427 research outputs found

    Localized Tensional Forces on PECAM-1 Elicit a Global Mechanotransduction Response via the Integrin-RhoA Pathway

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    SummaryBackgroundMechanical forces regulate cell behavior and function during development, differentiation, and tissue morphogenesis. In the vascular system, forces produced by blood flow are critical determinants not only of morphogenesis and function, but also of pathological states such as atherosclerosis. Endothelial cells (ECs) have numerous mechanotransducers, including platelet endothelial cell adhesion molecule-1 (PECAM-1) at cell-cell junctions and integrins at cell-matrix adhesions. However, the processes by which forces are transduced to biochemical signals and subsequently translated into downstream effects are poorly understood.ResultsHere, we examine mechanochemical signaling in response to direct force application on PECAM-1. We demonstrate that localized tensional forces on PECAM-1 result in, surprisingly, global signaling responses. Specifically, force-dependent activation of phosphatidylinositol 3-kinase (PI3K) downstream of PECAM-1 promotes cell-wide activation of integrins and the small GTPase RhoA. These signaling events facilitate changes in cytoskeletal architecture, including growth of focal adhesions and adaptive cytoskeletal stiffening.ConclusionsTaken together, our work provides the first evidence of a global signaling event in response to a localized mechanical stress. In addition, these data provide a possible mechanism for the differential stiffness of vessels exposed to distinct hemodynamic force patterns in vivo

    Localized Tensional Forces on PECAM-1 Elicit a Global Mechanotransduction Response via the Integrin-RhoA Pathway

    Get PDF
    Mechanical forces regulate cell behavior and function during development, differentiation, and tissue morphogenesis. In the vascular system, forces produced by blood flow are critical determinants not only of morphogenesis and function, but also pathological states such as atherosclerosis. Endothelial cells (ECs) have numerous mechanotransducers, including platelet endothelial cell adhesion molecule-1 (PECAM-1) at cell-cell junctions and integrins at cell-matrix adhesions. However, the processes by which forces are transduced to biochemical signals and subsequently translated into downstream effects are poorly understood

    Invasive Streptococcus pneumoniae in Children, Malawi, 2004–2006

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    Of 176 invasive Streptococcus pneumoniae isolates from children in Malawi, common serotypes were 1 (23%), 6A/B (18%), 14 (6%), and 23F (6%). Coverage with the 7-valent pneumococcal conjugate vaccine (PCV) was 39%; PCV10 and PCV13 increased coverage to 66% and 88%, respectively. We found chloramphenicol resistance in 27% of isolates and penicillin nonsusceptibility in 10% (by using meningitis breakpoints); all were ceftriaxone susceptible

    “I didn’t realise I was such a sausage”: Men’s Accounts of Whole-body Scanning, Body Image, and Expected Changes in Health-related Behaviours

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    Objective: Whole-body scanning is now available in stores to assist buyers in choosing well-fitting clothes. This study was designed to investigate men’s accounts of scanning, body image, and expectations of behaviour change. Design: Ten men aged 18-39 years without histories of eating disorders or previous experience of whole-body scanning, took part in semi-structured interviews before and after scanning. Data were analysed using inductive thematic analysis. Results: Pre-scan, men’s body ideals were tall, slender, and relatively muscular. Post-scan, seven reported looking shorter, fatter, thinner, and/or less symmetrical than they hoped; three were pleasantly surprised by the images. Men were interested in scans as an objective view of their bodies and as a “wake-up call” to motivate healthy behaviours. Five men intended to change their behaviour as a result of scanning, and repeat scanning was seen as a good way to monitor behavioural changes. Participants suggested that scanning may raise body concerns in other men, though downplayed impacts on their own body image. Conclusion: Whole-body scanning may encourage men to exercise and eat more healthily. However, men became more negative about their bodies as a result of seeing their body scans, so scanning needs to be carried out with supervision and support

    Simple Guide to Using Generative Artificial Intelligence Writing Tools in Research & Scholarship at UNH

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    While Artificial Intelligence (AI) technologies have existed for years, the recent arrival of widespread generative AI writing tools such as ChatGPT has provoked varied reactions in the scholarly community worldwide. Undoubtedly easy access to such tools may help to level the scholarly playing field for certain groups, particularly those with limited writing skills or proficiency with English as the primary language for written and oral communication of research and scholarship. There are, however, concerns about these tools, including, but not limited to, the accuracy, consistency, and bias of the information generated, appropriate acknowledgement of source material, and the tools’ lack of ability to reason or to understand meaning when generating output. This simple guide was developed to assist researchers and trainees to understand the fundamental issues with these technologies regarding research integrity

    Decision-making and referral processes for patients with motor neurone disease: a qualitative study of GP experiences and evaluation of a new decision-support tool

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    Background The diagnosis of motor neurone disease (MND) is known to be challenging and there may be delay in patients receiving a correct diagnosis. This study investigated the referral process for patients who had been diagnosed with MND, and whether a newly-developed tool (The Red Flags checklist) might help General Practitioners (GPs) in making referral decisions. Methods We carried out interviews with GPs who had recently referred a patient diagnosed with MND, and interviews/surveys with GPs who had not recently referred a patient with suspected MND. We collected data before the Red Flags checklist was introduced; and again one year later. We analysed the data to identify key recurring themes. Results Forty two GPs took part in the study. The presence of fasciculation was the clinical feature that most commonly led to consideration of a potential MND diagnosis. GPs perceived that their role was to make onward referrals rather than attempting to make a diagnosis, and delays in correct diagnosis tended to occur at the specialist level. A quarter of participants had some awareness of the newly-developed tool; most considered it useful, if incorporated into existing systems. Conclusions While fasciculation is the most common symptom associated with MND, other bulbar, limb or respiratory features, together with progression should be considered. There is a need for further research into how decision-support tools should be designed and provided, in order to best assist GPs with referral decisions. There is also a need for further work at the level of secondary care, in order that referrals made are re-directed appropriately

    Community science for coastal acidification monitoring and research

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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 Gassett, P. R., O’Brien-Clayton, K., Bastidas, C., Rheuban, J. E., Hunt, C., Turner, E., Liebman, M., Silva, E., Pimenta, A., Grear, J., Motyka, J., McCorkle, D., Stancioff, E., Brady, D., & Strong, A. Community science for coastal acidification monitoring and research. Coastal Management, 49(5), (2021): 510-531, https://doi.org/10.1080/08920753.2021.1947131.Ocean and coastal acidification (OCA) present a unique set of sustainability challenges at the human-ecological interface. Extensive biogeochemical monitoring that can assess local acidification conditions, distinguish multiple drivers of changing carbonate chemistry, and ultimately inform local and regional response strategies is necessary for successful adaptation to OCA. However, the sampling frequency and cost-prohibitive scientific equipment needed to monitor OCA are barriers to implementing the widespread monitoring of dynamic coastal conditions. Here, we demonstrate through a case study that existing community-based water monitoring initiatives can help address these challenges and contribute to OCA science. We document how iterative, sequential outreach, workshop-based training, and coordinated monitoring activities through the Northeast Coastal Acidification Network (a) assessed the capacity of northeastern United States community science programs and (b) engaged community science programs productively with OCA monitoring efforts. Our results (along with the companion manuscript) indicate that community science programs are capable of collecting robust scientific information pertinent to OCA and are positioned to monitor in locations that would critically expand the coverage of current OCA research. Furthermore, engaging community stakeholders in OCA science and outreach enabled a platform for dialogue about OCA among other interrelated environmental concerns and fostered a series of co-benefits relating to public participation in resource and risk management. Activities in support of community science monitoring have an impact not only by increasing local understanding of OCA but also by promoting public education and community participation in potential adaptation measures.AGU Centennial Grant NOAA OAP OFFICE North American Association for Environmental Education Curtis and Edith Munson Foundation Sea Grant programs within the region Senator George J. Mitchell Center for Sustainability Solutions Funding acknowledgment: MIT Sea Grant award NA18OAR4170105 to Bastidas NERACOOS The WestWind foundation (to Rheuban) Woods Hole Sea Grant (NOAA Grant No. NA18OAR4170104

    Potential of Australian Bermudagrasses (\u3cem\u3eCynodon\u3c/em\u3e spp.) for Pasture in Subtropical Australia

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    In Australia, little work has been carried out on the improvement of tropical or subtropical pastures in recent years. There seems to be an increasing demand for pastures that can withstand heavy grazing, while producing high yields of high quality forage in the humid subtropical regions of Australia. Most graziers, who live in these areas, have small acreages, which they graze intensively. Cynodon spp. represent a potential source of grasses with these attributes. This study will evaluate the pasture potential of a large number of bermudagrass (Cynodon spp.) ecotypes collected from across Australia

    The effects of anthropogenic noise and urban habitats on song structure in a vocal mimic; the gray catbird (Dumetella carolinensis) sings higher frequencies in noisier habitats

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    In urban and human-modified landscapes, animals face novel selection pressures resulting from differences in habitat structure and increased anthropogenic noise. Urban noise pollution can negatively impact songbirds because low-frequency noise often masks portions of birds’ mating signals and reduces signal transmission. Previous research has demonstrated that the songs of birds in more urban habitats have structural differences that can enhance signal transmission when noise is present. The majority of these studies have focused on species that deliver short, stereotyped songs and have limited repertoires. Gray catbirds (Dumetella carolinensis, family: Mimidae) sing long bouts containing imitated, improvised, and invented song elements, and therefore may have an increased ability to vary songs in response to noise. We hypothesized that aspects of developed habitats including loud anthropogenic noise and changes to land cover would impact catbirds’ song structural parameters, including song minimum, peak, and maximum frequency, frequency bandwidth, and entropy. We recorded and processed songs from 42 male catbirds and analyzed over 18,000 song elements from sites along an urban gradient from western Virginia to the Washington, DC metropolitan region. We quantified the urban intensity at each site-centroid based on percent canopy cover, percent impervious surface, and noise level. Song features such as minimum, maximum, and peak frequency increased significantly as noise levels increased, demonstrating that catbirds in noisier areas sing higher frequency songs compared to individuals in quieter habitats. Land cover variables also significantly predicted certain song features such as maximum frequency (impervious surface) or entropy (canopy cover). These structural differences in catbird song can limit the negative effects of environmental noise-masking, even for their long song bouts, and suggest that vocal mimics respond to anthropogenic noise. Future studies could investigate repertoire size and composition along an urban gradient and if these structural differences lead to functional consequences for the songs of vocal mimics

    Biotransformation of Silver Released from Nanoparticle Coated Titanium Implants Revealed in Regenerating Bone

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    Antimicrobial silver nanoparticle coatings have attracted interest for reducing prosthetic joint infection. However, few studies report in vivo investigations of the biotransformation of silver nanoparticles within the regenerating tissue and its impact on bone formation. We present a longitudinal investigation of the osseointegration of silver nanoparticle-coated additive manufactured titanium implants in rat tibial defects. Correlative imaging at different time points using nanoscale secondary ion mass spectrometry, transmission electron microscopy (TEM), histomorphometry, and 3D X-ray microcomputed tomography provided quantitative insight from the nano- to macroscales. The quality and quantity of newly formed bone is comparable between the uncoated and silver coated implants. The newly formed bone demonstrates a trabecular morphology with bone being located at the implant surface, and at a distance, at two weeks. Nanoscale elemental mapping of the bone−implant interface showed that silver was present primarily in the osseous tissue and colocalized with sulfur. TEM revealed silver sulfide nanoparticles in the newly regenerated bone, presenting strong evidence that the previously in vitro observed biotransformation of silver to silver sulfide occurs in vivo
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