Search PubMed⌕ Search

Biomedical subjects

P B Moore

Publications and source records attributed to P B Moore.

At least 19 recordsLinked to original sources
PubMed2001

Cerebral white matter lesions in bipolar affective disorder: relationship to outcome.

BACKGROUND: Twenty per cent of patients with bipolar affective disorder suffer an illness that responds inadequately to treatment and has a poor outcome. Many patients, but not all, with bipolar disorder show white matter abnormalities on T(2)-weighted magnetic resonance imaging (MRI). AIMS: To explore the hypothesis that white matter abnormalities on MRI are seen more frequently in subjects whose illness has a poor outcome compared with those with a good outcome or controls. METHOD: Two groups of age- and gender-matched patients with bipolar disorder (14 with a good outcome and 15 with a poor outcome) and 15 controls, aged 20-65 years, were studied. Axial T(2)-weighted MRI scans were examined for the presence and severity of white matter abnormalities. RESULTS: Significantly more poor outcome group members had deep subcortical punctate, but not periventricular, white matter hyperintensities than the good outcome group (P:=0.035) or controls (P:=0.003) and these abnormalities were of greater severity (P:=0.030 and P:<0.014, respectively). CONCLUSIONS: Subcortical white matter lesions are associated with poor outcome bipolar disorder.

Adult↗
PubMed2000

Randomized comparison of GR-II stent and Palmaz-Schatz stent for elective treatment of coronary stenoses.

BACKGROUND: This prospective multicenter randomized clinical trial was designed to evaluate the long-term angiographic and clinical outcomes of elective treatment with the GR-II stent compared with the Palmaz-Schatz (PS) stent in patients with coronary stenoses. METHODS AND RESULTS: Seven hundred fifty-five patients with myocardial ischemia and de novo native coronary stenoses in 3- to 4-mm vessels were randomly assigned to the PS (375 patients) or the GR-II stent (380 patients). The primary end point was 12-month target lesion revascularization (TLR)-free survival. Angiography was performed at baseline and at follow-up in the first 300 consecutive patients to assess the frequency of angiographic restenosis. Procedure success was 98.5% for the GR-II stent and 99.4% for the PS stent (P:=0.19). At 30 days, patients assigned to the GR-II stent had a higher stent thrombosis rate (3.9% versus 0.3% for PS stent, P:<0.001) and TLR rate (3.9% versus 0.5% for PS stent, P:<0.001). The GR-II group had a higher follow-up restenosis frequency (47.3% versus 20.6% for the PS group, P:<0.001) and a lower 12-month TLR-free survival rate (71.7% versus 83.9% for the PS group, P:<0. 001). Multivariate logistic regression analysis identified a smaller final stent minimal lumen diameter (odds ratio [OR] 2.49, 95% CI 1. 56 to 3.98; P:<0.001), diabetes mellitus (OR 2.14, 95% CI 1.42 to 3. 22; P:<0.001), and use of the GR-II stent (OR 1.78, 95% CI 1.20 to 2. 64; P:<0.01) as independent determinants of 12-month TLR. CONCLUSIONS: On the basis of these long-term follow-up data, we conclude that use of the GR-II stent should be limited to the acute treatment of abrupt or threatened closure after failed conventional balloon angioplasty procedures.

Analysis of Variance↗
PubMed2000

The complete atomic structure of the large ribosomal subunit at 2.4 A resolution.

The large ribosomal subunit catalyzes peptide bond formation and binds initiation, termination, and elongation factors. We have determined the crystal structure of the large ribosomal subunit from Haloarcula marismortui at 2.4 angstrom resolution, and it includes 2833 of the subunit's 3045 nucleotides and 27 of its 31 proteins. The domains of its RNAs all have irregular shapes and fit together in the ribosome like the pieces of a three-dimensional jigsaw puzzle to form a large, monolithic structure. Proteins are abundant everywhere on its surface except in the active site where peptide bond formation occurs and where it contacts the small subunit. Most of the proteins stabilize the structure by interacting with several RNA domains, often using idiosyncratically folded extensions that reach into the subunit's interior.

Archaeal Proteins↗
PubMed2000

The structural basis of ribosome activity in peptide bond synthesis.

Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli) playing the same general base role as histidine-57 in chymotrypsin. The unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.

Archaeal Proteins↗
PubMed2000

The crystal structure of yeast phenylalanine tRNA at 1.93 A resolution: a classic structure revisited.

The crystal structure of the monoclinic form of yeast phenylalanine tRNA has been redetermined at a resolution of 1.93 A. The structure of yeast tRNAphe described here is more accurate than its predecessors not only because it incorporates higher resolution data, but also because it has been refined using techniques that had not been developed when its predecessors were determined more than 20 years ago. The 1.93 A resolution version of this structure differs interestingly from its predecessors in its details. In loop regions particularly, the backbone torsion angles in the new structure are not the same as those reported earlier. Several new divalent cation binding sites have been identified, and the water structure that has emerged is also different.

Base Sequence↗
PubMed1999

Phosphorylation of ribosomal protein L18 is required for its folding and binding to 5S rRNA.

Ribosomal protein L18 from Bacillus stearothermophilus (bL18) includes a previously unreported phosphoserine residue. The folded conformation of the protein is stabilized by the dianionic form of the phosphate group of that residue. In the absence of Mg2+, the pK(a) of the phosphate group is so high that the protein is not fully folded at pH 7. In the presence of Mg2+, its pK(a) drops significantly, and consequently the native conformation of bL18 becomes stable at pH 7 and the protein is able to bind to 5S rRNA. Dephosphorylated bL18 does not bind to 5S rRNA at neutral pH.

Amino Acid Sequence↗
PubMed1999

Placement of protein and RNA structures into a 5 A-resolution map of the 50S ribosomal subunit.

We have calculated at 5.0 A resolution an electron-density map of the large 50S ribosomal subunit from the bacterium Haloarcula marismortui by using phases derived from four heavy-atom derivatives, intercrystal density averaging and density-modification procedures. More than 300 base pairs of A-form RNA duplex have been fitted into this map, as have regions of non-A-form duplex, single-stranded segments and tetraloops. The long rods of RNA crisscrossing the subunit arise from the stacking of short, separate double helices, not all of which are A-form, and in many places proteins crosslink two or more of these rods. The polypeptide exit channel was marked by tungsten cluster compounds bound in one heavy-atom-derivatized crystal. We have determined the structure of the translation-factor-binding centre by fitting the crystal structures of the ribosomal proteins L6, L11 and L14, the sarcin-ricin loop RNA, and the RNA sequence that binds L11 into the electron density. We can position either elongation factor G or elongation factor Tu complexed with an aminoacylated transfer RNA and GTP onto the factor-binding centre in a manner that is consistent with results from biochemical and electron microscopy studies.

Archaeal Proteins↗
PubMed1999

Comparison of the crystal and solution structures of two RNA oligonucleotides.

Until recently, there were no examples of RNAs whose structures had been determined by both NMR and x-ray crystallography, and thus there was no experimental basis for assessing the accuracy of RNA solution structures. A comparison of the solution and the crystal structures of two RNAs is presented, which demonstrates that NMR can produce solution structures that resemble crystal structures and thus validates the application to RNA of a methodology developed initially for the determination of protein conformations. Models for RNA solution structures are appreciably affected by the parameters used for their refinement that describe intramolecular interactions. For the RNAs of interest here, the more realistic those parameters, the greater the similarity between solution structures and crystal structures.

Base Sequence↗
PubMed1999

Sensory and hedonic associations with macronutrient and energy intakes of lean and obese consumers.

OBJECTIVE: To establish differences between lean and obese subjects in subjective reports of predominant taste and texture attributes of 'foods as eaten', and the relationships of these qualities to hedonic preference and objective measures of dietary intake and composition. DESIGN: Free-living subjects received instruction in a laboratory and kept diaries of foods eaten at home. SUBJECTS: 41 lean (body mass index (BMI) 20-25 kg/m2) and 35 obese (BMI > or = 30 kg/m2), non-dieting healthy adults. MEASUREMENTS: Subjects kept four-day weighed dietary intake records, simultaneously assigning ratings for perceived pleasantness and predominant sensory attributes (taste and texture) of food eaten, and completed the Dutch Eating Behaviour questionnaire (DEBQ). Anthropometric measures included body composition assessed by bioelectrical impedance. RESULTS: By all anthropometric measures (except height) the obese group was significantly larger than the lean group, but no significant differences were found for DEBQ scores. There were no significant group differences between pleasantness scores overall, nor for foods classified by predominant taste. Whilst macronutrient intakes did not differ, the obese group's mean dietary energy density was significantly higher, and they reported significantly greater dietary energy from 'salty' foods. For the obese group, the percentage of 'salty' foods eaten correlated strongly with energy density. A strong positive association was found between 'liking extremely' and 'sweet' foods for the lean group, but no clear associations were found for any particular taste and hedonic rating for the obese group. Whilst both groups used similar texture descriptors, there were not clear or unambiguous differences in their assignment or association with other measures. CONCLUSIONS: The results suggest that obese and lean subjects do not self-select diets with markedly different perceived sensory or hedonic attributes. However obese subjects appear to consume a diet higher in energy density, which is particularly associated with intakes of salty/savoury (rather than sweet) food items.

Adolescent↗
PubMed1999

Structural motifs in RNA.

An RNA motif is a discrete sequence or combination of base juxtapositions found in naturally occurring RNAs in unexpectedly high abundance. Because all the motifs examined so far have three-dimensional structures independent of the context in which they are embedded, they are important components of the "kit" of structural elements from which RNAs are constructed. This review discusses the structures of the motifs that have been identified so far and speculates on the importance of their role in determining RNA conformation and their evolutionary origin.

Nucleic Acid Conformation↗
PubMed1998

The M2 channel of influenza A virus: a molecular dynamics study.

Molecular dynamics simulations have been performed on a tetramer of the 25-residue (SSDPLVVAASIIGILHLILWILDRL) synthetic peptide [1] which contains the transmembrane domain of the influenza A virus M2 coat protein. The peptide bundle was initially assembled as a parallel alpha-helix bundle in the octane portion of a phase separated water/octane system, which provided a membrane-mimetic environment. A 4-ns dynamics trajectory identified a left-handed coiled coil state of the neutral bundle, with a water filled funnel-like structural motif at the N-terminus involving the long hydrophobic sequence. The neck of the funnel begins at V27 and terminates at H37, which blocks the channel. The C-terminus is held together by inter-helix hydrogen bonds and contains water below H37. Solvation of the S23 and D24 residues, located at the rim of the funnel, appears to be important for stability of the structure. The calculated average tilt of the helices in the neutral bundle is 27 +/- 5 degrees, which agrees well with recent NMR data.

Amino Acid Sequence↗
PubMed1998

N 2-methylguanosine is iso-energetic with guanosine in RNA duplexes and GNRA tetraloops.

Modified nucleotides are resource-intensive alternatives to the four nucleotides that constitute the bulk of natural RNAs. Yet, even in cases where modifications are highly conserved, their functions are difficult to identify. One possible function might be to modulate the stability of RNA structures. To investigate this possibility for N 2-methylguanosine (m2G), which is present in a wide variety of RNAs, we have determined the thermodynamic consequences of substituting m2G for G in G-C Watson-Crick pairs and G@U wobble pairs within RNA duplexes. The m2G substitution is iso-energetic with G in all cases, except for aninternal m2G@U pair, where it has a modest (0.3 kcal/mol) stabilizing effect. We have also examined theconsequences of replacing G by m2G, and A by N 6, N 6-dimethyladenosine (m26A) in the helix 45 tetraloop of 16S rRNA, which would otherwise be a standard GNRA tetraloop. This loop is a conserved, hypermethylated region of the ribosome where methylation appears to modulate activity. m26A substitution destabilizes the tetraloop, presumably because it prevents the formation of the G@A sheared pair it would otherwise contain. m2G substitution has no effect on tetraloop stability. Together, these results suggest that m2G is equally stable as either the s-cis or s-trans rotamer. The lack of a significant effect on secondary structural stability in these systems suggests that m2G is introduced into naturally occurring RNAs for reasons other than modulation of duplex stability.

Base Composition↗
PubMed1998

Simulation of the HIV-1 Vpu transmembrane domain as a pentameric bundle.

The transmembrane domain of oligomeric protein Vpu encoded by HIV-1 has been studied by means of a molecular dynamics simulation. A pentameric bundle of unconstrained helices (residues 6-28 of Vpu) with a water filled pore was initially assembled in a membrane mimetic octane/water system. This system was simulated, using the CHARMm19 and OPLS united atom force fields with no constraints at a temperature of 300 K and a pressure of 1 atm. For these forcefields and the initial conditions tested, the oligomeric bundle expelled most of the pore water molecules. The resulting bundle and residual waters adopt a conical structural motif with some resemblance to a potassium channel.

Amino Acid Sequence↗
PubMed1998

Structural and functional abnormalities in elderly patients clinically recovered from early- and late-onset depression.

BACKGROUND: Structural and functional brain changes have been described in elderly patients with unipolar affective disorder. Changes appear to be more marked in patients with late-onset depression, but the reversibility of such changes after clinical recovery is not known. METHODS: Magnetic resonance imaging, electroencephalography (EEG), and cognitive tests were performed in 23 elderly patients (mean age 66.5 years) clinically recovered from major depression. Twelve had late-onset depression (first episode over 55 years of age); 11 had early onset (first episode before 50 years). EEG and cognitive testing were also performed on 15 control subjects. RESULTS: Patients with late-onset depression had larger third and lateral ventricles, increased ventricular-brain ratio, and greater frequency and severity of subcortical white matter lesions than those with early onset. There was no difference between early- and late-onset patients in EEG and cognitive measures, but compared with controls patients showed significant changes in EEG evoked potentials and increased slow-wave activity, slowed reaction times, and global impairments in cognitive function. CONCLUSIONS: These results suggest that structural changes are greater in patients with late-onset depression, and that EEG and cognitive impairments persist after recovery, regardless of age of onset of depression, and are independent of structural changes.

Age of Onset↗
PubMed1998

A 9 A resolution X-ray crystallographic map of the large ribosomal subunit.

The 50S subunit of the ribosome catalyzes the peptidyl-transferase reaction of protein synthesis. We have generated X-ray crystallographic electron density maps of the large ribosomal subunit from Haloarcula marismortui at various resolutions up to 9 A using data from crystals that diffract to 3 A. Positioning a 20 A resolution EM image of these particles in the crystal lattice produced phases accurate enough to locate the bound heavy atoms in three derivatives using difference Fourier maps, thus demonstrating the correctness of the EM model and its placement in the unit cell. At 20 A resolution, the X-ray map is similar to the EM map; however, at 9 A it reveals long, continuous, but branched features whose shape, diameter, and right-handed twist are consistent with segments of double-helical RNA that crisscross the subunit.

Crystallography, X-Ray↗
PubMed1998

The structure of a methylated tetraloop in 16S ribosomal RNA.

BACKGROUND: Ribosomal RNAs contain many modified nucleotides. The functions of these nucleotides are poorly understood and few of them are strongly conserved. The final stem loop in 16S-like rRNAs is an exception in both regards. In both prokaryotes and eukaryotes, the tetranucleotide loop that caps the 3'-terminal stem contains two N6, N6-dimethyladenosine residues. The sequence and pattern of methylation are conserved within the loop, and there is evidence that these methylated nucleotides play an important role in subunit association and the initiation of protein synthesis. Because of the integral role that helix 45 plays in ribosome function, it is important to know what consequences these methylated nucleotides have on its structure. RESULTS: We have solved the solution structure of a 14-nucleotide analog of the terminal stem loop of bacterial 16S rRNA, which contains N2-methylguanosine as well as two N6,N6-dimethyladenosines. CONCLUSIONS: The methylation of the 16S rRNA stem loop completely alters its conformation, which would otherwise be a GNRA tetraloop. It is likely that the conformation of this loop is crucial for its function, having implications for its interaction with ribosomal subunits and its role in the initiation of protein synthesis.

Adenosine↗
PubMed1998

Molecular dynamics study of the LS3 voltage-gated ion channel.

Molecular dynamics calculations have been carried out on a model of the LS3 synthetic ion channel in a membrane mimetic environment. In the absence of an external electrostatic field, the LS3 channel, which consists of a bundle of six alpha-helices with sequence Ac-(LSSLLSL)3-CONH2, exhibits large structural fluctuations. However, in the presence of the field, the bundle adopts a well defined coiled-coil structure with an inner pore of water. The observed structural changes induced by the applied field are consistent with the proposed gating mechanism of the ion channel.

Computer Simulation↗