PubMed Health⌕ Search

Biomedical subjects

J E Mittenthal

Publications and source records attributed to J E Mittenthal.

18 recordsLinked to original sources
PubMed1997

An algorithm to assemble pathways from processes.

To understand or to modify a biological pathway, the first step is to determine the patterns of coupling among its processes that are compatible with its input-output relation. Algorithms for this purpose have been devised for metabolic pathways, in which the reactions typically leave the enzymes unmodified. As shown here, one of these algorithms can also assemble molecular networks in which reactions modify proteins, if the proteins are included among the inputs to the reactions. Thus one procedure suffices to assemble pathways for metabolism, cytoplasmic signal transduction, and gene regulation.

Algorithms↗
PubMed1993

A model for the evolution of networks of genes.

An organism persists through the activity of structural genes, which is co-ordinated by clusters of coupled regulatory genes. During evolution, changes of coupling within a cluster can increase the reliability with which its structural genes perform a task. To study the evolution of coupling, we have simulated and analyzed a stochastic model for a simple problem. The assumptions of the model are these: A network of regulatory genes co-ordinates the synthesis of four structural proteins, which associate in distinct heterodimers that form a heterotetramer. Mutation in cis-regulatory regions produces transitions among 64 types of network. In a population, each network reproduces in proportion to its fitness, which depends on its probability (reliability) of synthesizing the tetramer. Fitness-dependent attrition keeps the size of the population constant. Regulatory genes occur in a sequence of levels; each level is associated with a different family of transcription factors. The following results emerge: Because different messengers within a family can give networks with the same connectivity, the 64 types of networks cluster into eight equivalence classes. During evolution with a low mutation rate, high-fitness classes can be approached through various paths on a fitness landscape. With a higher mutation rate, networks remain more uniformly distributed among the 64 types, and lower-fitness networks remain preponderant. An initially homogeneous population becomes more heterogeneous through mutation, but selection according to fitness later reduces its diversity. During this process the dispersion of the population over the possible networks increases, then decreases as the population approaches a unique steady state.

Animals↗
PubMed1988

Discontinuities of pattern and rules for regeneration in limbs of crayfish.

The most caudal limb in crayfish, the uropod, has two rami, the exopodite and the endopodite. Results of earlier experiments (J.E. Mittenthal et al. (1985) W. Roux's Arch. Dev. Biol. 194, 121-130) indicated that ramus morphogenetic fields in the two rami are equivalent and tandem. Thus the proximal (inner) junction of the rami, where intersegmental membrane separates them from each other and from the coxa, is analogous to a boundary between segments of the body or of a leg. In this region a discontinuity in the positional information carried by the ramus fields might occur. To characterize the morphogenetic fields in the region near this junction we have exchanged the medial and lateral margins of the two rami, performing the four possible grafting operations of this kind. While an experimentally generated discontinuity between the lateral margin of the exopodite and the medial margin of the endopodite (outer-to-outer junction) triggers intercalation of supernumerary rami, a discontinuity of pattern between the medial margin of the exopodite and the lateral margin of the endopodite (inner-to-inner junction) is stable despite the absence of intervening intersegmental membrane. Where intercalation does occur, it can proceed in either direction along the margin of a supernumerary ramus. These results suggest that there is no discontinuity of positional value at the boundary between the rami. The results of all of our experiments on the uropod indicate that a conjunction of separate proximodistal, dorsoventral, and mediolateral component fields may give positional information for generating the uropod. Intercalation restores the continuity of pattern in the proximodistal field. In the mediolateral field a discontinuity of pattern may result from a preferred polarity of intercalation: Outer cells may be competent to generate inner cells, but not vice versa. According to this hypothesis the two rami have tandem ramus fields but mirror-symmetric polarity of competence. Alternatively, intercalation may eliminate a mediolateral discontinuity only if the mismatch of mediolateral positional values at the discontinuity exceeds a threshold. The threshold criterion may be a weighted sum of limb field and ramus field positional values.

Animals↗
PubMed1984

Intercalary regeneration in legs of crayfish: proximal segments.

An arthropod leg represents a protuberance of the body segmental integument which bears distinctive markers in both the mediolateral and the anteroposterior axes. To clarify the biaxial organization of the body segmental morphogenetic field, and to study the relation among the whole-limb, limb segmental, and body segmental fields previously recognized in arthropods, we have grafted a proximal leg segment into the ventral midline in crayfish. After this operation the majority of animals regenerated a mirror-symmetric pair of supernumerary legs at the host site. Some of these legs had the most proximal segment, the coxa, partially fused to the adjacent body surface. Minority patterns of regeneration included one midline leg with a gill, three midline legs with a gill, and two normal legs with a third double-half leg. These results are compatible with the principle that intercalary regeneration restores the continuity of positional information.

Animals↗
PubMed1983

A model for shape generation by strain and cell-cell adhesion in the epithelium of an arthropod leg segment.

We present a model for the energetic factors determining the most stable shape of a tubular epithelium such as the hypodermis of an arthropod leg segment. The model uses the analysis by Steinberg (1963) of rearrangement of cells in aggregates under the influence of differential adhesion, combining this analysis with the assumption that the epithelium behaves as an elastic sheet. The epithelium is assumed to consist of blocks of cells with different adhesive affinities, which remain unmixed in a quilt pattern. Rearrangement of cells within each block can adjust the shape of the tube by changing the shapes of the blocks. By means of such rearrangements the tube develops that shape which minimizes a free energy. The free energy is the difference between the energy of mechanical strain due to bending of the epithelium and the work of adhesion among cells. Minimization of the free energy for a cylindrical segment yields a scaling relation involving the length and radius of the segment. Leg segments of Drosophila conformed approximately to this relation, with deviations which suggest that a whole-limb pattern of adhesive affinities modulates the shaping effects of an adhesive pattern repeated in each leg segment. The model also predicts a transient deformation in an epithelium following a grafting operation. For example, deleting a slab of tissue from a tubular segment and reuniting the cut ends should produce a constriction of the tube at the host-graft junction. We propose that patterns of strain and adhesion can provide positional information which regulates subsequent development. Local increases in strain or adhesive disparity may stimulate mitoses; the resulting changes in distribution of cells will affect morphogenesis.

Animals↗
PubMed1977

Complexity of branching dendritic trees: dependence on number of trees per cell and effects of branch loss during sectioning.

We have investigated whether the complexity of dendritic trees is correlated with the number of primary dendrites per neuron (trees per cell). In estimating the average number of branches of centrifugal orders 1-5 per tree we used statistical methods to compensate for loss of parts of trees during sectioning. Limitations of these methods are discussed. Neurons from four populations, stained by the Golgi-Cox method, were examined: stellate cells from layer IV, area 17 of visual cortex, in normal and dark-reared cats; the pyramidal cells from layer V, somatosensory cortex, in two strains of rats. In all four groups of neurons the average number of branches of higher orders (3, 4, 5) per tree tended to be smaller in neurons bearing more trees. Thus all trees from a population of neurons should not be assumed to be equivalent. The decreasin high-order branches per tree tended to offset the increase in number of trees per cell. In three of the four groups these opposed tendencies maintained the average number of high-order branches per neuron nearly independent of the number of trees per cell. Natural selection may have favoured near-constancy in the number of high-order branches to reduce dispersion among neurons of one type in functional input-output rleations.

Animals↗
PubMed1973

Connectivity patterns of crayfish giant interneurons: visualization of synaptic regions with cobalt dye.

Intracellular injection of cobalt dye was used to visualize electrical synapses between two pairs of central giant interneurons and giant motoneurons in the crayfish central nervous system. A pair of giant motoneurons in each ganglion contacts the interneurons, but not all contact points are functional synapses. Cobalt dye reveals numerous fine projections that are present at synaptic contact points and absent at nonsynaptic contacts; intracellular recording confirms this correlation. The different connectivity patterns of the two pairs of interneurons are consistent with the different behavior patterns which they evoke.

Action Potentials↗
PubMed1971

Transient phases of the isometric tetanus in Frog's striated muscle.

In an isometric tetanus in frog's sartorius muscle tension approaches the plateau exponentially with rate constant alpha. alpha a depends on sarcomere length, s, and temperature, T, according to the Arrhenius equation See PDF for Equation for temperatures between 1 and 20 degrees C and for sarcomere lengths 2.0-2.8 microm. The energy of activation, E, does not vary significantly with s; E = 13.9 +/- 2.4 kcal/mole. A(s) decreases monotonically with s; A(2.1 microm) is about three times greater than A(2.8 microm). Late in relaxation active tension approaches zero exponentially with rate constant r. r decreases exponentially with increasing duration of tetanus, D, from r(0) in a twitch to r(infinity) for large D. The rate constant for decrease of r with D increases with s and with T. r(0) and r(infinity) obey the Arrhenius equation and decrease with increasing s.

Animals↗