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Biomedical subjects

J B Thomas

Publications and source records attributed to J B Thomas.

At least 91 records · Page 5Linked to original sources

Molecular genetics of the single-minded locus: a gene involved in the development of the Drosophila nervous system.

The embryonic neuroepithelium of Drosophila gives rise to the central nervous system. We have studied the mutant phenotype and expression of a gene, single-minded (sim), which is involved in generating a specific region of this neuroepithelium. In sim mutant embryos, a subset of neuronal and nonneuronal precursor cells lying along the midline fail to emerge with the rest of the neuroepithelium. We have identified the sim transcription unit and have shown by in situ hybridization to embryos that the sim gene is expressed specifically in the midline neuroepithelium. Both the mutant phenotype and the temporal and spatial expression of transcripts suggest that the sim gene plays a key role in the emergence of this subset of cells along the midline of the developing central nervous system.

Animals↗

The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product.

Mutations in the single-minded (sim) gene of Drosophila result in the loss of the precursor cells giving rise to the midline cells of the embryonic central nervous system. We have examined the structure of the sim product by sequencing a sim cDNA clone, and have also determined the subcellular localization of the protein and its developmental expression by staining embryos with an antiserum against a sim fusion protein. The results indicate that sim is a nuclear protein specifically expressed along the midline of the neuroepithelium, the same subset of cells that are missing in the mutant. No similarity is observed between sim and any known nuclear protein, but, surprisingly, it is similar to the Drosophila period (per) locus gene product, which controls the periodicity of biological rhythms.

Amino Acid Sequence↗

Malignant fibrous histiocytoma in a dog.

A large tumour present on the proximal tibia of a Bull Mastiff dog was diagnosed on histological appearance as a Malignant Fibrous Histiocytoma. These tumours, rarely identified in domestic animals, but well recognised in humans, are typically pleomorphic sarcomas with histiocytic and fibroblastic differentiation. Less commonly, one cell type predominates. In this case there was prominent histiocytic differentiation.

Animals↗

The use of decision analysis for organizational design: reorganizing a community hospital.

Organizational design is presented as a decision process, with specific structures seen as providing alternative choices. To illustrate this, the authors present the case of a major metropolitan hospital that used the process to coordinate service delivery (nursing care versus patient care) and service focus (product oriented versus function oriented). Through interviews with more than 40 hospital administrators and staff, the authors created a list of 20 attributes, and used simple multi-attribute utility analysis to generate six design alternatives. The decision makers unanimously chose one alternative, even though potential for significant conflict existed because of differing values and objectives. The authors find decision analytic techniques useful for both the problem formulation and for generating and evaluating structural alternatives, and conclude that in this case consensus was facilitated by the decision process used.

Data Collection↗

Cell recognition during neuronal development.

Insect embryos, with their relatively simple nervous systems, provide a model system with which to study the cellular and molecular mechanisms underlying cell recognition during neuronal development. Such an approach can take advantage of the accessible cells of the grasshopper embryo and the accessible genes of Drosophila. The growth cones of identified neurons express selective affinities for specific axonal surfaces; such specificities give rise to the stereotyped patterns of selective fasciculation common to both species. These and other results suggest that early in development cell lineage and cell interactions lead to the differential expression of cell recognition molecules on the surfaces of small subsets of embryonic neurons whose axons selectively fasciculate with one another. Monoclonal antibodies reveal surface molecules in the Drosophila embryo whose expression correlates with this prediction. It should now be possible to isolate the genes encoding these potential cell recognition molecules and to test their function through the use of molecular genetic approaches in Drosophila.

Animals↗

Duplicated neural structure in bithorax mutant Drosophila.

The bithorax complex (BX-C) of genes in Drosophila control the segmental identity of the thoracic and abdominal cuticle. In flies containing BX-C mutations causing meta- to mesothoracic transformation, the mesothoracic branching pattern of a well-studied identified neuron is faithfully duplicated in the metathoracic ganglion. Thus these mutations also cause the duplication of mesothoracic cues involved in this neuron's branching.

Abdomen↗

Mutations altering synaptic connectivity between identified neurons in Drosophila.

By studying the effects of mutations on a simple circuit of identified neurons in Drosophila, we have found genes whose proper functioning is necessary to produce normal synaptic connections between the neurons. These neurons comprise the giant fiber (GF) system; the GFs are command neurons activated by a light-off stimulus and evoke a stereotyped pattern of activity in the thoracic muscles producing an escape jump. Each GF monosynaptically drives a motor neuron innervating the tergotrochanteral muscle (jump muscle, TTM). Each GF also disynaptically drives the motor neurons innervating the dorsal longitudinal flight muscle (DLM) via the peripherally synapsing interneuron (PSI) (King, D. G., and R. J. Wyman (1980) J. Neurocytol. 9: 753-770; M. A. Tanouye and R. J. Wyman (1980) J. Neurophysiol. 44: 405-421). A search was made for mutations affecting these identified synapses. Fifty thousand mutagenized flies were screened for nonjumping behavior to the light-off stimulus. Fifty-seven nonjumping mutant lines were established from individuals selected in the screen. Members of the lines were then tested for abnormal GF motor output to the TTM and DLM. From these lines, four X-linked mutations (representing three complementation groups) were isolated which affect the circuit. The mutations differentially disrupt specific synapses within the GF system. One mutation, bendless, disrupts synaptic transmission between the GF and the TTM motor neuron. Another, gfA, disrupts the synaptic connections of the PSI, and a third mutation, passover, disrupts transmission in both pathways.

Animals↗

The mathematics of mosaic analysis. I: The relationship between sturts and distance.

In mosaic fate mapping the fraction of mosaics in which two structures are of different genotype is calculated. This frequency of separation has been called a "distance" and the units of this distance are called "sturts". The fundamental assumption of fate mapping is that the frequency of separation increases continuously with the actual distance between the anlage for these structures on the blastoderm. This paper shows that the frequency of separation does not increase beyond a certain value. --For the current theory to work as proposed, each mosaic animal must be half mutant and half normal. This is rarely the case in collections of mosaics. It has been thought that if some flies are less than half mutant and others more than half, these two types would introduce compensating errors in mapping distance. We show that this is not true and describe the nature of the errors introduced. It is probable that these errors are the main reason that mapping distances reported from different sets of mosaics have not been reproducible. This paper presents methods for the proper handling of data from mosaics with different amounts of mutant tissue.--We prove here that for mosaics with an arbitrary fraction of mutant tissue (m), the largest frequency of separation that can occur is 2m. We prove that sturts underestimate actual distance on the blastoderm by a factor of r/m, where r is the radius of the mutant patch, and that sturts give no information on distances greater than 2r. This, and not double crossing over, is the reason for the nonadditivity of sturts and the shrinking of large distances in sturt measures. Sturtoids overestimate distances by a factor of 1/(2r) and also give no information on distances over 2r. This paper gives formulae for correctly estimating distance when using a collection of mosaics with varying amounts of mutant tissue. We also describe the nature of the errors introduced by convoluted or elongate mosaic boundaries and by multiple mosaic patches.

Animals↗

The morphology of the cervical giant fiber neuron of Drosophila.

The morphology of the cervical giant fiber (CGF) neuron of Drosophila melanogaster was studied by intracellular injection of Lucifer yellow dye. The CGF neuron is the command cell in a motor circuit causing visually driven escape behavior: a single action potential in a CGF axon produces patterned activity in jump and flight muscles. The present study identified the CGF cell body, a large soma located in the posterior part of the lower ipsilateral protocerebrum. The main process runs anteriorly from the cell body, extends three branches, and turns posteromedially while descending through the brain. The CGF axon courses through the cervical connective and ends within the mesothoracic neuromere of the thoracic ganglion. Thus, the CGF neuron is an interneuron, not a motoneuron as previously believed. We have been isolating mutants that affect CGF neuron-mediated behavior. Comparison of CGF neuron morphology in wildtype strains with that in these mutants will allow identification of genes that affect the development, structure, and connections of the CGF neuron.

Action Potentials↗

Intramembranous particles and chlorophyll complexes in chloroplasts.

The size and population density of large and small particles from freeze-fractured chloroplasts of three wild-type algae and of normal spinach were determined. Computer analyses of low-temperature absorption spectra of chloroplast preparations from these species were performed, and a possible correlation between the occurrence of seven chlorophyll complexes and the aforementioned properties of the intramembranous particles was studies. It was found that only single-sized particles occur in a species containing neither chlorophyll b nor chlorophyll a-685 complexes. The three remaining species carry particles of two sizes, termed large and small particles. However, from quantitative considerations it is concluded that the chlorophyll content of none of the various pigment complexes is related to the size and the population density of the studied particles. If such a relationship exists, it seems likely to be due to the carrier moiety of the chorophyll b-chlorophyll a-685 complex.

Chlorophyll↗

Septal lesions facilitate the shift from conditioned escape to conditioned avoidance behavior in the rat.

Normal rats were given 1000 training trials in a discriminated lever-press avoidance task. Those animals which exhibited consistent escape behavior but minimal avoidance responding were subjected to either septal lesions or control operations. One week later they were retested in the avoidance apparatus for an additional 1000 trials. Rats with large septal lesions exhibited an immediate increase in avoidance performance relative to the control rats. This increase occurred without a concomitant increase in number of lever-press responses. The performance of 3 out of 4 rats with smaller more dorsal septal lesions was unaffected by the surgery.

Animals↗

VMH lesions facilitate baitshyness in the rat.

Normal rats and rats with lesions of the ventromedial hypothalamus were compared on the acquisition of a single trial, long CS-US interval, conditioning task (baitshyness). The rats with hypothalamic damage exhibited facilitated baitshyness when tested both shortly after surgery and several months after surgery. The magnitude of the suppression observed in these animals could not be related to either specific anatomical structures within the hypothalamus or to the amount of obesity exhibited following the lesions. Similarities and differences between the results of the present study and previous studies are discussed.

Animals↗

Interactive effects of training condition and septal lesions on perseverative responding in the rat.

Rats that had received septal lesions either prior to acquisition of a position habit (Group SAR) or immediately after position habit acquisition (Group SR) were tested on two reversals of the task. Compared with control-operated rats, both groups of rats with septal lesions exhibited position-habit reversal deficits. The two groups with septal lesions could not be distinguished in terms of the total number of errors made during reversal learning, but could be distinguished on the basis of the type of error committed. Compared with Group SR, Group SAR made significantly more perservative errors on the first reversal and significantly fewer perserverative errors on the second reversal. Group SR made significantly more nonperservative errors than Group SAR on both reversals.

Animals↗