SEARCH · PubMed Health

Results for “TPR”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed2004

Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with congenital heart defects and pulmonary arterial hypertension.

BACKGROUND: It was previously demonstrated that in adults with congenital heart disease and pulmonary arterial hypertension and/or the Eisenmenger syndrome, the pulmonary circulation remained responsive to inhaled nitric oxide (iNO). We wanted to evaluate whether the responsiveness to iNO was related to mid-term outcome in these patients. METHODS: In 21 consecutive patients, total pulmonary vascular resistance (TPR) was measured at baseline, after 5 min iNO (80 ppm), and after NO withdrawal. Patients were considered responders when TPR was reduced by at least 20% during NO inhalation or when TPR increased by more than 10% after NO withdrawal. Responders and non-responders were followed prospectively and the primary endpoint of the study was cardiopulmonary death, the secondary endpoint the combination of death, need for treatment with prostacyclin or heart-lung transplantation. Kaplan-Meier survival curves for both groups were plotted and compared using log rank testing. RESULTS: Ten patients were considered responders (four male, median age 25 years, Q1 19 and Q3 66 years), while 11 patients did not respond (two male, median age 27 years, Q1 18 and Q3 40 years). The median follow-up time of the total group was 5.0 years (Q1 3.2 and Q3 5.7 years). Four of the non-responders died a cardiovascular death; none of the responders died. The difference in survival between responders and non-responders was statistically significant. For the secondary endpoint, no significant differences were found between both groups. CONCLUSIONS: The responsiveness to inhaled NO in adult patients with pulmonary arterial hypertension and/or the Eisenmenger syndrome is related to mid-term outcome. These findings might be important for risk stratification and the choice of treatment in this specific patient population.

Administration, Inhalation↗

PubMed2006

The chaperone function of cyclophilin 40 maps to a cleft between the prolyl isomerase and tetratricopeptide repeat domains.

Cyclophilin 40 (CyP40), an immunophilin cochaperone present in steroid receptor-Hsp90 complexes, contains an N-terminal peptidylprolyl isomerase (PPIase) domain separated from a C-terminal Hsp90-binding tetratricopeptide repeat (TPR) domain by a 30-residue linker. To map CyP40 chaperone function, CyP40 deletion mutants were prepared and analysed for chaperone activity. CyP40 fragments containing the PPIase domain plus linker or the linker region and the adjoining TPR domain retained chaperone activity, whilst individually, the catalytic and TPR domains were devoid of chaperoning ability. CyP40 chaperone function then, is localized within the linker that forms a binding cleft with potential to accommodate non-native substrates.

Amino Acid Sequence↗

PubMed2004

Power consumption measurement and temperature recording during granulation.

This study was performed to elucidate the influences of process and formulation design using power consumption and temperature measurements during granulation. Power consumption was recorded "in process" using a previously introduced computer program for optimal end-point detection at an early stage. The temperature increase (DeltaT) during granulation was recorded using a temperature sensor. The temperature increase in the wet powder bed expresses the friction forces at interparticle contacts occurring during granulation. The maxima of temperature profile occurred at 130% saturation, whereas the maxima of power consumption were determined at 100% saturation. The ratio of temperature and power consumption (TPR factor) is introduced as a signature of formulation design. TPR factor was found to be dependent on particle size, particle surface, water absorption capacity and solubility of the excipient and model drug, respectively. However, TPR factor was found to be independent of process design, such as the filling level of the mixer. Understanding and controlling the granulation process is a key factor in robust dosage form design. The "in process" control fits ideally the prerequisites of a drug quality system for the 21st century and FDA's Process Analytical Technology (PAT) initiative. The results of previous and present works of our research group will be used in a following step to develop an artificial neural network for granulation "in process" control.

Dosage Forms↗

PubMed2004

Hostility differentially predicts cardiovascular risk factors in African American and White young adults.

OBJECTIVE: Hostility may influence racial disparities in cardiovascular disease through differential associations with cardiovascular risk factors. This study explored racial variations in relations between hostility and selected cardiovascular risk factors. METHODS: Cook-Medley Hostility (Ho) scores and 11 risk factors were examined among 66 healthy, White and African American young adults. RESULTS: Controlling for age, gender, and body mass index, the interaction of hostility and race yielded significant (or marginal) associations with resting systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI; i.e. cardiac output adjusted for body size), total peripheral resistance (TPR), insulin (INS), triglycerides (TG) and percent body fat (PBF). Contributing substantial variance, hostility was positively associated with SBP, DBP, TPR, TG and INS, and negatively associated with CI among African Americans. Conversely, hostility was negatively associated with TPR and PBF among Whites. CONCLUSION: Hostility may confer greater cardiovascular risk among young African Americans than Whites.

Adult↗

PubMed1998

Nonprescription chlorpheniramine maleate and submaximal exercise responses.

OBJECTIVE: To determine if a single, over-the-counter dose of the H1 antagonist chlorpheniramine maleate (CM) alters total peripheral resistance (TPR) and oxygen uptake (VO2) during submaximal exercise. DESIGN: The study was a prospective, longitudinal, double-blind, random crossover analysis of the cardiovascular and respiratory responses to a single bout of moderately intense exercise. SETTING: Exercise tests were conducted in an exercise laboratory equipped with expired gas analysis and bioelectrical impedance cardiographic monitoring capabilities. PARTICIPANTS: Subjects were 18 (9 men, 9 women) volunteers (age=29.5+/-3.6yrs; weight=70.7+/-1.1kg), free from exercise-limiting pathology and rhinitis. INTERVENTION: Each subject completed a maximal exercise tolerance test on the cycle ergometer followed by two randomly ordered submaximal exercise tests at a power output of 50% of the peak power attained on the maximal test: the first, 2 hours after ingesting 4mg of CM, the second, 2 hours after ingesting a placebo. The submaximal exercise tests lasted 20min and data were recorded at 5, 10, 15, and 20min of exercise during both the CM and placebo tests. Tests were completed approximately 48 hours apart. RESULTS: Average VO2 was 1,488+/-367mL/min for the CM test and 1,477+/-351mL/min for the placebo test. TPR was 12.3+/-7.4PRU for the CM and 11.3+/-4.5PRU for the placebo tests. Analysis of variance revealed that these scores were statistically similar. CONCLUSION: A single over-the-counter dose of CM does not alter TPR or VO2 during submaximal exercise.

Adult↗

PubMed1998

Estimating the accuracy of screening mammography: a meta-analysis.

OBJECTIVE: To estimate the accuracy of mammographic screening. DESIGN: A meta-analysis of published literature. DATA SOURCES: Published English-language randomized controlled trials, case-control studies, and demonstration projects involving screening mammography were identified using recent review articles. We found additional references using MEDLINE searches combining the MeSH terms "mammography," "screening," and/or study authors and locations. STUDY SELECTION: We included all studies that provided information to calculate the true-positive rate (TPR) and the false-positive rate (FPR) for breast cancer screening. DATA EXTRACTION: Reported data were reviewed independently by the authors; calculations were compared and discrepancies resolved. We calculated the sensitivity as the number of breast cancers detected during the first round of screening (true positives) divided by the sum of the true positives and the false negatives (defined as cancer discovered within 1 year of screening). False-positives were determined by biopsy. DATA SYNTHESIS: TPR and FPR values from each study were plotted in receiver operating characteristic (ROC) space. Tests of homogeneity were performed to assess the validity of using summary ROC curves or a single point to summarize the data. The reported TPR and FPR of mammography ranged from 83% to 95% and 0.9% to 6.5%, respectively. The sensitivity of mammography is higher in women over the age of 50 years. CONCLUSIONS: The accuracy of mammography should be recognized and included in discussions about policies for screening for breast cancer. This meta-analysis, by quantifying the expected TPR/FPR, should assist program planners, physicians, and women to understand better the cost and clinical implications of such screening programs.

Adult↗

PubMed1996

Prealbumin in nutrition evaluation.

We compressed 16 test-pattern classes of albumin (ALB), cholesterol (CHOL), and total protein (TPR) in 545 chemistry profiles to 4 classes by converting decision values to a number code to separate malnourished (1 or 2) from nonmalnourished (NM) (0) patients, using as cutoff values for nonmalnourished (0), mild (1), and moderate (2): ALB 35, 27 g/L; TPR 63, 53 g/L; CHOL 3.9, 2.8 mmol/L; and BUN 9.3, 3.6 mmol/L. The BUN was found to have too low an S-value to make a contribution to the compressed classification. The cutoff values for classifying the data were assigned prior to statistical analysis, after examining information in the structured data. The data was obtained by a natural experiment in which the test profiles routinely done by the laboratory were randomly extracted. The analysis identifies the values for the variables used that best classify the data and are not dependent on distributional assumptions. The data were converted to 0, 1, or 2 as outcomes, to create a ternary truth table (each row is nnnn, the n value is 0 to 2). This allows for 3(4) (81) possible patterns, without the inclusion of prealbumin (PAB). The emerging system has much fewer patterns in the information-rich truth table formed (a purposeful, far from random, event). We added PAB, coded, and examined the data for 129 patients. The classes are a compressed truth table of n-coded patients with outcomes of 0, 1, or 2 with protein-energy malnutrition (PEM) increasing from an all-0 to all-2 pattern. Pattern class (F = 154), PAB (F = 35), ALB (F = 56), and CHOL (F = 18) were different across PEM class and predicted PEM class (R2 = 0.7864, F = 119, p < E-5). Kruskal-Wallis analysis of class by ranks was significant for pattern class (1E-18), PAB (6.1E-15), ALB (1E-16), CHOL (9E-10), and TPR (5.3E-13). The medians and standard error (SEM) for PAB, ALB, and CHOL of all four PABCLASSES (NM, mild, moderate, severe) are: PAB = 209, 8.7; 159, 9.3; 137, 10.4; 72, 11.1 mg/L, ALB = 36, 0.7; 30.5, 0.8; 25.0, 0.8; 24.5, 0.8 g/L; CHOL = 4.43, 0.17; 4.04, 0.20; 3.11, 0.21; 2.54, 0.22 mmol/L. PAB and CHOL values show the effect of nutrition support on PAB and CHOL in PEM. Moderately malnourished patients receiving nutrition support have PAB values in the normal range at 137 mg/L and at 159 mg/L when the ALB is at 25 g/L or at 30.5 g/L.

Biomarkers↗

PubMed1997

The influence of established and new antiepileptic drugs on visual perception. II. A controlled study in patients with epilepsy under long-term antiepileptic medication.

In this study, we investigated visual performance under chronic antiepileptic drug treatment. Patients were under carbamazepine (CBZ) (n = 18), valproic acid (VPA) (n = 9), CBZ and vigabatrin (VGB) (n = 4), CBZ and gabapentin (GBP) (n = 8), and under CBZ and topiramate (TPR) (n = 6), respectively. Seven untreated patients with epilepsy and 42 healthy volunteers served as controls. The test battery comprised the Lanthony-D15-désaturé colour perception test, increment, postadaptation and transient tritanopia (TT) threshold measurements, visual perception threshold assessments for monochromatic and chromatic gratings and gaussian dots, and critical flicker fusion (CFF) tests. No differences were seen between naive patients and healthy controls. Patients under drug treatment always showed alterations of visual perception. Postadaptation and TT thresholds were altered under each drug regimen after short delays between switching off the adaptation light and switching on the blue test light. Threshold elevations were maximum under the combination of CBZ and TPR and lowest under CBZ and GBP. Consistent impairment of the CFF was seen under combined CBZ and TPR whereas VPA as well as combined CBZ and VGB led to ameliorations the mechanisms of which are discussed. The other tests were less sensitive. In conclusion, alterations of visual function were apparent under chronic antiepileptic drug treatment both with established and new agents. However, it may be difficult to distinguish between effects based on specific modes of action and nonspecific retino- and neurotoxicity.

Adaptation, Ocular↗

PubMed2002

Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity.

The Galpha subunits of the G(12) family of heterotrimeric G proteins, defined by Galpha(12) and Galpha(13), are involved in many signaling pathways and diverse cellular functions. In an attempt to elucidate downstream effectors of Galpha(12) for cellular functions, we have performed a yeast two-hybrid screening of a rat brain cDNA library and revealed that Ser/Thr protein phosphatase type 5 (PP5) is a novel effector of Galpha(12) and Galpha(13). PP5 is a newly identified phosphatase and consists of a C-terminal catalytic domain and an N-terminal regulatory tetratricopeptide repeat (TPR) domain [2]. Arachidonic acid was recently shown to activate PP5 phosphatase activity by binding to its TPR domain, however the precise regulatory mechanism of PP5 phosphatase activity is not fully determined. In this study, we show that active forms of Galpha(12) and Galpha(13) specifically interact with PP5 through its TPR domain and activate its phosphatase activity about 2.5-fold. Active forms of Galpha(12) and Galpha(13) also enhance the arachidonic acid-stimulated PP5 phosphatase activity about 2.5-fold. Moreover, we demonstrate that the active form of Galpha(12) translocates PP5 to the cell periphery and colocalizes with PP5. These results propose a new signaling pathway of G(12) family G proteins.

Animals↗

PubMed2001

Nonlinear parameters estimation from sequential short time data series.

Procedures of nonlinear parameter estimation require large samples of data. In stationary physiological situations, usually short time series are available. The method of dynamics-dependent windowing and data aggregation procedure are proposed. This technique was tested on chaotic signal generated by Lorenz model and applied to investigate beat-to-beat control of the cardiovascular system in 10 healthy volunteers. Nonivasively recorded blood pressure, respiratory activity and blood oxygen saturation were digitized and saved for further off-line analysis. The experimental procedure consisted of 10 min control--C, 20 voluntary apneas 1 min each-A, interapnea 20 periods of 1 min spontaneous breathing--B, and 10 min free-breathing recovery--R. Respiration signal served as a reference for apnea and interapnea free-breathing identification period. Correlation dimension-CD, according to Grassberger and Procaccia, and recurrence plot strategy, according to Webber and Zbilut, were applied to check dynamical properties of the signals. Results of numerical experiment on Lorenz model, original and transformed by segmentation and aggregation, support our assumption of similarity of their dynamics. Error in CD and recurrence parameters estimation strongly depended on segment length and was about 5% for 600 to 1,200 data points. However, even for segments of 75 to 100 samples, it did not exceed 10% for all, but one, periodic testing signal. Segmentation and aggregation applied to interbeat interval (IBI) and total peripheral resistance (TPR) data showed that CD and recurrence variables estimated separately for apneic and interapneic period and those calculated for mixed (apneic and interapneic) intervals were different. Average CD and recurrence parameters of IBI and TPR for 10 subjects during apnea and interapnea intervals were significantly different than during control and recovery. The lowest CD (mean +/- S.D.) of 6.38 +/- 0.4, 5.62 +/- 0.2 and %recurrence 10.35 +/- 0.8, 6.62 +/- 0.6 (highest ratio 4.95 +/- 0.2, 5.13 +/- 0.3) were observed in apnea for IBI and TPR, respectively. Low values of the estimates computed for mixed periods may suggest the influence of slowly varying, quasiperiodic driving force due to experimental procedure regime. Signal dynamics-dependent windowing and data aggregation regardless of the sequence of data could be a practical solution for nonlinear analysis of very short repeatable time series.

Adult↗

PubMed2001

Epinephrine, vasodilation and hemoconcentration in syncopal, healthy men and women.

Healthy young people may become syncopal during standing, head up tilt (HUT) or lower body negative pressure (LBNP). To evaluate why this happens we measured hormonal indices of autonomic activity along with arterial pressure (AP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and measures of plasma volume. Three groups of normal volunteers (n = 56) were studied supine, before and during increasing levels of orthostatic stress: slow onset, low level, lower body negative pressure (LBNP) (Group 1), 70 degrees head up tilt (HUT) (Group 2) or rapid onset, high level, LBNP (Group 3). In all groups, syncopal subjects demonstrated a decline in TPR that paralleled the decline in AP over the last 40 s of orthostatic stress. Ten to twenty seconds after the decline in TPR. HR also started to decline but SV increased, resulting in a net increase of CO during the same period. Plasma volume (PV, calculated from change in hematocrit) declined in both syncopal and nonsyncopal subjects to a level commensurate with the stress, i.e. Group 3 > Group 2 > Group 1. The rate of decline of PV, calculated from the change in PV divided by the time of stress, was greater (p < 0.01) in syncopal than in nonsyncopal subjects. When changes in vasoactive hormones were normalized by time of stress, increases in norepinephrine (p < 0.012, Groups 2 and 3) and epinephrine (p < 0.025, Group 2) were greater and increases in plasma renin activity were smaller (p < 0.05, Group 2) in syncopal than in nonsyncopal subjects. We conclude that the presyncopal decline in blood pressure in otherwise healthy young people resulted from declining peripheral resistance associated with plateauing norepinephrine and plasma renin activity, rising epinephrine and rising blood viscosity. The increased hemoconcentration probably reflects increased rate of venous pooling rather than rate of plasma filtration and, together with cardiovascular effects of imbalances in norepinephrine, epinephrine and plasma renin activity may provide afferent information leading to syncope.

Adult↗

PubMed1998

Two mutant forms of the S1/TPR-containing protein Rrp5p affect the 18S rRNA synthesis in Saccharomyces cerevisiae.

The genetic depletion of yeast Rrp5p results in a synthesis defect of both 18S and 5.8S ribosomal RNAs (Venema J, Tollervey D. 1996. EMBO J 15:5701-5714). We have isolated the RRP5gene in a genetic approach aimed to select for yeast factors interfering with protein import into mitochondria. We describe here a striking feature of Rrp5p amino acid sequence, namely the presence of twelve putative S1 RNA-binding motifs and seven tetratricopeptide repeats (TPR) motifs. We have constructed two conditional temperature-sensitive alleles of RRP5 gene and analyzed them for associated rRNA-processing defects. First, a functional "bipartite gene" was generated revealing that the S1 and TPR parts of the protein can act independently of each other. We also generated a two amino acid deletion in TPR unit 1 (rrp5delta6 allele). The two mutant forms of Rrp5p were shown to cause a defect in 18S rRNA synthesis with no detectable effects on 5.8S rRNA production. However, the rRNA processing pathway was differently affected in each case. Interestingly, the ROK1 gene which, like RRP5, was previously isolated in a screen for synthetic lethal mutations with snR10 deletion, was here identified as a high copy suppressor of the rrp5delta6 temperature-sensitive allele. ROK1 also acts as a low copy suppressor but cannot bypass the cellular requirement for RRP5. Furthermore, we show that suppression by the Rok1p putative RNA helicase rescues the 18S rRNA synthesis defect caused by the rrp5delta6 mutation.

Alleles↗

PubMed1999

Yeast ortholog of the Drosophila crooked neck protein promotes spliceosome assembly through stable U4/U6.U5 snRNP addition.

Mutants in the Drosophila crooked neck (crn) gene show an embryonic lethal phenotype with severe developmental defects. The unusual crn protein consists of sixteen tandem repeats of the 34 amino acid tetratricopeptide (TPR) protein recognition domain. Crn-like TPR elements are found in several RNA processing proteins, although it is unknown how the TPR repeats or the crn protein contribute to Drosophila development. We have isolated a Saccharomyces cerevisiae gene, CLF1, that encodes a crooked neck-like factor. CLF1 is an essential gene but the lethal phenotype of a clf1::HIS3 chromosomal null mutant can be rescued by plasmid-based expression of CLF1 or the Drosophila crn open reading frame. Clf1p is required in vivo and in vitro for pre-mRNA 5' splice site cleavage. Extracts depleted of Clf1p arrest spliceosome assembly after U2 snRNP addition but prior to productive U4/U6.U5 association. Yeast two-hybrid analyses and in vitro binding studies show that Clf1p interacts specifically and differentially with the U1 snRNP-Prp40p protein and the yeast U2AF65 homolog, Mud2p. Intriguingly, Prp40p and Mud2p also bind the phylogenetically conserved branchpoint binding protein (BBP/SF1). Our results indicate that Clf1p acts as a scaffolding protein in spliceosome assembly and suggest that Clf1p may support the cross-intron bridge during the prespliceosome-to-spliceosome transition.

Amino Acid Sequence↗

PubMed2003

Heat shock protein-90 (Hsp90) acts as a repressor of peroxisome proliferator-activated receptor-alpha (PPARalpha) and PPARbeta activity.

The nuclear receptor (NR) peroxisome proliferator-activated receptor-alpha (PPARalpha) mediates the effects of several hypolipidemic drugs, endogenous fatty acids, and peroxisome proliferators. Despite belonging to a class of NR not known to interact with cytosolic chaperone complexes, we have recently shown that PPARalpha interacts with heat shock protein 90 (Hsp90), although the biological consequence of this association was unknown. In the present study, PPARalpha directly associated with Hsp90 in vitro to a much greater extent than either PPARbeta or PPARgamma. This interaction is similar to other NR-Hsp90 complexes with association occurring between the middle of Hsp90 and the hinge (D) and ligand binding domain (EF) of PPARalpha. Using several different approaches to disrupt Hsp90 complexes within the cell, we demonstrate that Hsp90 is a repressor of both PPARalpha and PPARbeta activity. Treatment with geldanamycin (GA) increased the activity of PPARalpha and in the presence of ligand in transient transfection assays. PPARalpha-response element (PPRE)-reporter assays in a stable cell line treated with GA resulted in enhanced expression of a known target gene, acyl-CoA oxidase. Similarly, overexpression of the tetratricopeptide repeat (TPR) of protein phosphatase 5 (PP5) increased PPARalpha or PPARbeta activity in a PPRE-reporter assay and decreased the interaction between PPARalpha or PPARbeta and Hsp90 in a mammalian two-hybrid assay. Finally, cotransfection with the C-terminal hsp-interacting protein (CHIP) construct, a TPR-containing ubiquitin ligase that interacts with hsp90, increased PPARalpha's and decreased PPARbeta's ability to regulate PPRE-reporter activity upon ligand activation. All three methods to disrupt Hsp90 function (GA, PP5-TPR, CHIP) resulted in an alteration in PPARalpha or PPARbeta activity to a much greater extent than PPARgamma. While FKBP52 had no effect on PPARalpha activity, p23 greatly enhanced constitutive and Wy14 643 induced PPRE-reporter activity. Thus, we describe the chaperone complex as being a regulator of PPARalpha and PPARbeta activity and have identified a novel, subtype-specific, inhibitory role for Hsp90.

Acyl-CoA Oxidase↗

PubMed2005

Oligomerization-induced differential dephosphorylation of c-Met receptor tyrosine kinase.

Although protein tyrosine phosphatases (PTPs) are significant negative regulators of receptor tyrosine kinase (RTK)-initiated cell signaling, it is unknown how RTK oligomerization modulates the equilibrium established between kinase and phosphatase activity. To determine the impact of oligomerization on the ability of c-MET RTK to undergo dephosphorylation, we examined the relative dephosphorylation kinetics of similarly phosphorylated dimeric TPR-MET and monomeric cytoMET. Notably, we observed that the dephosphorylation kinetics of phosphorylated MET were significantly modulated by its oligomeric state, with the global dephosphorylation rate of TPR-MET severalfold slower than the dephosphorylation rate of monomeric cytoMET. Furthermore, there were important site-specific differences in the dephosphorylation patterns of cytoMET and TPR-MET. Reduced dephosphorylation activity was predicted to eliminate or reduce the requirement of ligand-dependent oligomerization for MET autophosphorylation. This was demonstrated by the rapid phosphorylation of unstimulated c-MET on its activation loop and carboxy-terminal tyrosines following pervanadate treatment of cells expressing c-MET. We conclude that the MET oligomerization state is a critical regulator of its dephosphorylation rate. Thus, oligomerization plays a role in modifying the receptor's kinase and dephosphorylation rates to change the equilibrium levels of phosphorylated and dephosphorylated receptor in response to ligand stimulation, and that this may be a general mechanism utilized by many oligomeric receptor tyrosine kinases for regulation of their activity.

Animals↗

PubMed1996

Binding of immunophilins to the 90 kDa heat shock protein (hsp90) via a tetratricopeptide repeat domain is a conserved protein interaction in plants.

In animal cell lysates, multiprotein complexes containing hsp90, hsp70, p60, p23, and several immunophilins can assemble steroid receptors and oncogenic protein kinases, such as v-Src and v-Raf, into heterocomplexes that contain hsp90 and either immunophilins or, in the case of protein kinases, p50. The complexes with hsp90 are required for the proper functioning of these signal transduction systems. Wheat germ lysate contains a similar protein folding activity that forms functional steroid receptor complexes with hsp90, but not all the components of this system have been identified. The plant chaperone system has conserved interactions with animal chaperones in that wheat hsp70 functions in the rabbit reticulocyte lysate heterocomplex assembly system and human p23 functions in the wheat germ lysate. Here, we ask if wheat germ lysate also contains immunophilins of the FK506-binding class (FKBPs) that bind to the hsp90 component of the chaperone complex via tetratricopeptide repeat (TPR) domains. To demonstrate the plant heterocomplex, we add purified mammalian p23, preadsorbed with the JJ3 antibody to protein A-Sepharose, to wheat germ lysate and allow ATP-dependent formation of an animal p23. plant hsp90 complex. The complex is then washed and incubated with the radiolabeled immunosuppressant drug [3H]FK506, which binds in a specific manner to a coimmunoadsorbed plant FKBP. Binding of the plant FKBP to plant hsp90 is prevented by adding to wheat germ lysate a purified fragment containing the TPR domains of human cyclophilin-40. Geldanamycin, a benzoquinone ansamycin that binds to animal hsp90s and prevents their chaperone activity, binds in a temperature-dependent manner to wheat hsp90 to block formation of the p23.hsp90.FKBP heterocomplex. These data show that immunophilin binding to hsp90 via TPR domains is conserved in the plant kingdom as well as in the animal kingdom and that geldanamycin will be an important tool for the study of hsp90-mediated protein chaperoning in plant cells.

Adenosine Triphosphate↗

PubMed2005

Synthesis and characterization of highly ordered Ni-MCM-41 mesoporous molecular sieves.

Highly ordered Ni-MCM-41 samples with nearly atomically dispersed nickel ions were prepared reproducibly and characterized. Similar to the Co-MCM-41 samples, the pore diameter and porosity can be precisely controlled by changing the synthesis surfactant chain length. Nickel was incorporated by isomorphous substitution of silicon in the MCM-41 silica framework, which makes the Ni-MCM-41 a physically stable catalyst in harsh reaction conditions such as CO disproportionation to single wall carbon nanotubes or CO2 methanation. X-ray absorption spectroscopy results indicate that the overall local environment of nickel in Ni-MCM-41 was a tetrahedral or distorted tetrahedral coordination with surrounding oxygen anions. Hydrogen TPR revealed that our Ni-MCM-41 samples have high stability against reduction; however, compared to Co-MCM-41, the Ni-MCM-41 has a lower reduction temperature, and both the H2-TPR and in situ XANES TPR reveal that the reducibility of nickel is not clearly correlated with the pore radius of curvature, as in the case of Co-MCM-41. This is probably a result of nickel being thermodynamically more easily reduced than cobalt. The stability of the structural order of Ni-MCM-41 has been investigated under SWNT synthesis and CO2 methanation reaction conditions as both require catalyst exposure to reducing environments leading to formation of metallic Ni clusters. Nitrogen physisorption and XRD results show that structural order was maintained under both SWNT synthesis and CO2 methanation reaction conditions. EXAFS results demonstrate that the nickel particle size can be controlled by different prereduction temperatures but not by the pore radius of curvature as in the case of Co-MCM-41.

Journal Article↗

PubMed2006

Controlled synthesis, characterization, and catalytic properties of Mn(2)O(3) and Mn(3)O(4) nanoparticles supported on mesoporous silica SBA-15.

A method established in the present study has proven to be effective in the synthesis of Mn(2)O(3) nanocrystals by the thermolysis of manganese(III) acetyl acetonate ([CH(3)COCH=C(O)CH(3)](3)-Mn) and Mn(3)O(4) nanocrystals by the thermolysis of manganese(II) acetyl acetonate ([CH(3)COCH=C(O)-CH(3)](2)Mn) on a mesoporous silica, SBA-15. In particular, Mn(2)O(3) nanocrystals are the first to be reported to be synthesized on SBA-15. The structure, texture, and electronic properties of nanocomposites were studied using various characterization techniques such as N2 physisorption, X-ray diffraction (XRD), laser Raman spectroscopy (LRS), temperature-programmed reduction (TPR), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The results of powder XRD at low angles show that the framework of SBA-15 remains unaffected after generation of the manganese oxide (MnO(x)) nanoparticles, whereas the pore volume and the surface area of SBA-15 dramatically decreased as indicated by N2 adsorption-desorption. TEM images reveal that the pores of SBA-15 are progressively blocked with MnO(x) nanoparticles. The formation of the hausmannite Mn(3)O(4) and bixbyite Mn(2)O(3) structures was clearly confirmed by XRD. The surface structures of MnO(x) were also determined by LRS, XPS, and TPR. The crystalline phases of MnO(x) were identified by LRS with corresponding out-of-plane bending and symmetric stretching vibrations of bridging oxygen species (M-O-M) of both MnO(x) nanoparticles and bulk MnO(x). We also observed the terminal Mn=O bonds corresponding to vibrations at 940 and 974 cm-1 for Mn(3)O(4)/SBA-15 and Mn(2)O(3)/SBA-15, respectively. These results show that the MnO(x) species to be highly dispersed inside the channels of SBA-15. The nanostructure of the particles was further identified by the TPR profiles. Furthermore, the chemical states of the surface manganese (Mn) determined by XPS agreed well with the findings of LRS and XRD. These results suggest that the method developed in the present study resulted in the production of MnO(x) nanoparticles on mesoporous silica SBA-15 by controlling the crystalline phases precisely. The thus-prepared nanocomposites of MnO(x) showed significant catalytic activity toward CO oxidation below 523 K. In particular, the MnO(x) prepared from manganese acetyl acetonate showed a higher catalytic reactivity than that prepared from Mn(NO(3))2.

Journal Article↗