摘要:

Stochastic models explaining the hierarchical organization and the learning potentialities of a neural net are presented. The elements of the neural net appear as states of chains with infinite memory. The ergodic properties of the net allow to explain naturally the hierarchical organization of neural networks with an abundance of branchings and stable states. The stochastic model is able to describe some properties of nets e.g. the memory, the adaptability, the storage of information, the sensitivity to initial conditions. Three frameworks of the time are outlined; rest, uniform time and continuously but purely singular time. The possibilities of using stochastic and non‐archimedean methods in higher nervous activity modelling are illustrated.

ISSN:0094-243X    

DOI:10.1063/1.40592

出版商:AIP    

年代:1991

数据来源: AIP

ISSN:0094-243X    

DOI:10.1063/1.40593

出版商:AIP    

年代:1991

数据来源: AIP

ISSN:0094-243X    

DOI:10.1063/1.40594

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

The X‐ray solution scattering profiles of taxol microtubules made of purified tubulin and control microtubules, assembled either from purified tubulin in glycerol buffer (a non‐specific enhancer of the polymerization of tubulin) or from microtubule protein (a preparation containing tubulin plus microtubule associated proteins), were obtained to 3.3 nm resolution. These profiles show features of the microtubule wall structure which had not been observed in solution before. Comparison of the different profiles indicated that the structure of the microtubule wall is very similar in the three types of microtubules to the resolution of the measurements, however the mean diameter of the taxol microtubules is smaller than that of the control microtubules, by approximately one protofilament less. Actually, only 12 protofilament computer models of microtubules could fit the position of the maxima in the experimental scattering profile of the taxol microtubules. Having only 12 protofilaments implies a discontinuity on the microtubule wall, irrespective of whether the lateral contacts follow the A or B microtubule lattice, and also requires adjustment of the normal lattice to one protofilament axis with respect to the cylinder axis.The fact that the majority of these taxol microtubules assembled from purified tubulin have 12 protofilaments has been visualized by electron micrographs of tannic acid stained microtubule thin sections, and is fully consistent with the microtubule wall projections (fringe patterns) observed in negatively stained and cryo‐electron microscopy specimens, which correspond to a 12 protofilament‐three start lattice type.

ISSN:0094-243X    

DOI:10.1063/1.40595

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Double rings assembled from 26±4 &agr;‐&bgr; tubulin dimers have been observed both as depolymerization products of microtubules and as the end product of the self‐assembly of pure dimeric tubulin. Analysis of the self‐assembly thermodynamics from &agr;‐&bgr; tubulin with the E‐site occupied by GTP or GDP has shown that the polymerization is stronger in the GDP state. This advantage is localized in the ring closure step, while the chain growth equilibrium constants are essentially identical for the two states of tubulin. This has led to the proposal that tubulin can exist in two conformational states, one is ‘‘straight’’ or microtubule‐forming, the other is ‘‘curved’’ or double ring forming. The interconversion is controlled allosterically by occupation of the E‐site on tubulin by GTP or GDP. Direct participation of double rings in the tubulin‐microtubule cycle is suggested by the slow depolymerization of these structures. This can account for the period of the spontaneous oscillations sometimes observed in microtubule assembly at high tubulin concentrations. Due to the slow depolymerization of double rings, GDP‐tubulin can become temporarily sequestered in these structures and, as a consequence, they can be regarded as a ‘‘dormant,’’ or storage state of tubulin.

ISSN:0094-243X    

DOI:10.1063/1.40596

出版商:AIP    

年代:1991

数据来源: AIP

ISSN:0094-243X    

DOI:10.1063/1.40597

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Microtubule dynamic instability involves the existence, within a population of microtubules, of sub‐populations of growing and shrinking microtubules which interconvert apparently at random. We consider the scope and limitation of experimental observations of individual microtubules by video enhanced dark‐field microscopy.This unique experimental phenomenon has been rationalized by the presence of a ‘‘cap’’ of tubulin‐GTP which can stabilize the growing state. We have modelled this process quantitatively by numerical simulation and illustrate the basic principles by computer graphics.The inherent &agr;‐&bgr; asymmetry of the microtubule lattice determines that the relationship between the addition reaction of tubulin‐GTP and the related hydrolysis of a polymer tubulin‐GTP is different at the two ends of the microtubule. In the single layer, Lateral Cap model for microtubule dynamic instability, a plausible mechanism has been proposed for the dynamic properties at the ‘‘active’’ (presumed &bgr;‐out) end in which the tubulin‐GTP which is hydrolyzed is related longitudinally to the binding site by the 13‐start protofilament helix. [1,2].We now show a similar but distinct mechanism could hold for the ‘‘inactive’’ (presumed &agr;‐out) end of the microtubule. Lateral hydrolysis rules (related to 5‐ or 8‐ start helical contacts) predict that the &agr;‐end could in fact be less dynamic and cooperative in terms of reduced amplitudes of growth and shrinking. This would make a distinctive contribution to the J(c) plot of microtubule growth versus [tubulin‐GTP]. These predictions are thus amenable to experimental verification.This approach illustrates how the helical lattice symmetry of the microtubule polymer can confer unique dynamic characteristics, which derive from the heterodimeric structure and guanine nucleotide binding properties of the component protein tubulin. It also provides a basis for the interpretation of the interactions of microtubules with anti‐mitotic drugs used in chemotherapy.

ISSN:0094-243X    

DOI:10.1063/1.40598

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

We have developed methods using video‐enhanced differential interference contrast light microscopy (VE‐DIC) to measure the association and dissociation rate constants and transition frequencies of microtubule dynamic instability for microtubules assembled from pure tubulin, plus brain microtubule assoicated proteins (MAPs), and for microtubule assembly in living cells and cytosol extracts. Following nucleation, a microtubule end is seen to elongate at constant velocity until it abruptly begins rapid shortening, a transition termed catastrophe. The microtubule either disappears, or converts back to the elongation phase, a transition termed rescue. Catastrophes and rescues occur stochastically and infrequently in comparison to the durations of the elongation and shortening phases. In purified tubulin preparations from both mammalian brain and sea urchin embryos, the elongation and shortening phases exhibit distinctly different association and dissociation rate constants; in particular, the rate of dissocation during rapid shortening can be 100 times or more greater than during elongation particularly at high Mg2+.Brain MAPs (MAP2and Tau) promote faster elongation, but suppress dynamic instability mainly by decreasing the frequency of catastrophe and increasing the frequency of rescue. In contrast, there are unknown factors in living dividing cells and in extracts from dividing cells which enhance dynamic instability by producing high frequencies of catastrophe (.01–.05 sec−1) at fast elongation velocities (10 &mgr;m min−1). Using a microscope perfusion chamber, we have shown for microtubules assembled from pure tubulin that dilution induces rapid shortening within several seconds independent of the elongation velocity or microtubule length. Thus, the stabilizing cap at elongating microtubule ends is small and sensitive to transient changes in the rate of tubulin association, even at high elongation velocities. This means that substantial changes in microtubule assembly can be regulated by cellular factors which increase the frequency of catastrophe by transiently interfering with tubulin association at elongating microtubule ends without significantly effecting the average rate of elongation.

ISSN:0094-243X    

DOI:10.1063/1.40582

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Microtubules at steady state show dynamic instability. This implies that two populations of microtubules exist: a high concentration of slow growers and a small concentration of fast shrinkers. Transitions between the two are possible. The rate constants of these transitions have been derived from the observations of the switching frequency of single microtubules in the microscope.It would be interesting to derive the switching kinetics from a whole population of microtubules. An attempt has been made by Caplowet al. (1988) J. B. C. 263, 10344–10352, however, using a slow temperature perturbation. We have repeated these experiments using a very fast (0.2 millisec) pressure perturbation.Equations have been derived for the decription of the relaxation process of steady state microtubules, taking into account the existence of a growth to shrinkage interconversion. These relations predict a rather small amplitude for the switching relaxation if the T.GTP or T.GDP.Pi cap is small.Experimental results show that the relaxation data can be described by a single exponential. These results indicate that the reshuffling of the growth to shrinkage interconversion does not show up in steady state relaxations, indicating a rather small T.GTP or T.GDP.Pi cap.

ISSN:0094-243X    

DOI:10.1063/1.40583

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

In living organisms microtubules exist as highly labile or very stable structures. In higher eucaryotes, the main, and probably the only, physiological effectors capable of triggering microtubule transtions between lability and stability, are specialized proteins.In the present paper, general methods to assay and isolate these effectors are proposed. The properties of a particular protein (STOP protein) are shown. Finally the potential significance of such effectors in the generation of organelle movement and microtubule spatial self organization are discussed.

ISSN:0094-243X    

DOI:10.1063/1.40584

出版商:AIP    

年代:1991

数据来源: AIP