266 research outputs found

    A new synthetic route to chiral 3-aryl-5-ethyl-1,4,2-oxazaphosphorines

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    © 2018 Diastereoselective synthesis of racemic and enantiopure 3-aryl-5-ethyl-1,4,2-oxazaphosphorines, including those bearing phenolic hydroxyl groups in the exocyclic aromatic fragment, was implemented by the reaction of imines derived from (±)-and (R)-(−)-2-aminobutan-1-ol and (hydroxy)benzaldehydes with triethyl phosphite and trifluoroacetic acid, followed by the one-pot dealkylation of the intermediate esters

    Phosphorylation of Betti Base with Bis(diethylamino)phosphoryl Chloride

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    © 2018, Pleiades Publishing, Ltd. The reaction of bis(diethylamino)phosphoryl chloride with N-Boc-protected 1-(α-aminobenzyl)-2- naphthol (Betti base) proceeded via O-phosphorylation of the phenolic OH group to form the target product as trifluoroacetate salt. The latter reacted with O,O-diethyl thiophosphorylisothiocyanate to give thiourea bearing a chiral Betti base fragment

    SYNTHESIS, STRUCTURE, SIZE AND CONDUCTIVE PROPERTIES OF LOW-SYMMETRY MOLYBDATES OF BISMUTH Bi13-XAXMo5-YBYO34±δ (A - Ba; B-V, CO)

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    Substitution in Bi13Mo5O34±δ is possible in the position of molybdenum and isolated bismuth atoms. The formulas of substitutional solid solutions look like Bi13-XAXMo5-YBYO34±δ . The paper discusses the research of the availability and property measurement of oxygenic ionic conductors based on bismuth molibdates with a double substitution (A: Ba and B: V, Co).The samples were synthesized by the standard ceramic technology in two stages, the phase composition was controlled by the method of x-ray analysis. The electrical conductivity of complex oxides studied using impedance spectroscopy. The significant increase in conductivity compared to the matrix compound.Работа выполнена при финансовой поддержке гранта Президента МК-7979.2016.3

    The detection of neutrino interactions in the emulsion/lead target of the OPERA experiment

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    The OPERA neutrino detector in the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in appearance mode through the study of νμντ\nu_\mu\to\nu_\tau oscillations. The apparatus consists of an emulsion/lead target complemented by electronic detectors and it is placed in the high energy long-baseline CERN to LNGS beam (CNGS) 730 km away from the neutrino source. Runs with CNGS neutrinos were successfully carried out in 2007 and 2008 with the detector fully operational with its related facilities for the emulsion handling and analysis. After a brief description of the beam and of the experimental setup we report on the collection, reconstruction and analysis procedures of first samples of neutrino interaction events

    First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

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    We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

    The Telomere Binding Protein TRF2 Induces Chromatin Compaction

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    Mammalian telomeres are specialized chromatin structures that require the telomere binding protein, TRF2, for maintaining chromosome stability. In addition to its ability to modulate DNA repair activities, TRF2 also has direct effects on DNA structure and topology. Given that mammalian telomeric chromatin includes nucleosomes, we investigated the effect of this protein on chromatin structure. TRF2 bound to reconstituted telomeric nucleosomal fibers through both its basic N-terminus and its C-terminal DNA binding domain. Analytical agarose gel electrophoresis (AAGE) studies showed that TRF2 promoted the folding of nucleosomal arrays into more compact structures by neutralizing negative surface charge. A construct containing the N-terminal and TRFH domains together altered the charge and radius of nucleosomal arrays similarly to full-length TRF2 suggesting that TRF2-driven changes in global chromatin structure were largely due to these regions. However, the most compact chromatin structures were induced by the isolated basic N-terminal region, as judged by both AAGE and atomic force microscopy. Although the N-terminal region condensed nucleosomal array fibers, the TRFH domain, known to alter DNA topology, was required for stimulation of a strand invasion-like reaction with nucleosomal arrays. Optimal strand invasion also required the C-terminal DNA binding domain. Furthermore, the reaction was not stimulated on linear histone-free DNA. Our data suggest that nucleosomal chromatin has the ability to facilitate this activity of TRF2 which is thought to be involved in stabilizing looped telomere structures

    MECP2 Isoform-Specific Vectors with Regulated Expression for Rett Syndrome Gene Therapy

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    BACKGROUND:Rett Syndrome (RTT) is an Autism Spectrum Disorder and the leading cause of mental retardation in females. RTT is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment. Our objective is to develop viral vectors for MECP2 gene transfer into Neural Stem Cells (NSC) and neurons suitable for gene therapy of Rett Syndrome. METHODOLOGY/PRINCIPAL FINDINGS:We generated self-inactivating (SIN) retroviral vectors with the ubiquitous EF1alpha promoter avoiding known silencer elements to escape stem-cell-specific viral silencing. High efficiency NSC infection resulted in long-term EGFP expression in transduced NSC and after differentiation into neurons. Infection with Myc-tagged MECP2-isoform-specific (E1 and E2) vectors directed MeCP2 to heterochromatin of transduced NSC and neurons. In contrast, vectors with an internal mouse Mecp2 promoter (MeP) directed restricted expression only in neurons and glia and not NSC, recapitulating the endogenous expression pattern required to avoid detrimental consequences of MECP2 ectopic expression. In differentiated NSC from adult heterozygous Mecp2(tm1.1Bird)+/- female mice, 48% of neurons expressed endogenous MeCP2 due to random inactivation of the X-linked Mecp2 gene. Retroviral MECP2 transduction with EF1alpha and MeP vectors rescued expression in 95-100% of neurons resulting in increased dendrite branching function in vitro. Insulated MECP2 isoform-specific lentiviral vectors show long-term expression in NSC and their differentiated neuronal progeny, and directly infect dissociated murine cortical neurons with high efficiency. CONCLUSIONS/SIGNIFICANCE:MeP vectors recapitulate the endogenous expression pattern of MeCP2 in neurons and glia. They have utility to study MeCP2 isoform-specific functions in vitro, and are effective gene therapy vectors for rescuing dendritic maturation of neurons in an ex vivo model of RTT

    A global agenda for advancing freshwater biodiversity research

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    This manuscript is a contribution of the Alliance for Freshwater Life (www.allianceforfreshwaterlife.org). We thank Nick Bond, Lisa Bossenbroek, Lekima Copeland, Dean Jacobsen, Maria Cecilia Londo?o, David Lopez, Jaime Ricardo Garcia Marquez, Ketlhatlogile Mosepele, Nunia Thomas-Moko, Qiwei Wei and the authors of Living Waters: A Research Agenda for the Biodiversity of Inland and Coastal Waters for their contributions. We also thank Peter Thrall, Ian Harrison and two anonymous referees for their valuable comments that helped improve the manuscript. Open access funding enabled and organised by Projekt DEAL

    Regulation of immune cell function and differentiation by the NKG2D receptor

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    NKG2D is one of the most intensively studied immune receptors of the past decade. Its unique binding and signaling properties, expression pattern, and functions have been attracting much interest within the field due to its potent antiviral and anti-tumor properties. As an activating receptor, NKG2D is expressed on cells of the innate and adaptive immune system. It recognizes stress-induced MHC class I-like ligands and acts as a molecular sensor for cells jeopardized by viral infections or DNA damage. Although the activating functions of NKG2D have been well documented, recent analysis of NKG2D-deficient mice suggests that this receptor may have a regulatory role during NK cell development. In this review, we will revisit known aspects of NKG2D functions and present new insights in the proposed influence of this molecule on hematopoietic differentiation
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