192 research outputs found

    Twilight zone observation network: a distributed observation network for sustained, real-time interrogation of the ocean’s twilight zone

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Thorrold, S. R., Adams, A., Bucklin, A., Buesseler, K., Fischer, G., Govindarajan, A., Hoagland, P., Jin, D., Lavery, A., Llopez, J., Madin, L., Omand, M., Renaud, P. G., Sosik, H. M., Wiebe, P., Yoerger, D. R., & Zhang, W. Twilight zone observation network: a distributed observation network for sustained, real-time interrogation of the Ocean’s Twilight Zone. Marine Technology Society Journal, 55(3), (2021): 92–93, https://doi.org/10.4031/MTSJ.55.3.46.The ocean's twilight zone (TZ) is a vast, globe-spanning region of the ocean. Home to myriad fishes and invertebrates, mid-water fishes alone may constitute 10 times more biomass than all current ocean wild-caught fisheries combined. Life in the TZ supports ocean food webs and plays a critical role in carbon capture and sequestration. Yet the ecological roles that mesopelagic animals play in the ocean remain enigmatic. This knowledge gap has stymied efforts to determine the effects that extraction of mesopelagic biomass by industrial fisheries, or alterations due to climate shifts, may have on ecosystem services provided by the open ocean. We propose to develop a scalable, distributed observation network to provide sustained interrogation of the TZ in the northwest Atlantic. The network will leverage a “tool-chest” of emerging and enabling technologies including autonomous, unmanned surface and underwater vehicles and swarms of low-cost “smart” floats. Connectivity among in-water assets will allow rapid assimilation of data streams to inform adaptive sampling efforts. The TZ observation network will demonstrate a bold new step towards the goal of continuously observing vast regions of the deep ocean, significantly improving TZ biomass estimates and understanding of the TZ's role in supporting ocean food webs and sequestering carbon.This research is part of the Woods Hole Oceanographic Institution’s Ocean Twilight Zone Project, funded as part of The Audacious Project housed at TED

    Chromogranin-A production and fragmentation in patients with Takayasu arteritis

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    BACKGROUND: Chromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA). METHODS: Plasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1-76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling. RESULTS: Levels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension. CONCLUSIONS: The plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available

    The Lipid Transfer Protein CERT Interacts with the Chlamydia Inclusion Protein IncD and Participates to ER-Chlamydia Inclusion Membrane Contact Sites

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    Bacterial pathogens that reside in membrane bound compartment manipulate the host cell machinery to establish and maintain their intracellular niche. The hijacking of inter-organelle vesicular trafficking through the targeting of small GTPases or SNARE proteins has been well established. Here, we show that intracellular pathogens also establish direct membrane contact sites with organelles and exploit non-vesicular transport machinery. We identified the ER-to-Golgi ceramide transfer protein CERT as a host cell factor specifically recruited to the inclusion, a membrane-bound compartment harboring the obligate intracellular pathogen Chlamydia trachomatis. We further showed that CERT recruitment to the inclusion correlated with the recruitment of VAPA/B-positive tubules in close proximity of the inclusion membrane, suggesting that ER-Inclusion membrane contact sites are formed upon C. trachomatis infection. Moreover, we identified the C. trachomatis effector protein IncD as a specific binding partner for CERT. Finally we showed that depletion of either CERT or the VAP proteins impaired bacterial development. We propose that the presence of IncD, CERT, VAPA/B, and potentially additional host and/or bacterial factors, at points of contact between the ER and the inclusion membrane provides a specialized metabolic and/or signaling microenvironment favorable to bacterial development

    Glioma imaging in Europe: A survey of 220 centres and recommendations for best clinical practice

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    Objectives: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. Methods: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists’ societies and distributed via social media. Results: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24–72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minori

    The effectiveness and cost-effectiveness of strength and balance Exergames to reduce falls risk for people aged 55 years and older in UK assisted living facilities: A multi-centre, cluster randomised controlled trial

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    Background: Falls are the leading cause of fatal and non-fatal unintentional injuries in older people. The use of Exergames (active, gamified video-based exercises) is a possible innovative, community-based approach. This study aimed to determine the effectiveness of a tailored OTAGO/FaME based strength and balance Exergame programme for improving balance, maintaining function and reducing falls risk in older people. Methods: A two-arm cluster randomised controlled trial recruiting adults aged 55 years and older living in 18 assisted-living (sheltered housing) facilities (clusters) in the UK. Standard care (physiotherapy advice and leaflet) was compared to a tailored 12-week strength and balance Exergame programme, supported by physiotherapists or trained assistants. Complete-case analysis (intention to treat) was used to compare Berg Balance Scale (BBS) at baseline and at 12 weeks. Secondary outcomes included: fear of falling, mobility, falls risk, pain, mood, fatigue, cognition, healthcare utilisation and health-related quality of life; self-reported physical activity and falls. Results: Eighteen clusters were randomised (9 to each arm) with 56 participants allocated to the intervention and 50 to the control (78% female, mean age 78 years). Fourteen participants withdrew over the 12 weeks (both arms), mainly for ill health. There was an adjusted mean improvement in balance (BBS) of 6.2 (95% CI 2.4 to 10.0), reduced fear of falling (p=0.007) and pain (p=0.02) in Exergame group. Mean attendance at sessions was 69% (mean exercising time of 33 minutes/week). 24% of control group and 20% of Exergame group fell over trial period. The change in falls rates significantly favoured the intervention (incident rate ratio 0.31 (95% CI 0.16 to 0.62, p=0.001)). The point estimate of the incremental cost effectiveness ratio (ICER) was £15,209.80 per QALY. Using 10,000 bootstrap replications, at the lower bound of the NICE threshold of £20,000 per QALY, there was a 61% probability of Exergames being cost-effective, rising to 73% at the upper bound of £30,000 per QALY. Conclusions: Exergames, as delivered in this trial, improve balance, pain and fear of falling and are a cost-effective fall prevention strategy in assisted living facilities for people aged 55 years or older

    Assembly, organization, and function of the COPII coat

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    A full mechanistic understanding of how secretory cargo proteins are exported from the endoplasmic reticulum for passage through the early secretory pathway is essential for us to comprehend how cells are organized, maintain compartment identity, as well as how they selectively secrete proteins and other macromolecules to the extracellular space. This process depends on the function of a multi-subunit complex, the COPII coat. Here we describe progress towards a full mechanistic understanding of COPII coat function, including the latest findings in this area. Much of our understanding of how COPII functions and is regulated comes from studies of yeast genetics, biochemical reconstitution and single cell microscopy. New developments arising from clinical cases and model organism biology and genetics enable us to gain far greater insight in to the role of membrane traffic in the context of a whole organism as well as during embryogenesis and development. A significant outcome of such a full understanding is to reveal how the machinery and processes of membrane trafficking through the early secretory pathway fail in disease states

    Phospholipase D signaling: orchestration by PIP2 and small GTPases

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    Hydrolysis of phosphatidylcholine by phospholipase D (PLD) leads to the generation of the versatile lipid second messenger, phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be dramatically stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and, particularly, by the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 is well known as substrate for the generation of second messengers by phospholipase C, but is now also understood to recruit and/or activate a variety of actin regulatory proteins, ion channels and other signaling proteins, including PLD, by direct interaction. The synthesis of PIP2 by phosphoinositide 5-kinase (PIP5K) isoforms is tightly regulated by small GTPases and, interestingly, by PA as well, and the concerted formation of PIP2 and PA has been shown to mediate receptor-regulated cellular events. This review highlights the regulation of PLD by membrane receptors, and describes how the close encounter of PLD and PIP5K isoforms with small GTPases permits the execution of specific cellular functions
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