) in the human bipedal walking mode and question traditional distinctions in only two modes (walking and running) in human gait.

Adult↗

Aromatase.

Aromatase catalyzes the conversion of androgens to estrogens through a series of monooxygenations to achieve the 19-desmolation and aromatization of the neutral steroid ring-A structure. We have separated two forms of aromatase, a major (P2a) and a minor (P3) form, from human term placenta through solubilization and chromatography. Partially purified aromatase in each form was immunoaffinity chromatographed to give a single band (SDS-PAGE) cytochrome P-450 of 55 kDa, utilizing a mouse monoclonal anti-human placental aromatase cytochrome P-450 IgGi (MAb3-2C2) which is capable of suppressing placental aromatase activity. The purified cytochrome P-450 showed specific aromatase activity of 25-30 nmol/min per mg with Km of 20-30 nM for androstenedione on reconstitution with NADPH-cyt P-450 reductase and dilauroyl L-alpha-phosphatidylcholine. This one step represents a higher than 100-fold purification with maintenance of the same Km. The stability analysis showed a half-life of more than 5 yr for solubilized aromatase and 2 months for the aromatase cytochrome P-450 on storage at -90 degrees C. Contrary to the recent claim that estrogen biosynthesis by reconstituted human placental cytochrome P-450 is by trans-diaxial 1 alpha,2 beta-hydrogen elimination, all of our partially purified forms and reconstituted aromatase synthesized estrogens by cis-1 beta, 2 beta-hydrogen elimination. Use of purified aromatase and [19-3H3, 4-14C]androstenedione led us to discover a metabolic switching by aromatase to 2 beta-hydroxylation of androgen. Results of the MAb3-2C2 suppression of aromatase activity in different species and tissues including human, baboons, horses, cows, pigs and rats indicated the presence of various isozymes of aromatase.

Androgens↗

A reaction-diffusion theory of morphogenesis with inherent pattern invariance under scale variations.

In the framework of reaction-diffusion theory we deal with the problem of pattern regulation in morphogenesis. A generic model is proposed where the kinetic terms follow constraints imposed by scale invariance considerations. These constraints allow a class of kinetic schemes to be formulated so that, starting with an initially homogeneous morphogen distribution in the field, a stable gradient is established of the form: S(chi,L) = Lpf(chi/L). Here L is the length of the morphogenetic field, chi is the position variable and f(chi/L) is some monotonic function of the relative distance. With this distribution a scale invariant gradient can be constructed which leads to pattern regulation. A linear stability analysis of the model permits the definition of the parameter values enabling the system to abandon the homogeneous state spontaneously. Simulations of the evolution of the system towards its final stable state result in approximate pattern invariance for different field lengths. The accuracy of this invariance is in agreement with some recent quantitative experimental findings in both developing and regenerating systems.

Animals↗

Growth of nonnecrotic tumors in the presence and absence of inhibitors.

In this article a model for the evolution of a spherically symmetric, nonnecrotic tumor is presented. The effects of nutrients and inhibitors on the existence and stability of time-independent solutions are studied. With a single nutrient and no inhibitors present, the trivial solution, which corresponds to a state in which no tumor is present, persists for all parameter values, whereas the nontrivial solution, which corresponds to a tumor of finite size, exists for only a prescribed range of parameters, which corresponds to a balance between cell proliferation and cell death. Stability analysis, based on a two-timing method, suggests that, where it exists, the nontrivial solution is stable and the trivial solution unstable. Otherwise, the trivial solution is stable. Modification to these characteristic states brought about by the presence of different types of inhibitors are also investigated and shown to have significant effect. Implications of the model for the treatment of cancer are also discussed.

Cell Division↗

Disease regulation of age-structured host populations.

A lethal, contagious disease can generate a density-dependent regulation of its host, provided the hosts' contact rate grows with population size. The condition for disease-induced population control is that the expected number of offspring of an infected newborn be less than one. In vertebrates that acquired immunity if they survive infection, the disease changes the age structure of its host population. The steady-state age structure of a disease-regulated host with age-dependent fecundity is computed. Local stability analysis indicates that the equilibrium age structure is always stable. However, when the usual exponentially distributed duration of the disease is replaced by a constant duration, the population can exhibit oscillations with a long period.

Age Factors↗

Assortative mating and grandparental transmission facilitate the persistence of a sign language.

Conditions for the persistence (i.e., protection from loss) of a sign language are investigated assuming monogenic recessive inheritance of deafness, assortative mating for deafness or hearing, and cultural transmission of the sign language to deaf individuals from their deaf parents and deaf maternal grandparents. A new method is introduced to deal with the problem of grandparental transmission in which the basic variables are the frequencies of triplets comprising a mother, a father, and their daughter of permissible phenogenotypes. Usual stability analysis is then done on the system of linear recursions in the frequencies of these triplets, derived on the assumption that signers (users of the sign language) are rare. It is shown that assortative mating is the most important factor contributing to persistence, but that grandparental transmission can also have a significant effect when assortment is as strong as observed in England and the United States.

Deafness↗

A generalized reaction diffusion model for spatial structure formed by motile cells.

A non-linear stability analysis using a multi-scale perturbation procedure is carried out on a model of a generalized reaction diffusion mechanism which involves only a single equation but which nevertheless exhibits bifurcation to non-uniform states. The patterns generated by this model by variation in a parameter related to the scalar dimensions of domain of definition, indicate its capacity to represent certain key morphogenetic features of multicellular systems formed by motile cells.

Animals↗

Turing structures in an enzyme-induction system with gap junction-mediated non-linear diffusion.

Two cells, each containing a reaction system modeling genetic induction, are coupled by diffusion. The substrate is moving through gap junctions, the number of which is regulated by the adjacent cells. This leads to a non-linear substrate diffusion term in the rate equations. Stability analysis reveals the conditions for the emergence of stable asymmetric solutions (dissipative structures). Due to non-linear diffusion rigid restrictions on the ratio of the two diffusion constants no longer exist. We demonstrate that substances operating as regulators of intercellular communication and participating in cellular metabolism may exhibit morphogenetic functions.

Animals↗

M.V. Volkenstein, evolutionary thinking and the structure of fitness landscapes.

High dimensional fitness landscapes are robustly dominated by saddle points, not isolated peaks. We present an argument to this effect that is reminiscent of May's complexity stability analysis and trace out the significance for the dynamics of speciation, the connection between the neutral and punctuated aspects of evolution and evolution on moving landscapes. The paper is written in honor of M.V. Volkenstein (October 23rd, 1912-February 18th, 1992), who devoted his last papers to uniting dynamics with evolutionary thinking.

Biological Evolution↗

Turing structures in a system with regulated gap-junctions.

In two coupled cells, each containing a bisubstrate-kinetics reaction system, the two substrates can cross the membranes through gap-junction protein channels (gating). Passing through the gap-junctions is controlled by one of the substrates, thus resulting in non-linear diffusion. Linear stability analysis gives the conditions, under which the symmetric fixpoint becomes unstable, leading to spatial asymmetry (Turing structures). The implications for morphogenesis are discussed.

Animals↗

Adaptation in a stochastic Prisoner's Dilemma with delayed information.

Players in a Prisoner's Dilemma are modeled as learning automata that receive feedback from the environment and coadaptively adjust their strategies. Theory and simulations show the coevolutionary dynamics of the reward-inaction and reward-penalty schemes. The players are assumed to be physically distributed or, at least, in an environment where the effects of decisions are lagged. These systems include biological and social systems with constraints on instantaneous information or where environmental responses do not necessarily reflect the true state of the system. Linear stability analysis determines the conditions for persistent oscillations in the players' mixed strategies. Using a parameterized stochastic version of the dilemma, the results indicate that if the environment modifies the payoffs, and thus 'releases' the prisoners from their dilemma, the prisoners become prone to instabilities in their strategies given sufficient delays. Again, the prisoners fail to coordinate their actions.

Biological Evolution↗

Effects of androgens on the transcription of secretory protein genes in rat seminal vesicle.

Run-on transcription in isolated nuclei has been used to study the effects of testosterone on gene expression in rat seminal vesicles. General transcriptional rates were increased by about 6-fold with an additional 2- to 3-fold differential stimulation of the genes for secretory proteins IV and V. These transcriptional changes are insufficient to explain overall changes in cellular mRNA levels, indicating that androgens must also have major effects on post-transcriptional processing of RNA transcripts or on mRNA stability. Analysis of nuclear RNA by Northern blotting with intron probes suggests substantial androgen effects on primary transcript processing.

Animals↗

Stability of the pBR322 plasmid as affected by the promoter region of the tetracycline-resistance gene.

A region affecting the pBR322 plasmid maintenance has been located within the region of the TcR gene promoter. On the basis of stability analysis of pBR322 derivatives comprising the modified region of the TcR gene, we deduced that it is the nucleotide sequence localized in the region of the HindIII site that causes destabilization of the plasmid and not the TcR gene product or active transcription of this region. The destabilizing effect is manifested both in cis and in trans.

Chromosome Deletion↗

Mixed micelles formed from graft and diblock copolymers for application in intracellular drug delivery.

A novel mixed micelle that comprised of poly(N-isopropylacrylamide-co-methacrylic acid)-graft-poly(D,L-lactide) (P(NIPAAm-co-MAAc)-g-PLA) with methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PLA) was developed for application in cancer therapy. The mixed micelle had an multi-functional inner core of P(NIPAAm-co-MAAc)-g-PLA to enable intracellular drug delivery and an extended hydrophilic outer shell of mPEG to hide the inner core. Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicates that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of graft copolymer were efficiently screened by mPEG. From the drug release study, the mPEG-PLA diblock copolymer in mixed micelles slightly affected the functionalities of the P(NIPAAm-co-MAAc)-g-PLA graft copolymer; the graft copolymer still exhibited pH- and thermo-sensitivities in this core-shell structure. A change in pH deformed the structure of the inner core from that of aggregated P(NIPAAm-co-MAAc), causing the release of a significant quantity of doxorubicin (Dox) from mixed micelles. Clear differences between free Dox and Dox-mixed micelles were observed using confocal laser scanning microscopy (CLSM). This study presents not only a new micelle structure for a graft-diblock copolymer system, but also a method for overcoming some of the limitations on biomaterials used in intravenous injection.

Acrylic Resins↗