1,721,030 research outputs found
Solution equilibria in YbDOTMA, a chiral analogue of one of the most successful contrast agents for MRI, GdDOTA
No full textThe structure and the conformational equilibria in aqueous and methanolic solutions of YbDOTMA (DOTMA = (1R,4R,7R,10R)-alpha,alpha',alpha",alpha""-tetramethyl-1,4,7,10-tetraaza- cyclododecane-1,4,7,10-tetraacetic acid) are investigated and the dynamics studied by means of NMR methods. The presence of two isomeric forms in slow exchange is confirmed and quantitatively characterized by EXSY. The exchange peaks are assigned to the inversion of the conformation of the macrocycle ring. No evidence is obtained of a reorientation of the methyl acetate substituents. The protons switch between positions with the same geometrical factors, i.e. positions that would have the same pseudocontact shifts were it not for the different magnetic susceptibility anisotropies of the two species; steady-state NOE spectra on the major form allow unequivocal assignment of the conformations of the two isomers
Function by structure: Spotlights on xist long non-coding RNA
No full textRecent experimental evidence indicates that lncRNAs can act as regulatory molecules in the context of development and disease. Xist, the master regulator of X chromosome inactivation, is a classic example of how lncRNAs can exert multi-layered and fine-tuned regulatory functions, by acting as a molecular scaffold for recruitment of distinct protein factors. In this review, we discuss the methodologies employed to define Xist RNA structures and the tight interplay between structural clues and functionality of lncRNAs. This model of modular function dictated by structure, can be also generalized to other lncRNAs, beyond the field of X chromosome inactivation, to explain common features of similarly folded RNAs
Stereoselection in the Binding of Ln DOTA to gamma-Cyclodextrin: A Near Infrared Circular Dichroism Study
No full textThe formation of an inclusion complex between gamma-cyclodextrin and Ln DOTA has been reported in the literature. All Ln DOTA complexes in solution give rise to a network of equilibria between different stereoisomers, which are pairs of enantiomers. By means of near infrared circular dichroism of the Yb derivative, we demonstrate that upon the formation of the host-guest complex, there is a complete stereoselection and that only the Lambda (delta delta delta delta) binds. Chirality 22:E11-E16, 2010
Stereochemistry and Near-Infrared Circular Dichroism of a Chiral Yb Complex
No full textThe near-infrared CD spectrum of ytterbium complexed by DOTMA, [DOTMA = (1R,4R,7R, 10R)-alpha, alpha', alpha ", alpha'''-tetramethyl-1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)] is presented. This is the first report of a near-infrared CD spectrum in solution of the f-f transitions of ytterbium in a complex whose solution structure and dynamics are completely defined. The spectrum shows several well-resolved transitions around 980 nm with very high dissymmetry factors. In water and in methanol, there are two diastereomeric conformations of YbDOTMA in equilibrium, Lambda(delta delta delta delta) or n and Lambda(lambda lambda lambda lambda) or p, being the latter always in a large excess. The relative proportion depends on temperature and solvent composition, but the CD spectrum is rather insensitive to these parameters, which demonstrates that neglecting the minor form contribution is an acceptable approximation. On lowering the temperature, the presence of hot bands is highlighted, which leads to a tentative assignment of the transitions. The absorption counterpart compares very well with that of YbDOTA, an achiral analogue, largely studied and well understood
X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells
Full text linkX chromosome inactivation (XCI) is the dosage compensation mechanism that evolved in female mammals to correct the genetic imbalance of X-linked genes between sexes. X chromosome inactivation occurs in early development when one of the two X chromosomes of females is nearly-completely silenced. Differentiating Embryonic Stem cells (ESC) are regarded as a useful tool to study XCI, since they recapitulate many events occurring during early development. In this review we aim to summarise the advances in the field and to discuss the close connection between cell differentiation and X chromosome inactivation, with a particular focus on mouse ESCs
The structure of metal adducts of anthracyclines probed by absorption, circular dichroism and paramagnetic NMR
No full textA structural study of metal ion adducts of a new anthracycline disaccharide (MEN 10755) was undertaken. The trivalent lanthanide ion Yb(III) was employed as paramagnetic structural probe for H-1 NMR analysis. Through a comparative spectroscopic investigation [UV-Vis absorption and circular dichroism (CD), H-1 NMR], the isomorphism between its adducts with lanthanide ions (La3+, Yb3+, Lu3+) and calcium (one of the most representative biological cations) was verified. Solution behavior and cation binding were also investigated by means of optical titrations. In agreement with other anthracyclines, MEN 10755 was found to dimerize in aqueous solution [estimated K-dim (pH 7.6) = 7 x 10(3)], but not in methanol. A prevalent complex Yb3+-MEN 10755 (1:1) in both buffered aqueous and methanolic solutions (estimated K-compl = 2100 M-1) was observed. A numerical analysis of the LIR and LIS H-1 NMR literature data for a similar adduct (Yb3+-daunorubicin) was performed using newly developed software, PERSEUS (Paramagnetic Enhanced Relaxation and Shifts for Eliciting Ultimate Structures), and the structure of the complex was characterized, locating definitely the binding site on the O-11, O-12 quinone system. The components of the anisotropic part of the magnetic susceptibility tensor were also determined. Finally, a study of the time-dependent formation of an Yb3+-MEN 10755 complex through H-1 NMR, UV-Vis CD and induced NIR CD was carried out
Xist localization and function: New insights from multiple levels
Full text linkIn female m ammals, one of the two X chromosomes in each cell is transcriptionally silenced in order to achieve dosage compensation between the genders in a process called X chromosome inactivation. The master regulator of this process is the long non-coding RNA Xist. During X-inactivation, Xist accumulates in cis on the future inactive X chromosome, triggering a cascade of events that provoke the stable silencing of the entire chromosome, with relatively few genes remaining active. How Xist spreads, what are its binding sites, how it recruits silencing factors and how it induces a specific topological and nuclear organization of the chromatin all remain largely unanswered questions. Recent studies have improved our understanding of Xist localization and the proteins with which it interacts, allowing a reappraisal of ideas about Xist function. We discuss recent advances in our knowledge of Xist-mediated silencing, focusing on Xist spreading, the nuclear organization of the inactive X chromosome, recruitment of the polycomb complex and the role of the nuclear matrix in the process of X chromosome inactivation
Monitoring proton dissociation and solution conformation of chiral ytterbium complexes with near-IR CD
No full textThe ytterbium complex [Yb((S)-THP)](3+) ((S)-THP = (IS,4S,7S,10S-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane) is investigated in solution through NMR, near-IR absorption, and CD spectroscopy. Quantitative analysis of the paramagnetic pseudocontact NMR shift shows A helicity of the ligand cage around the metal. The NIR CD spectrum recorded at acidic pH is found to be very similar to that of [Yb((R)-DOTMA)] (R)-DOTMA = (IR,4R,7R,10R)-alpha,alpha ',alpha '',alpha '''-tetramethyl-1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetic acid), which in solution assumes a twisted square antiprism (`FSA) conformation. The similarity of the NIR CD spectra is discussed, and it is the first proof of the A(lambda,lambda,lambda,lambda) conformation of [Yb((S)-THP)](3+). NIR CD spectra recorded in the pH range of 2-9 allow one to easily follow proton dissociation and to calculate the pK of this equilibrium in water (PKA = 6.4 +/- 0.1). This value agrees well with that determined for [Lu((S)-THP)](3+) using potentiometric methods. This demonstrates once again that NIR CD spectroscopy is a powerful technique for investigating the solution structure and dynamics of these complexes
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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