bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation
Authors: Acton Richard J. , Yuan Wei , Gao Fei , Xia Yudong , Bourne Emma , Wozniak Eva , Bell Jordana , Lillycrop Karen , Wang Jun , Dennison Elaine , Harvey Nicholas C. , Mein Charles A. , Spector Tim D. , Hysi Pirro G. , Cooper Cyrus , Bell Christopher G. 
Published: May 2021

AbstractThe epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ˜46 kb (<0.002% genome), is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. We identify a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16–82 years), identifies 44 and 21 hypermethylating specific tRNAs at study-and genome-wide significance, respectively, contrasting with none hypomethylating. Validation and replication (450k array and independent targeted Bisuphite-sequencing) supported the hypermethylation of this functional unit. Tissue-specificity is a significant driver, although the strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age.
Probing subwavelength in-plane anisotropy with antenna-assisted infrared nano-spectroscopy
Authors: Yao Ziheng , Chen Xinzhong , Wehmeier Lukas , Xu Suheng , Shao Yinming , Zeng Zimeng , Liu Fanwei , Mcleod Alexander S. , Gilbert Corder Stephanie N. , Tsuneto Makoto , Shi Wu , Wang Zihang , Zheng Wenjun , Bechtel Hans A. , Carr G. L. , Martin Michael C. , Zettl Alex , Basov D. N. , Chen Xi , Eng Lukas M. , Kehr Susanne C. , Liu Mengkun 
Published: May 2021

AbstractInfrared nano-spectroscopy based on scattering-type scanning near-field optical microscopy (s-SNOM) is commonly employed to probe the vibrational fingerprints of materials at the nanometer length scale. However, due to the elongated and axisymmetric tip shank, s-SNOM is less sensitive to the in-plane sample anisotropy in general. In this article, we report an easy-to-implement method to probe the in-plane dielectric responses of materials with the assistance of a metallic disk micro-antenna. As a proof-of-concept demonstration, we investigate here the in-plane phonon responses of two prototypical samples, i.e. in (100) sapphire and x-cut lithium niobate (LiNbO3). In particular, the sapphire in-plane vibrations between 350 cm−1 to 800 cm−1 that correspond to LO phonon modes along the crystal b- and c-axis are determined with a spatial resolution of < λ/10, without needing any fitting parameters. In LiNbO3, we identify the in-plane orientation of its optical axis via the phonon modes, demonstrating that our method can be applied without prior knowledge of the crystal orientation. Our method can be elegantly adapted to retrieve the in-plane anisotropic response of a broad range of materials, i.e. subwavelength microcrystals, van-der-Waals materials, or topological insulators.
Deriving the skyrmion Hall angle from skyrmion lattice dynamics
Authors: Brearton R. , Turnbull L. A. , Verezhak J. A. T. , Balakrishnan G. , Hatton P. D. , van der Laan G. , Hesjedal T. 
Published: May 2021

AbstractMagnetic skyrmions are topologically non-trivial, swirling magnetization textures that form lattices in helimagnetic materials. These magnetic nanoparticles show promise as high efficiency next-generation information carriers, with dynamics that are governed by their topology. Among the many unusual properties of skyrmions is the tendency of their direction of motion to deviate from that of a driving force; the angle by which they diverge is a materials constant, known as the skyrmion Hall angle. In magnetic multilayer systems, where skyrmions often appear individually, not arranging themselves in a lattice, this deflection angle can be easily measured by tracing the real space motion of individual skyrmions. Here we describe a reciprocal space technique which can be used to determine the skyrmion Hall angle in the skyrmion lattice state, leveraging the properties of the skyrmion lattice under a shear drive. We demonstrate this procedure to yield a quantitative measurement of the skyrmion Hall angle in the room-temperature skyrmion system FeGe, shearing the skyrmion lattice with the magnetic field gradient generated by a single turn Oersted wire.
The tepary bean genome provides insight into evolution and domestication under heat stress
Authors: Moghaddam Samira Mafi , Oladzad Atena , Koh Chushin , Ramsay Larissa , Hart John P. , Mamidi Sujan , Hoopes Genevieve , Sreedasyam Avinash , Wiersma Andrew , Zhao Dongyan , Grimwood Jane , Hamilton John P. , Jenkins Jerry , Vaillancourt Brieanne , Wood Joshua C. , Schmutz Jeremy , Kagale Sateesh , Porch Timothy , Bett Kirstin E. , Buell C. Robin , McClean Phillip E. 
Published: May 2021

AbstractTepary bean (Phaseolus acutifolis A. Gray), native to the Sonoran Desert, is highly adapted to heat and drought. It is a sister species of common bean (Phaseolus vulgaris L.), the most important legume protein source for direct human consumption, and whose production is threatened by climate change. Here, we report on the tepary genome including exploration of possible mechanisms for resilience to moderate heat stress and a reduced disease resistance gene repertoire, consistent with adaptation to arid and hot environments. Extensive collinearity and shared gene content among these Phaseolus species will facilitate engineering climate adaptation in common bean, a key food security crop, and accelerate tepary bean improvement.
Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells
Authors: Sun Xuan , Cao Benjamin , Naval-Sanchez Marina , Pham Tony , Sun Yu Bo Yang , Williams Brenda , Heazlewood Shen Y. , Deshpande Nikita , Li Jinhua , Kraus Felix , Rae James , Nguyen Quan , Yari Hamed , Schröder Jan , Heazlewood Chad K. , Fulton Madeline , Hatwell-Humble Jessica , Das Gupta Kaustav , Kapetanovic Ronan , Chen Xiaoli , Sweet Matthew J. , Parton Robert G. , Ryan Michael T. , Polo Jose M. , Nefzger Christian M. , Nilsson Susan K. 
Published: May 2021

AbstractWith age, hematopoietic stem cells (HSC) undergo changes in function, including reduced regenerative potential and loss of quiescence, which is accompanied by a significant expansion of the stem cell pool that can lead to haematological disorders. Elevated metabolic activity has been implicated in driving the HSC ageing phenotype. Here we show that nicotinamide riboside (NR), a form of vitamin B3, restores youthful metabolic capacity by modifying mitochondrial function in multiple ways including reduced expression of nuclear encoded metabolic pathway genes, damping of mitochondrial stress and a decrease in mitochondrial mass and network-size. Metabolic restoration is dependent on continuous NR supplementation and accompanied by a shift of the aged transcriptome towards the young HSC state, more youthful bone marrow cellular composition and an improved regenerative capacity in a transplant setting. Consequently, NR administration could support healthy ageing by re-establishing a more youthful hematopoietic system.
Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines
Authors: He Linling , Chaudhary Anshul , Lin Xiaohe , Sou Cindy , Alkutkar Tanwee , Kumar Sonu , Ngo Timothy , Kosviner Ezra , Ozorowski Gabriel , Stanfield Robyn L. , Ward Andrew B. , Wilson Ian A. , Zhu Jiang 
Published: May 2021

AbstractEbola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1Cmodifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1Cexert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display.
A machine learning model for identifying patients at risk for wild-type transthyretin amyloid cardiomyopathy
Authors: Huda Ahsan , Castaño Adam , Niyogi Anindita , Schumacher Jennifer , Stewart Michelle , Bruno Marianna , Hu Mo , Ahmad Faraz S. , Deo Rahul C. , Shah Sanjiv J. 
Published: May 2021

AbstractTransthyretin amyloid cardiomyopathy, an often unrecognized cause of heart failure, is now treatable with a transthyretin stabilizer. It is therefore important to identify at-risk patients who can undergo targeted testing for earlier diagnosis and treatment, prior to the development of irreversible heart failure. Here we show that a random forest machine learning model can identify potential wild-type transthyretin amyloid cardiomyopathy using medical claims data. We derive a machine learning model in 1071 cases and 1071 non-amyloid heart failure controls and validate the model in three nationally representative cohorts (9412 cases, 9412 matched controls), and a large, single-center electronic health record-based cohort (261 cases, 39393 controls). We show that the machine learning model performs well in identifying patients with cardiac amyloidosis in the derivation cohort and all four validation cohorts, thereby providing a systematic framework to increase the suspicion of transthyretin cardiac amyloidosis in patients with heart failure.
Inverse-design magnonic devices
Authors: Wang Qi , Chumak Andrii V. , Pirro Philipp 
Published: May 2021

AbstractThe field of magnonics offers a new type of low-power information processing, in which magnons, the quanta of spin waves, carry and process data instead of electrons. Many magnonic devices were demonstrated recently, but the development of each of them requires specialized investigations and, usually, one device design is suitable for one function only. Here, we introduce the method of inverse-design magnonics, in which any functionality can be specified first, and a feedback-based computational algorithm is used to obtain the device design. We validate this method using the means of micromagnetic simulations. Our proof-of-concept prototype is based on a rectangular ferromagnetic area that can be patterned using square-shaped voids. To demonstrate the universality of this approach, we explore linear, nonlinear and nonreciprocal magnonic functionalities and use the same algorithm to create a magnonic (de-)multiplexer, a nonlinear switch and a circulator. Thus, inverse-design magnonics can be used to develop highly efficient rf applications as well as Boolean and neuromorphic computing building blocks.
A seamlessly integrated device of micro-supercapacitor and wireless charging with ultrahigh energy density and capacitance
Authors: Gao Chang , Huang Jiancheng , Xiao Yukun , Zhang Guoqiang , Dai Chunlong , Li Zengling , Zhao Yang , Jiang Lan , Qu Liangti 
Published: May 2021

AbstractMicrodevice integrating energy storage with wireless charging could create opportunities for electronics design, such as moveable charging. Herein, we report seamlessly integrated wireless charging micro-supercapacitors by taking advantage of a designed highly consistent material system that both wireless coils and electrodes are of the graphite paper. The transferring power efficiency of the wireless charging is 52.8%. Benefitting from unique circuit structure, the intact device displays low resistance and excellent voltage tolerability with a capacitance of 454.1 mF cm−2, superior to state-of-the-art conventional planar micro-supercapacitors. Besides, a record high energy density of 463.1 μWh cm−2 exceeds the existing metal ion hybrid micro-supercapacitors and even commercial thin film battery (350 μWh cm−2). After charging for 6 min, the integrated device reaches up to a power output of 45.9 mW, which can drive an electrical toy car immediately. This work brings an insight for contactless micro-electronics and flexible micro-robotics.
The RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium
Authors: Wang Minhui , Ma Tianling , Wang Haixia , Liu Jianzhao , Chen Yun , Shim Won Bo , Ma Zhonghua 
Published: May 2021

AbstractPrecursor messenger RNA (pre-mRNA) splicing is an essential and tightly regulated process in eukaryotic cells; however, the regulatory mechanisms for the splicing are not well understood. Here, we characterize a RNA binding protein named FgRbp1 in Fusarium graminearum, a fungal pathogen of cereal crops worldwide. Deletion of FgRbp1 leads to reduced splicing efficiency in 47% of the F. graminearum intron-containing gene transcripts that are involved in various cellular processes including vegetative growth, development, and virulence. The human ortholog RBM42 is able to fully rescue the growth defects of ΔFgRbp1. FgRbp1 binds to the motif CAAGR in its target mRNAs, and interacts with the splicing factor FgU2AF23, a highly conserved protein involved in 3’ splice site recognition, leading to enhanced recruitment of FgU2AF23 to the target mRNAs. This study demonstrates that FgRbp1 is a splicing regulator and regulates the pre-mRNA splicing in a sequence-dependent manner in F. graminearum.
Coherent vibrational dynamics reveals lattice anharmonicity in organic–inorganic halide perovskite nanocrystals
Authors: Debnath Tushar , Sarker Debalaya , Huang He , Han Zhong-Kang , Dey Amrita , Polavarapu Lakshminarayana , Levchenko Sergey V. , Feldmann Jochen 
Published: May 2021

AbstractThe halide ions of organic-inorganic hybrid perovskites can strongly influence the interaction between the central organic moiety and the inorganic metal halide octahedral units and thus their lattice vibrations. Here, we report the halide-ion-dependent vibrational coherences in formamidinium lead halide (FAPbX3, X = Br, I) perovskite nanocrystals (PNCs) via the combination of femtosecond pump–probe spectroscopy and density functional theory calculations. We find that the FAPbX3 PNCs generate halide-dependent coherent vibronic wave packets upon above-bandgap non-resonant excitation. More importantly, we observe several higher harmonics of the fundamental modes for FAPbI3 PNCs as compared to FAPbBr3 PNCs. This is likely due to the weaker interaction between the central FA moiety and the inorganic cage for FAPbI3 PNCs, and thus the PbI64− unit can vibrate more freely. This weakening reveals the intrinsic anharmonicity in the Pb-I framework, and thus facilitating the energy transfer into overtone and combination bands. These findings not only unveil the superior stability of Br–based PNCs over I–based PNCs but are also important for a better understanding of their electronic and polaronic properties.
Confinement effects and acid strength in zeolites
Authors: Grifoni Emanuele , Piccini GiovanniMaria , Lercher Johannes A. , Glezakou Vassiliki-Alexandra , Rousseau Roger , Parrinello Michele 
Published: May 2021

AbstractChemical reactivity and sorption in zeolites are coupled to confinement and—to a lesser extent—to the acid strength of Brønsted acid sites (BAS). In presence of water the zeolite Brønsted acid sites eventually convert into hydronium ions. The gradual transition from zeolite Brønsted acid sites to hydronium ions in zeolites of varying pore size is examined by ab initio molecular dynamics combined with enhanced sampling based on Well-Tempered Metadynamics and a recently developed set of collective variables. While at low water content (1–2 water/BAS) the acidic protons prefer to be shared between zeolites and water, higher water contents (n > 2) invariably lead to solvation of the protons within a localized water cluster adjacent to the BAS. At low water loadings the standard free energy of the formed complexes is dominated by enthalpy and is associated with the acid strength of the BAS and the space around the site. Conversely, the entropy increases linearly with the concentration of waters in the pores, favors proton solvation and is independent of the pore size/shape.
Following replicative DNA synthesis by time-resolved X-ray crystallography
Authors: Chim Nicholas , Meza Roman A. , Trinh Anh M. , Yang Kefan , Chaput John C. 
Published: May 2021

AbstractThe mechanism of DNA synthesis has been inferred from static structures, but the absence of temporal information raises longstanding questions about the order of events in one of life’s most central processes. Here we follow the reaction pathway of a replicative DNA polymerase using time-resolved X-ray crystallography to elucidate the order and transition between intermediates. In contrast to the canonical model, the structural changes observed in the time-lapsed images reveal a catalytic cycle in which translocation precedes catalysis. The translocation step appears to follow a push-pull mechanism where the O-O1 loop of the finger subdomain acts as a pawl to facilitate unidirectional movement along the template with conserved tyrosine residues 714 and 719 functioning as tandem gatekeepers of DNA synthesis. The structures capture the precise order of critical events that may be a general feature of enzymatic catalysis among replicative DNA polymerases.
Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival
Authors: Dispinseri Stefania , Secchi Massimiliano , Pirillo Maria Franca , Tolazzi Monica , Borghi Martina , Brigatti Cristina , De Angelis Maria Laura , Baratella Marco , Bazzigaluppi Elena , Venturi Giulietta , Sironi Francesca , Canitano Andrea , Marzinotto Ilaria , Tresoldi Cristina , Ciceri Fabio , Piemonti Lorenzo , Negri Donatella , Cara Andrea , Lampasona Vito , Scarlatti Gabriella 
Published: May 2021

AbstractUnderstanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5–8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization.
The ubiquitylation of IL-1β limits its cleavage by caspase-1 and targets it for proteasomal degradation
Authors: Vijayaraj Swarna L. , Feltham Rebecca , Rashidi Maryam , Frank Daniel , Liu Zhengyang , Simpson Daniel S. , Ebert Gregor , Vince Angelina , Herold Marco J. , Kueh Andrew , Pearson Jaclyn S. , Dagley Laura F. , Murphy James M. , Webb Andrew I. , Lawlor Kate E. , Vince James E. 
Published: May 2021

AbstractInterleukin-1β (IL-1β) is activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in a variety of other inflammatory diseases. Therefore, IL-1β activity must be fine-tuned to enable anti-microbial responses whilst limiting collateral damage. Here, we show that precursor IL-1β is rapidly turned over by the proteasome and this correlates with its decoration by K11-linked, K63-linked and K48-linked ubiquitin chains. The ubiquitylation of IL-1β is not just a degradation signal triggered by inflammasome priming and activating stimuli, but also limits IL-1β cleavage by caspase-1. IL-1β K133 is modified by ubiquitin and forms a salt bridge with IL-1β D129. Loss of IL-1β K133 ubiquitylation, or disruption of the K133:D129 electrostatic interaction, stabilizes IL-1β. Accordingly, Il1bK133R/K133R mice have increased levels of precursor IL-1β upon inflammasome priming and increased production of bioactive IL-1β, both in vitro and in response to LPS injection. These findings identify mechanisms that can limit IL-1β activity and safeguard against damaging inflammation.
Timescales of the permafrost carbon cycle and legacy effects of temperature overshoot scenarios
Authors: de Vrese Philipp , Brovkin Victor 
Published: May 2021

AbstractMinimizing the risks and impacts of climate change requires limiting the global temperature increase to 1.5 °C above preindustrial levels, while the difficulty of reducing carbon emissions at the necessary rate increases the likelihood of temporarily overshooting this climate target. Using simulations with the land surface model JSBACH, we show that it takes high-latitude ecosystems and the state of permafrost-affected soils several centuries to adjust to the atmospheric conditions that arise at the 1.5 °C-target. Here, a temporary warming of the Arctic entails important legacy effects and we show that feedbacks between water-, energy- and carbon cycles allow for multiple steady-states in permafrost regions, which differ with respect to the physical state of the soil, the soil carbon concentrations and the terrestrial carbon uptake and -release. The steady-states depend on the soil organic matter content at the point of climate stabilization, which is significantly affected by an overshoot-induced soil carbon loss.
Conformational rearrangement of the NMDA receptor amino-terminal domain during activation and allosteric modulation
Authors: Vyklicky Vojtech , Stanley Cherise , Habrian Chris , Isacoff Ehud Y. 
Published: May 2021

AbstractN-Methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors essential for synaptic plasticity and memory. Receptor activation involves glycine- and glutamate-stabilized closure of the GluN1 and GluN2 subunit ligand binding domains that is allosterically regulated by the amino-terminal domain (ATD). Using single molecule fluorescence resonance energy transfer (smFRET) to monitor subunit rearrangements in real-time, we observe a stable ATD inter-dimer distance in the Apo state and test the effects of agonists and antagonists. We find that GluN1 and GluN2 have distinct gating functions. Glutamate binding to GluN2 subunits elicits two identical, sequential steps of ATD dimer separation. Glycine binding to GluN1 has no detectable effect, but unlocks the receptor for activation so that glycine and glutamate together drive an altered activation trajectory that is consistent with ATD dimer separation and rotation. We find that protons exert allosteric inhibition by suppressing the glutamate-driven ATD separation steps, and that greater ATD separation translates into greater rotation and higher open probability.