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Biomedical subjects

M Carlson

Publications and source records attributed to M Carlson.

At least 235 records · Page 13Linked to original sources
PubMed1984

Structure and expression of the SNF1 gene of Saccharomyces cerevisiae.

The SNF1 gene of Saccharomyces cerevisiae is essential for normal regulation of gene expression by glucose repression. A functional SNF1 gene product is required to derepress many glucose-repressible genes in response to conditions of low external glucose. In the case of the SUC2 structural gene for invertase, SNF1 acts at the RNA level. We have reported the isolation of a cloned gene that complements the snf1 defect in S. cerevisiae and that is homologous to DNA at the SNF1 locus (J. L. Celenza and M. Carlson, Mol. Cell. Biol. 4:49-53, 1984). In this work we identified a 2.4-kilobase polyadenylate-containing RNA encoded by the SNF1 gene and showed that its level is neither regulated by glucose repression nor dependent on a functional SNF1 product. The position of the SNF1 RNA relative to the cloned DNA was mapped, and the direction of transcription was determined. The cloned DNA was used to disrupt the SNF1 gene at its chromosomal locus. Gene disruption resulted in A Snf1- phenotype, thereby proving that the cloned gene is the SNF1 gene and showing that the phenotype of a true null mutation is indistinguishable from that of previously isolated snf1 mutations.

Chromosome Mapping↗
PubMed1984

Upstream region required for regulated expression of the glucose-repressible SUC2 gene of Saccharomyces cerevisiae.

The SUC2 gene produces two mRNAs with different 5' ends that encode two forms of invertase. The 1.9-kilobase mRNA encoding secreted invertase is regulated by glucose repression (carbon catabolite repression), and the 1.8-kilobase mRNA encoding intracellular invertase is produced constitutively at low levels. To identify 5' noncoding sequences essential for regulated expression of SUC2, we constructed in vitro a series of deletions and inserted them into the yeast genome at the chromosomal SUC2 locus. Analysis of the effects of each deletion on SUC2 gene expression identified an upstream region required for derepression of secreted invertase synthesis. The 3' boundary of this region is near -418. The 5' boundary does not appear to be sharply defined, but lies ca. 100 base pairs upstream. A deletion extending from -418 to -140 allowed high-level derepression, indicating that no essential sequences lie between the upstream region and the TATA box at -133 and that the upstream region can be moved 279 base pairs closer to the transcriptional start site. Interactions between the deletions and several unlinked mutations affecting the regulation of SUC2 gene expression were examined. Sequences between -1,900 and -86 are dispensable for expression of the 1.8-kilobase mRNA.

Base Sequence↗
PubMed1983

Nucleotide sequence of the yeast SUC2 gene for invertase.

The yeast SUC2 gene is a structural gene for both the secreted and intracellular forms of invertase. We have determined the nucleotide sequence of the coding region and the 5' and 3' flanking regions. The coding regions for the signal peptide-containing precursor to secreted invertase and for the intracellular invertase begin at different initiation codons within the SUC2 gene but share the same reading frame. The amino acid sequences predicted for the two forms of invertase from the nucleotide sequence are consistent with the properties of the purified enzymes. Potential sites for glycosylation of the secreted invertase are identified.

Amino Acid Sequence↗
PubMed1983

Organization of the SUC gene family in Saccharomyces.

The SUC gene family of yeast (Saccharomyces) includes six structural genes for invertase (SUC1 through SUC5 and SUC7) found at unlinked chromosomal loci. A given yeast strain does not usually carry SUC+ alleles at all six loci; the natural negative alleles are called suc0 alleles. Cloned SUC2 DNA probes were used to investigate the physical structure of the SUC gene family in laboratory strains, commercial wine strains, and different Saccharomyces species. The active SUC+ genes are homologous. The suc0 allele at the SUC2 locus (suc2(0) in some strains is a silent gene or pseudogene. Other SUC loci carrying suc0 alleles appear to lack SUC DNA sequences. These findings imply that SUC genes have transposed to different chromosomal locations in closely related Saccharomyces strains.

Alleles↗
PubMed1983

The secreted form of invertase in Saccharomyces cerevisiae is synthesized from mRNA encoding a signal sequence.

The SUC2 gene of Saccharomyces cerevisiae encodes two differently regulated mRNAs (1.8 and 1.9 kilobases) that differ at their 5' ends. The larger RNA encodes a secreted, glycosylated form of invertase and the smaller RNA encodes an intracellular, nonglycosylated form. We have determined the nucleotide sequence of the amino-terminal coding region of the SUC2 gene and its upstream flanking region and have mapped the 5' ends of the SUC2 mRNAs relative to the DNA sequence. The 1.9-kilobase RNA contains a signal peptide coding sequence and presumably encodes a precursor to secreted invertase. The 1.8-kilobase RNA does not include the complete coding sequence for the signal peptide. The nucleotide sequence data prove that SUC2 is a structural gene for invertase, and translation of the coding information provides the complete amino acid sequence of an S. cerevisiae signal peptide.

Amino Acid Sequence↗
PubMed1982

Topography, cytoarchitecture, and sulcal patterns in primary somatic sensory cortex (SmI) prosimian primate, Perodicticus potto.

The topographic organization of the primary somatic sensory projection area (SmI) in relation to cytoarchitectural fields and sulcal patterns was examined in the prosimian primate Perodicticus potto. The area of cortex responding to low threshold (LT) cutaneous stimulation of the glabrous and hairy surfaces of the hand was determined by microelectrode mapping techniques, with standardized threshold stimuli for defining receptive fields. A single somatotopic projection of the two hand surfaces was found; the glabrous projection area is rostral to that of the hairy hand. Within both the glabrous and hairy areas, receptive fields on the distal digits are found anterior to those on the proximal hand. The glabrous hand projection area is coextensive with a dense granular area typical of koniocortex. The hairy hand area corresponds to a cytoarchitectural field which is less granular than the glabrous field. While koniocortex occupies the crown of the gyrus caudal to the coronally oriented sulcus, a large more rostral field, which contains both granule and large pyramidal cells, occupies the whole of the caudal bank of the sulcus. Force thresholds of many receptive fields (RFs) in Perodicticus were high both on the borders and within the LT area (perhaps because of the advanced age of these animals). However, the receptive field sizes for both the glabrous and hairy hand areas were of the same magnitude as those of Nycticebus (Carlson and FitzPatrick, '82). From the combined studies of three species of Lorisidae, Perodicticus, Galago (Carlson and Welt, '80), and Nycticebus (Carlson and FitzPatrick, '81), using similar mapping and stimulation techniques, both general and specific features of SmI hand area organization can be illustrated. A single projection of the glabrous and hairy hand is common to Perodicticus and Galago, but two glabrous projection areas are seen in Nycticebus. The projection area for the hand in Perodicticus is twice as large (relative to brain size) as in Galago and Perodicticus. The possible behavioral significance of increased differentiation of the hand area in Nycticebus and elaboration of the area in Perodicticus could be examined by study of hand use and tactile capacity in these same species.

Animals↗
PubMed1982

Two differentially regulated mRNAs with different 5' ends encode secreted with intracellular forms of yeast invertase.

The SUC2 gene of yeast (Saccharomyces) encodes two forms of invertase: a secreted, glycosylated form, the synthesis of which is regulated by glucose repression, and an intracellular, nonglycosylated enzyme that is produced constitutively. The SUC2 gene has been cloned and shown to encode two RNAs (1.8 and 1.9 kb) that differ at their 5' ends. The stable level of the larger RNA is regulated by glucose; the level of the smaller RNA is not. A correspondence between the presence of the 1.9 kb RNA and the secreted invertase, and between the 1.8 kb RNA and the intracellular invertase, was observed in glucose-repressed and -derepressed wild-type cells. In addition, cells carrying a mutation at the SNF1 locus fail to derepress synthesis of the secreted invertase and also fail to produce stable 1.9 kb RNA during growth in low glucose. Glucose regulation of invertase synthesis thus is exerted, at least in part, at the RNA level. A naturally silent allele (suc2 degrees) of the SUC2 locus that does not direct the synthesis of active invertase was found to produce both the 1.8 and 1.9 kb RNAs under normal regulation by glucose. A model is proposed to account for the synthesis and regulation of the two forms of invertase: the larger, regulated mRNA contains the initiation codon for the signal sequence required for synthesis of the secreted, glycosylated form of invertase; the smaller, constitutively transcribed mRNA begins within the coding region of the signal sequence, resulting in synthesis of the intracellular enzyme.

Cell Compartmentation↗
PubMed1981

Characteristics of sensory deficits following lesions of Brodmann's areas 1 and 2 in the postcentral gyrus of Macaca mulatta.

This study re-examines the double dissociation of tactile deficits resulting from restricted surgical removals of Brodmann's areas 1 and 2 in the postcentral gyrus of macaque monkeys. Area 1-operated animals showed selective deficits on texture tasks, roughness and line discriminations, while area 2-operated animals showed deficits only on angle tasks, size and curve discriminations. Severe deficits were evident in spite of preoperative training, forced correction trials, and the presentation of tasks of graded difficulty.

Animals↗
PubMed1981

A clinical study of the periodontal status of abutment teeth supporting swinglock removable partial dentures--a pilot study.

Eleven patients wearing mandibular swinglock bilateral distal extension removable partial dentures opposing maxillary complete dentures were studied for a period up to 2 years. They had moderate to advanced periodontal disease with retrograde mobility patterns. Periodontal therapy, as well as treatment of dental carious lesions, was completed before fabrication of the prosthesis. Recordings of the gingival status, pocket depth, plaque score, tooth mobility, and dental caries were made at the time of the placement of the prosthesis and thereafter at 6-month intervals. Final results were obtained at the end of 2 years in six patients (group A) and at 1 1/2 years in five patients (group B). Our findings show that both groups had a statistically significant increase in gingival inflammation. However, no differences in degree of inflammation were observed between the two groups with regard to the status of gingival tissues that were covered and uncovered by the components of the swinglock removable partial denture. Also, no statistically significant differences in pocket depths and plaque scores were found between the time of placement of the swinglock removable partial denture and the final recall visit. Of the 61 abutment teeth, 85.2% had no significant change in mobility, 11.5% showed a substantial decrease in mobility, and 3.3% showed a considerable increase in mobility. The patients were able to successfully wear the swinglock removable partial denture without clinically significant changes in the supporting structures of the abutment teeth. This report is part of an ongoing study to determine the efficacy of swinglock removable partial dentures.

Adult↗
PubMed1981

Mutants of yeast defective in sucrose utilization.

Utilization of sucrose as a source of carbon and energy in yeast (Saccharomyces) is controlled by the classical SUC genes, which confer the ability to produce the sucrose-degrading enzyme invertase (Mortimer and Hawthorne 1969). Mutants of S. cerevisiae strain S288C (SUC2+) unable to grow anaerobically on sucrose, but still able to use glucose, were isolated. Two major complementation groups were identified: twenty-four recessive mutations at the SUC2 locus (suc2-); and five recessive mutations defining a new locus, SNF1 (for sucrose nonfermenting), essential for sucrose utilization. Two minor complementation groups, each comprising a single member with a leaky sucrose-nonfermenting phenotype, were also identified. The Suc2 mutations isolated include four suppressible amber mutations and five mutations apparently exhibiting intragenic complementation; complementation analysis and mitotic mapping studies indicated that all of the suc2 mutations are alleles of a single gene. These results suggest that SUC2 encodes a protein, probably a dimer or multimer. No invertase activity was detected in suc2 probably a dimer or multimer. No invertase activity was detected in suc2 mutants,--The SNF1 locus is not tightly linked to SUC2. The snf1 mutations were found to be pleiotropic, preventing sucrose utilization by SUC2+ and SUC7+ strains, and also preventing utilization of galactose, maltose and several nonfermentable carbon sources. Although snf1 mutants thus display a petite phenotype, classic petite mutations do not interfere with utilization of sucrose, galactose or maltose. A common feature of all the carbon utilization systems affected by SNF1 is that all are regulated by glucose repression. The snf1 mutants were found to produce the constitutive nonglycosylated form of invertase, but failed to produce the glucose-repressible, glycosylated, secreted invertase. This failure cannot be attributed to a general defect in production of glycosylated and secreted proteins because synthesis of acid phosphatase, a glycosylated secreted protein not subject to glucose repression, was not affected by snf1 mutations. These findings suggest that the SNF1 locus is involved in the regulation of gene expression by glucose repression.

Genetic Code↗
PubMed1981

Genetic evidence for a silent SUC gene in yeast.

The SUC genes (SUC1-SUC7) of Saccharomyces are a family of genes that are dispersed in the yeast genome. A SUC+ allele at any locus confers the ability to produce the enzyme invertase and, thus, to ferment sucrose. Most yeast strains do not carry SUC+ alleles at all possible SUC loci. We have investigated the naturally occurring negative (suc0) alleles present at SUC loci with the aim of distinguishing between two possible models for the structure of suc0 alleles: (1) suc0 alleles correspond to a simple absence of SUC genetic information; (2) suc0 alleles are "silent" SUC genes that either produce a defective product or are not expressed. To facilitate these studies, sucrose-nonfermenting strains were constructed that are congenic to S. cerevisiae strain S288C (SUC2+), but carry at the SUC2 locus the naturally occurring negative allele, suc2(0), of strain FL100 (Lacroute 1968). These strains were used to study the genetic properties of the suc2(0) allele of FL100 and the suc0 alleles (suc1(0), suc3(0), etc.) of S288C. The suc2(0) allele was shown to revert to an active Suc+ state and to provide functional information at three points in the SUC2 gene in recombination experiments; this suc2(0) gene thus appears to be a "silent" gene. Similar tests for silent SUC genes in S288C (corresponding to loci other than SUC2) failed to reveal any additional silent genes.

Alleles↗