bluuebunny/crossref_metadata_2025_split huggingface dataset:
A TAD boundary is preserved upon deletion of the CTCF-rich Firre locus
Authors: Barutcu A. Rasim , Maass Philipp G. , Lewandowski Jordan P. , Weiner Catherine L. , Rinn John L. 
Published: April 2018

AbstractThe binding of the transcriptional regulator CTCF to the genome has been implicated in the formation of topologically associated domains (TADs). However, the general mechanisms of folding the genome into TADs are not fully understood. Here we test the effects of deleting a CTCF-rich locus on TAD boundary formation. Using genome-wide chromosome conformation capture (Hi-C), we focus on one TAD boundary on chromosome X harboring ~ 15 CTCF binding sites and located at the long non-coding RNA (lncRNA) locus Firre. Specifically, this TAD boundary is invariant across evolution, tissues, and temporal dynamics of X-chromosome inactivation. We demonstrate that neither the deletion of this locus nor the ectopic insertion of Firre cDNA or its ectopic expression are sufficient to alter TADs in a sex-specific or allele-specific manner. In contrast, Firre’s deletion disrupts the chromatin super-loop formation of the inactive X-chromosome. Collectively, our findings suggest that apart from CTCF binding, additional mechanisms may play roles in establishing TAD boundary formation.
Quantum metrology with quantum-chaotic sensors
Authors: Fiderer Lukas J. , Braun Daniel 
Published: April 2018

AbstractQuantum metrology promises high-precision measurements of classical parameters with far reaching implications for science and technology. So far, research has concentrated almost exclusively on quantum-enhancements in integrable systems, such as precessing spins or harmonic oscillators prepared in non-classical states. Here we show that large benefits can be drawn from rendering integrable quantum sensors chaotic, both in terms of achievable sensitivity as well as robustness to noise, while avoiding the challenge of preparing and protecting large-scale entanglement. We apply the method to spin-precession magnetometry and show in particular that the sensitivity of state-of-the-art magnetometers can be further enhanced by subjecting the spin-precession to non-linear kicks that renders the dynamics chaotic.
Sign epistasis caused by hierarchy within signalling cascades
Authors: Nghe Philippe , Kogenaru Manjunatha , Tans Sander J. 
Published: April 2018

AbstractSign epistasis is a central evolutionary constraint, but its causal factors remain difficult to predict. Here we use the notion of parameterised optima to explain epistasis within a signalling cascade, and test these predictions in Escherichia coli. We show that sign epistasis arises from the benefit of tuning phenotypic parameters of cascade genes with respect to each other, rather than from their complex and incompletely known genetic bases. Specifically, sign epistasis requires only that the optimal phenotypic parameters of one gene depend on the phenotypic parameters of another, independent of other details, such as activating or repressing nature, position within the cascade, intra-genic pleiotropy or genotype. Mutational effects change sign more readily in downstream genes, indicating that optimising downstream genes is more constrained. The findings show that sign epistasis results from the inherent upstream-downstream hierarchy between signalling cascade genes, and can be addressed without exhaustive genotypic mapping.
Towards a new approach to reveal dynamical organization of the brain using topological data analysis
Authors: Saggar Manish , Sporns Olaf , Gonzalez-Castillo Javier , Bandettini Peter A. , Carlsson Gunnar , Glover Gary , Reiss Allan L. 
Published: April 2018

AbstractLittle is known about how our brains dynamically adapt for efficient functioning. Most previous work has focused on analyzing changes in co-fluctuations between a set of brain regions over several temporal segments of the data. We argue that by collapsing data in space or time, we stand to lose useful information about the brain’s dynamical organization. Here we use Topological Data Analysis to reveal the overall organization of whole-brain activity maps at a single-participant level—as an interactive representation—without arbitrarily collapsing data in space or time. Using existing multitask fMRI datasets, with the known ground truth about the timing of transitions from one task-block to next, our approach tracks both within- and between-task transitions at a much faster time scale (~4–9 s) than before. The individual differences in the revealed dynamical organization predict task performance. In summary, our approach distills complex brain dynamics into interactive and behaviorally relevant representations.
How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin
Authors: Doud Michael B. , Lee Juhye M. , Bloom Jesse D. 
Published: April 2018

AbstractInfluenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.
Improved calcium sensor GCaMP-X overcomes the calcium channel perturbations induced by the calmodulin in GCaMP
Authors: Yang Yaxiong , Liu Nan , He Yuanyuan , Liu Yuxia , Ge Lin , Zou Linzhi , Song Sen , Xiong Wei , Liu Xiaodong 
Published: April 2018

AbstractGCaMP, one popular type of genetically-encoded Ca2+ indicator, has been associated with various side-effects. Here we unveil the intrinsic problem prevailing over different versions and applications, showing that GCaMP containing CaM (calmodulin) interferes with both gating and signaling of L-type calcium channels (CaV1). GCaMP acts as an impaired apoCaM and Ca2+/CaM, both critical to CaV1, which disrupts Ca2+ dynamics and gene expression. We then design and implement GCaMP-X, by incorporating an extra apoCaM-binding motif, effectively protecting CaV1-dependent excitation–transcription coupling from perturbations. GCaMP-X resolves the problems of detrimental nuclear accumulation, acute and chronic Ca2+ dysregulation, and aberrant transcription signaling and cell morphogenesis, while still demonstrating excellent Ca2+-sensing characteristics partly inherited from GCaMP. In summary, CaM/CaV1 gating and signaling mechanisms are elucidated for GCaMP side-effects, while allowing the development of GCaMP-X to appropriately monitor cytosolic, submembrane or nuclear Ca2+, which is also expected to guide the future design of CaM-based molecular tools.
Somatic activating mutations in MAP2K1 cause melorheostosis
Authors: Kang Heeseog , Jha Smita , Deng Zuoming , Fratzl-Zelman Nadja , Cabral Wayne A. , Ivovic Aleksandra , Meylan Françoise , Hanson Eric P. , Lange Eileen , Katz James , Roschger Paul , Klaushofer Klaus , Cowen Edward W. , Siegel Richard M. , Marini Joan C. , Bhattacharyya Timothy 
Published: April 2018

AbstractMelorheostosis is a sporadic disease of uncertain etiology characterized by asymmetric bone overgrowth and functional impairment. Using whole exome sequencing, we identify somatic mosaic MAP2K1 mutations in affected, but not unaffected, bone of eight unrelated patients with melorheostosis. The activating mutations (Q56P, K57E and K57N) cluster tightly in the MEK1 negative regulatory domain. Affected bone displays a mosaic pattern of increased p-ERK1/2 in osteoblast immunohistochemistry. Osteoblasts cultured from affected bone comprise two populations with distinct p-ERK1/2 levels by flow cytometry, enhanced ERK1/2 activation, and increased cell proliferation. However, these MAP2K1 mutations inhibit BMP2-mediated osteoblast mineralization and differentiation in vitro, underlying the markedly increased osteoid detected in affected bone histology. Mosaicism is also detected in the skin overlying bone lesions in four of five patients tested. Our data show that the MAP2K1 oncogene is important in human bone formation and implicate MEK1 inhibition as a potential treatment avenue for melorheostosis.
Performance of the Trioplex real-time RT-PCR assay for detection of Zika, dengue, and chikungunya viruses
Authors: Santiago Gilberto A. , Vázquez Jesús , Courtney Sean , Matías Katia Y. , Andersen Lauren E. , Colón Candimar , Butler Angela E. , Roulo Rebecca , Bowzard John , Villanueva Julie M. , Muñoz-Jordan Jorge L. 
Published: April 2018

AbstractThe emergence and spread of Zika virus (ZIKV) presented a challenge to the diagnosis of ZIKV infections in areas with transmission of dengue (DENV) and chikungunya (CHIKV) viruses. To facilitate detection of ZIKV infections, and differentiate these infections from DENV and CHIKV, we developed the Trioplex real-time RT-PCR assay (Trioplex assay). Here, we describe the optimization of multiplex and singleplex formats of the assay for a variety of chemistries and instruments to facilitate global standardization and implementation. We evaluated the analytical performance of all Trioplex modalities for detection of these three pathogens in serum and whole blood, and for ZIKV in urine. The limit of detection for the three viruses and in different RNA-extraction modalities is near 103 genome copy equivalents per milliliter (GCE/mL). Simultaneous testing of more than one specimen type from each patient provides a 6.4% additional diagnostic sensitivity. Overall, the high sensitivity of the Trioplex assay demonstrates the utility of this assay ascertaining Zika cases.
STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection
Authors: Ding Siyuan , Diep Jonathan , Feng Ningguo , Ren Lili , Li Bin , Ooi Yaw Shin , Wang Xin , Brulois Kevin F. , Yasukawa Linda L. , Li Xingnan , Kuo Calvin J. , Solomon David A. , Carette Jan E. , Greenberg Harry B. 
Published: April 2018

AbstractCohesin is a multi-subunit nuclear protein complex that coordinates sister chromatid separation during cell division. Highly frequent somatic mutations in genes encoding core cohesin subunits have been reported in multiple cancer types. Here, using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, we demonstrate that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids. Mechanistically, STAG2 deficiency results in spontaneous genomic DNA damage and robust interferon (IFN) expression via the cGAS-STING cytosolic DNA-sensing pathway. The resultant activation of JAK-STAT signaling and IFN-stimulated gene (ISG) expression broadly protects against virus infections, including RVs. Our work highlights a previously undocumented role of the cohesin complex in regulating IFN homeostasis and identifies new therapeutic avenues for manipulating the innate immunity.
Multicomponent reactions provide key molecules for secret communication
Authors: Boukis Andreas C. , Reiter Kevin , Frölich Maximiliane , Hofheinz Dennis , Meier Michael A. R. 
Published: April 2018

AbstractA convenient and inherently more secure communication channel for encoding messages via specifically designed molecular keys is introduced by combining advanced encryption standard cryptography with molecular steganography. The necessary molecular keys require large structural diversity, thus suggesting the application of multicomponent reactions. Herein, the Ugi four-component reaction of perfluorinated acids is utilized to establish an exemplary database consisting of 130 commercially available components. Considering all permutations, this combinatorial approach can unambiguously provide 500,000 molecular keys in only one synthetic procedure per key. The molecular keys are transferred nondigitally and concealed by either adsorption onto paper, coffee, tea or sugar as well as by dissolution in a perfume or in blood. Re-isolation and purification from these disguises is simplified by the perfluorinated sidechains of the molecular keys. High resolution tandem mass spectrometry can unequivocally determine the molecular structure and thus the identity of the key for a subsequent decryption of an encoded message.
GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease
Authors: Lozovaya N. , Eftekhari S. , Cloarec R. , Gouty-Colomer L. A. , Dufour A. , Riffault B. , Billon-Grand M. , Pons-Bennaceur A. , Oumar N. , Burnashev N. , Ben-Ari Y. , Hammond C. 
Published: April 2018

AbstractWe report that half striatal cholinergic interneurons are dual transmitter cholinergic and GABAergic interneurons (CGINs) expressing ChAT, GAD65, Lhx7, and Lhx6 mRNAs, labeled with GAD and VGAT, generating monosynaptic dual cholinergic/GABAergic currents and an inhibitory pause response. Dopamine deprivation increases CGINs ongoing activity and abolishes GABAergic inhibition including the cortico-striatal pause because of high [Cl−]i levels. Dopamine deprivation also dramatically increases CGINs dendritic arbors and monosynaptic interconnections probability, suggesting the formation of a dense CGINs network. The NKCC1 chloride importer antagonist bumetanide, which reduces [Cl−]i levels, restores GABAergic inhibition, the cortico-striatal pause-rebound response, and attenuates motor effects of dopamine deprivation. Therefore, most of the striatal cholinergic excitatory drive is balanced by a concomitant powerful GABAergic inhibition that is impaired by dopamine deprivation. The attenuation by bumetanide of cardinal features of Parkinson’s disease paves the way to a novel therapeutic strategy based on a restoration of low [Cl−]i levels and GABAergic inhibition.
Allosteric regulation alters carrier domain translocation in pyruvate carboxylase
Authors: Liu Yumeng , Budelier Melissa M. , Stine Katelyn , St. Maurice Martin 
Published: April 2018

AbstractPyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. The reaction occurs in two separate catalytic domains, coupled by the long-range translocation of a biotinylated carrier domain (BCCP). Here, we use a series of hybrid PC enzymes to examine multiple BCCP translocation pathways in PC. These studies reveal that the BCCP domain of PC adopts a wide range of translocation pathways during catalysis. Furthermore, the allosteric activator, acetyl CoA, promotes one specific intermolecular carrier domain translocation pathway. These results provide a basis for the ordered thermodynamic state and the enhanced carboxyl group transfer efficiency in the presence of acetyl CoA, and reveal that the allosteric effector regulates enzyme activity by altering carrier domain movement. Given the similarities with enzymes involved in the modular synthesis of natural products, the allosteric regulation of carrier domain movements in PC is likely to be broadly applicable to multiple important enzyme systems.
Two-dimensional electronic transport and surface electron accumulation in MoS2
Authors: Siao M. D. , Shen W. C. , Chen R. S. , Chang Z. W. , Shih M. C. , Chiu Y. P. , Cheng C.-M. 
Published: April 2018

AbstractBecause the surface-to-volume ratio of quasi-two-dimensional materials is extremely high, understanding their surface characteristics is crucial for practically controlling their intrinsic properties and fabricating p-type and n-type layered semiconductors. Van der Waals crystals are expected to have an inert surface because of the absence of dangling bonds. However, here we show that the surface of high-quality synthesized molybdenum disulfide (MoS2) is a major n-doping source. The surface electron concentration of MoS2is nearly four orders of magnitude higher than that of its inner bulk. Substantial thickness-dependent conductivity in MoS2nanoflakes was observed. The transfer length method suggested the current transport in MoS2following a two-dimensional behavior rather than the conventional three-dimensional mode. Scanning tunneling microscopy and angle-resolved photoemission spectroscopy measurements confirmed the presence of surface electron accumulation in this layered material. Notably, the in situ-cleaved surface exhibited a nearly intrinsic state without electron accumulation.
Arctic sea ice is an important temporal sink and means of transport for microplastic
Authors: Peeken Ilka , Primpke Sebastian , Beyer Birte , Gütermann Julia , Katlein Christian , Krumpen Thomas , Bergmann Melanie , Hehemann Laura , Gerdts Gunnar 
Published: April 2018

AbstractMicroplastics (MP) are recognized as a growing environmental hazard and have been identified as far as the remote Polar Regions, with particularly high concentrations of microplastics in sea ice. Little is known regarding the horizontal variability of MP within sea ice and how the underlying water body affects MP composition during sea ice growth. Here we show that sea ice MP has no uniform polymer composition and that, depending on the growth region and drift paths of the sea ice, unique MP patterns can be observed in different sea ice horizons. Thus even in remote regions such as the Arctic Ocean, certain MP indicate the presence of localized sources. Increasing exploitation of Arctic resources will likely lead to a higher MP load in the Arctic sea ice and will enhance the release of MP in the areas of strong seasonal sea ice melt and the outflow gateways.
Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration
Authors: Harada Akihito , Maehara Kazumitsu , Ono Yusuke , Taguchi Hiroyuki , Yoshioka Kiyoshi , Kitajima Yasuo , Xie Yan , Sato Yuko , Iwasaki Takeshi , Nogami Jumpei , Okada Seiji , Komatsu Tetsuro , Semba Yuichiro , Takemoto Tatsuya , Kimura Hiroshi , Kurumizaka Hitoshi , Ohkawa Yasuyuki 
Published: April 2018

AbstractRegulation of gene expression requires selective incorporation of histone H3 variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but their functions are unclear. Here we characterize the function of histone H3.3 sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrate an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes. The crystal structure of the nucleosome containing H3mm7 reveals that, unlike the S57 residue of other H3 proteins, the H3mm7-specific A57 residue cannot form a hydrogen bond with the R40 residue of the cognate H4 molecule. Consequently, the H3mm7 nucleosome is unstable in vitro and exhibited higher mobility in vivo compared with the H3.3 nucleosome. We conclude that the unstable H3mm7 nucleosome may be required for proper skeletal muscle differentiation.
Rice auxin influx carrier OsAUX1 facilitates root hair elongation in response to low external phosphate
Authors: Giri Jitender , Bhosale Rahul , Huang Guoqiang , Pandey Bipin K. , Parker Helen , Zappala Susan , Yang Jing , Dievart Anne , Bureau Charlotte , Ljung Karin , Price Adam , Rose Terry , Larrieu Antoine , Mairhofer Stefan , Sturrock Craig J. , White Philip , Dupuy Lionel , Hawkesford Malcolm , Perin Christophe , Liang Wanqi , Peret Benjamin , Hodgman Charlie T. , Lynch Jonathan , Wissuwa Matthias , Zhang Dabing , Pridmore Tony , Mooney Sacha J. , Guiderdoni Emmanuel , Swarup Ranjan , Bennett Malcolm J. 
Published: April 2018

AbstractRoot traits such as root angle and hair length influence resource acquisition particularly for immobile nutrients like phosphorus (P). Here, we attempted to modify root angle in rice by disrupting the OsAUX1 auxin influx transporter gene in an effort to improve rice P acquisition efficiency. We show by X-ray microCT imaging that root angle is altered in the osaux1 mutant, causing preferential foraging in the top soil where P normally accumulates, yet surprisingly, P acquisition efficiency does not improve. Through closer investigation, we reveal that OsAUX1 also promotes root hair elongation in response to P limitation. Reporter studies reveal that auxin response increases in the root hair zone in low P environments. We demonstrate that OsAUX1 functions to mobilize auxin from the root apex to the differentiation zone where this signal promotes hair elongation when roots encounter low external P. We conclude that auxin and OsAUX1 play key roles in promoting root foraging for P in rice.
Electron density modulation of NiCo2S4 nanowires by nitrogen incorporation for highly efficient hydrogen evolution catalysis
Authors: Wu Yishang , Liu Xiaojing , Han Dongdong , Song Xianyin , Shi Lei , Song Yao , Niu Shuwen , Xie Yufang , Cai Jinyan , Wu Shaoyang , Kang Jian , Zhou Jianbin , Chen Zhiyan , Zheng Xusheng , Xiao Xiangheng , Wang Gongming 
Published: April 2018

AbstractMetal sulfides for hydrogen evolution catalysis typically suffer from unfavorable hydrogen desorption properties due to the strong interaction between the adsorbed H and the intensely electronegative sulfur. Here, we demonstrate a general strategy to improve the hydrogen evolution catalysis of metal sulfides by modulating the surface electron densities. The N modulated NiCo2S4 nanowire arrays exhibit an overpotential of 41 mV at 10 mA cm−2 and a Tafel slope of 37 mV dec−1, which are very close to the performance of the benchmark Pt/C in alkaline condition. X-ray photoelectron spectroscopy, synchrotron-based X-ray absorption spectroscopy, and density functional theory studies consistently confirm the surface electron densities of NiCo2S4 have been effectively manipulated by N doping. The capability to modulate the electron densities of the catalytic sites could provide valuable insights for the rational design of highly efficient catalysts for hydrogen evolution and beyond.
Shallow magma diversions during explosive diatreme-forming eruptions
Authors: Le Corvec Nicolas , Muirhead James D. , White James D. L. 
Published: April 2018

AbstractThe diversion of magma is an important mechanism that may lead to the relocation of a volcanic vent. Magma diversion is known to occur during explosive volcanic eruptions generating subterranean excavation and remobilization of country and volcanic rocks. However, feedbacks between explosive crater formation and intrusion processes have not been considered previously, despite their importance for understanding evolving hazards during volcanic eruptions. Here, we apply numerical modeling to test the impacts of excavation and subsequent infilling of diatreme structures on stress states and intrusion geometries during the formation of maar–diatreme complexes. Explosive excavation and infilling of diatremes affects local stress states which inhibits magma ascent and drives lateral diversion at various depths, which are expected to promote intra-diatreme explosions, host rock mixing, and vent migration. Our models demonstrate novel mechanisms explaining the generation of saucer-shaped sills, linked with magma diversion and enhanced intra-diatreme explosive fragmentation during maar-diatreme volcanism. Similar mechanisms will occur at other volcanic vents producing crater-forming eruptions.