bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3
Authors: Choi Eun Shik , Cheon Youngseo , Kang Keunsoo , Lee Daeyoup 
Published: September 2017

AbstractThe centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-ACnp1 chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1Hrp1. CENP-ACnp1 chromatin actively recruits the Ino80 complex to centromeres to elicit eviction of histone H3-containing nucleosomes. Artificial targeting of Ino80 subunits to a non-centromeric DNA sequence placed in a native centromere enhances the spreading of CENP-ACnp1 chromatin into the non-centromeric DNA. Based on these results, we propose that CENP-ACnp1 chromatin employs the Ino80 complex to mediate the replacement of histone H3 with CENP-ACnp1, and thereby reinforces itself.
Muscle pathology from stochastic low level DUX4 expression in an FSHD mouse model
Authors: Bosnakovski Darko , Chan Sunny S. K. , Recht Olivia O. , Hartweck Lynn M. , Gustafson Collin J. , Athman Laura L. , Lowe Dawn A. , Kyba Michael 
Published: September 2017

AbstractFacioscapulohumeral muscular dystrophy is a slowly progressive but devastating myopathy caused by loss of repression of the transcription factor DUX4; however, DUX4 expression is very low, and protein has not been detected directly in patient biopsies. Efforts to model DUX4 myopathy in mice have foundered either in being too severe, or in lacking muscle phenotypes. Here we show that the endogenous facioscapulohumeral muscular dystrophy-specific DUX4 polyadenylation signal is surprisingly inefficient, and use this finding to develop an facioscapulohumeral muscular dystrophy mouse model with muscle-specific doxycycline-regulated DUX4 expression. Very low expression levels, resulting in infrequent DUX4 + myonuclei, evoke a slow progressive degenerative myopathy. The degenerative process involves inflammation and a remarkable expansion in the fibroadipogenic progenitor compartment, leading to fibrosis. These animals also show high frequency hearing deficits and impaired skeletal muscle regeneration after injury. This mouse model will facilitate in vivo testing of therapeutics, and suggests the involvement of fibroadipogenic progenitors in facioscapulohumeral muscular dystrophy.
An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides
Authors: Armour Sean M. , Remsberg Jarrett R. , Damle Manashree , Sidoli Simone , Ho Wesley Y. , Li Zhenghui , Garcia Benjamin A. , Lazar Mitchell A. 
Published: September 2017

AbstractThe histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR–HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by hepatocyte nuclear factor 4α (HNF4α). The HDAC3–PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism.
Invasive Andropogon gayanus (Gamba grass) alters litter decomposition and nitrogen fluxes in an Australian tropical savanna
Authors: Rossiter-Rachor N. A. , Setterfield S. A. , Hutley L. B. , McMaster D. , Schmidt S. , Douglas M. M. 
Published: September 2017

AbstractThe African grass Andropogon gayanus Kunth. is invading Australian savannas, altering their ecological and biogeochemical function. To assess impacts on nitrogen (N) cycling, we quantified litter decomposition and N dynamics of grass litter in native grass and A. gayanus invaded savanna using destructive in situ grass litter harvests and litterbag incubations (soil surface and aerial position). Only 30% of the A. gayanus in situ litter decomposed, compared to 61% of the native grass litter, due to the former being largely comprised of highly resistant A. gayanus stem. In contrast to the stem, A. gayanus leaf decomposition was approximately 3- and 2-times higher than the dominant native grass, Alloteropsis semilata at the surface and aerial position, respectively. Lower initial lignin concentrations, and higher consumption by termites, accounted for the greater surface decomposition rate of A. gayanus. N flux estimates suggest the N release of A. gayanus litter is insufficient to compensate for increased N uptake and N loss via fire in invaded plots. Annually burnt invaded savanna may lose up to 8.2% of the upper soil N pool over a decade. Without additional inputs via biological N fixation, A. gayanus invasion is likely to diminish the N capital of Australia’s frequently burnt savannas.
Multidimensional encoding of brain connectomes
Authors: Caiafa Cesar F. , Pestilli Franco 
Published: September 2017

AbstractThe ability to map brain networks in living individuals is fundamental in efforts to chart the relation between human behavior, health and disease. Advances in network neuroscience may benefit from developing new frameworks for mapping brain connectomes. We present a framework to encode structural brain connectomes and diffusion-weighted magnetic resonance (dMRI) data using multidimensional arrays. The framework integrates the relation between connectome nodes, edges, white matter fascicles and diffusion data. We demonstrate the utility of the framework forin vivowhite matter mapping and anatomical computing by evaluating 1,490 connectomes, thirteen tractography methods, and three data sets. The framework dramatically reduces storage requirements for connectome evaluation methods, with up to 40x compression factors. Evaluation of multiple, diverse datasets demonstrates the importance of spatial resolution in dMRI. We measured large increases in connectome resolution as function of data spatial resolution (up to 52%). Moreover, we demonstrate that the framework allows performing anatomical manipulations on white matter tracts for statistical inference and to study the white matter geometrical organization. Finally, we provide open-source software implementing the method and data to reproduce the results.
Synthesis of flower-like magnetite nanoassembly: Application in the efficient reduction of nitroarenes
Authors: Datta Kasibhatta J. , Rathi Anuj K. , Kumar Pawan , Kaslik Josef , Medrik Ivo , Ranc Vaclav , Varma Rajender S. , Zboril Radek , Gawande Manoj B. 
Published: September 2017

AbstractA facile approach for the synthesis of magnetite microspheres with flower-like morphology is reported that proceeds via the reduction of iron(III) oxide under a hydrogen atmosphere. The ensuing magnetic catalyst is well characterized by XRD, FE-SEM, TEM, N2 adsorption-desorption isotherm, and Mössbauer spectroscopy and explored for a simple yet efficient transfer hydrogenation reduction of a variety of nitroarenes to respective anilines in good to excellent yields (up to 98%) employing hydrazine hydrate. The catalyst could be easily separated at the end of a reaction using an external magnet and can be recycled up to 10 times without any loss in catalytic activity.
Identification of sites of 2′-O-methylation vulnerability in human ribosomal RNAs by systematic mapping
Authors: Sharma Sunny , Marchand Virginie , Motorin Yuri , Lafontaine Denis L. J. 
Published: September 2017

AbstractRibosomal RNA modifications are important in optimizing ribosome function. Sugar 2′-O-methylation performed by fibrillarin-associated box C/D antisense guide snoRNAs impacts all steps of translation, playing a role in disease etiology (cancer). As it renders adjacent phosphodiester bonds resistant to alkaline treatment, 2′-O-methylation can be monitored qualitatively and quantitatively by applying next-generation sequencing to fragments of randomly cleaved RNA. We remapped all sites of 2′-O-methylation in human rRNAs in two isogenic diploid cell lines, one producing and one not producing the antitumor protein p53. We identified sites naturally modified only partially (confirming the existence in cells of compositionally distinct ribosomes with potentially specialized functions) and sites whose 2′-O-methylation is sensitive to p53. We mapped sites particularly vulnerable to a reduced level of the methyltransferase fibrillarin. The remarkable fact that these are largely sites of natural hypomodification provides initial insights into the mechanism of partial RNA modification. Sites where methylation appeared vulnerable lie peripherally on the 3-D structure of the ribosomal subunits, whereas the numerous modifications present at the core of the subunits, where the functional centers lie, appeared robustly made. We suggest that vulnerable sites of 2′-O-methylation are highly likely to undergo specific regulation during normal and pathological processes.
Reduced basal forebrain atrophy progression in a randomized Donepezil trial in prodromal Alzheimer’s disease
Authors: Cavedo Enrica , Grothe Michel J. , Colliot Olivier , Lista Simone , Chupin Marie , Dormont Didier , Houot Marion , Lehéricy Stephane , Teipel Stefan , Dubois Bruno , Hampel Harald ,   Hippocampus Study Group, Croisile Bernard , Louis Tisserand Guy , Bonafe Alain , Ousset Pierre J , Rouaud Olivier , Ricolfi Fréderic , Vighetto Alain , Pasquier Florence , Delmaire Christine , Ceccaldi Mathieu , Girard Nadine , Duveau Françoise , Sarazin Marie 
Published: September 2017

AbstractAcetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer’s disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day). Reduced annual BFCS rates of atrophy were found in the Donepezil group compared to the Placebo treated arm. Secondary analyses on BFCS subregions demonstrated the largest treatment effects in the Nucleus Basalis of Meynert (NbM) and the medial septum/diagonal band (Ch1/2). Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).
Statistical Modeling of the Default Mode Brain Network Reveals a Segregated Highway Structure
Authors: Stillman Paul E. , Wilson James D. , Denny Matthew J. , Desmarais Bruce A. , Bhamidi Shankar , Cranmer Skyler J. , Lu Zhong-Lin 
Published: September 2017

AbstractWe investigate the functional organization of the Default Mode Network (DMN) – an important subnetwork within the brain associated with a wide range of higher-order cognitive functions. While past work has shown the whole-brain network of functional connectivity follows small-world organizational principles, subnetwork structure is less well understood. Current statistical tools, however, are not suited to quantifying the operating characteristics of functional networks as they often require threshold censoring of information and do not allow for inferential testing of the role that local processes play in determining network structure. Here, we develop the correlation Generalized Exponential Random Graph Model (cGERGM) – a statistical network model that uses local processes to capture the emergent structural properties of correlation networks without loss of information. Examining the DMN with the cGERGM, we show that, rather than demonstrating small-world properties, the DMN appears to be organized according to principles of a segregated highway – suggesting it is optimized for function-specific coordination between brain regions as opposed to information integration across the DMN. We further validate our findings through assessing the power and accuracy of the cGERGM on a testbed of simulated networks representing various commonly observed brain architectures.
The sensitivity of a radical pair compass magnetoreceptor can be significantly amplified by radical scavengers
Authors: Kattnig Daniel R. , Hore P. J. 
Published: September 2017

AbstractBirds have a remarkable ability to obtain navigational information from the Earth’s magnetic field. The primary detection mechanism of this compass sense is uncertain but appears to involve the quantum spin dynamics of radical pairs formed transiently in cryptochrome proteins. We propose here a new version of the current model in which spin-selective recombination of the radical pair is not essential. One of the two radicals is imagined to react with a paramagnetic scavenger via spin-selective electron transfer. By means of simulations of the spin dynamics of cryptochrome-inspired radical pairs, we show that the new scheme offers two clear and important benefits. The sensitivity to a 50 μT magnetic field is greatly enhanced and, unlike the current model, the radicals can be more than 2 nm apart in the magnetoreceptor protein. The latter means that animal cryptochromes that have a tetrad (rather than a triad) of tryptophan electron donors can still be expected to be viable as magnetic compass sensors. Lifting the restriction on the rate of the spin-selective recombination reaction also means that the detrimental effects of inter-radical exchange and dipolar interactions can be minimised by placing the radicals much further apart than in the current model.
Deconvolution of DNA methylation identifies differentially methylated gene regions on 1p36 across breast cancer subtypes
Authors: Titus Alexander J. , Way Gregory P. , Johnson Kevin C. , Christensen Brock C. 
Published: September 2017

AbstractBreast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P). These regions were consistently differentially methylated in every subtype and all implicated genes are localized to the chromosomal cytoband 1p36.3. Seventeen of these DMGRs were independently validated in a similar analysis of an external data set. The identification and validation of shared DNAm alterations across tumor subtypes in early stage tumors advances our understanding of common biology underlying breast carcinogenesis and may contribute to biomarker development. We also discuss evidence of the specific importance and potential function of 1p36 in cancer.
Global organization of a binding site network gives insight into evolution and structure-function relationships of proteins
Authors: Lee Juyong , Konc Janez , Janežič Dušanka , Brooks Bernard R. 
Published: September 2017

AbstractThe global organization of protein binding sites is analyzed by constructing a weighted network of binding sites based on their structural similarities and detecting communities of structurally similar binding sites based on the minimum description length principle. The analysis reveals that there are two central binding site communities that play the roles of the network hubs of smaller peripheral communities. The sizes of communities follow a power-law distribution, which indicates that the binding sites included in larger communities may be older and have been evolutionary structural scaffolds of more recent ones. Structurally similar binding sites in the same community bind to diverse ligands promiscuously and they are also embedded in diverse domain structures. Understanding the general principles of binding site interplay will pave the way for improved drug design and protein design.
Whole body and hematopoietic ADAM8 deficiency does not influence advanced atherosclerotic lesion development, despite its association with human plaque progression
Authors: Theodorou Kosta , van der Vorst Emiel P. C. , Gijbels Marion J. , Wolfs Ine M. J. , Jeurissen Mike , Theelen Thomas L. , Sluimer Judith C. , Wijnands Erwin , Cleutjens Jack P. , Li Yu , Jansen Yvonne , Weber Christian , Ludwig Andreas , Bentzon Jacob F. , Bartsch Jörg W. , Biessen Erik A. L. , Donners Marjo M. P. C. 
Published: September 2017

AbstractAlthough A Disintegrin And Metalloproteinase 8 (ADAM8) is not crucial for tissue development and homeostasis, it has been implicated in various inflammatory diseases by regulating processes like immune cell recruitment and activation. ADAM8 expression has been associated with human atherosclerosis development and myocardial infarction, however a causal role of ADAM8 in atherosclerosis has not been investigated thus far. In this study, we examined the expression of ADAM8 in early and progressed human atherosclerotic lesions, in which ADAM8 was significantly upregulated in vulnerable lesions. In addition, ADAM8 expression was most prominent in the shoulder region of human atherosclerotic lesions, characterized by the abundance of foam cells. In mice, Adam8 was highly expressed in circulating neutrophils and in macrophages. Moreover, ADAM8 deficient mouse macrophages displayed reduced secretion of inflammatory mediators. Remarkably, however, neither hematopoietic nor whole-body ADAM8 deficiency in mice affected atherosclerotic lesion size. Additionally, except for an increase in granulocyte content in plaques of ADAM8 deficient mice, lesion morphology was unaffected. Taken together, whole body and hematopoietic ADAM8 does not contribute to advanced atherosclerotic plaque development, at least in female mice, although its expression might still be valuable as a diagnostic/prognostic biomarker to distinguish between stable and unstable lesions.
Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography
Authors: Corso Giulia , Mäger Imre , Lee Yi , Görgens André , Bultema Jarred , Giebel Bernd , Wood Matthew J. A. , Nordin Joel Z. , Andaloussi Samir EL 
Published: September 2017

AbstractExtracellular vesicles (EVs) play a pivotal role in cell-to-cell communication and have been shown to take part in several physiological and pathological processes. EVs have traditionally been purified by ultracentrifugation (UC), however UC has limitations, including resulting in, operator-dependant yields, EV aggregation and altered EV morphology, and moreover is time consuming. Here we show that commercially available bind-elute size exclusion chromatography (BE-SEC) columns purify EVs with high yield (recovery ~ 80%) in a time-efficient manner compared to current methodologies. This technique is reproducible and scalable, and surface marker analysis by bead-based flow cytometry revealed highly similar expression signatures compared with UC-purified samples. Furthermore, uptake of eGFP labelled EVs in recipient cells was comparable between BE-SEC and UC samples. Hence, the BE-SEC based EV purification method represents an important methodological advance likely to facilitate robust and reproducible studies of EV biology and therapeutic application.
Aspirin inhibits LPS-induced macrophage activation via the NF-κB pathway
Authors: Liu Yitong , Fang Silian , Li Xiaoyan , Feng Jie , Du Juan , Guo Lijia , Su Yingying , Zhou Jian , Ding Gang , Bai Yuxing , Wang Songling , Wang Hao , Liu Yi 
Published: September 2017

AbstractAspirin (acetylsalicylic acid, ASA) has been shown to improve bone marrow mesenchymal stem cell-based calvarial bone regeneration by promoting osteogenesis and inhibiting osteoclastogenesis. However, it remains unknown whether aspirin influences other immune cells during bone formation. In the present study, we investigated whether ASA treatment influenced macrophage activation during the LPS inducement. We found that ASA could downregulate the expressions of iNOS and TNF-α both in mouse peritoneum macrophages and RAW264.7 cells induced by LPS via the IκK/IκB/NF-κB pathway and a COX2/PGE2/EP2/NF-κB feedback loop, without affecting the expressions of FIZZ/YM-1/ARG1 induced by IL-4. Furthermore, we created a rat mandibular bone defect model and showed that ASA treatment improved bone regeneration by inhibiting LPS-induced macrophage activation in the early stages of inflammation. Taken together, our results indicated that ASA treatment was a feasible strategy for improving bone regeneration, particularly in inflammatory conditions.
Electric field and aging effects of uniaxial ferroelectrics Sr x Ba1−x Nb2O6 probed by Brillouin scattering
Authors: Aftabuzzaman M. , Helal M. A. , Paszkowski R. , Dec J. , Kleemann W. , Kojima S. 
Published: September 2017

AbstractStatic and dynamic heterogeneity of disordered system is one of the current topics in materials science. In disordered ferroelectric materials with random fields, dynamic polar nanoregions (PNRs) appear at Burns temperature and freeze into nanodomain state below Curie temperature (TC). This state is very sensitive to external electric field and aging by which it gradually switches into macrodomain state. However, the role of PNRs in such states belowTCis still a puzzling issue of materials science. Electric field and aging effects of uniaxial ferroelectric SrxBa1−xNb2O6(x = 0.40, SBN40) single crystals were studied using Brillouin scattering to clarify the critical nature of PNRs in domain states belowTC. On field heating, a broad anomaly in longitudinal acoustic (LA) velocity at low temperature region was due to an incomplete alignment of nanodomains caused by the interaction between PNRs. A sharp anomaly nearTCwas attributed to the complete switching of nanodomain to macrodomain state owing to the lack of interaction among PNRs. After isothermal aging belowTC, the noticeable increase of LA velocity was observed. It was unaffected by cyclic temperature measurements up toTC, and recovered to initial state outside of a narrow temperature range above and below aging temperature.