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Article
| Open AccessMapping protein states and interactions across the tree of life with co-fractionation mass spectrometry
Co-fractionation mass spectrometry (CF-MS) is a powerful technique for mapping protein interactions under physiological conditions. Here, the authors uniformly re-process 411 CF-MS experiments and carry out meta-analyses of protein abundance, protein-protein interactions, and phosphorylation sites in the resulting resource.
- Michael A. Skinnider
- , Mopelola O. Akinlaja
- & Leonard J. Foster
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Article
| Open AccessEvolutionary modelling indicates that mosquito metabolism shapes the life-history strategies of Plasmodium parasites
Little is known about how malaria parasites adapt the speed of their development to their mosquito vectors. Using an evolutionary modelling framework, this study predicts that the metabolic status of mosquitoes shapes the parasites’ life-history strategies and transmission dynamics.
- Paola Carrillo-Bustamante
- , Giulia Costa
- & Elena A. Levashina
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Article
| Open AccessCompetition and evolutionary selection among core regulatory motifs in gene expression control
Regulators represent a bioenergetic cost in gene expression control. Here, the author shows how functionally equivalent regulatory motifs have fundamentally different impacts on population structure, growth dynamics, and evolutionary outcomes.
- Andras Gyorgy
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Article
| Open AccessSingle-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology
The authors developed a framework for joint protein-metabolite profiling at the single-cell level in human tissue combining targeted multiplexed protein imaging and untargeted spatial metabolomics in a single pipeline.
- Thomas Hu
- , Mayar Allam
- & Ahmet F. Coskun
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Article
| Open AccessGNTD: reconstructing spatial transcriptomes with graph-guided neural tensor decomposition informed by spatial and functional relations
Reconstructing transcriptome-wide spatially-resolved gene expressions requires modelling nonlinear patterns and spatial structures in RNA profiling data. Here, authors introduce a graph-guided neural hierarchical tensor decomposition model that incorporates spatial and functional relations for the task.
- Tianci Song
- , Charles Broadbent
- & Rui Kuang
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Article
| Open AccessAn integrated workflow for quantitative analysis of the newly synthesized proteome
Analysis of newly synthesized proteins upon perturbation can provide detailed insights into immediate proteome remodeling, which drives cellular responses. Here, the authors report an optimized semi-automated workflow for the quantitative analysis of the newly synthesized proteome.
- Toman Borteçen
- , Torsten Müller
- & Jeroen Krijgsveld
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Article
| Open AccessIn vivo RNA interactome profiling reveals 3’UTR-processed small RNA targeting a central regulatory hub
Here the authors report a new approach to profile RNA-RNA interactions in live bacterial cells. The charted RNA interaction networks unveil a key mRNA regulatory hub targeted by twelve small RNAs, including a novel RNA involved in fatty acid metabolism.
- Fang Liu
- , Ziying Chen
- & Yanjie Chao
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Article
| Open AccessEnvironmental modulation of global epistasis in a drug resistance fitness landscape
Global epistasis can be used to reconstruct fitness landscapes and infer adaptive trajectories. Here, the authors investigate how environmental variation impacts patterns of global epistasis, finding that global epistasis in the malaria parasite P. falciparum can be modulated by drug concentration in the environment.
- Juan Diaz-Colunga
- , Alvaro Sanchez
- & C. Brandon Ogbunugafor
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Article
| Open AccessAutoencoder neural networks enable low dimensional structure analyses of microbial growth dynamics
Here, the authors apply autoencoder neural networks to show that microbial growth dynamics can be compressed into low-dimensional representations and reconstructed with high fidelity, facilitating quantitative predictions and deduction of potential mechanisms.
- Yasa Baig
- , Helena R. Ma
- & Lingchong You
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Article
| Open AccessBuilding a eukaryotic chromosome arm by de novo design and synthesis
In Saccharomyces cerevisiae, the left arm of chromosome XII only requires 12 genes to maintain cell viability, whereas 25 genes are needed for robust fitness. Here the authors demonstrate that the entire arm can be replaced by a neochromosome with completely artificial sequences.
- Shuangying Jiang
- , Zhouqing Luo
- & Junbiao Dai
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Article
| Open AccessA dynamic partitioning mechanism polarizes membrane protein distribution
Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.
- Tatsat Banerjee
- , Satomi Matsuoka
- & Pablo A. Iglesias
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Article
| Open AccessTime-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle
Stress granules (SGs) are dynamic compartments with a poorly characterized transition in composition and function during prolonged stress. In this study, the authors investigated the dynamic changes in SG constituents during acute to prolonged heat shock using time-resolved proteomic profiling.
- Shuyao Hu
- , Yufeng Zhang
- & Yun Bai
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Article
| Open AccessSis2 regulates yeast replicative lifespan in a dose-dependent manner
Using a microfluidic single-cell aging platform, the authors report how single-cell lifespan varies across more than 300 yeast strains, each missing a single gene. Their top hit, Sis2, was found to regulate yeast lifespan in a dose-dependent fashion.
- Tolga T. Ölmez
- , David F. Moreno
- & Murat Acar
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Article
| Open AccessA semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening
Cell-based phenotypic assays link in vitro discovery to disease pathology. Here, the authors report a semiconductor-based microplate platform to perform high-throughput, high-dimensional “electrical imaging” for label-free assessment of live cell morphology and function.
- Shalaka Chitale
- , Wenxuan Wu
- & Jeffrey Abbott
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Article
| Open AccessMaintenance of appropriate size scaling of the C. elegans pharynx by YAP-1
Imbalance in the growth rate of two organs can perturb their appropriate scaling. Here, Stojanovski et al., identify a mechanism involving the mechanotransducer YAP-1 which ensures proper proportions of the pharynx and the body length of C. elegans.
- Klement Stojanovski
- , Ioana Gheorghe
- & Benjamin D. Towbin
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Article
| Open AccessMorphological evolution of bird wings follows a mechanical sensitivity gradient determined by the aerodynamics of flapping flight
Morphological trait evolution is partly driven by biomechanical function, but a general framework for this relationship is lacking. Here, the authors test two possible frameworks and find that mechanical sensitivity provides the best prediction of morphological evolution in bird wings
- Jonathan A. Rader
- & Tyson L. Hedrick
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Article
| Open AccessRegulation of species metabolism in synthetic community systems by environmental pH oscillations
Most synthetic communities are unidirectional or two-way interaction without dynamic feedback. Here, the authors report a dynamic feedback system involving artificial cell species, biological cell species, and their environment using pH-sensitive molecule that phase-shift between fluid and gel phases.
- Shubin Li
- , Yingming Zhao
- & Xiaojun Han
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Article
| Open AccessSynthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions
Here, Rueff et al engineered a CRISPRi-based oscillator to rewire capsule production in Streptococcus pneumoniae from its native control. They show that heterogeneity in capsule production is beneficial for fitness in several virulence associated traits.
- Anne-Stéphanie Rueff
- , Renske van Raaphorst
- & Jan-Willem Veening
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Article
| Open AccessConstructing temporal networks with bursty activity patterns
Many real-world systems are characterized by bursty dynamics with interchanging periods of intense activity and quiescence. The authors propose a method to construct temporal networks that match a given activity pattern, and apply it to empirical bursty patterns.
- Anzhi Sheng
- , Qi Su
- & Joshua B. Plotkin
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Article
| Open AccessSpeos: an ensemble graph representation learning framework to predict core gene candidates for complex diseases
Understanding phenotype-genotype relationships is a grand challenge of current biological research. Here, the authors use graph representation learning to identify human genes which display key characteristics of core genes for five complex diseases.
- Florin Ratajczak
- , Mitchell Joblin
- & Matthias Heinig
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Article
| Open AccessNIPMAP: niche-phenotype mapping of multiplex histology data by community ecology
Multiplex histology faces the challenge of integrating tissue architecture with the identification of relevant spatial cellular phenotypes. Using community ecology principles, the authors propose NIPMAP, a tool for niche-phenotype mapping of multiplex histology data.
- Anissa El Marrahi
- , Fabio Lipreri
- & Jean Hausser
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Article
| Open AccessVegetation controls on channel network complexity in coastal wetlands
Channel networks are key to coastal wetland functioning. Here, the authors show how vegetation enhances network branching, and hypothesize that this may enhance the storm surge buffering capacity of wetlands and their resilience under sea-level rise.
- Roeland C. van de Vijsel
- , Jim van Belzen
- & Johan van de Koppel
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Article
| Open AccessDisrupting cellular memory to overcome drug resistance
Identifying memory and state switching in single cells remains elusive. Here, the authors develop a method, scMemorySeq, by combining cell barcoding and scRNA-seq and apply it to human melanoma cells to track lineages as they switch states between a drug-susceptible state and a state primed for drug resistance.
- Guillaume Harmange
- , Raúl A. Reyes Hueros
- & Sydney M. Shaffer
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Article
| Open AccessA generative adversarial network model alternative to animal studies for clinical pathology assessment
Generative AI has the potential to transform the way chemical and drug safety research is conducted. Here the authors show AnimalGAN, a model developed using Generative Adversarial Networks, which simulates virtual animal experiments to generate multidimensional rat clinical pathology measurements.
- Xi Chen
- , Ruth Roberts
- & Weida Tong
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Article
| Open AccessGrowth in fluctuating light buffers plants against photorespiratory perturbations
The detoxification pathway photorespiration has been thought to be photoprotective in dynamic light. The authors report that, instead, growth in dynamic light buffers plants against photorespiratory lesions by reducing photosynthesis and inducing metabolite re-routing.
- Thekla von Bismarck
- , Philipp Wendering
- & Ute Armbruster
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Article
| Open AccessEngineering a scalable and orthogonal platform for synthetic communication in mammalian cells
The rational design and implementation of synthetic mammalian communication systems can unravel fundamental design principles of cell communication circuits and offer a framework for engineering of designer cell consortia with potential applications in cell therapeutics. Here the authors present a synthetic communication platform in mammalian cells based on diffusible dipeptide ligands and synthetic receptors, that is by design highly orthogonal, scalable, and programmable.
- Anna-Maria Makri Pistikou
- , Glenn A. O. Cremers
- & Tom F. A. de Greef
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Perspective
| Open AccessThe potential of CO2-based production cycles in biotechnology to fight the climate crisis
The utilization of one-carbon assimilation pathways for bioproduction represents a promising direction towards a more sustainable bio-based economy. Here, the authors compare the thermodynamic efficiencies and energy demand of C1-assimilation pathways and discuss their implementation for energy, material, and food production.
- Simone Bachleitner
- , Özge Ata
- & Diethard Mattanovich
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Article
| Open AccessRemodeling the cellular stress response for enhanced genetic code expansion in mammalian cells
Genetic code expansion (GCE) is a protein engineering tool that enables programmed and site-specific installation of noncanonical amino acids into proteins. Here, authors show that cellular stress remodelling boosts GCE in mammalian cells including GCE realized by orthogonally translating organelles.
- Mikhail E. Sushkin
- , Christine Koehler
- & Edward A. Lemke
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Article
| Open AccessA genome-scale metabolic model of parasitic whipworm
In this work, Bay et al describe the construction of the first genome-scale metabolic model for the parasitic whipworm, Trichuris muris and use it to identify novel metabolic pathways and predict critical enzymes and essential metabolites for worm survival.
- Ömer F. Bay
- , Kelly S. Hayes
- & Ian S. Roberts
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Article
| Open AccessOptogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation
The transcriptional regulator YAP controls cellular decisions such as proliferation, differentiation, and pluripotency. Here, the authors show a concentration-dependent and temporal communication code for YAP that enables cells to choose between these programs.
- Kirstin Meyer
- , Nicholas C. Lammers
- & Orion D. Weiner
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Article
| Open AccessReconstructing disease dynamics for mechanistic insights and clinical benefit
Understanding disease progression dynamics is critical for diagnostics and treatment, but capturing dynamics is difficult. Here, the authors present a method for modelling disease progression from high dimensional molecular data that enables patient stratification and high-risk disease state identification, showcased in bladder cancer.
- Amit Frishberg
- , Neta Milman
- & Shai S. Shen-Orr
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Perspective
| Open AccessSynergistic investigation of natural and synthetic C1-trophic microorganisms to foster a circular carbon economy
Using one carbon (C1) molecules as primary feedstock for bioproduction holds great potential for a circular and carbon neutral economy. Here, the authors discuss the potential of merging knowledge gained from natural and synthetic C1-trophic organisms to expedite the development of efficient C1-based biomanufacturing.
- Enrico Orsi
- , Pablo Ivan Nikel
- & Stefano Donati
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Article
| Open AccessCD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production
Control of HIV and SIV infection is largely thought to be achieved through direct lysis of target cells. Here, using mathematical modelling of viral load data from rhesus macaques, the authors propose that virus control is best explained by the combination of cytolytic and non-cytolytic effects.
- Benjamin B. Policicchio
- , Erwing Fabian Cardozo-Ojeda
- & Ruy M. Ribeiro
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Article
| Open AccessPaired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors
Combinations of transcription factors (TFs) bind DNA to fine-tune gene expression. Here, the authors map cooperative and antagonistic DNA binding across hundreds of TF-pairs. TF-TF relationships vary depending on DNA targets and TF isoforms.
- Anna Berenson
- , Ryan Lane
- & Juan I. Fuxman Bass
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Article
| Open AccessStochastic gene expression and environmental stressors trigger variable somite segmentation phenotypes
Mutations of several genes cause variable phenotypes. Here, the authors show stochastic her1 and her7 gene expression, which is affected by environmental conditions, underlies variability of somite segmentation defects.
- Kemal Keseroglu
- , Oriana Q. H. Zinani
- & Ertuğrul M. Özbudak
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Article
| Open AccessA robust yeast biocontainment system with two-layered regulation switch dependent on unnatural amino acid
Synthetic auxotrophy in which cell viability depends on the presence of an unnatural amino acid provides a powerful strategy to restrict unwanted propagation of genetically modified organisms in open environments and potentially prevent industrial espionage. Here the authors establish a general framework for the creation and optimization of synthetic auxotrophs in yeast.
- Tiantian Chang
- , Weichao Ding
- & Xian Fu
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Article
| Open AccessDigital data storage on DNA tape using CRISPR base editors
DNA is an alternative to data storage materials for its durability, density, and energetics. Here the authors demonstrate the storage of digital information on DNA molecules using base-editing.
- Afsaneh Sadremomtaz
- , Robert F. Glass
- & Reza Zadegan
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Article
| Open AccessProteogenetic drug response profiling elucidates targetable vulnerabilities of myelofibrosis
Myelofibrosis is a form of myeloproliferative neoplasm with few treatment options available. Here, the authors profiled drug responses and proteomics ex vivo and identify molecularly-guided treatment strategies, including HDAC and BET inhibitors for CALR mutant myelofibrosis patients.
- Mattheus H. E. Wildschut
- , Julien Mena
- & Berend Snijder
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Article
| Open AccessDeep flanking sequence engineering for efficient promoter design using DeepSEED
Designing promoters with desired properties is crucial in synthetic biology. Here, authors introduce DeepSEED, an AI-aided flanking sequence optimisation framework which combines expert knowledge with deep learning techniques to efficiently design promoters in both eukaryotic and prokaryotic cells.
- Pengcheng Zhang
- , Haochen Wang
- & Xiaowo Wang
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Article
| Open AccessDeep mutational scanning reveals the molecular determinants of RNA polymerase-mediated adaptation and tradeoffs
Mutations in an RNA polymerase fragment, frequently found in lab adaptation, cluster in two modules favoring growth or maintenance via loss of interactions. Combining mutations in both modules enhances both traits, promoting compensatory evolution.
- Alaksh Choudhury
- , Benoit Gachet
- & Olivier Tenaillon
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Article
| Open AccessFitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
Generating and controlling cell collective behavior is important for synthetic biology and bioproduction. Here, the authors show the diversification dynamic and the fitness cost associated with cell switching are coupled in yeast and bacteria, and demonstrate the feasibility of controlling diversification regimes.
- Lucas Henrion
- , Juan Andres Martinez
- & Frank Delvigne
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Article
| Open AccessProteomic and genetic analyses of influenza A viruses identify pan-viral host targets
Using a multi-OMICS approach, Haas et al identify 54 human genes and 16 host-targeting chemical compounds that regulate influenza A virus infection in lung epithelial cells, including AHNAK and COBP1 which are also essential for SARS-CoV-2 infection.
- Kelsey M. Haas
- , Michael J. McGregor
- & Nevan J. Krogan
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Article
| Open AccessEngineering microbial division of labor for plastic upcycling
Plastic pollution is rapidly increasing worldwide, causing adverse impacts on the environment, wildlife and human health. Here the authors present a synthetic microbial consortium that efficiently degrades polyethylene terephthalate hydrolysate and upcycles it to desired chemicals through cellular division of labor.
- Teng Bao
- , Yuanchao Qian
- & Ting Lu
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Article
| Open AccessMaintenance of pluripotency-like signature in the entire ectoderm leads to neural crest stem cell potential
How the neural crest gains its pluripotency-like stem cell potential is unclear. Here, the authors show that the entire post-gastrula ectoderm maintains expression of pluripotency genes, leading to the high stem cell capacity in the neural crest.
- Ceren Pajanoja
- , Jenny Hsin
- & Laura Kerosuo
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Article
| Open AccessExploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition
Single-cell proteomics by Mass Spectrometry (scpMS) provides unparalleled insights into cellular mechanisms from a proteome-centric standpoint. Here, the authors leverage sensitivity-tailored data acquisition methods to profile cell state heterogeneity in cultured model systems.
- Valdemaras Petrosius
- , Pedro Aragon-Fernandez
- & Erwin M. Schoof
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Article
| Open AccessEvidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
TMAO is known to be atherothrombotic. Here the authors show that i) kidney function is the main determinant of serum TMAO, ii) TMAO increases kidney scarring with TGF-β1 signalling and iii) anti-diabetic drugs with reno-protective properties such as GLP1R agonists reduce plasma TMAO.
- Petros Andrikopoulos
- , Judith Aron-Wisnewsky
- & Marc-Emmanuel Dumas
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Article
| Open AccessGenome-wide promoter responses to CRISPR perturbations of regulators reveal regulatory networks in Escherichia coli
Measuring gene expression responses for every transcription factor (TF)-gene pair in living prokaryotic cells is challenging. Here the authors report pooled promoter responses to TF perturbation sequencing (PPTP-seq) using CRISPRi, which they use to address this problem in E. coli.
- Yichao Han
- , Wanji Li
- & Fuzhong Zhang
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Article
| Open AccessActivator-blocker model of transcriptional regulation by pioneer-like factors
How gene expression timing is regulated during development remains a key area of research. Here they show that zebrafish genome activators Pou5f3 and Nanog block each other’s activity on the enhancers of differentiation genes, preventing their premature expression.
- Aileen Julia Riesle
- , Meijiang Gao
- & Daria Onichtchouk
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Article
| Open AccessProtein engineering and iterative multimodule optimization for vitamin B6 production in Escherichia coli
Pyridoxine (PN), the most common commercial form of vitamin B6, has been chemically synthesized using expensive and toxic chemicals. Here, the authors employ parallel pathway engineering, protein engineering, and iterative multimodule optimization for high level PN production in E. coli.
- Linxia Liu
- , Jinlong Li
- & Dawei Zhang
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