2-[4-(2-Meth­oxy­phen­yl)piperazin-1-yl]-N-(pyridin-2-yl)acetamide

In the title compound, C18H22N4O2, the piperizine ring adopts a chair conformation and the dihedral angle between the pyridine and benzene rings is 67.6 (9)°. The conformations of the attachment of the anisole and N-ethyl­pyridin-2-amine groups to the piperazine ring are (+)anti­periplanar. Intra­molecular C—H⋯O and N—H⋯N inter­actions occur. In the crystal, inter­molecular C—H⋯N hydrogen bonds are present. There are two crystallographically independent but identical mol­ecules per asymmetric unit

Role of the substrate conformation and of the S1 protein in the cleavage efficiency of the T4 endoribonuclease RegB.

[[abstract]]The T4 endoribonuclease RegB is involved in the inactivation of the phage early messengers. It cuts specifically in the middle of GGAG sequences found in early messenger intergenic regions but not GGAG sequences located in coding sequences or in late messengers. In vitro RegB activity is very low but is enhanced by a factor up to 100 by the ribosomal protein S1. In the absence of clear sequence motif distinguishing substrate and non-substrate GGAG-containing RNAs, we postulated the existence of a structural determinant. To test this hypothesis, we correlated the structure, probed by NMR spectroscopy, with the cleavage propensity of short RNA molecules derived from an artificial substrate. A kinetic analysis of the cleavage was performed in the presence and absence of S1. In the absence of S1, RegB efficiently hydrolyses substrates in which the last G of the GGAG motif is located in a short stem between two loops. Both strengthening and weakening of this structure strongly decrease the cleavage rate, indicating that this structure constitutes a positive cleavage determinant. Based on our results and those of others, we speculate that S1 favors the formation of the structure recognized by RegB and can thus be considered a “presentation protein.

N-{2-[4-(2-Meth­oxy­phen­yl)piperazin-1-yl]eth­yl}pyridin-2-amine monohydrate

In the title compound, C18H24N4O·H2O, the piperizine ring adopts a chair conformation and the dihedral angle between the phenyl and pyridine rings is 39.9 (3)°. The comformations of the attachment of the anisole and N-ethyl­pyridin-2-amine groups to the piperazine ring are +anti­periplanar. An intra­molecular C—H⋯O inter­action occurs. In the crystal, the water mol­ecule links the mol­ecules into chains through O—H⋯N hydrogen bonds. Weak N—H⋯O, C—H⋯N and C—H⋯O inter­actions further stabilize the crystal structure

Stase veineuse et croissance osseuse

Servelle Marceau, Simonnet Henri, Lebars H. Stase veineuse et croissance osseuse. In: Bulletin de l'Académie Vétérinaire de France tome 103 n°7, 1950. pp. 355-359

Exploring TAR–RNA aptamer loop–loop interaction by X-ray crystallography, UV spectroscopy and surface plasmon resonance

In HIV-1, trans-activation of transcription of the viral genome is regulated by an imperfect hairpin, the trans-activating responsive (TAR) RNA element, located at the 5′ untranslated end of all viral transcripts. TAR acts as a binding site for viral and cellular proteins. In an attempt to identify RNA ligands that would interfere with the virus life-cycle by interacting with TAR, an in vitro selection was previously carried out. RNA hairpins that formed kissing-loop dimers with TAR were selected [Ducongé F. and Toulmé JJ (1999) RNA, 5:1605–1614]. We describe here the crystal structure of TAR bound to a high-affinity RNA aptamer. The two hairpins form a kissing complex and interact through six Watson–Crick base pairs. The complex adopts an overall conformation with an inter-helix angle of 28.1°, thus contrasting with previously reported solution and modelling studies. Structural analysis reveals that inter-backbone hydrogen bonds between ribose 2′ hydroxyl and phosphate oxygens at the stem-loop junctions can be formed. Thermal denaturation and surface plasmon resonance experiments with chemically modified 2′-O-methyl incorporated into both hairpins at key positions, clearly demonstrate the involvement of this intermolecular network of hydrogen bonds in complex stability

Beating quantum limits in interferometers with quantum locking of mirrors

The sensitivity in interferometric measurements such as gravitational-wave detectors is ultimately limited by quantum noise of light. We discuss the use of feedback mechanisms to reduce the quantum effects of radiation pressure. Recent experiments have shown that it is possible to reduce the thermal motion of a mirror by cold damping. The mirror motion is measured with an optomechanical sensor based on a high-finesse cavity, and reduced by a feedback loop. We show that this technique can be extended to lock the mirror at the quantum level. In gravitational-waves interferometers with Fabry-Perot cavities in each arms, it is even possible to use a single feedback mechanism to lock one cavity mirror on the other. This quantum locking greatly improves the sensitivity of the interferometric measurement. It is furthermore insensitive to imperfections such as losses in the interferometer

Effects of Tetrodotoxin in Mouse Models of Visceral Pain

Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis. The subcutaneous administration of TTX dose-dependently inhibited the number of pain-related behaviors in all evaluated pain models and reversed the referred mechanical hyperalgesia (examined by stimulation of the abdomen with von Frey filaments) induced by capsaicin and cyclophosphamide, but not that induced by mustard oil. Morphine inhibited both pain responses and the referred mechanical hyperalgesia in all tests. Conditional nociceptor‑specific Nav1.7 knockout mice treated with TTX showed the same responses as littermate controls after the administration of the algogens. No motor incoordination after the administration of TTX was observed. These results suggest that blockade of TTX-sensitive sodium channels, but not Nav1.7 subtype alone, by systemic administration of TTX might be a potential therapeutic strategy for the treatment of visceral pain.R. González-Cano was supported by a postdoctoral grant from the Contratos-Puente Research Program of the University of Granada. M.A. Tejada was supported by a predoctoral grant from the University of Granada. F. R. Nieto was supported by a postdoctoral Juan de la Cierva grant (Spanish Goverment). This study was partially supported by grant GREIB (CEB-005) from the University of Granada and grant CTS 109 from the Junta de Andalucía

Noise reduction in gravitational wave interferometers using feedback

We show that the quantum locking scheme recently proposed by Courty {\it et al.} [Phys. Rev. Lett. {\bf 90}, 083601 (2003)] for the reduction of back action noise is able to significantly improve the sensitivity of the next generation of gravitational wave interferometers.Comment: 12 pages, 2 figures, in print in the Special Issue of J. Opt. B on Fluctuations and Noise in Photonics and Quantum Optic

Nucleic Acids Res

Site-directed spin labeling is emerging as an essential tool to investigate the structural and dynamical features of RNA. We propose here an enzymatic method, which allows the insertion of a paramagnetic center at a specific position in an RNA molecule. The technique is based on a segmental approach using a ligation protocol with T4 RNA ligase 2. One transcribed acceptor RNA is ligated to a donor RNA in which a thio-modified nucleotide is introduced at its 5'-end by in vitro transcription with T7 RNA polymerase. The paramagnetic thiol-specific reagent is subsequently attached to the RNA ligation product. This novel strategy is demonstrated by introducing a paramagnetic probe into the 55 nucleotides long RNA corresponding to K-turn and Specifier Loop domains from the Bacillus subtilis tyrS T-Box leader RNA. The efficiency of the coupling reaction and the quality of the resulting spin-labeled RNA were assessed by Mass Spectrometry, Electron Paramagnetic Resonance (EPR) and Nuclear Magnetic Resonance (NMR). This method enables various combinations of isotopic segmental labeling and spin labeling schemes, a strategy that will be of particular interest to investigate the structural and dynamical properties of large RNA complexes by NMR and EPR spectroscopies