Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension

Background: Disruption of cyclic nucleotide signaling in sympathetic postganglionic neurons contributes to impaired intracellular calcium handling (Ca2+) and the development of dysautonomia during the early stages of hypertension, although how this occurs is poorly understood. Emerging evidence supports the uncoupling of signalosomes in distinct cellular compartments involving cyclic nucleotide-sensitive PDEs (phosphodiesterases), which may underpin the autonomic phenotype in stellate neurons. Methods: Using a combination of single-cell RNA sequencing together with Forster resonance energy transfer-based sensors to monitor cyclic adenosine 3',5'-monophosphate, PKA (protein kinase A)-dependent phosphorylation and cGMP (cyclic guanosine 3',5'-monophosphate), we tested the hypothesis that dysregulation occurs in a sub-family of PDEs in the cytosol and outer mitochondrial membrane of neurons from the stellate ganglion. Results: PDE2A, 6D, 7A, 9A genes were highly expressed in young Wistar neurons and also conserved in neurons from spontaneously hypertensive rats (SHRs). In stellate neurons from prehypertensive SHRs, we found the levels of cyclic adenosine 3',5'-monophosphate and cGMP at the outer mitochondrial membrane were decreased compared with normal neurons. The reduced cyclic adenosine 3',5'-monophosphate response was due to the hydrolytic activity of overexpressed PDE2A2 located at the mitochondria. Normal cyclic adenosine 3',5'-monophosphate levels were re-established by inhibition of PDE2A. There was also a greater PKA-dependent phosphorylation in the cytosol and at the outer mitochondrial membrane in spontaneously hypertensive rat neurons, where this response was regulated by protein phosphatases. The cGMP response was only restored by inhibition of PDE6. Conclusions: When taken together, these results suggest that site-specific inhibition of PDE2A and PDE6D at the outer mitochondrial membrane may provide a therapeutic target to ameliorate cardiac sympathetic impairment during the onset of hypertension

Molecular cloning and characterization of drought stress responsive abscisic acid-stress-ripening (Asr 1) gene from wild jujube, Ziziphus nummularia (Burm.f.) Wight & Arn

Drought is a calamitous abiotic stress hampering agricultural productivity all over the world and its severity is likely to increase further. Abscisic acid-stress-ripening proteins (ASR), are a group of small hydrophilic proteins which are induced by abscisic acid, stress and ripening in many plants. In the present study, ZnAsr1 gene was fully characterized for the first time from Ziziphus nummularia, which is one of the most low water forbearing plant. Full length ZnAsr1 gene was characterised and in silico analysis of ZnASR1 protein was done for predicting its phylogeny and physiochemical properties. To validate transcriptional pattern of ZnAsr1 in response to drought stress, expression profiling in polyethylene glycol (PEG) induced Z. nummularia seedlings was studied by RT-qPCR analysis and heterologous expression of the recombinant ZnAsr1 in Escherichia coli. The nucleotide sequence analysis revealed that the complete open reading frame of ZnAsr1 is 819 bp long encoding a protein of 273 amino acid residues, consisting of a histidine rich N terminus with an abscisic acid/water deficit stress domain and a nuclear targeting signal at the C terminus. In expression studies, ZnAsr1 gene was found to be highly upregulated under drought stress and recombinant clones of E. coli cells expressing ZnASR1 protein showed better survival in PEG containing media. ZnAsr1 was proven to enhance drought stress tolerance in the recombinant E.coli cells expressing ZnASR1. The cloned ZnAsr1 after proper validation in a plant system, can be used to develop drought tolerant transgenic crops

Measurements of double-helicity asymmetries in inclusive J/ψJ/\psi production in longitudinally polarized p+pp+p collisions at s=510\sqrt{s}=510 GeV

We report the double helicity asymmetry, $A_{LL}^{J/\psi}$, in inclusive $J/\psi$ production at forward rapidity as a function of transverse momentum $p_T$ and rapidity $|y|$. The data analyzed were taken during $\sqrt{s}=510$ GeV longitudinally polarized $p$$+$$p$ collisions at the Relativistic Heavy Ion Collider (RHIC) in the 2013 run using the PHENIX detector. At this collision energy, $J/\psi$ particles are predominantly produced through gluon-gluon scatterings, thus $A_{LL}^{J/\psi}$ is sensitive to the gluon polarization inside the proton. We measured $A_{LL}^{J/\psi}$ by detecting the decay daughter muon pairs $\mu^+ \mu^-$ within the PHENIX muon spectrometers in the rapidity range $1.2<|y|<2.2$. In this kinematic range, we measured the $A_{LL}^{J/\psi}$ to be $0.012 \pm 0.010$~(stat)~$\pm$~$0.003$(syst). The $A_{LL}^{J/\psi}$ can be expressed to be proportional to the product of the gluon polarization distributions at two distinct ranges of Bjorken $x$: one at moderate range $x \approx 0.05$ where recent RHIC data of jet and $\pi^0$ double helicity spin asymmetries have shown evidence for significant gluon polarization, and the other one covering the poorly known small-$x$ region $x \approx 2\times 10^{-3}$. Thus our new results could be used to further constrain the gluon polarization for $x< 0.05$.Comment: 335 authors, 10 pages, 4 figures, 3 tables, 2013 data. Version accepted for publication by Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Galactic Cosmic Rays from Supernova Remnants (I) - a Cosmic Ray Composition controlled by Volatility and Mass-to-Charge Ratio

This is the first of a series of papers analysing the Galactic Cosmic Ray composition and origin. We show that the Galactic Cosmic Ray source (GCRS) composition is best described in terms of (i) a general enhancement of the refractory elements relative to the volatile ones, and (ii) among the volatile elements, an enhancement of the heavier elements relative to the lighter ones; this mass dependence most likely reflects a mass-to-charge (A/Q) dependence of the acceleration efficiency; among the refractory elements, there is NO such enhancement of heavier species, or only a much weaker one. We regard as coincidental the similarity between the GCRS composition and that of the solar corona, which is biased according to first ionization potential. In a companion paper, this GCRS composition is interpreted in terms of an acceleration by supernova shock waves of interstellar and/or circumstellar (eg Ne22 rich Wolf-Rayet wind) gas-phase and especially dust material.Comment: 23 pages plain TeX and 6 postscript figures, to appear in ApJ, also available from ftp://wonka.physics.ncsu.edu/pub/elliso

Nuclear dependence of the transverse single-spin asymmetry in the production of charged hadrons at forward rapidity in polarized p+pp+p, p+p+Al, and p+p+Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

We report on the nuclear dependence of transverse single-spin asymmetries (TSSAs) in the production of positively-charged hadrons in polarized $p^{\uparrow}+p$, $p^{\uparrow}+$Al and $p^{\uparrow}+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. The measurements have been performed at forward rapidity ($1.4<\eta<2.4$) over the range of $1.8<p_{T}<7.0$ GeV$/c$ and $0.1<x_{F}<0.2$. We observed a positive asymmetry $A_{N}$ for positively-charged hadrons in \polpp collisions, and a significantly reduced asymmetry in $p^{\uparrow}$+$A$ collisions. These results reveal a nuclear dependence of charged hadron $A_N$ in a regime where perturbative techniques are relevant. These results provide new opportunities to use \polpA collisions as a tool to investigate the rich phenomena behind TSSAs in hadronic collisions and to use TSSA as a new handle in studying small-system collisions.Comment: 303 authors from 66 institutions, 9 pages, 2 figures, 1 table. v1 is version accepted for publication in Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized pp++AA collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized $p$$+$$p$ collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in $p$$+$$p$ collisions predicts only a moderate atomic-mass-number ($A$) dependence. In contrast, the asymmetries observed at RHIC in $p$$+$$A$ collisions showed a surprisingly strong $A$ dependence in inclusive forward neutron production. The observed asymmetry in $p$$+$Al collisions is much smaller, while the asymmetry in $p$$+$Au collisions is a factor of three larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed $A$ dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm