Biomedical subjects

John Rose

Publications and source records attributed to John Rose.

At least 37 records · Page 2Linked to original sources

PubMed2005

Factors associated with the efficacy of a group intervention for anger in people with intellectual disabilities.

OBJECTIVES: There is a growing literature that suggests cognitive behavioural interventions aimed at reducing inappropriately expressed anger by people with intellectual disabilities are effective. However, interventions provide little information about which aspects of the individual or their treatment may be contributing to the overall efficacy of the approach. DESIGN: A group intervention is compared with a waiting list control. A cross-sectional regressional method was used to explore the relationship between change in a provocation inventory score over the course of an intervention and a number of other variables. METHODS: Data was collected from 50 participants who attended a series of groups with the aim of reducing aggressive behaviour. This was compared with a waiting list control of 36. Outcome was measured by a provocation inventory, which was administered pre-, post-group, and at follow-up. Other variables were also measured including, receptive vocabulary, age, gender, experience of primary therapist and whether staff accompanied participants to the group or not. RESULTS: A 2 x 2 split plot ANOVA identified a statistically significant treatment effect. However, analysis examining clinical significance was more equivocal with only 11 of the individuals in the intervention group showing reliable change as defined by Jacobson and Truax (1991). Regression analysis indicated that 17.5% of the variance in change of provocation inventory scores could be accounted for by the independent variables. Immediately on completion of the group, being accompanied by a member of staff and increased receptive language scores contributed significantly to the variance. CONCLUSIONS: A reduction in provocation inventory scores immediately after the group was more likely to occur if the participant was accompanied by a member of staff who knew them and if they had a higher score on the test of receptive vocabulary. This pattern changed with time. The implications of the results will be discussed and the relatively large amount of variance that is not accounted for will also be considered.

Adolescent↗

PubMed2004

Crystal structure of a Ca2+-discharged photoprotein: implications for mechanisms of the calcium trigger and bioluminescence.

Ca2+-regulated photoproteins are members of the EF-hand calcium-binding protein family. The addition of Ca2+ produces a blue bioluminescence by triggering a decarboxylation reaction of protein-bound hydroperoxycoelenterazine to form the product, coelenteramide, in an excited state. Based on the spatial structures of aequorin and several obelins, we have postulated mechanisms for the Ca2+ trigger and for generation of the different excited states that are the origin of the different colors of bioluminescence. Here we report the crystal structure of the Ca2+-discharged photoprotein obelin at 1.96-A resolution. The results lend support to the proposed mechanisms and provide new structural insight into details of these processes. Global conformational changes caused by Ca2+ association are typical of the class of calcium signal modulators within the EF-hand protein superfamily. Accommodation of the Ca2+ ions into the loops of the EF-hands is seen to propagate into the active site of the protein now occupied by the coelenteramide where there is a significant repositioning and flipping of the His-175 imidazole ring as crucially required in the trigger hypothesis. Also the H-bonding between His-22 and the coelenterazine found in the active photoprotein is preserved at the equivalent position of coelenteramide, confirming the proposed rapid excited state proton transfer that would lead to the excited state of the phenolate ion pair, which is responsible for the blue emission of bioluminescence.

Calcium↗

PubMed2004

Structure of mouse Golgi alpha-mannosidase IA reveals the molecular basis for substrate specificity among class 1 (family 47 glycosylhydrolase) alpha1,2-mannosidases.

Three subfamilies of mammalian Class 1 processing alpha1,2-mannosidases (family 47 glycosidases) play critical roles in the maturation of Asn-linked glycoproteins in the endoplasmic reticulum (ER) and Golgi complex as well as influencing the timing and recognition for disposal of terminally unfolded proteins by ER-associated degradation. In an effort to define the structural basis for substrate recognition among Class 1 mannosidases, we have crystallized murine Golgi mannosidase IA (space group P2(1)2(1)2(1)), and the structure was solved to 1.5-A resolution by molecular replacement. The enzyme assumes an (alphaalpha)(7) barrel structure with a Ca(2+) ion coordinated at the base of the barrel similar to other Class 1 mannosidases. Critical residues within the barrel structure that coordinate the Ca(2+) ion or presumably bind and catalyze the hydrolysis of the glycone are also highly conserved. A Man(6)GlcNAc(2) oligosaccharide attached to Asn(515) in the murine enzyme was found to extend into the active site of an adjoining protein unit in the crystal lattice in a presumed enzyme-product complex. In contrast to an analogous complex previously isolated for Saccharomyces cerevisiae ER mannosidase I, the oligosaccharide in the active site of the murine Golgi enzyme assumes a different conformation to present an alternate oligosaccharide branch into the active site pocket. A comparison of the observed protein-carbohydrate interactions for the murine Golgi enzyme with the binding cleft topologies of the other family 47 glycosidases provides a framework for understanding the structural basis for substrate recognition among this class of enzymes.

Amino Acid Sequence↗

PubMed2004

X-ray crystal structure of Desulfovibrio vulgaris rubrerythrin with zinc substituted into the [Fe(SCys)4] site and alternative diiron site structures.

The X-ray crystal structure of recombinant Desulfovibrio vulgaris rubrerythrin (Rbr) that was subjected to metal constitution first with zinc and then iron, yielding ZnS(4)Rbr, is reported. A [Zn(SCys)(4)] site with no iron and a diiron site with no appreciable zinc in ZnS(4)Rbr were confirmed by analysis of the anomalous scattering data. Partial reduction of the diiron site occurred during the synchrotron X-ray irradiation at 95 K, resulting in two different diiron site structures in the ZnS(4)Rbr crystal. These two structures can be classified as containing mixed-valent Fe1(III)(mu-OH(-))(mu-GluCO(2)(-))(2)Fe2(II) and Fe1(II)(mu-GluCO(2)(-))(2)Fe2(III)-OH(-) cores. The data do not show any evidence for alternative positions of the protein or solvent ligands. The iron and ligand positions of the solvent-bridged site are close to those of the diferric site in all-iron Rbr. The diiron site with only the two carboxylato bridges differs by an approximately 2 A shift in the position of Fe1, which changes from six- to four-coordination. The Fe1- - -Fe2 distance (3.6 A) in this latter site is significantly longer than that of the site with the additional solvent bridge (3.4 A) but significantly shorter than that previously reported for the diferrous site (4.0 A) in all-iron Rbr. The apparent redox-induced movement of Fe1 at 95 K in the ZnS(4)Rbr crystal implies an extremely low activation barrier, which is consistent with the rapid (approximately 30 s(-1)) room temperature turnover of the all-iron Rbr during its catalysis of two-electron reduction of hydrogen peroxide. ZnS(4)Rbr does not show peroxidase activity, presumably because the [Zn(SCys)(4)] site, unlike the [Fe(SCys)(4)] site, cannot mediate electron transfer to the diiron site. One or both of the diiron site structures in the cryoreduced ZnS(4)Rbr crystal are likely to represent that (those) of transient mixed-valent diiron site(s) that must occur upon return of the diferric to the diferrous oxidation level during peroxidase turnover.

Bacterial Proteins↗

PubMed2004

Preparation and X-ray crystallographic analysis of the Ca2+-discharged photoprotein obelin.

Ca(2+)-regulated photoproteins belong to the EF-hand Ca(2+)-binding protein family. The addition of calcium ions initiates bright blue bioluminescence of the photoproteins, a result of the oxidative breakdown of coelenterazine peroxide to coelenteramide. Crystals of the Ca(2+)-discharged W92F mutant of obelin from Obelia longissima have been grown, representing the first crystallization of a photoprotein after the Ca(2+)-triggered bioluminescence. A green fluorescence observed from the crystals clearly demonstrates that coelenteramide, the bioluminescence product of coelenterazine peroxide, is bound within the protein. The diffraction pattern exhibits tetragonal Laue symmetry. Systematic absences indicate that the space group is either P4(3)2(1)2 or P4(1)2(1)2. The unit-cell parameters are a = b = 53.4, c = 144.0 A. The crystals diffract to 1.9 A resolution.

Animals↗

PubMed2004

Crystallization and preliminary X-ray analysis of GlcNAc alpha 1,4Gal-releasing endo-beta-galactosidase from Clostridium perfringens.

The unique clostridial endo-beta-galactosidase (Endo-beta-Gal(GnGa)) capable of releasing the disaccharide GlcNAc alpha 1,4Gal from O-glycans expressed in the gastric gland mucous cell-type mucin has been crystallized. The crystal belongs to space group P6(3), with unit-cell parameters a = 160.4, c = 86.1 A. Under cryocooled conditions and using a synchrotron X-ray source, the crystals diffract to 1.82 A resolution. The asymmetric unit contains two or three molecules.

Bacterial Proteins↗

PubMed2004

Displacement of iron by zinc at the diiron site of Desulfovibrio vulgaris rubrerythrin: X-ray crystal structure and anomalous scattering analysis.

X-ray crystal structures of recombinant Desulfovibrio (D.) vulgaris rubrerythrin (Rbr) have shown a diiron site, whereas the crystal structure of Rbr "as-isolated" from D. vulgaris was reported to contain a mixed Zn,Fe binuclear site. To investigate the possibility that zinc had displaced iron during isolation or crystallization of the "as-isolated" D. vulgaris Rbr, the X-ray crystal structure of recombinant D. vulgaris all-iron Rbr that had been incubated with excess zinc sulfate prior to crystallization, yielding a protein labeled Zn,FeRbr, was solved. Analysis of the anomalous scattering data obtained at two different wavelengths showed that zinc had displaced a significant proportion of iron from both iron centers of the diiron site, and that no iron had been displaced from the [Fe(SCys)(4)] site. UV-visible absorption spectra of the redissolved Zn,FeRbr crystals showed 30-40% retention of oxo-bridged diferric sites, and the redissolved crystals had 37% of the peroxidase specific activity of the starting all-iron Rbr, which, together with the crystallographic results, indicate a predominant mixture of Fe1,Fe2 and Zn1,Zn2 sites. The structure of the Zn(Fe)1,Fe(Zn)2 binuclear site in the Zn,FeRbr crystals was very similar to that of the Zn,Fe binuclear site reported for the "as-isolated" D. vulgaris Rbr, including tetrahedral four-coordination at the Zn(Fe)1 site. The diiron sites in the recombinant Zn,FeRbr crystals were likely at least partially reduced during synchrotron irradiation. Our results suggest that the mixed-metal binuclear site reported for the "as-isolated" D. vulgaris Rbr could be due to displacement of iron from a native diiron site by adventitious zinc during isolation and/or crystallization, and that reduced diiron and dizinc sites can adopt very similar structures in Rbr.

Bacterial Proteins↗

PubMed2004

Measuring the attitudes of human service professionals toward deafness.

The Attitudes to Deafness Scale is a 22-item measure of attitudes toward people who are deaf designed for use with human service professionals. Attitude statements were generated from personal accounts by deaf people in the literature and from a focus group in which deaf people discussed their experience of hearing people's attitudes toward them. A 60-item scale was administered to a group of 121 clinical and forensic psychologists during their training. Item analysis was conducted to select items that effectively distinguished participants with a positive attitude from those with a negative attitude toward deaf people. The scale may be used in any context where a professional group comes into contact with people who are deaf.

Adult↗

PubMed2003

Atomic resolution structure of obelin: soaking with calcium enhances electron density of the second oxygen atom substituted at the C2-position of coelenterazine.

The spatial structure of the Ca(2+)-regulated photoprotein obelin has been solved to resolution of 1.1A. Two oxygen atoms are revealed substituted at the C2-position of the coelenterazine in contrast to the obelin structure at 1.73A resolution where one oxygen atom only was disclosed. The electron density of the second oxygen atom was very weak but after exposing the crystals to a trace of Ca(2+), the electron densities of both oxygen atoms became equally intense. In addition, one Ca(2+) was found bound in the loop of the first EF-hand motif. Four of the ligands were provided by protein residues Asp30, Asn32, Asn34, and the main chain oxygen of Lys36. The other two were from water molecules. From a comparison of B-factors for the residues constituting the active site, it is suggested that the variable electron densities observed in various photoprotein structures could be attributed to different mobilities of the peroxy oxygen atoms.

Binding Sites↗

PubMed2003

An unusual case of haemobilia.

Arterio-biliary fistula is an uncommon cause of haemobilia. We describe a case of right hepatic artery pseudo-aneurysm causing arterio-biliary fistula and presenting as severe melaena and cholangitis. Gastroduodenoscopy failed to establish the exact source of bleeding and hepatic artery angiography and selective embolization of the pseudo-aneurysm successfully controlled the bleeding. Pseudo-aneurysm of the hepatic artery is mostly iatrogenic due to biliary intervention, as demonstrated in this case. Difficulty in diagnosis and management is discussed together with a review of the literature.

Aneurysm, False↗

PubMed2003

Potentially fatal haemobilia due to inappropriate use of an expanding biliary stent.

AIM: To highlight the fatal complication caused by expanding biliary stents and the importance of avoiding use of expanding stent in potentially curable diseases. METHODS: Arteriobiliary fistula is an uncommon cause of haemobilia. We describe a case of right hepatic artery pseudoaneurysm causing arteriobiliary fistula and presenting as severe malena and cholangitis, in a patient with a mesh metal biliary stent. The patient had lymphoma causing bile duct obstruction. RESULTS: Gastroduodenoscopy failed to establish the exact source of bleeding and hepatic artery angiography and selective embolisation of the pseudo aneurysm successfully controlled the bleeding. CONCLUSION: Bleeding from the pseudo aneurysm of the hepatic artery can be fatal. Mesh metal stents in biliary tree can cause this complication as demonstrated in this case. So mesh metal stent insertion should be avoided in potentially benign or in curable conditions. Difficulty in diagnosis and management is discussed along with the review of the literature.

Aneurysm, False↗

PubMed2002

X-ray crystal structures of reduced rubrerythrin and its azide adduct: a structure-based mechanism for a non-heme diiron peroxidase.

Rubrerythrin (Rbr) is a 44-kDa homodimeric protein, found in many air-sensitive bacteria and archaea, which contains a unique combination of a rubredoxin-like [Fe(SCys)(4)] site and a non-sulfur, oxo/dicarboxylato-bridged diiron site. The diiron site structure resembles those found in O2-activating diiron enzymes. However, Rbr instead appears to function as a hydrogen peroxide reductase (peroxidase). The diferrous site in all-ferrous Rbr (Rbr(red)) shows a much greater reactivity with H2O2 than does the diferric site in all-ferric Rbr (Rbr(ox)), but only the latter structure has been reported. Here we report the X-ray crystal structures of the recombinant Rbr(red) from the sulfate reducing bacterium, Desulfovibrio vulgaris, as well as its azide adduct (Rbr(red)N3). We have also redetermined the structure of Rbr(ox) to a higher resolution than previously reported. The structural differences between Rbr(ox) and Rbr(red) are localized entirely at the diiron site. The most striking structural change upon reduction of the diferric to the diferrous site of Rbr is a 1.8-A movement of one iron away from a unique glutamate carboxylate ligand and toward a trans-disposed histidine side chain, which replaces the glutamate as a ligand. This movement increases the inter-iron distance from 3.3 to 4 A. Rbr(red)N(3) shows this same iron movement and His-->Glu ligand replacement relative to Rbr(ox), and, in addition, an azide coordinated to the diiron site in a cis mu-1,3 fashion, replacing two solvent ligands in Rbr(red). Relative to those in O2-activating enzymes, the bridging carboxylate ligation of the Rbr diiron site is less flexible upon diferric/diferrous interconversion. The diferrous site is also much more rigid, symmetrical, and solvent-exposed than those in O2-activating enzymes. On the basis of these unique structural features, a mechanism is proposed for facile reduction of hydrogen peroxide by Rbr involving a cis mu-eta(2) H2O2 diferrous intermediate.

Azides↗

PubMed2002

In silico ADME/Tox: the state of the art.

The field of computational (in silico) ADME/Tox (absorption, distribution, metabolism, excretion, and toxicity) is receiving increased attention due a better appreciation that these molecular properties should be considered earlier in the drug discovery process. This report briefly reviews selected papers presented at the 220th National Meeting of the American Chemical Society, Washington, DC, 20-24 August, 2000, and describes the types of ADME/Tox computational models presented, the results obtained, and relevant recent publications that coincide with the work reported.

Biological Availability↗

PubMed2002

Sweet spot size of virtual acoustic imaging systems at asymmetric listener locations.

Virtual acoustic imaging systems are effective when the listener's head location is close to the head location assumed when the system was designed. The "sweet spot" refers to the spatial bubble of head location in which the system is still effective. Some of the previous work investigating the "stereo dipole" acoustic imaging system shows that for the traditional on-axis listener location the "sweet spot" is about +/-5 cm for lateral head translations. Larger head movements than this require an update of the virtual acoustic imaging filters. The interest here is the "sweet spot" size at off-axis asymmetric listener locations or an understanding of how often one needs to update the filters to ensure the listener perceives a stable virtual image as they move. The examination of the off-axis "sweet spot" size comprises a theoretical acoustic analysis, computer simulations, and a subjective study. The simulations and subjective evaluation both demonstrate that the width of tolerable lateral head translations is comparable for the symmetric on-axis listener location and asymmetric listener locations that are as far as 25 cm off-axis.

Acoustics↗

PubMed1998

BISMARC: a biologically inspired system for map-based autonomous rover control.

As the complexity of the missions to planetary surfaces increases, so too does the need for autonomous rover systems. This need is complicated by the power, mass and computer storage restrictions on such systems (Miller, D. P. (1992). Reducing software mass through behaviour control. In Proceedings SPIE conference on cooperative intelligent robotics in space III (Vol. 1829, pp. 472-475, 1992). Boston, MA. To address these problems, we have recently developed a system called BISMARC (Biologically Inspired System for Map-based Autonomous Rover Control) for planetary missions involving multiple small, lightweight surface rovers (Huntsberger, T. L. (1997). Autonomous multirover system for complex planetary retrieval operations. In P. S. Schenker, and G. T. McKee (Eds.), Proceedings SPIE symposium on sensor fusion and decentralized control in autonomous robotic systems (pp. 221-227). Pittsburgh, PA). BISMARC is capable of cooperative planetary surface retrieval operations such as a multiple cache recovery mission to Mars. The system employs autonomous navigation techniques, behavior-based control for surface retrieval operations, and an action selection mechanism based on a modified form of free flow hierarchy (Rosenblatt, J. K. and Payton, D. W. (1989). A fine-grained alternative to the subsumption architecture for mobile robot control. In Proceedings IEEE/INNS joint conference on neural networks (pp. 317-324). Washington, DC). This paper primarily describes the navigation and map-mapping subsystems of BISMARC. They are inspired by some recent studies of London taxi drivers indicating that the right hippocampal region of the brain is activated for path planning but not for landmark identification (Maguire, E. A. et al. (1997). Recalling routes around London: activation of the right hippocampus in taxi drivers. Journal of Neuroscience, 17(18), 7103-7110). We also report the results of some experimental studies of simulated navigation in planetary environments.

Journal Article↗

PubMedDate not supplied

Mental health professionals' attitudes towards people who are deaf.

Mental health professionals' attitudes towards deaf people were examined in relation to their previous contact with deaf people and their knowledge of deafness. Data were gathered regarding different aspects of contact, including the number and type of relationships participants had had with deaf people. A cognitive-processing theory of attitude change following contact (Rothbart & John, 1985) was explored. Knowledge of deafness did not correlate with attitudes towards deaf people but a relationship was found between the amount of contact that professionals had with deaf people of equal or higher status and more positive attitudes.

Attitude of Health Personnel↗

PubMedDate not supplied

Stent-grafts for unruptured abdominal aortic aneurysms: current status.

Aortic stent-grafts were introduced at the beginning of the 1990s as a less invasive method of dealing with aortic aneurysms in patients with poor cardiovascular reserve. The numbers of procedures performed worldwide has increased exponentially despite the current lack of any substantial evidence for long-term efficacy in comparison with the gold standard of open surgical grafting. This review summarizes the evolution of the abdominal aortic stent-graft, the techniques used for assessment and deployment, and the effect of the procedure on both the patient and the device. The recent publication of two national multicenter trials has confirmed that the endovascular technique confers a 2.5-fold reduction in 30-day mortality in comparison with open surgery. However, over 4 years of follow-up, there is a 3-fold increase in the risk of reintervention and the overall costs are 30% greater with endovascular repair. Although the improvement in aneurysm-related mortality persists in the mid-term, because of the initial reduction in perioperative mortality, the all-cause mortality rate at 4 years is actually no better than for open surgery. Longer-term data from the randomized trials are awaited as well as results from the latest trials utilizing state-of-the-art devices. Whilst the overall management of abdominal aortic aneurysms has undoubtedly benefited from the introduction of stent-grafts, open repair currently remains the gold standard treatment.

Angiography↗

PubMedDate not supplied

Improving solubility of Shewanella oneidensis MR-1 and Clostridium thermocellum JW-20 proteins expressed into Esherichia coli.

Low solubility of proteins overexpressed in E. coli is a frequent problem in high-throughput structural genomics. To improve solubility of proteins from mesophilic Shewanella oneidensis MR-1 and thermophilic Clostridium thermocellum JW20, an approach was attempted that included a fusion of the target protein to a maltose-binding protein (MBP) and a decrease of induction temperature. The MBP was selected as the most efficient solubilizing carrier when compared to a glutathione S-transferase and a Nus A protein. A tobacco etch virus (TEV) protease recognition site was introduced between fused proteins using a double polymerase-chain reaction and four primers. In this way, 79 S. oneidensis proteins have been expressed in one case with an N-terminal 30-residue tag and in another case as a fusion protein with MBP. A foreign tag might significantly affect the properties of the target polypeptide. At 37 degrees C and 18 degrees C induction temperatures, only 5 and 17 tagged proteins were soluble, respectively. In fusion with MBP 4, 34, and 38 proteins were soluble upon induction at 37 degrees, 28 degrees, and 18 degrees C, respectively. The MBP is assumed to increase stability and solubility of a target protein by changing both the mechanism and the cooperativity of folding/unfolding. The 66 C. thermocellum proteins were expressed as fusion proteins with MBP. Induction at 37 degrees, 28 degrees, and 18 degrees C produced 34, 57, and 60 soluble proteins, respectively. The higher solubility of C. thermocellum proteins in comparison with the S. oneidensis proteins under similar conditions of induction correlates with the thermophilicity of the host. The two-factor Wilkinson-Harrison statistical model was used to identify soluble and insoluble proteins. Theoretical and experimental data showed good agreement for S. oneidensis proteins; however, the model failed to identify soluble/insoluble Clostridium proteins. A suggestion has been made that the Wilkinson-Harrison model is not applicable to C. thermocellum proteins because it did not account for the peculiarities of protein sequences from thermophiles.

Amino Acid Sequence↗