Helen Bradley | University of South Australia (original) (raw)

Papers by Helen Bradley

This has been an eighteen-month half-time project, designed to make widely available, and to anal... more This has been an eighteen-month half-time project, designed to make widely available, and to analyse, information contained in an important, but under-used, collection of documents relating to the trading activities of alien merchants in fifteenth century England.

International Journal of Sports Physical Therapy, Feb 1, 2014

Study Design:Experimental designBackground:Normal breathing mechanics play a key role in posture ... more Study Design:Experimental designBackground:Normal breathing mechanics play a key role in posture and spinal stabilization. Breathing Pattern Disorders (BPD) have been shown to contribute to pain and motor control deficits, which can result in dysfunctional movement patterns. The Functional Movement Screen™ (FMS™) has been shown to accurately predict injury in individuals who demonstrate poor movement patterns. The role BPD play on functional movement is not well established. Furthermore, there is currently no single test to clinically diagnose BPD. A variety of methods are used, but correlations between them are poor.Purpose:To examine the relationship between BPD and functional movement and identify correlations between different measures of BPD.Methods:Breathing was assessed in 34 healthy individuals using a multi‐dimensional approach that included biomechanical, biochemical, breathing related symptoms, and breathing functionality measures. Movement was assessed using the FMS™. Analysis, involving independent t‐tests and Pearson correlation were performed to identify associations between measures.Results:Individuals who exhibited biochemical and biomechanical signs of BPD were significantly more likely to score poorly on the FMS™. These studied measures of BPD correlated highly with each other.Conclusion:These results demonstrate the importance of diaphragmatic breathing on functional movement. Inefficient breathing could result in muscular imbalance, motor control alterations, and physiological adaptations that are capable of modifying movement. These findings provide evidence for improved breathing evaluations by clinicians.Level of Evidence:2B

International journal of sports physical therapy, 2014

Experimental design. Normal breathing mechanics play a key role in posture and spinal stabilizati... more Experimental design. Normal breathing mechanics play a key role in posture and spinal stabilization. Breathing Pattern Disorders (BPD) have been shown to contribute to pain and motor control deficits, which can result in dysfunctional movement patterns. The Functional Movement Screen™ (FMS™) has been shown to accurately predict injury in individuals who demonstrate poor movement patterns. The role BPD play on functional movement is not well established. Furthermore, there is currently no single test to clinically diagnose BPD. A variety of methods are used, but correlations between them are poor. To examine the relationship between BPD and functional movement and identify correlations between different measures of BPD. Breathing was assessed in 34 healthy individuals using a multi-dimensional approach that included biomechanical, biochemical, breathing related symptoms, and breathing functionality measures. Movement was assessed using the FMS™. Analysis, involving independent t-test...

Background: Pin-site infection is a common complication in the treatment of fragility fractures o... more Background: Pin-site infection is a common complication in the treatment of fragility fractures of the distal radius in the older population. There is a need for evidence-based practice guidelines for pin-site care as few studies have compared the associated infection rates of different treatment methods. Objectives: A clinical study was conducted over a 24-month period to record the clinical outcome

Molecular Pharmacology, 2008

P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibit... more P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibited by submicromolar concentrations of zinc and copper. The molecular basis for the strong functional inhibition by zinc and copper at this purinergic ionotropic receptor is controversial. We hypothesized that it involves a direct interaction of zinc and copper with residues in the ectodomain of the P2X 7 receptor. Fourteen potential metal interacting residues are conserved in the ectodomain of all mammalian P2X 7 receptors, none of which is homologous to previously identified sites in other P2X receptors shown to be important for functional potentiation by zinc. We introduced alanine substitutions into each of these residues, expressed wild-type and mutated receptors in human embryonic kidney 293 cells, and recorded resulting ATP and BzATP-evoked membrane currents. Agonist concentration-response curves were similar for all 12 functional mutant receptors. Alanine substitution at His 62 or Asp 197 strongly attenuated both zinc and copper inhibition, and the double mutant [H62A/D197A] mutant receptor was virtually insensitive to inhibition by zinc or copper. Thus, we conclude that zinc and copper inhibition is due to a direct interaction of these divalent cations with ectodomain residues of the P2X 7 receptor, primarily involving combined interaction with His 62 and Asp 197 residues. This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (L.-H.J., A.S.), the Royal Society (H.-J. M., L.-H.J.), a UK Overseas Research Scholarship (R.X.), and a BBSRC doctoral training grant (H.B.).

Journal of Psychiatric Research, 2010

Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorp... more Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorphisms (SNPs) in the human P2RX7 gene in individuals with affective mood disorders. The P2RX7 gene encodes the P2X 7 receptor (P2X 7 R) that operates as an ATP-activated Ca 2+ -permeable cationic channel and induces formation of a large pore, the two functional properties that are critical for the physiological and pathological roles of the receptor. The current knowledge regarding the effects of SNPs on the P2X 7 R functional properties, which is indispensable to help elucidate the disease mechanism, is limited. In this study, we introduced by site-directed mutagenesis twelve SNP mutations in the human P2X 7 receptor that were previously identified in or associated with affective mood disorders, expressed the resultant mutants in human embryonic kidney cells, and characterized their functional properties by electrophysiology. All mutations except Q460R gave rise to profound effects on the P2X 7 R function. G150R, E186K and I568N conferred complete loss of function. V76A, R117W, L191P, T357S and E496A resulted in strong impairment of, whereas H155Y and A348T caused significant increase in, both ATP-activated ion channel function and pore formation. Q521H reduced the receptor's sensitivity to extracellular Ca 2+ inhibition. An atomic structure model of the human P2X 7 R, based on the crystal structure of the zebrafish P2X 4 receptor, suggests that the SNP mutational effects may result from changes in subunit interaction, agonist binding and/or channel gating. These results provide essential knowledge for a better understanding of the relationships between human P2RX7 SNPs and associated pathologies as well as the receptor structure-function relationships.

... END OF AWARD RESEARCH REPORT. Dr Helen Bradley and Dr Matthew Davies. ... Thrupp, SL 1969, &#... more ... END OF AWARD RESEARCH REPORT. Dr Helen Bradley and Dr Matthew Davies. ... Thrupp, SL 1969, 'Aliens in and around London in the 15th century', in Studies in London history presented to PEJones, ed. AEJ Hollaender and W. Kellaway (London). Warner, GF, Sir (ed.) 1926. ...

Physiological reports, 2016

Synaptosomal-associated protein 23 (SNAP23) is a SNARE protein expressed abundantly in human skel... more Synaptosomal-associated protein 23 (SNAP23) is a SNARE protein expressed abundantly in human skeletal muscle. Its established role is to mediate insulin-stimulated docking and fusion of glucose transporter 4 (GLUT4) with the plasma membrane. Recent in vitro research has proposed that SNAP23 may also play a role in the fusion of growing lipid droplets (LDs) and the channeling of LD-derived fatty acids (FAs) into neighboring mitochondria for β-oxidation. This study investigates the subcellular distribution of SNAP23 in human skeletal muscle using immunofluorescence microscopy to confirm that SNAP23 localization supports the three proposed metabolic roles. Percutaneous biopsies were obtained from the m. vastus lateralis of six lean, healthy males in the rested, overnight fasted state. Cryosections were stained with antibodies targeting SNAP23, the mitochondrial marker cytochrome c oxidase and the plasma membrane marker dystrophin, whereas intramuscular LDs were stained using the neutra...

Background: Pin-site infection is a common complication in the treatment of fragility fractures o... more Background: Pin-site infection is a common complication in the treatment of fragility fractures of the distal radius in the older population. There is a need for evidence-based practice guidelines for pin-site care as few studies have compared the associated infection rates of different treatment methods. Objectives: A clinical study was conducted over a 24-month period to record the clinical outcome in patients treated with Acticoat 7, a nanocrystalline silver-release dressing, and OpSite Post-Op, a barrier dressing, in the management of pin-site infection. A secondary objective was to compare these outcomes with those of patients treated with oral antimicrobials. Methods:Twenty-one outpatients with a K-wire fixation for osteoporotic distal radius fracture with established pin-track infection were studied. The first 10 patients were treated with a one-week course of an appropriate antibiotic determined by culture and the rest were treated with Acticoat 7 and OpSite Post-Op dressing...

Novartis Foundation Symposia, 1984

Physiological reports, Jan 11, 2015

Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in par... more Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of ten insulin-sensitive men in the basal state and following 30 min of cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and dystrophin colocalization, measured using the Pearson's correlation coefficient, was increased following 30 min of cycling exercise (baseline r = 0.47 ± 0.01; post exercise r = 0.58 ± 0.02; P &...

Journal of perioperative practice, 2008

This prospective, single-centre study compared wound closure methods in patients undergoing arthr... more This prospective, single-centre study compared wound closure methods in patients undergoing arthroscopy. Closure of arthroscopic portal wounds with sterile adhesive strips is effective and convenient for wound management. The method was associated with a reduced potential for infection, faster renewal of tensile strength, greater cost effectiveness, and better cosmetic effects comparing with suture closure. This method of wound closure may also reduce the incidence of needle stick injury in the theatre environment. Thereby the incidence of percutaneous exposure following a surgical procedure may not facilitate transmission of blood borne pathogens such as human immunodeficiency virus (HIV), hepatitis C virus and hepatitis B virus. As a result it may reduce litigation in today's changing healthcare climate.

Physiological reports, 2014

Increases in insulin-mediated glucose uptake following endurance training (ET) and sprint interva... more Increases in insulin-mediated glucose uptake following endurance training (ET) and sprint interval training (SIT) have in part been attributed to concomitant increases in glucose transporter 4 (GLUT4) protein content in skeletal muscle. This study used an immunofluorescence microscopy method to investigate changes in subcellular GLUT4 distribution and content following ET and SIT. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of 16 sedentary males in the overnight fasted state before and after 6 weeks of ET and SIT. An antibody was fully validated and used to show large (> 1 μm) and smaller (<1 μm) GLUT4-containing clusters. The large clusters likely represent trans-Golgi network stores and the smaller clusters endosomal stores and GLUT4 storage vesicles (GSVs). Density of GLUT4 clusters was higher at the fibre periphery especially in perinuclear regions. A less dense punctate distribution was seen in the rest of the muscle fibre. Total GLUT4 fluor...

Journal of Orthopaedic Nursing, 2005

Telecommunications Policy, 1979

The authors discuss the characteristics and benefits of network information services (NIS), which... more The authors discuss the characteristics and benefits of network information services (NIS), which are developing into an important new industry likely to have profound effects on society. Many of the services and possible applications are described. Three scenarios are analysed, in which the future of the industry may be directed by technology, the market, and policy issues. It is concluded

Physiological Entomology, 1985

Molecular Pharmacology, 2007

P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibit... more P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibited by submicromolar concentrations of zinc and copper. The molecular basis for the strong functional inhibition by zinc and copper at this purinergic ionotropic receptor is controversial. We hypothesized that it involves a direct interaction of zinc and copper with residues in the ectodomain of the P2X 7 receptor. Fourteen potential metal interacting residues are conserved in the ectodomain of all mammalian P2X 7 receptors, none of which is homologous to previously identified sites in other P2X receptors shown to be important for functional potentiation by zinc. We introduced alanine substitutions into each of these residues, expressed wild-type and mutated receptors in human embryonic kidney 293 cells, and recorded resulting ATP and BzATP-evoked membrane currents. Agonist concentration-response curves were similar for all 12 functional mutant receptors. Alanine substitution at His 62 or Asp 197 strongly attenuated both zinc and copper inhibition, and the double mutant [H62A/D197A] mutant receptor was virtually insensitive to inhibition by zinc or copper. Thus, we conclude that zinc and copper inhibition is due to a direct interaction of these divalent cations with ectodomain residues of the P2X 7 receptor, primarily involving combined interaction with His 62 and Asp 197 residues. This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (L.-H.J., A.S.), the Royal Society (H.-J. M., L.-H.J.), a UK Overseas Research Scholarship (R.X.), and a BBSRC doctoral training grant (H.B.).

Journal of Psychiatric Research, 2010

Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorp... more Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorphisms (SNPs) in the human P2RX7 gene in individuals with affective mood disorders. The P2RX7 gene encodes the P2X 7 receptor (P2X 7 R) that operates as an ATP-activated Ca 2+ -permeable cationic channel and induces formation of a large pore, the two functional properties that are critical for the physiological and pathological roles of the receptor. The current knowledge regarding the effects of SNPs on the P2X 7 R functional properties, which is indispensable to help elucidate the disease mechanism, is limited. In this study, we introduced by site-directed mutagenesis twelve SNP mutations in the human P2X 7 receptor that were previously identified in or associated with affective mood disorders, expressed the resultant mutants in human embryonic kidney cells, and characterized their functional properties by electrophysiology. All mutations except Q460R gave rise to profound effects on the P2X 7 R function. G150R, E186K and I568N conferred complete loss of function. V76A, R117W, L191P, T357S and E496A resulted in strong impairment of, whereas H155Y and A348T caused significant increase in, both ATP-activated ion channel function and pore formation. Q521H reduced the receptor's sensitivity to extracellular Ca 2+ inhibition. An atomic structure model of the human P2X 7 R, based on the crystal structure of the zebrafish P2X 4 receptor, suggests that the SNP mutational effects may result from changes in subunit interaction, agonist binding and/or channel gating. These results provide essential knowledge for a better understanding of the relationships between human P2RX7 SNPs and associated pathologies as well as the receptor structure-function relationships.

Journal of Biological Chemistry, 2011

Short title: Expression and function of P2X 7 receptors P2X 7 receptors are important in mediatin... more Short title: Expression and function of P2X 7 receptors P2X 7 receptors are important in mediating the physiological functions of extracellular ATP, and altered receptor expression and function have a causative role in the disease pathogenesis. Here we investigated the mechanisms determining the P2X 7 receptor function by following two human SNP mutations that replace H155 and A348 in the hP2X 7 receptor with the corresponding residues Y155 and T348 in the rP2X 7 receptor. H155Y and A348T mutations in the hP2X 7 receptor increased ATP-induced currents, whereas the reciprocal mutations Y155H and T348A in the rP2X 7 receptor caused the opposite effects. Such functional switch is a compelling indication that these residues are critical for the P2X 7 receptor function. Additional mutations of H155 and A348 in the hP2X 7 receptor to residues with diverse side-chains reveal different dependence on the side-chain properties, supporting specificity of these two residues. Substitutions of the residues surrounding H155 and A348 in the hP2X 7 receptor with the equivalent ones in the rP2X 7 receptor also affected ATP-induced currents, but were not fully reminiscent of the H155Y and A348T effects. Immunofluorescent imaging and biotin-labelling assays showed that H155Y in the hP2X 7 receptor increased, whereas Y155H in the rP2X 7 receptor decreased, cell surface expression. Such contrasting effects were not obvious with the reciprocal mutations of residue 348. Taken together, our results suggest that residues at positions 155 and 348 contribute to P2X 7 receptor function via determining the surface expression and the single channel function respectively. Such interpretations are consistent with the location of the residues in the structural model of the hP2X 7 receptor.

This has been an eighteen-month half-time project, designed to make widely available, and to anal... more This has been an eighteen-month half-time project, designed to make widely available, and to analyse, information contained in an important, but under-used, collection of documents relating to the trading activities of alien merchants in fifteenth century England.

International Journal of Sports Physical Therapy, Feb 1, 2014

Study Design:Experimental designBackground:Normal breathing mechanics play a key role in posture ... more Study Design:Experimental designBackground:Normal breathing mechanics play a key role in posture and spinal stabilization. Breathing Pattern Disorders (BPD) have been shown to contribute to pain and motor control deficits, which can result in dysfunctional movement patterns. The Functional Movement Screen™ (FMS™) has been shown to accurately predict injury in individuals who demonstrate poor movement patterns. The role BPD play on functional movement is not well established. Furthermore, there is currently no single test to clinically diagnose BPD. A variety of methods are used, but correlations between them are poor.Purpose:To examine the relationship between BPD and functional movement and identify correlations between different measures of BPD.Methods:Breathing was assessed in 34 healthy individuals using a multi‐dimensional approach that included biomechanical, biochemical, breathing related symptoms, and breathing functionality measures. Movement was assessed using the FMS™. Analysis, involving independent t‐tests and Pearson correlation were performed to identify associations between measures.Results:Individuals who exhibited biochemical and biomechanical signs of BPD were significantly more likely to score poorly on the FMS™. These studied measures of BPD correlated highly with each other.Conclusion:These results demonstrate the importance of diaphragmatic breathing on functional movement. Inefficient breathing could result in muscular imbalance, motor control alterations, and physiological adaptations that are capable of modifying movement. These findings provide evidence for improved breathing evaluations by clinicians.Level of Evidence:2B

International journal of sports physical therapy, 2014

Experimental design. Normal breathing mechanics play a key role in posture and spinal stabilizati... more Experimental design. Normal breathing mechanics play a key role in posture and spinal stabilization. Breathing Pattern Disorders (BPD) have been shown to contribute to pain and motor control deficits, which can result in dysfunctional movement patterns. The Functional Movement Screen™ (FMS™) has been shown to accurately predict injury in individuals who demonstrate poor movement patterns. The role BPD play on functional movement is not well established. Furthermore, there is currently no single test to clinically diagnose BPD. A variety of methods are used, but correlations between them are poor. To examine the relationship between BPD and functional movement and identify correlations between different measures of BPD. Breathing was assessed in 34 healthy individuals using a multi-dimensional approach that included biomechanical, biochemical, breathing related symptoms, and breathing functionality measures. Movement was assessed using the FMS™. Analysis, involving independent t-test...

Background: Pin-site infection is a common complication in the treatment of fragility fractures o... more Background: Pin-site infection is a common complication in the treatment of fragility fractures of the distal radius in the older population. There is a need for evidence-based practice guidelines for pin-site care as few studies have compared the associated infection rates of different treatment methods. Objectives: A clinical study was conducted over a 24-month period to record the clinical outcome

Molecular Pharmacology, 2008

P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibit... more P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibited by submicromolar concentrations of zinc and copper. The molecular basis for the strong functional inhibition by zinc and copper at this purinergic ionotropic receptor is controversial. We hypothesized that it involves a direct interaction of zinc and copper with residues in the ectodomain of the P2X 7 receptor. Fourteen potential metal interacting residues are conserved in the ectodomain of all mammalian P2X 7 receptors, none of which is homologous to previously identified sites in other P2X receptors shown to be important for functional potentiation by zinc. We introduced alanine substitutions into each of these residues, expressed wild-type and mutated receptors in human embryonic kidney 293 cells, and recorded resulting ATP and BzATP-evoked membrane currents. Agonist concentration-response curves were similar for all 12 functional mutant receptors. Alanine substitution at His 62 or Asp 197 strongly attenuated both zinc and copper inhibition, and the double mutant [H62A/D197A] mutant receptor was virtually insensitive to inhibition by zinc or copper. Thus, we conclude that zinc and copper inhibition is due to a direct interaction of these divalent cations with ectodomain residues of the P2X 7 receptor, primarily involving combined interaction with His 62 and Asp 197 residues. This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (L.-H.J., A.S.), the Royal Society (H.-J. M., L.-H.J.), a UK Overseas Research Scholarship (R.X.), and a BBSRC doctoral training grant (H.B.).

Journal of Psychiatric Research, 2010

Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorp... more Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorphisms (SNPs) in the human P2RX7 gene in individuals with affective mood disorders. The P2RX7 gene encodes the P2X 7 receptor (P2X 7 R) that operates as an ATP-activated Ca 2+ -permeable cationic channel and induces formation of a large pore, the two functional properties that are critical for the physiological and pathological roles of the receptor. The current knowledge regarding the effects of SNPs on the P2X 7 R functional properties, which is indispensable to help elucidate the disease mechanism, is limited. In this study, we introduced by site-directed mutagenesis twelve SNP mutations in the human P2X 7 receptor that were previously identified in or associated with affective mood disorders, expressed the resultant mutants in human embryonic kidney cells, and characterized their functional properties by electrophysiology. All mutations except Q460R gave rise to profound effects on the P2X 7 R function. G150R, E186K and I568N conferred complete loss of function. V76A, R117W, L191P, T357S and E496A resulted in strong impairment of, whereas H155Y and A348T caused significant increase in, both ATP-activated ion channel function and pore formation. Q521H reduced the receptor's sensitivity to extracellular Ca 2+ inhibition. An atomic structure model of the human P2X 7 R, based on the crystal structure of the zebrafish P2X 4 receptor, suggests that the SNP mutational effects may result from changes in subunit interaction, agonist binding and/or channel gating. These results provide essential knowledge for a better understanding of the relationships between human P2RX7 SNPs and associated pathologies as well as the receptor structure-function relationships.

... END OF AWARD RESEARCH REPORT. Dr Helen Bradley and Dr Matthew Davies. ... Thrupp, SL 1969, &#... more ... END OF AWARD RESEARCH REPORT. Dr Helen Bradley and Dr Matthew Davies. ... Thrupp, SL 1969, 'Aliens in and around London in the 15th century', in Studies in London history presented to PEJones, ed. AEJ Hollaender and W. Kellaway (London). Warner, GF, Sir (ed.) 1926. ...

Physiological reports, 2016

Synaptosomal-associated protein 23 (SNAP23) is a SNARE protein expressed abundantly in human skel... more Synaptosomal-associated protein 23 (SNAP23) is a SNARE protein expressed abundantly in human skeletal muscle. Its established role is to mediate insulin-stimulated docking and fusion of glucose transporter 4 (GLUT4) with the plasma membrane. Recent in vitro research has proposed that SNAP23 may also play a role in the fusion of growing lipid droplets (LDs) and the channeling of LD-derived fatty acids (FAs) into neighboring mitochondria for β-oxidation. This study investigates the subcellular distribution of SNAP23 in human skeletal muscle using immunofluorescence microscopy to confirm that SNAP23 localization supports the three proposed metabolic roles. Percutaneous biopsies were obtained from the m. vastus lateralis of six lean, healthy males in the rested, overnight fasted state. Cryosections were stained with antibodies targeting SNAP23, the mitochondrial marker cytochrome c oxidase and the plasma membrane marker dystrophin, whereas intramuscular LDs were stained using the neutra...

Background: Pin-site infection is a common complication in the treatment of fragility fractures o... more Background: Pin-site infection is a common complication in the treatment of fragility fractures of the distal radius in the older population. There is a need for evidence-based practice guidelines for pin-site care as few studies have compared the associated infection rates of different treatment methods. Objectives: A clinical study was conducted over a 24-month period to record the clinical outcome in patients treated with Acticoat 7, a nanocrystalline silver-release dressing, and OpSite Post-Op, a barrier dressing, in the management of pin-site infection. A secondary objective was to compare these outcomes with those of patients treated with oral antimicrobials. Methods:Twenty-one outpatients with a K-wire fixation for osteoporotic distal radius fracture with established pin-track infection were studied. The first 10 patients were treated with a one-week course of an appropriate antibiotic determined by culture and the rest were treated with Acticoat 7 and OpSite Post-Op dressing...

Novartis Foundation Symposia, 1984

Physiological reports, Jan 11, 2015

Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in par... more Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of ten insulin-sensitive men in the basal state and following 30 min of cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and dystrophin colocalization, measured using the Pearson's correlation coefficient, was increased following 30 min of cycling exercise (baseline r = 0.47 ± 0.01; post exercise r = 0.58 ± 0.02; P &...

Journal of perioperative practice, 2008

This prospective, single-centre study compared wound closure methods in patients undergoing arthr... more This prospective, single-centre study compared wound closure methods in patients undergoing arthroscopy. Closure of arthroscopic portal wounds with sterile adhesive strips is effective and convenient for wound management. The method was associated with a reduced potential for infection, faster renewal of tensile strength, greater cost effectiveness, and better cosmetic effects comparing with suture closure. This method of wound closure may also reduce the incidence of needle stick injury in the theatre environment. Thereby the incidence of percutaneous exposure following a surgical procedure may not facilitate transmission of blood borne pathogens such as human immunodeficiency virus (HIV), hepatitis C virus and hepatitis B virus. As a result it may reduce litigation in today's changing healthcare climate.

Physiological reports, 2014

Increases in insulin-mediated glucose uptake following endurance training (ET) and sprint interva... more Increases in insulin-mediated glucose uptake following endurance training (ET) and sprint interval training (SIT) have in part been attributed to concomitant increases in glucose transporter 4 (GLUT4) protein content in skeletal muscle. This study used an immunofluorescence microscopy method to investigate changes in subcellular GLUT4 distribution and content following ET and SIT. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of 16 sedentary males in the overnight fasted state before and after 6 weeks of ET and SIT. An antibody was fully validated and used to show large (> 1 μm) and smaller (<1 μm) GLUT4-containing clusters. The large clusters likely represent trans-Golgi network stores and the smaller clusters endosomal stores and GLUT4 storage vesicles (GSVs). Density of GLUT4 clusters was higher at the fibre periphery especially in perinuclear regions. A less dense punctate distribution was seen in the rest of the muscle fibre. Total GLUT4 fluor...

Journal of Orthopaedic Nursing, 2005

Telecommunications Policy, 1979

The authors discuss the characteristics and benefits of network information services (NIS), which... more The authors discuss the characteristics and benefits of network information services (NIS), which are developing into an important new industry likely to have profound effects on society. Many of the services and possible applications are described. Three scenarios are analysed, in which the future of the industry may be directed by technology, the market, and policy issues. It is concluded

Physiological Entomology, 1985

Molecular Pharmacology, 2007

P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibit... more P2X 7 receptors are distinct from other ATP-gated P2X receptors in that they are potently inhibited by submicromolar concentrations of zinc and copper. The molecular basis for the strong functional inhibition by zinc and copper at this purinergic ionotropic receptor is controversial. We hypothesized that it involves a direct interaction of zinc and copper with residues in the ectodomain of the P2X 7 receptor. Fourteen potential metal interacting residues are conserved in the ectodomain of all mammalian P2X 7 receptors, none of which is homologous to previously identified sites in other P2X receptors shown to be important for functional potentiation by zinc. We introduced alanine substitutions into each of these residues, expressed wild-type and mutated receptors in human embryonic kidney 293 cells, and recorded resulting ATP and BzATP-evoked membrane currents. Agonist concentration-response curves were similar for all 12 functional mutant receptors. Alanine substitution at His 62 or Asp 197 strongly attenuated both zinc and copper inhibition, and the double mutant [H62A/D197A] mutant receptor was virtually insensitive to inhibition by zinc or copper. Thus, we conclude that zinc and copper inhibition is due to a direct interaction of these divalent cations with ectodomain residues of the P2X 7 receptor, primarily involving combined interaction with His 62 and Asp 197 residues. This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (L.-H.J., A.S.), the Royal Society (H.-J. M., L.-H.J.), a UK Overseas Research Scholarship (R.X.), and a BBSRC doctoral training grant (H.B.).

Journal of Psychiatric Research, 2010

Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorp... more Genetic linkage studies have previously identified many single non-synonymous nucleotide polymorphisms (SNPs) in the human P2RX7 gene in individuals with affective mood disorders. The P2RX7 gene encodes the P2X 7 receptor (P2X 7 R) that operates as an ATP-activated Ca 2+ -permeable cationic channel and induces formation of a large pore, the two functional properties that are critical for the physiological and pathological roles of the receptor. The current knowledge regarding the effects of SNPs on the P2X 7 R functional properties, which is indispensable to help elucidate the disease mechanism, is limited. In this study, we introduced by site-directed mutagenesis twelve SNP mutations in the human P2X 7 receptor that were previously identified in or associated with affective mood disorders, expressed the resultant mutants in human embryonic kidney cells, and characterized their functional properties by electrophysiology. All mutations except Q460R gave rise to profound effects on the P2X 7 R function. G150R, E186K and I568N conferred complete loss of function. V76A, R117W, L191P, T357S and E496A resulted in strong impairment of, whereas H155Y and A348T caused significant increase in, both ATP-activated ion channel function and pore formation. Q521H reduced the receptor's sensitivity to extracellular Ca 2+ inhibition. An atomic structure model of the human P2X 7 R, based on the crystal structure of the zebrafish P2X 4 receptor, suggests that the SNP mutational effects may result from changes in subunit interaction, agonist binding and/or channel gating. These results provide essential knowledge for a better understanding of the relationships between human P2RX7 SNPs and associated pathologies as well as the receptor structure-function relationships.

Journal of Biological Chemistry, 2011

Short title: Expression and function of P2X 7 receptors P2X 7 receptors are important in mediatin... more Short title: Expression and function of P2X 7 receptors P2X 7 receptors are important in mediating the physiological functions of extracellular ATP, and altered receptor expression and function have a causative role in the disease pathogenesis. Here we investigated the mechanisms determining the P2X 7 receptor function by following two human SNP mutations that replace H155 and A348 in the hP2X 7 receptor with the corresponding residues Y155 and T348 in the rP2X 7 receptor. H155Y and A348T mutations in the hP2X 7 receptor increased ATP-induced currents, whereas the reciprocal mutations Y155H and T348A in the rP2X 7 receptor caused the opposite effects. Such functional switch is a compelling indication that these residues are critical for the P2X 7 receptor function. Additional mutations of H155 and A348 in the hP2X 7 receptor to residues with diverse side-chains reveal different dependence on the side-chain properties, supporting specificity of these two residues. Substitutions of the residues surrounding H155 and A348 in the hP2X 7 receptor with the equivalent ones in the rP2X 7 receptor also affected ATP-induced currents, but were not fully reminiscent of the H155Y and A348T effects. Immunofluorescent imaging and biotin-labelling assays showed that H155Y in the hP2X 7 receptor increased, whereas Y155H in the rP2X 7 receptor decreased, cell surface expression. Such contrasting effects were not obvious with the reciprocal mutations of residue 348. Taken together, our results suggest that residues at positions 155 and 348 contribute to P2X 7 receptor function via determining the surface expression and the single channel function respectively. Such interpretations are consistent with the location of the residues in the structural model of the hP2X 7 receptor.