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Article
| Open AccessA chromosomal-scale genome assembly of modern cultivated hybrid sugarcane provides insights into origination and evolution
Modern sugarcane cultivars have complicated genome due to interspecific crosses and multiple backcrossing. Here, the authors report the haplotype-resolved, chromosome-level genome assembly of a modern hybrid sugarcane cultivar and reveal the expansion of genes related to sugar accumulation and smut resistance.
- Yixue Bao
- , Qing Zhang
- & Muqing Zhang
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Article
| Open AccessSingle-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma
Hepatoblastoma (HB) is the most frequent paediatric liver tumour with heterogeneous cellular phenotypes that influence clinical outcomes. Here, the authors integrate bulk, single-cell, and spatial multi-omics to characterise HB cells, and find that clonal evolution and epigenetic plasticity shape response to therapy.
- Amélie Roehrig
- , Theo Z. Hirsch
- & Eric Letouzé
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Article
| Open AccessEngineering an artificial catch bond using mechanical anisotropy
Catch bonds are unique protein-protein interactions where the bond lifetime increases under external pulling forces. Here, the authors engineer an artificial catch bond based on a non-catch bonding human gut bacterial adhesion protein complex.
- Zhaowei Liu
- , Haipei Liu
- & Michael A. Nash
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Article
| Open AccessA chemical proteomics approach for global mapping of functional lysines on cell surface of living cell
Ligand discovery against membrane proteins has been a major challenge, mainly due to the peculiar nature of their natural habitat. Here, the authors designed a new chemical proteomic probe that targets the lysines exposed on the cell surface and developed a chemical proteomic strategy for global analysis of surface functionality in living cells.
- Ting Wang
- , Shiyun Ma
- & Haojie Lu
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Article
| Open AccessCryo-EM structure of the human Asc-1 transporter complex
The human Asc-1-4F2hc complex plays an important role in the neural development and stability. Here, authors determine the cryo-EM structures of Asc-1-4F2hc complex in three states, revealing its substrate recognition and transport mechanism.
- Yaning Li
- , Yingying Guo
- & Renhong Yan
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Article
| Open AccessAccurately clustering biological sequences in linear time by relatedness sorting
Accurately clustering biological sequences is an increasingly important task but is challenging for large datasets. This study introduces a new approach called ‘relatedness sorting’ to accurately cluster sequences with linear-time scalability.
- Erik Wright
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Article
| Open AccessCis-regulatory interfaces reveal the molecular mechanisms underlying the notochord gene regulatory network of Ciona
The notochord is an essential hallmark of the chordate phylum. Here, Negrón-Piñeiro et al. study the notochord gene regulatory network in Ciona, and their findings illustrate how notochord transcription factors are coordinated by Brachyury and Foxa2.
- Lenny J. Negrón-Piñeiro
- , Yushi Wu
- & Anna Di Gregorio
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Article
| Open AccessStress increases hepatic release of lipocalin 2 which contributes to anxiety-like behavior in mice
Cross talk between periphery and the central nervous system may contribute to stress associated behaviours. Here the authors identified liver-derived lipocalin 2 as a peripheral factor that elicits anxiety-like behaviours via modulating medial prefrontal neural activity.
- Lan Yan
- , Fengzhen Yang
- & Li Zhang
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Article
| Open AccessBasal actomyosin pulses expand epithelium coordinating cell flattening and tissue elongation
Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. Here, Li et al. reveal a morphological cell expansion wave behaviour that coordinates epithelial flattening and tissue elongation during Drosophila oogenesis.
- Shun Li
- , Zong-Yuan Liu
- & Xiaobo Wang
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Article
| Open AccessConcerted transformation of a hyper-paused transcription complex and its reinforcing protein
Here, authors use cryoEM, biochemistry and molecular dynamics simulations to delineate a functional cycle of RfaH, a universally conserved transcription factor that undergoes a fold-switch during recruitment to the transcribing RNA polymerase.
- Philipp K. Zuber
- , Nelly Said
- & Stefan H. Knauer
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Article
| Open AccessMetabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii
Ribose-5-phosphate (R5P) is a precursor for nucleic acid biogenesis. Here, Guo and Ji et al. show that multiple routes can flexibly supply R5P to enable Toxoplasma gondii growth.
- Xuefang Guo
- , Nuo Ji
- & Ningbo Xia
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Article
| Open AccessMulticore fiber optic imaging reveals that astrocyte calcium activity in the mouse cerebral cortex is modulated by internal motivational state
Astrocyte calcium increases can alter brain state, but their dynamics during different behaviors have not been fully described. Here, the authors use multicore fiber optic imaging in freely moving mice to show that astrocyte engagement in behavior is influenced by the motivational state.
- Yung-Tian A. Gau
- , Eric T. Hsu
- & Dwight E. Bergles
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Article
| Open AccessIntegration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
Risk prediction for prognosis in colorectal cancer is an important tool. Here, the authors utilise GWAS from 5 cohorts of colorectal cancer patients, and show a healthy lifestyle is associated with a 7.6% improvement in overall survival among patients with high pathologic and genetic risk.
- Junyi Xin
- , Dongying Gu
- & Meilin Wang
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Article
| Open Accessp53 promotes revival stem cells in the regenerating intestine after severe radiation injury
The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.
- Clara Morral
- , Arshad Ayyaz
- & David G. Kirsch
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Article
| Open AccessA live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections
Authors utilise a murine model of Escherichia coli infection to immunologically characterise the properties of their live attenuated vaccine candidate. They also demonstrate protection of newborn mice following maternal immunisation.
- Youssouf Sereme
- , Cécile Schrimp
- & David Skurnik
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Article
| Open AccessStroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma
Therapeutic resistance to immune checkpoint inhibitor treatment is incompletely understood in adolescent and young-adult (AYA) patients with melanoma. Here, the authors demonstrate that AYA patients exhibit a unique stroma-infiltrating T cell immunogenomic profile compared with adults, which impacts on their responsiveness to immunotherapy.
- Xinyu Bai
- , Grace H. Attrill
- & Camelia Quek
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Article
| Open AccessAccelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation
Here the authors find that erythroblasts of myelodysplastic syndromes with SF3B1 mutation leading to inefficient erythropoiesis show DNA replication stress with accelerated forks and reduced R-loops. Restoring R-loops by a histone deacetylase inhibitor rescues erythroid differentiation.
- David Rombaut
- , Carine Lefèvre
- & Michaela Fontenay
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Article
| Open AccessLarge-volume focus control at 10 MHz refresh rate via fast line-scanning amplitude-encoded scattering-assisted holography
This study presents a wavefront shaping scheme to control optical focus in a large 3D space at the unprecedented rate of 30 MHz with micron-scale precision and random accessibility via reallocation of degrees of freedom in spatiotemporal domain.
- Atsushi Shibukawa
- , Ryota Higuchi
- & Mooseok Jang
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Article
| Open AccessscButterfly: a versatile single-cell cross-modality translation method via dual-aligned variational autoencoders
Technical limitations of simultaneously multi-omics profiling lead to highly noisy multi-modal data and substantial costs. Here, authors proposed a versatile framework and data augmentation schemes, capable of single-cell cross-modality translation and multiple extensive applications.
- Yichuan Cao
- , Xiamiao Zhao
- & Shengquan Chen
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Article
| Open AccessPhage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model
Bacteriophage can be used to target bacterial infection and used as a therapeutic approach for antibiotic resistant bacteria. Here the authors show that the use of bacteriophage to target antibiotic resistant bacteria in a mouse model of infection can induce phage specific immune responses and may impair their therapeutic efficacy.
- Julia D. Berkson
- , Claire E. Wate
- & Paul E. Carlson Jr.
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Article
| Open AccessTiming along the cardiac cycle modulates neural signals of reward-based learning
Previous work has shown that natural cardiac rhythms modulate the perception and reaction to sensory cues through changes in associated neural signals. Here, the authors show that sensitivity to prediction errors during reward learning is related to the phase of the cardiac cycle.
- Elsa F. Fouragnan
- , Billy Hosking
- & Alejandra Sel
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Article
| Open AccessDifferentiation granules, a dynamic regulator of T. brucei development
The African trypanosome Trypanosoma brucei has been shown to form stress granules in vitro that might be repurposed to enable differentiation and facilitate parasite transmission. Here, Cayla et al. show that differentiation between slender and stumpy forms does involve membrane-less granules that are different from nutritional stress granules.
- Mathieu Cayla
- , Christos Spanos
- & Keith R. Matthews
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Article
| Open AccessSystematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis
Authors perform an in vivo mass spectrometry-based interactome analysis of HOIL-1-interacting protein, a key component of linear ubiquitination assembly complex.
- Yesheng Fu
- , Lei Li
- & Lingqiang Zhang
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Article
| Open AccessRewiring of a KNOXI regulatory network mediated by UFO underlies the compound leaf development in Medicago truncatula
This study reveals a pathway in which the transformation of trifoliate leaves into pinnate-like pentafoliate leaves is regulated by the conserved regulators of floral development (MtUFO) and leaf development (MtKNOXI) in M. truncatula.
- Zhichao Lu
- , Juanjuan Zhang
- & Chuanen Zhou
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Article
| Open AccessHalogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus
Modulating amyloid protein phase separation and fibrilization may help in addressing neurodegenerative diseases. This study demonstrates that halogen-doped graphene quantum dots can modulate these processes in TDP-43 in both nucleus and cytoplasm.
- Hong Zhang
- , Huazhang Guo
- & Bin Dai
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Article
| Open AccessProbing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling
Binding modes of antigenically drifted hemagglutinins of human influenza A viruses have been determined by NMR using synthetic N-glycans having 13C-labeled monosaccharides to pinpoint which monosaccharides of extended LacNAc chains engage with the HAs.
- Luca Unione
- , Augustinus N. A. Ammerlaan
- & Geert-Jan Boons
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Article
| Open AccessStructure and mechanisms of transport of human Asc1/CD98hc amino acid transporter
Asc1/CD98hc is a key regulator of small neutral amino acid transport in the brain and adipose tissue. Here, authors report the structure of semi-occluded hAsc1/CD98hc and provide a model for Asc1 exchange and facilitated diffusion modes of transport.
- Josep Rullo-Tubau
- , Maria Martinez-Molledo
- & Oscar Llorca
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Article
| Open AccessExtracellular DNA traps in a ctenophore demonstrate immune cell behaviors in a non-bilaterian
Identifying core mechanisms of immune cells is critical for understanding the evolution of animal immune function. Here, Vandepas et al. report that ctenophore immune-like cells release extracellular DNA traps when exposed to microbes.
- Lauren E. Vandepas
- , Caroline Stefani
- & Adam Lacy-Hulbert
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Article
| Open AccessPotent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains
Nipah virus is a WHO priority pathogen, and there is currently no approved drug for clinical therapy. Here, the authors identified potent human neutralizing antibodies that block receptor binding and provide protection against NiV infection in vivo.
- Li Chen
- , Mengmeng Sun
- & Sandra Chiu
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Article
| Open AccessEEG decoders track memory dynamics
Successful memorization could be decoded from brain activity. Here the authors decode human memory success from EEG recordings, suggesting memory is linked to context.
- Yuxuan Li
- , Jesse K. Pazdera
- & Michael J. Kahana
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Article
| Open AccessPaternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring
The dietary factors causing varying intergenerational responses are not fully identified. Here, the authors show that the relative proportion of protein, fats, and carbohydrates in paternal diets before conception differentially influences the phenotype of the next-generation offspring on energy metabolism and behaviour.
- Angela Jane Crean
- , Alistair McNair Senior
- & Stephen James Simpson
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Article
| Open AccessGadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms
Different gene mutations have been reported as drivers for myeloproliferative neoplasms (MPN). Here, the authors show that Gadd45g insufficiency induces MPN in mouse models and associates with MPN in patients.
- Peiwen Zhang
- , Na You
- & Xiaotong Ma
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Article
| Open AccessTumor-activated in situ synthesis of single-atom catalysts for O2-independent photodynamic therapy based on water-splitting
The utility of single-atom catalysts (SACs) for photodynamic therapy (PDT) has been limited by tumor hypoxia and side effects on normal tissues. Here the authors address these issues by developing an approach of tumor microenvironment-activated in situ synthesis of SACs for tumor-specific water-based PDT.
- Yiyan Yin
- , Xiyang Ge
- & Na Na
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Article
| Open AccessThe secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation
Microbiome-secreted proteins act as key modulators of host-microbiome crosstalk. Here, the authors show that Amuc_1409 protein, secreted from Akkermansia muciniphila, plays a key role in intestinal homeostasis by regulating intestinal stem cells through interaction with E-cadherin, indicating its potential as a biomolecule for improving gut health.
- Eun-Jung Kang
- , Jae-Hoon Kim
- & Chul-Ho Lee
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Article
| Open AccessSOXC are critical regulators of adult bone mass
Angelozzi et al. uncover key mechanisms involved in physiological and pathological bone mass remodeling by showing that SOXC transcription factors regulate the bone formation and resorption balance via critical roles in LepR+ mesenchymal stem cells.
- Marco Angelozzi
- , Anirudha Karvande
- & Véronique Lefebvre
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Article
| Open AccessSeeding the meiotic DNA break machinery and initiating recombination on chromosome axes
Meiotic cells deliberately break their DNA to allow chromosomes to swap genetic material. Here, authors reveal genetically separable pathways controlling the seeding and growth of chromosome-bound protein condensates responsible for DNA breaks.
- Ihsan Dereli
- , Vladyslav Telychko
- & Attila Tóth
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Article
| Open AccessGlobal latitudinal gradients and the evolution of body size in dinosaurs and mammals
Bergmann’s Rule predicts larger body sizes in colder climates. Here, the authors examine extinct and extant dinosaurs (birds) and mammaliaforms, finding no evidence of body size variation with latitude in any group, but a small variation with temperature in extant birds.
- Lauren N. Wilson
- , Jacob D. Gardner
- & Chris L. Organ
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Article
| Open AccessCryo-EM structures of prokaryotic ligand-gated ion channel GLIC provide insights into gating in a lipid environment
Gloeobacter proton-gated ion channel (GLIC) is a convenient model of pentameric ligand-gated ion channels. Here, Bharambe & Li et al. report structures and simulations of GLIC with insights into the role of lipids in GLIC gating mechanism.
- Nikhil Bharambe
- , Zhuowen Li
- & Sandip Basak
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Article
| Open AccessCompensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs
How growing organs recover from transient injuries is unclear. Here, authors used mouse models of transient cell death in the limb cartilage to identify cellular and molecular mechanisms (e.g. mTORC1) involved in cartilage repair and catch-up growth.
- Chee Ho H’ng
- , Shanika L. Amarasinghe
- & Alberto Rosello-Diez
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Article
| Open AccessSubcellular pathways through VGluT3-expressing mouse amacrine cells provide locally tuned object-motion-selective signals in the retina
How the spatial distribution of synapses relates to the subcellular integration and transmission of signals is not fully understood. Here authors combine functional and connectomic analysis to map the subcellular flow of information in retinal amacrine cells.
- Karl Friedrichsen
- , Jen-Chun Hsiang
- & Josh L. Morgan
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Article
| Open AccessTranslation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations
An emerging therapeutic strategy is to suppress nonsense mutations with engineered suppressor tRNAs. Here, the authors show that the mRNA translation velocity is a key parameter determining the efficacy of suppressor tRNAs.
- Nikhil Bharti
- , Leonardo Santos
- & Zoya Ignatova
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Article
| Open AccessDe novo diploid genome assembly using long noisy reads
Most existing assemblers failed to generate high-quality phased assemblies using long noisy reads. Here, the authors present PECAT, a Phased Error Correction and Assembly Tool, for reconstructing diploid genomes from long noisy reads.
- Fan Nie
- , Peng Ni
- & Jianxin Wang
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Article
| Open AccessNon-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells
DNA methylation is an essential epigenetic mark in mammals. The maintenance of this mark relies on two key proteins: DNMT1 and UHRF1. Here the authors show that, beyond activating DNMT1, UHRF1 has crucial regulatory functions in cancer cells.
- Kosuke Yamaguchi
- , Xiaoying Chen
- & Pierre-Antoine Defossez
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Article
| Open AccessCryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms
Pannexins are large pore channels involved in ion and ATP release. Here the authors use cryo-EM structures of Pannexins 1 and 3 to demonstrate the effects of distinct residue substitutions on channel structure and function.
- Nazia Hussain
- , Ashish Apotikar
- & Aravind Penmatsa
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Article
| Open AccessDiscovery of a small-molecule inhibitor that traps Polθ on DNA and synergizes with PARP inhibitors
Here the authors discover a small-molecule that inhibits DNA polymerase theta by trapping the enzyme on DNA in the closed conformation. The inhibitor selectively kills BRCA-mutant cells and exhibits strong synergistic activity with PARP inhibitors.
- William Fried
- , Mrityunjay Tyagi
- & Richard T. Pomerantz
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Article
| Open AccessDeepDOF-SE: affordable deep-learning microscopy platform for slide-free histology
Histopathology can be limited by the time-consuming and labour-intensive preparation of slides from resected tissue. Here, the authors report DeepDOF-SE, a deep-learning-enabled microscope to rapidly scan intact tissue at cellular resolution without the need for physical sectioning.
- Lingbo Jin
- , Yubo Tang
- & Ashok Veeraraghavan
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Article
| Open AccessStatins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1
Endothelial dysfunction has been shown to occur in HFpEF and we know that statins can target endothelial dysfunction by inhibiting miR-133a. Here the authors show that statins improve diastolic dysfunction in HFpEF by increasing the levels of a circRNA which, in turns, binds to miR-133a modulating its downstream targets.
- Bin Li
- , Wen-Wu Bai
- & Shuang-Xi Wang
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Article
| Open AccessDecoding early stress signaling waves in living plants using nanosensor multiplexing
Upon stress, plants activate a signaling cascade leading to resistance or stress adaptation. Here, Ang & Saju et al. use sensor multiplexing to elucidate the interplay between H2O2 and SA signaling as plants mount stress-specific defense responses.
- Mervin Chun-Yi Ang
- , Jolly Madathiparambil Saju
- & Rajani Sarojam
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Article
| Open AccessOrigin and dispersal history of Hepatitis B virus in Eastern Eurasia
Hepatitis B virus is an ancient human pathogen that dates back more than 10,000 years. Here, the authors investigate the evolutionary history of the virus in Eastern Eurasia by sequencing 34 genomes dating from approximately 400–5,000 years ago and comparing them with other contemporary sequences.
- Bing Sun
- , Aida Andrades Valtueña
- & Yinqiu Cui
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