bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceleration of Ions in Jovian Plasmoids: Does Turbulence Play a Role?
Authors: Kronberg E. A. , Grigorenko E. E. , Malykhin A. , Kozak L. , Petrenko B. , Vogt M. F. , Roussos E. , Kollmann P. , Jackman C. M. , Kasahara S. , Malova Kh. V. , Tao C. , Radioti A. , Masters A. 
Published: June 2019

AbstractThe dissipation processes which transform electromagnetic energy into kinetic particle energy in space plasmas are still not fully understood. Of particular interest is the distribution of the dissipated energy among different species of charged particles. The Jovian magnetosphere is a unique laboratory to study this question because outflowing ions from the moon Io create a high diversity in ion species. In this work, we use multispecies ion observations and magnetic field measurements by the Galileo spacecraft. We limit our study to observations of plasmoids in the Jovian magnetotail, because there is strong ion acceleration in these structures. Our model predicts that electromagnetic turbulence in plasmoids plays an essential role in the acceleration of oxygen, sulfur, and hydrogen ions. The observations show a decrease of the oxygen and sulfur energy spectral index γ at ∼30 to ∼400 keV/nuc with the wave power indicating an energy transfer from electromagnetic waves to particles, in agreement with the model. The wave power threshold for effective acceleration is of the order of 10 nT2Hz−1, as in terrestrial plasmoids. However, this is not observed for hydrogen ions, implying that processes other than wave‐particle interaction are more important for the acceleration of these ions or that the time and energy resolution of the observations is too coarse. The results are expected to be confirmed by improved plasma measurements by the Juno spacecraft.
High Survivability of Micrometeorites on Mars: Sites With Enhanced Availability of Limiting Nutrients
Authors: Tomkins Andrew G. , Genge Matthew J. , Tait Alastair W. , Alkemade Sarah L. , Langendam Andrew D. , Perry Prudence P. , Wilson Sasha 
Published: June 2019

AbstractNASA's strategy in exploring Mars has been to follow the water, because water is essential for life, and it has been found that there are many locations where there was once liquid water on the surface. Now perhaps, to narrow down the search for life on a barren basalt‐dominated surface, there needs to be a refocusing to a strategy of “follow the nutrients.” Here we model the entry of metallic micrometeoroids through the Martian atmosphere, and investigate variations in micrometeorite abundance at an analogue site on the Nullarbor Plain in Australia, to determine where the common limiting nutrients available in these (e.g., P, S, Fe) become concentrated on the surface of Mars. We find that dense micrometeorites are abundant in a range of desert environments, becoming concentrated by aeolian processes into specific sites that would be easily investigated by a robotic rover. Our modeling suggests that micrometeorites are currently far more abundant on the surface of Mars than on Earth, and given the far greater abundance of water and warmer conditions on Earth and thus much more active weather system, this was likely true throughout the history of Mars. Because micrometeorites contain a variety of redox sensitive minerals including FeNi alloys, sulfide and phosphide minerals, and organic compounds, the sites where these become concentrated are far more nutrient rich, and thus more compatible with chemolithotrophic life than most of the Martian surface.
Use and abuse of correlation analyses in microbial ecology
Authors: Carr Alex , Diener Christian , Baliga Nitin S , Gibbons Sean M 
Published: June 2019

Abstract
Correlation analyses are often included in bioinformatic pipelines as methods for inferring taxon–taxon interactions. In this perspective, we highlight the pitfalls of inferring interactions from covariance and suggest methods, study design considerations, and additional data types for improving high-throughput interaction inferences. We conclude that correlation, even when augmented by other data types, almost never provides reliable information on direct biotic interactions in real-world ecosystems. These bioinformatically inferred associations are useful for reducing the number of potential hypotheses that we might test, but will never preclude the necessity for experimental validation.
DNA requirement in FANCD2 deubiquitination by USP1-UAF1-RAD51AP1 in the Fanconi anemia DNA damage response
Authors: Liang Fengshan , Miller Adam S. , Longerich Simonne , Tang Caroline , Maranon David , Williamson Elizabeth A. , Hromas Robert , Wiese Claudia , Kupfer Gary M. , Sung Patrick 
Published: June 2019

AbstractFanconi anemia (FA) is a multigenic disease of bone marrow failure and cancer susceptibility stemming from a failure to remove DNA crosslinks and other chromosomal lesions. Within the FA DNA damage response pathway, DNA-dependent monoubiquitinaton of FANCD2 licenses downstream events, while timely FANCD2 deubiquitination serves to extinguish the response. Here, we show with reconstituted biochemical systems, which we developed, that efficient FANCD2 deubiquitination by the USP1-UAF1 complex is dependent on DNA and DNA binding by UAF1. Surprisingly, we find that the DNA binding activity of the UAF1-associated protein RAD51AP1 can substitute for that of UAF1 in FANCD2 deubiquitination in our biochemical system. We also reveal the importance of DNA binding by UAF1 and RAD51AP1 in FANCD2 deubiquitination in the cellular setting. Our results provide insights into a key step in the FA pathway and help define the multifaceted role of the USP1-UAF1-RAD51AP1 complex in DNA damage tolerance and genome repair.
Efficient base editing for multiple genes and loci in pigs using base editors
Authors: Xie Jingke , Ge Weikai , Li Nan , Liu Qishuai , Chen Fangbing , Yang Xiaoyu , Huang Xingyun , Ouyang Zhen , Zhang Quanjun , Zhao Yu , Liu Zhaoming , Gou Shixue , Wu Han , Lai Chengdan , Fan Nana , Jin Qin , Shi Hui , Liang Yanhui , Lan Ting , Quan Longquan , Li Xiaoping , Wang Kepin , Lai Liangxue 
Published: June 2019

AbstractCytosine base editors (CBEs) enable programmable C-to-T conversion without DNA double-stranded breaks and homology-directed repair in a variety of organisms, which exhibit great potential for agricultural and biomedical applications. However, all reported cases only involved C-to-T substitution at a single targeted genomic site. Whether C-to-T substitution is effective in multiple sites/loci has not been verified in large animals. Here, by using pigs, an important animal for agriculture and biomedicine, as the subjective animal, we showed that CBEs could efficiently induce C-to-T conversions at multiple sites/loci with the combination of three genes, including DMD, TYR, and LMNA, or RAG1, RAG2, and IL2RG, simultaneously, at the embryonic and cellular levels. CBEs also could disrupt genes (pol gene of porcine endogenous retrovirus) with dozens of copies by introducing multiple premature stop codons. With the CBEs, pigs carrying single gene or multiple gene point mutations were generated through embryo injection or nuclear transfer approach.
Artificial coiled coil biomineralisation protein for the synthesis of magnetic nanoparticles
Authors: Rawlings Andrea E. , Somner Lori A. , Fitzpatrick-Milton Michaela , Roebuck Thomas P. , Gwyn Christopher , Liravi Panah , Seville Victoria , Neal Thomas J. , Mykhaylyk Oleksandr O. , Baldwin Stephen A. , Staniland Sarah S. 
Published: June 2019

AbstractGreen synthesis of precise inorganic nanomaterials is a major challenge. Magnetotactic bacteria biomineralise magnetite nanoparticles (MNPs) within membrane vesicles (magnetosomes), which are embedded with dedicated proteins that control nanocrystal formation. Some such proteins are used in vitro to control MNP formation in green synthesis; however, these membrane proteins self-aggregate, making their production and use in vitro challenging and difficult to scale. Here, we provide an alternative solution by displaying active loops from biomineralisation proteins Mms13 and MmsF on stem-loop coiled-coil scaffold proteins (Mms13cc/MmsFcc). These artificial biomineralisation proteins form soluble, stable alpha-helical hairpin monomers, and MmsFcc successfully controls the formation of MNP when added to magnetite synthesis, regulating synthesis comparably to native MmsF. This study demonstrates how displaying active loops from membrane proteins on coiled-coil scaffolds removes membrane protein solubility issues, while retains activity, enabling a generic approach to readily-expressible, versatile, artificial membrane proteins for more accessible study and exploitation.
Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases
Authors: Singhania Akul , Graham Christine M. , Gabryšová Leona , Moreira-Teixeira Lúcia , Stavropoulos Evangelos , Pitt Jonathan M. , Chakravarty Probir , Warnatsch Annika , Branchett William J. , Conejero Laura , Lin Jing-Wen , Davidson Sophia , Wilson Mark S. , Bancroft Gregory , Langhorne Jean , Frickel Eva , Sesay Abdul K. , Priestnall Simon L. , Herbert Eleanor , Ioannou Marianna , Wang Qian , Humphreys Ian R. , Dodd Jonathan , Openshaw Peter J. M. , Mayer-Barber Katrin D. , Jankovic Dragana , Sher Alan , Lloyd Clare M. , Baldwin Nicole , Chaussabel Damien , Papayannopoulos Venizelos , Wack Andreas , Banchereau Jacques F. , Pascual Virginia M. , O’Garra Anne 
Published: June 2019

AbstractUnderstanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either IFN-γ and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-γ-inducible, but not IL-17- or allergy-associated signatures, are preserved in the blood. While IL-17-associated genes identified in lung are detected in blood, the allergy signature is only detectable in blood CD4+effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-γ signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology duringToxoplasma gondiiinfection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.
Orbital-flop Induced Magnetoresistance Anisotropy in Rare Earth Monopnictide CeSb
Authors: Xu Jing , Wu Fengcheng , Bao Jin-Ke , Han Fei , Xiao Zhi-Li , Martin Ivar , Lyu Yang-Yang , Wang Yong-Lei , Chung Duck Young , Li Mingda , Zhang Wei , Pearson John E. , Jiang Jidong S. , Kanatzidis Mercouri G. , Kwok Wai-Kwong 
Published: June 2019

AbstractThe charge and spin of the electrons in solids have been extensively exploited in electronic devices and in the development of spintronics. Another attribute of electrons—their orbital nature—is attracting growing interest for understanding exotic phenomena and in creating the next-generation of quantum devices such as orbital qubits. Here, we report on orbital-flop induced magnetoresistance anisotropy in CeSb. In the low temperature high magnetic-field driven ferromagnetic state, a series of additional minima appear in the angle-dependent magnetoresistance. These minima arise from the anisotropic magnetization originating from orbital-flops and from the enhanced electron scattering from magnetic multidomains formed around the first-order orbital-flop transition. The measured magnetization anisotropy can be accounted for with a phenomenological model involving orbital-flops and a spin-valve-like structure is used to demonstrate the viable utilization of orbital-flop phenomenon. Our results showcase a contribution of orbital behavior in the emergence of intriguing phenomena.
Lead halide perovskites for photocatalytic organic synthesis
Authors: Zhu Xiaolin , Lin Yixiong , San Martin Jovan , Sun Yue , Zhu Dian , Yan Yong 
Published: June 2019

AbstractNature is capable of storing solar energy in chemical bonds via photosynthesis through a series of C–C, C–O and C–N bond-forming reactions starting from CO2 and light. Direct capture of solar energy for organic synthesis is a promising approach. Lead (Pb)-halide perovskite solar cells reach 24.2% power conversion efficiency, rendering perovskite a unique type material for solar energy capture. We argue that photophysical properties of perovskites already proved for photovoltaics, also should be of interest in photoredox organic synthesis. Because the key aspects of these two applications are both relying on charge separation and transfer. Here we demonstrated that perovskites nanocrystals are exceptional candidates as photocatalysts for fundamental organic reactions, for example C–C, C–N and C–O bond-formations. Stability of CsPbBr3 in organic solvents and ease-of-tuning their bandedges garner perovskite a wider scope of organic substrate activations. Our low-cost, easy-to-process, highly-efficient, air-tolerant and bandedge-tunable perovskites may bring new breakthrough in organic chemistry.
Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses
Authors: Wu Ting , Guan Jing , Handel Andreas , Tscharke David C. , Sidney John , Sette Alessandro , Wakim Linda M. , Sng Xavier Y. X. , Thomas Paul G. , Croft Nathan P. , Purcell Anthony W. , La Gruta Nicole L. 
Published: June 2019

AbstractThe magnitude of T cell responses to infection is a function of the naïve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)366–374presentation, while cross-presentation is optimal for acid polymerase (PA)224–233presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
Authors: Linscheid Nora , Logantha Sunil Jit R. J. , Poulsen Pi Camilla , Zhang Shanzhuo , Schrölkamp Maren , Egerod Kristoffer Lihme , Thompson Jonatan James , Kitmitto Ashraf , Galli Gina , Humphries Martin J. , Zhang Henggui , Pers Tune H. , Olsen Jesper Velgaard , Boyett Mark , Lundby Alicia 
Published: June 2019

AbstractThe sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. The molecular underpinnings of its pacemaking abilities are debated. Using high-resolution mass spectrometry, we here quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveal significant differences in ion channels responsible for the membrane clock, but not in Ca2+ clock proteins, suggesting that the membrane clock underpins pacemaking. Consistently, incorporation of ion channel expression differences into a biophysically-detailed atrial action potential model result in pacemaking and a sinus node-like action potential. Combining our quantitative proteomics data with computational modeling, we estimate ion channel copy numbers for sinus node myocytes. Our findings provide detailed insights into the unique molecular make-up of the cardiac pacemaker.
CRISPR-Cas9 fusion to dominant-negative 53BP1 enhances HDR and inhibits NHEJ specifically at Cas9 target sites
Authors: Jayavaradhan Rajeswari , Pillis Devin M. , Goodman Michael , Zhang Fan , Zhang Yue , Andreassen Paul R. , Malik Punam 
Published: June 2019

AbstractPrecise genome editing/correction of DNA double-strand breaks (DSBs) induced by CRISPR-Cas9 by homology-dependent repair (HDR) is limited by the competing error-prone non-homologous end-joining (NHEJ) DNA repair pathway. Here, we define a safer and efficient system that promotes HDR-based precise genome editing, while reducing NHEJ locally, only at CRISPR-Cas9-induced DSBs. We fused a dominant-negative mutant of 53BP1, DN1S, to Cas9 nucleases, and the resulting Cas9-DN1S fusion proteins significantly block NHEJ events specifically at Cas9 cut sites and improve HDR frequency; HDR frequency reached 86% in K562 cells. Cas9-DN1S protein maintains this effect in different human cell types, including leukocyte adhesion deficiency (LAD) patient-derived immortalized B lymphocytes, where nearly 70% of alleles were repaired by HDR and 7% by NHEJ. Our CRISPR-Cas9-DN1S system is clinically relevant to improve the efficiencies of precise gene correction/insertion, significantly reducing error-prone NHEJ events at the nuclease cleavage site, while avoiding the unwanted effects of global NHEJ inhibition.
The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression
Authors: Huang Jian , Zhao Lan , Fan Yunshan , Liao Lifan , Ma Peter X. , Xiao Guozhi , Chen Di 
Published: June 2019

AbstractOsteoarthritis (OA) is a common, painful disease. Currently OA is incurable, and its etiology largely unknown, partly due to limited understanding of OA as a whole-joint disease. Here we report that two homologous microRNAs, miR-204 and miR-211, maintain joint homeostasis to suppress OA pathogenesis. Specific knockout of miR-204/-211 in mesenchymal progenitor cells (MPCs) results in Runx2 accumulation in multi-type joint cells, causing whole-joint degeneration. Specifically, miR-204/-211 loss-of-function induces matrix-degrading proteases in articular chondrocytes and synoviocytes, stimulating articular cartilage destruction. Moreover, miR-204/-211 ablation enhances NGF expression in a Runx2-dependent manner, and thus hyper-activates Akt signaling and MPC proliferation, underlying multiplex non-cartilaginous OA conditions including synovial hyperplasia, osteophyte outgrowth and subchondral sclerosis. Importantly, miR-204/-211-deficiency-induced OA is largely rescued by Runx2 insufficiency, confirming the miR-204/-211-Runx2 axis. Further, intraarticular administration of miR-204-expressing adeno-associated virus significantly decelerates OA progression. Collectively, miR-204/-211 are essential in maintaining healthy homeostasis of mesenchymal joint cells to counteract OA pathogenesis.
Transcriptome and organellar sequencing highlights the complex origin and diversification of allotetraploid Brassica napus
Authors: An Hong , Qi Xinshuai , Gaynor Michelle L. , Hao Yue , Gebken Sarah C. , Mabry Makenzie E. , McAlvay Alex C. , Teakle Graham R. , Conant Gavin C. , Barker Michael S. , Fu Tingdong , Yi Bin , Pires J. Chris 
Published: June 2019

AbstractBrassica napus, an allotetraploid crop, is hypothesized to be a hybrid from unknown varieties of Brassica rapa and Brassica oleracea. Despite the economic importance of B. napus, much is unresolved regarding its phylogenomic relationships, genetic structure, and diversification. Here we conduct a comprehensive study among diverse accessions from 183 B. napus (including rapeseed, rutabaga, and Siberian kale), 112 B. rapa, and 62 B. oleracea and its wild relatives. Using RNA-seq of B. napus accessions, we define the genetic diversity and sub-genome variance of six genetic clusters. Nuclear and organellar phylogenies for B. napus and its progenitors reveal varying patterns of inheritance and post-formation introgression. We discern regions with signatures of selective sweeps and detect 8,187 differentially expressed genes with implications for B. napus diversification. This study highlights the complex origin and evolution of B. napus providing insights that can further facilitate B. napus breeding and germplasm preservation.
Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification
Authors: Czarnewski Paulo , Parigi Sara M. , Sorini Chiara , Diaz Oscar E. , Das Srustidhar , Gagliani Nicola , Villablanca Eduardo J. 
Published: June 2019

AbstractClinical manifestations and response to therapies in ulcerative colitis (UC) are heterogeneous, yet patient classification criteria for tailored therapies are currently lacking. Here, we present an unsupervised molecular classification of UC patients, concordant with response to therapy in independent retrospective cohorts. We show that classical clustering of UC patient tissue transcriptomic data sets does not identify clinically relevant profiles, likely due to associated covariates. To overcome this, we compare cross-sectional human data sets with a newly generated longitudinal transcriptome profile of murine DSS-induced colitis. We show that the majority of colitis risk-associated gene expression peaks during the inflammatory rather than the recovery phase. Moreover, we achieve UC patient clustering into two distinct transcriptomic profiles, differing in neutrophil-related gene activation. Notably, 87% of patients in UC1 cluster are unresponsive to two most widely used biological therapies. These results demonstrate that cross-species comparison enables stratification of patients undistinguishable by other molecular approaches.
The structure of a 15-stranded actin-like filament from Clostridium botulinum
Authors: Koh Fujiet , Narita Akihiro , Lee Lin Jie , Tanaka Kotaro , Tan Yong Zi , Dandey Venkata P. , Popp David , Robinson Robert C. 
Published: June 2019

AbstractMicrofilaments (actin) and microtubules represent the extremes in eukaryotic cytoskeleton cross-sectional dimensions, raising the question of whether filament architectures are limited by protein fold. Here, we report the cryoelectron microscopy structure of a complex filament formed from 15 protofilaments of an actin-like protein. This actin-like ParM is encoded on the large pCBH Clostridium botulinum plasmid. In cross-section, the ~26 nm diameter filament comprises a central helical protofilament surrounded by intermediate and outer layers of six and eight twisted protofilaments, respectively. Alternating polarity of the layers allows for similar lateral contacts between each layer. This filament design is stiffer than the actin filament, and has likely been selected for during evolution to move large cargos. The comparable sizes of microtubule and pCBH ParM filaments indicate that larger filament architectures are not limited by the protomer fold. Instead, function appears to have been the evolutionary driving force to produce broad, complex filaments.