1,447 research outputs found
Gendered bodies under scrutiny: women’s embodied experiences of aquatic physical activity in the United Kingdom
Aquatic activity remains the second most popular form of exercise in the UK. Despite the delivery recent participation-based programmes, however, aquatic activity continues to be dominated by older women, and younger women participating with younger children. Moreover, the embodied experiences and lived meaning of participation in aquatic activity remain under-investigated. This paper presents results from five interview-based studies investigating women’s embodiment and aquatic activity. In total, 55 women were interviewed across the research programme. A number of key themes emerged, highlighting the centrality of the gendered, lived body as a key social construct contouring participant perceptions in the swimming pool environment. Feelings of anxiety and angst were reported in relation to women’s self-perceived physical deficiencies when wearing revealing swimming costumes, particularly under the critical gaze of ‘other’ bodies, whether present or imagined. Both younger and older women objectified and contrasted their bodies with those of other participants, often in a negative manner. As a consequence self-exclusion from ‘mainstream’ (i.e. mixed gender) aquatic activity was common. The shifting nature of intercorporeality emerged in the findings, with the presence of the ‘dependent’ bodies of infants shifting bodily intentionality away from the self towards others, particularly in view of perceived maternal responsibilities. Both participants’ bodies and the bodies of dependent others were perceived to be at risk of environmental and physical dangers in the swimming pool environment. Perceived risks were corporeally grounded in sensory elements of participation, relating to temperature and the threat of water and ‘dirt’ breaching bodily boundaries. Ongoing research into the implications of such sensory perceptions upon postnatal women and children’s participation in aquatic activity will also be outlined
Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib.
BackgroundEarly detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.MethodsA nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.ResultsPlasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.ConclusionsHeretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264
A novel live cell assay to measure diacylglycerol lipase α activity
Diacylglycerol lipase α (DAGLα) hydrolyses DAG to generate the principal endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) in the central nervous system. DAGLα dependent cannabinoid (CB) signalling has been implicated in numerous processes including axonal growth and guidance, adult neurogenesis and retrograde signalling at the synapse. Recent studies have implicated DAGLα as an emerging drug target for several conditions including pain and obesity. Activity assays are critical to the drug discovery process; however, measurement of diacylglycerol lipase (DAGL) activity using its native substrate generally involves low-throughput MS techniques. Some relatively high-throughput membrane based assays utilizing surrogate substrates have been reported, but these do not take into account the rate-limiting effects often associated with the ability of a drug to cross the cell membrane. In the present study, we report the development of a live cell assay to measure DAGLα activity. Two previously reported DAGLα surrogate substrates, p-nitrophenyl butyrate (PNPB) and 6,8-difluoro-4-methylumbelliferyl octanoate (DiFMUO), were evaluated for their ability to detect DAGLα activity in live cell assays using a human cell line stably expressing the human DAGLα transgene. Following optimization, the small molecule chromogenic substrate PNPB proved to be superior by providing lower background activity along with a larger signal window between transfected and parental cells when compared with the fluorogenic substrate DiFMUO. The assay was further validated using established DAGL inhibitors. In summary, the live cell DAGLα assay reported here offers an economical and convenient format to screen for novel inhibitors as part of drug discovery programmes and compliments previously reported high-throughput membrane based DAGL assays
Volumetric Flow Imaging Reveals the Importance of Vortex Ring Formation in Squid Swimming Tail-First and Arms-First
Squids use a pulsed jet and fin movements to swim both arms-first (forward) and tail-first (backward). Given the complexity of the squid multi-propulsor system, 3D velocimetry techniques are required for the comprehensive study of wake dynamics. Defocusing digital particle tracking velocimetry, a volumetric velocimetry technique, and high-speed videography were used to study arms-first and tail-first swimming of brief squid Lolliguncula brevis over a broad range of speeds [0-10 dorsal mantle lengths (DML) s-1) in a swim tunnel. Although there was considerable complexity in the wakes of these multi-propulsor swimmers, 3D vortex rings and their derivatives were prominent reoccurring features during both tail-first and arms-first swimming, with the greatest jet and fin flow complexity occurring at intermediate speeds (1.5-3.0 DML s-1). The jet generally produced the majority of thrust during rectilinear swimming, increasing in relative importance with speed, and the fins provided no thrust at speeds \u3e4.5 DML s-1. For both swimming orientations, the fins sometimes acted as stabilizers, producing negative thrust (drag), and consistently provided lift at low/intermediate speeds (\u3c2.0 DML s-1) to counteract negative buoyancy. Propulsive efficiency (η) increased with speed irrespective of swimming orientation, and eta for swimming sequences with clear isolated jet vortex rings was significantly greater (η=78.6 +/- 7.6%, mean +/- s.d.) than that for swimming sequences with clear elongated regions of concentrated jet vorticity (η=67.9 +/- 19.2%). This study reveals the complexity of 3D vortex wake flows produced by nekton with hydrodynamically distinct propulsors
Toward Morphologically Relevant Extracellular Matrix in Vitro Models: 3D Fiber Reinforced Hydrogels
The extracellular matrix (ECM) is known to play an important role in the health of cells and tissues. Not only are chemical signals transmitted via bonds and tightly controlled diffusion, but the structure of the ECM also provides important physical signaling for the cells attached to it. The structure is composed of a mesh of fibrous proteins, such as collagen, embedded in a hydrated gel matrix of glycosaminoglycans. To study cell behavior with respect to the combined morphology and mechanics of such matrices is not currently possible with the types of 3D cell culture matrices available. Most of the cell culture matrices are single-phase bio- or polymeric hydrogels. Therefore, here we developed a continuous hybrid manufacturing process to make fiber-reinforced composite hydrogels. A far field electrospinning process was used to deposit the fibrous component with the aid of guiding electrodes; and a gravity-assisted, droplet-based system controlled the rate of addition of the cell-laden hydrogel component. The addition of the fibrous component slightly increased the elastic modulus of the pure hydrogel. The cells that were embedded into the fiber-reinforced hydrogels were viable for 8 days. The cells were randomly placed in the matrix such that some had no contact to the fibers and others were initially in proximity to fibers. The cells with no contact to fibers grew into spheroidal clusters within the hydrogel, and those in proximity to the fibers spread out and grew along the fibers showing that the fiber-reinforced hydrogels are able to control cell behavior with morphological cues
Meter- to Millimeter Emission from Cool Stellar Systems : Latest Results, Synergies Across the Spectrum, and Outlook for the Next Decade
Splinter session summary, to appear in the proceedings of the 20th Cambridge Workshop on Cool Stars, Stellar Systems, and the Sun (ed. S. J. Wolk)Radio observations of cool stellar systems provide unique information on their magnetic fields, high-energy processes, and chemistry. Buoyed by powerful new instruments (e.g. ALMA, JVLA, LOFAR), advances in related fields (e.g., the Gaia astrometric revolution), and above all a renewed interest in the relevant stellar astrophysics, stellar radio astronomy is experiencing a renaissance. In this splinter session, participants took stock of the present state of stellar radio astronomy to chart a course for the field's future
Facilitating Pedagogies of Possibility in Teacher Education: Experiences of Faculty Members in a Self-Study Learning Group
This collaborative self-study explores how seven members of a Faculty Self-Study Learning Group (FS-SLG) attempt to foster cultures of inquiry with teacher candidates. In so doing, we simultaneously describe a professional learning community of teacher educators engaging in reflective practice via the teaching, learning, and enacting of self-study methodology. Findings from this collaborative self-study highlight how we attempt to translate our own efforts to be more purposeful and reflective into our teacher education practice through modeling, as well as the tensions we felt in promoting a view of teaching as a process of critical inquiry. The discussion focuses on lessons learned and potential ways forward for educators who similarly desire to embrace inquiry-based pedagogies of possibility within the existing landscape of teaching and teacher preparation
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