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M Carlson

Publications and source records attributed to M Carlson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Expression of the SUC2 gene of Saccharomyces cerevisiae is induced by low levels of glucose.

High levels of glucose repress expression of the SUC2 gene in the yeast Saccharomyces cerevisiae. We have discovered that low levels of glucose are required for maximal transcription of SUC2: SUC2 expression is induced about five- to ten-fold in cells growing on low levels of glucose (0.1%) compared to cells growing on galactose or glycerol. Two pieces of evidence suggest that this low-glucose-induced expression is mediated by a repression mechanism that involves an upstream repression site in the SUC2 promoter (URS(SUC2)). First, deletion of the URS(SUC2) results in expression of the SUC2 gene in the absence of glucose, and second the URS(SUC2) mediates a six-fold repression of a reporter gene when inserted into a heterologous promoter. However, this URS(SUC2) mediated repression occurs on all tested carbon sources, suggesting that this URS element acts in concert with all other promoter elements to respond to low concentrations of glucose. This repression requires the general repressor SSn6p. SNF3, which encodes a glucose transporter that appears to be a sensor of low levels of glucose, is also required for low-glucose-induced expression of SUC2.

DNA-Binding Proteins↗
PubMed1997

Mutations in GSF1 and GSF2 alter glucose signaling in Saccharomyces cerevisiae.

One function of the Saccharomyces cerevisiae Snf1 protein kinase is to relieve glucose repression of SUC, GAL, and other genes in response to glucose depletion. To identify genes that regulate Snf1 kinase activity, we have selected mutants that inappropriately express a SUC2promoter::HIS3 gene fusion when grown in glucose and that require Snf1 function for this phenotype. Mutations representing two new complementation groups (gsf1 and gsf2) were isolated. gsf1 mutations affect two distinct responses to glucose: the Snf1-regulated glucose repression of SUC2 and GAL10 transcription and the Snf1-independent induction by glucose of HXT1 transcription. gsf2 mutations relieve glucose repression of SUC2 and GAL10 transcription and, in combination with snf1 delta, cause an extreme slow growth phenotype. The GSF2 gene was cloned by complementation of the gsf2-1 snf1 delta slow growth phenotype and encodes a previously uncharacterized 46kD protein.

Alleles↗
PubMed1997

Interaction of a Swi3 homolog with Sth1 provides evidence for a Swi/Snf-related complex with an essential function in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae Swi/Snf complex has a role in remodeling chromatin structure to facilitate transcriptional activation. The complex has 11 components, including Swi1/Adr6, Swi2/Snf2, Swi3, Snf5, Snf6, Snf11, Swp73/Snf12, and Tfg3. Mammalian homologs of these proteins have been shown to form multiple Swi/Snf-related complexes. Here we characterize an S. cerevisiae Swi3 homolog (Swh3) and present evidence that it associates in a complex with a Snf2 homolog, Sthl. We identified Swh3 as a protein that interacts with the N terminus of Snf2 in the two-hybrid system. Swh3 and Swi3 are functionally distinct, and overexpression of one does not compensate for loss of the other. Swh3 is essential for viability and does not activate transcription of reporters. The Snf2 sequence that interacts with Swh3 was mapped to a region conserved in Sth1. We show that Swh3 and Sth1 fusion proteins interact in the two-hybrid system and coimmunoprecipitate from yeast cell extracts. We also map interactions between Swh3 and Sth1 and examine the role of a leucine zipper motif in self-association of Swh3. These findings, together with previous analysis of Sth1, indicate that Swh3 and Sth1 are associated in a complex that is functionally distinct from the Swi/Snf complex and essential for viability.

Adenosine Triphosphatases↗
PubMed1997

The Snf1 protein kinase and its activating subunit, Snf4, interact with distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex.

The Snf1 protein kinase plays a central role in the response to glucose starvation in the yeast Saccharomyces cerevisiae. Previously, we showed that two-hybrid interaction between Snf1 and its activating subunit, Snf4, is inhibited by high levels of glucose. These findings, together with biochemical evidence that Snf1 and Snf4 remain associated in cells grown in glucose, suggested that another protein (or proteins) anchors Snf1 and Snf4 into a complex. Here, we examine the possibility that a family of proteins, comprising Sip1, Sip2, and Gal83, serves this purpose. We first show that the fraction of cellular Snf4 protein that is complexed with Snf1 is reduced in a sip1delta sip2delta gal83delta triple mutant. We then present evidence that Sip1, Sip2, and Gal83 each interact independently with both Snf1 and Snf4 via distinct domains. A conserved internal region binds to the Snf1 regulatory domain, and the conserved C-terminal ASC domain binds to Snf4. Interactions were mapped by using the two-hybrid system and were confirmed by in vitro binding studies. These findings indicate that the Sip1/Sip2/Gal83 family anchors Snf1 and Snf4 into a complex. Finally, the interaction of the yeast Sip2 protein with a plant Snf1 homolog suggests that this function is conserved in plants.

AMP-Activated Protein Kinases↗
PubMed1997

Genetics of transcriptional regulation in yeast: connections to the RNA polymerase II CTD.

Transcriptional regulation is important in all eukaryotic organisms for cell growth, development, and responses to environmental change. Saccharomyces cerevisiae, or bakers' yeast, has provided a powerful system for genetic analysis of transcriptional regulation, and findings from the study of this model system have proven broadly applicable to higher organisms. Transcriptional regulation requires the interactions of regulatory proteins with various components of the transcription machinery. Recently, genetic analysis of a diverse set of transcriptional regulatory responses has converged with studies of the function of the RNA polymerase II carboxy-terminal domain (CTD) to reveal regulatory roles for proteins associated with the CTD. These proteins, designated Srb/mediator proteins, are broadly involved in both positive and negative regulatory responses in vivo. This review focuses on the connections between genetic analysis of transcriptional regulation and the functions of the Srb/mediator proteins associated with the RNA polymerase II CTD.

Amino Acid Sequence↗
PubMed1997

Regression of nifedipine-induced gingival hyperplasia following switch to a same class calcium channel blocker, isradipine.

Patients with nifedipine-induced gingival hyperplasia (GH) often require continued calcium channel blocker therapy. Switches to diltiazem and verapamil have been described; however, these drugs are of a different chemical class and present therapeutic limitations in some patients. The purpose of this study was to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine derivative with a low incidence of GH. Fourteen patients with nifedipine-induced GH were given a medical exam and a periodontal exam. The following parameters were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT), plaque index (PI), and gingival index (GI). Intraoral photographs, study models, and a gingival biopsy for histological examination were taken. Following baseline measures, patients were randomized to continued treatment with nifedipine or an equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected to receive 4 weeks of open label isradipine therapy, with biweekly examination continuing through the open label phase. The isradipine treatment arm showed a mean decrease in PD of 0.59 mm at week 8 (P < 0.05). No other measured parameter (GM, GT, PI, GI) was significantly changed, compared either to baseline or to the alternate treatment arm. Clinically, 60% of patients treated with isradipine exhibited a decrease in hyperplasia, while 66% of patients treated with nifedipine demonstrated an increase in hyperplasia, a significant difference (P < 0.05). When combined with open label data, patients switching therapy to isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an increase in gingival overgrowth. All patients exhibited adequate control of hypertension. We conclude that in hypertensive patients with nifedipine-induced GH, switching hypertensive therapy to isradipine may result in a regression of GH. When coupled with aggressive oral hygiene treatment, this drug may provide a reasonable option for patients requiring dihydropyridine treatment.

Adult↗
PubMed1996

Glucose regulates protein interactions within the yeast SNF1 protein kinase complex.

The SNF1 protein kinase is broadly conserved in eukaryotes and has been implicated in responses to environmental and nutritional stress. In yeast, the SNF1 kinase has a central role in the response to glucose starvation. SNF1 is associated with its activating subunit, SNF4, and other proteins in complexes. Using the two-hybrid system, we show that interaction between SNF1 and SNF4 is strongly regulated by the glucose signal. Moreover, this interaction is appropriately affected by mutations in regulators, including protein phosphatase 1. We show that SNF4 binds to the SNF1 regulatory domain in low glucose, whereas in high glucose the regulatory domain binds to the kinase domain of SNF1 itself. Genetic analysis further suggests that the SNF1 regulatory domain autoinhibits the kinase activity and that in low glucose SNF4 antagonizes this inhibition. Finally, these interactions have been conserved from yeast to plants, indicating that homologs of the SNF1 kinase complex respond to regulatory signals by analogous mechanisms.

AMP-Activated Protein Kinases↗
PubMed1996

Measurement of lung mechanics at different lung volumes and esophageal levels in normal subjects: effect of posture change.

Lung elastance and resistance increase in the supine posture. To evaluate the effects of change in posture on regional lung mechanics at different lung volumes, lung elastance and resistance were measured at graded volume subdivisions and three esophageal levels at seated and supine body positions, using the esophageal balloon technique. Volumes were adjusted to be the same in both postures. In general, lung elastance (both static and dynamic) tended to be higher in supine posture and uniform at all lung volumes, except at 80% vital capacity, where it increased sharply. The ratio of dynamic to static lung elastance was slightly higher at the cephalad esophageal level, where regional flow rates and relative volume expansion are lower. Lung resistance varied inversely with lung volume but was higher at corresponding volume subdivisions in the supine posture. It decreased at more cephalad esophageal levels, where volume expansion and flow are less. Thus, the increase in regional flow at low volume subdivisions (most marked in the supine position) also contributed to higher lung resistance at these volumes. These findings are explained on the basis of a combination of Newtonian physics as well as nonlinear viscoelastic properties of the lung as applied to regional flow and volume expansion.

Adult↗
PubMed1996

Immediate response to inspiratory resistive loading in anesthetized patients with kyphoscoliosis: spirometric and neural effects.

In kyphoscoliosis (KS), lung volumes are reduced, respiratory elastance and resistance are increased, and breathing pattern is rapid and shallow, attributes that may contribute to defense of tidal volume (VT) in the face of inspiratory resistive loading. The control of ventilation of 12 anesthetized patients about to undergo corrective spinal surgery was compared to that of 11 anesthetized patients free of cardiothoracic disease during quiet breathing and the first breath through one of three linear resistors. Mean forced vital capacity (FVC) of the KS group was 48% that of the controls (C). Passive elastance (Ers) and active elastance and resistance (E'rs and R'rs, respectively) were computed according to previously described techniques (Behrakis PK, Higgs BD, Baydur A, Zin WA, Milic-Emili J (1983) Active inspiratory impedance in halothane-anesthetized humans. J Appl Physiol 54: 1477-1481). Baseline tidal volume VT, inspiratory duration Tl, expiratory duration TE, duration of total breathing cycle TT, and inspiratory duty cycle TI/TT were significantly reduced, while VE was slightly decreased in the KS. Ers, E'rs, and R'rs, were, respectively, 72, 69, and 89% greater in the KS. Driving pressure (Pmus) was derived from the equation of motion, using active values of respiratory elastance. With resistive loading, there was greater prolongation of TI in the C, while percent reduction in VT and minute ventilation VE was less in KS. Compensation in both groups was achieved through three changes in the Pmus waveform. (1) Peak amplitude increased. (2) The duration of the rising phase increased. (3) The rising Pmus curve became more concave to the time axis. These changes were most marked with application of the highest resistance in both groups. Peak driving pressure and mean rate of rise of Pmus were greater in the KS. Increased intrinsic impedance, Pmus, and differences in changes in neural timing in anesthetized kyphoscoliotics contribute to modestly greater VT defense, compared to that of anesthetized subjects free of cardiorespiratory disease.

Adolescent↗
PubMed1996

Recurrence of conduction following radiofrequency catheter ablation procedures: relationship to ablation target and electrode temperature. The Atakr Multicenter Investigators Group.

INTRODUCTION: More than 1 in 10 patients may develop recurrence of conduction after undergoing a successful radiofrequency catheter ablation procedure. The physiologic basis for recurrence following successful ablation procedures remains uncertain. The purpose of this study was to evaluate the role of electrode temperature as a predictor of recurrence following radiofrequency catheter ablation procedures. METHODS AND RESULTS: The subjects of this study were 538 patients who underwent a successful attempt at radiofrequency catheter ablation of AV nodal reentrant tachycardia, an accessory pathway, and/or the AV junction. Patients were followed for a mean of 215 +/- 138 days. Conduction recurred in 35 (6.5%) of the 538 patients. Recurrence of conduction occurred in 25 (9.3%) of 270 patients undergoing ablation of an accessory pathway, 7 (3.5%) of 201 patients undergoing ablation of AV nodal reentrant tachycardia, and in 3 (4.5%) of 67 patients undergoing ablation of the AV junction. The electrode temperature achieved at successful sites associated with recurrence was not different from the temperature achieved at successful sites without recurrence (61.1 +/- 8.9 vs 61.6 +/- 9.1; P = 0.8). The likelihood of developing a recurrence was higher following ablation of accessory pathways than following ablation of AV nodal reentrant tachycardia or the AV junction (P = 0.03). Patients experiencing a recurrence following ablation of an accessory pathway had longer procedure durations (P = 0.0001). Ablation of left free-wall pathways was associated with a lower incidence of recurrence as compared with all other locations (P = 0.008). CONCLUSION: The results of this study suggest that electrode temperature at the successful ablation site cannot be used to identify patients at highest risk of recurrence.

Adolescent↗
PubMed1996

SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II.

The RNA polymerase II of Saccharomyces cerevisiae exists in holoenzyme forms containing a complex, known as the mediator, associated with the carboxyl-terminal domain. The mediator includes several SRB proteins and is required for transcriptional activation. Previous work showed that a cyclin-dependent kinase-cyclin pair encoded by SSN3 and SSN8, two members of the SSN suppressor family, are identical to two SRB proteins in the mediator. Here we have identified the remaining SSN genes by cloning and genetic analysis. SSN2 and SSN5 are identical to SRB9 and SRB8, respectively, which encode additional components of the mediator. Genetic evidence implicates the SSN genes in transcriptional repression. Thus, these identities provide genetic insight into mediator and carboxyl-terminal domain function, strongly suggesting a role in mediating transcriptional repression as well as activation. We also show that SSN4 and SSN7 are the same as SIN4 and ROX3, respectively, raising the possibility that these genes also encode mediator proteins.

Base Sequence↗
PubMed1996

Yeast SNF1 protein kinase interacts with SIP4, a C6 zinc cluster transcriptional activator: a new role for SNF1 in the glucose response.

The SNF1 protein kinase has been widely conserved in plants and mammals. In Saccharomyces cerevisiae, SNF1 is essential for expression of glucose-repressed genes in response to glucose deprivation. Previous studies supported a role for SNF1 in relieving transcriptional repression. Here, we report evidence that SNF1 modulates function of a transcriptional activator, SIP4, which was identified in a two-hybrid screen for interaction with SNF1. The N terminus of the predicted 96-kDa SIP4 protein is homologous to the DNA-binding domain of the GAL4 family of transcriptional activators, with a C6 zinc cluster adjacent to a coiled-coil motif The C terminus contains a leucine zipper motif and an acidic region. When bound to DNA, a LexA-SIP4 fusion activates transcription of a reporter gene. Transcriptional activation by SIP4 is regulated by glucose and depends on the SNF1 protein kinase. Moreover, SIP4 is differentially phosphorylated in response to glucose availability, and phosphorylation requires SNF1. These findings suggest that the SNF1 kinase interacts with a transcriptional activator to modulate its activity and provide the first direct evidence for a role of SNF1 in activating transcription in response to glucose limitation.

Amino Acid Sequence↗
PubMed1996

Protein phosphatase type 1 interacts with proteins required for meiosis and other cellular processes in Saccharomyces cerevisiae.

Protein phosphatase type I (PP1) is involved in diverse cellular processes, and its activity toward specific substrates is thought to be controlled by different regulatory or targeting subunits. To identify regulatory subunits and substrates of the Saccharomyces cerevisiae PP1, encoded by GLC7, we used the two-hybrid system to detect interacting proteins. Among the many proteins identified were Gac1, a known glycogen regulatory subunit, and a protein with homology to Gac1. We also characterized a new gene designated GIP1, for Glc7-interacting protein. We show that a Gip1 fusion protein coimmunoprecipitates with PP1 from cell extracts. Molecular and genetic analyses indicate that GIP1 is expressed specifically during meiosis, affects transcription of late meiotic genes, and is essential for sporulation. Thus, the Gip1 protein is a candidate for a meiosis-specific substrate or regulator of PP1. Finally, we recovered two genes, RED1 and SCD5, with roles in meiosis and the vesicular secretory pathway, respectively. These results provide strong evidence implicating PP1 function in meiosis. In addition, this study indicates that the two-hybrid system offers a promising approach to understanding the multiple roles and interactions of PP1 in cellular regulation.

Amino Acid Sequence↗
PubMed1996

A meta-analysis of the effectiveness of occupational therapy for older persons.

Given the current health care debate, it is imperative to document the usefulness of various health services for older persons, a rapidly growing population at increased risk for a wide variety of physical and functional impairments. A meta-analysis was conducted to examine the degree of effectiveness of occupational therapy for older persons. For a sample of 15 distinct tests of occupational therapy, a positive unweighted mean effect size of .51 (.54 when corrected for instrument unreliability) was obtained, along with a highly significant cumulative result for treatment success (p < .001). Beneficial treatment effects extended to activities of daily living-functional and psychosocial outcomes. The results for physical outcomes suggested a beneficial effect, although not every meta-analytic test yielded significant results. It was concluded that factors such as publication bias or poor study design are incapable of accounting for the positive meta-analytic result and that occupational therapy represents a worthwhile treatment option for older persons.

Activities of Daily Living↗
PubMed1996

Life domains and adaptive strategies of a group of low-income, well older adults.

Older adults are at increased risk for a variety of physical and functional limitations that threaten their ability to lead independent and fulfilling lives. Consequently, they stand to benefit from personalized strategies of adaptation that enable them to achieve successful outcomes in their daily activities and desired goals. In the current investigation, a qualitative descriptive methodology was used to document the perceived life domains of importance and associated strategies of adaptation of 29 residents of Angelus Plaza, a federally subsidized apartment complex in downtown Los Angeles for low-income, well older adults. On the basis of interview data, 10 life domains were identified, and within each domain, a typology of adaptive strategies was derived. The domains were activities of daily living (ADL), adaptation to a multicultural environment, free time usage, grave illness and death-spirituality, health maintenance, mobility maintenance, personal finances, personal safety, psychological well-being and happiness, and relationships with others. Although the typology should not be generalized to a geriatric population, therapists may wish to refer to it to gain a sense of the extent to which certain adaptive strategies may be applicable to the lives of particular older adults to whom they deliver services. The teaching of these adaptive strategies could then be incorporated into an individualized treatment plan. The typology also provides a broad picture of the kinds of adaptive strategies used by the older adults as a way of coping and adapting to their setting. Although some of the domains do not differ from those typically addressed in occupational therapy textbooks on geriatric care (e.g., ADL, health maintenance), others seem uniquely tailored to the specifics of the Angelus Plaza context (e.g., personal safety). Finally, certain domains emerged that may be highly relevant to older adults in most settings but are not typically the focus of occupational therapy programs (e.g., grave illness and death-spirituality, relationships with others). The emergence of these domains from our data suggests that therapists may wish to consider them more in treatment if they are convinced that they possess local relevance.

Activities of Daily Living↗
PubMed1995

REG1 binds to protein phosphatase type 1 and regulates glucose repression in Saccharomyces cerevisiae.

Protein phosphatase type 1 (PP1) is encoded by GLC7, an essential gene in Saccharomyces cerevisiae. The GLC7 phosphatase is required for glucose repression and appears to function antagonistically to the SNF1 protein kinase. Previously, we characterized a mutation, glc7-T152K, that relieves glucose repression but does not interfere with the function of GLC7 in glycogen metabolism. We proposed that the mutant GLC7T152K phosphatase is defective in its interaction with a regulatory subunit that directs participation of PP1 in the glucose repression mechanism. Here, we present evidence that REG1, a protein required for glucose repression, is one such regulatory subunit. We show that REG1 is physically associated with GLC7. REG1 interacts with GLC7 strongly and specifically in the two-hybrid system, and REG1 and GLC7 fusion proteins co-immunoprecipitate from cell extracts. Moreover, overexpression of a REG1 fusion protein suppresses the glc7-T152K mutant defect in glucose repression. This and other genetic evidence indicate that the two proteins function together in regulating glucose repression. These results suggest that REG1 is a regulatory subunit of PP1 that targets its activity to proteins in the glucose repression regulatory pathway.

Base Sequence↗