Adenine, guanine and pyridine nucleotides in blood during physical exercise and restitution in healthy subjects

Maximal physical exertion is accompanied by increased degradation of purine nucleotides in muscles with the products of purine catabolism accumulating in the plasma. Thanks to membrane transporters, these products remain in an equilibrium between the plasma and red blood cells where they may serve as substrates in salvage reactions, contributing to an increase in the concentrations of purine nucleotides. In this study, we measured the concentrations of adenine nucleotides (ATP, ADP, AMP), inosine nucleotides (IMP), guanine nucleotides (GTP, GDP, GMP), and also pyridine nucleotides (NAD, NADP) in red blood cells immediately after standardized physical effort with increasing intensity, and at the 30th min of rest. We also examined the effect of muscular exercise on adenylate (guanylate) energy charge—AEC (GEC), and on the concentration of nucleosides (guanosine, inosine, adenosine) and hypoxanthine. We have shown in this study that a standardized physical exercise with increasing intensity leads to an increase in IMP concentration in red blood cells immediately after the exercise, which with a significant increase in Hyp concentration in the blood suggests that Hyp was included in the IMP pool. Restitution is accompanied by an increase in the ATP/ADP and ADP/AMP ratios, which indicates an increase in the phosphorylation of AMP and ADP to ATP. Physical effort applied in this study did not lead to changes in the concentrations of guanine and pyridine nucleotides in red blood cells

The X-Ray Forest: A New Prediction of Hierarchical Structure Formation Models

We use numerical simulations of structure formation in a Cold Dark Matter model to predict the absorption lines in the soft X-rays produced by heavy elements in the shock-heated intergalactic medium at low redshift. The simulation incorporates a model for metal production in galaxies and the subsequent dispersion of the metals to the intergalactic medium. We analyze in particular absorption lines produced by oxygen, and calculate the ionization stage taking into account the observed X-ray background at the present time. We find that oxygen is fully ionized by the X-ray background in low-density voids, and is mostly in the form of OVII and OVIII in the sheets and filamentary regions. Strong absorption lines of OVII and OVIII with equivalent widths W ~ 100 km/s are produced in filamentary regions of overdensities ~ 100 and temperatures ~ 10^6 K, located in the outskirts of groups and clusters of galaxies. The OVII line at E = 574 eV is generally the strongest one in these systems. Our model predicts that any X-ray source (such as a quasar) should typically show about one OVII absorption line with W > 100 km/s in the interval from z=0 to z=0.3. These lines could be detected with the upcoming generation of X-ray telescopes, and their origin in intervening systems could be confirmed by the association with groups of galaxies and X-ray emitting halos near the line-of-sight at the same redshift. The hot intergalactic medium may be one of the main reservoirs of baryons in the present universe, and the heavy element X-ray absorption lines offer a promising possibility of detecting this new component in the near future.Comment: Accepted by ApJ. The full resolution color GIF version of Fig.2 is include

Ischemic Preconditioning Improves Microvascular Endothelial Function in Remote Vasculature by Enhanced Prostacyclin Production.

BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. METHODS AND RESULTS A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand-grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (P<0.05) the remote vasodilator response to intra-arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6-fold increase (P<0.05) in femoral venous plasma prostacyclin levels and with a transient increase (P<0.05) in arterial plasma levels of brain-derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand-grip exercise did not influence remote microvascular function. CONCLUSIONS These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral-mediated potentiation of prostacyclin formation

The impact of acute remote ischaemic preconditioning on cerebrovascular function

Purpose: Remote ischaemic preconditioning (RIPC) refers to the protection conferred to tissues and organs via brief periods of ischaemia in a remote vascular territory, including the brain. Recent studies in humans report that RIPC provides neuroprotection against recurrent (ischaemic) stroke. To better understand the ability of RIPC to improve brain health, the present study explored the potential for RIPC to acutely improve cerebrovascular function. Methods: Eleven young healthy (Females n=6, Age; 28.1±3.7yrs) and 9 older individuals (Females n=4, Age 52.5±6.7yrs) at increased risk for stroke (cardiovascular disease risk factors) underwent assessments of cerebrovascular function, assessed by carbon dioxide (CO2) reactivity and cerebral autoregulation during normo- and hypercapnia (5%CO2) following 40mins of bilateral arm RIPC or a sham condition. Squat-to-stand manoeuvres were performed to induce changes in blood pressure to assess cerebral autoregulation (0.10 Hz) and analysed via transfer function. Results: We found no change in middle cerebral artery velocity or blood pressure across 40mins of RIPC. Application of RIPC resulted in no change in CO2 reactivity slopes (sham vs RIPC, 1.97±0.88 vs 2.06±0.69 cm/s/mmHg P=0.61) or parameters of cerebral autoregulation during normocapnia (sham vs RIPC, normalised gain%, 1.27±0.25 vs 1.22±0.35, P=0.46). Conclusion: This study demonstrates that a single bout of RIPC does not influence cerebrovascular function acutely in healthy individuals, or those at increased cardiovascular risk. Given the previously reported protective role of RIPC on stroke recurrence in humans, it is possible that repeated bouts of RIPC may be necessary in order to impart beneficial effects on cerebrovascular function

Implicit media frames: Automated analysis of public debate on artificial sweeteners

The framing of issues in the mass media plays a crucial role in the public understanding of science and technology. This article contributes to research concerned with diachronic analysis of media frames by making an analytical distinction between implicit and explicit media frames, and by introducing an automated method for analysing diachronic changes of implicit frames. In particular, we apply a semantic maps method to a case study on the newspaper debate about artificial sweeteners, published in The New York Times (NYT) between 1980 and 2006. Our results show that the analysis of semantic changes enables us to filter out the dynamics of implicit frames, and to detect emerging metaphors in public debates. Theoretically, we discuss the relation between implicit frames in public debates and codification of information in scientific discourses, and suggest further avenues for research interested in the automated analysis of frame changes and trends in public debates

Perpendicular momentum injection by lower hybrid wave in a tokamak

The injection of lower hybrid waves for current drive into a tokamak affects the profile of intrinsic rotation. In this article, the momentum deposition by the lower hybrid wave on the electrons is studied. Due to the increase in the poloidal momentum of the wave as it propagates into the tokamak, the parallel momentum of the wave increases considerably. The change of the perpendicular momentum of the wave is such that the toroidal angular momentum of the wave is conserved. If the perpendicular momentum transfer via electron Landau damping is ignored, the transfer of the toroidal angular momentum to the plasma will be larger than the injected toroidal angular momentum. A proper quasilinear treatment proves that both perpendicular and parallel momentum are transferred to the electrons. The toroidal angular momentum of the electrons is then transferred to the ions via different mechanisms for the parallel and perpendicular momentum. The perpendicular momentum is transferred to ions through an outward radial electron pinch, while the parallel momentum is transferred through collisions.Comment: 22 pages, 4 figure

Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state

Exponential Stellar Disks in Low Surface Brightness Galaxies: A Critical Test of Viscous Evolution

Viscous redistribution of mass in Milky Way-type galactic disks is an appealing way of generating an exponential stellar profile over many scale lengths, almost independent of initial conditions, requiring only that the viscous timescale and star formation timescale are approximately equal. However, galaxies with solid-body rotation curves cannot undergo viscous evolution. Low surface brightness (LSB) galaxies have exponential surface brightness profiles, yet have slowly rising, nearly solid-body, rotation curves. Because of this, viscous evolution may be inefficient in LSB galaxies: the exponential profiles, instead would give important insight into initial conditions for galaxy disk formation. Using star formation laws from the literature, and tuning the efficiency of viscous processes to reproduce an exponential stellar profile in Milky Way-type galaxies, I test the role of viscous evolution in LSB galaxies. Under the conservative and not unreasonable condition that LSB galaxies are gravitationally unstable for at least a part of their lives, I find that it is impossible to rule out a significant role for viscous evolution. This type of model still offers an attractive way of producing exponential disks, even in LSB galaxies with slowly-rising rotation curves

Seven day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study

Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. Methods: Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4x5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. Results: For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95%CI: 0.69 to 3.80; P=0.09) and 0.23 %cm s-1 %.mmHg-1mm Hg/% (-0.12, 0.59; P=0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P&lt;0.05) between-group difference in a randomised controlled trial. Conclusion: We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM