bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice
Authors: Cebula Anna , Kuczma Michal , Szurek Edyta , Pietrzak Maciej , Savage Natasha , Elhefnawy Wessam R. , Rempala Grzegorz , Kraj Piotr , Ignatowicz Leszek 
Published: October 2019

AbstractThymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3− T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3+ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4+Foxp3− cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including self-peptides that select them in the thymus. Our data thus suggest that identification of most potentially autoreactive CD4+ T cells in the peripheral repertoire is critical to harness or redirect these cells for therapeutic advantage.
de Haas-van Alphen effect of correlated Dirac states in kagome metal Fe3Sn2
Authors: Ye Linda , Chan Mun K. , McDonald Ross D. , Graf David , Kang Mingu , Liu Junwei , Suzuki Takehito , Comin Riccardo , Fu Liang , Checkelsky Joseph G. 
Published: October 2019

AbstractPrimarily considered a medium of geometric frustration, there has been a growing recognition of the kagome network as a harbor of lattice-borne topological electronic phases. In this study we report the observation of magnetoquantum de Haas-van Alphen oscillations of the ferromagnetic kagome lattice metal Fe3Sn2. We observe a pair of quasi-two-dimensional Fermi surfaces arising from bulk massive Dirac states and show that these band areas and effective masses are systematically modulated by the rotation of the ferromagnetic moment. Combined with measurements of Berry curvature induced Hall conductivity, our observations suggest that the ferromagnetic Dirac fermions in Fe3Sn2 are subject to intrinsic spin-orbit coupling in the d electron sector which is likely of Kane-Mele type. Our results provide insights for spintronic manipulation of magnetic topological electronic states and pathways to realizing further highly correlated topological materials from the lattice perspective.
A secreted metal-binding protein protects necrotrophic phytopathogens from reactive oxygen species
Authors: Liu Lulu , Gueguen-Chaignon Virginie , Gonçalves Isabelle R , Rascle Christine , Rigault Martine , Dellagi Alia , Loisel Elise , Poussereau Nathalie , Rodrigue Agnès , Terradot Laurent , Condemine Guy 
Published: October 2019

AbstractFew secreted proteins involved in plant infection common to necrotrophic bacteria, fungi and oomycetes have been identified except for plant cell wall-degrading enzymes. Here we study a family of iron-binding proteins that is present in Gram-negative and Gram-positive bacteria, fungi, oomycetes and some animals. Homolog proteins in the phytopathogenic bacterium Dickeya dadantii (IbpS) and the fungal necrotroph Botrytis cinerea (BcIbp) are involved in plant infection. IbpS is secreted, can bind iron and copper, and protects the bacteria against H2O2-induced death. Its 1.7 Å crystal structure reveals a classical Venus Fly trap fold that forms dimers in solution and in the crystal. We propose that secreted Ibp proteins binds exogenous metals and thus limit intracellular metal accumulation and ROS formation in the microorganisms.
Genome-wide microhomologies enable precise template-free editing of biologically relevant deletion mutations
Authors: Grajcarek Janin , Monlong Jean , Nishinaka-Arai Yoko , Nakamura Michiko , Nagai Miki , Matsuo Shiori , Lougheed David , Sakurai Hidetoshi , Saito Megumu K. , Bourque Guillaume , Woltjen Knut 
Published: October 2019

AbstractThe functional effect of a gene edit by designer nucleases depends on the DNA repair outcome at the targeted locus. While non-homologous end joining (NHEJ) repair results in various mutations, microhomology-mediated end joining (MMEJ) creates precise deletions based on the alignment of flanking microhomologies (µHs). Recently, the sequence context surrounding nuclease-induced double strand breaks (DSBs) has been shown to predict repair outcomes, for which µH plays an important role. Here, we survey naturally occurring human deletion variants and identify that 11 million or 57% are flanked by µHs, covering 88% of protein-coding genes. These biologically relevant mutations are candidates for precise creation in a template-free manner by MMEJ repair. Using CRISPR-Cas9 in human induced pluripotent stem cells (hiPSCs), we efficiently create pathogenic deletion mutations for demonstrable disease models with both gain- and loss-of-function phenotypes. We anticipate this dataset and gene editing strategy to enable functional genetic studies and drug screening.
Fouling-resistant biofilter of an anaerobic electrochemical membrane reactor
Authors: Yu Qilin , Zhang Yaobin 
Published: October 2019

AbstractMembrane fouling is a considerable challenge for the stable operation of anaerobic membrane-based bioreactors. Membrane used as a cathode is a common measure to retard fouling growth in anaerobic electrochemical membrane bioreactors (AnEMBR), which; however, cannot avoid the fouling growth. Here we report a strategy using the membrane as an anode to resist membrane fouling in an AnEMBR. Although aggravating in the initial stage, the fouling on the anode membrane is gradually alleviated by the anode oxidation with enriching exoelectrogens to finally achieve a dynamic equilibrium between fouling growth and decomposition to maintain the operation stable. A mesh-like biofilter layer composed of cells with less extracellular polymeric substance (EPS) is formed on the membrane surface to lower the trans-membrane pressure and promote the interception of the anode membrane. The membrane has high electron storage and transfer capacities to accelerate the oxidation of the intercepted fouling materials, especially, the redundant EPSs of the biofilter layer.
Bacterial MgrB peptide activates chemoreceptor Fpr3 in mouse accessory olfactory system and drives avoidance behaviour
Authors: Bufe Bernd , Teuchert Yannick , Schmid Andreas , Pyrski Martina , Pérez-Gómez Anabel , Eisenbeis Janina , Timm Thomas , Ishii Tomohiro , Lochnit Günter , Bischoff Markus , Mombaerts Peter , Leinders-Zufall Trese , Zufall Frank 
Published: October 2019

AbstractInnate immune chemoreceptors of the formyl peptide receptor (Fpr) family are expressed by vomeronasal sensory neurons (VSNs) in the accessory olfactory system. Their biological function and coding mechanisms remain unknown. We show that mouse Fpr3 (Fpr-rs1) recognizes the core peptide motif f-MKKFRW that is predominantly present in the signal sequence of the bacterial protein MgrB, a highly conserved regulator of virulence and antibiotic resistance in Enterobacteriaceae. MgrB peptide can be produced and secreted by bacteria, and is selectively recognized by a subset of VSNs. Exposure to the peptide also stimulates VSNs in freely behaving mice and drives innate avoidance. Our data shows that Fpr3 is required for neuronal detection and avoidance of peptides derived from a conserved master virulence regulator of enteric bacteria.
Late-stage trifluoromethylthiolation of benzylic C-H bonds
Authors: Xu Wentao , Wang Wenliang , Liu Tao , Xie Jin , Zhu Chengjian 
Published: October 2019

AbstractThe benzylic positions in drugs are sites that readily react with cytochrome P450 oxidases via single-electron oxidation. New synthetic methodologies to incorporate a fluoroalkyl group at the benzylic site are continually being developed, and in this paper, we report a metal-free and site-selective organophotoredox-catalyzed trifluoromethylthiolation of benzylic C-H bonds for a wide variety of alkyl arenes and heteroarenes. The precise and predictive regioselectivity among various C(sp3)-H bonds originates from an inner-sphere benzylic radical initiation mechanism, and avoids the use of external oxidants or hydrogen atom abstractors. Its practicality stems from the trifluoromethylthiolation of a series of drugs and complex organic molecules, which is overwhelmingly selective for benzyl groups. This operationally simple protocol can provide a general and practical access to structurally diverse benzylic trifluoromethyl sulfides produced from ubiquitous benzylic C-H bonds. Large scale trifluoromethylthiolation can be achieved with continuous flow photoredox technology.
Nuclear calcium signatures are associated with root development
Authors: Leitão Nuno , Dangeville Pierre , Carter Ross , Charpentier Myriam 
Published: October 2019

AbstractIn plants, nuclear Ca2+ releases are essential to the establishment of nitrogen-fixing and phosphate-delivering arbuscular mycorrhizal endosymbioses. In the legume Medicago truncatula, these nuclear Ca2+ signals are generated by a complex of nuclear membrane-localised ion channels including the DOES NOT MAKE INFECTIONS 1 (DMI1) and the cyclic nucleotide-gated channels (CNGC) 15s. DMI1 and CNCG15s are conserved among land plants, suggesting roles for nuclear Ca2+ signalling that extend beyond symbioses. Here we show that nuclear Ca2+ signalling initiates in the nucleus of Arabidopsis root cells and that these signals are correlated with primary root development, including meristem development and auxin homeostasis. In addition, we demonstrate that altering genetically AtDMI1 is sufficient to modulate the nuclear Ca2+ signatures, and primary root development. This finding supports the postulate that stimulus-specific information can be encoded in the frequency and duration of a Ca2+ signal and thereby regulate cellular function.
A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging
Authors: An Hong-Wei , Li Li-Li , Wang Yi , Wang Ziqi , Hou Dayong , Lin Yao-Xin , Qiao Sheng-Lin , Wang Man-Di , Yang Chao , Cong Yong , Ma Yang , Zhao Xiao-Xiao , Cai Qian , Chen Wen-Ting , Lu Chu-Qi , Xu Wanhai , Wang Hao , Zhao Yuliang 
Published: October 2019

AbstractAchieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders.
Specific ion effects at graphitic interfaces
Authors: Zhan Cheng , Cerón Maira R. , Hawks Steven A. , Otani Minoru , Wood Brandon C. , Pham Tuan Anh , Stadermann Michael , Campbell Patrick G. 
Published: October 2019

AbstractImproved understanding of aqueous solutions at graphitic interfaces is critical for energy storage and water desalination. However, many mechanistic details remain unclear, including how interfacial structure and response are dictated by intrinsic properties of solvated ions under applied voltage. In this work, we combine hybrid first-principles/continuum simulations with electrochemical measurements to investigate adsorption of several alkali-metal cations at the interface with graphene and within graphene slit-pores. We confirm that adsorption energy increases with ionic radius, while being highly dependent on the pore size. In addition, in contrast with conventional electrochemical models, we find that interfacial charge transfer contributes non-negligibly to this interaction and can be further enhanced by confinement. We conclude that the measured interfacial capacitance trends result from a complex interplay between voltage, confinement, and specific ion effects-including ion hydration and charge transfer.
Manipulating topological transformations of polar structures through real-time observation of the dynamic polarization evolution
Authors: Du K. , Zhang M. , Dai C. , Zhou Z. N. , Xie Y. W. , Ren Z. H. , Tian H. , Chen L. Q. , Van Tendeloo Gustaaf , Zhang Z. 
Published: October 2019

AbstractTopological structures based on controllable ferroelectric or ferromagnetic domain configurations offer the opportunity to develop microelectronic devices such as high-density memories. Despite the increasing experimental and theoretical insights into various domain structures (such as polar spirals, polar wave, polar vortex) over the past decade, manipulating the topological transformations of polar structures and comprehensively understanding its underlying mechanism remains lacking. By conducting an in-situ non-contact bias technique, here we systematically investigate the real-time topological transformations of polar structures in PbTiO3/SrTiO3 multilayers at an atomic level. The procedure of vortex pair splitting and the transformation from polar vortex to polar wave and out-of-plane polarization are observed step by step. Furthermore, the redistribution of charge in various topological structures has been demonstrated under an external bias. This provides new insights for the symbiosis of polar and charge and offers an opportunity for a new generation of microelectronic devices.
Cellular sequestrases maintain basal Hsp70 capacity ensuring balanced proteostasis
Authors: Ho Chi-ting , Grousl Tomas , Shatz Oren , Jawed Areeb , Ruger-Herreros Carmen , Semmelink Marije , Zahn Regina , Richter Karsten , Bukau Bernd , Mogk Axel 
Published: October 2019

AbstractMaintenance of cellular proteostasis is achieved by a multi-layered quality control network, which counteracts the accumulation of misfolded proteins by refolding and degradation pathways. The organized sequestration of misfolded proteins, actively promoted by cellular sequestrases, represents a third strategy of quality control. Here we determine the role of sequestration within the proteostasis network in Saccharomyces cerevisiae and the mechanism by which it occurs. The Hsp42 and Btn2 sequestrases are functionally intertwined with the refolding activity of the Hsp70 system. Sequestration of misfolded proteins by Hsp42 and Btn2 prevents proteostasis collapse and viability loss in cells with limited Hsp70 capacity, likely by shielding Hsp70 from misfolded protein overload. Btn2 has chaperone and sequestrase activity and shares features with small heat shock proteins. During stress recovery Btn2 recruits the Hsp70-Hsp104 disaggregase by directly interacting with the Hsp70 co-chaperone Sis1, thereby shunting sequestered proteins to the refolding pathway.
Semiarid climate and hyposaline lake on early Mars inferred from reconstructed water chemistry at Gale
Authors: Fukushi Keisuke , Sekine Yasuhito , Sakuma Hiroshi , Morida Koki , Wordsworth Robin 
Published: October 2019

AbstractSalinity, pH, and redox states are fundamental properties that characterize natural waters. These properties of surface waters on early Mars reflect palaeoenvironments, and thus provide clues on the palaeoclimate and habitability. Here we constrain these properties of pore water within lacustrine sediments of Gale Crater, Mars, using smectite interlayer compositions. Regardless of formation conditions of smectite, the pore water that last interacted with the sediments was of Na-Cl type with mild salinity (~0.1–0.5 mol/kg) and circumneutral pH. To interpret this, multiple scenarios for post-depositional alterations are considered. The estimated Na-Cl concentrations would reflect hyposaline, early lakes developed in 104–106-year-long semiarid climates. Assuming that post-depositional sulfate-rich fluids interacted with the sediments, the redox disequilibria in secondary minerals suggest infiltration of oxidizing fluids into reducing sediments. Assuming no interactions, the redox disequilibria could have been generated by interactions of upwelling groundwater with oxidized sediments in early post-depositional stages.
Intestinal microbiome composition and its relation to joint pain and inflammation
Authors: Boer Cindy G. , Radjabzadeh Djawad , Medina-Gomez Carolina , Garmaeva Sanzhima , Schiphof Dieuwke , Arp Pascal , Koet Thomas , Kurilshikov Alexander , Fu Jingyuan , Ikram M. Arfan , Bierma-Zeinstra Sita , Uitterlinden André G. , Kraaij Robert , Zhernakova Alexandra , van Meurs Joyce B. J. 
Published: October 2019

AbstractMacrophage-mediated inflammation is thought to have a causal role in osteoarthritis-related pain and severity, and has been suggested to be triggered by endotoxins produced by the gastrointestinal microbiome. Here we investigate the relationship between joint pain and the gastrointestinal microbiome composition, and osteoarthritis-related knee pain in the Rotterdam Study; a large population based cohort study. We show that abundance of Streptococcus species is associated with increased knee pain, which we validate by absolute quantification of Streptococcus species. In addition, we replicate these results in 867 Caucasian adults of the Lifelines-DEEP study. Finally we show evidence that this association is driven by local inflammation in the knee joint. Our results indicate the microbiome is a possible therapeutic target for osteoarthritis-related knee pain.
Chloroplastic metabolic engineering coupled with isoprenoid pool enhancement for committed taxanes biosynthesis in Nicotiana benthamiana
Authors: Li Jianhua , Mutanda Ishmael , Wang Kaibo , Yang Lei , Wang Jiawei , Wang Yong 
Published: October 2019

AbstractProduction of the anticancer drug Taxol and its precursors in heterologous hosts is more sustainable than extraction from tissues of yew trees or chemical synthesis. Although attempts to engineer the Taxol pathway in microbes have made significant progress, challenges such as functional expression of plant P450 enzymes remain to be addressed. Here, we introduce taxadiene synthase, taxadiene-5α-hydroxylase, and cytochrome P450 reductase in a high biomass plant Nicotiana benthamiana. Using a chloroplastic compartmentalized metabolic engineering strategy, combined with enhancement of isoprenoid precursors, we show that the engineered plants can produce taxadiene and taxadiene-5α-ol, the committed taxol intermediates, at 56.6 μg g−1 FW and 1.3 μg g−1 FW, respectively. In addition to the tools and strategies reported here, this study highlights the potential of Nicotiana spp. as an alternative platform for Taxol production.
Three-dimensional open nano-netcage electrocatalysts for efficient pH-universal overall water splitting
Authors: Zhuang Zewen , Wang Yu , Xu Cong-Qiao , Liu Shoujie , Chen Chen , Peng Qing , Zhuang Zhongbin , Xiao Hai , Pan Yuan , Lu Siqi , Yu Rong , Cheong Weng-Chon , Cao Xing , Wu Konglin , Sun Kaian , Wang Yu , Wang Dingsheng , Li Jun , Li Yadong 
Published: October 2019

AbstractHigh-efficiency water electrolysis is the key to sustainable energy. Here we report a highly active and durable RuIrOx (x ≥ 0) nano-netcage catalyst formed during electrochemical testing by in-situ etching to remove amphoteric ZnO from RuIrZnOx hollow nanobox. The dispersing-etching-holing strategy endowed the porous nano-netcage with a high exposure of active sites as well as a three-dimensional accessibility for substrate molecules, thereby drastically boosting the electrochemical surface area (ECSA). The nano-netcage catalyst achieved not only ultralow overpotentials at 10 mA cm−2 for hydrogen evolution reaction (HER; 12 mV, pH = 0; 13 mV, pH = 14), but also high-performance overall water electrolysis over a broad pH range (0 ~ 14), with a potential of mere 1.45 V (pH = 0) or 1.47 V (pH = 14) at 10 mA cm−2. With this universal applicability of our electrocatalyst, a variety of readily available electrolytes (even including waste water and sea water) could potentially be directly used for hydrogen production.
Dynamic oxygen adsorption on single-atomic Ruthenium catalyst with high performance for acidic oxygen evolution reaction
Authors: Cao Linlin , Luo Qiquan , Chen Jiajia , Wang Lan , Lin Yue , Wang Huijuan , Liu Xiaokang , Shen Xinyi , Zhang Wei , Liu Wei , Qi Zeming , Jiang Zheng , Yang Jinlong , Yao Tao 
Published: October 2019

AbstractAchieving active and stable oxygen evolution reaction (OER) in acid media based on single-atom catalysts is highly promising for cost-effective and sustainable energy supply in proton electrolyte membrane electrolyzers. Here, we report an atomically dispersed Ru1-N4 site anchored on nitrogen-carbon support (Ru-N-C) as an efficient and durable electrocatalyst for acidic OER. The single-atom Ru-N-C catalyst delivers an exceptionally intrinsic activity, reaching a mass activity as high as 3571 A gmetal−1 and turnover frequency of 3348 O2 h−1 with a low overpotential of 267 mV at a current density of 10 mA cm−2. The catalyst shows no evident deactivation or decomposition after 30-hour operation in acidic environment. Operando synchrotron radiation X-ray absorption spectroscopy and infrared spectroscopy identify the dynamic adsorption of single oxygen atom on Ru site under working potentials, and theoretical calculations demonstrate that the O-Ru1-N4 site is responsible for the high OER activity and stability.
A merged copper(I/II) cluster isolated from Glaser coupling
Authors: Zhang Siqi , Zhao Liang 
Published: October 2019

AbstractUbiquitous copper-oxygen species are pivotal in enabling multifarious oxidation reactions in biological and chemical transformations. We herein construct a macrocycle-protected mixed-valence cluster [(tBuC≡CCuI3)-(μ2-OH)-CuII] by merging a copper acetylide cluster with a copper-oxygen moiety formed in Glaser coupling. This merged Cu(I/II) cluster shows remarkably strong oxidation capacity, whose reduction potential is among the most positive for Cu(II) and even comparable with some Cu(III) species. Consequently, the cluster exhibits high hydrogen atom transfer (HAT) reactivity with inert hydrocarbons. In contrast, the degraded [CuII-(μ2-OH)-CuII] embedded in a small macrocyclic homologue shows no HAT reactivity. Theoretical calculations indicate that the strong oxidation ability of Cu(II) in [(tBuC≡CCuI3)-(μ2-OH)-CuII] is mainly ascribed to the uneven charge distribution of Cu(I) ions in the tBuC≡CCuI3 unit because of significant [dCu(I) → π*(C≡C)] back donation. The present study on in situ formed metal clusters opens a broad prospect for mechanistic studies of Cu-based catalytic reactions.