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N Gibbs

Publications and source records attributed to N Gibbs.

At least 19 recordsLinked to original sources
PubMed2001

Location and properties of metal-binding sites on the human prion protein.

Although a functional role in copper binding has been suggested for the prion protein, evidence for binding at affinities characteristic of authentic metal-binding proteins has been lacking. By presentation of copper(II) ions in the presence of the weak chelator glycine, we have now characterized two high-affinity binding sites for divalent transition metals within the human prion protein. One is in the N-terminal octapeptide-repeat segment and has a K(d) for copper(II) of 10(-14) M, with other metals (Ni(2+), Zn(2+), and Mn(2+)) binding three or more orders of magnitude more weakly. However, NMR and fluorescence data reveal a previously unreported second site around histidines 96 and 111, a region of the molecule known to be crucial for prion propagation. The K(d) for copper(II) at this site is 4 x 10(-14) M, whereas nickel(II), zinc(II), and manganese(II) bind 6, 7, and 10 orders of magnitude more weakly, respectively, regardless of whether the protein is in its oxidized alpha-helical (alpha-PrP) or reduced beta-sheet (beta-PrP) conformation. A role for prion protein (PrP) in copper metabolism or transport seems likely and disturbance of this function may be involved in prion-related neurotoxicity.

Amino Acid Sequence↗
PubMed2001

Ab initio protein structure prediction using physicochemical potentials and a simplified off-lattice model.

This study describes a computational method for ab inito protein structure prediction. Protein conformation has been modeled by using six optimized backbone torsion angles and fixed side chains approximating rotationally averaged real side chains. The approximations aim to keep complexity of the structure description to a minimum without seriously compromising the accuracy of the structural representation. An evolutionary Monte Carlo algorithm has been developed to search through this restricted conformational space to locate low-energy protein structures. A simple physicochemical force field has been developed to assess the energies of different conformations within this structural description. The corresponding residue interaction energies are based on hydrophobic, hydrophilic, steric, and hydrogen-bonding potentials. The search procedure has been used to locate native energy minima from primary sequence alone. The 3-D structures of polypeptides up to 38 residues with both beta and alpha secondary structural elements have been accurately predicted. The search procedure has been found to be highly efficient and follows an energetically and structurally plausible pathway to locate native populations. The simple force field described in the study has been compared with a more complex all-atom model and been found to be similarly effective in predicting the structures of proposed independent folding units. Proteins 2001;43:186-202.

Algorithms↗
PubMed2000

The pill arrives.

Explore the source record for details and available documents.

Abortifacient Agents, Steroidal↗
PubMed2000

Relative cost of autologous red cell salvage versus allogeneic red cell transfusion during abdominal aortic aneurysm repair.

The costs of washed autologous red cell concentrate obtained by intraoperative red cell salvage were compared to the costs of allogeneic packed red cell transfusion during 110 consecutive abdominal aortic aneurysm repairs. The mean volume of scavenged blood during elective procedures was 1350 ml (range 350 to 6675 ml, n = 90) and emergency procedures 2750 ml (range 750 to 9400 ml, n = 20). The mean volume of processed (washed) blood returned during elective repairs was 759 ml (range 150 to 2900 ml, n = 51) and emergency repairs 1117 ml (range 0 to 4100 ml, n = 20). During elective repairs, the cost of routine autologous red cell salvage ($151 per 285 ml unit) was only slightly greater than the estimated cost of cross-matched, leucocyte-reduced, allogeneic blood ($143 per 285 ml unit). During emergency repairs, washed autologous red cells ($83 per 285 ml unit) were less expensive than allogeneic packed red cells. These findings indicate that, compared with the use of allogeneic packed red cells, red cell salvage during emergency abdominal aortic aneurysm repair can be justified on an economic basis alone, and that routine red cell salvage during elective repair can achieve the benefits of autologous blood at little extra cost to the community.

Aged↗
PubMed1998

A week in the life of a hospital.

The same urgency and intellect that America's teaching hospitals apply to saving lives is now also going into saving the institutions themselves. All across the country, academic medical centers are trying to figure out how to marry progress with profits. At the Duke University Medical Center, TIME visits the front line in the war between money and medicine.

Budgets↗
PubMed1998

Hydrogen bonding in helical polypeptides from molecular dynamics simulations and amide hydrogen exchange analysis: alamethicin and melittin in methanol.

Molecular dynamics simulations of ion channel peptides alamethicin and melittin, solvated in methanol at 27 degrees C, were run with either regular alpha-helical starting structures (alamethicin, 1 ns; melittin 500 ps either with or without chloride counterions), or with the x-ray crystal coordinates of alamethicin as a starting structure (1 ns). The hydrogen bond patterns and stabilities were characterized by analysis of the dynamics trajectories with specified hydrogen bond angle and distance criteria, and were compared with hydrogen bond patterns and stabilities previously determined from high-resolution NMR structural analysis and amide hydrogen exchange measurements in methanol. The two alamethicin simulations rapidly converged to a persistent hydrogen bond pattern with a high level of 3(10) hydrogen bonding involving the amide NH's of residues 3, 4, 9, 15, and 18. The 3(10) hydrogen bonds stabilizing amide NH's of residues C-terminal to P2 and P14 were previously proposed to explain their high amide exchange stabilities. The absence, or low levels of 3(10) hydrogen bonds at the N-terminus or for A15 NH, respectively, in the melittin simulations, is also consistent with interpretations from amide exchange analysis. Perturbation of helical hydrogen bonding in the residues before P14 (Aib10-P14, alamethicin; T11-P14, melittin) was characterized in both peptides by variable hydrogen bond patterns that included pi and gamma hydrogen bonds. The general agreement in hydrogen bond patterns determined in the simulations and from spectroscopic analysis indicates that with suitable conditions (including solvent composition and counterions where required), local hydrogen-bonded secondary structure in helical peptides may be predicted from dynamics simulations from alpha-helical starting structures. Each peptide, particularly alamethicin, underwent some large amplitude structural fluctuations in which several hydrogen bonds were cooperatively broken. The recovery of the persistent hydrogen bonding patterns after these fluctuations demonstrates the stability of intramolecular hydrogen-bonded secondary structure in methanol (consistent with spectroscopic observations), and is promising for simulations on extended timescales to characterize the nature of the backbone fluctuations that underlie amide exchange from isolated helical polypeptides.

Alamethicin↗
PubMed1998

Safe Child Penarth: experience with a Safe Community strategy for preventing injuries to children.

OBJECTIVES: To evaluate the process of establishing a Safe Community project for children. DESIGN: A descriptive study. SETTING: Penarth, a town (population 20,430) Vale of Glamorgan, South Wales. SUBJECTS: 3943 children and their families in Penarth. MAIN OUTCOME MEASURES: Whether the 12 criteria for a Safe Community project (World Health Organisation) were met. Implementation of the safety agenda set by the community. RESULTS: Safe Child Penarth met 10 of the 12 criteria for the Safe Community network. All the items on the agenda were introduced in the initial two years of the project. There were difficulties, however, achieving sustained community ownership of the project. CONCLUSIONS: The Safe Community concept stimulated work to improve child safety in Penarth. Community safety initiatives should involve all local agencies to identify the problems and work with the community to set and meet the safety agenda. Partnership with the local authority is valuable to improve the safety of the environment. The experience generated from Safe Child Penarth has been used to develop a county wide, all age community safety project.

Accident Prevention↗
PubMed1997

Helix bending in alamethicin: molecular dynamics simulations and amide hydrogen exchange in methanol.

Molecular dynamics simulations of alamethicin in methanol were carried out with either a regular alpha-helical conformation or the x-ray crystal structure as starting structures. The structures rapidly converged to a well-defined hydrogen-bonding pattern with mixed alpha-helical and 3(10)-helical hydrogen bonds, consistent with NMR structural characterization, and did not unfold throughout the 1-ns simulation, despite some sizable backbone fluctuations involving reversible breaking of helical hydrogen bonds. Bending of the helical structure around residues Aib10-Aib13 was associated with reversible flips of the peptide bonds involving G11 (Aib10-G11 or G11-L12 peptide bonds), yielding discrete structural states in which the Aib10 carbonyl or (rarely) the G11 carbonyl was oriented away from the peptide helix. These peptide bond reversals could be accommodated without greatly perturbing the adjacent helical structure, and intramolecular hydrogen bonding was generally maintained in bent states through the formation of new (non-alpha or 3[10]) hydrogen bonds with good geometries: G11 NH-V9 CO (inverse gamma turn), Aib13 NH-Aib8 CO (pi-helix) and, rarely, L12 NH- Q7 NH (pi-helix). These observations may reconcile potentially conflicting NMR structural information for alamethicin in methanol, in which evidence for conformational flexibility in the peptide sequence before P14 (G11-Aib13) contrasts with the stability of backbone amide NH groups to exchange with solvent. Similar reversible reorientation of the Thr11-Gly12 peptide bond of melittin is also observed in dynamics simulations in methanol (R. B. Sessions, N. Gibbs, and C. E. Dempsey, submitted). This phenomenon may have some role in the orientation of the peptide carbonyl in solvating the channel lumen in membrane ion channel states of these peptides.

Alamethicin↗
PubMed1997

Thoracic spinal fracture in a rugby league footballer.

PURPOSE: The report describes the mechanisms and sequelae of the first case of thoracic vertebral fracture to be reported in a rugby league footballer. CASE SUMMARY: The injury was sustained as the result of a legal shoulder tackle. The player exhibited no sign other than dorsal midthoracic tenderness and paraspinal muscle spasm. Investigations commenced the next day because of persistent pain. CT and MRI revealed complex T6/7 fractures not evident on plain x-ray. The player was managed conservatively with analgesia and rest and has made a full recovery. DISCUSSION: Football is the most common cause of cervical spinal fractures in sport, whereas thoracic spinal fractures are very rare. Although in this case significant damage occurred to the posterior elements of the column, there were no neurological complications. RELEVANCE: The anatomical and physiological bracing of the thoracic spine accounts for the rarity of fractures in contact sport and favors conservative management.

Adolescent↗