bluuebunny/crossref_metadata_2025_split huggingface dataset:
2D vanadium carbide MXenzyme to alleviate ROS-mediated inflammatory and neurodegenerative diseases
Authors: Feng Wei , Han Xiuguo , Hu Hui , Chang Meiqi , Ding Li , Xiang Huijing , Chen Yu , Li Yuehua 
Published: April 2021

AbstractReactive oxygen species (ROS) are generated and consumed in living organism for normal metabolism. Paradoxically, the overproduction and/or mismanagement of ROS have been involved in pathogenesis and progression of various human diseases. Here, we reported a two-dimensional (2D) vanadium carbide (V2C) MXene nanoenzyme (MXenzyme) that can mimic up to six naturally-occurring enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione peroxidase (GPx), thiol peroxidase (TPx) and haloperoxidase (HPO). Based on these enzyme-mimicking properties, the constructed 2D V2C MXenzyme not only possesses high biocompatibility but also exhibits robust in vitro cytoprotection against oxidative stress. Importantly, 2D V2C MXenzyme rebuilds the redox homeostasis without perturbing the endogenous antioxidant status and relieves ROS-induced damage with benign in vivo therapeutic effects, as demonstrated in both inflammation and neurodegeneration animal models. These findings open an avenue to enable the use of MXenzyme as a remedial nanoplatform to treat ROS-mediated inflammatory and neurodegenerative diseases.
Stabilization of supramolecular membrane protein–lipid bilayer assemblies through immobilization in a crystalline exoskeleton
Authors: Herbert Fabian C. , Abeyrathna Sameera S. , Abeyrathna Nisansala S. , Wijesundara Yalini H. , Brohlin Olivia R. , Carraro Francesco , Amenitsch Heinz , Falcaro Paolo , Luzuriaga Michael A. , Durand-Silva Alejandra , Diwakara Shashini D. , Smaldone Ronald A. , Meloni Gabriele , Gassensmith Jeremiah J. 
Published: April 2021

AbstractArtificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamellar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins into supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization of these complexes remains challenging because of their chemical composition, the hydrophobicity and structural instability of membrane proteins, and the lability of interactions between protein, detergent, and lipids within micelles and lipid bilayers. In this work we demonstrate that metastable lipid, protein-detergent, and protein-lipid supramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework (ZIF) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF bio-composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embedded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional characterization of the assemblies upon exfoliation reveal that all these complexes encapsulated within the framework maintain their native morphology, structure, and activity, which is otherwise lost rapidly without immobilization.
On the limitations in assessing stability of oxygen evolution catalysts using aqueous model electrochemical cells
Authors: Knöppel Julius , Möckl Maximilian , Escalera-López Daniel , Stojanovski Kevin , Bierling Markus , Böhm Thomas , Thiele Simon , Rzepka Matthias , Cherevko Serhiy 
Published: April 2021

AbstractRecent research indicates a severe discrepancy between oxygen evolution reaction catalysts dissolution in aqueous model systems and membrane electrode assemblies. This questions the relevance of the widespread aqueous testing for real world application. In this study, we aim to determine the processes responsible for the dissolution discrepancy. Experimental parameters known to diverge in both systems are individually tested for their influence on dissolution of an Ir-based catalyst. Ir dissolution is studied in an aqueous model system, a scanning flow cell coupled to an inductively coupled plasma mass spectrometer. Real dissolution rates of the Ir OER catalyst in membrane electrode assemblies are measured with a specifically developed, dedicated setup. Overestimated acidity in the anode catalyst layer and stabilization over time in real devices are proposed as main contributors to the dissolution discrepancy. The results shown here lead to clear guidelines for anode electrocatalyst testing parameters to resemble realistic electrolyzer operating conditions.
Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters
Authors: Pidathala Shabareesh , Mallela Aditya Kumar , Joseph Deepthi , Penmatsa Aravind 
Published: April 2021

AbstractNorepinephrine is a biogenic amine neurotransmitter that has widespread effects on alertness, arousal and pain sensation. Consequently, blockers of norepinephrine uptake have served as vital tools to treat depression and chronic pain. Here, we employ the Drosophila melanogaster dopamine transporter as a surrogate for the norepinephrine transporter and determine X-ray structures of the transporter in its substrate-free and norepinephrine-bound forms. We also report structures of the transporter in complex with inhibitors of chronic pain including duloxetine, milnacipran and a synthetic opioid, tramadol. When compared to dopamine, we observe that norepinephrine binds in a different pose, in the vicinity of subsite C within the primary binding site. Our experiments reveal that this region is the binding site for chronic pain inhibitors and a determinant for norepinephrine-specific reuptake inhibition, thereby providing a paradigm for the design of specific inhibitors for catecholamine neurotransmitter transporters.
Interacting with volatile environments stabilizes hidden-state inference and its brain signatures
Authors: Weiss Aurélien , Chambon Valérian , Lee Junseok K. , Drugowitsch Jan , Wyart Valentin 
Published: April 2021

AbstractMaking accurate decisions in uncertain environments requires identifying the generative cause of sensory cues, but also the expected outcomes of possible actions. Although both cognitive processes can be formalized as Bayesian inference, they are commonly studied using different experimental frameworks, making their formal comparison difficult. Here, by framing a reversal learning task either as cue-based or outcome-based inference, we found that humans perceive the same volatile environment as more stable when inferring its hidden state by interaction with uncertain outcomes than by observation of equally uncertain cues. Multivariate patterns of magnetoencephalographic (MEG) activity reflected this behavioral difference in the neural interaction between inferred beliefs and incoming evidence, an effect originating from associative regions in the temporal lobe. Together, these findings indicate that the degree of control over the sampling of volatile environments shapes human learning and decision-making under uncertainty.
Metabolic pathways inferred from a bacterial marker gene illuminate ecological changes across South Pacific frontal boundaries
Authors: Raes Eric J. , Karsh Kristen , Sow Swan L. S. , Ostrowski Martin , Brown Mark V. , van de Kamp Jodie , Franco-Santos Rita M. , Bodrossy Levente , Waite Anya M. 
Published: April 2021

AbstractGlobal oceanographic monitoring initiatives originally measured abiotic essential ocean variables but are currently incorporating biological and metagenomic sampling programs. There is, however, a large knowledge gap on how to infer bacterial functions, the information sought by biogeochemists, ecologists, and modelers, from the bacterial taxonomic information (produced by bacterial marker gene surveys). Here, we provide a correlative understanding of how a bacterial marker gene (16S rRNA) can be used to infer latitudinal trends for metabolic pathways in global monitoring campaigns. From a transect spanning 7000 km in the South Pacific Ocean we infer ten metabolic pathways from 16S rRNA gene sequences and 11 corresponding metagenome samples, which relate to metabolic processes of primary productivity, temperature-regulated thermodynamic effects, coping strategies for nutrient limitation, energy metabolism, and organic matter degradation. This study demonstrates that low-cost, high-throughput bacterial marker gene data, can be used to infer shifts in the metabolic strategies at the community scale.
Mediator subunit Med15 dictates the conserved “fuzzy” binding mechanism of yeast transcription activators Gal4 and Gcn4
Authors: Tuttle Lisa M. , Pacheco Derek , Warfield Linda , Wilburn Damien B. , Hahn Steven , Klevit Rachel E. 
Published: April 2021

AbstractThe acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in transcription repression and activation through binding to Gal80 repressor and Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a “fuzzy” protein interface. Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two intrinsically disordered ADs of different sequence, interact nearly identically with Med15. The finding that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts strongly with Gal80 via a distinct structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein–protein interaction.
Timely and atomic-resolved high-temperature mechanical investigation of ductile fracture and atomistic mechanisms of tungsten
Authors: Zhang Jianfei , Li Yurong , Li Xiaochen , Zhai Yadi , Zhang Qing , Ma Dongfeng , Mao Shengcheng , Deng Qingsong , Li Zhipeng , Li Xueqiao , Wang Xiaodong , Liu Yinong , Zhang Ze , Han Xiaodong 
Published: April 2021

AbstractRevealing the atomistic mechanisms for the high-temperature mechanical behavior of materials is important for optimizing their properties for service at high-temperatures and their thermomechanical processing. However, due to materials microstructure’s dynamic recovery and the absence of available in situ techniques, the high-temperature deformation behavior and atomistic mechanisms of materials are difficult to evaluate. Here, we report the development of a microelectromechanical systems-based thermomechanical testing apparatus that enables mechanical testing at temperatures reaching 1556 K inside a transmission electron microscope for in situ investigation with atomic-resolution. With this unique technique, we first uncovered that tungsten fractures at 973 K in a ductile manner via a strain-induced multi-step body-centered cubic (BCC)-to-face-centered cubic (FCC) transformation and dislocation activities within the strain-induced FCC phase. Both events reduce the stress concentration at the crack tip and retard crack propagation. Our research provides an approach for timely and atomic-resolved high-temperature mechanical investigation of materials at high-temperatures.
A compendium and comparative epigenomics analysis of cis-regulatory elements in the pig genome
Authors: Zhao Yunxia , Hou Ye , Xu Yueyuan , Luan Yu , Zhou Huanhuan , Qi Xiaolong , Hu Mingyang , Wang Daoyuan , Wang Zhangxu , Fu Yuhua , Li Jingjin , Zhang Saixian , Chen Jianhai , Han Jianlin , Li Xinyun , Zhao Shuhong 
Published: April 2021

AbstractAlthough major advances in genomics have initiated an exciting new era of research, a lack of information regardingcis-regulatory elements has limited the genetic improvement or manipulation of pigs as a meat source and biomedical model. Here, we systematically characterizecis-regulatory elements and their functions in 12 diverse tissues from four pig breeds by adopting similar strategies as the ENCODE and Roadmap Epigenomics projects, which include RNA-seq, ATAC-seq, and ChIP-seq. In total, we generate 199 datasets and identify more than 220,000cis-regulatory elements in the pig genome. Surprisingly, we find higher conservation ofcis-regulatory elements between human and pig genomes than those between human and mouse genomes. Furthermore, the differences of topologically associating domains between the pig and human genomes are associated with morphological evolution of the head and face. Beyond generating a major new benchmark resource for pig epigenetics, our study provides basic comparative epigenetic data relevant to using pigs as models in human biomedical research.
B1a and B2 cells are characterized by distinct CpG modification states at DNMT3A-maintained enhancers
Authors: Mahajan Vinay S. , Mattoo Hamid , Sun Na , Viswanadham Vinayak , Yuen Grace J. , Allard-Chamard Hugues , Ahmad Maimuna , Murphy Samuel J. H. , Cariappa Annaiah , Tuncay Yesim , Pillai Shiv 
Published: April 2021

AbstractThe B1 and B2 lineages of B cells contribute to protection from pathogens in distinct ways. The role of the DNA CpG methylome in specifying these two B-cell fates is still unclear. Here we profile the CpG modifications and transcriptomes of peritoneal B1a and follicular B2 cells, as well as their respective proB cell precursors in the fetal liver and adult bone marrow from wild-type and CD19-Cre Dnmt3a floxed mice lacking DNMT3A in the B lineage. We show that an underlying foundational CpG methylome is stably established during B lineage commitment and is overlaid with a DNMT3A-maintained dynamic methylome that is sculpted in distinct ways in B1a and B2 cells. This dynamic DNMT3A-maintained methylome is composed of novel enhancers that are closely linked to lineage-specific genes. While DNMT3A maintains the methylation state of these enhancers in both B1a and B2 cells, the dynamic methylome undergoes a prominent programmed demethylation event during B1a but not B2 cell development. We propose that the methylation pattern of DNMT3A-maintained enhancers is determined by the coincident recruitment of DNMT3A and TET enzymes, which regulate the developmental expression of B1a and B2 lineage-specific genes.
Spreading depression as an innate antiseizure mechanism
Authors: Tamim Isra , Chung David Y. , de Morais Andreia Lopes , Loonen Inge C. M. , Qin Tao , Misra Amrit , Schlunk Frieder , Endres Matthias , Schiff Steven J. , Ayata Cenk 
Published: April 2021

AbstractSpreading depression (SD) is an intense and prolonged depolarization in the central nervous systems from insect to man. It is implicated in neurological disorders such as migraine and brain injury. Here, using an in vivo mouse model of focal neocortical seizures, we show that SD may be a fundamental defense against seizures. Seizures induced by topical 4-aminopyridine, penicillin or bicuculline, or systemic kainic acid, culminated in SDs at a variable rate. Greater seizure power and area of recruitment predicted SD. Once triggered, SD immediately suppressed the seizure. Optogenetic or KCl-induced SDs had similar antiseizure effect sustained for more than 30 min. Conversely, pharmacologically inhibiting SD occurrence during a focal seizure facilitated seizure generalization. Altogether, our data indicate that seizures trigger SD, which then terminates the seizure and prevents its generalization.
EpCAM promotes endosomal modulation of the cortical RhoA zone for epithelial organization
Authors: Gaston Cécile , De Beco Simon , Doss Bryant , Pan Meng , Gauquelin Estelle , D’Alessandro Joseph , Lim Chwee Teck , Ladoux Benoit , Delacour Delphine 
Published: April 2021

AbstractAt the basis of cell shape and behavior, the organization of actomyosin and its ability to generate forces are widely studied. However, the precise regulation of this contractile network in space and time is unclear. Here, we study the role of the epithelial-specific protein EpCAM, a contractility modulator, in cell shape and motility. We show that EpCAM is required for stress fiber generation and front-rear polarity acquisition at the single cell level. In fact, EpCAM participates in the remodeling of a transient zone of active RhoA at the cortex of spreading epithelial cells. EpCAM and RhoA route together through the Rab35/EHD1 fast recycling pathway. This endosomal pathway spatially organizes GTP-RhoA to fine tune the activity of actomyosin resulting in polarized cell shape and development of intracellular stiffness and traction forces. Impairment of GTP-RhoA endosomal trafficking either by silencing EpCAM or by expressing Rab35/EHD1 mutants prevents proper myosin-II activity, stress fiber formation and ultimately cell polarization. Collectively, this work shows that the coupling between co-trafficking of EpCAM and RhoA, and actomyosin rearrangement is pivotal for cell spreading, and advances our understanding of how biochemical and mechanical properties promote cell plasticity.
Incommensurate smectic phase in close proximity to the high-Tc superconductor FeSe/SrTiO3
Authors: Yuan Yonghao , Fan Xuemin , Wang Xintong , He Ke , Zhang Yan , Xue Qi-Kun , Li Wei 
Published: April 2021

AbstractSuperconductivity is significantly enhanced in monolayer FeSe grown on SrTiO3, but not for multilayer films, in which large strength of nematicity develops. However, the link between the high-transition temperature superconductivity in monolayer and the correlation related nematicity in multilayer FeSe films is not well understood. Here, we use low-temperature scanning tunneling microscopy to study few-layer FeSe thin films grown by molecular beam epitaxy. We observe an incommensurate long-range smectic phase, which solely appears in bilayer FeSe films. The smectic order still locally exists and gradually fades away with increasing film thickness, while it suddenly vanishes in monolayer FeSe, indicative of an abrupt smectic phase transition. Surface alkali-metal doping can suppress the smectic phase and induce high-Tc superconductivity in bilayer FeSe. Our observations provide evidence that the monolayer FeSe is in close proximity to the smectic phase, and its superconductivity is likely enhanced by this electronic instability as well.
Considerations for bioanalytical characterization and batch release of COVID-19 vaccines
Authors: Sanyal Gautam , Särnefält Anna , Kumar Arun 
Published: April 2021

AbstractThe COVID-19 pandemic has prompted hundreds of laboratories around the world to employ traditional as well as novel technologies to develop vaccines against SARS-CoV-2. The hallmarks of a successful vaccine are safety and efficacy. Analytical evaluation methods, that can ensure the high quality of the products and that can be executed speedily, must be in place as an integral component of Chemistry, Manufacturing, and Control (CMC). These methods or assays are developed to quantitatively test for critical quality attributes (CQAs) of a vaccine product. While clinical (human) efficacy of a vaccine can never be predicted from pre-clinical evaluation of CQA, precise and accurate measurements of antigen content and a relevant biological activity (termed “potency”) elicited by the antigen allow selection of potentially safe and immunogenic doses for entry into clinical trials. All available vaccine technology platforms, novel and traditional, are being utilized by different developers to produce vaccines against SARS-CoV-2. It took less than a year from the publication of SARS-CoV-2 gene sequence to Emergency Use Authorization (EUA) of the first vaccine, setting a record for speed in the history of vaccine development. The largest ever global demand for vaccines has prompted some vaccine developers to enter multiple manufacturing partnerships in different countries in addition to implementing unprecedented scale-up plans. Quantitative, robust, and rapid analytical testing for CQA of a product is essential in ensuring smooth technology transfer between partners and allowing analytical bridging between vaccine batches used in different clinical phases leading up to regulatory approvals and commercialization. We discuss here opportunities to improve the speed and quality of the critical batch release and characterization assays.
Autofluorescence enhancement for label-free imaging of myelinated fibers in mammalian brains
Authors: Costantini Irene , Baria Enrico , Sorelli Michele , Matuschke Felix , Giardini Francesco , Menzel Miriam , Mazzamuto Giacomo , Silvestri Ludovico , Cicchi Riccardo , Amunts Katrin , Axer Markus , Pavone Francesco Saverio 
Published: April 2021

AbstractAnalyzing the structure of neuronal fibers with single axon resolution in large volumes is a challenge in connectomics. Different technologies try to address this goal; however, they are limited either by the ineffective labeling of the fibers or in the achievable resolution. The possibility of discriminating between different adjacent myelinated axons gives the opportunity of providing more information about the fiber composition and architecture within a specific area. Here, we propose MAGIC (Myelin Autofluorescence imaging by Glycerol Induced Contrast enhancement), a tissue preparation method to perform label-free fluorescence imaging of myelinated fibers that is user friendly and easy to handle. We exploit the high axial and radial resolution of two-photon fluorescence microscopy (TPFM) optical sectioning to decipher the mixture of various fiber orientations within the sample of interest. We demonstrate its broad applicability by performing mesoscopic reconstruction at a sub-micron resolution of mouse, rat, monkey, and human brain samples and by quantifying the different fiber organization in control and Reeler mouse's hippocampal sections. Our study provides a novel method for 3D label-free imaging of nerve fibers in fixed samples at high resolution, below micrometer level, that overcomes the limitation related to the myelinated axons exogenous labeling, improving the possibility of analyzing brain connectivity.
Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model
Authors: Jiang Jiayue-Clara , Rothnagel Joseph A. , Upton Kyle R. 
Published: April 2021

AbstractWhile transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis of transcription factor binding and transcriptomic data to identify transposon-derived promoters that are activated in specific diseases and developmental states. We applied this pipeline to a breast cancer model, and found that the L1PA2 transposon subfamily contributes abundant regulatory sequences to co-ordinated transcriptional regulation in breast cancer. Transcription factor profiling demonstrates that over 27% of L1PA2 transposons harbour co-localised binding sites of functionally interacting, cancer-associated transcription factors in MCF7 cells, a cell line used to model breast cancer. Transcriptomic analysis reveals that L1PA2 transposons also contribute transcription start sites to up-regulated transcripts in MCF7 cells, including some transcripts with established oncogenic properties. In addition, we verified the utility of our pipeline on other transposon subfamilies, as well as on leukemia and lung carcinoma cell lines. We demonstrate that the normally quiescent regulatory activities of transposons can be activated and alter the cancer transcriptome. In particular, the L1PA2 subfamily contributes abundant regulatory sequences, and likely plays a global role in modulating breast cancer transcriptional regulation. Understanding the regulatory impact of L1PA2 on breast cancer genomes provides additional insights into cancer genome regulation, and may provide novel biomarkers for disease diagnosis, prognosis and therapy.