Abstract:
:The ability of cytosolic lipopolysaccharide (LPS) to activate caspase-11-dependent nonclassical inflammasome is intricately controlled to avoid excessive inflammatory responses. However, very little is known about the regulatory role of various metabolic pathways in the control of caspase-11 activation. Here, we demonstrate that l-adrenaline can act on receptor ADRA2B to inhibit the activation of the caspase-11 inflammasome by cytosolic LPS or Escherichia coli infection in macrophages. l-adrenaline-induced cAMP production via the enzyme ADCY4 promotes protein kinase A (PKA) activation, which then blocks the caspase-11-mediated proteolytic maturation of interleukin-1β, gasdermin D (GSDMD) cleavage, and consequent DAMP release. Inhibition of PDE8A-mediated cAMP hydrolysis limits caspase-11 inflammasome activation and pyroptosis in macrophages. Consequently, pharmacological modulation of the ADRA2B-ADCY4-PDE8A-PKA axis, knockout of caspase-11 (Casp11-/- ), or Gsdmd inactivation (GsdmdI105N/I105N ) similarly protects against LPS-induced lethality in poly(I:C)-primed mice. Our results provide previously unidentified mechanistic insight into immune regulation by cAMP and represent a proof of concept that immunometabolism constitutes a potential therapeutic target in sepsis.
journal_name
Sci Advjournal_title
Science advancesauthors
Chen R,Zeng L,Zhu S,Liu J,Zeh HJ,Kroemer G,Wang H,Billiar TR,Jiang J,Tang D,Kang Rdoi
10.1126/sciadv.aav5562subject
Has Abstractpub_date
2019-05-22 00:00:00pages
eaav5562issue
5issn
2375-2548pii
aav5562journal_volume
5pub_type
杂志文章相关文献
Science Advances文献大全abstract::Granular dynamics govern earthquakes, avalanches, and landslides and are of fundamental importance in a variety of industries ranging from energy to pharmaceuticals to agriculture. Nonetheless, our understanding of the underlying physics is poor because we lack spatially and temporally resolved experimental measuremen...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1701879
更新日期:2017-09-15 00:00:00
abstract::Presently, the Indian Ocean (IO) resides in a climate state that prevents strong year-to-year climate variations. This may change under greenhouse warming, but the mechanisms remain uncertain, thus limiting our ability to predict future changes in climate extremes. Using climate model simulations, we uncover the emerg...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay7684
更新日期:2020-05-06 00:00:00
abstract::To achieve global elimination of hepatitis C virus (HCV), an effective cross-genotype vaccine is needed. The HCV envelope glycoprotein E2 is the main target for neutralizing antibodies (nAbs), which aid in HCV clearance and protection. E2 is structurally flexible and functions in engaging host receptors. Many nAbs bin...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb5642
更新日期:2020-07-24 00:00:00
abstract::The structure of many real-world systems is best captured by networks consisting of several interaction layers. Understanding how a multilayered structure of connections affects the synchronization properties of dynamical systems evolving on top of it is a highly relevant endeavor in mathematics and physics and has po...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1601679
更新日期:2016-11-16 00:00:00
abstract::The fabrication of three-dimensional (3D) objects by polymer self-assembly in solution is extremely challenging. Here, multi-tori mesostructures were obtained from the crystallization-driven self-assembly of a coil-crystalline block copolymer (BCP) in mixed solvents. The formation of these structures follows a multist...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz7301
更新日期:2020-04-15 00:00:00
abstract::Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is one of the smallest known repressors (66 amino acids), and activators are typically much larger (e.g., λ cI, 237 amino acids). Previ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aba2728
更新日期:2020-06-10 00:00:00
abstract::The Wiedemann-Franz (WF) law has been tested in numerous solids, but the extent of its relevance to the anomalous transverse transport and the topological nature of the wave function, remains an open question. Here, we present a study of anomalous transverse response in the noncollinear antiferromagnet Mn3Ge extended ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz3522
更新日期:2020-04-24 00:00:00
abstract::By developing new computational models, we examine how enzymatic reactions on an underlying surface can be harnessed to direct the motion and organization of reagent-laden microcapsules in a fluid-filled microchannel. In the presence of appropriate reagents, surface-bound enzymes can act as pumps, which drive large-sc...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1501835
更新日期:2016-03-18 00:00:00
abstract::Mimicking subcellular compartments containing enzymes in organisms is considered a promising approach to substitute for missing or lost cellular functions. Inspired by the multicompartment structures of cellular architectures, we present a novel multienzyme system based on hollow hydrogel microcapsules with flexible e...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat2816
更新日期:2018-06-15 00:00:00
abstract::Modeling a complex system is almost invariably a challenging task. The incorporation of experimental observations can be used to improve the quality of a model and thus to obtain better predictions about the behavior of the corresponding system. This approach, however, is affected by a variety of different errors, esp...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1501177
更新日期:2016-01-22 00:00:00
abstract::The histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors. In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells, triggering degradation of the PML-RAR oncogene. AP...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aax2746
更新日期:2020-04-08 00:00:00
abstract::We present a physically inspired model and an efficient algorithm to infer hierarchical rankings of nodes in directed networks. It assigns real-valued ranks to nodes rather than simply ordinal ranks, and it formalizes the assumption that interactions are more likely to occur between individuals with similar ranks. It ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aar8260
更新日期:2018-07-20 00:00:00
abstract::In traditional models of heteroepitaxy, the substrate serves mainly as a crystalline template for the thin-film lattice, dictating the initial roughness of the film and the degree of coherent strain. Here, performing in situ surface x-ray diffraction during the heteroepitaxial growth of LaTiO3 on SrTiO3 (001), we find...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aav0764
更新日期:2019-04-12 00:00:00
abstract::Anti-programmed cell death 1 ligand 1 (PD-L1) therapy is extraordinarily effective in select patients with cancer. However, insufficient lymphocytic infiltration, weak T cell-induced inflammation, and immunosuppressive cell accumulation in the tumor microenvironment (TME) may greatly diminish the efficacy. Here, we re...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz9240
更新日期:2020-05-15 00:00:00
abstract::Compound climate extremes are receiving increasing attention because of their disproportionate impacts on humans and ecosystems. However, risks assessments generally focus on univariate statistics. We analyze the co-occurrence of hot and dry summers and show that these are correlated, inducing a much higher frequency ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1700263
更新日期:2017-06-28 00:00:00
abstract::The source regions of mid-ocean ridge basalts (MORB) are heterogeneous, consisting of chemically and lithologically distinct domains of variable size. Partial melting of such heterogeneous mantle sources gives rise to diverse isotopic compositions of MORB and abyssal peridotites. Variations in radiogenic isotope ratio...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1701872
更新日期:2017-11-22 00:00:00
abstract::Honeybees use the waggle dance to share information about food-site locations with nestmates. However, the importance of this behavior in colony foraging success remains unclear. We tested whether spatial dance information affects colony foraging success in a human-modified temperate environment by comparing colonies ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat0450
更新日期:2019-02-13 00:00:00
abstract::Mass loss from the West Antarctic ice shelves and glaciers has been linked to basal melt by ocean heat flux. The Totten Ice Shelf in East Antarctica, which buttresses a marine-based ice sheet with a volume equivalent to at least 3.5 m of global sea-level rise, also experiences rapid basal melt, but the role of ocean f...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1601610
更新日期:2016-12-16 00:00:00
abstract::Ontogenetic studies provide clues for understanding important paleobiological aspects of extinct species. When compared to that of modern humans, the adult Neanderthal thorax was shorter, deeper, and wider. This is related to the wide Neanderthal body and is consistent with their hypothetical large requirements for en...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb4377
更新日期:2020-10-07 00:00:00
abstract::Hydrogen sulfide (H2S) is a gasotransmitter and a potential therapeutic agent. However, molecular targets relevant to its therapeutic actions remain enigmatic. Sulfide-quinone oxidoreductase (SQR) irreversibly oxidizes H2S. Therefore, SQR is assumed to inhibit H2S signaling. We now report that SQR-mediated oxidation o...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz5752
更新日期:2020-08-26 00:00:00
abstract::In Arabidopsis, the root clock regulates the spacing of lateral organs along the primary root through oscillating gene expression. The core molecular mechanism that drives the root clock periodicity and how it is modified by exogenous cues such as auxin and gravity remain unknown. We identified the key elements of the...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abd4722
更新日期:2021-01-01 00:00:00
abstract::Protected areas (PAs) are essential to biodiversity conservation, but their static boundaries may undermine their potential for protecting species under climate change. We assessed how the climatic conditions within global terrestrial PAs may change over time. By 2070, protection is expected to decline in cold and war...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay0814
更新日期:2020-06-17 00:00:00
abstract::Mobile genetic elements, such as human endogenous retroviruses (HERVs), produce proteins that regulate brain cell functions and synaptic transmission and have been implicated in the etiology of neurological and neurodevelopmental psychiatric disorders. However, the mechanisms by which these proteins of retroviral orig...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abc0708
更新日期:2020-07-17 00:00:00
abstract::A novel, thin-film platform that preserves live viruses, bacteria, antibodies, and enzymes without refrigeration for extended periods of time is described. Studies with recombinant adenovirus in an optimized formulation that supports recovery of live virus through 16 freeze-thaw cycles revealed that production of an a...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aau4819
更新日期:2020-03-04 00:00:00
abstract::The concept of repair is widely used by nature to heal molecules such as proteins, lipids, sugars, and DNA that are damaged by hydrogen atom abstraction resulting from oxidative stress. We show that this strategy, rather undocumented in the field of synthetic organic chemistry, can be used in a radical chain reaction ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat6031
更新日期:2018-07-20 00:00:00
abstract::Stroke is the most common cause of adult disability in developed countries, largely because spontaneous recovery is often incomplete, and no pharmacological means to hasten the recovery exist. It was recently shown that mesencephalic astrocyte-derived neurotrophic factor (MANF) induces alternative or M2 activation of ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aap8957
更新日期:2018-05-23 00:00:00
abstract::When a medium is rapidly heated and cooled, heat transfers to its surroundings as sound. A controllable source of this sound is realized through joule heating of thin, conductive films by an alternating current. Here, we show that arrays of these sources generate sound unique to this mechanism. From the sound alone, w...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb2752
更新日期:2020-07-01 00:00:00
abstract::Here, we demonstrate the use of pump-probe microscopy for high-resolution studies of vermilion degradation. Vermilion (mostly α-HgS), an important red pigment used in historical paintings, blackens over time, and metallic Hg and β-HgS have been implicated as possible degradation products. Conventional analysis techniq...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaw3136
更新日期:2019-06-21 00:00:00
abstract::Membrane proteins must balance the sequence constraints associated with folding and function against the hydrophobicity required for solvation within the bilayer. We recently found the expression and maturation of rhodopsin are limited by the hydrophobicity of its seventh transmembrane domain (TM7), which contains pol...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay7505
更新日期:2020-03-04 00:00:00
abstract::Rising sea levels will have overwhelmingly negative impacts on coastal communities globally. With previous research focused on how sea-level rise (SLR) affects storm-induced flooding, we show that SLR will also increase both the frequency and the intensity of tsunami-induced flooding, another significant coastal hazar...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat1180
更新日期:2018-08-15 00:00:00