bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor p73 regulates Th1 differentiation
Authors: Ren Min , Kazemian Majid , Zheng Ming , He JianPing , Li Peng , Oh Jangsuk , Liao Wei , Li Jessica , Rajaseelan Jonathan , Kelsall Brian L. , Peltz Gary , Leonard Warren J. 
Published: March 2020

AbstractInter-individual differences in T helper (Th) cell responses affect susceptibility to infectious, allergic and autoimmune diseases. To identify factors contributing to these response differences, here we analyze in vitro differentiated Th1 cells from 16 inbred mouse strains. Haplotype-based computational genetic analysis indicates that the p53 family protein, p73, affects Th1 differentiation. In cells differentiated under Th1 conditions in vitro, p73 negatively regulates IFNγ production. p73 binds within, or upstream of, and modulates the expression of Th1 differentiation-related genes such as Ifng and Il12rb2. Furthermore, in mouse experimental autoimmune encephalitis, p73-deficient mice have increased IFNγ production and less disease severity, whereas in an adoptive transfer model of inflammatory bowel disease, transfer of p73-deficient naïve CD4+ T cells increases Th1 responses and augments disease severity. Our results thus identify p73 as a negative regulator of the Th1 immune response, suggesting that p73 dysregulation may contribute to susceptibility to autoimmune disease.
Bringing biocatalytic deuteration into the toolbox of asymmetric isotopic labelling techniques
Authors: Rowbotham J. S. , Ramirez M. A. , Lenz O. , Reeve H. A. , Vincent K. A. 
Published: March 2020

AbstractEnzymes dependent on nicotinamide cofactors are important components of the expanding range of asymmetric synthetic techniques. New challenges in asymmetric catalysis are arising in the field of deuterium labelling, where compounds bearing deuterium (2H) atoms at chiral centres are becoming increasingly desirable targets for pharmaceutical and analytical chemists. However, utilisation of NADH-dependent enzymes for2H-labelling is not straightforward, owing to difficulties in supplying a suitably isotopically-labelled cofactor ([4-2H]-NADH). Here we report on a strategy that combines a clean reductant (H2) with a cheap source of2H-atoms (2H2O) to generate and recycle [4-2H]-NADH. By coupling [4-2H]-NADH-recycling to an array of C=O, C=N, and C=C bond reductases, we demonstrate asymmetric deuteration across a range of organic molecules under ambient conditions with near-perfect chemo-, stereo- and isotopic selectivity. We demonstrate the synthetic utility of the system by applying it in the isolation of the heavy drug (1S,3’R)-[2’,2’,3’-2H3]-solifenacin fumarate on a preparative scale.
Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer
Authors: Färkkilä Anniina , Gulhan Doga C. , Casado Julia , Jacobson Connor A. , Nguyen Huy , Kochupurakkal Bose , Maliga Zoltan , Yapp Clarence , Chen Yu-An , Schapiro Denis , Zhou Yinghui , Graham Julie R. , Dezube Bruce J. , Munster Pamela , Santagata Sandro , Garcia Elizabeth , Rodig Scott , Lako Ana , Chowdhury Dipanjan , Shapiro Geoffrey I. , Matulonis Ursula A. , Park Peter J. , Hautaniemi Sampsa , Sorger Peter K. , Swisher Elizabeth M. , D’Andrea Alan D. , Konstantinopoulos Panagiotis A. 
Published: March 2020

AbstractCombined PARP and immune checkpoint inhibition has yielded encouraging results in ovarian cancer, but predictive biomarkers are lacking. We performed immunogenomic profiling and highly multiplexed single-cell imaging on tumor samples from patients enrolled in a Phase I/II trial of niraparib and pembrolizumab in ovarian cancer (NCT02657889). We identify two determinants of response; mutational signature 3 reflecting defective homologous recombination DNA repair, and positive immune score as a surrogate of interferon-primed exhausted CD8 + T-cells in the tumor microenvironment. Presence of one or both features associates with an improved outcome while concurrent absence yields no responses. Single-cell spatial analysis reveals prominent interactions of exhausted CD8 + T-cells and PD-L1 + macrophages and PD-L1 + tumor cells as mechanistic determinants of response. Furthermore, spatial analysis of two extreme responders shows differential clustering of exhausted CD8 + T-cells with PD-L1 + macrophages in the first, and exhausted CD8 + T-cells with cancer cells harboring genomic PD-L1 and PD-L2 amplification in the second.
Identification and characterization of N9-methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea
Authors: Zhang Yue-Hong , Li Yi-Fang , Wang Yongjin , Tan Li , Cao Zhi-Qin , Xie Chao , Xie Guo , Gong Hai-Biao , Sun Wan-Yang , Ouyang Shu-Hua , Duan Wen-Jun , Lu Xiaoyun , Ding Ke , Kurihara Hiroshi , Hu Dan , Zhang Zhi-Min , Abe Ikuro , He Rong-Rong 
Published: March 2020

AbstractCaffeine is a major component of xanthine alkaloids and commonly consumed in many popular beverages. Due to its occasional side effects, reduction of caffeine in a natural way is of great importance and economic significance. Recent studies reveal that caffeine can be converted into non-stimulatory theacrine in the rare tea plant Camellia assamica var. kucha (Kucha), which involves oxidation at the C8 and methylation at the N9 positions of caffeine. However, the underlying molecular mechanism remains unclear. Here, we identify the theacrine synthase CkTcS from Kucha, which possesses novel N9-methyltransferase activity using 1,3,7-trimethyluric acid but not caffeine as a substrate, confirming that C8 oxidation takes place prior to N9-methylation. The crystal structure of the CkTcS complex reveals the key residues that are required for the N9-methylation, providing insights into how caffeine N-methyltransferases in tea plants have evolved to catalyze regioselective N-methylation through fine tuning of their active sites. These results may guide the future development of decaffeinated drinks.
Multiscale computational understanding and growth of 2D materials: a review
Authors: Momeni Kasra , Ji Yanzhou , Wang Yuanxi , Paul Shiddartha , Neshani Sara , Yilmaz Dundar E. , Shin Yun Kyung , Zhang Difan , Jiang Jin-Wu , Park Harold S. , Sinnott Susan , van Duin Adri , Crespi Vincent , Chen Long-Qing 
Published: March 2020

AbstractThe successful discovery and isolation of graphene in 2004, and the subsequent synthesis of layered semiconductors and heterostructures beyond graphene have led to the exploding field of two-dimensional (2D) materials that explore their growth, new atomic-scale physics, and potential device applications. This review aims to provide an overview of theoretical, computational, and machine learning methods and tools at multiple length and time scales, and discuss how they can be utilized to assist/guide the design and synthesis of 2D materials beyond graphene. We focus on three methods at different length and time scales as follows: (i) nanoscale atomistic simulations including density functional theory (DFT) calculations and molecular dynamics simulations employing empirical and reactive interatomic potentials; (ii) mesoscale methods such as phase-field method; and (iii) macroscale continuum approaches by coupling thermal and chemical transport equations. We discuss how machine learning can be combined with computation and experiments to understand the correlations between structures and properties of 2D materials, and to guide the discovery of new 2D materials. We will also provide an outlook for the applications of computational approaches to 2D materials synthesis and growth in general.
Imaging mechanism for hyperspectral scanning probe microscopy via Gaussian process modelling
Authors: Ziatdinov Maxim , Kim Dohyung , Neumayer Sabine , Vasudevan Rama K. , Collins Liam , Jesse Stephen , Ahmadi Mahshid , Kalinin Sergei V. 
Published: March 2020

AbstractWe investigate the ability to reconstruct and derive spatial structure from sparsely sampled 3D piezoresponse force microcopy data, captured using the band-excitation (BE) technique, via Gaussian Process (GP) methods. Even for weakly informative priors, GP methods allow unambiguous determination of the characteristic length scales of the imaging process both in spatial and frequency domains. We further show that BE data set tends to be oversampled in the spatial domains, with ~30% of original data set sufficient for high-quality reconstruction, potentially enabling faster BE imaging. At the same time, reliable reconstruction along the frequency domain requires the resonance peak to be within the measured band. This behavior suggests the optimal strategy for the BE imaging on unknown samples. Finally, we discuss how GP can be used for automated experimentation in SPM, by combining GP regression with non-rectangular scans.
Impact of UV irradiation at full scale on bacterial communities in drinking water
Authors: Pullerits Kristjan , Ahlinder Jon , Holmer Linda , Salomonsson Emelie , Öhrman Caroline , Jacobsson Karin , Dryselius Rikard , Forsman Mats , Paul Catherine J. , Rådström Peter 
Published: March 2020

AbstractWater in a full-scale drinking water treatment plant was irradiated with ultraviolet (UV) doses of 250, 400, and 600 J/m2, and the effect on bacterial communities investigated using 16s rRNA gene amplicon sequencing, heterotrophic plate counts (HPCs), coliform, andEscherichia colicounts. The bacteria in the irradiated water were also analyzed following storage for 6 days at 7 °C, to approximate the conditions in the distribution system. The log10reduction of HPCs at 400 J/m2was 0.43 ± 0.12. Phylogenetic examination, including DESeq2 analysis, showed thatActinobacteriawas more resistant to UV irradiation, whereasBacteroideteswas sensitive to UV. PhylumProteobacteriacontained monophyletic groups that were either sensitive or resistant to UV exposure. The amplicon sequence variants (ASVs) resistant to UV irradiation had a greater average GC content than the ASVs sensitive to UV, at 55% ± 1.7 (n = 19) and 49% ± 2.5 (n = 16), respectively. FamiliesChitinophagaceae,Pelagibacteraceae,Holophagaceae,Methylophilaceae, andCytophagaceaedecreased linearly in relative abundance, with increasing UV dose (P < 0.05, Pearson’s correlation). When irradiated water was stored,Chitinophagaceae,Comamonadaceae, andFlavobacteriaceaefamilies decreased in relative abundance, whereasACK-M1,Mycobacteriaceae, andNitrosomonadaceaewere increasing in relative abundance. This suggests that the impact of UV irradiation cannot only be considered directly after application but that this treatment step likely continues to influence microbial dynamics throughout the distribution system.
Multidisciplinary database of permeability of fault zones and surrounding protolith rocks at world-wide sites
Authors: Scibek Jacek 
Published: March 2020

AbstractBrittle faults and fault zones are important fluid flow conduits through the upper part of Earth’s crust that are involved in many well-known phenomena (e.g. earthquakes, thermal water and gas transport, or water leakage to underground tunnels). The permeability property, or the ability of porous materials to conduct water and gas, is one of the key parameters required in understanding and predicting fluid flow. Although close to a thousand studies have been done, and permeability tested in parts of fault zones, a sytematic summary and database is lacking. This data descriptor is for a multi-disciplinary world-wide compilation and review of bulk and matrix permeability of fault zones: 410 datasets, 521 reviewed sites, 379 locations, >10000 publications searched. The review covers studies of faulting processes, geothermal engineering, radioactive waste repositories, groundwater resources, petroleum reservoirs, and underground engineering projects. The objectives are to stimulate the cross-disciplinary data sharing and communication about fault zone hydrogeology, document the biases and strategies for testing of fault zones, and provide the basic statistics of permeability values for models that require these parameters.
A database of freshwater fish species of the Amazon Basin
Authors: Jézéquel Céline , Tedesco Pablo A. , Bigorne Rémy , Maldonado-Ocampo Javier A. , Ortega Hernan , Hidalgo Max , Martens Koen , Torrente-Vilara Gislene , Zuanon Jansen , Acosta Astrid , Agudelo Edwin , Barrera Maure Soraya , Bastos Douglas A. , Bogotá Gregory Juan , Cabeceira Fernando G. , Canto André L. C. , Carvajal-Vallejos Fernando M. , Carvalho Lucélia N. , Cella-Ribeiro Ariana , Covain Raphaël , Donascimiento Carlos , Dória Carolina R. C. , Duarte Cleber , Ferreira Efrem J. G. , Galuch André V. , Giarrizzo Tommaso , Leitão Rafael P. , Lundberg John G. , Maldonado Mabel , Mojica José I. , Montag Luciano F. A. , Ohara Willian M. , Pires Tiago H. S. , Pouilly Marc , Prada-Pedreros Saúl , de Queiroz Luiz J. , Rapp Py-Daniel Lucia , Ribeiro Frank R. V. , Ríos Herrera Raúl , Sarmiento Jaime , Sousa Leandro M. , Stegmann Lis F. , Valdiviezo-Rivera Jonathan , Villa Francisco , Yunoki Takayuki , Oberdorff Thierry 
Published: March 2020

AbstractThe Amazon Basin is an unquestionable biodiversity hotspot, containing the highest freshwater biodiversity on earth and facing off a recent increase in anthropogenic threats. The current knowledge on the spatial distribution of the freshwater fish species is greatly deficient in this basin, preventing a comprehensive understanding of this hyper-diverse ecosystem as a whole. Filling this gap was the priority of a transnational collaborative project, i.e. the AmazonFish project - https://www.amazon-fish.com/. Relying on the outputs of this project, we provide the most complete fish species distribution records covering the whole Amazon drainage. The database, including 2,406 validated freshwater native fish species, 232,936 georeferenced records, results from an extensive survey of species distribution including 590 different sources (e.g. published articles, grey literature, online biodiversity databases and scientific collections from museums and universities worldwide) and field expeditions conducted during the project. This database, delivered at both georeferenced localities (21,500 localities) and sub-drainages grains (144 units), represents a highly valuable source of information for further studies on freshwater fish biodiversity, biogeography and conservation.
Mechanics of near-field deformation during co- and post-seismic shallow fault slip
Authors: Nevitt Johanna M. , Brooks Benjamin A. , Catchings Rufus D. , Goldman Mark R. , Ericksen Todd L. , Glennie Craig L. 
Published: March 2020

AbstractPoor knowledge of how faults slip and distribute deformation in the shallow crust hinders efforts to mitigate hazards where faults increasingly intersect with the expanding global population at Earth’s surface. Here we analyze two study sites along the 2014M6.0 South Napa, California, earthquake rupture, each dominated by either co- or post-seismic shallow fault slip. We combine mobile laser scanning (MLS), active-source seismic tomography, and finite element modeling to investigate how deformation rate and mechanical properties of the shallow crust affect fault behavior. Despite four orders-of-magnitude difference in the rupture velocities, MLS-derived shear strain fields are remarkably similar at the two sites and suggest deceleration of the co-seismic rupture near Earth’s surface. Constrained by the MLS and seismic data, finite element models indicate shallow faulting is more sensitive to lithologic layering and plastic yielding than to the presence of fault compliant zones (i.e., regions surrounding faults with reduced stiffness). Although both elastic and elastoplastic models can reproduce the observed surface displacement fields within the uncertainty of MLS data, elastoplastic models likely provide the most reliable representations of subsurface fault behavior, as they produce geologically reasonable stress states and are consistent with field, geodetic, and seismological observations.
Specific functions for Mediator complex subunits from different modules in the transcriptional response of Arabidopsis thaliana to abiotic stress
Authors: Crawford Tim , Karamat Fazeelat , Lehotai Nóra , Rentoft Matilda , Blomberg Jeanette , Strand Åsa , Björklund Stefan 
Published: March 2020

AbstractAdverse environmental conditions are detrimental to plant growth and development. Acclimation to abiotic stress conditions involves activation of signaling pathways which often results in changes in gene expression via networks of transcription factors (TFs). Mediator is a highly conserved co-regulator complex and an essential component of the transcriptional machinery in eukaryotes. Some Mediator subunits have been implicated in stress-responsive signaling pathways; however, much remains unknown regarding the role of plant Mediator in abiotic stress responses. Here, we use RNA-seq to analyze the transcriptional response of Arabidopsis thaliana to heat, cold and salt stress conditions. We identify a set of common abiotic stress regulons and describe the sequential and combinatorial nature of TFs involved in their transcriptional regulation. Furthermore, we identify stress-specific roles for the Mediator subunits MED9, MED16, MED18 and CDK8, and putative TFs connecting them to different stress signaling pathways. Our data also indicate different modes of action for subunits or modules of Mediator at the same gene loci, including a co-repressor function for MED16 prior to stress. These results illuminate a poorly understood but important player in the transcriptional response of plants to abiotic stress and identify target genes and mechanisms as a prelude to further biochemical characterization.
Nuclear receptor CAR-ERα signaling regulates the estrogen sulfotransferase gene in the liver
Authors: Yi MyeongJin , Fashe Muluneh , Arakawa Shingo , Moore Rick , Sueyoshi Tatsuya , Negishi Masahiko 
Published: March 2020

AbstractEstrogen sulfotransferase (SULT1E1) inactivates estrogen and regulates its metabolic homeostats. Whereas SULT1E1 is expressed low in the liver of adult mice, it is induced by phenobarbital (PB) treatment or spontaneously in diabetic livers via nuclear receptors. Utilizing constitutive active/androstane receptor (CAR) KO, estrogen receptor α (ERα KO, phosphorylation-blocked ERα S216A KI mice, it is now demonstrated that, after being activated by PB, CAR binds and recruits ERα onto the Sulte1 promoter for subsequent phosphorylation at Ser216. This phosphorylation tightens CAR interacting with ERα and to activates the promoter. Hepatic SULT1E1 mRNA levels are constitutively up-regulated in type 1 diabetic Akita mice; CAR spontaneously accumulates in the nucleus and activates the Sult1e1 promoter by recruiting phosphorylated ERα in the liver as observed with PB-induced livers. Thus, this CAR-phosphorylated ERα signaling enables these two nuclear receptors to communicate, activating the Sult1e1 gene in response to either PB or diabetes in mice. ERα phosphorylation may integrate CAR into estrogen actions, providing insights into understanding drug-hormone interactions in clinical therapy.
Improving detection of protein-ligand binding sites with 3D segmentation
Authors: Stepniewska-Dziubinska Marta M. , Zielenkiewicz Piotr , Siedlecki Pawel 
Published: March 2020

AbstractIn recent years machine learning (ML) took bio- and cheminformatics fields by storm, providing new solutions for a vast repertoire of problems related to protein sequence, structure, and interactions analysis. ML techniques, deep neural networks especially, were proven more effective than classical models for tasks like predicting binding affinity for molecular complex. In this work we investigated the earlier stage of drug discovery process – finding druggable pockets on protein surface, that can be later used to design active molecules. For this purpose we developed a 3D fully convolutional neural network capable of binding site segmentation. Our solution has high prediction accuracy and provides intuitive representations of the results, which makes it easy to incorporate into drug discovery projects. The model’s source code, together with scripts for most common use-cases is freely available at http://gitlab.com/cheminfIBB/kalasanty.
Spin-photon module for scalable network architecture in quantum dots
Authors: Zhu Xing-Yu , Tu Tao , Guo Ao-Lin , Zhou Zong-Quan , Guo Guang-Can , Li Chuan-Feng 
Published: March 2020

AbstractReliable information transmission between spatially separated nodes is fundamental to a network architecture for scalable quantum technology. Spin qubit in semiconductor quantum dots is a promising candidate for quantum information processing. However, there remains a challenge to design a practical path from the existing experiments to scalable quantum processor. Here we propose a module consisting of spin singlet-triplet qubits and single microwave photons. We show a high degree of control over interactions between the spin qubit and the quantum light field can be achieved. Furthermore, we propose preparation of a shaped single photons with an efficiency of 98%, and deterministic quantum state transfer and entanglement generation between remote nodes with a high fidelity of 90%. This spin-photon module has met the threshold of particular designed error-correction protocols, thus provides a feasible approach towards scalable quantum network architecture.
Identification of metabolite biomarkers in serum of rats exposed to chlorpyrifos and cadmium
Authors: Xu Ming-Yuan , Wang Pan , Sun Ying-Jian , Yang Lin , Wu Yi-Jun 
Published: March 2020

AbstractChlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometer-based metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.