bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response
Authors: Gajewska K. A. , Lescesen H. , Ramialison M. , Wagstaff K. M. , Jans D. A. 
Published: October 2021

AbstractThe importin superfamily member Importin-13 is a bidirectional nuclear transporter. To delineate its functional roles, we performed transcriptomic analysis on wild-type and Importin-13-knockout mouse embryonic stem cells, revealing enrichment of differentially expressed genes involved in stress responses and apoptosis regulation. De novo promoter motif analysis on 277 Importin-13-dependent genes responsive to oxidative stress revealed an enrichment of motifs aligned to consensus sites for the transcription factors specificity protein 1, SP1, or Kruppel like factor 4, KLF4. Analysis of embryonic stem cells subjected to oxidative stress revealed that Importin-13-knockout cells were more resistant, with knockdown of SP1 or KLF4 helping protect wild-type embryonic stem cells against stress-induced death. Importin-13 was revealed to bind to SP1 and KLF4 in a cellular context, with a key role in oxidative stress-dependent nuclear export of both transcription factors. The results are integral to understanding stress biology, highlighting the importance of Importin-13 in the stress response.
CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression
Authors: Schneider Enja , Winzer Riekje , Rissiek Anne , Ricklefs Isabell , Meyer-Schwesinger Catherine , Ricklefs Franz L. , Bauche Andreas , Behrends Jochen , Reimer Rudolph , Brenna Santra , Wasielewski Hauke , Lauten Melchior , Rissiek Björn , Puig Berta , Cortesi Filippo , Magnus Tim , Fliegert Ralf , Müller Christa E. , Gagliani Nicola , Tolosa Eva 
Published: October 2021

AbstractImmune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribute to adenosine production by releasing CD73-containing extracellular vesicles upon activation. These extracellular vesicles have AMPase activity, and the resulting adenosine mediates immune suppression independently of regulatory T cells. In addition, we show that extracellular vesicles isolated from the synovial fluid of patients with juvenile idiopathic arthritis contribute to T cell suppression in a CD73-dependent manner. Our results suggest that the generation of adenosine upon T cell activation is an intrinsic mechanism of human effector T cells that complements regulatory T cell-mediated suppression in the inflamed tissue. Finally, our data underscore the role of immune cell-derived extracellular vesicles in the control of immune responses.
Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease
Authors: Scortecci Jessica Fernandes , Molday Laurie L. , Curtis Susan B. , Garces Fabian A. , Panwar Pankaj , Van Petegem Filip , Molday Robert S. 
Published: October 2021

AbstractABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor membranes. Loss-of-function mutations cause Stargardt disease (STGD1), a macular dystrophy associated with severe vision loss. To define the mechanisms underlying substrate binding and STGD1, we determine the cryo-EM structure of ABCA4 in its substrate-free and bound states. The two structures are similar and delineate an elongated protein with the two transmembrane domains (TMD) forming an outward facing conformation, extended and twisted exocytoplasmic domains (ECD), and closely opposed nucleotide binding domains. N-Ret-PE is wedged between the two TMDs and a loop from ECD1 within the lumen leaflet consistent with a lateral access mechanism and is stabilized through hydrophobic and ionic interactions with residues from the TMDs and ECDs. Our studies provide a framework for further elucidating the molecular mechanism associated with lipid transport and disease and developing promising disease interventions.
Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex
Authors: Klug Yoel A. , Deme Justin C. , Corey Robin A. , Renne Mike F. , Stansfeld Phillip J. , Lea Susan M. , Carvalho Pedro 
Published: October 2021

AbstractLipid droplets (LDs) are universal lipid storage organelles with a core of neutral lipids, such as triacylglycerols, surrounded by a phospholipid monolayer. This unique architecture is generated during LD biogenesis at endoplasmic reticulum (ER) sites marked by Seipin, a conserved membrane protein mutated in lipodystrophy. Here structural, biochemical and molecular dynamics simulation approaches reveal the mechanism of LD formation by the yeast Seipin Sei1 and its membrane partner Ldb16. We show that Sei1 luminal domain assembles a homooligomeric ring, which, in contrast to other Seipins, is unable to concentrate triacylglycerol. Instead, Sei1 positions Ldb16, which concentrates triacylglycerol within the Sei1 ring through critical hydroxyl residues. Triacylglycerol recruitment to the complex is further promoted by Sei1 transmembrane segments, which also control Ldb16 stability. Thus, we propose that LD assembly by the Sei1/Ldb16 complex, and likely other Seipins, requires sequential triacylglycerol-concentrating steps via distinct elements in the ER membrane and lumen.
A frequency-amplitude coordinator and its optimal energy consumption for biological oscillators
Authors: Qin Bo-Wei , Zhao Lei , Lin Wei 
Published: October 2021

AbstractBiorhythm including neuron firing and protein-mRNA interaction are fundamental activities with diffusive effect. Their well-balanced spatiotemporal dynamics are beneficial for healthy sustainability. Therefore, calibrating both anomalous frequency and amplitude of biorhythm prevents physiological dysfunctions or diseases. However, many works were devoted to modulate frequency exclusively whereas amplitude is usually ignored, although both quantities are equally significant for coordinating biological functions and outputs. Especially, a feasible method coordinating the two quantities concurrently and precisely is still lacking. Here, for the first time, we propose a universal approach to design a frequency-amplitude coordinator rigorously via dynamical systems tools. We consider both spatial and temporal information. With a single well-designed coordinator, they can be calibrated to desired levels simultaneously and precisely. The practical usefulness and efficacy of our method are demonstrated in representative neuronal and gene regulatory models. We further reveal its fundamental mechanism and optimal energy consumption providing inspiration for biorhythm regulation in future.
Circa-SCOPE: high-throughput live single-cell imaging method for analysis of circadian clock resetting
Authors: Manella Gal , Aizik Dan , Aviram Rona , Golik Marina , Asher Gad 
Published: October 2021

AbstractCircadian clocks are self-sustained and cell-autonomous oscillators. They respond to various extracellular cues depending on the time-of-day and the signal intensity. Phase Transition Curves (PTCs) are instrumental in uncovering the full repertoire of responses to a given signal. However, the current methodologies for reconstructing PTCs are low-throughput, laborious, and resource- and time-consuming. We report here the development of an efficient and high throughput assay, dubbed Circadian Single-Cell Oscillators PTC Extraction (Circa-SCOPE) for generating high-resolution PTCs. This methodology relies on continuous monitoring of single-cell oscillations to reconstruct a full PTC from a single culture, upon a one-time intervention. Using Circa-SCOPE, we characterize the effects of various pharmacological and blood-borne resetting cues, at high temporal resolution and a wide concentration range. Thus, Circa-SCOPE is a powerful tool for comprehensive analysis and screening for circadian clocks’ resetting cues, and can be valuable for basic as well as translational research.
Human cell based directed evolution of adenine base editors with improved efficiency
Authors: Fu Junhao , Li Qing , Liu Xiaoyu , Tu Tianxiang , Lv Xiujuan , Yin Xidi , Lv Jineng , Song Zongming , Qu Jia , Zhang Jinwei , Li Jinsong , Gu Feng 
Published: October 2021

AbstractAdenine base editors (ABE) are genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion. However, the low activity of ABE at certain sites remains a major bottleneck that precludes efficacious applications. Here, to address it, we develop a directional screening system in human cells to evolve the deaminase component of the ABE, and identify three high-activity NG-ABEmax variants: NG-ABEmax-SGK (R101S/D139G/E140K), NG-ABEmax-R (Q154R) and NG-ABEmax-K (N127K). With further engineering, we create a consolidated variant [NG-ABEmax-KR (N127K/Q154R)] which exhibit superior editing activity both in human cells and in mouse disease models, compared to the original NG-ABEmax. We also find that NG-ABEmax-KR efficiently introduce natural mutations in gamma globin gene promoters with more than four-fold increase in editing activity. This work provides a broadly applicable, rapidly deployable platform to directionally screen and evolve user-specified traits in base editors that extend beyond augmented editing activity.
Addressing MRSA infection and antibacterial resistance with peptoid polymers
Authors: Xie Jiayang , Zhou Min , Qian Yuxin , Cong Zihao , Chen Sheng , Zhang Wenjing , Jiang Weinan , Dai Chengzhi , Shao Ning , Ji Zhemin , Zou Jingcheng , Xiao Ximian , Liu Longqiang , Chen Minzhang , Li Jin , Liu Runhui 
Published: October 2021

AbstractMethicillin-Resistant Staphylococcus aureus (MRSA) induced infection calls for antibacterial agents that are not prone to antimicrobial resistance. We prepare protease-resistant peptoid polymers with variable C-terminal functional groups using a ring-opening polymerization of N-substituted N-carboxyanhydrides (NNCA), which can provide peptoid polymers easily from the one-pot synthesis. We study the optimal polymer that displays effective activity against MRSA planktonic and persister cells, effective eradication of highly antibiotic-resistant MRSA biofilms, and potent anti-infectious performance in vivo using the wound infection model, the mouse keratitis model, and the mouse peritonitis model. Peptoid polymers show insusceptibility to antimicrobial resistance, which is a prominent merit of these antimicrobial agents. The low cost, convenient synthesis and structure diversity of peptoid polymers, the superior antimicrobial performance and therapeutic potential in treating MRSA infection altogether imply great potential of peptoid polymers as promising antibacterial agents in treating MRSA infection and alleviating antibiotic resistance.
High-spatial and colourimetric imaging of histone modifications in single senescent cells using plasmonic nanoprobes
Authors: An Hyun Ji , Kim Yun , Chang Soojeong , Kim Hakchun , Song Jihwan , Park Hyunsung , Choi Inhee 
Published: October 2021

AbstractHistones are closely related to the state of chromatin, and epigenetic modification of their tail results in regulation in cells. Therefore, developing various analytical tools to map the changes in position and distribution of histone modifications is helpful in studying underlying mechanisms. Herein, we propose a high-spatial and colourimetric imaging method using plasmonic nanoparticles as probes to visualize heterochromatin histone markers in a single nucleus. We visualized the reorganization between repressive histone markers, H3K9me3 and H3K27me3, caused by oncogene-induced senescence based on the scattering colours and spectral shift of plasmonic nanoprobes to longer wavelengths using their distance-dependent coupling effect. The measured scattering profiles were correlated with the computation results simulating the scattering spectra according to the arrangements and distances among the plasmonic nanoprobes. The plasmonic nanoprobe-based high-spatial hyperspectral imaging provides an advanced way to study the dynamics of histone modifications for predicting the progression of diseases or senescence.
Symmetry-aware recursive image similarity exploration for materials microscopy
Authors: Nguyen Tri N. M. , Guo Yichen , Qin Shuyu , Frew Kylie S. , Xu Ruijuan , Agar Joshua C. 
Published: October 2021

AbstractIn pursuit of scientific discovery, vast collections of unstructured structural and functional images are acquired; however, only an infinitesimally small fraction of this data is rigorously analyzed, with an even smaller fraction ever being published. One method to accelerate scientific discovery is to extract more insight from costly scientific experiments already conducted. Unfortunately, data from scientific experiments tend only to be accessible by the originator who knows the experiments and directives. Moreover, there are no robust methods to search unstructured databases of images to deduce correlations and insight. Here, we develop a machine learning approach to create image similarity projections to search unstructured image databases. To improve these projections, we develop and train a model to include symmetry-aware features. As an exemplar, we use a set of 25,133 piezoresponse force microscopy images collected on diverse materials systems over five years. We demonstrate how this tool can be used for interactive recursive image searching and exploration, highlighting structural similarities at various length scales. This tool justifies continued investment in federated scientific databases with standardized metadata schemas where the combination of filtering and recursive interactive searching can uncover synthesis-structure-property relations. We provide a customizable open-source package (https://github.com/m3-learning/Recursive_Symmetry_Aware_Materials_Microstructure_Explorer) of this interactive tool for researchers to use with their data.
Power-optimal, stabilized entangling gate between trapped-ion qubits
Authors: Blümel Reinhold , Grzesiak Nikodem , Pisenti Neal , Wright Kenneth , Nam Yunseong 
Published: October 2021

AbstractTo achieve scalable quantum computing, improving entangling-gate fidelity and its implementation efficiency are of utmost importance. We present here a linear method to construct provably power-optimal entangling gates on an arbitrary pair of qubits on a trapped-ion quantum computer. This method leverages simultaneous modulation of amplitude, frequency, and phase of the beams that illuminate the ions and, unlike the state of the art, does not require any search in the parameter space. The linear method is extensible, enabling stabilization against external parameter fluctuations to an arbitrary order at a cost linear in the order. We implement and demonstrate the power-optimal, stabilized gate on a trapped-ion quantum computer.
Ferromagnetism out of charge fluctuation of strongly correlated electrons in κ-(BEDT-TTF)2Hg(SCN)2Br
Authors: Yamashita Minoru , Sugiura Shiori , Ueda Akira , Dekura Shun , Terashima Taichi , Uji Shinya , Sunairi Yoshiya , Mori Hatsumi , Zhilyaeva Elena I. , Torunova Svetlana A. , Lyubovskaya Rimma N. , Drichko Natalia , Hotta Chisa 
Published: October 2021

AbstractWe perform magnetic susceptibility and magnetic torque measurements on the organic κ-(BEDT-TTF)2Hg(SCN)2Br, which is recently suggested to host an exotic quantum dipole-liquid in its low-temperature insulating phase. Below the metal-insulator (MI) transition temperature, the magnetic susceptibility follows a Curie–Weiss law with a positive Curie–Weiss temperature, and a particular $$M\propto \sqrt{H}$$

M
∝

H

curve is observed. The emergent ferromagnetically interacting spins amount to about 1/6 of the full spin moment of localized charges. Taking account of the possible inhomogeneous quasi-charge-order that forms a dipole-liquid, we construct a model of antiferromagnetically interacting spin chains in two adjacent charge-ordered domains, which are coupled via fluctuating charges on a Mott-dimer at the boundary. We find that the charge fluctuations can draw a weak ferromagnetic moment out of the spin singlet domains.
Metformin accelerates zebrafish heart regeneration by inducing autophagy
Authors: Xie Fangjing , Xu Shisan , Lu Yingying , Wong Kin Fung , Sun Lei , Hasan Kazi Md Mahmudul , Ma Alvin C. H. , Tse Gary , Manno Sinai H. C. , Tian Li , Yue Jianbo , Cheng Shuk Han 
Published: October 2021

AbstractMetformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction in humans, and demonstrated that autophagy was significantly induced in the injured area. Through a systematic evaluation of the multiple cell types related to cardiac regeneration, we found that metformin enhanced the autophagic flux and improved epicardial, endocardial and vascular endothelial regeneration, accelerated transient collagen deposition and resolution, and induced cardiomyocyte proliferation. Whereas, when the autophagic flux was blocked, then all these processes were delayed. We also showed that metformin transiently enhanced the systolic function of the heart. Taken together, our results indicate that autophagy is positively involved in the metformin-induced acceleration of heart regeneration in zebrafish and suggest that this well-known diabetic drug has clinical value for the prevention and amelioration of myocardial infarction.
Step detection and energy expenditure at different speeds by three accelerometers in a controlled environment
Authors: Stenbäck Ville , Leppäluoto Juhani , Leskelä Nelli , Viitala Linda , Vihriälä Erkki , Gagnon Dominique , Tulppo Mikko , Herzig Karl-Heinz 
Published: October 2021

AbstractPhysical activity (PA) is one of the most efficient ways to prevent obesity and its associated diseases worldwide. In the USA, less than 10% of the adult population were able to meet the PA recommendations when accelerometers were used to assess PA habituation. Accelerometers significantly differ from each other in step recognition and do not reveal raw data. The aim of our study was to compare a novel accelerometer, Sartorio Xelometer, which enables to gather raw data, with existing accelerometers ActiGraph GT3X+ and activPAL in terms of step detection and energy expenditure estimation accuracy. 53 healthy subjects were divided into 2 cohorts (cohort 1 optimization; cohort 2 validation) and wore 3 accelerometers and performed an exercise routine consisting of the following speeds: 1.5, 3, 4.5, 9 and 10.5 km/h (6 km/h for 2nd cohort included). Data from optimization cohort was used to optimize Sartorio step detection algorithm. Actual taken steps were recorded with a video camera and energy expenditure (EE) was measured. To observe the similarity between video and accelerometer step counts, paired samples t test and intraclass correlation were used separately for step counts in different speeds and for total counts as well as EE estimations. In speeds of 1.5, 3, 4.5, 6, 9 and 10.5 km/h mean absolute percentage error (MAPE) % were 8.1, 3.5, 4.3, 4.2, 3.1 and 7.8 for the Xelometer, respectively (after optimization). For ActiGraph GT3X+ the MAPE-% were 96.93 (87.4), 34.69 (23.1), 2.13 (2.3), 1.96 (2.6) and 2.99 (3.8), respectively and for activPAL 6.55 (5.6), 1.59 (0.6), 0.81 (1.1), 10.60 (10.3) and 15.76 (13.8), respectively. Significant intraclass correlations were observed with Xelometer estimates and actual steps in all speeds. Xelometer estimated the EE with a MAPE-% of 30.3, activPAL and ActiGraph GT3X+ with MAPE percentages of 20.5 and 24.3, respectively. The Xelometer is a valid device for assessing step counts at different gait speeds. MAPE is different at different speeds, which is of importance when assessing the PA in obese subjects and elderly. EE estimates of all three devices were found to be inaccurate when compared with indirect calorimetry.
A topology-preserving dimensionality reduction method for single-cell RNA-seq data using graph autoencoder
Authors: Luo Zixiang , Xu Chenyu , Zhang Zhen , Jin Wenfei 
Published: October 2021

AbstractDimensionality reduction is crucial for the visualization and interpretation of the high-dimensional single-cell RNA sequencing (scRNA-seq) data. However, preserving topological structure among cells to low dimensional space remains a challenge. Here, we present the single-cell graph autoencoder (scGAE), a dimensionality reduction method that preserves topological structure in scRNA-seq data. scGAE builds a cell graph and uses a multitask-oriented graph autoencoder to preserve topological structure information and feature information in scRNA-seq data simultaneously. We further extended scGAE for scRNA-seq data visualization, clustering, and trajectory inference. Analyses of simulated data showed that scGAE accurately reconstructs developmental trajectory and separates discrete cell clusters under different scenarios, outperforming recently developed deep learning methods. Furthermore, implementation of scGAE on empirical data showed scGAE provided novel insights into cell developmental lineages and preserved inter-cluster distances.
Sexual dimorphism in size and shape of the head in the sea snake Emydocephalus annulatus (Hydrophiinae, Elapidae)
Authors: Shine Richard , Goiran Claire 
Published: October 2021

AbstractIn snakes, divergence in head size between the sexes has been interpreted as an adaptation to intersexual niche divergence. By overcoming gape-limitation, a larger head enables snakes of one sex to ingest larger prey items. Under this hypothesis, we do not expect a species that consumes only tiny prey items to exhibit sex differences in relative head size, or to show empirical links between relative head size and fitness-relevant traits such as growth and fecundity. Our field studies on the sea snake Emydocephalus annulatus falsify these predictions. Although these snakes feed exclusively on fish eggs, the heads of female snakes are longer and wider than those of males at the same body length. Individuals with wider heads grew more rapidly, reproduced more often, and produced larger litters. Thus, head shape can affect fitness and can diverge between the sexes even without gape-limitation. Head size and shape may facilitate other aspects of feeding (such as the ability to scrape eggs off coral) and locomotion (hydrodynamics); and a smaller head may advantage the sex that is more mobile, and that obtains its prey in narrow crevices rather than in more exposed situations (i.e., males).