bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA TUG1/microRNA-187-3p/TESC axis modulates progression of pituitary adenoma via regulating the NF-κB signaling pathway
Authors: Zhang Rui , Yang Fan , Fan Haitao , Wang Haocong , Wang Qinghao , Yang Jianxin , Song Tao 
Published: May 2021

AbstractThe molecule mechanisms of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in human diseases have been broadly studied recently, therefore, our research aimed to assess the effect of lncRNA taurine upregulated gene 1 (TUG1)/miR-187-3p/tescalcin (TESC) axis in pituitary adenoma (PA) by regulating the nuclear factor-kappa B (NF-κB) signaling pathway. We observed that TUG1 was upregulated in PA tissues and was associated with invasion, knosp grade and tumor size. TUG1 particularly bound to miR-187-3p. TUG1 knockdown inhibited cell proliferation, invasion, migration, and epithelial–mesenchymal transition, promoted apoptosis, and regulated the expression of NF-κB p65 and inhibitor of κB (IκB)-α in PA cells lines in vitro, and also inhibited tumor growth in vivo, and these effects were reversed by miR-187-3p reduction. Similarly, miR-187-3p elevation inhibited PA cell malignant behaviors and modulated the expression of NF-κB p65 and IκB-α in PA cells, and reduced in vivo tumor growth as well. TUG1 inhibition downregulated TESC, which was targeted by miR-187-3p. In conclusion, this study suggests that TUG1 sponges miR-187-3p to affect PA development by elevating TESC and regulating the NF-κB signaling pathway.
CD36 promotes NLRP3 inflammasome activation via the mtROS pathway in renal tubular epithelial cells of diabetic kidneys
Authors: Hou Yanjuan , Wang Qian , Han Baosheng , Chen Yiliang , Qiao Xi , Wang Lihua 
Published: May 2021

AbstractTubulointerstitial inflammation plays a key role in the pathogenesis of diabetic nephropathy (DN). Interleukin-1β (IL-1β) is the key proinflammatory cytokine associated with tubulointerstitial inflammation. The NLRP3 inflammasome regulates IL-1β activation and secretion. Reactive oxygen species (ROS) represents the main mediator of NLRP3 inflammasome activation. We previously reported that CD36, a class B scavenger receptor, mediates ROS production in DN. Here, we determined whether CD36 is involved in NLRP3 inflammasome activation and explored the underlying mechanisms. We observed that high glucose induced-NLRP3 inflammasome activation mediate IL-1β secretion, caspase-1 activation, and apoptosis in HK-2 cells. In addition, the levels of CD36, NLRP3, and IL-1β expression (protein and mRNA) were all significantly increased under high glucose conditions. CD36 knockdown resulted in decreased NLRP3 activation and IL-1β secretion. CD36 knockdown or the addition of MitoTempo significantly inhibited ROS production in HK-2 cells. CD36 overexpression enhanced NLRP3 activation, which was reduced by MitoTempo. High glucose levels induced a change in the metabolism of HK-2 cells from fatty acid oxidation (FAO) to glycolysis, which promoted mitochondrial ROS (mtROS) production after 72 h. CD36 knockdown increased the level of AMP-activated protein kinase (AMPK) activity and mitochondrial FAO, which was accompanied by the inhibition of NLRP3 and IL-1β. The in vivo experimental results indicate that an inhibition of CD36 could protect diabetic db/db mice from tubulointerstitial inflammation and tubular epithelial cell apoptosis. CD36 mediates mtROS production and NLRP3 inflammasome activation in db/db mice. CD36 inhibition upregulated the level of FAO-related enzymes and AMPK activity in db/db mice. These results suggest that NLRP3 inflammasome activation is mediated by CD36 in renal tubular epithelial cells in DN, which suppresses mitochondrial FAO and stimulates mtROS production.
Quantum loop states in spin-orbital models on the honeycomb lattice
Authors: Savary Lucile 
Published: May 2021

AbstractThe search for truly quantum phases of matter is a center piece of modern research in condensed matter physics. Quantum spin liquids, which host large amounts of entanglement—an entirely quantum feature where one part of a system cannot be measured without modifying the rest—are exemplars of such phases. Here, we devise a realistic model which relies upon the well-known Haldane chain phase, i.e. the phase of spin-1 chains which host fractional excitations at their ends, akin to the hallmark excitations of quantum spin liquids. We tune our model to exactly soluble points, and find that the ground state realizes Haldane chains whose physical supports fluctuate, realizing both quantum spin liquid like and symmetry-protected topological phases. Crucially, this model is expected to describe actual materials, and we provide a detailed set of material-specific constraints which may be readily used for an experimental realization.
Synaptic FUS accumulation triggers early misregulation of synaptic RNAs in a mouse model of ALS
Authors: Sahadevan Sonu , Hembach Katharina M. , Tantardini Elena , Pérez-Berlanga Manuela , Hruska-Plochan Marian , Megat Salim , Weber Julien , Schwarz Petra , Dupuis Luc , Robinson Mark D. , De Rossi Pierre , Polymenidou Magdalini 
Published: May 2021

AbstractMutations disrupting the nuclear localization of the RNA-binding protein FUS characterize a subset of amyotrophic lateral sclerosis patients (ALS-FUS). FUS regulates nuclear RNAs, but its role at the synapse is poorly understood. Using super-resolution imaging we determined that the localization of FUS within synapses occurs predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosomes, we identified synaptic FUS RNA targets, encoding proteins associated with synapse organization and plasticity. Significant increase of synaptic FUS during early disease in a mouse model of ALS was accompanied by alterations in density and size of GABAergic synapses. mRNAs abnormally accumulated at the synapses of 6-month-old ALS-FUS mice were enriched for FUS targets and correlated with those depicting increased short-term mRNA stability via binding primarily on multiple exonic sites. Our study indicates that synaptic FUS accumulation in early disease leads to synaptic impairment, potentially representing an initial trigger of neurodegeneration.
Mattertronics for programmable manipulation and multiplex storage of pseudo-diamagnetic holes and label-free cells
Authors: Goudu Sandhya Rani , Kim Hyeonseol , Hu Xinghao , Lim Byeonghwa , Kim Kunwoo , Torati Sri Ramulu , Ceylan Hakan , Sheehan Devin , Sitti Metin , Kim CheolGi 
Published: May 2021

AbstractManipulating and separating single label-free cells without biomarker conjugation have attracted significant interest in the field of single-cell research, but digital circuitry control and multiplexed individual storage of single label-free cells remain a challenge. Herein, by analogy with the electrical circuitry elements and electronical holes, we develop a pseudo-diamagnetophoresis (PsD) mattertronic approach in the presence of biocompatible ferrofluids for programmable manipulation and local storage of single PsD holes and label-free cells. The PsD holes conduct along linear negative micro-magnetic patterns. Further, eclipse diode patterns similar to the electrical diode can implement directional and selective switching of different PsD holes and label-free cells based on the diode geometry. Different eclipse heights and junction gaps influence the switching efficiency of PsD holes for mattertronic circuitry manipulation and separation. Moreover, single PsD holes are stored at each potential well as in an electrical storage capacitor, preventing multiple occupancies of PsD holes in the array of individual compartments due to magnetic Coulomb-like interaction. This approach may enable the development of large programmable arrays of label-free matters with high throughput, efficiency, and reliability as multiplex cell research platforms.
RTEL1 influences the abundance and localization of TERRA RNA
Authors: Ghisays Fiorella , Garzia Aitor , Wang Hexiao , Canasto-Chibuque Claudia , Hohl Marcel , Savage Sharon A. , Tuschl Thomas , Petrini John H. J. 
Published: May 2021

AbstractTelomere repeat containing RNAs (TERRAs) are a family of long non-coding RNAs transcribed from the subtelomeric regions of eukaryotic chromosomes. TERRA transcripts can form R-loops at chromosome ends; however the importance of these structures or the regulation of TERRA expression and retention in telomeric R-loops remain unclear. Here, we show that the RTEL1 (Regulator of Telomere Length 1) helicase influences the abundance and localization of TERRA in human cells. Depletion of RTEL1 leads to increased levels of TERRA RNA while reducing TERRA-containing R loops at telomeres. In vitro, RTEL1 shows a strong preference for binding G-quadruplex structures which form in TERRA. This binding is mediated by the C-terminal region of RTEL1, and is independent of the RTEL1 helicase domain. RTEL1 binding to TERRA appears to be essential for cell viability, underscoring the importance of this function. Degradation of TERRA-containing R-loops by overexpression of RNAse H1 partially recapitulates the increased TERRA levels and telomeric instability associated with RTEL1 deficiency. Collectively, these data suggest that regulation of TERRA is a key function of the RTEL1 helicase, and that loss of that function may contribute to the disease phenotypes of patients with RTEL1 mutations.
2,6-diaminopurine promotes repair of DNA lesions under prebiotic conditions
Authors: Szabla Rafał , Zdrowowicz Magdalena , Spisz Paulina , Green Nicholas J. , Stadlbauer Petr , Kruse Holger , Šponer Jiří , Rak Janusz 
Published: May 2021

AbstractHigh-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments.
Electronic metal–support interaction modulates single-atom platinum catalysis for hydrogen evolution reaction
Authors: Shi Yi , Ma Zhi-Rui , Xiao Yi-Ying , Yin Yun-Chao , Huang Wen-Mao , Huang Zhi-Chao , Zheng Yun-Zhe , Mu Fang-Ya , Huang Rong , Shi Guo-Yue , Sun Yi-Yang , Xia Xing-Hua , Chen Wei 
Published: May 2021

AbstractTuning metal–support interaction has been considered as an effective approach to modulate the electronic structure and catalytic activity of supported metal catalysts. At the atomic level, the understanding of the structure–activity relationship still remains obscure in heterogeneous catalysis, such as the conversion of water (alkaline) or hydronium ions (acid) to hydrogen (hydrogen evolution reaction, HER). Here, we reveal that the fine control over the oxidation states of single-atom Pt catalysts through electronic metal–support interaction significantly modulates the catalytic activities in either acidic or alkaline HER. Combined with detailed spectroscopic and electrochemical characterizations, the structure–activity relationship is established by correlating the acidic/alkaline HER activity with the average oxidation state of single-atom Pt and the Pt–H/Pt–OH interaction. This study sheds light on the atomic-level mechanistic understanding of acidic and alkaline HER, and further provides guidelines for the rational design of high-performance single-atom catalysts.
Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology
Authors: Kargapolova Yulia , Rehimi Rizwan , Kayserili Hülya , Brühl Joanna , Sofiadis Konstantinos , Zirkel Anne , Palikyras Spiros , Mizi Athanasia , Li Yun , Yigit Gökhan , Hoischen Alexander , Frank Stefan , Russ Nicole , Trautwein Jonathan , van Bon Bregje , Gilissen Christian , Laugsch Magdalena , Gusmao Eduardo Gade , Josipovic Natasa , Altmüller Janine , Nürnberg Peter , Längst Gernot , Kaiser Frank J. , Watrin Erwan , Brunner Han , Rada-Iglesias Alvaro , Kurian Leo , Wollnik Bernd , Bouazoune Karim , Papantonis Argyris 
Published: May 2021

AbstractMembers of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. By combining genomics with functional in vivo and in vitro assays, we show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS mutation affects CHD6 protein folding and impairs its ability to recruit co-remodelers in response to DNA damage or autophagy stimulation. This leads to accumulation of DNA damage burden and senescence-like phenotypes. We therefore uncovered a molecular mechanism explaining HSS onset via chromatin control of autophagic flux and genotoxic stress surveillance.
DNA origami single crystals with Wulff shapes
Authors: Wang Yong , Dai Lizhi , Ding Zhiyuan , Ji Min , Liu Jiliang , Xing Hang , Liu Xiaoguo , Ke Yonggang , Fan Chunhai , Wang Peng , Tian Ye 
Published: May 2021

AbstractDNA origami technology has proven to be an excellent tool for precisely manipulating molecules and colloidal elements in a three-dimensional manner. However, fabrication of single crystals with well-defined facets from highly programmable, complex DNA origami units is a great challenge. Here, we report the successful fabrication of DNA origami single crystals with Wulff shapes and high yield. By regulating the symmetries and binding modes of the DNA origami building blocks, the crystalline shapes can be designed and well-controlled. The single crystals are then used to induce precise growth of an ultrathin layer of silica on the edges, resulting in mechanically reinforced silica-DNA hybrid structures that preserve the details of the single crystals without distortion. The silica-infused microcrystals can be directly observed in the dry state, which allows meticulous analysis of the crystal facets and tomographic 3D reconstruction of the single crystals by high-resolution electron microscopy.
Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes
Authors: Renner Kerstin , Schwittay Tobias , Chaabane Sophia , Gottschling Johanna , Müller Christine , Tiefenböck Charlotte , Salewski Jan-Niklas , Winter Frederike , Buchtler Simone , Balam Saidou , Malfertheiner Maximilian V. , Lubnow Matthias , Lunz Dirk , Graf Bernhard , Hitzenbichler Florian , Hanses Frank , Poeck Hendrik , Kreutz Marina , Orsó Evelyn , Burkhardt Ralph , Niedermair Tanja , Brochhausen Christoph , Gessner André , Salzberger Bernd , Mack Matthias 
Published: May 2021

AbstractCoronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity.
Structural basis of substrate recognition and thermal protection by a small heat shock protein
Authors: Yu Chuanyang , Leung Stephen King Pong , Zhang Wenxin , Lai Louis Tung Faat , Chan Ying Ki , Wong Man Chit , Benlekbir Samir , Cui Yong , Jiang Liwen , Lau Wilson Chun Yu 
Published: May 2021

AbstractSmall heat shock proteins (sHsps) bind unfolding proteins, thereby playing a pivotal role in the maintenance of proteostasis in virtually all living organisms. Structural elucidation of sHsp-substrate complexes has been hampered by the transient and heterogeneous nature of their interactions, and the precise mechanisms underlying substrate recognition, promiscuity, and chaperone activity of sHsps remain unclear. Here we show the formation of a stable complex between Arabidopsis thaliana plastid sHsp, Hsp21, and its natural substrate 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) under heat stress, and report cryo-electron microscopy structures of Hsp21, DXPS and Hsp21-DXPS complex at near-atomic resolution. Monomeric Hsp21 binds across the dimer interface of DXPS and engages in multivalent interactions by recognizing highly dynamic structural elements in DXPS. Hsp21 partly unfolds its central α-crystallin domain to facilitate binding of DXPS, which preserves a native-like structure. This mode of interaction suggests a mechanism of sHsps anti-aggregation activity towards a broad range of substrates.
Accurate and scalable graph neural network force field and molecular dynamics with direct force architecture
Authors: Park Cheol Woo , Kornbluth Mordechai , Vandermause Jonathan , Wolverton Chris , Kozinsky Boris , Mailoa Jonathan P. 
Published: May 2021

AbstractRecently, machine learning (ML) has been used to address the computational cost that has been limiting ab initio molecular dynamics (AIMD). Here, we present GNNFF, a graph neural network framework to directly predict atomic forces from automatically extracted features of the local atomic environment that are translationally-invariant, but rotationally-covariant to the coordinate of the atoms. We demonstrate that GNNFF not only achieves high performance in terms of force prediction accuracy and computational speed on various materials systems, but also accurately predicts the forces of a large MD system after being trained on forces obtained from a smaller system. Finally, we use our framework to perform an MD simulation of Li7P3S11, a superionic conductor, and show that resulting Li diffusion coefficient is within 14% of that obtained directly from AIMD. The high performance exhibited by GNNFF can be easily generalized to study atomistic level dynamics of other material systems.
Optimal provable robustness of quantum classification via quantum hypothesis testing
Authors: Weber Maurice , Liu Nana , Li Bo , Zhang Ce , Zhao Zhikuan 
Published: May 2021

AbstractQuantum machine learning models have the potential to offer speedups and better predictive accuracy compared to their classical counterparts. However, these quantum algorithms, like their classical counterparts, have been shown to also be vulnerable to input perturbations, in particular for classification problems. These can arise either from noisy implementations or, as a worst-case type of noise, adversarial attacks. In order to develop defense mechanisms and to better understand the reliability of these algorithms, it is crucial to understand their robustness properties in the presence of natural noise sources or adversarial manipulation. From the observation that measurements involved in quantum classification algorithms are naturally probabilistic, we uncover and formalize a fundamental link between binary quantum hypothesis testing and provably robust quantum classification. This link leads to a tight robustness condition that puts constraints on the amount of noise a classifier can tolerate, independent of whether the noise source is natural or adversarial. Based on this result, we develop practical protocols to optimally certify robustness. Finally, since this is a robustness condition against worst-case types of noise, our result naturally extends to scenarios where the noise source is known. Thus, we also provide a framework to study the reliability of quantum classification protocols beyond the adversarial, worst-case noise scenarios.
Probing the interplay between lattice dynamics and short-range magnetic correlations in CuGeO3 with femtosecond RIXS
Authors: Paris E. , Nicholson C. W. , Johnston S. , Tseng Y. , Rumo M. , Coslovich G. , Zohar S. , Lin M. F. , Strocov V. N. , Saint-Martin R. , Revcolevschi A. , Kemper A. , Schlotter W. , Dakovski G. L. , Monney C. , Schmitt T. 
Published: May 2021

AbstractInvestigations of magnetically ordered phases on the femtosecond timescale have provided significant insights into the influence of charge and lattice degrees of freedom on the magnetic sub-system. However, short-range magnetic correlations occurring in the absence of long-range order, for example in spin-frustrated systems, are inaccessible to many ultrafast techniques. Here, we show how time-resolved resonant inelastic X-ray scattering (trRIXS) is capable of probing such short-ranged magnetic dynamics in a charge-transfer insulator through the detection of a Zhang–Rice singlet exciton. Utilizing trRIXS measurements at the O K-edge, and in combination with model calculations, we probe the short-range spin correlations in the frustrated spin chain material CuGeO3 following photo-excitation, revealing a strong coupling between the local lattice and spin sub-systems.