EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B

Wu HC, Chang CH, Peng HY, Chen GD, Lai CY, Hsieh MC, Lin TB. EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B. Am J Physiol Renal Physiol 300: F403-F411, 2011. First published December 8, 2010; doi:10.1152/ajprenal.00520.2010.-Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in pain-related neural plasticity at the spinal cord level have been identified. To test whether Src-family tyrosine kinase-dependent glutamatergic N-methyl-D-aspartate receptor NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate pelvic-urethra reflex potentiation, we recorded external urethra sphincter electromyogram reflex activity and analyzed protein expression in the lumbosacral (L(6)-S(2)) dorsal horn in response to intrathecal ephrinB2 injections. When compared with vehicle solution, exogenous ephrinB2 (5 mu g/rat it)-induced reflex potentiation, in associated with phosphorylation of EphB1/2, Src-family kinase, NR2B Y1336 and Y1472 tyrosine residues. Both intrathecal EphB1 and EphB2 immunoglobulin fusion protein (both 10 mu g/rat it) prevented ephrinB2-dependent reflex potentiation, as well as protein phosphorylation. Pretreatment with PP2 (50 mu M, 10 mu l it), an Src-family kinase antagonist, reversed the reflex potentiation, as well as Src kinase and NR2B phosphorylation. Together, these results suggest the ephrinB2-dependent EphBR activation, which subsequently provokes Src kinase-mediated N-methyl-D-aspartate receptor NR2B phosphorylation in the lumbosacral dorsal horn, is crucial for the induction of spinal reflex potentiation contributing to the development of visceral pain and/or hyperalgesia in the pelvic area

Grating and interferometric devices in POF

To date, much of the development work associated with polymer optical fibre (POF) applications has been aimed at exploiting the potential of the technology to provide low cost solutions. Here we argue that, in the sensing area at least, POF offers a number of other, more relevant advantages. In this paper we describe work on a range of devices based on photoinscribed gratings and on fibre interferometers, which are designed to take advantage of the unique properties of POF

Nicotine-activated descending facilitation on spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats

This study was conducted to investigate the possible neurotransmitter that activates the descending pathways coming from the dorsolateral pontine tegmentum (DPT) to modulate spinal pelvic-urethra reflex potentiation. External urethra sphincter electromyogram (EUSE) activity in response to test stimulation (TS, 1/30 Hz) and repetitive stimulation (RS, 1 Hz) on the pelvic afferent nerve of 63 anesthetized rats were recorded with or without microinjection of nicotinic cholinergic receptor (nAChR) agonists, ACh and nicotine, to the DPT. TS evoked a baseline reflex activity with a single action potential (1.00 +/- 0.00 spikes/stimulation, n = 40), whereas RS produced a long-lasting reflex potentiation (16.14 +/- 0.96 spikes/stimulation, n = 40) that was abolished by D-2-amino-5-phosphonovaleric acid (1.60 +/- 0.89 spikes/stimulation, n = 40) and was attenuated by 2,3-dihydroxy-6-nitro-7sulfamoyl-benzo (F) quinoxaline (7.10 +/- 0.84 spikes/stimulation, n = 40). ACh and nicotine microinjections to DPT both produced facilitation on the RS-induced reflex potentiation (23.57 +/- 2.23 and 28.29 +/- 2.36 spikes/stimulation, P = 0.01, n = 10 and 20, respectively). Pretreatment of selective nicotinic receptor antagonist, chlorisondamine, reversed the facilitation on RS-induced reflex potentiation caused by nicotine (19.41 +/- 1.21 spikes/stimulation, P = 0.01, n = 10) Intrathecal WAY-100635 and spinal transection at the T(1) level both abolished the facilitation on reflex potentiation resulting from the DPT nicotine injection (12.86 +/- 3.13 and 15.57 +/- 1.72 spikes/stimulation, P < 0.01, n = 10 each). Our findings suggest that activation of nAChR at DPT may modulate N-methyl-D-aspartic acid-dependent reflex potentiation via descending serotonergic neurotransmission. This descending modulation may have physiological/pathological relevance in the neural controls of urethral closure

Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats

The impact of acute anal stretch on the pelvic-urethra reflex potentiation was examined in urethane-anesthetized rats by recording the external urethra sphincter electromyogram activity evoked by the pelvic afferent stimulation. Test stimulation (1 stimulation/30 s) evoked a baseline reflex activity with a single action potential that was abolished by gallamine (5 mg/kg iv). On the other hand, the repetitive stimulation (1 stimulation/1 s) induced spinal reflex potentiation (SRP) that was attenuated by intrathecal 6-cyano-7-nitroquinoxaline- 2,4-dione (a glutamatergic alpha-amino-3-hydroxy-5-methyl- 4-isoxazoleproprionat receptor antagonist, 100 mu M, 10 mu l) and D-2-amino-5-phosphonovalerate [a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, 100 mu M, 10 mu l]. Acute anal stretch using a mosquito clamp with a distance of 4 mm exhibited no effect, whereas distances of 8 mm attenuated and 12 mm abolished the repetitive stimulation-induced SRP. Intrathecal NMDA (100 mu M, 10 mu l) reversed the abolition on SRP caused by anal stretch. On the other hand, pretreated bicuculline [gamma-aminobutyric acid (GABA) A receptor antagonist, 100 mu M, 10 mu l] but not hydroxysaclofen (GABA(B) receptor antagonist) counteracted the abolition on the repetitive stimulation-induced SRP caused by the anal stretch. All of the results suggested that anal stretch may be used as an adjunct to assist voiding dysfunction in patients with overactive urethra sphincter and that GABAergic neurotransmission is important in the neural mechanisms underlying external urethra sphincter activity inhibited by anal stretch

The Comprehensive Roadmap Toward Malaria Elimination Using Graphene and its Promising 2D Analogs

Malaria is a major public health concern with over 200 million new cases annually, resulting in significant financial costs. Preventive measures and diagnostic remedies are crucial in saving lives from malaria, and especially in developing nations. 2D materials are, therefore, ideal for fighting such an epidemic. Graphene and its derivatives are extensively studied due to their exceptional properties in this case. The biomedical applications of graphene-based nanomaterials have gained significant interest in recent years due to their remarkable biocompatibility, solubility, and selectivity. Their unique physicochemical characteristics, like ample surface area, biofunctionality, high purity, solubility, substantial drug-loading capacity, and superior ability to penetrate cell membranes, make them up-and-coming candidates as biodelivery carriers. In this review, crucial graphene-based technologies to combat malaria are discussed. The advancements in preventing and diagnosing malaria and the biocompatibility of graphene-based nanomaterials are emphasized. The roadmap for using graphene-based technology toward achieving the WHO global malaria elimination by 2030 is presented and discussed in detail. Graphene oxide, the most critical biocompatible graphene derivative for health sensors, is also discussed. Additionally, 2D chalcogenides, specifically sulfide-based transition-metal dichalcogenides, are reviewed in detecting malaria during its early stages

Quark helicity distributions from longitudinal spin asymmetries in muon-proton and muon-deuteron scattering

Double-spin asymmetries for production of charged pions and kaons in semi-inclusive deep-inelastic muon scattering have been measured by the COMPASS experiment at CERN. The data, obtained by scattering a 160 GeV muon beam off a longitudinally polarised NH_3 target, cover a range of the Bjorken variable x between 0.004 and 0.7. A leading order evaluation of the helicity distributions for the three lightest quarks and antiquark flavours derived from these asymmetries and from our previous deuteron data is presented. The resulting values of the sea quark distributions are small and do not show any sizable dependence on x in the range of the measurements. No significant difference is observed between the strange and antistrange helicity distributions, both compatible with zero. The integrated value of the flavour asymmetry of the helicity distribution of the light-quark sea, \Delta u-bar - \Delta d-bar, is found to be slightly positive, about 1.5 standard deviations away from zero.Comment: 13 pages, 5 figure

Search for Doubly-Charged Higgs Boson Production at HERA

A search for the single production of doubly-charged Higgs bosons H^{\pm \pm} in ep collisions is presented. The signal is searched for via the Higgs decays into a high mass pair of same charge leptons, one of them being an electron. The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment at HERA. No evidence for doubly-charged Higgs production is observed and mass dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only decays into an electron and a muon via a coupling of electromagnetic strength h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3, masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl

Dynamic Assessment of Baroreflex Control of Heart Rate During Induction of Propofol Anesthesia Using a Point Process Method

In this article, we present a point process method to assess dynamic baroreflex sensitivity (BRS) by estimating the baroreflex gain as focal component of a simplified closed-loop model of the cardiovascular system. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by linear and bilinear bivariate regressions on both the previous R−R intervals (RR) and blood pressure (BP) beat-to-beat measures. The instantaneous baroreflex gain is estimated as the feedback branch of the loop with a point-process filter, while the RRBP feedforward transfer function representing heart contractility and vasculature effects is simultaneously estimated by a recursive least-squares filter. These two closed-loop gains provide a direct assessment of baroreflex control of heart rate (HR). In addition, the dynamic coherence, cross bispectrum, and their power ratio can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics. To illustrate the application, we have applied the proposed point process model to experimental recordings from 11 healthy subjects in order to monitor cardiovascular regulation under propofol anesthesia. We present quantitative results during transient periods, as well as statistical analyses on steady-state epochs before and after propofol administration. Our findings validate the ability of the algorithm to provide a reliable and fast-tracking assessment of BRS, and show a clear overall reduction in baroreflex gain from the baseline period to the start of propofol anesthesia, confirming that instantaneous evaluation of arterial baroreflex control of HR may yield important implications in clinical practice, particularly during anesthesia and in postoperative care.National Institutes of Health (U.S.) (Grant R01-HL084502)National Institutes of Health (U.S.) (Grant K25-NS05758)National Institutes of Health (U.S.) (Grant DP2- OD006454)National Institutes of Health (U.S.) (Grant T32NS048005)National Institutes of Health (U.S.) (Grant T32NS048005)National Institutes of Health (U.S.) (Grant R01-DA015644)Massachusetts General Hospital (Clinical Research Center, UL1 Grant RR025758

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter