Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory cells. The mechanisms underlying psoriasis in humans and in mouse models are poorly understood, although evidence strongly points to crucial contributions of IL-17 cytokines, which signal via the obligatory adaptor CIKS/Act1. Here we identify critical roles of CIKS/Act1-mediated signaling in imiquimod-induced psoriatic inflammation, a mouse model that shares features with the human disease. We found that IL-17 cytokines/CIKS-mediated signaling into keratinocytes is essential for neutrophilic microabscess formation and contributes to hyperproliferation and markedly attenuated differentiation of keratinocytes, at least in part via direct effects. In contrast, IL-17 cytokines/CIKS-mediated signaling into nonkeratinocytes, particularly into dermal fibroblasts, promotes cellular infiltration and, importantly, leads to enhanced the accumulation of IL-17-producing γδT cells in skin, comprising a positive feed-forward mechanism. Thus, CIKS-mediated signaling is central in the development of both dermal and epidermal hallmarks of psoriasis, inducing distinct pathologies via target cell-specific effects. CIKS-mediated signaling represents a potential therapeutic target in psoriasis.
Marine N2 fixation supports a significant portion of oceanic primary production by making N2 bioavailable to planktonic communities, in the process influencing atmosphere-ocean carbon fluxes and our global climate. However, the geographical distribution and controlling factors of marine N2 fixation remain elusive largely due to sparse observations. Here we present unprecedented high-resolution underway N2 fixation estimates across over 6000 kilometers of the western North Atlantic. Unexpectedly, we find increasing N2 fixation rates from the oligotrophic Sargasso Sea to North America coastal waters, driven primarily by cyanobacterial diazotrophs. N2 fixation is best correlated to phosphorus availability and chlorophyll-a concentration. Globally, intense N2 fixation activity in the coastal oceans is validated by a meta-analysis of published observations and we estimate the annual coastal N2 fixation flux to be 16.7 Tg N. This study broadens the biogeography of N2 fixation, highlights the interplay of regulating factors, and reveals thriving diazotrophic communities in coastal waters with potential significance to the global nitrogen and carbon cycles.
Diazotrophs play a critical role in the biogeochemical cycling of nitrogen, carbon, and other elements in the global ocean. Despite their well‐recognized role, the diversity, abundance, and distribution of diazotrophs in the world's ocean remain poorly characterized largely due to limited observations. Here we update the database of diazotroph nifH gene abundances and assess how environmental factors may regulate diazotrophs at the global scale. Our meta‐analysis more than doubles the number of observations in the previous database. Using linear and nonlinear regressions, we find that the abundances of Trichodesmium, UCYN‐A, UCYN‐B, and Richelia relate differently to temperature, light, and nutrients. We further apply a random forest algorithm to estimate the global distributions of these diazotrophic groups, identifying undersampled potential hot spots of diazotrophy in the South Atlantic and southern Indian Ocean, and in coastal waters. The distinct ecophysiologies of diazotrophs highlighted here argue for separate parameterizations of different diazotrophs in model simulations.
Interleukin-17 (IL-17) is essential in host defense against extracellular bacteria and fungi, especially at mucosal sites, but it also contributes significantly to inflammatory and autoimmune disease pathologies. Binding of IL-17 to its receptor leads to recruitment of adaptor protein CIKS/Act1 via heterotypic association of their respective SEFIR domains and activation of transcription factor NF-B; it is not known whether CIKS and/or NF-B are required for all gene induction events. Here we report that CIKS is essential for all IL-17-induced immediate-early genes in primary mouse embryo fibroblasts, whereas NF-B is profoundly involved. We also identify a novel subdomain in the N terminus of CIKS that is essential for IL-17-mediated NF-B activation. This domain is both necessary and sufficient for interaction between CIKS and TRAF6, an adaptor required for NF-B activation. The ability of decoy peptides to block this interaction may provide a new therapeutic strategy for intervention in IL-17-driven autoimmune and inflammatory diseases.
Marine nitrogen (N2) fixation supplies “new” nitrogen to the global ocean, supporting uptake and sequestration of carbon. Despite its central role, marine N2 fixation and its controlling factors remain elusive. In this study, we compile over 1,100 published observations to identify the dominant predictors of marine N2 fixation and derive global estimates based on the machine learning algorithms of random forest and support vector regression. We find that no single environmental property predicts N2 fixation at global scales. Our random forest and support vector regression algorithms, trained with sampling coordinates and month, solar radiation, wind speed, sea surface temperature, sea surface salinity, surface nitrate, surface phosphate, surface excess phosphorus, minimum oxygen in upper 500 m, photosynthetically available radiation, mixed layer depth, averaged photosynthetically available radiation in the mixed layer, and chlorophyll‐a concentration, estimate global marine N2 fixation ranging from 68 to 90 Tg N/year. Comparison of our machine learning estimates and 11 other model outputs currently available in literature shows substantial discrepancies in the global magnitude and spatial distribution of marine N2 fixation, especially in the tropics and in high latitudes. The large uncertainties in marine N2 fixation highlighted in our study argue for increased and more coordinated efforts using geochemical tracers, modeling, and observations over broad ocean regions.
Summary Bcl-3 is an atypical member of the IκB family that modulates transcription in the nucleus via association with p50 (NF-κB1) or p52 (NF-κB2) homodimers. Despite evidence attesting to the overall physiologic importance of Bcl-3, little is known about its cell-specific functions or mechanisms. Here we demonstrate a T cell-intrinsic function of Bcl-3 in autoimmunity. Bcl-3-deficient T cells failed to induce disease in T cell transfer-induced colitis and experimental autoimmune encephalomyelitis. The protection against disease correlated with a decrease in Th1 cells that produced the cytokines IFNγ- and GM-CSF, and an increase in Th17 cells. Although differentiation into Th1 cells was not impaired in the absence of Bcl-3, differentiated Th1 cells converted to less pathogenic Th17-like cells, in part via mechanisms involving expression of the RORγt transcription factor. Thus, Bcl-3 constrained Th1 cell plasticity and promoted pathogenicity by blocking conversion to Th17-like cells, revealing a unique type of regulation that shapes adaptive immunity.
Droughts and climate-change-driven warming are leading to more frequent and intense wildfires [1][2][3] , arguably contributing to the severe 2019-2020 Australian wildfires 4 . The environmental and ecological impacts of the fires include loss of habitats and the emission of substantial amounts of atmospheric aerosols [5][6][7] . Aerosol emissions from wildfires can lead to the atmospheric transport of macronutrients and bio-essential trace metals such as nitrogen and iron, respectively [8][9][10] . It has been suggested that the oceanic deposition of wildfire aerosols can relieve nutrient limitations and, consequently, enhance marine productivity 11,12 , but direct observations are lacking. Here we use satellite and autonomous biogeochemical Argo float data to evaluate the effect of 2019-2020 Australian wildfire aerosol deposition on phytoplankton productivity. We find anomalously widespread phytoplankton blooms from December 2019 to March 2020 in the Southern Ocean downwind of Australia. Aerosol samples originating from the Australian wildfires contained a high iron content and atmospheric trajectories show that these aerosols were likely to be transported to the bloom regions, suggesting that the blooms resulted from the fertilization of the iron-limited waters of the Southern Ocean. Climate models project more frequent and severe wildfires in many regions [1][2][3] . A greater appreciation of the links between wildfires, pyrogenic aerosols 13 , nutrient cycling and marine photosynthesis could improve our understanding of the contemporary and glacialinterglacial cycling of atmospheric CO 2 and the global climate system.Human activity is altering the global water and carbon cycles 14 . While the risk of drought associated with climate change varies regionally, warming and drying will increase the risk of more frequent and intense wildfires 1-3 . In turn, wildfires are increasingly viewed as a first-order control on climate. Among other things, wildfires change the Earth's radiative forcing by emitting greenhouse gases and aerosols 15 . The feedbacks between climate and wildfires are complex and often poorly represented in climate models, leading to high uncertainty in future projections.The austral summer of 2019-2020 was one of the most severe wildfire seasons in Australian history. Millions of hectares of vegetation were burned, having ecological, environmental and socioeconomical impacts 5,16 . It is estimated that nearly 3 billion animals may have died or been displaced 17 . According to a study by van der Velde et al. published in this issue of Nature 18 , approximately 715 million tonnes of CO 2 (195 Tg C) were released into the atmosphere during the fire period, exceeding Australia's 2018 anthropogenic CO 2 emissions of 537.4 million tonnes (147 Tg C) 19 .The 2019-2020 Australian wildfires (known in Australia as bushfires) also released an enormous amount of aerosols into the atmosphere 6,7 . Aerosols can influence terrestrial and marine biogeochemistry 20 , via supplying soluble forms of nitrogen 8 , ph...
The goal of the EXport Processes in the Ocean from RemoTe Sensing (EXPORTS) field campaign is to develop a predictive understanding of the export, fate, and carbon cycle impacts of global ocean net primary production. To accomplish this goal, observations of export flux pathways, plankton community composition, food web processes, and optical, physical, and biogeochemical (BGC) properties are needed over a range of ecosystem states. Here we introduce the first EXPORTS field deployment to Ocean Station Papa in the Northeast Pacific Ocean during summer of 2018, providing context for other papers in this special collection. The experiment was conducted with two ships: a Process Ship, focused on ecological rates, BGC fluxes, temporal changes in food web, and BGC and optical properties, that followed an instrumented Lagrangian float; and a Survey Ship that sampled BGC and optical properties in spatial patterns around the Process Ship. An array of autonomous underwater assets provided measurements over a range of spatial and temporal scales, and partnering programs and remote sensing observations provided additional observational context. The oceanographic setting was typical of late-summer conditions at Ocean Station Papa: a shallow mixed layer, strong vertical and weak horizontal gradients in hydrographic properties, sluggish sub-inertial currents, elevated macronutrient concentrations and low phytoplankton abundances. Although nutrient concentrations were consistent with previous observations, mixed layer chlorophyll was lower than typically observed, resulting in a deeper euphotic zone. Analyses of surface layer temperature and salinity found three distinct surface water types, allowing for diagnosis of whether observed changes were spatial or temporal. The 2018 EXPORTS field deployment is among the most comprehensive biological pump studies ever conducted. A second deployment to the North Atlantic Ocean occurred in spring 2021, which will be followed by focused work on data synthesis and modeling using the entire EXPORTS data set.
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