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Biomedical subjects

M L Goldberg

Publications and source records attributed to M L Goldberg.

At least 19 recordsLinked to original sources

The Drosophila l(1)zw10 gene product, required for accurate mitotic chromosome segregation, is redistributed at anaphase onset.

Mutations in the gene l(1)zw10 disrupt the accuracy of chromosome segregation in a variety of cell types during the course of Drosophila development. Cytological analysis of mutant larval brain neuroblasts shows very high levels of aneuploid cells. Many anaphase figures are aberrant, the most frequent abnormality being the presence of lagging chromosomes that remain in the vicinity of the metaphase plate when the other chromosomes have migrated toward the spindle poles. Finally, the centromeric connection between sister chromatids in mutant neuroblasts treated with colchicine often appears to be broken, in contrast with similarly treated control neuroblasts. The 85-kD protein encoded by the l(1)zw10 locus displays a dynamic pattern of localization in the course of the embryonic cell cycle. It is excluded from the nuclei during interphase, but migrates into the nuclear zone during prometaphase. At metaphase, the zw10 antigen is found in a novel filamentous structure that may be specifically associated with kinetochore microtubules. Upon anaphase onset, there is an extremely rapid redistribution of the zw10 protein to a location at or near the kinetochores of the separating chromosomes.

Amino Acid Sequence

Molecular analysis of a cytochrome P450 gene of family 4 on the Drosophila X chromosome.

A member of the cytochrome P450 superfamily has been identified within region 2D of the Drosophila X chromosome. The sequence of this gene shows strongest homology with P450 family 4 genes, and has thus been named CYP4D1 in accordance with convention. This P450 gene is expressed throughout Drosophila development, with the highest levels of transcript accumulation occurring during late larval stages. A fragment of Drosophila genomic DNA including the CYP4D1 gene has been reintroduced into the germ line by P-element-mediated transformation. This transduced fragment does not rescue any of the lethal mutations that have been identified in this genetically well-characterized region of the Drosophila genome.

Amino Acid Sequence

Biofeedback in back muscle strengthening.

This study was undertaken to investigate the use of electromyography (EMG) biofeedback as an add-on therapy to standard exercise in the restoration of the functional abilities of the trunk extensor muscles in patients suffering from chronic low-back pain (CLBP). A controlled experimental investigation was conducted to study the effectiveness of using the proposed treatment modality in the management of the low-back pain problem. The results obtained indicate that the proposed methodology was an effective tool to achieve a significant improvement in the strength of lumbar paraspinal muscles of chronic low-back pain patients.

Adult

The Drosophila zeste gene and transvection.

The zeste locus of Drosophila melanogaster encodes a DNA-binding protein that can influence transcription. A number of sites recognized by this protein fall within genes associated with transvection, a phenomenon suggesting a form of gene regulation that is responsive to the proximity of a gene to its homologous allele on another chromosome. These recent observations continue a history of studies concerning zeste and transvection which has inspired molecular models linking chromosome structure and positioning to the modulation of gene expression.

Alleles

The Drosophila zeste locus is nonessential.

Diepoxybutane-induced mutations of the Drosophila zeste locus were generated in an effort to obtain a null allele. Of 33 mutations of this X-linked gene isolated, 16 were associated with multilocus deletions of zeste and adjacent complementation groups, while the remainder were defects restricted to zeste undetectable by Southern blot analysis. Two of these multilocus deletions (Df(1)zdeb3 and Df(1)zdeb92) were employed in the synthesis of females completely deleted for zeste. Such "zesteless" flies were produced, though at frequencies lower than Mendelian expectations. zeste-deleted females are fertile, and can give rise to zeste-deleted female progeny. These results demonstrate that the product of the zeste gene is not essential to viability or to female fertility, even if absent both as a maternal contribution and as a product of the zygotic genome. However, the possibility that zeste may influence relative viability cannot be excluded. In spite of previous in vitro indications that the zeste protein may activate transcription of the Ultrabithorax (Ubx) gene, zeste -deleted flies are Ubx+ in phenotype. This suggests that the zeste protein normally is either a very weak transcription factor, or that its function can be substituted by that of other regulatory proteins.

Animals

Nucleotide sequence and structural analysis of the zeste locus of Drosophila melanogaster.

The zeste locus plays a central role in transvection phenomena, where the synaptic pairing of chromosomes carrying genes with which zeste interacts influences the expression of these genes. To explore the possible functions of the zeste gene product in this process, we have determined the DNA sequences both of a fragment of Drosophila genomic DNA capable of rescuing mutant zeste phenotypes, and of a near full-length cDNA clone derived from the 2.4-kb zeste mRNA. These data show that the zeste gene is interrupted by two small introns, and suggest that the majority of zeste sequences are contained within an intron of another transcriptional unit of opposite polarity. A large region of the predicted zeste product is comprised almost exclusively of glutamine and alanine residues. A domain near the N terminus of this protein, which is sufficient for site-specific DNA binding, is highly charged, as is the C-terminal region of the protein. A breakpoint of the rearrangement In (1)e(bx), which is associated with a za-like phenotype, is found within sequences encoding the zeste product, and would produce a truncated protein. The neomorphic mutation zv77h is correlated with a 300-bp deletion of sequences determining the untranslated 5' leader of the zeste messenger, but may also remove the initiating ATG codon, resulting in a zeste protein with an altered N terminus.

Amino Acid Sequence

DNA-binding properties of the Drosophila melanogaster zeste gene product.

The ability of the zeste moiety of beta-galactosidase-zeste fusion proteins synthesized in Escherichia coli to bind specific DNA sequences was examined. Such fusion proteins recognize a region of the white locus upstream of the start of transcription; this region has previously been shown to be required for genetic interaction between the zeste and white loci. Another strong binding site was localized to a region between 50 and 205 nucleotides before the start of the Ubx transcriptional unit; expression of the bithorax complex is also known to be influenced by the zeste locus. Weaker binding sites were also seen in the vicinity of the bxd and Sgs-4 genes, but it is currently unclear whether these binding sites play a role in transvection effects. The DNA-binding activity of the zeste protein is restricted to a domain of approximately 90 amino acids near the N terminus. This domain does not appear to contain homeobox or zinc finger motifs found in other DNA-binding proteins. The DNA-binding domain is not disrupted by any currently characterized zeste mutations.

Animals

Acceptable maximum effort (AME). A psychophysical measure of strength in back pain patients.

A new quantitative method for measuring functional abilities of chronic low-back pain patients is introduced. The method is based upon a psychophysical model referred to as acceptable maximum effort (AME). AME is the highest level of voluntary effort that a person can achieve without inducing unacceptable pain. In the current study, the AME method was applied to strength measurement. By use of a static strength measurement procedure, arm, leg, shoulder, back, and composite strengths were assessed upon admission to and discharge from a 4-week, nonsurgical comprehensive pain treatment program. The reliability of the AME method for each strength measure was assessed. In addition, the method was used to evaluate pre- to post-treatment changes in strength. Results indicate the AME method to be highly reliable and useful in determining treatment outcome. Reliability coefficients for all strength measures were above .90. The results are discussed in terms of their implications for standardized functional ability measurement in the area of chronic pain.

Back Pain

Molecular cloning, germ-line transformation, and transcriptional analysis of the zeste locus of Drosophila melanogaster.

Approximately 170 kilobase pairs (kb) of contiguous DNA sequences derived from bands 3A3,4 of the Drosophila melanogaster X chromosome have been isolated by molecular cloning. Sequences required for the wild-type expression of the zeste locus are located within a 6-kb fragment of this chromosomal region, as shown by phenotypic rescue of zeste mutants in P element-mediated germ-line transformation. Expression of zeste is correlated with a 2.2-kb poly(A)+ RNA species transcribed at all postzygotic stages of Drosophila development. Many zeste alleles, including several producing neomorphic phenotypes, are not associated with detectable rearrangements of DNA.

Animals

Laser angioplasty.

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Coronary Disease

Eyes as the center of focus in the visual examination of human faces.

An experiment was conducted to determine the degree to which individuals focus upon the eye region of others while visually inspecting their faces. Using an eye-tracking camera, 16 male subjects spent approximately 40% of their looking time focused upon the eye region of facial photographs, with each of the remaining parts of the face being looked at less.

Eye

Plasma cyclic nucleotide levels in juvenile-onset diabetes.

In patients with juvenile-onset diabetes, plasma concentrations of 3',5'-adenosine cyclic monophosphate (cAMP) were significantly lower than those of norman subjects [16 +/- 4 and 24 +/- 7 pmol per milliliter (p less than 0.025), respectively] as determined in this laboratory; whereas there were essentially no differences in plasma levels of 3',5'-guanosine cyclic monophosphate (cGMP). Because cAMP inhibits cell growth and cGMP stimulates it, these findings may represent an important factor in the atherosclerotic and obliterative angiopathies of diabetic individuals. We observed that cyclic nucleotide values were the same whether or not the subjects were receiving insulin. Those given insulin plus enough glucose to maintain hyperglycemia revealed modest elevations in cyclic nucleotide levels. Thus, the ratio of cAMP to cGMP, abnormally low in juvenile-onset diabetes, is relatively independent of short-term variations in plasma levels of either glucose of insulin.

Adult