Search Results - (Author, Cooperation:C. Guy)

2016-04-21

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

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Animals ; Antigen-Antibody Complex/metabolism ; Autoantibodies/blood ; *Autophagy/genetics ; Cytokines/biosynthesis/blood ; Inflammation/blood/genetics/*pathology ; Interleukin-10/biosynthesis ; Kidney/metabolism/pathology ; Lupus Erythematosus, Systemic/blood/genetics/*immunology/*pathology ; Male ; Mice ; Microtubule-Associated Proteins/metabolism ; Phagocytes/cytology/physiology ; Phagosomes/physiology

2013-08-06

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Autoimmunity/immunology ; Cell Survival ; Colitis/immunology ; Female ; Forkhead Transcription Factors/metabolism ; HEK293 Cells ; Homeostasis/immunology ; Humans ; Immune Tolerance/immunology ; Immunological Synapses ; Lymphocytes, Tumor-Infiltrating/cytology/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasms/genetics/immunology/pathology ; Neuropilin-1/deficiency/*metabolism ; PTEN Phosphohydrolase/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Semaphorins/*metabolism ; Signal Transduction ; T-Lymphocytes, Regulatory/cytology/*immunology/*metabolism ; TOR Serine-Threonine Kinases/metabolism

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2014

Ganzheitlichkeit ; Motorische Leistungsfähigkeit ; Förderung ; Aktivität ; Curriculum ; Bewegung (Motorische) ; Sportpädagogik ; Sportunterricht ; Konzeption ; Lebensführung ; Situationsanalyse ; Zielsetzung ; Australien ; Deutschland ; Großbritannien ; Kanada ; USA

International journal of physical education, Bd. 51 (2014) H. 2, S. 2-19, 0341-8685

English

2018-01-24

American Chemical Society (ACS)

0002-7863

1520-5126

Chemistry and Pharmacology

2018-06-05

BMJ Publishing

2044-6055

Medicine

Open access, Paediatrics

2018-02-01

American Association for the Advancement of Science (AAAS)

2375-2548

Natural Sciences in General

2018-08-22

American Chemical Society (ACS)

0002-7863

1520-5126

Chemistry and Pharmacology

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Co-localization of activated microglia and damaged neurones seen in brain injury suggests microglia-induced neurodegeneration. Activated microglia release two potential neurotoxins, excitatory amino acids and nitric oxide (NO), but their contribution to mechanisms of injury is poorly understood. Using co-cultures of rat microglia and embryonic cortical neurones, we show that inducible NO synthase (iNOS)-derived NO aloneis responsible for neuronal death from interferon γ(IFNγ) +lipopolysaccharide (LPS)-activated microglia. Neurones remain sensitive to NO irrespective of maturation state but, whereas blocking NMDA receptor activation with MK801 has no effect on NO-mediated toxicity to immature neurones, MK801 rescues 60–70% of neurones matured in culture for 12 days. Neuronal expression of NMDA receptors increases with maturation in culture, accounting for increased susceptibility to excitotoxins seen in more mature cultures. We show that MK801 delays the death of more mature neurones caused by the NO-donor DETA/NO indicating that NO elicits an excitotoxic mechanism, most likely through neuronal glutamate release. Thus, similar concentrations of nitric oxide cause neuronal death by two distinct mechanisms: NO acts directly upon immature neurones but indirectly, via NMDA receptors, on more mature neurones. Our results therefore extend existing evidence for NO-mediated toxicity and show a complex interaction between inflammatory and excitotoxic mechanisms of injury in mature neurones.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Previous reports have demonstrated the presence of functional thromboxane A2 (TP) receptors in astrocytes and oligodendrocytes. In these experiments, the presence and function of TP receptors in primary rat Schwann cells (rSC) and a neurofibrosarcoma-derived human Schwann cell line (T265) was investigated. Immunocytochemical and immunoblot analyses using polyclonal anti-TP receptor antibodies demonstrate that both cell types express TP receptors. Treatment with the stable thromboxane A2 mimetic U46619 (10 µm) did not stimulate intracellular calcium mobilization in rSC, whereas T265 cells demonstrated a calcium response that was inhibited by prior treatment with TP receptor antagonists. U46619 also stimulated CREB phosphorylation on Ser133 in T265 cells and, to a lesser extent, in rSC. To identify potential mechanisms of CREB phosphorylation in rSC, we monitored intracellular cAMP levels following U46619 stimulation. Elevated levels of cAMP were detected in both rSC (20-fold) and T265 (15-fold) cells. These results demonstrate that TP receptor activation specifically stimulates CREB phosphorylation in T265 cells, possibly by a calcium- and/or cAMP-dependent mechanism. In contrast, TP receptor activation in rSC stimulates increases in cAMP and CREB phosphorylation but does not elicit changes in intracellular calcium.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Nitric oxide (NO) can trigger either necrotic or apoptotic cell death. We have used PC12 cells to investigate the extent to which NO-induced cell death is mediated by mitochondria. Addition of NO donors, 1 mMS-nitroso-N-acetyl-DL-penicillamine (SNAP) or 1 mM diethylenetriamine-NO adduct (NOC-18), to PC12 cells resulted in a steady-state level of 1-3 μM NO, rapid and almost complete inhibition of cellular respiration (within 1 min), and a rapid decrease in mitochondrial membrane potential within the cells. A 24-h incubation of PC12 cells with NO donors (SNAP or NOC-18) or specific inhibitors of mitochondrial respiration (myxothiazol, rotenone, or azide), in the absence of glucose, caused total ATP depletion and resulted in 80-100% necrosis. The presence of glucose almost completely prevented the decrease in ATP level and the increase in necrosis induced by the NO donors or mitochondrial inhibitors, suggesting that the NO-induced necrosis in the absence of glucose was due to the inhibition of mitochondrial respiration and subsequent ATP depletion. However, in the presence of glucose, NO donors and mitochondrial inhibitors induced apoptosis of PC12 cells as determined by nuclear morphology. The presence of apoptotic cells was prevented completely by benzyloxycarbonyl-Val-Ala-fluoromethyl ketone (a nonspecific caspase inhibitor), indicating that apoptosis was mediated by caspase activation. Indeed, both NO donors and mitochondrial inhibitors in PC12 cells caused the activation of caspase-3- and caspase-3-processing-like proteases. Caspase-1 activity was not activated. Cyclosporin A (an inhibitor of the mitochondrial permeability transition pore) decreased the activity of caspase-3- and caspase-3-processing-like proteases after treatment with NO donors, but was not effective in the case of the mitochondrial inhibitors. The activation of caspases was accompanied by the release of cytochrome c from mitochondria into the cytosol, which was partially prevented by cyclosporin A in the case of NO donors. These results indicate that NO donors (SNAP or NOC-18) may trigger apoptosis in PC12 cells partially mediated by opening the mitochondrial permeability transition pores, release of cytochrome c, and subsequent caspase activation. NO-induced apoptosis is blocked completely in the absence of glucose, probably due to the lack of ATP. Our findings suggest that mitochondria may be involved in both types of cell death induced by NO donors: necrosis by respiratory inhibition and apoptosis by opening the permeability transition pore. Further, our results indicate that the mode of cell death (necrosis versus apoptosis) induced by either NO or mitochondrial inhibitors depends critically on the glycolytic capacity of the cell.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: We determined the ability of pathological levels of nitric oxide (NO) to cause glutamate release from isolated rat brain nerve terminals using a fluorometric assay. It was found that NO (0.7 and 2 µM) produced (4 and 10 nmol/mg of synaptosomal protein) Ca2+-independent glutamate release from synaptosomes (after 1 min of exposure). Spermine/NO complex (spermine NONOate; a slow NO donor) and potassium cyanide (an inhibitor of cytochrome oxidase) also caused Ca2+-independent glutamate release. Preincubation of synaptosomes with 5 µM 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase) had no effect on NO-induced Ca2+-independent glutamate release. Ca2+-independent glutamate release produced by NO was greater in a low-oxygen medium. NO, spermine NONOate, and potassium cyanide inhibited synaptosomal respiration with a similar order of potency with respect to their ability to cause glutamate release. Because NO has been shown previously to inhibit reversibly cytochrome oxidase in competition with oxygen, our findings in this study suggest that NO (and cyanide) causes glutamate release following inhibition of mitochondrial respiration at the level of cytochrome oxidase. Thus, elevated NO production leading to mitochondrial dysfunction, glutamate release, and excitotoxicity may contribute to neuronal death in neurological diseases.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

We have investigated the mechanism by which nitric oxide (NO) induces the death of mouse astrocytes. We show that NO (from donor diethylenetriamine-NO adduct) induces death with several features of apoptosis, including chromatin condensation, phosphatidylserine exposure on the outer leaflet of the plasma membrane, Bax translocation to the mitochondria and cytochrome c release, but no caspase activation or nuclear fragmentation is observed. Nitric oxide also elevates p53 expression, causing a concomitant increase in p53 serine 18 phosphorylation and p53 translocation from the cytoplasm to the nucleus. Activation of Bax and p53 is important for NO-induced apoptosis-like cell death because Bax- or p53-deficient astrocytes are much more resistant than wild-type cells to the same NO treatment. We further demonstrate that LY294002-sensitive kinases are responsible for controlling serine 18 phosphorylation of p53, thereby regulating the pro-apoptotic activity of p53 in astrocytes. While apoptosis is suppressed in the presence of LY294002, however, death by necrosis is increased, suggesting that LY294002-sensitive kinases additionally suppress a latent necrotic response to NO. We conclude that NO-induced death in astrocytes is mediated by p53- and Bax-dependent mechanisms, although full manifestation of apoptosis is aborted by concomitant inhibition of caspase activation. More generally, our data suggest that apoptotic mediators should be evaluated as the cause of cell death even in cases where a full apoptotic phenotype is lacking.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Thromboxane A2 receptors (TP) were previously localized to discrete regions in the rat brain on myelinated fiber tracts and oligodendrocytes (OLGs). The present studies extended these findings and investigated the effects of TP signaling on cell proliferation, survival, and gene expression in OLG progenitor cells (OPCs) and OLGs. It was found that the TP agonist, U46619 stimulated the proliferation of OPCs and promoted the survival of mature OLGs. Examination of the early gene expression events involved in OPC proliferation, revealed that c-fos expression was substantially increased by U46619 stimulation. Treatment of OPCs or OLGs with U46619 caused activation of the mitogen-activated protein kinases (MAPK) ERK 1/2. In OPCs this activation was blocked by inhibition of src. However, in OLGs this phosphorylation was not only blocked by inhibition of src but also by inhibition of protein kinase C (PKC). Furthermore, U46619 was found to increase CREB phosphorylation in both OPCs and OLGs. Similar to ERK 1/2 activation, there was a divergence in the mechanism of the TP-mediated CREB response for each cell type. Specifically, U46619 activation was attenuated by src and protein kinase A (PKA) inhibition in OPCs, whereas in OLGs this effect was blocked by inhibition of src, PKA as well as by inhibition of PKC. Collectively, these results provide the first demonstration that TP-activated nuclear signaling events are involved in the proliferation of OPCs, the survival of mature OLGs, and the stimulation of gene expression.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

In this study we investigated the mechanisms of neuronal cell death induced by lipoteichoic acid (LTA) and muramyl dipeptide (MDP) from Gram-positive bacterial cell walls using primary cultures of rat cerebellum granule cells (CGCs) and rat cortical glial cells (astrocytes and microglia). LTA (± MDP) from Staphylococcus aureus induced a strong inflammatory response of both types of glial cells (release of interleukin-1β, tumour necrosis factor-α and nitric oxide). The death of CGCs was caused by activated glia because in the absence of glia (treatment with 7.5 µm cytosine-d-arabinoside to inhibit non-neuronal cell proliferation) LTA + MDP did not cause significant cell death (less than 20%). In addition, staining with rhodamine-labelled LTA confirmed that LTA was bound only to microglia and astrocytes (not neurones). Neuronal cell death induced by LTA (± MDP)-activated glia was partially blocked by an inducible nitric oxide synthase inhibitor (1400 W; 100 µm), and completely blocked by a superoxide dismutase mimetic [manganese (III) tetrakis (4-benzoic acid)porphyrin chloride; 50 µm] and a peroxynitrite scavenger [5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III); 100 µm] suggesting that nitric oxide and peroxynitrite contributed to LTA-induced cell death. Moreover, neuronal cell death was inhibited by selective inhibitors of caspase-3 (z-DEVD-fmk; 50 µm) and caspase-8 (z-Ile-Glu(O-Me)-Thr-Asp(O-Me) fluoromethyl ketone; 50 µm) indicating that they were involved in LTA-induced neuronal cell death.

Electronic Resource

1469-8986

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Psychology

A novel noise source whose fundamental frequencies are congruent with typical physiological events is presented. Design criteria are given for using it to simulate the waking and sleeping EEG and suggestions for using it as a general random event programmer.

Electronic Resource

1469-8986

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Psychology

A circuit is described which generates microvolt signals for calibrating or testing differential amplifiers. All parameters of the waveform can be easily adjusted through ranges normal to low level biological signals.

Electronic Resource

1477-9730

Blackwell Publishing Journal Backfiles 1879-2005

Architecture, Civil Engineering, Surveying

This paper describes work undertaken to measure deformation of a pavement within the Newcastle University Rolling Load Facility (NUROLF). Precise three dimensional measurements of the pavement have been produced from stereo-imagery taken with diVerent cameras, using both analytical and digital photogrammetric instrumentation. The photogrammetric measurements, and those from the existing system consisting of an array of linear voltage displacement transducers, have been compared with measurements produced using a digital level. Encouraging results have been achieved and photogrammetry has been shown to be capable of producing a similar accuracy to the existing system. There are many advantages associated with a photogrammetric survey but attempts to establish a permanent, automated photogrammetric system for the rolling load facility at a reasonable cost have so far been unsuccessful. It is anticipated that, with the falling cost of high resolution digital sensors, such a system will soon be possible.

Electronic Resource

1365-3040

Blackwell Publishing Journal Backfiles 1879-2005

Biology

Abstract Seasonal cold-acclimation patterns and the effects of photoperiod and temperature on cold-hardiness of Hibiscus rosa-sinensis L. and Hibiscus syriacus L. were determined. Field-grown H. rosasinensis consistently failed to survive freezing at - 2°C. Two genotypes of field- and container-grown H. syriacus initiated cold-acclimation in mid September, in response to decreasing daylength, and continued to an ultimate midwinter hardiness level of - 27°C in early February. Controlled environment experiments using combinations of short days (SD) and cool day/night temperatures were unable to induce even minimal cold acclimation of H. rosasinensis. In controlled environments, H. syriacus attained a moderate amount of cold tolerance at warm temperatures and long days (LD). Low night temperature combined with LD, warm day produced the same degree of cold-acclimation as the SD treatments. While not essential, SD enhanced H. syriacus cold-acclimation in controlled environments. A - 5°C frost treatment of intact plants did not enhance cold-hardiness of H. syriacus.

Electronic Resource

1365-3040

Blackwell Publishing Journal Backfiles 1879-2005

Biology

Abstract Cold-acclimated stems of red-osier dogwood (Cornus sericea L.) were sampled in midwinter and early spring and subjected to the following low temperature treatments: (a)0 →−40 → 0°C; (b) 0 →−40 →− 196 → 0°C; (c) 0 →−40 →−196 →−269 →−196 → 0°C; (d) 0 →−40 →−269 →−196 → 0°C; (e) 0 →−196 → 0°C; (f) 0 →−269 →−196 →0°C. The cortical parenchyma cells of the outer stem layers survived exposure to −269°C when pre-frozen to −40°C and either transferred directly to −269°C or to −196°C and then to −269°C (treatments c and d). Acclimated stems transferred to a greenhouse (22°C) 2 weeks prior to the low temperature treatments deacclimated and were not able to survive freezing to −10°C. Cortical cells of stem samples taken in March, near the time when dogwood naturally deacclimates, survived −196°C (treatment b), but not −269°C (treatment cord). Thus, the freezing tolerance of dogwood varies seasonally from near −10°C to below −269°C.

Electronic Resource