bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-promoting macrophages prevail in malignant ascites of advanced gastric cancer
Authors: Eum Hye Hyeon , Kwon Minsuk , Ryu Daeun , Jo Areum , Chung Woosung , Kim Nayoung , Hong Yourae , Son Dae-Soon , Kim Seung Tae , Lee Jeeyun , Lee Hae-Ock , Park Woong-Yang 
Published: December 2020

AbstractGastric cancer (GC) patients develop malignant ascites as the disease progresses owing to peritoneal metastasis. GC patients with malignant ascites have a rapidly deteriorating clinical course with short survival following the onset of malignant ascites. Better optimized treatment strategies for this subset of patients are needed. To define the cellular characteristics of malignant ascites of GC, we used single-cell RNA sequencing to characterize tumor cells and tumor-associated macrophages (TAMs) from four samples of malignant ascites and one sample of cerebrospinal fluid. Reference transcriptomes for M1 and M2 macrophages were generated by in vitro differentiation of healthy blood-derived monocytes and applied to assess the inflammatory properties of TAMs. We analyzed 180 cells, including tumor cells, macrophages, and mesothelial cells. Dynamic exchange of tumor-promoting signals, including the CCL3–CCR1 or IL1B–IL1R2 interactions, suggests macrophage recruitment and anti-inflammatory tuning by tumor cells. By comparing these data with reference transcriptomes for M1-type and M2-type macrophages, we found noninflammatory characteristics in macrophages recovered from the malignant ascites of GC. Using public datasets, we demonstrated that the single-cell transcriptome-driven M2-specific signature was associated with poor prognosis in GC. Our data indicate that the anti-inflammatory characteristics of TAMs are controlled by tumor cells and present implications for treatment strategies for GC patients in which combination treatment targeting cancer cells and macrophages may have a reciprocal synergistic effect.
Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication
Authors: Li Zhanghao , Wang Feixia , Liang Baoyu , Su Ying , Sun Sumin , Xia Siwei , Shao Jiangjuan , Zhang Zili , Hong Min , Zhang Feng , Zheng Shizhong 
Published: December 2020

AbstractAs one of the bicyclic metabolic pathways of one-carbon metabolism, methionine metabolism is the pivot linking the folate cycle to the transsulfuration pathway. In addition to being a precursor for glutathione synthesis, and the principal methyl donor for nucleic acid, phospholipid, histone, biogenic amine, and protein methylation, methionine metabolites can participate in polyamine synthesis. Methionine metabolism disorder can aggravate the damage in the pathological state of a disease. In the occurrence and development of chronic liver diseases (CLDs), changes in various components involved in methionine metabolism can affect the pathological state through various mechanisms. A methionine-deficient diet is commonly used for building CLD models. The conversion of key enzymes of methionine metabolism methionine adenosyltransferase (MAT) 1 A and MAT2A/MAT2B is closely related to fibrosis and hepatocellular carcinoma. In vivo and in vitro experiments have shown that by intervening related enzymes or downstream metabolites to interfere with methionine metabolism, the liver injuries could be reduced. Recently, methionine supplementation has gradually attracted the attention of many clinical researchers. Most researchers agree that adequate methionine supplementation can help reduce liver damage. Retrospective analysis of recently conducted relevant studies is of profound significance. This paper reviews the latest achievements related to methionine metabolism and CLD, from molecular mechanisms to clinical research, and provides some insights into the future direction of basic and clinical research.
Bioinspired carrier-free peptide conjugated BF2-oxasmaragdyrin dye-based nano self-assemblies: a photostable NIR cancer theragnostic agent
Authors: Laxman Kandala , Reddy B. Pradeep K. , Mishra Sumit K. , Robinson Andrea , De Abhijit , Srivastava Rohit , Ravikanth Mangalampalli 
Published: December 2020

AbstractPhotothermal therapy (PTT) has attracted great interest in cancer treatment, and the quest for potential organic photothermal agents is underway owing to the nonbiodegradable nature and chronic toxicity of existing inorganic nanomaterials. Organic material-based nanoformulations with good photothermal and fluorescence properties in the near-infrared (NIR-I) window are scarce. However, porphyrins are one category of biocompatible systems that are advantageous for photothermal therapy but are currently based in the visible region, causing limited depth of tissue penetration and leading to compromised photothermal and near-infrared fluorescence (NIRF) imaging applications. To overcome these limitations, we report the synthesis of L,L-diphenylalanine conjugated BF2-oxasmaragdyrin (FF-BSC) and the fabrication of monodispersed spherical self-assemblies (FF-BSC NPs) using a USP class 3 solvent-water mixture. The resulting product exhibited excellent photostability (NIR exposure), multicycle photothermal efficacy, and NIR fluorescence. In vitro studies revealed good biocompatibility, efficient cellular internalization, and photothermal efficacy. Preclinical studies of these nano-self-assemblies demonstrated nontoxicity, efficient whole-body NIRF imaging, fractional passive tumor homing, and excellent photothermal tumor ablation potential. The absorbance and fluorescence of FF-BSC NPs in NIR-I make them suitable for theragnostic applications over existing porphyrins/inorganic nanomaterials for future clinical applications.
3D projection electrophoresis for single-cell immunoblotting
Authors: Grist Samantha M. , Mourdoukoutas Andoni P. , Herr Amy E. 
Published: December 2020

AbstractImmunoassays and mass spectrometry are powerful single-cell protein analysis tools; however, interfacing and throughput bottlenecks remain. Here, we introduce three-dimensional single-cell immunoblots to detect both cytosolic and nuclear proteins. The 3D microfluidic device is a photoactive polyacrylamide gel with a microwell array-patterned face (xy) for cell isolation and lysis. Single-cell lysate in each microwell is “electrophoretically projected” into the 3rd dimension (z-axis), separated by size, and photo-captured in the gel for immunoprobing and confocal/light-sheet imaging. Design and analysis are informed by the physics of 3D diffusion. Electrophoresis throughput is > 2.5 cells/s (70× faster than published serial sampling), with 25 immunoblots/mm2 device area (>10× increase over previous immunoblots). The 3D microdevice design synchronizes analyses of hundreds of cells, compared to status quo serial analyses that impart hours-long delay between the first and last cells. Here, we introduce projection electrophoresis to augment the heavily genomic and transcriptomic single-cell atlases with protein-level profiling.
Epigenetic activation of a RAS/MYC axis in H3.3K27M-driven cancer
Authors: Pajovic Sanja , Siddaway Robert , Bridge Taylor , Sheth Javal , Rakopoulos Patricia , Kim Byungjin , Ryall Scott , Agnihotri Sameer , Phillips Lauren , Yu Man , Li Christopher , Milos Scott , Patel Palak , Srikanthan Dilakshan , Huang Annie , Hawkins Cynthia 
Published: December 2020

AbstractHistone H3 lysine 27 (H3K27M) mutations represent the canonical oncohistone, occurring frequently in midline gliomas but also identified in haematopoietic malignancies and carcinomas. H3K27M functions, at least in part, through widespread changes in H3K27 trimethylation but its role in tumour initiation remains obscure. To address this, we created a transgenic mouse expressing H3.3K27M in diverse progenitor cell populations. H3.3K27M expression drives tumorigenesis in multiple tissues, which is further enhanced by Trp53 deletion. We find that H3.3K27M epigenetically activates a transcriptome, enriched for PRC2 and SOX10 targets, that overrides developmental and tissue specificity and is conserved between H3.3K27M-mutant mouse and human tumours. A key feature of the H3K27M transcriptome is activation of a RAS/MYC axis, which we find can be targeted therapeutically in isogenic and primary DIPG cell lines with H3.3K27M mutations, providing an explanation for the common co-occurrence of alterations in these pathways in human H3.3K27M-driven cancer. Taken together, these results show how H3.3K27M-driven transcriptome remodelling promotes tumorigenesis and will be critical for targeting cancers with these mutations.
A substrate binding model for the KEOPS tRNA modifying complex
Authors: Beenstock Jonah , Ona Samara Mishelle , Porat Jennifer , Orlicky Stephen , Wan Leo C. K. , Ceccarelli Derek F. , Maisonneuve Pierre , Szilard Rachel K. , Yin Zhe , Setiaputra Dheva , Mao Daniel Y. L. , Khan Morgan , Raval Shaunak , Schriemer David C. , Bayfield Mark A. , Durocher Daniel , Sicheri Frank 
Published: December 2020

AbstractThe KEOPS complex, which is conserved across archaea and eukaryotes, is composed of four core subunits; Pcc1, Kae1, Bud32 and Cgi121. KEOPS is crucial for the fitness of all organisms examined. In humans, pathogenic mutations in KEOPS genes lead to Galloway–Mowat syndrome, an autosomal-recessive disease causing childhood lethality. Kae1 catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine, but the precise roles of all other KEOPS subunits remain an enigma. Here we show using structure-guided studies that Cgi121 recruits tRNA to KEOPS by binding to its 3’ CCA tail. A composite model of KEOPS bound to tRNA reveals that all KEOPS subunits form an extended tRNA-binding surface that we have validated in vitro and in vivo to mediate the interaction with the tRNA substrate and its modification. These findings provide a framework for understanding the inner workings of KEOPS and delineate why all KEOPS subunits are essential.
Arabidopsis calcium-dependent protein kinase 3 regulates actin cytoskeleton organization and immunity
Authors: Lu Yi-Ju , Li Pai , Shimono Masaki , Corrion Alex , Higaki Takumi , He Sheng Yang , Day Brad 
Published: December 2020

AbstractPattern-triggered immunity and effector-triggered immunity are two primary forms of innate immunity in land plants. The molecular components and connecting nodes of pattern-triggered immunity and effector-triggered immunity are not fully understood. Here, we report that the Arabidopsis calcium-dependent protein kinase CPK3 is a key regulator of both pattern-triggered immunity and effector-triggered immunity. In vitro and in vivo phosphorylation assays, coupled with genetic and cell biology-based analyses, show that actin-depolymerization factor 4 (ADF4) is a physiological substrate of CPK3, and that phosphorylation of ADF4 by CPK3 governs actin cytoskeletal organization associated with pattern-triggered immunity. CPK3 regulates stomatal closure induced by flg22 and is required for resistance to Pst DC3000. Our data further demonstrates that CPK3 is required for resistance to Pst DC3000 carrying the effector AvrPphB. These results suggest that CPK3 is a missing link between cytoskeleton organization, pattern-triggered immunity and effector-triggered immunity.
Early decarbonisation of the European energy system pays off
Authors: Victoria Marta , Zhu Kun , Brown Tom , Andresen Gorm B. , Greiner Martin 
Published: December 2020

AbstractFor a given carbon budget over several decades, different transformation rates for the energy system yield starkly different results. Here we consider a budget of 33 GtCO2 for the cumulative carbon dioxide emissions from the European electricity, heating, and transport sectors between 2020 and 2050, which represents Europe’s contribution to the Paris Agreement. We have found that following an early and steady path in which emissions are strongly reduced in the first decade is more cost-effective than following a late and rapid path in which low initial reduction targets quickly deplete the carbon budget and require a sharp reduction later. We show that solar photovoltaic, onshore and offshore wind can become the cornerstone of a fully decarbonised energy system and that installation rates similar to historical maxima are required to achieve timely decarbonisation. Key to those results is a proper representation of existing balancing strategies through an open, hourly-resolved, networked model of the sector-coupled European energy system.
Revealing the structures of megadalton-scale DNA complexes with nucleotide resolution
Authors: Kube Massimo , Kohler Fabian , Feigl Elija , Nagel-Yüksel Baki , Willner Elena M. , Funke Jonas J. , Gerling Thomas , Stömmer Pierre , Honemann Maximilian N. , Martin Thomas G. , Scheres Sjors H. W. , Dietz Hendrik 
Published: December 2020

AbstractThe methods of DNA nanotechnology enable the rational design of custom shapes that self-assemble in solution from sets of DNA molecules. DNA origami, in which a long template DNA single strand is folded by many short DNA oligonucleotides, can be employed to make objects comprising hundreds of unique DNA strands and thousands of base pairs, thus in principle providing many degrees of freedom for modelling complex objects of defined 3D shapes and sizes. Here, we address the problem of accurate structural validation of DNA objects in solution with cryo-EM based methodologies. By taking into account structural fluctuations, we can determine structures with improved detail compared to previous work. To interpret the experimental cryo-EM maps, we present molecular-dynamics-based methods for building pseudo-atomic models in a semi-automated fashion. Among other features, our data allows discerning details such as helical grooves, single-strand versus double-strand crossovers, backbone phosphate positions, and single-strand breaks. Obtaining this higher level of detail is a step forward that now allows designers to inspect and refine their designs with base-pair level interventions.
XBP1 links the 12-hour clock to NAFLD and regulation of membrane fluidity and lipid homeostasis
Authors: Meng Huan , Gonzales Naomi M. , Lonard David M. , Putluri Nagireddy , Zhu Bokai , Dacso Clifford C. , York Brian , O’Malley Bert W. 
Published: December 2020

AbstractA distinct 12-hour clock exists in addition to the 24-hour circadian clock to coordinate metabolic and stress rhythms. Here, we show that liver-specific ablation of X-box binding protein 1 (XBP1) disrupts the hepatic 12-hour clock and promotes spontaneous non-alcoholic fatty liver disease (NAFLD). We show that hepatic XBP1 predominantly regulates the 12-hour rhythmicity of gene transcription in the mouse liver and demonstrate that perturbation of the 12-hour clock, but not the core circadian clock, is associated with the onset and progression of this NAFLD phenotype. Mechanistically, we provide evidence that the spliced form of XBP1 (XBP1s) binds to the hepatic 12-hour cistrome to directly regulate the 12-hour clock, with a periodicity paralleling the harmonic activation of the 12-hour oscillatory transcription of many rate-limiting metabolic genes known to have perturbations in human metabolic disease. Functionally, we show that Xbp1 ablation significantly reduces cellular membrane fluidity and impairs lipid homeostasis via rate-limiting metabolic processes in fatty acid monounsaturated and phospholipid remodeling pathways. These findings reveal that genetic disruption of the hepatic 12-hour clock links to the onset and progression of NAFLD development via transcriptional regulator XBP1, and demonstrate a role for XBP1 and the 12-hour clock in the modulation of phospholipid composition and the maintenance of lipid homeostasis.
Stabilization of ε-iron carbide as high-temperature catalyst under realistic Fischer–Tropsch synthesis conditions
Authors: Lyu Shuai , Wang Li , Li Zhe , Yin Shukun , Chen Jie , Zhang Yuhua , Li Jinlin , Wang Ye 
Published: December 2020

AbstractThe development of efficient catalysts for Fischer–Tropsch (FT) synthesis, a core reaction in the utilization of non-petroleum carbon resources to supply energy and chemicals, has attracted much recent attention. ε-Iron carbide (ε-Fe2C) was proposed as the most active iron phase for FT synthesis, but this phase is generally unstable under realistic FT reaction conditions (> 523 K). Here, we succeed in stabilizing pure-phase ε-Fe2C nanocrystals by confining them into graphene layers and obtain an iron-time yield of 1258 μmolCOgFe−1s−1under realistic FT synthesis conditions, one order of magnitude higher than that of the conventional carbon-supported Fe catalyst. The ε-Fe2C@graphene catalyst is stable at least for 400 h under high-temperature conditions. Density functional theory (DFT) calculations reveal the feasible formation of ε-Fe2C by carburization of α-Fe precursor through interfacial interactions of ε-Fe2C@graphene. This work provides a promising strategy to design highly active and stable Fe-based FT catalysts.
Integrative modeling of membrane-associated protein assemblies
Authors: Roel-Touris Jorge , Jiménez-García Brian , Bonvin Alexandre M. J. J. 
Published: December 2020

AbstractMembrane proteins are among the most challenging systems to study with experimental structural biology techniques. The increased number of deposited structures of membrane proteins has opened the route to modeling their complexes by methods such as docking. Here, we present an integrative computational protocol for the modeling of membrane-associated protein assemblies. The information encoded by the membrane is represented by artificial beads, which allow targeting of the docking toward the binding-competent regions. It combines efficient, artificial intelligence-based rigid-body docking by LightDock with a flexible final refinement with HADDOCK to remove potential clashes at the interface. We demonstrate the performance of this protocol on eighteen membrane-associated complexes, whose interface lies between the membrane and either the cytosolic or periplasmic regions. In addition, we provide a comparison to another state-of-the-art docking software, ZDOCK. This protocol should shed light on the still dark fraction of the interactome consisting of membrane proteins.
Coupling of H3K27me3 recognition with transcriptional repression through the BAH-PHD-CPL2 complex in Arabidopsis
Authors: Zhang Yi-Zhe , Yuan Jianlong , Zhang Lingrui , Chen Chunxiang , Wang Yuhua , Zhang Guiping , Peng Li , Xie Si-Si , Jiang Jing , Zhu Jian-Kang , Du Jiamu , Duan Cheng-Guo 
Published: December 2020

AbstractHistone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes. However, the H3K27me3 recognition and transcriptional repression mechanisms are only partially understood. Here, we report a mechanism for H3K27me3 recognition and transcriptional repression. Our structural and biochemical data showed that the BAH domain protein AIPP3 and the PHD proteins AIPP2 and PAIPP2 cooperate to read H3K27me3 and unmodified H3K4 histone marks, respectively, in Arabidopsis. The BAH-PHD bivalent histone reader complex silences a substantial subset of H3K27me3-enriched loci, including a number of development and stress response-related genes such as the RNA silencing effector gene ARGONAUTE 5 (AGO5). We found that the BAH-PHD module associates with CPL2, a plant-specific Pol II carboxyl terminal domain (CTD) phosphatase, to form the BAH-PHD-CPL2 complex (BPC) for transcriptional repression. The BPC complex represses transcription through CPL2-mediated CTD dephosphorylation, thereby causing inhibition of Pol II release from the transcriptional start site. Our work reveals a mechanism coupling H3K27me3 recognition with transcriptional repression through the alteration of Pol II phosphorylation states, thereby contributing to our understanding of the mechanism of H3K27me3-dependent silencing.
Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy
Authors: Patterson E. I. , Elia G. , Grassi A. , Giordano A. , Desario C. , Medardo M. , Smith S. L. , Anderson E. R. , Prince T. , Patterson G. T. , Lorusso E. , Lucente M. S. , Lanave G. , Lauzi S. , Bonfanti U. , Stranieri A. , Martella V. , Solari Basano F. , Barrs V. R. , Radford A. D. , Agrimi U. , Hughes G. L. , Paltrinieri S. , Decaro N. 
Published: December 2020

AbstractSARS-CoV-2 emerged from animals and is now easily transmitted between people. Sporadic detection of natural cases in animals alongside successful experimental infections of pets, such as cats, ferrets and dogs, raises questions about the susceptibility of animals under natural conditions of pet ownership. Here, we report a large-scale study to assess SARS-CoV-2 infection in 919 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households. Understanding risk factors associated with this and their potential to infect other species requires urgent investigation.
Peroxisomes form intralumenal vesicles with roles in fatty acid catabolism and protein compartmentalization in Arabidopsis
Authors: Wright Zachary J. , Bartel Bonnie 
Published: December 2020

AbstractPeroxisomes are vital organelles that compartmentalize critical metabolic reactions, such as the breakdown of fats, in eukaryotic cells. Although peroxisomes typically are considered to consist of a single membrane enclosing a protein lumen, more complex peroxisomal membrane structure has occasionally been observed in yeast, mammals, and plants. However, technical challenges have limited the recognition and understanding of this complexity. Here we exploit the unusually large size of Arabidopsis peroxisomes to demonstrate that peroxisomes have extensive internal membranes. These internal vesicles accumulate over time, use ESCRT (endosomal sorting complexes required for transport) machinery for formation, and appear to derive from the outer peroxisomal membrane. Moreover, these vesicles can harbor distinct proteins and do not form normally when fatty acid β-oxidation, a core function of peroxisomes, is impaired. Our findings suggest a mechanism for lipid mobilization that circumvents challenges in processing insoluble metabolites. This revision of the classical view of peroxisomes as single-membrane organelles has implications for all aspects of peroxisome biogenesis and function and may help address fundamental questions in peroxisome evolution.
Prediction of the Curie temperature considering the dependence of the phonon free energy on magnetic states
Authors: Tanaka Tomonori , Gohda Yoshihiro 
Published: December 2020

AbstractPrediction of the Curie temperature is of significant importance for the design of ferromagnetic materials. One of the most widely used methods to estimate the Curie temperature from first principles relies on a spin Hamiltonian, for example, the Heisenberg Hamiltonian, and exchange coupling parameters obtained by first-principles calculations at zero temperature. Even though there have been attempts to include the effects of magnetism on phonons, the influence of magnetism-dependent phonons on magnetism has been disregarded in the theoretical estimation of the Curie temperature. Here, we propose a first-principles thermodynamic approach to minimise the total free energy considering both the influences of magnetism on phonons and the feedback effect from phonons to magnetism. By applying our scheme to body-centered cubic Fe, we find a significant reduction of the Curie temperature due to the feedback effect. This result indicates the importance of the feedback effect for a quantitative description of finite-temperature magnetism. In addition, we point out that the reduction in the theoretical Curie temperature arises in a wide range of ferromagnetic materials that exhibit phonon softening due to magnetic disordering.