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News Feature |
Why is exercise good for you? Scientists are finding answers in our cells
Decades of evidence shows that exercise leads to healthier, longer lives. Researchers are just starting to work out what it does to cells to reap this reward.
- Gemma Conroy
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Article |
Proteome-scale discovery of protein degradation and stabilization effectors
A synthetic proteome-scale strategy enables the identification of a diverse range of human proteins that can induce the degradation or stabilization of a target protein in a proximity-dependent way.
- Juline Poirson
- , Hanna Cho
- & Mikko Taipale
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Article
| Open AccessSpatially organized cellular communities form the developing human heart
Combining single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization reveals in detail the cellular interactions and specialization of cardiac cell types that form and remodel the human heart.
- Elie N. Farah
- , Robert K. Hu
- & Neil C. Chi
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Article |
Self-enhanced mobility enables vortex pattern formation in living matter
We demonstrate that self-enhanced mobility offers a simple physical mechanism for pattern formation in living systems and, more generally, in other active matter systems near the boundary of fluid- and solid-like behaviours.
- Haoran Xu
- & Yilin Wu
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Article
| Open AccessSynthetic reversed sequences reveal default genomic states
Introduction of a long synthetic DNA into yeast genomic loci results in high default transcriptional activity in yeast but low activity in mouse, suggesting distinct default levels of genomic activity in these organisms.
- Brendan R. Camellato
- , Ran Brosh
- & Jef D. Boeke
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Article |
Evolutionary novelties underlie sound production in baleen whales
Studies of vocal production in baleen whales show that their larynx has evolved unique structures that enable their low-frequency vocalizations but limit their active communication range.
- Coen P. H. Elemans
- , Weili Jiang
- & W. Tecumseh Fitch
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Article |
Transcription–replication interactions reveal bacterial genome regulation
Single-cell expression data from bacteria are used to classify gene regulatory architectures in relation to gene expression dynamics and the cell cycle, revealing distinct categories of gene regulatory mechanisms.
- Andrew W. Pountain
- , Peien Jiang
- & Itai Yanai
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Editorial |
Cities matter to the world’s future — science must serve them better
From governance to climate impacts, the world’s urban environments face many difficulties. A new journal, Nature Cities, aims to bring together researchers who are rising to the challenge.
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Article
| Open AccessThe energetic and allosteric landscape for KRAS inhibition
Analysis of the effects of more than 26,000 KRAS mutations on abundance and interactions with six other proteins is used to construct an energy landscape of KRAS and identify allosteric drug target sites.
- Chenchun Weng
- , Andre J. Faure
- & Ben Lehner
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Perspective |
Hold out the genome: a roadmap to solving the cis-regulatory code
A roadmap towards solving the cis-regulatory code using a combination of machine learning and massively parallel assays of exogenous DNA is proposed.
- Carl G. de Boer
- & Jussi Taipale
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Article
| Open AccessCell-type-directed design of synthetic enhancers
Deep learning models were used to design synthetic cell-type-specific enhancers that work in fruit fly brains and human cell lines, an approach that also provides insights into these gene regulatory elements.
- Ibrahim I. Taskiran
- , Katina I. Spanier
- & Stein Aerts
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Article
| Open AccessDictionary of immune responses to cytokines at single-cell resolution
An extensive global transcriptomics analysis of in vivo responses to 86 cytokines across more than 17 immune cell types reveals enormous complexity of cellular responses to cytokines, providing the basis of the Immune Dictionary and its companion software Immune Response Enrichment Analysis.
- Ang Cui
- , Teddy Huang
- & Nir Hacohen
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Article
| Open AccessThe social and structural architecture of the yeast protein interactome
A protein interaction network constructed with data from high-throughput affinity enrichment coupled to mass spectrometry provides a highly saturated yeast interactome with 31,004 interactions, including low-abundance complexes, membrane protein complexes and non-taggable protein complexes.
- André C. Michaelis
- , Andreas-David Brunner
- & Matthias Mann
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Article
| Open AccessUnraveling the functional dark matter through global metagenomics
A computational approach to generate reference-free protein families from the sequence space in metagenomes reveals an enormously diverse functional space.
- Georgios A. Pavlopoulos
- , Fotis A. Baltoumas
- & Nikos C. Kyrpides
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Editorial |
Want a sustainable future? Then look to the world’s cities
In a rapidly urbanizing world, what happens in cities matters — and sustainability success stories show what can be achieved when researchers and policymakers work together.
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Article
| Open AccessNuclear genetic control of mtDNA copy number and heteroplasmy in humans
We quantify mitochondrial DNA copy number and heteroplasmy levels and study their association with nuclear genetic loci in population-scale biobanks.
- Rahul Gupta
- , Masahiro Kanai
- & Vamsi K. Mootha
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Article
| Open AccessOrganization of the human intestine at single-cell resolution
Intestinal cell types are organized into distinct neighbourhoods and communities within the healthy human intestine, with distinct immunological niches.
- John W. Hickey
- , Winston R. Becker
- & Michael Snyder
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Article |
Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells
Anti-cancer treatment often results in a subset of the clonal cell population developing resistance to therapy, with resistant cells displaying a diversity of fate types resulting from the intrinsic variability among the clonal population before treatment.
- Yogesh Goyal
- , Gianna T. Busch
- & Arjun Raj
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Article
| Open AccessLoss of CDK4/6 activity in S/G2 phase leads to cell cycle reversal
We uncover the mechanism underlying the restriction point phenomenon, suggest a role for cyclin-dependent kinase 4 and 6 activity in S and G2 phases, and explain the behaviour of cells following loss of mitogen signalling.
- James A. Cornwell
- , Adrijana Crncec
- & Steven D. Cappell
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Article |
Transfer learning enables predictions in network biology
A context-aware, attention-based deep learning model pretrained on single-cell transcriptomes enables predictions in settings with limited data in network biology and could accelerate discovery of key network regulators and candidate therapeutic targets.
- Christina V. Theodoris
- , Ling Xiao
- & Patrick T. Ellinor
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Article |
Noncoding translation mitigation
Combining genome-wide CRISPR screens with massively parallel analyses of human and random DNA sequences reveal a unified mechanism for the surveillance and evolution of translation products from annotated noncoding DNA.
- Jordan S. Kesner
- , Ziheng Chen
- & Xuebing Wu
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Article |
Large-scale mapping and mutagenesis of human transcriptional effector domains
A high throughput recruitment assay testing the transcriptional activity of more than 100,000 protein fragments tiling across most human chromatin regulators and transcription factors maps the locations and strengths of activation, repression and bifunctional domains, and identifies the sequences necessary for these functions.
- Nicole DelRosso
- , Josh Tycko
- & Lacramioara Bintu
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Article |
Late Cenozoic cooling restructured global marine plankton communities
Analysis of Triton, a high-resolution dataset documenting the macroperforate planktonic foraminifera fossil record, reveals a global climate-linked equatorward shift of ecological and morphological community equitability over the past 8 million years.
- Adam Woodhouse
- , Anshuman Swain
- & Christopher M. Lowery
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News & Views |
An oracle predicts regulators of cell identity
A computational tool called CellOracle can predict how networks of genes interact to program cell identity during embryonic development. The tool should help to hone efforts to understand how development is regulated.
- Jeffrey A. Farrell
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Article |
Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
Immune responses to influenza vaccination are affected by previous mild COVID-19 in a sex-dimorphic manner.
- Rachel Sparks
- , William W. Lau
- & John S. Tsang
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Article
| Open AccessIntegrated intracellular organization and its variations in human iPS cells
A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.
- Matheus P. Viana
- , Jianxu Chen
- & Susanne M. Rafelski
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Article |
Periodic inhibition of Erk activity drives sequential somite segmentation
The zebrafish segmentation clock drives sequential segmentation of somites by periodically lowering double-phosphorylated Erk and therefore projecting its oscillation on the double-phosphorylated Erk gradient.
- M. Fethullah Simsek
- , Angad Singh Chandel
- & Ertuğrul M. Özbudak
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Article
| Open AccessProgramming multicellular assembly with synthetic cell adhesion molecules
Synthetic cell adhesion molecules yield customized cell–cell interactions with adhesion properties that are similar to native interactions, and offer abilities for cell and tissue engineering and for systematically studying multicellular organization.
- Adam J. Stevens
- , Andrew R. Harris
- & Wendell A. Lim
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Article |
A spatiotemporally resolved single-cell atlas of the Plasmodium liver stage
Single-cell RNA sequencing and single-molecule RNA transcript imaging have been used to characterize spatially and temporally resolved mouse liver and parasite expression programmes during infection with the rodent malaria parasite Plasmodium berghei ANKA.
- Amichay Afriat
- , Vanessa Zuzarte-Luís
- & Shalev Itzkovitz
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Article |
Real-time bioelectronic sensing of environmental contaminants
The combination of synthetic biology and materials engineering enabled the development of biosensors that produce electrical readouts and real-time detection capabilities.
- Joshua T. Atkinson
- , Lin Su
- & Caroline M. Ajo-Franklin
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Research Briefing |
A deep artificial neural network powered by enzymes
Molecular networks have been developed that can classify complex mixtures of DNA sequences that cannot be categorized by a single linear classifier. To do this, artificial ‘neurons’ powered by enzymes are wired together to form an architecture that mimics the structure of a neural network.
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Article |
Nonlinear decision-making with enzymatic neural networks
Mimicking traditional digital neural networks with DNA-encoded ‘enzymatic’ neurons overcomes issues with other chemical approaches, and could allow notable increases in miniaturization and molecular implementation of these AI models, with potential applications including DNA data storage or cancer diagnosis.
- S. Okumura
- , G. Gines
- & A. J. Genot
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News & Views |
Neurons that control walking go round in circles
Evidence from turtles and computer models indicates that a pattern of neuronal activity known as rotational dynamics governs locomotion. The finding challenges long-standing models of locomotor control.
- Martha W. Bagnall
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Article
| Open AccessInferring and perturbing cell fate regulomes in human brain organoids
A multi-omic atlas of brain organoid development facilitates the inference of an underlying gene regulatory network using the newly developed Pando framework and shows—in conjunction with perturbation experiments—that GLI3 controls forebrain fate establishment through interaction with HES4/5 regulomes.
- Jonas Simon Fleck
- , Sophie Martina Johanna Jansen
- & Barbara Treutlein
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Article |
Antibiotic combinations reduce Staphylococcus aureus clearance
Different pairs of antibiotics show qualitatively different bacterial clearance interactions—some pairs show reciprocal suppression whereby the drug mixture efficacy is weaker than the individual drugs alone, and the clearance efficacy decreases as more drugs are added.
- Viktória Lázár
- , Olga Snitser
- & Roy Kishony
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Article |
Control of cell state transitions
An approach called cell state transition assessment and regulation uses diverse multiomics data to map cell states, model their transitions, and understand the signalling networks that control them.
- Oleksii S. Rukhlenko
- , Melinda Halasz
- & Boris N. Kholodenko
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Article |
Living material assembly of bacteriogenic protocells
A bacteriogenic strategy for constructing membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells provides opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs.
- Can Xu
- , Nicolas Martin
- & Stephen Mann
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Research Briefing |
Engineered yeast brews precursors of anticancer drug vinblastine
We genetically reprogrammed yeast to produce the alkaloids vindoline and catharanthine — the longest biosynthetic pathway to be transferred from a plant to a microorganism. In principle, similarly engineered yeast strains could produce more than 3,000 other monoterpene indole alkaloids and unnatural analogues.
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Article
| Open Access4-bit adhesion logic enables universal multicellular interface patterning
A synthetic cell-cell adhesion logic using swarming E. coli with 4 bits of information is introduced, enabling the programming of interfaces that combine to form universal tessellation patterns over a large scale.
- Honesty Kim
- , Dominic J. Skinner
- & Ingmar H. Riedel-Kruse
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Article
| Open AccessA physical wiring diagram for the human immune system
Systematic measurements of the interactions between proteins found on the surfaces of human leukocytes provides a global view of the way that immune cells are dynamically connected by receptors.
- Jarrod Shilts
- , Yannik Severin
- & Gavin J. Wright
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Article |
Defining mitochondrial protein functions through deep multiomic profiling
A multiomics resource characterizing human mitochondrial proteins enables identification of biological functions and supports genetic diagnosis of mitochondrial pathologies.
- Jarred W. Rensvold
- , Evgenia Shishkova
- & David J. Pagliarini
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Article |
Compatibility rules of human enhancer and promoter sequences
A new high-throughput assay applied to 1,000 enhancers and 1,000 promoters in human cells reveals how different classes of enhancers and promoters control RNA expression.
- Drew T. Bergman
- , Thouis R. Jones
- & Jesse M. Engreitz
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Comment |
Weak links in finance and supply chains are easily weaponized
Russian sanctions highlight how network analysis is urgently needed to find and protect vulnerable parts of the global economy.
- Henry Farrell
- & Abraham L. Newman
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Article
| Open AccessIntron-mediated induction of phenotypic heterogeneity
Experiments in yeast show that introns have a role in inducing phenotypic heterogeneity and that intron-mediated regulation of ribosomal proteins confers a fitness advantage by enabling yeast populations to diversify under nutrient-scarce conditions.
- Martin Lukačišin
- , Adriana Espinosa-Cantú
- & Tobias Bollenbach
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Article |
Mapping the energetic and allosteric landscapes of protein binding domains
An approach that combines deep mutational scanning with neural network-based thermodynamic modelling is used to provide comprehensive maps of the energetic and allosteric effects of mutations in two common protein domains.
- Andre J. Faure
- , Júlia Domingo
- & Ben Lehner
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Article |
The evolution, evolvability and engineering of gene regulatory DNA
A framework for studying and engineering gene regulatory DNA sequences, based on deep neural sequence-to-expression models trained on large-scale libraries of random DNA, provides insight into the evolution, evolvability and fitness landscapes of regulatory DNA.
- Eeshit Dhaval Vaishnav
- , Carl G. de Boer
- & Aviv Regev
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Article
| Open AccessTwin study reveals non-heritable immune perturbations in multiple sclerosis
In monozygotic twins discordant for multiple sclerosis, the influence of genetic predisposition and environmental factors is determined using matched-pair analyses.
- Florian Ingelfinger
- , Lisa Ann Gerdes
- & Burkhard Becher
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Article
| Open AccessEvolution of enhanced innate immune evasion by SARS-CoV-2
The SARS-CoV-2 Alpha variant suppresses innate immune responses more effectively than isolates of first-wave SARS-CoV-2, and this is a result of mutations outside of the spike coding region that lead to upregulation of viral innate immune antagonists.
- Lucy G. Thorne
- , Mehdi Bouhaddou
- & Nevan J. Krogan
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Article |
Combinatorial, additive and dose-dependent drug–microbiome associations
An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.
- Sofia K. Forslund
- , Rima Chakaroun
- & Peer Bork
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