bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1,4,5-trisphosphate receptors
Authors: Liang Jingjing , Lyu Jun , Zhao Meng , Li Dan , Zheng Mingzhu , Fang Yan , Zhao Fangzhu , Lou Jun , Guo Chuansheng , Wang Lie , Wang Di , Liu Wanli , Lu Linrong 
Published: June 2017

AbstractThymocyte-expressed, positive selection-associated 1 (Tespa1) is important in T cell receptor (TCR)-driven thymocyte development. Downstream of the TCR, Tespa1 is a crucial component of the linker for activation of T cells (LAT) signalosome, facilitating calcium signalling and subsequent MAPK activation. However, it is unknown how Tespa1 elicits calcium signalling. Here, we show that inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) is crucial for Tespa1-optimized, TCR-induced Ca2+ flux and thymocyte development. Upon TCR stimulation, Tespa1 directly interacts with IP3R1 and recruits it to the TCR complex, where IP3R1 is phosphorylated at Y353 by Fyn. This Tespa1-IP3R1 interaction is mediated by the F187 and F188 residues of Tespa1 and the amino-terminus of IP3R1. Tespa1-F187A/F188A mutant mice phenocopy Tespa1-deficient mice with impaired late thymocyte development due to reduced IP3R1 translocation to the TCR-proximal region. Our work elucidates the function of Tespa1 in T cell development and the regulation of TCR-induced Ca2+ signalling through IP3R1.
An autonomous organic reaction search engine for chemical reactivity
Authors: Dragone Vincenza , Sans Victor , Henson Alon B. , Granda Jaroslaw M. , Cronin Leroy 
Published: June 2017

AbstractThe exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways.
Raptor regulates functional maturation of murine beta cells
Authors: Ni Qicheng , Gu Yanyun , Xie Yun , Yin Qinglei , Zhang Hongli , Nie Aifang , Li Wenyi , Wang Yanqiu , Ning Guang , Wang Weiqing , Wang Qidi 
Published: June 2017

AbstractDiabetes is associated with beta cell mass loss and islet dysfunctions. mTORC1 regulates beta cell survival, proliferation and function in physiological and pathological conditions, such as pregnancy and pancreatectomy. Here we show that deletion of Raptor, which is an essential component of mTORC1, in insulin-expressing cells promotes hypoinsulinemia and glucose intolerance. Raptor-deficient beta cells display reduced glucose responsiveness and exhibit a glucose metabolic profile resembling fetal beta cells. Knockout islets have decreased expression of key factors of functional maturation and upregulation of neonatal markers and beta cell disallowed genes, resulting in loss of functional maturity. Mechanistically, Raptor-deficient beta cells show reduced expression of DNA-methyltransferase 3a and altered patterns of DNA methylation at loci that are involved in the repression of disallowed genes. The present findings highlight a novel role of mTORC1 as a core mechanism governing postnatal beta cell maturation and physiologic beta cell mass during adulthood.
Vegetation recovery in tidal marshes reveals critical slowing down under increased inundation
Authors: van Belzen Jim , van de Koppel Johan , Kirwan Matthew L. , van der Wal Daphne , Herman Peter M. J. , Dakos Vasilis , Kéfi Sonia , Scheffer Marten , Guntenspergen Glenn R. , Bouma Tjeerd J. 
Published: June 2017

AbstractA declining rate of recovery following disturbance has been proposed as an important early warning for impending tipping points in complex systems. Despite extensive theoretical and laboratory studies, this ‘critical slowing down’ remains largely untested in the complex settings of real-world ecosystems. Here, we provide both observational and experimental support of critical slowing down along natural stress gradients in tidal marsh ecosystems. Time series of aerial images of European marsh development reveal a consistent lengthening of recovery time as inundation stress increases. We corroborate this finding with transplantation experiments in European and North American tidal marshes. In particular, our results emphasize the power of direct observational or experimental measures of recovery over indirect statistical signatures, such as spatial variance or autocorrelation. Our results indicate that the phenomenon of critical slowing down can provide a powerful tool to probe the resilience of natural ecosystems.
Ash1l and lnc-Smad3 coordinate Smad3 locus accessibility to modulate iTreg polarization and T cell autoimmunity
Authors: Xia Meng , Liu Juan , Liu Shuxun , Chen Kun , Lin Hongyu , Jiang Minghong , Xu Xiaoqing , Xue Yiquan , Liu Wei , Gu Yan , Zhang Xiang , Li Zhiqing , Yi Lin , Qian Youcun , Zhou Chen , Li Ru , Zhang Xuan , Li Zhanguo , Cao Xuetao 
Published: June 2017

AbstractRegulatory T (Treg) cells are important for the maintenance of immune homoeostasis and prevention of autoimmune diseases. Epigenetic modifications have been reported to modulate autoimmunity by altering Treg cell fate. Here we show that the H3K4 methyltransferase Ash1l facilitates TGF-β-induced Treg cell polarization in vitro and protects mice from T cell-mediated colitis in vivo. Ash1l upregulates Smad3 expression by directly targeting Smad3 promoter to increase local H3K4 trimethylation. Furthermore, we identify an lncRNA, namely lnc-Smad3, which interacts with the histone deacetylase HDAC1 and silences Smad3 transcription. After TGF-β stimulation, activated Smad3 suppresses lnc-Smad3 transcription, thereby recovering the Smad3 promoter accessibility to Ash1l. By revealing the opposite regulatory functions of Ash1l and lnc-Smad3 in Smad3 expression, our data provide insights for the epigenetic control of Treg cell fate to potentially aid in the development of therapeutic intervention for autoimmune diseases.
Controlling hybrid nonlinearities in transparent conducting oxides via two-colour excitation
Authors: Clerici M. , Kinsey N. , DeVault C. , Kim J. , Carnemolla E. G. , Caspani L. , Shaltout A. , Faccio D. , Shalaev V. , Boltasseva A. , Ferrera M. 
Published: June 2017

AbstractNanophotonics and metamaterials have revolutionized the way we think about optical space (ɛ,μ), enabling us to engineer the refractive index almost at will, to confine light to the smallest of the volumes, and to manipulate optical signals with extremely small footprints and energy requirements. Significant efforts are now devoted to finding suitable materials and strategies for the dynamic control of the optical properties. Transparent conductive oxides exhibit large ultrafast nonlinearities under both interband and intraband excitations. Here we show that combining these two effects in aluminium-doped zinc oxide via a two-colour laser field discloses new material functionalities. Owing to the independence of the two nonlinearities, the ultrafast temporal dynamics of the material permittivity can be designed by acting on the amplitude and delay of the two fields. We demonstrate the potential applications of this novel degree of freedom by dynamically addressing the modulation bandwidth and optical spectral tuning of a probe optical pulse.
Refinement of learned skilled movement representation in motor cortex deep output layer
Authors: Li Qian , Ko Ho , Qian Zhong-Ming , Yan Leo Y. C. , Chan Danny C. W. , Arbuthnott Gordon , Ke Ya , Yung Wing-Ho 
Published: June 2017

AbstractThe mechanisms underlying the emergence of learned motor skill representation in primary motor cortex (M1) are not well understood. Specifically, how motor representation in the deep output layer 5b (L5b) is shaped by motor learning remains virtually unknown. In rats undergoing motor skill training, we detect a subpopulation of task-recruited L5b neurons that not only become more movement-encoding, but their activities are also more structured and temporally aligned to motor execution with a timescale of refinement in tens-of-milliseconds. Field potentials evoked at L5b in vivo exhibit persistent long-term potentiation (LTP) that parallels motor performance. Intracortical dopamine denervation impairs motor learning, and disrupts the LTP profile as well as the emergent neurodynamical properties of task-recruited L5b neurons. Thus, dopamine-dependent recruitment of L5b neuronal ensembles via synaptic reorganization may allow the motor cortex to generate more temporally structured, movement-encoding output signal from M1 to downstream circuitry that drives increased uniformity and precision of movement during motor learning.
Predicting the outcomes of organic reactions via machine learning: are current descriptors sufficient?
Authors: Skoraczyński G. , Dittwald P. , Miasojedow B. , Szymkuć S. , Gajewska E. P. , Grzybowski B. A. , Gambin A. 
Published: June 2017

AbstractAs machine learning/artificial intelligence algorithms are defeating chess masters and, most recently, GO champions, there is interest – and hope – that they will prove equally useful in assisting chemists in predicting outcomes of organic reactions. This paper demonstrates, however, that the applicability of machine learning to the problems of chemical reactivity over diverse types of chemistries remains limited – in particular, with the currently available chemical descriptors, fundamental mathematical theorems impose upper bounds on the accuracy with which raction yields and times can be predicted. Improving the performance of machine-learning methods calls for the development of fundamentally new chemical descriptors.
Phenotypic, genotypic and antigenic characterization of emerging avian reoviruses isolated from clinical cases of arthritis in broilers in Saskatchewan, Canada
Authors: Ayalew Lisanework E. , Gupta Ashish , Fricke Jenny , Ahmed Khawaja Ashfaque , Popowich Shelly , Lockerbie Betty , Tikoo Suresh K. , Ojkic Davor , Gomis Susantha 
Published: June 2017

AbstractIn recent years, emerging strains of pathogenic arthrogenic avian reovirus (ARV) have become a challenge to the chicken industry across USA and Canada causing significant economic impact. In this study, we characterized emerging variant ARV strains and examined their genetic and antigenic relationship with reference strains. We isolated 37 emerging variant ARV strains from tendons of broiler chickens with clinical cases of arthritis/tenosynovitis at commercial farms in Saskatchewan, Canada. Viral characterization using immunocytochemistry, gold-immunolabeling and electron microscopy revealed distinct features characteristic of ARV. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses of the viral Sigma C gene revealed genetic heterogeneity between the field isolates. On phylogenetic analyses, the Sigma C amino acid sequences of the isolates were clustered into four distinct genotypic groups. These ARV field strains were genetically diverse and quite distant from the vaccine and vaccine related field strains. Antibodies produced against a commercial Reo 2177®vaccine did not neutralize these variants. Moreover, structure based analysis of the Sigma C protein revealed significant antigenic variability between the cluster groups and the vaccine strains. To the best of our knowledge, this is the first report on the genetic, phenotypic and antigenic characterization of emerging ARVs in Canada.
Phylogenomic Insight into Salinispora (Bacteria, Actinobacteria) Species Designations
Authors: Millán-Aguiñaga Natalie , Chavarria Krystle L. , Ugalde Juan A. , Letzel Anne-Catrin , Rouse Greg W. , Jensen Paul R. 
Published: June 2017

AbstractBacteria represent the most genetically diverse kingdom of life. While great progress has been made in describing this diversity, it remains difficult to identify the phylogenetic and ecological characteristics that delineate groups of bacteria that possess species-like properties. One major challenge associated with species delineations is that not all shared genes have the same evolutionary history, and thus the choice of loci can have a major impact on phylogenetic reconstruction. Sequencing the genomes of large numbers of closely related strains provides new opportunities to distinguish ancestral from acquired alleles and assess the effects of recombination on phylogenetic inference. Here we analyzed the genomes of 119 strains of the marine actinomycete genus Salinispora, which is currently comprised of three named species that share 99% 16S rRNA gene sequence identity. While 63% of the core genome showed evidence of recombination, this had no effect on species-level phylogenomic resolution. Recombination did however blur intra-species relationships and biogeographic resolution. The genome-wide average nucleotide identity provided a new perspective on Salinispora diversity, revealing as many as seven new species. Patterns of orthologous group distributions reveal a genetic basis to delineation the candidate taxa and insight into the levels of genetic cohesion associated with bacterial species.
High-throughput rapid-prototyping of low-cost paper-based microfluidics
Authors: Ghaderinezhad Fariba , Amin Reza , Temirel Mikail , Yenilmez Bekir , Wentworth Adam , Tasoglu Savas 
Published: June 2017

AbstractPaper-based micro analytical devices offer significant advantages compared to the conventional microfluidic chips including cost-effectiveness, ease of fabrication, and ease of use while preserving critical features including strong capillary action and biological compatibility. In this work, we demonstrate an inexpensive, rapid method for high-throughput fabrication of paper-based microfluidics by patterning hydrophobic barriers using a desktop pen plotter integrated with a custom-made, low-cost paper feeder. We tested various types of commercial permanent markers and compared their water-resistant capabilities for creating hydrophobic barriers. Additionally, we studied the performance of markers with different types of paper, plotting speeds, and pattern dimensions. To verify the effectiveness of the presented fabrication method, colorimetric analysis was performed on the results of a glucose assay.
Gene–physical activity interactions in lower extremity performance: inflammatory genes CRP, TNF-α, and LTA in community-dwelling elders
Authors: Liu Chiu-Shong , Li Tsai-Chung , Li Chia-Ing , Liao Li-Na , Yang Chuan-Wei , Lin Chih-Hsueh , Meng Nai-Hsin , Lin Wen-Yuan , Hu Sung-Lin , Hsiao Jen-Hao , Wu Fang-Yang , Lin Cheng-Chieh 
Published: June 2017

AbstractWe assessed gene–gene and gene-physical activity interactions of polymorphisms in C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and lymphotoxin α (LTA) genes on lower extremity performance in community-dwelling elders in Taiwan. Five SNPs (rs1205, rs1130864, rs1800947, rs2794520, and rs3093059) of CRP gene, three SNPs (rs909253, rs1041981, and rs2239704) of LTA gene, and three SNPs (rs3093662, rs1800629, and rs1799964) of TNF-α gene of 472 unrelated elders were genotyped. Lower extremity performance included timed up-and-go test (TUG), walking speed, weight-adjusted leg press (waLP), and timed chair stand (TCS). We detected significant interactions between physical activity with CRP rs2794520, rs1205, and rs3093059; LTA rs909253 and rs1041981; and TNF-α rs1799964 for TCS in women after covariate adjustment (all P < 0.05). In men, significant interactions between physical activity with CRP rs2794520, rs1205, and rs3093059; and LTA rs909253 and rs1041981 for TUG; with CRP rs2794520, rs1205, rs1130864, and rs3093059; and LTA rs909253 and rs1041981 for walking speed; and with TNF-α rs3093662 for waLP after covariate adjustment (all P < 0.05). These variants also significantly interacted with physical activity on TCS in women and on walking speed in men. These results show inflammatory genes are involved in lower extremity performance, likely via gene–physical activity interactions.
Mechanical stability of talin rod controls cell migration and substrate sensing
Authors: Rahikainen Rolle , von Essen Magdaléna , Schaefer Markus , Qi Lei , Azizi Latifeh , Kelly Conor , Ihalainen Teemu O. , Wehrle-Haller Bernhard , Bastmeyer Martin , Huang Cai , Hytönen Vesa P. 
Published: June 2017

AbstractCells adhere to the surrounding tissue and probe its mechanical properties by forming cell-matrix adhesions. Talin is a critical adhesion protein and participates in the transmission of mechanical signals between extracellular matrix and cell cytoskeleton. Force induced unfolding of talin rod subdomains has been proposed to act as a cellular mechanosensor, but so far evidence linking their mechanical stability and cellular response has been lacking. Here, by utilizing computationally designed mutations, we demonstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force generation, which affects talin and vinculin dynamics in cell-matrix adhesions and results in the formation of talin-rich but unstable adhesions. We observed a connection between talin stability and the rate of cell migration and also found that talin destabilization affects the usage of different integrin subtypes and sensing of extracellular matrix proteins. Experiments with truncated forms of talin confirm the mechanosensory role of the talin R3 subdomain and exclude the possibility that the observed effects are caused by the release of talin head-rod autoinhibition. In conclusion, this study provides evidence into how the controlled talin rod domain unfolding acts as a key regulator of adhesion structure and function and consequently controls central cellular processes such as cell migration and substrate sensing.
EZH2-mediated epigenetic silencing of TIMP2 promotes ovarian cancer migration and invasion
Authors: Yi Xiaoqing , Guo Jianfeng , Guo Jing , Sun Si , Yang Ping , Wang Junjie , Li Yuan , Xie Lisha , Cai Jing , Wang Zehua 
Published: June 2017

AbstractEnhancer of zeste homolog 2 (EZH2) is often increased in malignant tumors and is involved in metastasis. EZH2 silences gene expression by tri-methylating the lysine 27 residue of histone H3 (H3K27me3). However, the mechanism underlying EZH2 promotion of ovarian cancer metastasis remains elusive. Here, we showed that EZH2 is up-regulated in ovarian cancer and is associated with tumor metastasis and poor survival by mRNA sequencing and microarray results from databases. Tissue microarray and immunohistochemistry results revealed that EZH2 was negatively correlated with the expression of tissue inhibitor of metalloproteinases 2 (TIMP2). EZH2 overexpression inhibited TIMP2 expression and promoted proteolytic activities of matrix metalloproteinases 2 and 9 and vice versa. EZH2 promoted ovarian cancer invasion and migration, which could be largely reversed by TIMP2 down-regulation in vitro and in vivo. Both H3K27me3 inhibition and demethylation could reduce methylation of the TIMP2 promoter and finally reactivate TIMP2 transcription. The presence of EZH2 and H3K27me3 at the TIMP2 promoter was confirmed by chromatin immunoprecipitation. H3K27me3 and DNA methyltransferases at the promoter were significantly increased by EZH2 overexpression. These results suggest that EZH2 inhibits TIMP2 expression via H3K27me3 and DNA methylation, which relieve the repression of MMP and facilitate ovarian cancer invasion and migration.
Transcriptomic Analysis of the Regulation of Lipid Fraction Migration and Fatty Acid Biosynthesis in Schizochytrium sp.
Authors: Ren Lujing , Hu Xuechao , Zhao Xiaoyan , Chen Shenglan , Wu Yi , Li Dan , Yu Yadong , Geng Lingjun , Ji Xiaojun , Huang He 
Published: June 2017

AbstractSchizochytrium sp. is the main source of docosahexaenoic acid-rich oil, which is widely used in food additive and pharmaceutical industry. In this study, using RNA-seq, comparative transcriptomic analyses were performed at four stages of DHA fermentation by Schizochytrium sp to get potential genes related to cell transition from cell growth to lipid accumulation and then to lipid turnover. 1406, 385, 1384 differently expressed genes were identified by comparisons in pairs of S2 vs S1, S3 vs S2 and S4 vs S3. Functional analysis revealed that binding and single-organism process might be involve in the cell transition from cell growth to lipid accumulation while oxidation-reduction process played an important role in the transition from lipid accumulation to lipid turnover. pfaC in the PKS pathway showed higher sensitivity to the environmental change, which might be the key regulator for enhancing PUFA biosynthesis in the future. Some other genes in signal transduction and cell transport were revealed to be related to lipid turnover, which would enrich the current knowledge regarding lipid metabolism and help to enhance the DHA production and enrich different lipid fractions by Schizochytrium in the future.
One-Pot Synthesis of GeAs Ultrafine Particles from Coal Fly Ash by Vacuum Dynamic Flash Reduction and Inert Gas Condensation
Authors: Zhang Lingen , Xu Zhenming 
Published: June 2017

AbstractGe-monopnictides (GeAs) plays critical role in high-tech industry, especially in the field of advanced optical devices and infrared. As a secondary material, coal fly ash could be further recycled to retrieve germanium and prepare GeAs material with high added values. Hence, the aim of this paper is to propose a one-pot synthesis that uses vacuum flash reduction and inert-gas consolidation method to prepare GeAs ultrafine particles. Germanium in coal fly ash can be successfully recycled; simultaneously, GeAs ultrafine particles were prepared. Separation principle and feasibility of this process was discussed. Temperature, carrier gas flow rate and system pressure were the major factors on formation, morphology and distribution of particle size of GeAs ultrafine particles. A three steps synthetic mechanism was clarified, namely, thermal rupture of coal fly ash and release of GeO2 and As2O3, the gas-solid phase reaction of GeO2, As2O3 and coke to generate metallic Ge and As in vacuum flash reduction. Meantime, GeAs were produced in the gas phase reaction. Finally, GeAs ultrafine particles were obtained by carrier gas condensation. In short, this research developed a practical and environment-friendly one-pot synthesis to recycle germanium in coal fly ash and prepare GeAs ultrafine particles with high added values.
Avalanche of entanglement and correlations at quantum phase transitions
Authors: Krutitsky Konstantin V. , Osterloh Andreas , Schützhold Ralf 
Published: June 2017

AbstractWe study the ground-state entanglement in the quantum Ising model with nearest neighbor ferromagnetic coupling J and find a sequential increase of entanglement depth d with growing J. This entanglement avalanche starts with two-point entanglement, as measured by the concurrence, and continues via the three-tangle and four-tangle, until finally, deep in the ferromagnetic phase for J = ∞, arriving at a pure L-partite (GHZ type) entanglement of all L spins. Comparison with the two, three, and four-point correlations reveals a similar sequence and shows strong ties to the above entanglement measures for small J. However, we also find a partial inversion of the hierarchy, where the four-point correlation exceeds the three- and two-point correlations, well before the critical point is reached. Qualitatively similar behavior is also found for the Bose-Hubbard model, suggesting that this is a general feature of a quantum phase transition. This should be taken into account in the approximations starting from a mean-field limit.