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M J Simmons

Publications and source records attributed to M J Simmons.

At least 37 records · Page 2Linked to original sources
PubMed1990

Repression of P element-mediated hybrid dysgenesis in Drosophila melanogaster.

Inbred lines derived from a strain called Sexi were analyzed for their abilities to repress P element-mediated gonadal dysgenesis. One line had high repression ability, four had intermediate ability and two had very low ability. The four intermediate lines also exhibited considerable within-line variation for this trait; furthermore, in at least two cases, this variation could not be attributed to recurring P element movement. Repression of gonadal dysgenesis in the hybrid offspring of all seven lines was due primarily to a maternal effect; there was no evidence for repression arising de novo in the hybrids themselves. In one of the lines, repression ability was inherited maternally, indicating the involvement of cytoplasmic factors. In three other lines, repression ability appeared to be determined by partially dominant or additive chromosomal factors; however, there was also evidence for a maternal effect that reduced the expression of these factors in at least two of the lines. In another line, repression ability seemed to be due to recessive chromosomal factors. All seven lines possessed numerous copies of a particular P element, called KP, which has been hypothesized to produce a polypeptide repressor of gonadal dysgenesis. This hypothesis, however, does not explain why the inbred Sexi lines varied so much in their repression abilities. It is suggested that some of this variation may be due to differences in the chromosomal position of the KP elements, or that other nonautonomous P elements are involved in the repression of hybrid dysgenesis in these lines.

Animals↗
PubMed1990

Clinical evaluation of an automated chemical inhibition assay for lactate dehydrogenase isoenzyme 1.

We evaluated an automated assay for lactate dehydrogenase (LD; EC 1.1.1.27) isoenzymes, supplied by Boehringer Mannheim Diagnostics (BMD) and based on selective chemical inhibition of non-LD-1 isoenzymes by guanidine thiocyanate. Results were compared with the Roche Isomune LD-1 method. The Hitachi 717 analyzer was used to measure enzyme activity for both procedures in 229 serum samples. One hundred specimens were also analyzed by the Helena rapid electrophoresis (REP) method. We determined the limit of linearity of the BMD method to be about 1200 U of LD-1 per liter. The analytical correlation of BMD (y) with Isomune (x) yielded y = 1.0x + 0.5 U/L, r = 0.997, Sy/x = 16.9 (range 20-1397 U/L). The regression equation for BMD vs REP was y = 1.1x + 7.2% (r = 0.800, Sy/x = 7.4, range 14-83%). Average values for within-run precision for low (38 U/L), medium (180 U/L), and high (865 U/L) controls were 4.1%, 1.0%, and 0.5%, respectively (16 trials of six each). The average values for run-to-run precision were 4.1%, 1.7%, and 1.1%, respectively, for these controls (n = 16). We used receiver-operating characteristic curves to determine optimum decision limits. Using an LD-1 cutoff of 40% of total LD, we obtained a clinical sensitivity of 97-100% and a specificity of 95% when blood was collected during the optimum interval, 24-48 h after the onset of chest pain. We conclude that the BMD LD-1 assay is equivalent to the immunochemical and electrophoretic assays for measuring the LD-1 isoenzyme.

Autoanalysis↗
PubMed1988

Spontaneous formation of compound X chromosomes in Drosophila melanogaster.

Males carrying different X chromosomes were tested for the ability to produce daughters with attached-X chromosomes. This ability is characteristic of males carrying an X chromosome derived from 59b-z, a multiply marked X chromosome, and is especially pronounced in males carrying the unstable 59b-z chromosomes Uc and Uc-lr. Recombination experiments with one of the Uc-lr chromosomes showed that the formation of compound chromosomes depends on two widely separated segments. One of these is proximal to the forked locus and is probably proximal to the carnation locus. This segment may contain the actual site of chromosome attachment. The other essential segment lies between the crossveinless and vermilion loci and may contain multiple factors that influence the attachment process.

Animals↗
PubMed1987

The influence of nonautonomous P elements on hybrid dysgenesis in Drosophila melanogaster.

An inbred line of the M' strain Muller-5 Birmingham was studied for its abilities to affect P-M hybrid dysgenesis. This strain possesses 57 P elements, all of which are apparently defective in the production of the P transposase. In combination with transposase-producing elements, these nonautonomous elements can enhance or diminish the incidence of hybrid dysgenesis, depending on the trait that is studied. Dysgenic flies that have one or more paternally-derived chromosomes with these elements partially repress the instability of the P element insertion mutation, snw; however, such flies have elevated frequencies of another dysgenic trait, GD sterility, and also show distorted segregation ratios. An explanation is presented in which all of these phenomena are unified as manifestations of the kinetics of P element activation in the germ line. The progeny of Muller-5 Birmingham females exhibit partial repression of both snw instability and GD sterility. This repression appears to involve a factor that can be transmitted maternally through at least two generations. This mode of repression therefore conforms to the pattern of inheritance of the P cytotype, the condition that brings about nearly total repression of P element activity in some strains. Models in which this repression could arise from the nonautonomous P elements of Muller-5 Birmingham are discussed.

Animals↗
PubMed1986

Sterility and hypermutability in the P-M system of hybrid dysgenesis in Drosophila melanogaster.

Inbred wild strains of Drosophila melanogaster derived from the central and eastern United States were used to make dysgenic hybrids in the P-M system. These strains possessed P elements and the P cytotype, the condition that represses P element transposition. Their hybrids were studied for the mutability of the P element insertion mutation, snw, and for the incidence of gonadal dysgenesis (GD) sterility. All the strains tested were able to induce hybrid dysgenesis by one or both of these assays; however, high levels of dysgenesis were rare. Sets of X chromosomes and autosomes from the inbred wild strains were more effective at inducing GD sterility than were sets of Y chromosomes and autosomes. In two separate analyses, GD sterility was positively correlated with snw mutability, suggesting a linear relationship. However, one strain appeared to induce too much GD sterility for its level of snw destabilization, indicating an uncoupling of these two manifestations of hybrid dysgenesis.

Animals↗
PubMed1985

Transposase titration in Drosophila melanogaster: a model of cytotype in the P-M system of hybrid dysgenesis.

In the P-M system of hybrid dysgenesis of Drosophila melanogaster, some M strains possess chromosomal P elements. The chromosomes from one of these pseudo-M strains reduced the instability of a P element-insertion mutation of the singed bristle locus. We suggest that this reduction is an indication of competition for a transposase that binds to the P elements on the chromosomes from the pseudo-M strain as well as to the P elements at the singed locus; the pseudo-M strain's P elements might therefore be said to titrate the transposase, reducing its availability to interact with the P elements at the singed locus. We hypothesize that a similar mechanism regulates the movement of P elements in the P strains of D. melanogaster, although in this case we propose that the titrating elements are extrachromosomal and that they are generated by the action of the transposase itself.

Animals↗
PubMed1985

Chromosomal effects on mutability in the P-M system of hybrid dysgenesis in Drosophila melanogaster.

Two manifestations of hybrid dysgenesis were studied in flies with chromosomes derived from two different P strains. In one set of experiments, the occurrence of recessive X-linked lethal mutations in the germ cells of dysgenic males was monitored. In the other, the behavior of an X-linked P-element insertion mutation, snw, was studied in dysgenic males and also in dysgenic females. The chromosomes of one P strain were more proficient at causing dysgenesis in both sets of experiments. However, there was variation among the chromosomes of each strain in regard to the ability to induce lethals or to destabilize snw. The X chromosome, especially when it came from the stronger P strain, had a pronounced effect on both measures of dysgenesis, but in combination with the major autosomes, these effects were reduced. For the stronger P strain, the autosomes by themselves contributed significantly to the production of X-linked lethals and also had large effects on the behavior of snw, but they did not act additively on these two characters. For this strain, the effects of the autosomes on the X-linked lethal mutation rate suggest that only 1/100 P element transpositions causes a recessive lethal mutation. For the weaker P strain, the autosomes had only slight effects on the behavior of snw and appeared to have negligible effects on the X-linked lethal mutation rate. Combinations of chromosomes from either the strong or the weak P strain affected both aspects of dysgenesis in a nonadditive fashion, suggesting that the P elements on these chromosomes competed with each other for transposase, the P-encoded function that triggers P element activity. Age and sex also influenced the ability of chromosomes and combinations of chromosomes to cause dysgenesis.

Animals↗
PubMed1984

Effects of mutagenized X chromosomes of Drosophila melanogaster on viability and fitness in males.

Drosophila melanogaster males were treated with different doses of X-rays or ethyl methanesulfonate (EMS) and mated so that mutagenized X chromosomes could be recovered and tested for lethal mutations and for less drastic mutations affecting viability and other aspects of fitness. The lethals were detected in standard X-linked lethal tests. The less drastic mutations were detected in one generation tests for effects on viability and in multigeneration tests for effects on overall fitness. The Poisson-corrected frequencies of the lethal mutations increased linearly with dose for both X-rays and EMS. Based on the data, 1 Krad X-rays given acutely induces the same number of lethals as 0.55 mM EMS administered by feeding. For some of the X-ray and EMS doses, the mutagenized chromosomes that were nonlethal reduced the viability of their carriers by a small amount, but there was no discernable dose-effect relationship. However in every case where a viability effect was seen, the percentage reduction was less than the corresponding frequency of lethals. All the groups of mutagenized nonlethal chromosomes reduced overall fitness by a significant percentage. Wherever a meaningful comparison was possible, this reduction was 2-3 times the reduction in viability, but, as in the viability data, no dose-effect relationship was discernable.

Animals↗
PubMed1984

A comparison of mutation rates for specific loci and chromosome regions in dysgenic hybrid males of Drosophila melanogaster.

The mutation rates of specific loci and chromosome regions were estimated for two types of dysgenic hybrid males. These came from crosses between P or Q males and M females in the P-M system of hybrid dysgenesis. The M X P hybrids were the more mutable for each of the loci and chromosome regions tested. The Beadex locus was highly mutable in these hybrids but did not mutate at all in the sample of gametes from the M X Q hybrids. The singed locus had 75% of the mutability of Beadex in the M X P hybrids; it was also mutable in the M X Q hybrids. The white locus was only slightly mutable in the M X P hybrids and not at all mutable in the M X Q hybrids. The mutations in singed and white probably arose from the insertion of P elements into these loci; the mutations at Beadex probably involved the action of a P element located near this locus on the X chromosome of the P strain that was used in the experiments. Mutations in two chromosome regions, one including the zeste-white loci and the other near the miniature locus, were much more frequent in the M X P hybrids than in the M X Q hybrids. These mutations also probably arose from P element insertions. The implication is that insertion mutations occur infrequently in the M X Q hybrids, possibly because most of the P elements they carry are defective. In M X P hybrids, there is variation among loci with respect to P element mutagenesis, indicating that P elements possess a degree of insertional specificity.

Animals↗
PubMed1984

Analysis of dysgenesis-induced lethal mutations on the X chromosome of a Q strain of Drosophila melanogaster.

The Q strain known as v6 was tested for its ability to induce X-linked lethal mutations in male and female hybrids from crosses with M strains in the P-M system of hybrid dysgenesis. All measurements of the mutation rate were made on the X chromosome derived from the v6 strain. The lethal rate for young hybrid males from the cross M female X v6 male was 1.11% per chromosome. For older males, it was only 0.44%, suggesting that there is less mutational or more repair activity in the germ cells of the older males or that mutant cells are selectively eliminated as the hybrid males age. The lethal rate for hybrid females from comparable crosses was approximately the same for both ages that were tested. However, it was substantially less than the rate for the hybrid males--only 0.26% per chromosome. Genetically identical hybrid females from reciprocal crosses also showed a low mutation rate, 0.13% per chromosome. Again, there was no difference between young and old flies. Mapping experiments established that most of the lethal mutations that were recovered from the male and female hybrids were located in two regions on the X chromosome, one between bands 14B13 and 15A9 , the other between bands 19A1 and 20A , which encompasses the maroonlike locus. More refined mapping of the lethals in the maroonlike region demonstrated that the vast majority of these affected a single gene located in band 19C4 . Cytological analysis of the lethal chromosomes revealed that several carried rearrangements, including inversions, duplications and deficiencies. Chromosome breakage occurred primarily in bands 14D1 -3 and 18F- 20A , and most of the breaks in the latter segment were located in 19C . However, rearrangements involving 19C and mutations of the gene in 19C4 were mutually exclusive events. In situ hybridization of a P element probe to the chromosomes of v6 demonstrated that P elements reside at a minimum of five sites on the X chromosome. These P element sites correspond to the mutational and breakage hot spots on that chromosome. The combined genetic and cytological data imply that most of the X-linked lethal mutations that occur in M X v6 hybrids are due to local P element action. Consideration of these and other data suggest that v6 is a weak P strain in the P-M system of hybrid dysgenesis and that other Q strains might also be regarded in this way.

Animals↗
PubMed1983

Self-reported dark red bleeding as a marker comparable with occult blood testing in screening for large bowel neoplasms.

The study was designed to determine the prevalence of large bowel symptoms in an adult working population and to assess their value in screening for large bowel neoplasms. A symptom questionnaire was sent to workers in two large organizations and the results were compared with faecal occult blood testing in the same individuals using Haemoccult (Eaton Laboratories). Completed symptom questionnaires and Haemoccult test kits were returned by 916 out of a total of 1805 employees over the age of 40 (compliance 50.7 per cent). Twenty-eight (3.1 per cent) were Haemoccult positive and 114 (12.4 per cent) had one or more symptoms. All positives (129 persons) were examined by flexible sigmoidoscopy and barium enema. No cancer was found but 7 patients with adenomas greater than 10 mm diameter were discovered. Each of the 7 patients reported at least one symptom (dark red bleeding in 4, bright red bleeding in 2 and diarrhoea in 1) and 6 were Haemoccult positive. There was no individual with a Haemoccult positive adenoma without symptoms. Predictive values for adenomas over 10 mm for Haemoccult positive tests (21 per cent), self-reported dark bleeding (16 per cent) and diarrhoea (17 per cent), were significantly higher than for other symptoms. The predictive value rose significantly to 46 per cent for Haemoccult-positive patients who in addition had at least one symptom (P less than 0.05) and to 57 per cent for Haemoccult positive with dark bleeding. These combinations of Haemoccult- and symptom-positive results increased the specificity of 97.6 per cent for Haemoccult alone to values over 99 per cent without reducing sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1983

Homologue destabilization by a putative transposable element in Drosophila melanogaster.

We postulate the presence of a transposable element, designated the L factor, to explain the properties of an unstable X chromosome and its derivatives. These chromosomes generate recessive lethal mutations at high rates, as does a stable X chromosome that has been associated with them for only one generation. The stable X chromosome does not become highly mutable in the absence of the unstable X chromosome, even when autosomes from the unstable stock are present. These facts suggest that the L factor is confined to the X chromosome and that it transposes to other X chromosomes paired with it. We propose the term "homologue destabilization" to denote the change in the stable chromosome brought about by this transposition. The lethal mutations caused by the L factor occur preferentially in the region around the cut wing locus (ct) and are sometimes associated with recognizable chromosome aberrations. The breakpoints of these aberrations are most often in the vicinity of ct, implying that the L factor is located near ct on the unstable chromosome, but it may reside at other sites as well. Alternately, the ct region may simply be a preferred target for the insertion of this transposable element.

Animals↗
PubMed1981

An increase in the X-linked lethal mutation rate associated with an unstable locus in Drosophila melanogaster.

The behavior of an unstable allele of the singed-bristle locus on the X chromosome was studied in connection with the occurrence of lethal mutations on that same chromosome. The unstable allele, weak singed (snw), is under the control of the P-M system of hybrid dysgenesis and, in the M cytotype, mutates secondarily to extreme singed (sne) and to wild type (sn+) at high rates. Chromosomes whose snw allele had mutated in this fashion sustained lethal mutations at a rate of 3%; whereas, those whose snw allele had apparently remained unchanged, acquired lethals at a lower rate, 1.3%. The significant difference between these values indicates a statistical coincidence between the phenomena of snw instability and X-linked lethal mutation induction. This coincidence can be explained by postulating that mutations at the singed locus sometimes release a genetic element capable of reinserting elsewhere in the chromosome. Alternately, snw instability and lethal induction might be associated because they are the effects of a common cause, perhaps some mutation-inducing substance present in various amounts in the germ cells of dysgenic flies. The lethals that occurred on chromosomes whose snw allele had mutated to sne mapped preferentially close to singed. The lethals on the snw and sn+ chromosomes did not show this concentration on the map. Cytological analysis of samples of all three types of lethal chromosomes indicated that, with one exception, there was no detectable breakage at the singed locus itself. The single instance of breakage at singed was not associated with any change in the singed phenotype. Thus, the instability of snw apparently does not involve detectable breakage of the singed locus, or if it does, this breakage is not a common event.

Animals↗
PubMed1980

Site specificity of mutations arising in dysgenic hybrids of Drosophila melanogaster.

Mutations arising in dysgenic hybrids of Drosophila melanogaster were collected in the zeste-white region of the X chromosome. A preponderance of the mutations affected the zw1 locus; many of these were asociated with structural abnormalities including inversions, deficiencies, and insertions in the 3A3-4 region of the polytene chromosome map. The extreme sensitivity of the zw1 locus to the mutator activity of dysgenic hybrids contrasted with the apparent insensitivity of the zw2 locus. Other loci in the zeste-white region were weakly sensitive to the mutator activity. Insertions of two and six bands were seen between bands 3A4 and 3A6 in the chromosomes of one of the zw1 mutant stocks examined. Another insertion was detected at position 2F4-5 in a different stock. Many of the mutant chromosome were evidently unstable, as judged by secondary breakage in other parts of the X chromosome. The cytogenetic data are consistent with the idea that mutations arising in dysgenic hybrids are caused by transposable elements which insert preferentially at certain sites on the chromosomes.

Animals↗
PubMed1980

High mutability in male hybrids of Drosophila melanogaster.

The frequencies of sex-linked lethal mutations arising in hybrid male offspring from crosses and in nonhybrid controls were determined. The hybrids were produced by crossing representative strains of the P-M system of hybrid dysgenesis in all possible combinations. Males from the cross of P males x M females had a mutation rate about 15 times higher than that of nonhybrid males from the P strain. Genetically identical males from the reciprocal cross had a mutation rate 3 to 4 times that of the nonhybrids. For crosses involving a Q strain, a significant increase in the mutation rate was detected in males produced by matings of Q males with M females. No increase was observed in genetically identical males from the reciprocal mating. Crosses between P and Q strains gave male hybrids with mutation rates not different from those of nonhybrids. Many of the lethals that occurred in hybrids from the cross of P males x M females appeared to be unstable; fewer lethals that arose in hybrids from the cross of Q males x M females were unstable. The relationship between P and Q strains is discussed with respect to a model of mutation induction in dysgenic hybrids.

Animals↗
PubMed1978

Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster.

The heterozygous effects on fitness of second chromosomes carrying mutants induced with different doses of EMS were ascertained by monitoring changes in chromosome frequencies over time. These changes were observed in populations in which the treated chromosomes, as well as untreated competitors, remained heterozygous in males generation after generation. This situation was achieved by using a translocation which links the second chromosome to the X chromosome; however, only untranslocated second chromosomes were mutagenized. Chromosomes were classified according to their effects on viability in homozygous condition. A preliminary homozygosis identified completely lethal chromosomes; secondary tests distinguished between drastic (viability index < 0.1) and nondrastic chromosomes. Chromosomes that were nondrastic after treatment were found to reduce the fitness of their heterozygous carriers by 3-5%. The data show that flies homozygous for these chromosomes were about 2.7% less viable per treatment with 1 mm EMS than flies homozygous for untreated chromosomes. By comparing the fitness-depressing effects of nondrastic EMS-induced mutants in heterozygous condition with the corresponding viability-depressing effects measured by Temin, it is apparent that the total fitness effects are several times larger than the viability effects alone. Completely lethal chromosomes derived from the most heavily treated material reduced fitness by 11% in heterozygous condition; approximately half of this reduction was due to the lethal mutations themselves.

Animals↗
PubMed1977

Fitness effects of EMS-induced mutations on the X chromosome of Drosophila melanogaster. II. Hemizygous fitness effects.

X chromosomes mutagenized with EMS were tested for their effects on the fitness of hemizygous carriers. The tests were carried out in populations in which treated and untreated X chromosomes segregated from matings between males and attached-X females; the populations were maintained for several generations, during which time changes in the frequencies of the treated and untreated chromosomes were observed. From the rates at which the frequencies changed, the fitness effects of the treated chromosomes were determined. It was found that flies hemizygous for a mutagenized chromosome were 1.7% less fit per mM EMS treatment than those hemizygous for an untreated chromosome. Since the same flies were only 0.5% per mM less viable than their untreated counterparts, the total fitness effect of an X chromosome carrying EMS-induced mutants is three to four times greater than its viability effect. By comparing the heterozygous effect of a mutagenized X chromosome on fitness with the corresponding hemizygous effect, the dominance value for the chromosome is estimated to be about 0.25.

Animals↗