229 research outputs found

    Urbanization comprehensively impairs biological rhythms in coral holobionts

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    Coral reefs are in global decline due to climate change and anthropogenic influences (Hughes et al., Conservation Biology, 27: 261–269, 2013). Near coastal cities or other densely populated areas, coral reefs face a range of additional challenges. While considerable progress has been made in understanding coral responses to acute individual stressors (Dominoni et al., Nature Ecology & Evolution, 4: 502–511, 2020), the impacts of chronic exposure to varying combinations of sensory pollutants are largely unknown. To investigate the impacts of urban proximity on corals, we conducted a year-long in-natura study—incorporating sampling at diel, monthly, and seasonal time points—in which we compared corals from an urban area to corals from a proximal non-urban area. Here we reveal that despite appearing relatively healthy, natural biorhythms and environmental sensory systems were extensively disturbed in corals from the urban environment. Transcriptomic data indicated poor symbiont performance, disturbance to gametogenic cycles, and loss or shifted seasonality of vital biological processes. Altered seasonality patterns were also observed in the microbiomes of the urban coral population, signifying the impact of urbanization on the holobiont, rather than the coral host alone. These results should raise alarm regarding the largely unknown long-term impacts of sensory pollution on the resilience and survival of coral reefs close to coastal communities

    The Recent Volcanic History of Axial Seamount: Geophysical Insights into Past Eruption Dynamics with an Eye Toward Enhanced Observations of Future Eruptions

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    To understand the processes that form oceanic crust as well as the role of submarine volcanoes in exchanging heat and chemicals with the ocean and in supporting chemosynthetic biological communities, it is essential to study underwater eruptions. The world’s most advanced underwater volcano observatory—the Ocean Observatories Initiative Cabled Array at Axial Seamount—builds upon ~30 years of sustained geophysical monitoring at this site with autonomous and remote systems. In April 2015, only months after the Cabled Array’s installation, it recorded an eruption at Axial Seamount, adding to the records of two prior eruptions in 1998 and 2011. Between eruptions, magma recharge is focused beneath the southeast part of the summit caldera, leading to steady inflation and increasing rates of seismicity. During each eruption, the volcano deflates over days to weeks, coincident with high levels of seismicity as a dike is emplaced along one of the volcano’s rifts and lava erupts on the seafloor. Cabled Array seismic data show that motions on an outward-dipping ring fault beneath the caldera accommodate the inflation and deflation. Eruptions appear to occur at a predictable level of inflation; hence, it should be possible to time deployments of additional cabled and autonomous instrumentation to further enhance observations of the next eruption

    The impact of pre-transplantation nephrectomy on quality of life in patients with autosomal dominant polycystic kidney disease

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    PURPOSE: In selected ADPKD patients, a nephrectomy is required in the work-up for a kidney transplantation. Because the impact of this procedure is unknown, we investigated the effect of pre-transplantation nephrectomy on quality of life in this group.METHODS: In this retrospective cohort study all ADPKD patients, ≄ 18 years, who received a kidney transplantation in 2 ADPKD expertise centers between January 2000 and January 2016, were asked to participate. Quality of life was assessed using three validated questionnaires on three time points. Nephrectomy was performed in preparation for transplantation.RESULTS: Two hundred seventy-six ADPKD patients (53 ± 9 years, 56.2% male) were included. 98 patients (35.5%) underwent native nephrectomy in preparation for transplantation, of which 43 underwent bilateral nephrectomy. Pre-transplantation, ADPKD-IS scores were worse in the nephrectomy group vs. no-nephrectomy group (physical: 2.9 vs. 2.3, p &lt; 0.001; emotional: 2.0 vs. 1.8, p = 0.03; fatigue: 3.0 vs. 2.3, p = 0.01). Post-transplantation and post-nephrectomy, ADPKD-IS scores improved significantly in both groups, with a significantly higher improvement in the nephrectomy group. During follow-up, all scores were still better compared to pre-transplantation. Observed physical QoL (ADPKD-IS physical 1.3 vs. 1.7, p = 0.04; SF-36 physical 50.0 vs. 41.3, p = 0.03) was better post-transplantation after bilateral nephrectomy compared to unilateral nephrectomy. In retrospect, 19.7% of patients would have liked to undergo a nephrectomy, while the decision not to perform nephrectomy was made by the treating physician.CONCLUSION: This study shows that pre-transplantation nephrectomy improves quality of life in selected ADPKD patients. Bilateral nephrectomy may be preferred, although the risk of additional complications should be weighted.</p

    Recent Advances of Biliary Stent Management

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    Recent progress in chemotherapy has prolonged the survival of patients with malignant biliary strictures, leading to increased rates of stent occlusion. Even we employed metallic stents which contributed to higher rates and longer durations of patency, and occlusion of covered metallic stents now occurs in about half of all patients during their survival. We investigated the complication and patency rate for the removal of covered metallic stents, and found that the durations were similar for initial stent placement and re-intervention. In order to preserve patient quality of life, we currently recommend the use of covered metallic stents for patients with malignant biliary obstruction because of their removability and longest patency duration, even though uncovered metallic stents have similar patency durations

    Membrane anchored IL-18 linked to constitutively active TLR4 and CD40 improves human T cell antitumor capacities for adoptive cell therapy

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    BACKGROUND: Adoptive transfer of tumor-infiltrating lymphocytes (TILs) or blood T cells genetically redirected by an antitumor TCR or CAR induces a strong antitumor response in a proportion of patients with cancer; however, the therapeutic efficacy is often limited by rapid decline in T cell functions. Coadministering supportive cytokines frequently provokes systemic side effects preventing their broad clinical application. We recently showed that cytokines can be anchored to the cell membrane in a functional fashion and that cytokine receptor signaling can synergize with TLR4 and CD40 signaling. Here, we aimed at augmenting T cell activation by simultaneous signaling through the cytokine receptor, toll-like receptor and TNF-type receptor using IL-18, TLR4 and CD40 as prototypes. METHODS: Genes were expressed on electroporation of in vitro-transcribed mRNA in CD4(+) and CD8(+) T cells from healthy donors redirected against melanoma cells with an anti-melanotransferrin CAR and in TILs derived from melanoma patients. Functional assays included the activation of signaling pathways, expression of activation and differentiation markers, cytokine secretion and killing of melanoma target cells. RESULTS: To provide IL-18 costimulation to T cells in-cis while avoiding systemic effects, we genetically anchored IL-18 to the T cell membrane, either alone (memIL-18) or fused with constitutively active (ca)TLR4 and caCD40 signaling domains arranged in tandem, creating a synthetic ‘all-in-one’ memIL-18-TLR4-CD40 receptor. MemIL-18-TLR4-CD40, but not memIL-18, triggered strong NF-ÎșB activation in cells lacking the IL-18 receptor, attesting to functionality of the TLR-CD40 moiety. While the membrane-anchored cytokine was found to act mainly in-cis, some T cell activation in-trans was also observed. The electroporated T cells exhibited spontaneous T-bet upregulation and IFN-Îł and TNF-α secretion. Melanoma-induced activation of CAR-T cells and TILs as manifested by cytokine secretion and cytolytic activity was substantially augmented by both constructs, with memIL-18-TLR4-CD40 exerting stronger effects than memIL-18 alone. CONCLUSIONS: Linking membrane anchored IL-18 with caTLR4 and caCD40 signaling in one hybrid transmembrane protein provides simultaneous activation of three T cell costimulatory pathways through one genetically engineered membrane molecule, strongly amplifying T cell functions for adoptive T cell therapy of cancer

    The VIL gene CRAWLING ELEPHANT controls maturation and differentiation in tomato via polycomb silencing

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    VERNALIZATION INSENSITIVE 3-LIKE (VIL) proteins are PHD-finger proteins that recruit the repressor complex Polycomb Repressive Complex 2 (PRC2) to the promoters of target genes. Most known VIL targets are flowering repressor genes. Here, we show that the tomato VIL gene CRAWLING ELEPHANT (CREL) promotes differentiation throughout plant development by facilitating the trimethylation of Histone H3 on lysine 27 (H3K27me3). We identified the crel mutant in a screen for suppressors of the simple-leaf phenotype of entire (e), a mutant in the AUX/IAA gene ENTIRE/SlIAA9, involved in compound-leaf development in tomato. crel mutants have increased leaf complexity, and suppress the ectopic blade growth of e mutants. In addition, crel mutants are late flowering, and have delayed and aber rant stem, root and flower development. Consistent with a role for CREL in recruiting PRC2, crel mutants show drastically reduced H3K27me3 enrichment at approximately half of the 14,789 sites enriched in wild-type plants, along with upregulation of many underlying genes. Interestingly, this reduction in H3K27me3 across the genome in crel is also associated with gains in H3K27me3 at a smaller number of sites that normally have modest levels of the mark in wild-type plants, suggesting that PRC2 activity is no longer limiting in the absence of CREL. Our results uncover a wide role for CREL in plant and organ differentiation in tomato and suggest that CREL is required for targeting PRC2 activity to, and thus silencing, a spe cific subset of polycomb targets

    Six priorities to advance the science and practice of coral reef restoration worldwide

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    Coral reef restoration is a rapidly growing movement galvanized by the accelerating degradation of the world's tropical coral reefs. The need for concerted and collaborative action focused on the recovery of coral reef ecosystems coalesced in the creation of the Coral Restoration Consortium (CRC) in 2017. In March 2020, the CRC leadership team met for a biennial review of international coral reef restoration efforts and a discussion of perceived knowledge and implementation bottlenecks that may impair scalability and efficacy. Herein we present six priorities wherein the CRC will foster scientific advancement and collaboration to: (1) increase restoration efficiency, focusing on scale and cost-effectiveness of deployment; (2) scale up larval-based coral restoration efforts, emphasizing recruit health, growth, and survival; (3) ensure restoration of threatened coral species proceeds within a population-genetics management context; (4) support a holistic approach to coral reef ecosystem restoration; (5) develop and promote the use of standardized terms and metrics for coral reef restoration; and (6) support coral reef restoration practitioners working in diverse geographic locations. These priorities are not exhaustive nor do we imply that accomplishing these tasks alone will be sufficient to restore coral reefs globally; rather these are topics where we feel the CRC community of practice can make timely and significant contributions to facilitate the growth of coral reef restoration as a practical conservation strategy. The goal for these collective actions is to provide tangible, local-scale advancements in reef condition that offset declines resulting from local and global stressors including climate change
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