Abstract:
:A grand challenge of systems biology is to predict the kinetic responses of living systems to perturbations starting from the underlying molecular interactions. Changes in the nutrient environment have long been used to study regulation and adaptation phenomena in microorganisms and they remain a topic of active investigation. Although much is known about the molecular interactions that govern the regulation of key metabolic processes in response to applied perturbations, they are insufficiently quantified for predictive bottom-up modelling. Here we develop a top-down approach, expanding the recently established coarse-grained proteome allocation models from steady-state growth into the kinetic regime. Using only qualitative knowledge of the underlying regulatory processes and imposing the condition of flux balance, we derive a quantitative model of bacterial growth transitions that is independent of inaccessible kinetic parameters. The resulting flux-controlled regulation model accurately predicts the time course of gene expression and biomass accumulation in response to carbon upshifts and downshifts (for example, diauxic shifts) without adjustable parameters. As predicted by the model and validated by quantitative proteomics, cells exhibit suboptimal recovery kinetics in response to nutrient shifts owing to a rigid strategy of protein synthesis allocation, which is not directed towards alleviating specific metabolic bottlenecks. Our approach does not rely on kinetic parameters, and therefore points to a theoretical framework for describing a broad range of such kinetic processes without detailed knowledge of the underlying biochemical reactions.
journal_name
Naturejournal_title
Natureauthors
Erickson DW,Schink SJ,Patsalo V,Williamson JR,Gerland U,Hwa Tdoi
10.1038/nature24299subject
Has Abstractpub_date
2017-11-02 00:00:00pages
119-123issue
7678eissn
0028-0836issn
1476-4687pii
nature24299journal_volume
551pub_type
杂志文章相关文献
NATURE文献大全abstract::Many animals rely on an internal heading representation when navigating in varied environments1-10. How this representation is linked to the sensory cues that define different surroundings is unclear. In the fly brain, heading is represented by 'compass' neurons that innervate a ring-shaped structure known as the elli...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1767-1
更新日期:2019-12-01 00:00:00
abstract::In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05957
更新日期:2007-07-05 00:00:00
abstract::The cell adhesion molecules L1, N-CAM and Ng-CAM have been implicated in cell-cell interactions among developing neural cells. L1 and N-CAM are structurally and functionally distinct molecular entities and act synergistically in mediating Ca2+-independent adhesion between re-aggregating early postnatal cerebellar cell...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/316728a0
更新日期:1985-08-22 00:00:00
abstract::Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinyla...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07055
更新日期:2008-06-12 00:00:00
abstract::The nucleosome subunit of chromatin consists of DNA folded around a histone core as a 1.8-turn left-handed solenoid. The crystal structure of the nucleosome core particle revealed that it has a dyad symmetry axis and that the minor helix groove faces outwards from the protein core. Richmond et al. noticed that the pat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/328554a0
更新日期:1987-08-06 00:00:00
abstract::The hypothesis that animal population dynamics may be synchronized by climate is highly relevant in the context of climate change because it suggests that several populations might respond simultaneously to climatic trends if their dynamics are entrained by environmental correlation. The dynamics of many species throu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01064
更新日期:2002-11-14 00:00:00
abstract::The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the en...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature20104
更新日期:2016-11-10 00:00:00
abstract::Exoplanet detections have revolutionized astronomy, offering new insights into solar system architecture and planet demographics. While nearly 1,900 exoplanets have now been discovered and confirmed, none are still in the process of formation. Transition disks, protoplanetary disks with inner clearings best explained ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature15761
更新日期:2015-11-19 00:00:00
abstract::WAVE1--the Wiskott-Aldrich syndrome protein (WASP)--family verprolin homologous protein 1--is a key regulator of actin-dependent morphological processes in mammals, through its ability to activate the actin-related protein (Arp2/3) complex. Here we show that WAVE1 is phosphorylated at multiple sites by cyclin-dependen...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04976
更新日期:2006-08-17 00:00:00
abstract::A consequence of relativity is that in the presence of an electric field, the spin and momentum states of an electron can be coupled; this is known as spin-orbit coupling. Such an interaction opens a pathway to the manipulation of electron spins within non-magnetic semiconductors, in the absence of applied magnetic fi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02202
更新日期:2004-01-01 00:00:00
abstract::In this Letter, a citation to 'Fig. 1e' has been corrected to 'Fig. 1d' in the sentence starting "By contrast, the anti-tumour response…". This has been corrected online. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-019-1046-1
更新日期:2019-04-01 00:00:00
abstract::Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans1,2 may contribute to this failure in translation. We tested three independent neuroprotective approache...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2348-z
更新日期:2020-06-01 00:00:00
abstract::Visual working memory provides an essential link between perception and higher cognitive functions, allowing for the active maintenance of information about stimuli no longer in view. Research suggests that sustained activity in higher-order prefrontal, parietal, inferotemporal and lateral occipital areas supports vis...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07832
更新日期:2009-04-02 00:00:00
abstract::Extracellular signalling by the purine nucleotide ATP has long been associated with sensory function. In the periphery, ATP mediates nociception, mechanosensitivity, thermal sensitivity and O2 chemosensitivity. These processes share a common mechanism that involves the release of ATP to excite afferent fibres via acti...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03690
更新日期:2005-07-07 00:00:00
abstract::Alphabeta T lymphocytes are able to detect even a single peptide-major histocompatibility complex (MHC) on the surface of an antigen-presenting cell. This is despite clear evidence, at least with CD4+ T cells, that monomeric ligands are not stimulatory. In an effort to understand how this remarkable sensitivity is ach...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03391
更新日期:2005-03-10 00:00:00
abstract::Uridine at the first anticodon position (U34) of glutamate, lysine and glutamine transfer RNAs is universally modified by thiouridylase into 2-thiouridine (s2U34), which is crucial for precise translation by restricting codon-anticodon wobble during protein synthesis on the ribosome. However, it remains unclear how th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04896
更新日期:2006-07-27 00:00:00
abstract::Strong interactions between electrons in a solid material can lead to surprising properties. A prime example is the Mott insulator, in which suppression of conductivity occurs as a result of interactions rather than a filled Bloch band. Proximity to the Mott insulating phase in fermionic systems is the origin of many ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07244
更新日期:2008-09-11 00:00:00
abstract::In Fig. 3d this Letter, the R2 value should have been '0.19' instead of '0.66'; this has been corrected online. ...
journal_title:Nature
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41586-019-0893-0
更新日期:2019-02-01 00:00:00
abstract::The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature18637
更新日期:2016-07-21 00:00:00
abstract::In mammalian tissues the C-terminal amide structure has been found to occur only in neuroactive or hormonally-active peptides. About half known neuropeptide and peptide hormones have this unique chemical feature. Using a chemical detection method, a search for previously unknown peptides that possess the C-terminal am...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/324476a0
更新日期:1986-12-04 00:00:00
abstract::Recent advances in understanding the molecular basis of human X-linked muscular dystrophies have come from the identification of dystrophin, a cytoskeletal protein associated with the surface membrane. Although there is little or virtually no dystrophin in affected individuals, it is not known how this causes muscle d...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/344670a0
更新日期:1990-04-12 00:00:00
abstract::Stable associations of more than one species of symbiont within a single host cell or tissue are assumed to be rare in metazoans because competition for space and resources between symbionts can be detrimental to the host. In animals with multiple endosymbionts, such as mussels from deep-sea hydrothermal vents and ree...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35077067
更新日期:2001-05-17 00:00:00
abstract::The use of viscid silk in aerial webs as a means to capture prey was a key innovation of araneoid spiders and has contributed largely to their ecological success. Here I describe a single silk thread from a spider's web that bears glue droplets and has been preserved in Lebanese amber from the Early Cretaceous period ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/424636a
更新日期:2003-08-07 00:00:00
abstract::Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI. Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy. Here we ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11889
更新日期:2013-02-28 00:00:00
abstract::RecBCD enzyme is a processive DNA helicase and nuclease that participates in the repair of chromosomal DNA through homologous recombination. We have visualized directly the movement of individual RecBCD enzymes on single molecules of double-stranded DNA (dsDNA). Detection involves the optical trapping of solitary, flu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35053131
更新日期:2001-01-18 00:00:00
abstract::More than 50 copies of a phi X174 DNA template can be made in 60 min in an in vitro DNA replication system consisting of seven purfied replication proteins isolated from T4 bacteriophage-infected cells. By transfecting with the DNA products and assaying for the reversion of specific amber mutants, the high degree of b...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/285300a0
更新日期:1980-05-29 00:00:00
abstract::Myosin, a major contractile protein, characteristically possesses a long coiled-coil alpha-helical tail and two heads. Each head contains both an actin binding site and an ATPase site and is formed from the NH2-terminal half of one of the two heavy chains (relative molecular mass, Mr, 200,000) and a pair of light chai...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/324078a0
更新日期:1986-11-06 00:00:00
abstract::Features that were once considered exclusive to modern birds, such as feathers and a furcula, are now known to have first appeared in non-avian dinosaurs. However, relatively little is known of the early evolutionary history of the hyperinflated brain that distinguishes birds from other living reptiles and provides th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12424
更新日期:2013-09-05 00:00:00
abstract::The fusion pore is the first crucial intermediate formed during exocytosis, yet little is known about the mechanisms that determine the size and kinetic properties of these transient structures. Here, we reduced the number of available SNAREs (proteins that mediate vesicle fusion) in neurons and observed changes in tr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25481
更新日期:2018-02-08 00:00:00
abstract::Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized by elevated glycogen levels and fat deposition. These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs) secondary to von Hippel-Lindau (VHL) mutations that occu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13557
更新日期:2014-09-11 00:00:00