bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-lapse crystallography snapshots of a double-strand break repair polymerase in action
Authors: Jamsen Joonas A. , Beard William A. , Pedersen Lars C. , Shock David D. , Moon Andrea F. , Krahn Juno M. , Bebenek Katarzyna , Kunkel Thomas A. , Wilson Samuel H. 
Published: August 2017

AbstractDNA polymerase (pol) μ is a DNA-dependent polymerase that incorporates nucleotides during gap-filling synthesis in the non-homologous end-joining pathway of double-strand break repair. Here we report time-lapse X-ray crystallography snapshots of catalytic events during gap-filling DNA synthesis by pol μ. Unique catalytic intermediates and active site conformational changes that underlie catalysis are uncovered, and a transient third (product) metal ion is observed in the product state. The product manganese coordinates phosphate oxygens of the inserted nucleotide and PPi. The product metal is not observed during DNA synthesis in the presence of magnesium. Kinetic analyses indicate that manganese increases the rate constant for deoxynucleoside 5′-triphosphate insertion compared to magnesium. The likely product stabilization role of the manganese product metal in pol μ is discussed. These observations provide insight on structural attributes of this X-family double-strand break repair polymerase that impact its biological function in genome maintenance.
The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation
Authors: Wang Jing , Ge Pupu , Qiang Lihua , Tian Feng , Zhao Dongdong , Chai Qiyao , Zhu Mingzhao , Zhou Rongbin , Meng Guangxun , Iwakura Yoichiro , Gao George Fu , Liu Cui Hua 
Published: August 2017

AbstractMycobacterium tuberculosisPtpA is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-JNK, p-p38, and p-VPS33B, leading to suppression of host innate immunity. Here we show that, in addition, PtpA enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such asGADD45A). PtpA can bind directly to the promoter region ofGADD45Ain vitro. Both phosphatase activity and DNA-binding ability of PtpA are important in suppressing host innate immune responses. Furthermore, PtpA-expressingMycobacterium bovisBCG promotes proliferation and migration of human lung adenoma A549 cells in vitro and in a mouse xenograft model. Further research is needed to test whether mycobacteria, via PtpA, might affect cell proliferation or migration in humans.
Reduced and unstratified crust in CV chondrite parent body
Authors: Ganino Clément , Libourel Guy 
Published: August 2017

AbstractEarly Solar System planetesimal thermal models predict the heating of the chondritic protolith and the preservation of a chondritic crust on differentiated parent bodies. Petrological and geochemical analyses of chondrites have suggested that secondary alteration phases formed at low temperatures (<300 °C) by fluid-rock interaction where reduced and oxidized Vigarano type Carbonaceous (CV) chondrites witness different physicochemical conditions. From a thermodynamical survey of Ca-Fe-rich secondary phases in CV3 chondrites including silica activity (aSiO2), here we show that the classical distinction between reduced and oxidized chondrites is no longer valid and that their Ca-Fe-rich secondary phases formed in similar reduced conditions near the iron-magnetite redox buffer at low aSiO2 (log(aSiO2) <−1) and moderate temperature (210–610 °C). The various lithologies in CV3 chondrites are inferred to be fragments of an asteroid percolated heterogeneously via porous flow of hydrothermal fluid. Putative ‘onion shell’ structures are not anymore a requirement for the CV parent body crust.
Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation
Authors: Mkaddem Sanae Ben , Murua Amaya , Flament Héloise , Titeca-Beauport Dimitri , Bounaix Carine , Danelli Luca , Launay Pierre , Benhamou Marc , Blank Ulrich , Daugas Eric , Charles Nicolas , Monteiro Renato C. 
Published: August 2017

AbstractImmunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling. These SHP-1 signatures are relevant in vivo, as Lyn deficiency exacerbates nephritis and arthritis in mice, whereas Fyn deficiency is protective. Similarly, Fyn-activating signature is detected in patients with lupus nephritis, underlining the importance of this Lyn–Fyn balance. These data show how receptors discriminate negative from positive signals that respectively result in homeostatic or inflammatory conditions.
Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles
Authors: Chen Hsin-Yi , Wu Chien-Ting , Tang Chieh-Ju C. , Lin Yi-Nan , Wang Won-Jing , Tang Tang K. 
Published: August 2017

AbstractMutations in many centriolar protein-encoding genes cause primary microcephaly. Using super-resolution and electron microscopy, we find that the human microcephaly protein, RTTN, is recruited to the proximal end of the procentriole at early S phase, and is located at the inner luminal walls of centrioles. Further studies demonstrate that RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. CRISPR/Cas9-mediated RTTN gene knockout in p53-deficient cells induce amplification of primitive procentriole bodies that lack the distal-half centriolar proteins, POC5 and POC1B. Additional analyses show that RTTN serves as an upstream effector of CEP295, which mediates the loading of POC1B and POC5 to the distal-half centrioles. Interestingly, the naturally occurring microcephaly-associated mutant, RTTN (A578P), shows a low affinity for STIL binding and blocks centriole assembly. These findings reveal that RTTN contributes to building full-length centrioles and illuminate the molecular mechanism through which the RTTN (A578P) mutation causes primary microcephaly.
Bias induced up to 100% spin-injection and detection polarizations in ferromagnet/bilayer-hBN/graphene/hBN heterostructures
Authors: Gurram M. , Omar S. , Wees B. J. van 
Published: August 2017

AbstractWe study spin transport in a fully hBN encapsulated monolayer-graphene van der Waals heterostructure at room temperature. A top-layer of bilayer-hBN is used as a tunnel barrier for spin-injection and detection in graphene with ferromagnetic cobalt electrodes. We report surprisingly large and bias-induced (differential) spin-injection (detection) polarizations up to 50% (135%) at a positive voltage bias of + 0.6 V, as well as sign inverted polarizations up to −70% (−60%) at a reverse bias of −0.4 V. This demonstrates the potential of bilayer-hBN tunnel barriers for practical graphene spintronics applications. With such enhanced spin-injection and detection polarizations, we report a record two-terminal (inverted) spin-valve signals up to 800 Ω with a magnetoresistance ratio of 2.7%, and achieve spin accumulations up to 4.1 meV. We propose how these numbers can be increased further, for future technologically relevant graphene based spintronic devices.
Genome re-sequencing reveals the history of apple and supports a two-stage model for fruit enlargement
Authors: Duan Naibin , Bai Yang , Sun Honghe , Wang Nan , Ma Yumin , Li Mingjun , Wang Xin , Jiao Chen , Legall Noah , Mao Linyong , Wan Sibao , Wang Kun , He Tianming , Feng Shouqian , Zhang Zongying , Mao Zhiquan , Shen Xiang , Chen Xiaoliu , Jiang Yuanmao , Wu Shujing , Yin Chengmiao , Ge Shunfeng , Yang Long , Jiang Shenghui , Xu Haifeng , Liu Jingxuan , Wang Deyun , Qu Changzhi , Wang Yicheng , Zuo Weifang , Xiang Li , Liu Chang , Zhang Daoyuan , Gao Yuan , Xu Yimin , Xu Kenong , Chao Thomas , Fazio Gennaro , Shu Huairui , Zhong Gan-Yuan , Cheng Lailiang , Fei Zhangjun , Chen Xuesen 
Published: August 2017

AbstractHuman selection has reshaped crop genomes. Here we report an apple genome variation map generated through genome sequencing of 117 diverse accessions. A comprehensive model of apple speciation and domestication along the Silk Road is proposed based on evidence from diverse genomic analyses. Cultivated apples likely originate fromMalus sieversiiin Kazakhstan, followed by intensive introgressions fromM. sylvestris.M. sieversiiin Xinjiang of China turns out to be an “ancient” isolated ecotype not directly contributing to apple domestication. We have identified selective sweeps underlying quantitative trait loci/genes of important fruit quality traits including fruit texture and flavor, and provide evidences supporting a model of apple fruit size evolution comprising two major events with one occurring prior to domestication and the other during domestication. This study outlines the genetic basis of apple domestication and evolution, and provides valuable information for facilitating marker-assisted breeding and apple improvement.
Dirac point induced ultralow-threshold laser and giant optoelectronic quantum oscillations in graphene-based heterojunctions
Authors: Haider Golam , Ravindranath Rini , Chen Tzu-Pei , Roy Prathik , Roy Pradip Kumar , Cai Shu-Yi , Chang Huan-Tsung , Chen Yang-Fang 
Published: August 2017

AbstractThe occurrence of zero effective mass of electrons at the vicinity of the Dirac point is expected to create new paradigms for scientific research and technological applications, but the related discoveries are rather limited. Here, we demonstrate that a simple architecture composed of graphene quantum dots sandwiched by graphene layers can exhibit several intriguing features, including the Dirac point induced ultralow-threshold laser, giant peak-to-valley ratio (PVR) with ultra-narrow spectra of negative differential resistance and quantum oscillations of current as well as light emission intensity. In particular, the threshold of only 12.4 nA cm−2 is the lowest value ever reported on electrically driven lasers, and the PVR value of more than 100 also sets the highest record compared with all available reports on graphene-based devices. We show that all these intriguing phenomena can be interpreted based on the unique band structures of graphene quantum dots and graphene as well as resonant quantum tunneling.
The mTORC1-4E-BP-eIF4E axis controls de novo Bcl6 protein synthesis in T cells and systemic autoimmunity
Authors: Yi Woelsung , Gupta Sanjay , Ricker Edd , Manni Michela , Jessberger Rolf , Chinenov Yurii , Molina Henrik , Pernis Alessandra B. 
Published: August 2017

AbstractPost-transcriptional modifications can control protein abundance, but the extent to which these alterations contribute to the expression of T helper (TH) lineage-defining factors is unknown. Tight regulation of Bcl6 expression, an essential transcription factor for T follicular helper (TFH) cells, is critical as aberrant TFH cell expansion is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we show that lack of the SLE risk variant Def6 results in deregulation of Bcl6 protein synthesis in T cells as a result of enhanced activation of the mTORC1–4E-BP–eIF4E axis, secondary to aberrant assembly of a raptor–p62–TRAF6 complex. Proteomic analysis reveals that this pathway selectively controls the abundance of a subset of proteins. Rapamycin or raptor deletion ameliorates the aberrant TFH cell expansion in mice lacking Def6. Thus deregulation of mTORC1-dependent pathways controlling protein synthesis can result in T-cell dysfunction, indicating a mechanism by which mTORC1 can promote autoimmunity.
Formation pathways of mesoporous silica nanoparticles with dodecagonal tiling
Authors: Sun Yao , Ma Kai , Kao Teresa , Spoth Katherine A. , Sai Hiroaki , Zhang Duhan , Kourkoutis Lena F. , Elser Veit , Wiesner Ulrich 
Published: August 2017

AbstractConsiderable progress in the fabrication of quasicrystals demonstrates that they can be realized in a broad range of materials. However, the development of chemistries enabling direct experimental observation of early quasicrystal growth pathways remains challenging. Here, we report the synthesis of four surfactant-directed mesoporous silica nanoparticle structures, including dodecagonal quasicrystalline nanoparticles, as a function of micelle pore expander concentration or stirring rate. We demonstrate that the early formation stages of dodecagonal quasicrystalline mesoporous silica nanoparticles can be preserved, where precise control of mesoporous silica nanoparticle size down to <30 nm facilitates comparison between mesoporous silica nanoparticles and simulated single-particle growth trajectories beginning with a single tiling unit. Our results reveal details of the building block size distributions during early growth and how they promote quasicrystal formation. This work identifies simple synthetic parameters, such as stirring rate, that may be exploited to design other quasicrystal-forming self-assembly chemistries and processes.
Inference and interrogation of a coregulatory network in the context of lipid accumulation in Yarrowia lipolytica
Authors: Trébulle Pauline , Nicaud Jean-Marc , Leplat Christophe , Elati Mohamed 
Published: August 2017

AbstractComplex phenotypes, such as lipid accumulation, result from cooperativity between regulators and the integration of multiscale information. However, the elucidation of such regulatory programs by experimental approaches may be challenging, particularly in context-specific conditions. In particular, we know very little about the regulators of lipid accumulation in the oleaginous yeast of industrial interest Yarrowia lipolytica. This lack of knowledge limits the development of this yeast as an industrial platform, due to the time-consuming and costly laboratory efforts required to design strains with the desired phenotypes. In this study, we aimed to identify context-specific regulators and mechanisms, to guide explorations of the regulation of lipid accumulation in Y. lipolytica. Using gene regulatory network inference, and considering the expression of 6539 genes over 26 time points from GSE35447 for biolipid production and a list of 151 transcription factors, we reconstructed a gene regulatory network comprising 111 transcription factors, 4451 target genes and 17048 regulatory interactions (YL-GRN-1) supported by evidence of protein–protein interactions. This study, based on network interrogation and wet laboratory validation (a) highlights the relevance of our proposed measure, the transcription factors influence, for identifying phases corresponding to changes in physiological state without prior knowledge (b) suggests new potential regulators and drivers of lipid accumulation and (c) experimentally validates the impact of six of the nine regulators identified on lipid accumulation, with variations in lipid content from +43.2% to −31.2% on glucose or glycerol.
β1-adrenergic receptor O-glycosylation regulates N-terminal cleavage and signaling responses in cardiomyocytes
Authors: Park Misun , Reddy Gopireddy R. , Wallukat Gerd , Xiang Yang K. , Steinberg Susan F. 
Published: August 2017

Abstractβ1-adrenergic receptors (β1ARs) mediate catecholamine actions in cardiomyocytes by coupling to both Gs/cAMP-dependent and Gs-independent/growth-regulatory pathways. Structural studies of the β1AR define ligand-binding sites in the transmembrane helices and effector docking sites at the intracellular surface of the β1AR, but the extracellular N-terminus, which is a target for post-translational modifications, typically is ignored. This study identifies β1AR N-terminal O-glycosylation at Ser37/Ser41 as a mechanism that prevents β1AR N-terminal cleavage. We used an adenoviral overexpression strategy to show that both full-length/glycosylated β1ARs and N-terminally truncated glycosylation-defective β1ARs couple to cAMP and ERK-MAPK signaling pathways in cardiomyocytes. However, a glycosylation defect that results in N-terminal truncation stabilizes β1ARs in a conformation that is biased toward the cAMP pathway. The identification of O-glycosylation and N-terminal cleavage as novel structural determinants of β1AR responsiveness in cardiomyocytes could be exploited for therapeutic advantage.
Conductance fluctuations in InAs quantum wells possibly driven by Zitterbewegung
Authors: Iwasaki Yu , Hashimoto Yoshiaki , Nakamura Taketomo , Katsumoto Shingo 
Published: August 2017

AbstractThe highly successful Dirac equation predicts peculiar phenomena such as Klein tunnelling and Zitterbewegung (ZB) of electrons. From its conception by Erwin Schrödinger, ZB has been considered key in understanding relativistic quantum mechanics. However, observing the ZB of electrons has proved difficult, and instead various emulations of the phenomenon have been proposed producing several successes. Concerning charge transport in semiconductors and graphene, expectations were high but little has been reported. Here, we report a surprisingly large ZB effect on charge transport in a semiconductor nanostructure playing “flat pinball”. The setup is a narrow strip of InAs two-dimensional electron gas with strong Rashba spin–orbit coupling. Six quantum point contacts act as pinball pockets. In transiting between two contacts, ZB appears as a large reproducible conductance fluctuation that depends on the in-plane magnetic field. Numerical simulations successfully reproduced our experimental observations confirming that ZB causes this conductance fluctuation.
Reconstruction of a Genome-scale Metabolic Network of Komagataeibacter nataicola RZS01 for Cellulose Production
Authors: Zhang Heng , Ye Chao , Xu Nan , Chen Chuntao , Chen Xiao , Yuan Fanshu , Xu Yunhua , Yang Jiazhi , Sun Dongping 
Published: August 2017

AbstractBacterial cellulose (BC) is widely used in industries owing to its high purity and strength. Although Komagataeibacter nataicola is a representative species for BC production, its intracellular metabolism leading to BC secretion is unclear. In the present study, a genome-scale metabolic network of cellulose-producing K. nataicola strain RZS01 was reconstructed to understand its metabolic behavior. This model iHZ771 comprised 771 genes, 2035 metabolites, and 2014 reactions. Constraint-based analysis was used to characterize and evaluate the critical intracellular pathways. The analysis revealed that a total of 71 and 30 genes are necessary for cellular growth in a minimal medium and complex medium, respectively. Glycerol was identified as the optimal carbon source for the highest BC production. The minimization of metabolic adjustment algorithm identified 8 genes as potential targets for over-production of BC. Overall, model iHZ771 proved to be a useful platform for understanding the physiology and BC production of K. nataicola.
Fermentative hydrogen production from Jerusalem artichoke by Clostridium tyrobutyricum expressing exo-inulinase gene
Authors: Jiang Ling , Wu Qian , Xu Qing , Zhu Liying , Huang He 
Published: August 2017

AbstractClostridium tyrobutyricum ATCC25755 has been reported as being able to produce significant quantities of hydrogen. In this study, the exo-inulinase encoding gene cloned from Paenibacillus polymyxa SC-2 was into the expression plasmid pSY6 and expressed in the cells of C. tyrobutyricum. The engineered C. tyrobutyricum strain efficiently fermented the inulin-type carbohydrates from Jerusalem artichoke, without any pretreatment being necessary for the production of hydrogen. A comparatively high hydrogen yield (3.7 mol/mol inulin-type sugar) was achieved after 96 h in a batch process with simultaneous saccharification and fermentation (SSF), with an overall volumetric productivity rate of 620 ± 60 mL/h/L when the initial total sugar concentration of the inulin extract was increased to 100 g/L. Synthesis of inulinase in the batch SSF culture was closely associated with strain growth until the end of the exponential phase, reaching a maximum activity of 28.4 ± 0.26 U/mL. The overall results show that the highly productive and abundant biomass crop Jerusalem artichoke can be a good substrate for hydrogen production, and that the application of batch SSF for its conversion has the potential to become a cost-effective process in the near future.
Magnetic moment evolution and spin freezing in doped BaFe2As2
Authors: Pelliciari Jonathan , Huang Yaobo , Ishii Kenji , Zhang Chenglin , Dai Pengcheng , Chen Gen Fu , Xing Lingyi , Wang Xiancheng , Jin Changqing , Ding Hong , Werner Philipp , Schmitt Thorsten 
Published: August 2017

AbstractFe-K
β
X-ray emission spectroscopy measurements reveal an asymmetric doping dependence of the magnetic moments μbare in electron- and hole-doped BaFe2As2. At low temperature, μbare is nearly constant in hole-doped samples, whereas it decreases upon electron doping. Increasing temperature substantially enhances μbare in the hole-doped region, which is naturally explained by the theoretically predicted crossover into a spin-frozen state. Our measurements demonstrate the importance of Hund’s-coupling and electronic correlations, especially for hole-doped BaFe2As2, and the inadequacy of a fully localized or fully itinerant description of the 122 family of Fe pnictides.
A dynamical framework for complex fractional killing
Authors: Ballweg Richard , Paek Andrew L. , Zhang Tongli 
Published: August 2017

AbstractWhen chemotherapy drugs are applied to tumor cells with the same or similar genotypes, some cells are killed, while others survive. This fractional killing contributes to drug resistance in cancer. Through an incoherent feedforward loop, chemotherapy drugs not only activate p53 to induce cell death, but also promote the expression of apoptosis inhibitors which inhibit cell death. Consequently, cells in which p53 is activated early undergo apoptosis while cells in which p53 is activated late survive. The incoherent feedforward loop and the essential role of p53 activation timing makes fractional killing a complex dynamical challenge, which is hard to understand with intuition alone. To better understand this process, we have constructed a representative model by integrating the control of apoptosis with the relevant signaling pathways. After the model was trained to recapture the observed properties of fractional killing, it was analyzed with nonlinear dynamical tools. The analysis suggested a simple dynamical framework for fractional killing, which predicts that cell fate can be altered in three possible ways: alteration of bifurcation geometry, alteration of cell trajectories, or both. These predicted categories can explain existing strategies known to combat fractional killing and facilitate the design of novel strategies.