| 61. |
- Amar, D, et al.
(författare)
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Time trajectories in the transcriptomic response to exercise - a meta-analysis
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3471-
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training prevents multiple diseases, yet the molecular mechanisms that drive exercise adaptation are incompletely understood. To address this, we create a computational framework comprising data from skeletal muscle or blood from 43 studies, including 739 individuals before and after exercise or training. Using linear mixed effects meta-regression, we detect specific time patterns and regulatory modulators of the exercise response. Acute and long-term responses are transcriptionally distinct and we identify SMAD3 as a central regulator of the exercise response. Exercise induces a more pronounced inflammatory response in skeletal muscle of older individuals and our models reveal multiple sex-associated responses. We validate seven of our top genes in a separate human cohort. In this work, we provide a powerful resource (www.extrameta.org) that expands the transcriptional landscape of exercise adaptation by extending previously known responses and their regulatory networks, and identifying novel modality-, time-, age-, and sex-associated changes.
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| 62. |
- Amole, C., et al.
(författare)
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An experimental limit on the charge of antihydrogen
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3955-
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Tidskriftsartikel (refereegranskat)abstract
- The properties of antihydrogen are expected to be identical to those of hydrogen, and any differences would constitute a profound challenge to the fundamental theories of physics. The most commonly discussed antiatom- based tests of these theories are searches for antihydrogen- hydrogen spectral differences (tests of CPT (charge- parity- time) invariance) or gravitational differences (tests of the weak equivalence principle). Here we, the ALPHA Collaboration, report a different and somewhat unusual test of CPT and of quantum anomaly cancellation. A retrospective analysis of the influence of electric fields on antihydrogen atoms released from the ALPHA trap finds a mean axial deflection of 4.1 +/- 3.4mm for an average axial electric field of 0.51Vmm1. Combined with extensive numerical modelling, this measurement leads to a bound on the charge Qe of antihydrogen of Q (+/- 1.3 +/- 1.1 +/- 0.4)10 8. Here, e is the unit charge, and the errors are from statistics and systematic effects.
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| 63. |
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| 64. |
- Amora-Nogueira, Leonardo, et al.
(författare)
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Tropical forests as drivers of lake carbon burial
- 2022
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Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- A significant proportion of carbon (C) captured by terrestrial primary production is buried in lacustrine ecosystems, which have been substantially affected by anthropogenic activities globally. However, there is a scarcity of sedimentary organic carbon (OC) accumulation information for lakes surrounded by highly productive rainforests at warm tropical latitudes, or in response to land cover and climate change. Here, we combine new data from intensive campaigns spanning 13 lakes across remote Amazonian regions with a broad literature compilation, to produce the first spatially-weighted global analysis of recent OC burial in lakes (over ~50-100-years) that integrates both biome type and forest cover. We find that humid tropical forest lake sediments are a disproportionately important global OC sink of 7.4 Tg C yr−1 with implications for climate change. Further, we demonstrate that temperature and forest conservation are key factors in maintaining massive organic carbon pools in tropical lacustrine sediments.
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| 65. |
- Amran, Aqilah, et al.
(författare)
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The matrisome landscape controlling in vivo germ cell fates
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- The developmental fate of cells is regulated by intrinsic factors and the extracellular environment. The extracellular matrix (matrisome) delivers chemical and mechanical cues that can modify cellular development. However, comprehensive understanding of how matrisome factors control cells in vivo is lacking. Here we show that specific matrisome factors act individually and collectively to control germ cell development. Surveying development of undifferentiated germline stem cells through to mature oocytes in the Caenorhabditis elegans germ line enabled holistic functional analysis of 443 conserved matrisome-coding genes. Using high-content imaging, 3D reconstruction, and cell behavior analysis, we identify 321 matrisome genes that impact germ cell development, the majority of which (>80%) are undescribed. Our analysis identifies key matrisome networks acting autonomously and non-autonomously to coordinate germ cell behavior. Further, our results demonstrate that germ cell development requires continual remodeling of the matrisome landscape. Together, this study provides a comprehensive platform for deciphering how extracellular signaling controls cellular development and anticipate this will establish new opportunities for manipulating cell fates.
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| 66. |
- Amselem, Elias, et al.
(författare)
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Real-time single-molecule 3D tracking in E. coli based on cross-entropy minimization
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Reaching sub-millisecond 3D tracking of individual molecules in living cells would enable direct measurements of diffusion-limited macromolecular interactions under physiological conditions. Here, we present a 3D tracking principle that approaches the relevant regime. The method is based on the true excitation point spread function and cross-entropy minimization for position localization of moving fluorescent reporters. Tests on beads moving on a stage reaches 67 nm lateral and 109 nm axial precision with a time resolution of 0.84 ms at a photon count rate of 60 kHz; the measurements agree with the theoretical and simulated predictions. Our implementation also features a method for microsecond 3D PSF positioning and an estimator for diffusion analysis of tracking data. Finally, we successfully apply these methods to track the Trigger Factor protein in living bacterial cells. Overall, our results show that while it is possible to reach sub-millisecond live-cell single-molecule tracking, it is still hard to resolve state transitions based on diffusivity at this time scale.
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| 67. |
- An, T., et al.
(författare)
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Evolving parsec-scale radio structure in the most distant blazar known
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Blazars are a sub-class of quasars with Doppler boosted jets oriented close to the line of sight, and thus efficient probes of supermassive black hole growth and their environment, especially at high redshifts. Here we report on Very Long Baseline Interferometry observations of a blazar J0906 + 6930 at z = 5.47, which enabled the detection of polarised emission and measurement of jet proper motion at parsec scales. The observations suggest a less powerful jet compared with the general blazar population, including lower proper motion and bulk Lorentz factor. This coupled with a previously inferred high accretion rate indicate a transition from an accretion radiative power to a jet mechanical power based transfer of energy and momentum to the surrounding gas. While alternative scenarios could not be fully ruled out, our results indicate a possibly nascent jet embedded in and interacting with a dense medium resulting in a jet bending.
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| 68. |
- Andermann, Tobias, et al.
(författare)
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The origin and evolution of open habitats in North America inferred by Bayesian deep learning models
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Some of the most extensive terrestrial biomes today consist of open vegetation, including temperate grasslands and tropical savannas. These biomes originated relatively recently in Earth’s history, likely replacing forested habitats in the second half of the Cenozoic. However, the timing of their origination and expansion remains disputed. Here, we present a Bayesian deep learning model that utilizes information from fossil evidence, geologic models, and paleoclimatic proxies to reconstruct paleovegetation, placing the emergence of open habitats in North America at around 23 million years ago. By the time of the onset of the Quaternary glacial cycles, open habitats were covering more than 30% of North America and were expanding at peak rates, to eventually become the most prominent natural vegetation type today. Our entirely data-driven approachdemonstrates how deep learning can harness unexplored signals from complex data sets to provide insights into the evolution of Earth’s biomes in time and space.
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| 69. |
- Andersson, Alma, et al.
(författare)
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Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases. While transcriptomics have enhanced our understanding for cancer, spatial transcriptomics enable the characterisation of cellular interactions. Here, the authors integrate single cell data with spatial information for HER2 + tumours and develop tools for the prediction of interactions between tumour-infiltrating cells.
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| 70. |
- Andersson, David A., et al.
(författare)
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TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Delta(9)-tetrahydrocannabiorcol
- 2011
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- TRPA1 is a unique sensor of noxious stimuli and, hence, a potential drug target for analgesics. Here we show that the antinociceptive effects of spinal and systemic administration of acetaminophen (paracetamol) are lost in Trpa1(-/-) mice. The electrophilic metabolites N-acetyl-p-benzoquinoneimine and p-benzoquinone, but not acetaminophen itself, activate mouse and human TRPA1. These metabolites also activate native TRPA1 and, as a consequence, reduce voltage-gated calcium and sodium currents in primary sensory neurons. The N-acetyl-p-benzoquinoneimine metabolite l-cysteinyl-S-acetaminophen was detected in the mouse spinal cord after systemic acetaminophen administration. In the hot-plate test, intrathecal administration of N-acetyl-p-benzoquinoneimine, p-benzoquinone and the electrophilic TRPA1 activator cinnamaldehyde produced antinociception that was lost in Trpa1(-/-) mice. Intrathecal injection of a non-electrophilic cannabinoid, Delta(9)-tetrahydrocannabiorcol, also produced TRPA1-dependent antinociception in this test. Our study provides a molecular mechanism for the antinociceptive effect of acetaminophen and discloses spinal TRPA1 activation as a potential pharmacological strategy to alleviate pain.
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