166 research outputs found
Boost-HiC: computational enhancement of long-range contacts in chromosomal contact maps
International audienceGenome-wide chromosomal contact maps are widely used to uncover the 3D organisation of genomes. They rely on the collection of millions of contacting pairs of genomic loci. Contact frequencies at short range are usually well measured in experiments, while there is a lot of missing information about long-range contacts. We propose to use the sparse information contained in raw contact maps to determine high-confidence contact frequency between all pairs of loci. Our algorithmic procedure, Boost-HiC, enables the detection of Hi-C patterns such as chromosomal compartments at a resolution that would be otherwise only attainable by sequencing a hundred times deeper the experimental Hi-C library
Intramolecular hydrogen transfer reactions of thiyl radicals from glutathione: formation of carbon-centered radical at Glu, Cys and Gly
This document is the Accepted Manuscript version of a Published Work that appeared in final form in
Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher.
To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3000494Glutathione thiyl radicals (GS•) were generated in H2O and D2O by either exposure of GSH to AAPH#, photoirradiation of GSH in the presence of acetone, or photoirradiation of GSSG. Detailed interpretation of the fragmentation pathways of deuterated GSH and GSH-derivatives during mass spectrometry analysis allowed us to demonstrate that reversible intramolecular H-atom transfer reactions between GS• and C-H bonds at Cys[αC], Cys[βC], and Gly[αC] are possible
Mutations and deletions of the SUZ12 polycomb gene in myeloproliferative neoplasms
International audienceNo abstract availabl
The inner core hemispheric boundary near 180°W
The inner core (IC) east–west hemispheric dichotomy is widely recognized, but the reported position of the hemispheric boundary varies among studies due to uneven sampling coverage and the data analyzed. This study investigates the sharpness of the western hemispheric boundary (WHB) near 180°W by analyzing differential time residuals of PKiKP–PKPdf and PKP(bc–df) for PKPdf phases that sample 155°E–130°W in various azimuthal directions. Using PKiKP–PKPdf observations, the WHB is located at 175°E–180°W in the southern hemisphere, based mainly on the lateral isotropy–anisotropy transition. However, based on the lateral isotropic velocity contrast and this isotropy–anisotropy transition between the two hemispheres, its location is 170–160°W in the northern hemisphere. These findings indicate that the WHB is sharp and exhibits a latitudinal dependence with a 10°–20° kink, as well as 1.75% anisotropy in the uppermost IC across the 180–155°W range of the western hemisphere. As suggested by PKP(bc–df), the WHB could remain at 160°W at depth. The isotropic velocity contrast near the WHB (160°W) between the eastern and western hemispheres is lower than previous estimates using PKPdf phases sampling the bulk part of each hemisphere
An All-Atom Model of the Chromatin Fiber Containing Linker Histones Reveals a Versatile Structure Tuned by the Nucleosomal Repeat Length
In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties
Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.As the second of a 3-part series of articles in this issue concerning the development of a mathematical model for comparative characterization of complex mixture drugs using crofelemer (CF) as a model compound, this work focuses on the evaluation of the chemical stability profile of CF. CF is a biopolymer containing a mixture of proanthocyanidin oligomers which are primarily composed of gallocatechin with a small contribution from catechin. CF extracted from drug product was subjected to molecular weight–based fractionation and thiolysis. Temperature stress and metal-catalyzed oxidation were selected for accelerated and forced degradation studies. Stressed CF samples were size fractionated, thiolyzed, and analyzed with a combination of negative-ion electrospray ionization mass spectrometry (ESI-MS) and reversed-phase-HPLC with UV absorption and fluorescence detection. We further analyzed the chemical stability data sets for various CF samples generated from reversed-phase-HPLC-UV and ESI-MS using data-mining and machine learning approaches. In particular, calculations based on mutual information of over 800,000 data points in the ESI-MS analytical data set revealed specific CF cleavage and degradation products that were differentially generated under specific storage/degradation conditions, which were not initially identified using traditional analysis of the ESI-MS results
Self-assembly of artificial microtubules
Understanding the complex self-assembly of biomacromolecules is a major
outstanding question. Microtubules are one example of a biopolymer that
possesses characteristics quite distinct from standard synthetic polymers that
are derived from its hierarchical structure. In order to understand how to
design and build artificial polymers that possess features similar to those of
microtubules, we have initially studied the self-assembly of model monomers
into a tubule geometry. Our model monomer has a wedge shape with lateral and
vertical binding sites that are designed to form tubules. We used molecular
dynamics simulations to study the assembly process for a range of binding site
interaction strengths. In addition to determining the optimal regime for
obtaining tubules, we have calculated a diagram of the structures that form
over a wide range of interaction strengths. Unexpectedly, we find that the
helical tubules form, even though the monomer geometry is designed for
nonhelical tubules. We present the detailed dynamics of the tubule
self-assembly process and show that the interaction strengths must be in a
limited range to allow rearrangement within clusters. We extended previous
theoretical methods to treat our system and to calculate the boundaries between
different structures in the diagram.Comment: 15 pages, 11 figure
Multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) to identify recurrent chromosomal alterations in breast tumour cell lines
Recurrent chromosome breakpoints in tumour cells may point to cancer genes, but not many have been molecularly characterised. We have used multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) on breast tumour cell lines to identify regions of chromosome break created by inversions, duplications, insertions and translocations on chromosomes 1, 5, 8, 12 and 17. We delineate a total of 136 regions of break, some of them occurring with high frequency. We further describe two examples of dual-colour FISH characterisation of breakpoints, which target the 1p36 and 5p11–12 regions. Both breaks involve genes whose function is unknown to date. The mbanding-FISH strategy constitutes an efficient first step in the search for potential cancer genes
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