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| Open AccessCell-type specialization is encoded by specific chromatin topologies
A new technique called immunoGAM, which combines genome architecture mapping (GAM) with immunoselection, enabled the discovery of specialized chromatin conformations linked to gene expression in specific cell populations from mouse brain tissues.
- Warren Winick-Ng
- , Alexander Kukalev
- & Ana Pombo
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Article |
Systems-level effects of allosteric perturbations to a model molecular switch
Interface mutations in the GTPase switch protein Gsp1 (the yeast homologue of human RAN) allosterically affect the kinetics of the switch cycle, revealing a systems-level mechanism of multi-specificity.
- Tina Perica
- , Christopher J. P. Mathy
- & Tanja Kortemme
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Article
| Open AccessThe mouse cortico–basal ganglia–thalamic network
Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.
- Nicholas N. Foster
- , Joshua Barry
- & Hong-Wei Dong
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Article |
Bioaccumulation of therapeutic drugs by human gut bacteria
An analysis of the interactions between 15 drugs and 25 gut bacterial strains shows that bioaccumulation of drugs within bacterial cells is another mechanism through which gut microorganisms can alter drug availability and efficacy.
- Martina Klünemann
- , Sergej Andrejev
- & Kiran R. Patil
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Article |
Tracing oncogene-driven remodelling of the intestinal stem cell niche
By inducing changes in surrounding tissue, mutant intestinal stem cells create an unfavourable niche environment that gives them a competitive advantage over non-mutant neighbours.
- Min Kyu Yum
- , Seungmin Han
- & Benjamin D. Simons
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Article |
A proximity-dependent biotinylation map of a human cell
A proximity-dependent biotinylation technique defines the location of more than 4,000 proteins in a human cell, and almost 36,000 proximal interactions between proteins, including those at the interface of the mitochondria and ER.
- Christopher D. Go
- , James D. R. Knight
- & Anne-Claude Gingras
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News & Views |
Trip frequency is key ingredient in new law of human travel
An analysis of mobile-phone tracking data has revealed a universal pattern that describes the interplay between the distances travelled by humans on trips and the frequency with which those trips are made.
- Laura Alessandretti
- & Sune Lehmann
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Article |
MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration
The natural antisense transcript MAPT-AS1 interferes with translation of mRNA transcript into tau protein in the brain and may represent a general mechanism for controlling levels of intrinsically disordered proteins, with particular relevance for neurodegeneration.
- Roberto Simone
- , Faiza Javad
- & Rohan de Silva
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Article |
Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV
Multi-omics profiling of effects of SARS-CoV-2 and SARS-CoV on A549, a lung-derived human cell line, produces a dataset enabling identification of common and virus-specific mechanisms of infection.
- Alexey Stukalov
- , Virginie Girault
- & Andreas Pichlmair
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Article |
A multi-scale brain map derived from whole-brain volumetric reconstructions
Two complete volumetric reconstructions of the Caenorhabditis elegans main neuropil (the nerve ring) reveal multi-scale spatial organization that supports both conserved and variable circuitry, and enables the derivation of a modular structure–function model of the neuropil.
- Christopher A. Brittin
- , Steven J. Cook
- & Netta Cohen
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Article |
Pairing of segmentation clock genes drives robust pattern formation
The pairing of genes is essential for robust expression of segmentation clock genes during development in zebrafish embryos.
- Oriana Q. H. Zinani
- , Kemal Keseroğlu
- & Ertuğrul M. Özbudak
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Article |
The functional proteome landscape of Escherichia coli
Thermal proteome profiling combined with a reverse genetics approach provides insights into the abundance and thermal stability of the global proteome of Escherichia coli.
- André Mateus
- , Johannes Hevler
- & Mikhail M. Savitski
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Article |
Combinatorial expression of GPCR isoforms affects signalling and drug responses
Transcriptomics, proteomics, single-cell RNA sequencing, population-wide genetic association studies and structure–function analyses provide a picture of how the differential expression of G-protein-coupled receptor isoforms can diversify signalling in different tissues.
- Maria Marti-Solano
- , Stephanie E. Crilly
- & M. Madan Babu
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Article |
Dense and pleiotropic regulatory information in a developmental enhancer
A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution.
- Timothy Fuqua
- , Jeff Jordan
- & Justin Crocker
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Article |
Phenotypic landscape of intestinal organoid regeneration
An organoid-based screening platform maps the genetic interactions underlying intestinal development and regeneration, showing that retinoic acid metabolism maintains the balance between regeneration and homeostasis, and that an antagonist of the retinoid X receptor promotes regeneration in vivo.
- Ilya Lukonin
- , Denise Serra
- & Prisca Liberali
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Article |
Functional genomic landscape of cancer-intrinsic evasion of killing by T cells
Genome-wide CRISPR screens in mouse cancer cell lines are used to identify a core, conserved set of genes and pathways that govern how cancer cells evade killing by cytotoxic T lymphocytes.
- Keith A. Lawson
- , Cristovão M. Sousa
- & Jason Moffat
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Perspective |
LifeTime and improving European healthcare through cell-based interceptive medicine
The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.
- Nikolaus Rajewsky
- , Geneviève Almouzni
- & Frauke Zipp
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Article |
A universal trade-off between growth and lag in fluctuating environments
A model of sequential flux bottlenecks explains a universal trade-off between steady-state growth and physiological adaptation time in bacteria exposed to fluctuating growth conditions.
- Markus Basan
- , Tomoya Honda
- & Uwe Sauer
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Article |
Extensive signal integration by the phytohormone protein network
A systems-level map of the Arabidopsis hormone signalling network, comprising more than 2,000 binary protein–protein interactions, reveals hundreds of interpathway contact points, many of which mediate crosstalk between different hormone pathways.
- Melina Altmann
- , Stefan Altmann
- & Pascal Falter-Braun
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Article |
Structural cells are key regulators of organ-specific immune responses
Structural cells implement a broad range of immune-regulatory functions beyond their roles as barriers and connective tissues, and they utilize an epigenetically encoded potential for immune gene activation in their rapid response to viral infection.
- Thomas Krausgruber
- , Nikolaus Fortelny
- & Christoph Bock
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Article |
Single-molecule imaging of transcription dynamics in somatic stem cells
Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.
- Justin C. Wheat
- , Yehonatan Sella
- & Ulrich Steidl
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Article |
The proteome landscape of the kingdoms of life
An advanced proteomics workflow is used to identify 340,000 proteins from 100 taxonomically diverse species, providing a comparative view of proteomes across the evolutionary range.
- Johannes B. Müller
- , Philipp E. Geyer
- & Matthias Mann
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Technology Feature |
Microbial matters: modelling the complex web of host–microbiome interactions
Computational approaches help to map the extensive biochemical chatter between bacteria and their human hosts.
- Michael Eisenstein
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Article |
The online competition between pro- and anti-vaccination views
Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.
- Neil F. Johnson
- , Nicolas Velásquez
- & Yonatan Lupu
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Article |
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
- David E. Gordon
- , Gwendolyn M. Jang
- & Nevan J. Krogan
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Article |
A reference map of the human binary protein interactome
A human binary protein interactome map that includes around 53,000 protein–protein interactions involving more than 8,000 proteins provides a reference for the study of human cellular function in health and disease.
- Katja Luck
- , Dae-Kyum Kim
- & Michael A. Calderwood
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Article |
Construction of a human cell landscape at single-cell level
Single-cell RNA sequencing is used to generate a dataset covering all major human organs in both adult and fetal stages, enabling comparison with similar datasets for mouse tissues.
- Xiaoping Han
- , Ziming Zhou
- & Guoji Guo
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Article |
The single-cell pathology landscape of breast cancer
A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.
- Hartland W. Jackson
- , Jana R. Fischer
- & Bernd Bodenmiller
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Article |
Gene expression cartography
A new computational framework, novoSpaRc, leverages single-cell data to reconstruct spatial context for cells and spatial expression across tissues and organisms, on the basis of an organization principle for gene expression.
- Mor Nitzan
- , Nikos Karaiskos
- & Nikolaus Rajewsky
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Article |
Chemotaxis as a navigation strategy to boost range expansion
Pioneering bacterial cells use chemotaxis along self-generated attractant gradients to facilitate rapid colonization of nutrient-replete environments.
- Jonas Cremer
- , Tomoya Honda
- & Terence Hwa
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Article |
An evolutionarily stable strategy to colonize spatially extended habitats
To successfully colonize a habitat in the presence of competing chemotactic bacterial populations, the winner is required to expand its range at a speed given by the habitat size and the population doubling time.
- Weirong Liu
- , Jonas Cremer
- & Chenli Liu
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Article |
Engineering orthogonal signalling pathways reveals the sparse occupancy of sequence space
Engineered two-component signalling proteins in Escherichia coli have residue specificities different to their parent proteins and are orthogonal to all extant paralogues, demonstrating that sequence space is not densely occupied.
- Conor J. McClune
- , Aurora Alvarez-Buylla
- & Michael T. Laub
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News & Views |
Strategies for combating online hate
An analysis of the dynamics of online hate groups on social-media platforms reveals why current methods to ban hate content are ineffective, and provides the basis for four potential strategies to combat online hate.
- Noemi Derzsy
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Letter |
Dietary methionine influences therapy in mouse cancer models and alters human metabolism
In two patient-derived xenograft models of colorectal cancer and a mouse model of autochthonous soft-tissue sarcoma, dietary restriction of methionine influences the outcome of cancer and interacts with antimetabolite and radiation therapies, through effects on one-carbon metabolism.
- Xia Gao
- , Sydney M. Sanderson
- & Jason W. Locasale
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Letter |
scSLAM-seq reveals core features of transcription dynamics in single cells
A technique known as scSLAM-seq that combines single-cell RNA sequencing with metabolic RNA labelling and nucleoside conversion is used to study the onset of cytomegalovirus infection in single mouse fibroblasts.
- Florian Erhard
- , Marisa A. P. Baptista
- & Lars Dölken
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Letter |
A universal biomolecular integral feedback controller for robust perfect adaptation
A synthetic gene circuit implementing an integral feedback topology is shown to achieve robust perfect adaptation in living cells--mathematical analysis proves this topology is necessary for adaptation in networks with noisy dynamics.
- Stephanie K. Aoki
- , Gabriele Lillacci
- & Mustafa Khammash
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News & Views |
A universal control system for synthetic gene networks
A module for implementing robust feedback control in synthetic cellular networks has been reported. Its design is first proved mathematically to be universal for all networks, and then implemented in living cells.
- Noah Olsman
- & Johan Paulsson
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Article
| Open AccessMulti-omics of the gut microbial ecosystem in inflammatory bowel diseases
The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.
- Jason Lloyd-Price
- , Cesar Arze
- & Curtis Huttenhower
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News |
Murray Gell-Mann, father of quarks, dies
US physicist was one of the chief architects of the standard model of particle physics.
- Davide Castelvecchi
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Article |
Total synthesis of Escherichia coli with a recoded genome
High-fidelity convergent total synthesis is used to produce
Escherichia coli with a 61-codon synthetic genome that uses 59 codons to encode all of the canonical amino acids.- Julius Fredens
- , Kaihang Wang
- & Jason W. Chin
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Books & Arts |
The new physics needed to probe the origins of life
Stuart Kauffman’s provocative take on emergence and evolution energizes Sara Imari Walker.
- Sara Imari Walker
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Article |
Self-organization and symmetry breaking in intestinal organoid development
Single-cell-based imaging and sequencing approaches are used to characterize organoid development and the intestinal regeneration process, which is driven by transient activation of YAP1.
- Denise Serra
- , Urs Mayr
- & Prisca Liberali
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News Feature |
How secret conversations inside cells are transforming biology
Organelles — the cell’s workhorses — mingle far more than scientists ever appreciated.
- Elie Dolgin
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Letter |
Complete biosynthesis of cannabinoids and their unnatural analogues in yeast
Genetic engineering of yeast enables the production of cannabinoids and cannabinoid analogues from the simple sugar galactose, without the need to cultivate Cannabis.
- Xiaozhou Luo
- , Michael A. Reiter
- & Jay D. Keasling
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Article |
An integrative systems genetic analysis of mammalian lipid metabolism
The integration of liver and plasma quantitative lipidomic and proteomic data from 107 distinct mouse strains provides important insights into regulators of mammalian lipid metabolism.
- Benjamin L. Parker
- , Anna C. Calkin
- & Brian G. Drew
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News |
How machine learning could keep dangerous DNA out of terrorists’ hands
Sophisticated algorithms could help DNA-synthesis companies avoid making dangerous organisms on demand.
- Sara Reardon
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Letter |
Programmable design of orthogonal protein heterodimers
Computational design incorporating modular buried hydrogen networks produces highly orthogonal protein heterodimers.
- Zibo Chen
- , Scott E. Boyken
- & David Baker
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Letter |
Controlling orthogonal ribosome subunit interactions enables evolution of new function
Orthogonal ribosomes are engineered in which the two subunits are stapled together in a way that limits association with endogenous subunits in cells, enabling the evolution of new functionality in the orthogonal ribosome.
- Wolfgang H. Schmied
- , Zakir Tnimov
- & Jason W. Chin
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