Simple anthropometric and physical performance tests to predict maximal box-lifting ability

Box-lifting ability is an important characteristic of military personnel. The purpose of this paper was to determine the usefulness of the upright row free weight exercise, and simple anthropometric tests, to predict maximal box-lifting performance that simulates the loading of military supply vehicles. Two groups of adults performed maximal box lifts to 1.4 m (study one) and 1.7 m (study two) respectively. All subjects were also tested for upright row 1-repetition maximum (1RM) strength, body mass, height and body composition. In study one, a remarkably good prediction of maximal box-lift performance to 1.4 m (42 ? 12 kg) was obtained from a regression equation including the variables body mass, body composition and upright row 1RM. Approximately 95% of the variation in 1.4 m box-lifting performance could be accounted for. In contrast, in study two, only 80% of the variation in 1.7 m box-lifting performance (51 ? 15 kg) could be accounted for by the best predictor equation. Upright row 1RM strength appears to be a useful tool in the prediction of box-lifting ability to approximately chest height for most adults, probably due to a close match between the muscle groups and contraction modes required during both tasks. Military or other organizations could use the data reported here to substitute simple anthropometry and a 1RM test of strength and for the direct assessment of 1.4 m box-lifting performance

The PPARGC1A Gly482Ser polymorphism is associated with elite long-distance running performance

Success in long-distance running relies on multiple factors including oxygen utilisation and lactate metabolism, and genetic associations with athlete status suggest elite competitors are heritably predisposed to superior performance. The Gly allele of the PPARGC1A Gly482Ser rs8192678 polymorphism has been associated with endurance athlete status and favourable aerobic training adaptations. However, the association of this polymorphism with performance amongst long-distance runners remains unclear. Accordingly, this study investigated whether rs8192678 was associated with elite status and competitive performance of long-distance runners. Genomic DNA from 656 Caucasian participants including 288 long-distance runners (201 men, 87 women) and 368 non-athletes (285 men, 83 women) was analysed. Medians of the 10 best UK times (Top10) for 10 km, half-marathon and marathon races were calculated, with all included athletes having personal best (PB) performances within 20% of Top10 (this study’s definition of ‘elite’). Genotype and allele frequencies were compared between athletes and non-athletes, and athlete PB compared between genotypes. There were no differences in genotype frequency between athletes and non-athletes, but athlete Ser allele carriers were 2.5% faster than Gly/Gly homozygotes (p=0.030). This study demonstrates that performance differences between elite long-distance runners are associated with rs8192678 genotype, with the Ser allele appearing to enhance performance

Pulsed-source luminescence measurements using a computer-controlled spectrometer

Traditionally fluorescence and phosphorescence measurements are made on fluorescence spectrometers using a DC source such as a 150 Watt xenon lamp. Differentiation between the fast decaying fluorescence signal and the relatively long lived phosphorescence is temporally obtained using a mechanical phosphoroscope. By periodically interrupting the exciting light measurements are made at the instant of excitation (fluorescence) or during the periods of darkness (phosphorescence). [Continues.

Phospholipase A2 inhibitors protect against prion and Abeta mediated synapse degeneration.

BACKGROUND: An early event in the neuropathology of prion and Alzheimer's diseases is the loss of synapses and a corresponding reduction in the level of synaptophysin, a pre-synaptic membrane protein essential for neurotransmission. The molecular mechanisms involved in synapse degeneration in these diseases are poorly understood. In this study the process of synapse degeneration was investigated by measuring the synaptophysin content of cultured neurones incubated with the prion derived peptide (PrP82-146) or with Abeta1-42, a peptide thought to trigger pathogenesis in Alzheimer's disease. A pharmacological approach was used to screen cell signalling pathways involved in synapse degeneration. RESULTS: Pre-treatment with phospholipase A2 inhibitors (AACOCF3, MAFP and aristolochic acids) protected against synapse degeneration in cultured cortical and hippocampal neurones incubated with PrP82-146 or Abeta1-42. Synapse degeneration was also observed following the addition of a specific phospholipase A2 activating peptide (PLAP) and the addition of PrP82-146 or Abeta1-42 activated cytoplasmic phospholipase A2 within synapses. Activation of phospholipase A2 is the first step in the generation of platelet-activating factor (PAF) and PAF receptor antagonists (ginkgolide B, Hexa-PAF and CV6029) protected against synapse degeneration induced by PrP82-146, Abeta1-42 and PLAP. PAF facilitated the production of prostaglandin E2, which also caused synapse degeneration and pre-treatment with the prostanoid E receptor antagonist AH13205 protected against PrP82-146, Abeta1-42 and PAF induced synapse degeneration. CONCLUSIONS: Our results are consistent with the hypothesis that PrP82-146 and Abeta1-42trigger abnormal activation of cytoplasmic phospholipase A2 resident within synapses, resulting in elevated levels of PAF and prostaglandin E2that cause synapse degeneration. Inhibitors of this pathway that can cross the blood brain barrier may protect against the synapse degeneration seen during Alzheimer's or prion diseases.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Sialic Acid on the Glycosylphosphatidylinositol Anchor Regulates PrP-mediated Cell Signaling and Prion Formation.

The prion diseases occur following the conversion of the cellular prion protein (PrP(C)) into disease-related isoforms (PrP(Sc)). In this study, the role of the glycosylphosphatidylinositol (GPI) anchor attached to PrP(C) in prion formation was examined using a cell painting technique. PrP(Sc) formation in two prion-infected neuronal cell lines (ScGT1 and ScN2a cells) and in scrapie-infected primary cortical neurons was increased following the introduction of PrP(C). In contrast, PrP(C) containing a GPI anchor from which the sialic acid had been removed (desialylated PrP(C)) was not converted to PrP(Sc). Furthermore, the presence of desialylated PrP(C) inhibited the production of PrP(Sc) within prion-infected cortical neurons and ScGT1 and ScN2a cells. The membrane rafts surrounding desialylated PrP(C) contained greater amounts of sialylated gangliosides and cholesterol than membrane rafts surrounding PrP(C). Desialylated PrP(C) was less sensitive to cholesterol depletion than PrP(C) and was not released from cells by treatment with glimepiride. The presence of desialylated PrP(C) in neurons caused the dissociation of cytoplasmic phospholipase A2 from PrP-containing membrane rafts and reduced the activation of cytoplasmic phospholipase A2. These findings show that the sialic acid moiety of the GPI attached to PrP(C) modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrP(Sc) formation. These results suggest that pharmacological modification of GPI glycosylation might constitute a novel therapeutic approach to prion diseases.This work was supported by a grant from the European Commission FP6 “Neuroprion” – Network of Excellence. We also thank Dr Mourad Tayebi for supplying mAbs ICSM18 and ICSM35.This is the author accepted manuscript. The final version is available from ASBMB via http://dx.doi.org/10.1074/jbc.M115.67239

Inhibition of cytosolic Phospholipase A2 prevents prion peptide-induced neuronal damage and co-localisation with Beta III Tubulin.

BACKGROUND: Activation of phospholipase A2 (PLA2) and the subsequent metabolism of arachidonic acid (AA) to prostaglandins have been shown to play an important role in neuronal death in neurodegenerative disease. Here we report the effects of the prion peptide fragment HuPrP106-126 on the PLA2 cascade in primary cortical neurons and translocation of cPLA2 to neurites. RESULTS: Exposure of primary cortical neurons to HuPrP106-126 increased the levels of phosphorylated cPLA2 and caused phosphorylated cPLA2 to relocate from the cell body to the cellular neurite in a PrP-dependent manner, a previously unreported observation. HuPrP106-126 also induced significant AA release, an indicator of cPLA2 activation; this preceded synapse damage and subsequent cellular death. The novel translocation of p-cPLA2 postulated the potential for exposure to HuPrP106-126 to result in a re-arrangement of the cellular cytoskeleton. However p-cPLA2 did not colocalise significantly with F-actin, intermediate filaments, or microtubule-associated proteins. Conversely, p-cPLA2 did significantly colocalise with the cytoskeletal protein beta III tubulin. Pre-treatment with the PLA2 inhibitor, palmitoyl trifluoromethyl ketone (PACOCF3) reduced cPLA2 activation, AA release and damage to the neuronal synapse. Furthermore, PACOCF3 reduced expression of p-cPLA2 in neurites and inhibited colocalisation with beta III tubulin, resulting in protection against PrP-induced cell death. CONCLUSIONS: Collectively, these findings suggest that cPLA2 plays a vital role in the action of HuPrP106-126 and that the colocalisation of p-cPLA2 with beta III tubulin could be central to the progress of neurodegeneration caused by prion peptides. Further work is needed to define exactly how PLA2 inhibitors protect neurons from peptide-induced toxicity and how this relates to intracellular structural changes occurring in neurodegeneration.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Ginkgolide B inhibits the neurotoxicity of prions or amyloid-β(1-42)

BACKGROUND: Neuronal loss in Alzheimer's or prion diseases is preceded by the accumulation of fibrillar aggregates of toxic proteins (amyloid-β(1-42 )or the prion protein). Since some epidemiological studies have demonstrated that the EGb 761 extract, from the leaves of the Ginkgo biloba tree, has a beneficial effect on Alzheimer's disease, the effect of some of the major components of the EGb 761 extract on neuronal responses to amyloid-β(1-42), or to a synthetic miniprion (sPrP106), were investigated. METHODS: Components of the EGb 761 extract were tested in 2 models of neurodegeneration. SH-SY5Y neuroblastoma cells were pre-treated with ginkgolides A or B, quercetin or myricetin, and incubated with amyloid-β(1-42), sPrP106, or other neurotoxins. After 24 hours neuronal survival and the production of prostaglandin E(2 )that is closely associated with neuronal death was measured. In primary cortical neurons apoptosis (caspase-3) in response to amyloid-β(1-42 )or sPrP106 was measured, and in co-cultures the effects of the ginkgolides on the killing of amyloid-β(1-42 )or sPrP106 damaged neurons by microglia was tested. RESULTS: Neurons treated with ginkgolides A or B were resistant to amyloid-β(1-42 )or sPrP106. Ginkgolide-treated cells were also resistant to platelet activating factor or arachidonic acid, but remained susceptible to hydrogen peroxide or staurosporine. The ginkgolides reduced the production of prostaglandin E(2 )in response to amyloid-β(1-42 )or sPrP106. In primary cortical neurons, the ginkgolides reduced caspase-3 responses to amyloid-β(1-42 )or sPrP106, and in co-culture studies the ginkgolides reduced the killing of amyloid-β(1-42 )or sPrP106 damaged neurons by microglia. CONCLUSION: Nanomolar concentrations of the ginkgolides protect neurons against the otherwise toxic effects of amyloid-β(1-42 )or sPrP106. The ginkgolides also prevented the neurotoxicity of platelet activating factor and reduced the production of prostaglandin E(2 )in response to platelet activating factor, amyloid-β(1-42 )or sPrP106. These results are compatible with prior reports that ginkgolides inhibit platelet-activating factor, and that platelet-activating factor antagonists block the toxicity of amyloid-β(1-42 )or sPrP106. The results presented here suggest that platelet-activating factor antagonists such as the ginkgolides may be relevant treatments for prion or Alzheimer's diseases

Cholesterol synthesis inhibitors protect against platelet-activating factor-induced neuronal damage

BACKGROUND: Platelet-activating factor (PAF) is implicated in the neuronal damage that accompanies ischemia, prion disease and Alzheimer's disease (AD). Since some epidemiological studies demonstrate that statins, drugs that reduce cholesterol synthesis, have a beneficial effect on mild AD, we examined the effects of two cholesterol synthesis inhibitors on neuronal responses to PAF. METHODS: Primary cortical neurons were treated with cholesterol synthesis inhibitors (simvastatin or squalestatin) prior to incubation with different neurotoxins. The effects of these drugs on neuronal cholesterol levels and neuronal survival were measured. Immunoblots were used to determine the effects of simvastatin or squalestatin on the distribution of the PAF receptor and an enzyme linked immunoassay was used to quantify the amounts of PAF receptor. RESULTS: PAF killed primary neurons in a dose-dependent manner. Pre-treatment with simvastatin or squalestatin reduced neuronal cholesterol and increased the survival of PAF-treated neurons. Neuronal survival was increased 50% by 100 nM simvastatin, or 20 nM squalestatin. The addition of mevalonate restored cholesterol levels, and reversed the protective effect of simvastatin. Simvastatin or squalestatin did not affect the amounts of the PAF receptor but did cause it to disperse from within lipid rafts. CONCLUSION: Treatment of neurons with cholesterol synthesis inhibitors including simvastatin and squalestatin protected neurons against PAF. Treatment caused a percentage of the PAF receptors to disperse from cholesterol-sensitive domains. These results raise the possibility that the effects of statins on neurodegenerative disease are, at least in part, due to desensitisation of neurons to PAF

Arithmeticity of Orbifold Generalised Triangle Groups

Maclachlan and Martin have proved that only finitely many arithmetic Kleinian groups can be generated by 2 elliptic elements, and have classified these groups in the non-cocompact case. Here, we investigate the cocompact case, restricting to a class of generalisedtrianglegroups considered by Jones and Reid which arise as the fundamental groups of hyperbolic 3-dimensional orbifolds. We obtain 21 arithmetic groups and provide a description of the corresponding orbifolds

British scholarship on Greek colonisation in context 1780-1990

This thesis examines British scholarly perceptions of Greek colonisation from the eighteenth century to the present. Beginning with a study of the ancient sources for Greek colonisation and the key themes which preoccupied ancient authors, the thesis proceeds to argue that, modifying recent interpretations of work from this age of empire, British scholarship did not, as a whole, simplistically distort ancient evidence so as to create a version of Greek colonisation which mirrored, in a self-congratulatory way, contemporary British experiences. We should therefore position this scholarship within its appropriate historical context (with special attention to politics, empire, colonisation, and perceptions of antiquity). In addition to enabling us to trace the impact of the great events of the modern era upon classical scholarship, in doing so we can also gain insight into the complexities, hopes, and anxieties which characterised British thinking about such themes as empire, colonisation, political freedom, and the place of Western civilisation in historical perspective