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Biomedical subjects

S Portnoy

Publications and source records attributed to S Portnoy.

30 records · Page 2Linked to original sources

A non-cholinergic function for acetylcholinesterase in the substantia nigra: behavioural evidence.

Acetylcholinesterase is released from substantia nigra neurons, independently of cholinergic transmission. In an attempt to discover the functional significance of this phenomenon, the behavioural effects of injecting acetylcholinesterase into one substantia nigra of the rat were investigated. Following a single injection of the enzyme, intraperitoneal amphetamine evoked circling behaviour in a direction away from the side of injection. Purified acetylcholinesterase with a similar electrophoretic mobility to the endogenous secreted form, was far more potent in eliciting circling than much higher activities of commercial enzyme, consisting of several molecular species of acetylcholinesterase. Similar infusions of butyrylcholinesterase did not induce circling. Depending upon the amount of enzyme initially given, the behavioural effects of a single injection of acetylcholinesterase persisted for up to thirty days. During this period apomorphine, administered systemically, induced transient circling towards the acetylcholinesterase-treated side. It is concluded that secreted acetylcholinesterase has a functional significance within the substantia nigra, independent of cholinergic transmission. This released enzyme could exert long-term changes in the activity of the nigrostriatal system, involving modification of dopamine striatal receptors.

Acetylcholine↗

Distribution of mutants in aggregates of cultured cells.

The analysis of the distribution of mutants in an exponentially growing culture of cells that are aggregated into clumps of homogeneous size is described, given the mutation rate and a random process by which clumps divide to produce progeny. The mean and standard deviation of the proportion of clumps with a given number of mutant cells at a particular time are calculated. Since the standard deviation tends to be much smaller than the mean, the following conclusions can be drawn. Aggregation lowers the number of mutant-containing clumps in cultures grown to a standard number of cells, but raises the number of mutant-containing clumps in cultures grown to a standard number of clumps. In the absence of mutation, or at low mutation rates, clumps tend to become pure types (normal or mutant). The probability of finding pure, nonmutant-containing clumps, however, is approximately the initial fraction of nonmutant cells (given realistic forward and back mutation rates). Also, in terms of the given process, it is possible to compute the probability that all the cells in an aggregate descend from a single, common parent cell within a given number of generations, and thus to calculate the probability that all the cells in a clone grown from an aggregate descend from a single cell within a known number of generations.

Cell Aggregation↗

Perturbance analysis of nuclear determination in Tetrahymena: effects of nutrition, cell extracts, and CaCl2 on A/B hybrids.

Mating type frequencies were ascertained among the progeny of crosses of strains A x B, Tetrahymena thermophila under a number of different circumstances. The frequencies are different if the parents are severely starved than if they are well-fed at the time of conjugation; severe starvation of the progeny before the first post-zygotic division has an effect similar to that of starving the parents. Mating type frequencies may also be modified by isolating conjugating pairs into cell extracts before the new macronuclei begin to develop; the changes do not appear to be related in a meaningful way to the mating type of the cells used as a source of the cell extracts. A third means of changing the mating type frequencies involves the exposure of conjugating pairs to CaCl2 solutions. Finally, changed frequency patterns may appear "spontaneously", and reflect either some as yet unsuspected environmental variable, or else an intrinsic metastable state that conditions the probabilities of mating type fixation. With the exception of the starvation effects, the pattern variations seem to fall into two groups. No satisfactory mechanism to account for these results is yet available.

Animals↗

Perturbance analysis of nuclear determination in Tetrahymena: analysis of mating type frequency variations with reference to binary-switch models.

To test a 3-switch binary element model of mating type determination all possible assignments of the seven mating types of Tetrahymena thermophila to compound switch states have been examined, using a set of 77 experimentally obtained frequency patterns as a base. None of the assignments gives a satisfactory agreement with all the data. The result is similar whether the eighth switch state is considered forbidden or redundant. Moreover, further explorations of models in which the switches are not independent (as originally proposed), but coupled also fail to reveal a satisfactory agreement. Finally some 4-switch models are examined, again without discovering a satisfactory fit, though some evidence of structural relationship among the mating types is provided. The system is more complex than was assumed by the original models. To carry out this analysis certain statistical problems of a more general interest required solution. These include the management of samples from multinomial populations and the provision of efficient estimators for models of this sort.

Animals↗