bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1
Authors: Du Yushen , Hultquist Judd F. , Zhou Quan , Olson Anders , Tseng Yenwen , Zhang Tian-hao , Hong Mengying , Tang Kejun , Chen Liubo , Meng Xiangzhi , McGregor Michael J. , Dai Lei , Gong Danyang , Martin-Sancho Laura , Chanda Sumit , Li Xinming , Bensenger Steve , Krogan Nevan J. , Sun Ren 
Published: May 2020

AbstractA comprehensive examination of protein-protein interactions (PPIs) is fundamental for the understanding of cellular machineries. However, limitations in current methodologies often prevent the detection of PPIs with low abundance proteins. To overcome this challenge, we develop a mRNA display with library of even-distribution (md-LED) method that facilitates the detection of low abundance binders with high specificity and sensitivity. As a proof-of-principle, we apply md-LED to IAV NS1 protein. Complementary to AP-MS, md-LED enables us to validate previously described PPIs as well as to identify novel NS1 interactors. We show that interacting with FASN allows NS1 to directly regulate the synthesis of cellular fatty acids. We also use md-LED to identify a mutant of NS1, D92Y, results in a loss of interaction with CPSF1. The use of high-throughput sequencing as the readout for md-LED enables sensitive quantification of interactions, ultimately enabling massively parallel experimentation for the investigation of PPIs.
Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation
Authors: Bamford Natalie C. , Le Mauff François , Van Loon Jaime C. , Ostapska Hanna , Snarr Brendan D. , Zhang Yongzhen , Kitova Elena N. , Klassen John S. , Codée Jeroen D. C. , Sheppard Donald C. , Howell P. Lynne 
Published: May 2020

AbstractThe exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes.
Ribonucleotide incorporation in yeast genomic DNA shows preference for cytosine and guanosine preceded by deoxyadenosine
Authors: Balachander Sathya , Gombolay Alli L. , Yang Taehwan , Xu Penghao , Newnam Gary , Keskin Havva , El-Sayed Waleed M. M. , Bryksin Anton V. , Tao Sijia , Bowen Nicole E. , Schinazi Raymond F. , Kim Baek , Koh Kyung Duk , Vannberg Fredrik O. , Storici Francesca 
Published: May 2020

AbstractDespite the abundance of ribonucleoside monophosphates (rNMPs) in DNA, sites of rNMP incorporation remain poorly characterized. Here, by using ribose-seq and Ribose-Map techniques, we built and analyzed high-throughput sequencing libraries of rNMPs derived from mitochondrial and nuclear DNA of budding and fission yeast. We reveal both common and unique features of rNMP sites among yeast species and strains, and between wild type and different ribonuclease H-mutant genotypes. We demonstrate that the rNMPs are not randomly incorporated in DNA. We highlight signatures and patterns of rNMPs, including sites within trinucleotide-repeat tracts. Our results uncover that the deoxyribonucleotide immediately upstream of the rNMPs has a strong influence on rNMP distribution, suggesting a mechanism of rNMP accommodation by DNA polymerases as a driving force of rNMP incorporation. Consistently, we find deoxyadenosine upstream from the most abundant genomic rCMPs and rGMPs. This study establishes a framework to better understand mechanisms of rNMP incorporation in DNA.
Application of combinatorial optimization strategies in synthetic biology
Authors: Naseri Gita , Koffas Mattheos A. G. 
Published: May 2020

AbstractIn the first wave of synthetic biology, genetic elements, combined into simple circuits, are used to control individual cellular functions. In the second wave of synthetic biology, the simple circuits, combined into complex circuits, form systems-level functions. However, efforts to construct complex circuits are often impeded by our limited knowledge of the optimal combination of individual circuits. For example, a fundamental question in most metabolic engineering projects is the optimal level of enzymes for maximizing the output. To address this point, combinatorial optimization approaches have been established, allowing automatic optimization without prior knowledge of the best combination of expression levels of individual genes. This review focuses on current combinatorial optimization methods and emerging technologies facilitating their applications.
Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer
Authors: Saatci Ozge , Kaymak Aysegul , Raza Umar , Ersan Pelin G. , Akbulut Ozge , Banister Carolyn E. , Sikirzhytski Vitali , Tokat Unal Metin , Aykut Gamze , Ansari Suhail A. , Dogan Hayriye Tatli , Dogan Mehmet , Jandaghi Pouria , Isik Aynur , Gundogdu Fatma , Kosemehmetoglu Kemal , Dizdar Omer , Aksoy Sercan , Akyol Aytekin , Uner Aysegul , Buckhaults Phillip J. , Riazalhosseini Yasser , Sahin Ozgur 
Published: May 2020

AbstractChemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy. Similarly, inhibiting FAK/Src results in chemosensitization. These effects are observed in 3D-cultured cell lines, tumor organoids, chemoresistant xenografts, syngeneic tumors and PDX models. Re-expressing the hypoxia-repressed miR-142-3p, which targets HIF1A, LOX and ITGA5, causes further suppression of the HIF-1α/LOX/ITGA5/FN1 axis. Notably, higher LOX, ITGA5, or FN1, or lower miR-142-3p levels are associated with shorter survival in chemotherapy-treated TNBC patients. These results provide strong pre-clinical rationale for developing and testing LOX inhibitors to overcome chemoresistance in TNBC patients.
Universal mechanical exfoliation of large-area 2D crystals
Authors: Huang Yuan , Pan Yu-Hao , Yang Rong , Bao Li-Hong , Meng Lei , Luo Hai-Lan , Cai Yong-Qing , Liu Guo-Dong , Zhao Wen-Juan , Zhou Zhang , Wu Liang-Mei , Zhu Zhi-Li , Huang Ming , Liu Li-Wei , Liu Lei , Cheng Peng , Wu Ke-Hui , Tian Shi-Bing , Gu Chang-Zhi , Shi You-Guo , Guo Yan-Feng , Cheng Zhi Gang , Hu Jiang-Ping , Zhao Lin , Yang Guan-Hua , Sutter Eli , Sutter Peter , Wang Ye-Liang , Ji Wei , Zhou Xing-Jiang , Gao Hong-Jun 
Published: May 2020

AbstractTwo-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.
Large-scale network analysis captures biological features of bacterial plasmids
Authors: Acman Mislav , van Dorp Lucy , Santini Joanne M. , Balloux Francois 
Published: May 2020

AbstractMany bacteria can exchange genetic material through horizontal gene transfer (HGT) mediated by plasmids and plasmid-borne transposable elements. Here, we study the population structure and dynamics of over 10,000 bacterial plasmids, by quantifying their genetic similarities and reconstructing a network based on their shared k-mer content. We use a community detection algorithm to assign plasmids into cliques, which correlate with plasmid gene content, bacterial host range, GC content, and existing classifications based on replicon and mobility (MOB) types. Further analysis of plasmid population structure allows us to uncover candidates for yet undescribed replicon genes, and to identify transposable elements as the main drivers of HGT at broad phylogenetic scales. Our work illustrates the potential of network-based analyses of the bacterial ‘mobilome’ and opens up the prospect of a natural, exhaustive classification framework for bacterial plasmids.
Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
Authors: Hua Xing , Zhao Wei , Pesatori Angela C. , Consonni Dario , Caporaso Neil E. , Zhang Tongwu , Zhu Bin , Wang Mingyi , Jones Kristine , Hicks Belynda , Song Lei , Sampson Joshua , Wedge David C. , Shi Jianxin , Landi Maria Teresa 
Published: May 2020

AbstractIntratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 patients with LUAD. LUAD samples show substantial SCNA and methylation ITH, and clonal architecture analyses present congruent evolutionary trajectories for SCNAs and DNA methylation aberrations. Methylation ITH mapping to gene promoter areas or tumor suppressor genes is low. Moreover, ITH composed of genetic and epigenetic mechanisms altering the same cancer driver genes is shown in several tumors. To quantify ITH for valid statistical association analyses, we develope an average pairwise ITH index (APITH), which does not depend on the number of samples per tumor. Both APITH indexes for SCNAs and methylation aberrations show significant associations with poor prognosis. This study further establishes the important clinical implications of genetic and epigenetic ITH in LUAD.
Freeze-frame imaging of synaptic activity using SynTagMA
Authors: Perez-Alvarez Alberto , Fearey Brenna C. , O’Toole Ryan J. , Yang Wei , Arganda-Carreras Ignacio , Lamothe-Molina Paul J. , Moeyaert Benjamien , Mohr Manuel A. , Panzera Lauren C. , Schulze Christian , Schreiter Eric R. , Wiegert J. Simon , Gee Christine E. , Hoppa Michael B. , Oertner Thomas G. 
Published: May 2020

AbstractInformation within the brain travels from neuron to neuron across billions of synapses. At any given moment, only a small subset of neurons and synapses are active, but finding the active synapses in brain tissue has been a technical challenge. Here we introduce SynTagMA to tag active synapses in a user-defined time window. Upon 395–405 nm illumination, this genetically encoded marker of activity converts from green to red fluorescence if, and only if, it is bound to calcium. Targeted to presynaptic terminals, preSynTagMA allows discrimination between active and silent axons. Targeted to excitatory postsynapses, postSynTagMA creates a snapshot of synapses active just before photoconversion. To analyze large datasets, we show how to identify and track the fluorescence of thousands of individual synapses in an automated fashion. Together, these tools provide an efficient method for repeatedly mapping active neurons and synapses in cell culture, slice preparations, and in vivo during behavior.
Cooperative transport mechanism of human monocarboxylate transporter 2
Authors: Zhang Bo , Jin Qiuheng , Xu Lizhen , Li Ningning , Meng Ying , Chang Shenghai , Zheng Xiang , Wang Jiangqin , Chen Yuan , Neculai Dante , Gao Ning , Zhang Xiaokang , Yang Fan , Guo Jiangtao , Ye Sheng 
Published: May 2020

AbstractProton-linked monocarboxylate transporters (MCTs) must transport monocarboxylate efficiently to facilitate monocarboxylate efflux in glycolytically active cells, and transport monocarboxylate slowly or even shut down to maintain a physiological monocarboxylate concentration in glycolytically inactive cells. To discover how MCTs solve this fundamental aspect of intracellular monocarboxylate homeostasis in the context of multicellular organisms, we analyzed pyruvate transport activity of human monocarboxylate transporter 2 (MCT2). Here we show that MCT2 transport activity exhibits steep dependence on substrate concentration. This property allows MCTs to turn on almost like a switch, which is physiologically crucial to the operation of MCTs in the cellular context. We further determined the cryo-electron microscopy structure of the human MCT2, demonstrating that the concentration sensitivity of MCT2 arises from the strong inter-subunit cooperativity of the MCT2 dimer during transport. These data establish definitively a clear example of evolutionary optimization of protein function.
Mitigation of Arctic permafrost carbon loss through stratospheric aerosol geoengineering
Authors: Chen Yating , Liu Aobo , Moore John C. 
Published: May 2020

AbstractThe Arctic is warming far faster than the global average, threatening the release of large amounts of carbon presently stored in frozen permafrost soils. Increasing Earth’s albedo by the injection of sulfate aerosols into the stratosphere has been proposed as a way of offsetting some of the adverse effects of climate change. We examine this hypothesis in respect of permafrost carbon-climate feedbacks using the PInc-PanTher process model driven by seven earth system models running the Geoengineering Model Intercomparison Project (GeoMIP) G4 stratospheric aerosol injection scheme to reduce radiative forcing under the Representative Concentration Pathway (RCP) 4.5 scenario. Permafrost carbon released as CO2 is halved and as CH4 by 40% under G4 compared with RCP4.5. Economic losses avoided solely by the roughly 14 Pg carbon kept in permafrost soils amount to about US$ 8.4 trillion by 2070 compared with RCP4.5, and indigenous habits and lifestyles would be better conserved.
HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease
Authors: Pao Ping-Chieh , Patnaik Debasis , Watson L. Ashley , Gao Fan , Pan Ling , Wang Jun , Adaikkan Chinnakkaruppan , Penney Jay , Cam Hugh P. , Huang Wen-Chin , Pantano Lorena , Lee Audrey , Nott Alexi , Phan Trongha X. , Gjoneska Elizabeta , Elmsaouri Sara , Haggarty Stephen J. , Tsai Li-Huei 
Published: May 2020

AbstractDNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer’s disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration.
Suppression of superconductivity and enhanced critical field anisotropy in thin flakes of FeSe
Authors: Farrar Liam S. , Bristow Matthew , Haghighirad Amir A. , McCollam Alix , Bending Simon J. , Coldea Amalia I. 
Published: May 2020

AbstractFeSe is a unique superconductor that can be manipulated to enhance its superconductivity using different routes, while its monolayer form grown on different substrates reaches a record high temperature for a two-dimensional system. In order to understand the role played by the substrate and the reduced dimensionality on superconductivity, we examine the superconducting properties of exfoliated FeSe thin flakes by reducing the thickness from bulk down towards 9 nm. Magnetotransport measurements performed in magnetic fields up to 16 T and temperatures down to 2 K help to build up complete superconducting phase diagrams of different thickness flakes. While the thick flakes resemble the bulk behaviour, by reducing the thickness the superconductivity of FeSe flakes is suppressed. The observation of the vortex-antivortex unbinding transition in different flakes provide a direct signature of a dominant two-dimensional pairing channel. However, the upper critical field reflects the evolution of the multi-band nature of superconductivity in FeSe becoming highly two-dimensional and strongly anisotropic only in the thin limit. Our study provides detailed insights into the evolution of the superconducting properties of a multi-band superconductor FeSe in the thin limit in the absence of a dopant substrate.
Integrating water-quality analysis in national household surveys: water and sanitation sector learnings of Ecuador
Authors: Moreno Lorena , Pozo Mónica , Vancraeynest Koenraad , Bain Robert , Palacios Juan Carlos , Jácome Fausto 
Published: May 2020

AbstractTo respond to the global Sustainable Development Goals framework, Ecuador through the National Institute of Statistics and Censuses (INEC) has been strengthening its monitoring system since 2016, specifically on SDG 6.1 and 6.2. The World Bank Group, UNICEF Ecuador Country Office and WHO/UNICEF Joint Monitoring Programme provided initial support. Additional parameters were included in household surveys, including a water sample analysis to detect presence or absence of E. coli bacteria, and the SDG indicators were adapted to the national context. Ecuador collected water-quality data in two national household surveys in 2016 and 2019, including water quality at household's point of consumption for the 2019 survey. This opens opportunities to extend the analysis beyond access to safely managed drinking water services, toward comparison of water quality between source and point of consumption, and analyzing correlations with other parameters, such as handwashing with soap, water treatment, and safe storage and open defecation. This article describes the principal findings of the extended analysis carried out by INEC, as well as the opportunities to present the results for sector advocacy and decision-making purposes. This study concludes that alignment of the national monitoring systems to the SDG 6.1 framework provided strong evidence that water quality is the principal bottleneck in the water sector in Ecuador. Water-quality testing at the point of consumption was evidenced, as well as the importance of household water treatment and possible effects of other hygiene practices like handwashing with soap and open defecation on water quality at the point of consumption.
Large database for the analysis and prediction of spliced and non-spliced peptide generation by proteasomes
Authors: Specht Gerd , Roetschke Hanna P. , Mansurkhodzhaev Artem , Henklein Petra , Textoris-Taube Kathrin , Urlaub Henning , Mishto Michele , Liepe Juliane 
Published: May 2020

AbstractProteasomes are the main producers of antigenic peptides presented to CD8+ T cells. They can cut proteins and release their fragments or recombine non-contiguous fragments thereby generating novel sequences, i.e. spliced peptides. Understanding which are the driving forces and the sequence preferences of both reactions can streamline target discovery in immunotherapies against cancer, infection and autoimmunity. Here, we present a large database of spliced and non-spliced peptides generated by proteasomes in vitro, which is available as simple CSV file and as a MySQL database. To generate the database, we performed in vitro digestions of 55 unique synthetic polypeptide substrates with different proteasome isoforms and experimental conditions. We measured the samples using three mass spectrometers, filtered and validated putative peptides, identified 22,333 peptide product sequences (15,028 spliced and 7,305 non-spliced product sequences). Our database and datasets have been deposited to the Mendeley (doi:10.17632/nr7cs764rc.1) and PRIDE (PXD016782) repositories. We anticipate that this unique database can be a valuable source for predictors of proteasome-catalyzed peptide hydrolysis and splicing, with various future translational applications.
Detecting qualitative changes in biological systems
Authors: Mitrea Cristina , Bollig-Fischer Aliccia , Voichiţa Călin , Donato Michele , Romero Roberto , Drăghici Sorin 
Published: May 2020

AbstractCurrently, most diseases are diagnosed only after significant disease-associated transformations have taken place. Here, we propose an approach able to identify when systemic qualitative changes in biological systems happen, thus opening the possibility for therapeutic interventions before the occurrence of symptoms. The proposed method exploits knowledge from biological networks and longitudinal data using a system impact analysis. The method is validated on eight biological phenomena, three synthetic datasets and five real datasets, for seven organisms. Most importantly, the method accurately detected the transition from the control stage (benign) to the early stage of hepatocellular carcinoma on an eight-stage disease dataset.
Complete analytic solutions for convection-diffusion-reaction-source equations without using an inverse Laplace transform
Authors: Kim Albert S. 
Published: May 2020

AbstractTransient mass-transfer phenomena occurring in natural and engineered systems consist of convection, diffusion, and reaction processes. The coupled phenomena can be described by using the unsteady convection-diffusion-reaction (CDR) equation, which is classified in mathematics as a linear, parabolic partial-differential equation. The availability of analytic solutions is limited to simple cases, e.g., unsteady diffusion and steady convective diffusion. The CDR equation has been considered analytically intractable, depending on the initial and boundary conditions. If spatial adsorption and desorption of matter are super-positioned in the CDR equation as sink and source functions, respectively, then the governing equation becomes an unsteady convection-diffusion-reaction-source (CDRS) equation, of which general solutions are unknown. In this study, a general 1D analytic solution of the CDRS equation is obtained by using a one-sided Laplace transform, by assuming constant diffusivity, velocity, and reactivity. This paper also provides a general formalism to derive 1D analytic solutions for Dirichlet/Dirichlet and Dirichlet/Neumann boundary conditions. Derivations of the analytic solutions are found to be straightforward if a combination of the source function and the initial concentration provide a non-zero singularity pole of inverse Laplace transform.