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T Powers

Publications and source records attributed to T Powers.

At least 19 recordsLinked to original sources
PubMed2004

Yeast TOR signaling: a mechanism for metabolic regulation.

Understanding how cell growth is regulated in response to environmental signals remains a challenging biological problem. Recent studies indicate the TOR (target of rapamycin) kinase acts within an intracellular regulatory network used by eukaryotic cells to regulate their growth according to nutrient availability. This network affects all aspects of gene expression, including transcription, translation, and protein stability, making TOR an excellent candidate as a global regulator of cellular activity. Here we review our recent studies of two specific transcriptional outputs controlled by TOR in the budding yeast, S. cerevisiae: (1) positive regulation of genes involved in ribosome biogenesis, and (2) negative regulation of genes required for de novo biosynthesis of glutamate and glutamine. These studies have raised the important issue as to how diverse nutritional cues can pass through a common signaling pathway and yet ultimately generate distinct transcriptional responses.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2000

Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors.

De novo biosynthesis of amino acids uses intermediates provided by the TCA cycle that must be replenished by anaplerotic reactions to maintain the respiratory competency of the cell. Genome-wide expression analyses in Saccharomyces cerevisiae reveal that many of the genes involved in these reactions are repressed in the presence of the preferred nitrogen sources glutamine or glutamate. Expression of these genes in media containing urea or ammonia as a sole nitrogen source requires the heterodimeric bZip transcription factors Rtg1 and Rtg3 and correlates with a redistribution of the Rtg1p/Rtg3 complex from a predominantly cytoplasmic to a predominantly nuclear location. Nuclear import of the complex requires the cytoplasmic protein Rtg2, a previously identified upstream regulator of Rtg1 and Rtg3, whereas export requires the importin-beta-family member Msn5. Remarkably, nuclear accumulation of Rtg1/Rtg3, as well as expression of their target genes, is induced by addition of rapamycin, a specific inhibitor of the target of rapamycin (TOR) kinases. We demonstrate further that Rtg3 is a phosphoprotein and that its phosphorylation state changes after rapamycin treatment. Taken together, these results demonstrate that target of rapamycin signaling regulates specific anaplerotic reactions by coupling nitrogen quality to the activity and subcellular localization of distinct transcription factors.

Amino Acids↗
PubMed2000

Effectiveness of palivizumab: evaluation of outcomes from the 1998 to 1999 respiratory syncytial virus season. The Palivizumab Outcomes Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) remains a significant cause of morbidity, especially in premature infants and immunocompromised children, resulting in approximately 100 000 hospitalizations annually. A study was performed to evaluate the outcomes of those given palivizumab (Synagis; MedImmune, Inc., Gaithersburg, MD) during the 1998 to 1999 RSV season, its first season in general use. METHODS: A retrospective chart review of 1839 patients from 9 United States sites was conducted, representing all patients given palivizumab at each site. Those evaluated were to have a gestational age of < or =35 weeks, were to be <2 years old at their first injection and were to have received at least one dose of palivizumab (humanized monoclonal antibody against RSV) between September, 1998, and May, 1999. Gestational age, comorbidities, frequency of injections, hospitalizations and length of hospital stays were assessed. RESULTS: The antigen- or culture-positive RSV hospitalization rates for those given prophylaxis were 2.3% (42 of 1839) overall, 16/399 (4.0%) with chronic lung disease of infancy and 26 of 1227 (2.1%) born prematurely without chronic lung disease of infancy. Twenty-six patients had a gestational age of >35 weeks and were included in the analysis. CONCLUSIONS: Only 2.3% of children receiving palivizumab prophylaxis were hospitalized with RSV lower respiratory infection. This compares favorably with the rates observed in the pivotal trial (IMpact-RSV trial in 1996 to 1997), in which prophylaxis reduced hospitalization from 10.6% in the placebo group to 4.8% in those children receiving prophylaxis.

Antibodies, Monoclonal↗
PubMed1999

Determinants of power-frequency magnetic fields in residences located away from overhead power lines.

The Wertheimer-Leeper wire code, originally developed as a surrogate for magnetic-field exposure, has been associated with childhood leukemia in several epidemiologic investigations. However, these and other studies indicate that most between-residence variability in measured magnetic fields remains unexplained by wire codes. To better understand this remaining variability, engineering and demographic data were examined for 333 underground (UG) and very-low current configuration (VLCC) single-family or duplex residences, selected from a database of nearly 1000 residences specifically because their magnetic fields are most likely affected negligibly by overhead power lines. Using linear regression techniques, four factors predictive of the log-transformed residential field were identified: the square-root of the 24-h average net service drop current (this current is equivalent to the current in the grounding system), the log of the number of service drops on the same secondary serving the residence, residence age (four categories), and area type (rural, suburban, or urban). Complete data on ground current and service drops, the two factors with the strongest individual relationships to measured fields, were available for only half of the residences in the sample. However, these data were determined to be "missing at random" according to established statistical criteria. The full-sample or "composite" models thus relied on a method similar to regression imputation, accounting for missing data with binary dummy variables. When applied to the samples from which they were derived, these models accounted for 25% of the variance of the log-spot-measured magnetic field values in the full sample, while models that considered only those residences with complete data (n = 167) explained about 35%. The model validated well against a sample of 201 ordinary low current configuration (OLCC) homes selected from the same database.

Child↗
PubMed1999

Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae.

The TOR (target of rapamycin) signal transduction pathway is an important mechanism by which cell growth is controlled in all eucaryotic cells. Specifically, TOR signaling adjusts the protein biosynthetic capacity of cells according to nutrient availability. In mammalian cells, one branch of this pathway controls general translational initiation, whereas a separate branch specifically regulates the translation of ribosomal protein (r-protein) mRNAs. In Saccharomyces cerevisiae, the TOR pathway similarly regulates general translational initiation, but its specific role in the synthesis of ribosomal components is not well understood. Here we demonstrate that in yeast control of ribosome biosynthesis by the TOR pathway is surprisingly complex. In addition to general effects on translational initiation, TOR exerts drastic control over r-protein gene transcription as well as the synthesis and subsequent processing of 35S precursor rRNA. We also find that TOR signaling is a prerequisite for the induction of r-protein gene transcription that occurs in response to improved nutrient conditions. This induction has been shown previously to involve both the Ras-adenylate cyclase as well as the fermentable growth medium-induced pathways, and our results therefore suggest that these three pathways may be intimately linked.

Adenylyl Cyclases↗
PubMed1999

Screening for cerebral aneurysm in patients with polycystic liver disease.

BACKGROUND: Polycystic liver disease (PCLD) is an autosomal dominant disease characterized by multiple macrocystic lesions throughout the liver. The association between PCLD and cerebral aneurysm is well documented, and approximately 20% of patients with PCLD have demonstrable cerebral aneurysms at autopsy. The prevalence reported from autopsy series, however, may not reflect the true prevalence in patients with PCLD. We undertook this study to evaluate the prevalence and diagnosis of cerebral aneurysms in screening cerebral studies in patients with PCLD. METHODS: Patients were identified by searching the hepatobiliary surgical service data base and hospital medical records. Hospital charts were reviewed to confirm presence of PCLD and to identify screening studies for cerebral aneurysms. RESULTS: Ten patients with PCLD received screening studies of the cerebral vasculature during a 10 1/2-year period. One patient was found to have an asymptomatic cerebral aneurysm. A 45-year-old woman with no other significant medical history was referred for evaluation of PCLD. Screening magnetic resonance angiography (MRA) revealed a 5 mm aneurysm extending anteriorly near the origin of the right ophthalmic artery, without evidence of rupture. Cerebral angiography confirmed these findings, and the aneurysm was clipped. CONCLUSIONS: Because cerebral aneurysms can be an important source of morbidity and mortality in PCLD, we recommend screening by MRA or by computed tomographic angiography (CTA) of the cerebral vasculature in all patients who have PCLD.

Adult↗
PubMed1999

Neisseria gonorrhoeae PilA is an FtsY homolog.

The pilA gene of Neisseria gonorrhoeae was initially identified in a screen for transcriptional regulators of pilE, the expression locus for pilin, the major structural component of gonococcal pili. The predicted protein sequence for PilA has significant homology to two GTPases of the mammalian signal recognition particle (SRP), SRP54 and SRalpha. Homologs of SRP54 and SRalpha were subsequently identified in bacteria (Ffh and FtsY, respectively) and appear to form an SRP-like apparatus in prokaryotes. Of the two proteins, PilA is the most similar to FtsY (47% identical and 67% similar at the amino acid level). Like FtsY, PilA is essential for viability and hydrolyzes GTP. The similarities between PilA and the bacterial FtsY led us to ask whether PilA might function as the gonococcal FtsY. In this work, we show that overproduction of PilA in Escherichia coli leads to an accumulation of pre-beta-lactamase, similar to previous observations with other bacterial SRP components. Low-level expression of pilA in an ftsY conditional mutant can complement the ftsY mutation and restore normal growth to this strain under nonpermissive conditions. In addition, purified PilA can replace FtsY in an in vitro translocation assay using purified E. coli SRP components. A PilA mutant that is severely affected in its GTPase activity cannot replace FtsY in vivo or in vitro. However, overexpression of the GTPase mutant leads to the accumulation of pre-beta-lactamase, suggesting that the mutant protein may interact with the SRP apparatus to affect protein maturation. Taken together, these results show that the gonococcal PilA is an FtsY homolog and that the GTPase activity is necessary for its function.

Bacterial Proteins↗
PubMed1999

"The home infusion patient": patient profiles for the home infusion therapy market.

The authors review the relevant literature regarding home health care patient profiles. An empirical analysis is provided from archival data for a home infusion company servicing patients in urban and rural areas. The results are provided as a 2 x 2 matrix for patients in urban and rural areas seeing either a specialist or primary care physicians. A series of moderated regressions indicate that type of treating physician, patient's gender, geographic residence and level of acuity are cogent in predicting the complexity of prescribed infusion therapies. Managerial implications are provided for the home care marketer in segmenting patient markets for infusion services.

Female↗
PubMed1997

Co-translational protein targeting catalyzed by the Escherichia coli signal recognition particle and its receptor.

The Ffh-4.5S ribonucleoprotein particle (RNP) and FtsY from Escherichia coli are homologous to essential components of the mammalian signal recognition particle (SRP) and SRP receptor, respectively. The ability of these E. coli components to function in a bona fide co-translational targeting pathway remains unclear. Here we demonstrate that the Ffh-4.5S RNP and FtsY can efficiently replace their mammalian counterparts in targeting nascent secretory proteins to microsomal membranes in vitro. Targeting in the heterologous system requires a hydrophobic signal sequence, utilizes GTP and, moreover, occurs co-translationally. Unlike mammalian SRP, however, the Ffh-4.5S RNP is unable to arrest translational elongation, which results in a narrow time window for the ribosome nascent chain to interact productively with the membrane-bound translocation machinery. The highly negatively charged N-terminal domain of FtsY, which is a conserved feature among prokaryotic SRP receptor homologs, is important for translocation and acts to localize the protein to the membrane. Our data illustrate the extreme functional conservation between prokaryotic and eukaryotic SRP and SRP receptors and suggest that the basic mechanism of co-translational protein targeting is conserved between bacteria and mammals.

Animals↗
PubMed1996

The nascent polypeptide-associated complex modulates interactions between the signal recognition particle and the ribosome.

BACKGROUND: The first step in the co-translational targeting of secretory proteins to the endoplasmic reticulum membrane involves the recognition of signal sequences by the 54 kDa subunit of the signal recognition particle (SRP) as they emerge from the ribosome. It has recently been proposed that the nascent polypeptide-associated complex (NAC) contributes to the fidelity of targeting by modulating interactions that occur between the ribosome-nascent chain complex, the SRP and the endoplasmic reticulum membrane. Precisely how NAC influences SRP function is presently unclear. RESULTS: We have used immunoblotting experiments to monitor interactions between the SRP and the ribosome-nascent chain complex, in the absence and presence of NAC. In the absence of NAC, SRP binds in a high-salt-resistant manner only to ribosomes that contain a signal sequence, confirming the specificity of SRP for signal sequences. Binding of SRP to signalless ribosome nascent chains is observed at lower salt concentrations; however, the amount of SRP bound to this complex is indistinguishable from that bound to ribosomes lacking nascent chains. Thus, this salt-sensitive binding is likely to be the result of interactions between SRP and the ribosome that occur independently of the nascent chain. A minimal particle consisting of SRP54 and SRP RNA is sufficient to confer salt-resistant binding to ribosomes that contain signal sequences, whereas all of the SRP subunits are required for salt-sensitive binding to ribosomes that lack nascent chains. This salt-sensitive binding by SRP is inhibited by the addition of purified NAC. CONCLUSIONS: Based on our results, we define two distinct modes of interaction between SRP and the ribosome-nascent chain complex: salt-resistant interactions between SRP54 and signal sequences, and salt-sensitive interactions between additional components of SRP and the ribosome. We conclude that NAC does not directly influence signal sequence recognition by SRP but, rather, that it negatively modulates interactions that occur between SRP and the ribosome itself. These results are discussed in terms of a model wherein SRP and NAC regulate each others' activity during protein targeting.

Peptides↗
PubMed1996

Subfoveal neovascular membrane removal in patients with traumatic choroidal rupture.

PURPOSE: To describe the clinical outcomes of patients undergoing pars plana vitrectomy to remove subretinal neovascular membranes caused by traumatic choroidal ruptures. METHODS: Three patients with traumatic choroidal rupture in whom subfoveal choroidal neovascularization developed underwent pars plana vitrectomy with surgical excision of the neovascular membrane. Surgical specimens were examined histopathologically in two patients. RESULTS: The choroidal neovascularization was removed completely in each patient. Visual results were excellent with visual acuities improving to 20/30 or better in each patient. Recurrence of choroidal neovascularization has not been observed. Fibrovascular membranes with reactive retinal pigment epithelium were observed in two specimens examined histopathologically. CONCLUSION: Surgical removal of subretinal neovascular membranes emanating from traumatic choroidal ruptures produced an excellent visual outcome in three patients studied. The neovascular membranes, which were removed with minor disturbance to the underlying pigment epithelium, have similar characteristics to those obtained from patients with ocular histoplasmosis syndrome.

Adult↗
PubMed1996

A model of time-effective group psychotherapy for patients with personality disorders: the clinical model.

This article describes a model of time-limited psychotherapy for patients with personality disorders that emphasizes the group as a social microcosm. The patient population described is relatively high functioning, although the majority of the group members meet DSM-III-R (American Psychiatric Association, 1987) criteria for an Axis II diagnosis. The clinical model's key theoretical concepts, for example, interpersonal focus; active therapist stance; emphasis on group interaction and processes; use of time limits; primary care/intermittent treatment philosophy; and emphasis on patients' strengths, goals, and resources are described. The relationships between the phases of group therapy and the key theoretical concepts are delineated.

Adult↗
PubMed1995

Reciprocal stimulation of GTP hydrolysis by two directly interacting GTPases.

The Escherichia coli guanosine triphosphate (GTP)-binding proteins Ffh and FtsY have been proposed to catalyze the cotranslational targeting of proteins to the bacterial plasma membrane. A mutation was introduced into the GTP-binding domain of FtsY that altered its nucleotide specificity from GTP to xanthosine triphosphate (XTP). The mutant FtsY protein stimulated GTP hydrolysis by a ribonucleoprotein consisting of Ffh and 4.5S RNA in a reaction that required XTP, and it hydrolyzed XTP in a reaction that required both the Ffh-4.5S ribonucleoprotein and GTP. Thus, nucleotide triphosphate hydrolysis by Ffh and FtsY is likely to occur in reciprocally coupled reactions in which the two interacting guanosine triphosphatases act as regulatory proteins for each other.

Amino Acid Sequence↗
PubMed1995

A temperature-dependent conformational rearrangement in the ribosomal protein S4.16 S rRNA complex.

Ribosomal protein S4 protects a characteristic set of bases in 16 S rRNA from attack by chemical probes. Use of hydroxyl radical as a probe of the RNA backbone shows that ribose residues in these same regions are also protected by S4, confirming the localization of its interactions with 16 S rRNA to the junction of five helical elements in the proximal region of the 5' domain. At 0 degrees C, the nucleotides protected by S4 from base-specific probes are confined almost exclusively to the two compound helices formed by residues 404-499. After subsequent heating of the complex briefly at 30 or 42 degrees C, nucleotides in the three adjacent helices are additionally protected, resulting in a pattern of protection that is identical to that which is observed when S4 is incubated with 16 S rRNA under in vitro reconstitution conditions. Preincubation of the protein or the RNA (or both) separately at elevated temperature does not substitute for heating the S4.RNA complex. The regions in the RNA affected by the heat step are known to interact with proteins S12 and S16, both of which depend upon S4 for their binding to the RNA. Thus, the finding that S4 recruits additional sites of interaction in the RNA following its initial binding suggests a possible mechanism to insure the sequential addition of proteins during ribosomal assembly.

Cold Temperature↗