bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs
Authors: Wang Yushang , Wang Lihua , Sun Tianyong , Shen Song , Li Zixuan , Ma Xiaomei , Gu Xiufeng , Zhang Xiumei , Peng Ai , Xu Xin , Feng Qiang 
Published: February 2023

AbstractFusobacterium nucleatum(F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built anF. nucleatuminfectious model with human periodontal ligament stem cells (PDLSCs) and showed thatF. nucleatumcould inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. TheF. nucleatumadhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations ofF. nucleatuminfection. NFκB1 and NFκB2 upregulated after 3 h ofF. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects ofF. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms ofF. nucleatumand the host inflammatory response at the early stage ofF. nucleatuminfection.
Parameter estimation of the structured illumination pattern based on principal component analysis (PCA): PCA-SIM
Authors: Chen Xin , Hou Yiwei , Xi Peng 
Published: February 2023

AbstractPrincipal component analysis (PCA), a common dimensionality reduction method, is introduced into SIM to identify the frequency vectors and pattern phases of the illumination pattern with precise subpixel accuracy, fast speed, and noise-robustness, which is promising for real-time and long-term live-cell imaging.
Ecophysiology and genomics of the brackish water adapted SAR11 subclade IIIa
Authors: Lanclos V Celeste , Rasmussen Anna N , Kojima Conner Y , Cheng Chuankai , Henson Michael W , Faircloth Brant C , Francis Christopher A , Thrash J Cameron 
Published: February 2023

Abstract
The Order Pelagibacterales (SAR11) is the most abundant group of heterotrophic bacterioplankton in global oceans and comprises multiple subclades with unique spatiotemporal distributions. Subclade IIIa is the primary SAR11 group in brackish waters and shares a common ancestor with the dominant freshwater IIIb (LD12) subclade. Despite its dominance in brackish environments, subclade IIIa lacks systematic genomic or ecological studies. Here, we combine closed genomes from new IIIa isolates, new IIIa MAGS from San Francisco Bay (SFB), and 460 highly complete publicly available SAR11 genomes for the most comprehensive pangenomic study of subclade IIIa to date. Subclade IIIa represents a taxonomic family containing three genera (denoted as subgroups IIIa.1, IIIa.2, and IIIa.3) that had distinct ecological distributions related to salinity. The expansion of taxon selection within subclade IIIa also established previously noted metabolic differentiation in subclade IIIa compared to other SAR11 subclades such as glycine/serine prototrophy, mosaic glyoxylate shunt presence, and polyhydroxyalkanoate synthesis potential. Our analysis further shows metabolic flexibility among subgroups within IIIa. Additionally, we find that subclade IIIa.3 bridges the marine and freshwater clades based on its potential for compatible solute transport, iron utilization, and bicarbonate management potential. Pure culture experimentation validated differential salinity ranges in IIIa.1 and IIIa.3 and provided detailed IIIa cell size and volume data. This study is an important step forward for understanding the genomic, ecological, and physiological differentiation of subclade IIIa and the overall evolutionary history of SAR11.
Somatic mutations can induce a noninflamed tumour microenvironment via their original gene functions, despite deriving neoantigens
Authors: Ishino Takamasa , Kawashima Shusuke , Tanji Etsuko , Ueno Toshihide , Ueda Youki , Ogasawara Sadahisa , Sato Kazuhito , Mano Hiroyuki , Ishihara Soichiro , Kato Naoya , Kawazu Masahito , Togashi Yosuke 
Published: February 2023

Abstract
Background
Identifying biomarkers to predict immune checkpoint inhibitor (ICI) efficacy is warranted. Considering that somatic mutation-derived neoantigens induce strong immune responses, patients with a high tumour mutational burden reportedly tend to respond to ICIs. However, there are several conflicting data. Therefore, we focused on the original function of neoantigenic mutations and their impact on the tumour microenvironment (TME).

Methods
We evaluated 88 high-frequency microsatellite instability (MSI-H) colorectal cancers and analysed the function of the identified neoantigenic mutations and their influence on programmed cell death 1 (PD-1) blockade efficacy. The results were validated using The Cancer Genome Atlas (TCGA) datasets.

Results
We identified frameshift mutations in RNF43 as a common neoantigenic gene mutation in MSI-H tumours. However, loss-of-function RNF43 mutations induced noninflamed TME by activating the WNT/β-catenin signalling pathway. In addition, loss of RNF43 function induced resistance to PD-1 blockade even in neoantigen-rich tumours. TCGA dataset analyses demonstrated that passenger rather than driver gene mutations were related to the inflamed TME in diverse cancer types.

Conclusions
We propose a novel concept of “paradoxical neoantigenic mutations” that can induce noninflamed TME through their original gene functions, despite deriving neoantigens, suggesting the significance of qualities as well as quantities in neoantigenic mutations.
A high-fidelity quantum matter-link between ion-trap microchip modules
Authors: Akhtar M. , Bonus F. , Lebrun-Gallagher F. R. , Johnson N. I. , Siegele-Brown M. , Hong S. , Hile S. J. , Kulmiya S. A. , Weidt S. , Hensinger W. K. 
Published: February 2023

AbstractSystem scalability is fundamental for large-scale quantum computers (QCs) and is being pursued over a variety of hardware platforms. For QCs based on trapped ions, architectures such as the quantum charge-coupled device (QCCD) are used to scale the number of qubits on a single device. However, the number of ions that can be hosted on a single quantum computing module is limited by the size of the chip being used. Therefore, a modular approach is of critical importance and requires quantum connections between individual modules. Here, we present the demonstration of a quantum matter-link in which ion qubits are transferred between adjacent QC modules. Ion transport between adjacent modules is realised at a rate of 2424 s−1 and with an infidelity associated with ion loss during transport below 7 × 10−8. Furthermore, we show that the link does not measurably impact the phase coherence of the qubit. The quantum matter-link constitutes a practical mechanism for the interconnection of QCCD devices. Our work will facilitate the implementation of modular QCs capable of fault-tolerant utility-scale quantum computation.
Spatially non-uniform condensates emerge from dynamically arrested phase separation
Authors: Erkamp Nadia A. , Sneideris Tomas , Ausserwöger Hannes , Qian Daoyuan , Qamar Seema , Nixon-Abell Jonathon , St George-Hyslop Peter , Schmit Jeremy D. , Weitz David A. , Knowles Tuomas P. J. 
Published: February 2023

AbstractThe formation of biomolecular condensates through phase separation from proteins and nucleic acids is emerging as a spatial organisational principle used broadly by living cells. Many such biomolecular condensates are not, however, homogeneous fluids, but possess an internal structure consisting of distinct sub-compartments with different compositions. Notably, condensates can contain compartments that are depleted in the biopolymers that make up the condensate. Here, we show that such double-emulsion condensates emerge via dynamically arrested phase transitions. The combination of a change in composition coupled with a slow response to this change can lead to the nucleation of biopolymer-poor droplets within the polymer-rich condensate phase. Our findings demonstrate that condensates with a complex internal architecture can arise from kinetic, rather than purely thermodynamic driving forces, and provide more generally an avenue to understand and control the internal structure of condensates in vitro and in vivo.
Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT
Authors: Paul Indranil , Bolzan Dante , Youssef Ahmed , Gagnon Keith A. , Hook Heather , Karemore Gopal , Oliphant Michael U. J. , Lin Weiwei , Liu Qian , Phanse Sadhna , White Carl , Padhorny Dzmitry , Kotelnikov Sergei , Chen Christopher S. , Hu Pingzhao , Denis Gerald V. , Kozakov Dima , Raught Brian , Siggers Trevor , Wuchty Stefan , Muthuswamy Senthil K. , Emili Andrew 
Published: February 2023

AbstractA proper understanding of disease etiology will require longitudinal systems-scale reconstruction of the multitiered architecture of eukaryotic signaling. Here we combine state-of-the-art data acquisition platforms and bioinformatics tools to devise PAMAF, a workflow that simultaneously examines twelve omics modalities, i.e., protein abundance from whole-cells, nucleus, exosomes, secretome and membrane; N-glycosylation, phosphorylation; metabolites; mRNA, miRNA; and, in parallel, single-cell transcriptomes. We apply PAMAF in an established in vitro model of TGFβ-induced epithelial to mesenchymal transition (EMT) to quantify >61,000 molecules from 12 omics and 10 timepoints over 12 days. Bioinformatics analysis of this EMT-ExMap resource allowed us to identify; –topological coupling between omics, –four distinct cell states during EMT, –omics-specific kinetic paths, –stage-specific multi-omics characteristics, –distinct regulatory classes of genes, –ligand–receptor mediated intercellular crosstalk by integrating scRNAseq and subcellular proteomics, and –combinatorial drug targets (e.g., Hedgehog signaling and CAMK-II) to inhibit EMT, which we validate using a 3D mammary duct-on-a-chip platform. Overall, this study provides a resource on TGFβ signaling and EMT.
Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces
Authors: Peris David , Ubbelohde Emily J. , Kuang Meihua Christina , Kominek Jacek , Langdon Quinn K. , Adams Marie , Koshalek Justin A. , Hulfachor Amanda Beth , Opulente Dana A. , Hall David J. , Hyma Katie , Fay Justin C. , Leducq Jean-Baptiste , Charron Guillaume , Landry Christian R. , Libkind Diego , Gonçalves Carla , Gonçalves Paula , Sampaio José Paulo , Wang Qi-Ming , Bai Feng-Yan , Wrobel Russel L. , Hittinger Chris Todd 
Published: February 2023

AbstractSpecies is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary events leading to the diversification of this genus over the last 20 million years. Here, we show the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes.
Mode locking of hole spin coherences in CsPb(Cl, Br)3 perovskite nanocrystals
Authors: Kirstein E. , Kopteva N. E. , Yakovlev D. R. , Zhukov E. A. , Kolobkova E. V. , Kuznetsova M. S. , Belykh V. V. , Yugova I. A. , Glazov M. M. , Bayer M. , Greilich A. 
Published: February 2023

AbstractThe spin physics of perovskite nanocrystals with confined electrons or holes is attracting increasing attention, both for fundamental studies and spintronic applications. Here, stable $${{{{{{{\rm{CsPb}}}}}}}}{({{{{{{{{\rm{Cl}}}}}}}}}_{0.56}{{{{{{{{\rm{Br}}}}}}}}}_{0.44})}_{3}$$
CsPb

(

Cl

0.56

Br

0.44

)

3

lead halide perovskite nanocrystals embedded in a fluorophosphate glass matrix are studied by time-resolved optical spectroscopy to unravel the coherent spin dynamics of holes and their interaction with nuclear spins of the 207Pb isotope. We demonstrate the spin mode locking effect provided by the synchronization of the Larmor precession of single hole spins in each nanocrystal in the ensemble that are excited periodically by a laser in an external magnetic field. The mode locking is enhanced by nuclei-induced frequency focusing. An ensemble spin dephasing time $${T}_{2}^{ * }$$

T

2

*

of a nanosecond and a single hole spin coherence time of T2 = 13 ns are measured. The developed theoretical model accounting for the mode locking and nuclear focusing for randomly oriented nanocrystals with perovskite band structure describes the experimental data very well.
Systematically attenuating DNA targeting enables CRISPR-driven editing in bacteria
Authors: Collias Daphne , Vialetto Elena , Yu Jiaqi , Co Khoa , Almási Éva d. H. , Rüttiger Ann-Sophie , Achmedov Tatjana , Strowig Till , Beisel Chase L. 
Published: February 2023

AbstractBacterial genome editing commonly relies on chromosomal cleavage with Cas nucleases to counter-select against unedited cells. However, editing normally requires efficient recombination and high transformation efficiencies, which are unavailable in most strains. Here, we show that systematically attenuating DNA targeting activity enables RecA-mediated repair in different bacteria, allowing chromosomal cleavage to drive genome editing. Attenuation can be achieved by altering the format or expression strength of guide (g)RNAs; using nucleases with reduced cleavage activity; or engineering attenuated gRNAs (atgRNAs) with disruptive hairpins, perturbed nuclease-binding scaffolds, non-canonical PAMs, or guide mismatches. These modifications greatly increase cell counts and even improve the efficiency of different types of edits for Cas9 and Cas12a in Escherichia coli and Klebsiella oxytoca. We further apply atgRNAs to restore ampicillin sensitivity in Klebsiella pneumoniae, establishing a resistance marker for genetic studies. Attenuating DNA targeting thus offers a counterintuitive means to achieve CRISPR-driven editing across bacteria.
Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients
Authors: Rouet Romain , Henry Jake Y. , Johansen Matt D. , Sobti Meghna , Balachandran Harikrishnan , Langley David B. , Walker Gregory J. , Lenthall Helen , Jackson Jennifer , Ubiparipovic Stephanie , Mazigi Ohan , Schofield Peter , Burnett Deborah L. , Brown Simon H. J. , Martinello Marianne , Hudson Bernard , Gilroy Nicole , Post Jeffrey J. , Kelleher Anthony , Jäck Hans-Martin , Goodnow Christopher C. , Turville Stuart G. , Rawlinson William D. , Bull Rowena A. , Stewart Alastair G. , Hansbro Philip M. , Christ Daniel 
Published: February 2023

AbstractEmerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.
Temporal-iCLIP captures co-transcriptional RNA-protein interactions
Authors: Cordiner Ross A. , Dou Yuhui , Thomsen Rune , Bugai Andrii , Granneman Sander , Heick Jensen Torben 
Published: February 2023

AbstractDynamic RNA-protein interactions govern the co-transcriptional packaging of RNA polymerase II (RNAPII)-derived transcripts. Yet, our current understanding of this process in vivo primarily stems from steady state analysis. To remedy this, we here conduct temporal-iCLIP (tiCLIP), combining RNAPII transcriptional synchronisation with UV cross-linking of RNA-protein complexes at serial timepoints. We apply tiCLIP to the RNA export adaptor, ALYREF; a component of the Nuclear Exosome Targeting (NEXT) complex, RBM7; and the nuclear cap binding complex (CBC). Regardless of function, all tested factors interact with nascent RNA as it exits RNAPII. Moreover, we demonstrate that the two transesterification steps of pre-mRNA splicing temporally separate ALYREF and RBM7 binding to splicing intermediates, and that exon-exon junction density drives RNA 5′end binding of ALYREF. Finally, we identify underappreciated steps in snoRNA 3′end processing performed by RBM7. Altogether, our data provide a temporal view of RNA-protein interactions during the early phases of transcription.
Cartography of Genomic Interactions Enables Deep Analysis of Single-Cell Expression Data
Authors: Islam Md Tauhidul , Xing Lei 
Published: February 2023

AbstractRemarkable advances in single cell genomics have presented unique challenges and opportunities for interrogating a wealth of biomedical inquiries. High dimensional genomic data are inherently complex because of intertwined relationships among the genes. Existing methods, including emerging deep learning-based approaches, do not consider the underlying biological characteristics during data processing, which greatly compromises the performance of data analysis and hinders the maximal utilization of state-of-the-art genomic techniques. In this work, we develop an entropy-based cartography strategy to contrive the high dimensional gene expression data into a configured image format, referred to as genomap, with explicit integration of the genomic interactions. This unique cartography casts the gene-gene interactions into the spatial configuration of genomaps and enables us to extract the deep genomic interaction features and discover underlying discriminative patterns of the data. We show that, for a wide variety of applications (cell clustering and recognition, gene signature extraction, single cell data integration, cellular trajectory analysis, dimensionality reduction, and visualization), the proposed approach drastically improves the accuracies of data analyses as compared to the state-of-the-art techniques.
Discovery and optimization of a broadly-neutralizing human monoclonal antibody against long-chain α-neurotoxins from snakes
Authors: Ledsgaard Line , Wade Jack , Jenkins Timothy P. , Boddum Kim , Oganesyan Irina , Harrison Julian A. , Villar Pedro , Leah Rachael A. , Zenobi Renato , Schoffelen Sanne , Voldborg Bjørn , Ljungars Anne , McCafferty John , Lomonte Bruno , Gutiérrez José M. , Laustsen Andreas H. , Karatt-Vellatt Aneesh 
Published: February 2023

AbstractSnakebite envenoming continues to claim many lives across the globe, necessitating the development of improved therapies. To this end, broadly-neutralizing human monoclonal antibodies may possess advantages over current plasma-derived antivenoms by offering superior safety and high neutralization capacity. Here, we report the establishment of a pipeline based on phage display technology for the discovery and optimization of high affinity broadly-neutralizing human monoclonal antibodies. This approach yielded a recombinant human antibody with superior broadly-neutralizing capacities in vitro and in vivo against different long-chain α-neurotoxins from elapid snakes. This antibody prevents lethality induced by Naja kaouthia whole venom at an unprecedented low molar ratio of one antibody per toxin and prolongs the survival of mice injected with Dendroaspis polylepis or Ophiophagus hannah whole venoms.
Aberrant phase separation and nucleolar dysfunction in rare genetic diseases
Authors: Mensah Martin A. , Niskanen Henri , Magalhaes Alexandre P. , Basu Shaon , Kircher Martin , Sczakiel Henrike L. , Reiter Alisa M. V. , Elsner Jonas , Meinecke Peter , Biskup Saskia , Chung Brian H. Y. , Dombrowsky Gregor , Eckmann-Scholz Christel , Hitz Marc Phillip , Hoischen Alexander , Holterhus Paul-Martin , Hülsemann Wiebke , Kahrizi Kimia , Kalscheuer Vera M. , Kan Anita , Krumbiegel Mandy , Kurth Ingo , Leubner Jonas , Longardt Ann Carolin , Moritz Jörg D. , Najmabadi Hossein , Skipalova Karolina , Snijders Blok Lot , Tzschach Andreas , Wiedersberg Eberhard , Zenker Martin , Garcia-Cabau Carla , Buschow René , Salvatella Xavier , Kraushar Matthew L. , Mundlos Stefan , Caliebe Almuth , Spielmann Malte , Horn Denise , Hnisz Denes 
Published: February 2023

AbstractThousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that have poorly defined functions1–3. Intrinsically disordered regions can mediate phase separation and the formation of biomolecular condensates, such as the nucleolus4,5. This suggests that mutations in disordered proteins may alter condensate properties and function6–8. Here we show that a subset of disease-associated variants in disordered regions alter phase separation, cause mispartitioning into the nucleolus and disrupt nucleolar function. We discover de novo frameshift variants in HMGB1 that cause brachyphalangy, polydactyly and tibial aplasia syndrome, a rare complex malformation syndrome. The frameshifts replace the intrinsically disordered acidic tail of HMGB1 with an arginine-rich basic tail. The mutant tail alters HMGB1 phase separation, enhances its partitioning into the nucleolus and causes nucleolar dysfunction. We built a catalogue of more than 200,000 variants in disordered carboxy-terminal tails and identified more than 600 frameshifts that create arginine-rich basic tails in transcription factors and other proteins. For 12 out of the 13 disease-associated variants tested, the mutation enhanced partitioning into the nucleolus, and several variants altered rRNA biogenesis. These data identify the cause of a rare complex syndrome and suggest that a large number of genetic variants may dysregulate nucleoli and other biomolecular condensates in humans.