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R Auty

Publications and source records attributed to R Auty.

12 recordsLinked to original sources
PubMed2001

Rvb1p and Rvb2p are essential components of a chromatin remodeling complex that regulates transcription of over 5% of yeast genes.

Eukaryotic Rvb1p and Rvb2p are two highly conserved proteins related to the helicase subset of the AAA+ family of ATPases. Conditional mutants in both genes show rapid changes in the transcription of over 5% of yeast genes, with a similar number of genes being repressed and activated. Both Rvb1p and Rvb2p are required for maintaining the induced state of many inducible promoters. ATP binding and hydrolysis by Rvb1p and Rvb2p is individually essential in vivo, and the two proteins are associated with each other in a high molecular weight complex that shows ATP-dependent chromatin remodeling activity in vitro. Our findings show that Rvb1p and Rvb2p are essential components of a chromatin remodeling complex and determine genes regulated by the complex.

Adenosine Triphosphatases↗
PubMed2000

EMB-30: an APC4 homologue required for metaphase-to-anaphase transitions during meiosis and mitosis in Caenorhabditis elegans.

Here we show that emb-30 is required for metaphase-to-anaphase transitions during meiosis and mitosis in Caenorhabditis elegans. Germline-specific emb-30 mutant alleles block the meiotic divisions. Mutant oocytes, fertilized by wild-type sperm, set up a meiotic spindle but do not progress to anaphase I. As a result, polar bodies are not produced, pronuclei fail to form, and cytokinesis does not occur. Severe-reduction-of-function emb-30 alleles (class I alleles) result in zygotic sterility and lead to germline and somatic defects that are consistent with an essential role in promoting the metaphase-to-anaphase transition during mitosis. Analysis of the vulval cell lineages in these emb-30(class I) mutant animals suggests that mitosis is lengthened and eventually arrested when maternally contributed emb-30 becomes limiting. By further reducing maternal emb-30 function contributed to class I mutant animals, we show that emb-30 is required for the metaphase-to-anaphase transition in many, if not all, cells. Metaphase arrest in emb-30 mutants is not due to activation of the spindle assembly checkpoint but rather reflects an essential emb-30 requirement for M-phase progression. A reduction in emb-30 activity can suppress the lethality and sterility caused by a null mutation in mdf-1, a component of the spindle assembly checkpoint machinery. This result suggests that delaying anaphase onset can bypass the spindle checkpoint requirement for normal development. Positional cloning established that emb-30 encodes the likely C. elegans orthologue of APC4/Lid1, a component of the anaphase-promoting complex/cyclosome, required for the metaphase-to-anaphase transition. Thus, the anaphase-promoting complex/cyclosome is likely to be required for all metaphase-to-anaphase transitions in a multicellular organism.

Alleles↗
PubMed1999

Cloning and characterization of arylamine N-acetyltransferase genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: increased expression results in isoniazid resistance.

Arylamine N-acetyltransferases (NATs) are found in many eukaryotic organisms, including humans, and have previously been identified in the prokaryote Salmonella typhimurium. NATs from many sources acetylate the antitubercular drug isoniazid and so inactivate it. nat genes were cloned from Mycobacterium smegmatis and Mycobacterium tuberculosis, and expressed in Escherichia coli and M. smegmatis. The induced M. smegmatis NAT catalyzes the acetylation of isoniazid. A monospecific antiserum raised against pure NAT from S. typhimurium recognizes NAT from M. smegmatis and cross-reacts with recombinant NAT from M. tuberculosis. Overexpression of mycobacterial nat genes in E. coli results in predominantly insoluble recombinant protein; however, with M. smegmatis as the host using the vector pACE-1, NAT proteins from M. tuberculosis and M. smegmatis are soluble. M. smegmatis transformants induced to express the M. tuberculosis nat gene in culture demonstrated a threefold higher resistance to isoniazid. We propose that NAT in mycobacteria could have a role in acetylating, and hence inactivating, isoniazid.

Amino Acid Sequence↗
PubMed1998

Caenorhabditis elegans lin-25: cellular focus, protein expression and requirement for sur-2 during induction of vulval fates.

Induction of vulval fates in the C. elegans hermaphrodite is mediated by a signal transduction pathway involving Ras and MAP kinase. Previous genetic analysis has suggested that two potential targets of this pathway in the vulva precursor cells are two novel proteins, LIN-25 and SUR-2. In this report, we describe further studies of lin-25. The results of a genetic mosaic analysis together with those of experiments in which lin-25 was expressed under the control of an heterologous promoter suggest that the major focus of lin-25 during vulva induction is the vulva precursor cells themselves. We have generated antisera to LIN-25 and used these to analyse the pattern of protein expression. LIN-25 is present in all six precursor cells prior to and during vulva induction but later becomes restricted to cells of the vulval lineages. Mutations in genes in the Ras/MAP kinase pathway do not affect the pattern of expression but the accumulation of LIN-25 is reduced in the absence of sur-2. Overexpression of LIN-25 does not rescue sur-2 mutant defects suggesting that LIN-25 and SUR-2 may function together. LIN-25 is also expressed in the lateral hypodermis. Overexpression of LIN-25 disrupts lateral hypodermal cell fusion, suggesting that lin-25 may play a role in regulating cell fusions in C. elegans.

Animals↗
PubMed1994

Quality control of extemporaneously prepared microdose captopril capsules: weight variation versus content uniformity.

Microdose (1 mg) captopril therapy is commonly used for the initial dose titration in patients with congestive heart failure. Since this dosage form is not commercially available, it has to be extemporaneously compounded. Quality control of each batch is commonly evaluated using the weight variation technique described in the USP. Despite careful titration with microdose, captopril capsules variability in patient's response has been observed. In order to explain this fluctuation, the actual content of extemporaneously compounded microdose captopril capsules was evaluated using a high pressure liquid chromatographic assay. Microdose captopril capsules were prepared by triturating 25 mg tablets with lactose in a mortar using standard geometric dilution technique and a Sharpe-Dohme hand-operated capsule filling machine. Forty-eight microdose captopril capsules were randomly selected from the compounded batch and were individually assayed for captopril amount. The mean +/- standard deviation (SD) amount of captopril in each capsule was 1.27 g +/- 0.31 mg with a range of 0.84 g to 1.96 mg. The coefficient of variation was 24.5%. Ten captopril capsules were randomly selected from the compounded batch and were individually weighed. The capsules had a mean weight +/- SD of 198.3 g +/- 21.2 mg and a coefficient of variation of 7.3%. Even though the extemporaneously prepared microdose captopril capsules were within acceptable limits for weight variation described in the USP, the actual dose administered to the patients could vary by as much as 24.5%.

Capsules↗
PubMed1989

The chemical stability of captopril capsules.

Captopril therapy is effective in the management of congestive heart failure. The development of hypotension, using low or standard doses, frequently precludes many patients from continuing therapy. The use of 1 mg "microdose" captopril capsules has been used for dose titration to avoid complications associated with hypotension. This study evaluated the chemical stability of 1 mg microdose captopril capsules, extemporaneously prepared from commercially available captopril tablets for a period of 60 days which were stored in an amber vial at standard room temperature conditions. Captopril samples were analyzed in triplicate using high pressure liquid chromatographic method on days 0, 30, and 60 following perparation. There was no degradation observed on any of the sampling days. Therefore, the formulation of 1 mg captopril capsules remain stable for a period of 60 days.

Capsules↗
PubMed1976

Antagonism of endogenous mineralocorticoids in normal subjects by prorenoate potassium and spironolactone.

The pharmacological activity of single oral doses of a new aldosterone antagonist, prorenoate potassium, has been compared with spironolactone and placebo in a balanced double-blind crossover study in six healthy subject. Endogenous mineralocorticoids were stimulated by administration of frusemide followed by dietary sodium restriction, and the urinary excretion of electrolytes in response to prorenoate potassium, spironolactone and placebo was measured over a 24 hour period. Significant activity of prorenoate potassium and spironolactone was observed between 2 - 24 hours after medication, with peak activity at 6 - 8 hours. The active drugs significantly increased sodium excretion and the sodium : potassium (Na/K) ratio, but changes in potassium excretion were not significant. The total urine Na/K response to prorenoate potassium 45 mg was significantly greater than to spironolactone 100 mg.

Adult↗
PubMed1976

Prolactin, diuretics and urinary electrolytes in normal subjects.

The relationship of plasma prolactin concentration and renal electrolyte excretion has been investigated in six normal male volunteers. In two studies, 80 mg frusemide were administered at 18.00 h on Day 1 and followed by dietary sodium restriction. In study A, after 38 h of sodium depletion, a second dose of frusemide was administered at 08.00 h on Day 3. In study B, after 14 h of sodium depletion, the effect of administration of 100 mg spironolactone or 45 mg prorenoate potassium (another aldosterone antagonist) at 08.00 h on Day 2 was compared with that of a placebo. After the first dose of frusemide in study A, the mean plasma prolactin concentration correlated negatively with the urinary Na and K excretion over 5 h. After 38 h sodium depletion, the plasma prolactin concentration correlated positively with urinary Na excretion following the second dose of frusemide. In study B, after Na depletion for 14 h the plasma prolactin concentration of 08.00 h on Day 2 had a positive correlation with the 24 h urinary log10 Na:K ratio following placebo administration and had negative correlations with the true urinary log10 Na:K ratio following spironolactone and prorenoate potassium administration. Neither acute Na deprivation nor the administration of single doses of frusemide, spironolactone or proprenoate potassium appeared to affect the normal circadian rhythm of plasma prolactin concentrations which remained constant for each subject throughout the 3 months covered by the investigation. The correlations of plasma prolactin concentration to renal excretion of electrolytes, with no evidence for a negative feedback control mechanism, suggest an indirect relationship between prolactin and renal function.

Adult↗