Trajectories of childhood immune development and respiratory health relevant to asthma and allergy.

Abstract:

:Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk 'atopic' cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma.

journal_name

Elife

journal_title

eLife

authors

Tang HH,Teo SM,Belgrave DC,Evans MD,Jackson DJ,Brozynska M,Kusel MM,Johnston SL,Gern JE,Lemanske RF,Simpson A,Custovic A,Sly PD,Holt PG,Holt KE,Inouye M

doi

10.7554/eLife.35856

subject

Has Abstract

pub_date

2018-10-15 00:00:00

issn

2050-084X

pii

35856

journal_volume

7

pub_type

杂志文章

相关文献

eLife文献大全
  • Mapping mutational effects along the evolutionary landscape of HIV envelope.

    abstract::The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino a...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.34420

    authors: Haddox HK,Dingens AS,Hilton SK,Overbaugh J,Bloom JD

    更新日期:2018-03-28 00:00:00

  • Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease.

    abstract::Replication-dependent (RD) core histone mRNA produced during S-phase is the only known metazoan protein-coding mRNA presenting a 3' stem-loop instead of the otherwise universal polyA tail. A metallo β-lactamase (MBL) fold enzyme, cleavage and polyadenylation specificity factor 73 (CPSF73), is proposed to be the sole e...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.39865

    authors: Pettinati I,Grzechnik P,Ribeiro de Almeida C,Brem J,McDonough MA,Dhir S,Proudfoot NJ,Schofield CJ

    更新日期:2018-12-03 00:00:00

  • Homeostatic control of cell wall hydrolysis by the WalRK two-component signaling pathway in Bacillus subtilis.

    abstract::Bacterial cells are encased in a peptidoglycan (PG) exoskeleton that protects them from osmotic lysis and specifies their distinct shapes. Cell wall hydrolases are required to enlarge this covalently closed macromolecule during growth, but how these autolytic enzymes are regulated remains poorly understood. Bacillus s...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.52088

    authors: Dobihal GS,Brunet YR,Flores-Kim J,Rudner DZ

    更新日期:2019-12-06 00:00:00

  • Hedgehog signaling is required for endomesodermal patterning and germ cell development in the sea anemone Nematostella vectensis.

    abstract::Two distinct mechanisms for primordial germ cell (PGC) specification are observed within Bilatera: early determination by maternal factors or late induction by zygotic cues. Here we investigate the molecular basis for PGC specification in Nematostella, a representative pre-bilaterian animal where PGCs arise as paired ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.54573

    authors: Chen CY,McKinney SA,Ellington LR,Gibson MC

    更新日期:2020-09-24 00:00:00

  • Getting to grips with circular chromosomes.

    abstract::A strain of budding yeast that contains one large chromosome reveals how the telomere capping complex CST maintains linear but not circular chromosomes. ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.60150

    authors: Nugent C,Sugimoto K

    更新日期:2020-08-05 00:00:00

  • De-repression of the RAC activator ELMO1 in cancer stem cells drives progression of TGFβ-deficient squamous cell carcinoma from transition zones.

    abstract::Squamous cell carcinomas occurring at transition zones are highly malignant tumors with poor prognosis. The identity of the cell population and the signaling pathways involved in the progression of transition zone squamous cell carcinoma are poorly understood, hence representing limited options for targeted therapies....

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.22914

    authors: McCauley HA,Chevrier V,Birnbaum D,Guasch G

    更新日期:2017-02-21 00:00:00

  • Mutationally-activated PI3'-kinase-α promotes de-differentiation of lung tumors initiated by the BRAFV600E oncoprotein kinase.

    abstract::Human lung adenocarcinoma exhibits a propensity for de-differentiation, complicating diagnosis and treatment, and predicting poorer patient survival. In genetically engineered mouse models of lung cancer, expression of the BRAFV600E oncoprotein kinase initiates the growth of benign tumors retaining characteristics of ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.43668

    authors: van Veen JE,Scherzer M,Boshuizen J,Chu M,Liu A,Landman A,Green S,Trejo C,McMahon M

    更新日期:2019-08-27 00:00:00

  • Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing.

    abstract::In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated....

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.03790

    authors: Denoth-Lippuner A,Krzyzanowski MK,Stober C,Barral Y

    更新日期:2014-11-17 00:00:00

  • The structure of the COPII transport-vesicle coat assembled on membranes.

    abstract::Coat protein complex II (COPII) mediates formation of the membrane vesicles that export newly synthesised proteins from the endoplasmic reticulum. The inner COPII proteins bind to cargo and membrane, linking them to the outer COPII components that form a cage around the vesicle. Regulated flexibility in coat architect...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.00951

    authors: Zanetti G,Prinz S,Daum S,Meister A,Schekman R,Bacia K,Briggs JA

    更新日期:2013-09-17 00:00:00

  • Estimating and interpreting nonlinear receptive field of sensory neural responses with deep neural network models.

    abstract::Our understanding of nonlinear stimulus transformations by neural circuits is hindered by the lack of comprehensive yet interpretable computational modeling frameworks. Here, we propose a data-driven approach based on deep neural networks to directly model arbitrarily nonlinear stimulus-response mappings. Reformulatin...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.53445

    authors: Keshishian M,Akbari H,Khalighinejad B,Herrero JL,Mehta AD,Mesgarani N

    更新日期:2020-06-26 00:00:00

  • Viral genome structures are optimal for capsid assembly.

    abstract::Understanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermodynamics. In contra...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.00632

    authors: Perlmutter JD,Qiao C,Hagan MF

    更新日期:2013-06-14 00:00:00

  • The functional organization of descending sensory-motor pathways in Drosophila.

    abstract::In most animals, the brain controls the body via a set of descending neurons (DNs) that traverse the neck. DN activity activates, maintains or modulates locomotion and other behaviors. Individual DNs have been well-studied in species from insects to primates, but little is known about overall connectivity patterns acr...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.34272

    authors: Namiki S,Dickinson MH,Wong AM,Korff W,Card GM

    更新日期:2018-06-26 00:00:00

  • The palmitoyl acyltransferase ZDHHC14 controls Kv1-family potassium channel clustering at the axon initial segment.

    abstract::The palmitoyl acyltransferase (PAT) ZDHHC14 is highly expressed in the hippocampus and is the only PAT predicted to bind Type-I PDZ domain-containing proteins. However, ZDHHC14's neuronal roles are unknown. Here, we identify the PDZ domain-containing Membrane-associated Guanylate Kinase (MaGUK) PSD93 as a direct ZDHHC...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.56058

    authors: Sanders SS,Hernandez LM,Soh H,Karnam S,Walikonis RS,Tzingounis AV,Thomas GM

    更新日期:2020-11-13 00:00:00

  • Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery.

    abstract::Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell aut...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.16807

    authors: Mahoney RE,Azpurua J,Eaton BA

    更新日期:2016-08-15 00:00:00

  • Building for the future.

    abstract::As the staff of the MRC Laboratory of Molecular Biology settle into their new building in Cambridge, its director Hugh Pelham explains the challenges of living up to its prestigious past. ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.00856

    authors: Pelham H

    更新日期:2013-05-28 00:00:00

  • Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure.

    abstract::Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generate...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.42628

    authors: Bulley S,Fernández-Peña C,Hasan R,Leo MD,Muralidharan P,Mackay CE,Evanson KW,Moreira-Junior L,Mata-Daboin A,Burris SK,Wang Q,Kuruvilla KP,Jaggar JH

    更新日期:2018-12-04 00:00:00

  • Genomics against gonorrhoea.

    abstract::Surveillance strategies based on whole genome sequencing could help with the early identification and detection of new forms of drug-resistant gonorrhoea. ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.59379

    authors: Medland N

    更新日期:2020-06-30 00:00:00

  • Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1.

    abstract::Obesity produces a chronic inflammatory state involving the NFκB pathway, resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1. In this study, we report that these kinases attenuate β-adrenergic signaling in white adipose tissue. Treatment of 3T3-L1 adipocytes with specific inhibitors of the...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.01119

    authors: Mowers J,Uhm M,Reilly SM,Simon J,Leto D,Chiang SH,Chang L,Saltiel AR

    更新日期:2013-12-24 00:00:00

  • Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD+ in axon regeneration.

    abstract::The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.39756

    authors: Kim KW,Tang NH,Piggott CA,Andrusiak MG,Park S,Zhu M,Kurup N,Cherra SJ 3rd,Wu Z,Chisholm AD,Jin Y

    更新日期:2018-11-21 00:00:00

  • Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice.

    abstract::Hybrid sterility is one of the reproductive isolation mechanisms leading to speciation. Prdm9, the only known vertebrate hybrid-sterility gene, causes failure of meiotic chromosome synapsis and infertility in male hybrids that are the offspring of two mouse subspecies. Within species, Prdm9 determines the sites of pro...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.34282

    authors: Gregorova S,Gergelits V,Chvatalova I,Bhattacharyya T,Valiskova B,Fotopulosova V,Jansa P,Wiatrowska D,Forejt J

    更新日期:2018-03-14 00:00:00

  • Pathogen effectors and plant immunity determine specialization of the blast fungus to rice subspecies.

    abstract::Understanding how fungi specialize on their plant host is crucial for developing sustainable disease control. A traditional, centuries-old rice agro-system of the Yuanyang terraces was used as a model to show that virulence effectors of the rice blast fungus Magnaporthe oryzaeh play a key role in its specialization on...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.19377

    authors: Liao J,Huang H,Meusnier I,Adreit H,Ducasse A,Bonnot F,Pan L,He X,Kroj T,Fournier E,Tharreau D,Gladieux P,Morel JB

    更新日期:2016-12-23 00:00:00

  • Absent phasing of respiratory and locomotor rhythms in running mice.

    abstract::Examining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea during running exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and impose...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.61919

    authors: Hérent C,Diem S,Fortin G,Bouvier J

    更新日期:2020-12-01 00:00:00

  • How lamina-associated polypeptide 1 (LAP1) activates Torsin.

    abstract::Lamina-associated polypeptide 1 (LAP1) resides at the nuclear envelope and interacts with Torsins, poorly understood endoplasmic reticulum (ER)-localized AAA+ ATPases, through a conserved, perinuclear domain. We determined the crystal structure of the perinuclear domain of human LAP1. LAP1 possesses an atypical AAA+ f...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.03239

    authors: Sosa BA,Demircioglu FE,Chen JZ,Ingram J,Ploegh HL,Schwartz TU

    更新日期:2014-08-22 00:00:00

  • Trisomy 21 consistently activates the interferon response.

    abstract::Although it is clear that trisomy 21 causes Down syndrome, the molecular events acting downstream of the trisomy remain ill defined. Using complementary genomics analyses, we identified the interferon pathway as the major signaling cascade consistently activated by trisomy 21 in human cells. Transcriptome analysis rev...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.16220

    authors: Sullivan KD,Lewis HC,Hill AA,Pandey A,Jackson LP,Cabral JM,Smith KP,Liggett LA,Gomez EB,Galbraith MD,DeGregori J,Espinosa JM

    更新日期:2016-07-29 00:00:00

  • Real-time experimental control using network-based parallel processing.

    abstract::Modern neuroscience research often requires the coordination of multiple processes such as stimulus generation, real-time experimental control, as well as behavioral and neural measurements. The technical demands required to simultaneously manage these processes with high temporal fidelity is a barrier that limits the...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.40231

    authors: Kim B,Kenchappa SC,Sunkara A,Chang TY,Thompson L,Doudlah R,Rosenberg A

    更新日期:2019-02-07 00:00:00

  • Repeated outbreaks drive the evolution of bacteriophage communication.

    abstract::Recently, a small-molecule communication mechanism was discovered in a range of Bacillus-infecting bacteriophages, which these temperate phages use to inform their lysis-lysogeny decision. We present a mathematical model of the ecological and evolutionary dynamics of such viral communication, and show that a communica...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.58410

    authors: Doekes HM,Mulder GA,Hermsen R

    更新日期:2021-01-18 00:00:00

  • Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice.

    abstract::Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduc...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.03781

    authors: Gallardo CM,Darvas M,Oviatt M,Chang CH,Michalik M,Huddy TF,Meyer EE,Shuster SA,Aguayo A,Hill EM,Kiani K,Ikpeazu J,Martinez JS,Purpura M,Smit AN,Patton DF,Mistlberger RE,Palmiter RD,Steele AD

    更新日期:2014-09-12 00:00:00

  • An unexpected role for the yeast nucleotide exchange factor Sil1 as a reductant acting on the molecular chaperone BiP.

    abstract::Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we de...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.24141

    authors: Siegenthaler KD,Pareja KA,Wang J,Sevier CS

    更新日期:2017-03-03 00:00:00

  • Regulation of food intake by mechanosensory ion channels in enteric neurons.

    abstract::Regulation of food intake is fundamental to energy homeostasis in animals. The contribution of non-nutritive and metabolic signals in regulating feeding is unclear. Here we show that enteric neurons play a major role in regulating feeding through specialized mechanosensory ion channels in Drosophila. Modulating activi...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.04402

    authors: Olds WH,Xu T

    更新日期:2014-10-06 00:00:00

  • A common mechanism underlies changes of mind about decisions and confidence.

    abstract::Decisions are accompanied by a degree of confidence that a selected option is correct. A sequential sampling framework explains the speed and accuracy of decisions and extends naturally to the confidence that the decision rendered is likely to be correct. However, discrepancies between confidence and accuracy suggest ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.12192

    authors: van den Berg R,Anandalingam K,Zylberberg A,Kiani R,Shadlen MN,Wolpert DM

    更新日期:2016-02-01 00:00:00