114 research outputs found

    Controlled microfluidics to examine growth-factor induced migration of neural progenitors in the Drosophila visual system

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    BACKGROUND: The developing visual system in Drosophila melanogaster provides an excellent model with which to examine the effects of changing microenvironments on neural cell migration via microfluidics, because the combined experimental system enables direct genetic manipulation, in vivo observation, and in vitro imaging of cells, post-embryo. Exogenous signaling from ligands such as fibroblast growth factor (FGF) is well-known to control glia differentiation, cell migration, and axonal wrapping central to vision. NEW METHOD: The current study employs a microfluidic device to examine how controlled concentration gradient fields of FGF are able to regulate the migration of vision-critical glia cells with and without cellular contact with neuronal progenitors. RESULTS: Our findings quantitatively illustrate a concentration-gradient dependent chemotaxis toward FGF, and further demonstrate that glia require collective and coordinated neuronal locomotion to achieve directionality, sustain motility, and propagate long cell distances in the visual system. COMPARISON WITH EXISTING METHOD(S): Conventional assays are unable to examine concentration- and gradient-dependent migration. Our data illustrate quantitative correlations between ligand concentration/gradient and glial cell distance traveled, independent or in contact with neurons. CONCLUSIONS: Microfluidic systems in combination with a genetically-amenable experimental system empowers researchers to dissect the signaling pathways that underlie cellular migration during nervous system development. Our findings illustrate the need for coordinated neuron-glia migration in the Drosophila visual system, as only glia within heterogeneous populations exhibited increasing motility along distances that increased with increasing FGF concentration. Such coordinated migration and chemotactic dependence can be manipulated for potential therapeutic avenues for NS repair and/or disease treatment

    Hypotheses for the Origin of the Hypanis Fan-Shaped Deposit at the Edge of the Chryse Escarpment, Mars: Is it a Delta?

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    We investigated the origin of the fan-shaped deposit at the end of Hypanis Valles that has previously been proposed as an ExoMars, Mars 2020, and human mission candidate landing site, and found evidence that the landform is an ancient delta. Previous work suggests that the deposit originated from a time of fluvial activity both distinct from and prior to catastrophic outflow, and crater counting placed the deposit’s age at  ≥ 3.6 Ga. We found over 30 thin sedimentary strata in the proposed delta wall, and from our slope analysis conclude that the fluvial sequence is consistent with a lowering/retreating shoreline. We measured nearly horizontal bedding dip angles ranging from 0° to 2° over long stretches of cliff and bench exposures seen in HiRISE images and HiRISE stereo DTMs. From THEMIS night IR images we determined that the fan-shaped deposit has a low thermal inertia (150-240 Jm-2 K-1 s-1/2) and the surrounding darker-toned units correspond to thermal inertia values as high as 270-390 Jm-2 K-1 s-1/2. We interpret these findings to indicate that the fan-shaped deposit consists mostly of silt-sized and possibly finer grains, and that the extremely low grade and large lateral extent of these beds implies that the depositional environment was calm and relatively long-lived. We interpret the geomorphology and composition as incompatible with an alluvial fan or mudflow hypothesis. From our stratigraphic mapping we interpret the order of events which shaped the region. After the Chryse impact, sediment filled the basin, a confined lake or sea formed allowing a large delta to be deposited near its shoreline, the water level receded to the north, darker sedimentary/volcanic units covered the region and capped the light-toned deposit as hydro-volcanic eruptions shaped the interior of Lederberg crater, freeze/thaw cycles and desiccation induced local fracturing, and finally wrinkle ridges associated with rounded cones warped the landscape following trends in degraded crater rims and existing tectonic features. The ancient deltaic deposit we observe today was largely untouched by subsequent catastrophic outflows, and its surface has been only moderately reshaped by over 3 billion years of aeolian erosion

    A short report on knowledge exchange through research-based theatre: ‘Inside out of mind’

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    The short report describes the development from page to stage of a work of theatre based on an ethnographic study. The originating research focused on the work of health care assistants (nurse's aides) whose direct impact on the quality of life of highly dependent people is often overlooked. The research followed hospital personnel on wards specialising in the 'challenging behaviour' associated with dementia in central England. Conventional research outputs failed to engage the health care assistants themselves, so we turned to theatre to remedy this. The development of the field notes into theatre was characterised by the artistic freedom given to the playwright, in contrast to more data-led approaches to theatre making. The account of the process of creating the play, Inside Out of Mind, is followed a description of how the work was received by specialist and general audiences totalling 2000+. The discussion seeks to locate the whole enterprise in relation to the field of research-based theatre and explores how the production and its associated learning events relate to definitions of research-based theatre in the light of recent attempts to encapsulate this broad and diverse methodology

    Fluorescent polymer coated capillaries as optofluidic refractometric sensors

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    A capillary microresonator platform for refractometric sensing is demonstrated by coating the interior of thick-walled silica capillaries with a sub-wavelength layer of high refractive index, dye-doped polymer. No intermediate processing, such as etching or tapering, of the capillary is required. Side illumination and detection of the polymer layer reveals a fluorescence spectrum that is periodically modulated by whispering gallery mode resonances within the layer. Using a Fourier technique to calculate the spectral resonance shifts, the fabricated capillary resonators exhibited refractometric sensitivities up to approximately 30 nm/RIU upon flowing aqueous glucose through them. These sensors could be readily integrated with existing biological and chemical separation platforms such as capillary electrophoresis and gas chromatography where such thick walled capillaries are routinely used with polymer coatings. A review of the modelling required to calculate whispering gallery eigenmodes of such inverted cylindrical resonators is also presented.Kristopher J. Rowland, Alexandre François, Peter Hoffmann, and Tanya M. Monr

    Variability in depression prevalence in early rheumatoid arthritis: a comparison of the CES-D and HAD-D Scales

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    <p>Abstract</p> <p>Background</p> <p>Depression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression.</p> <p>Methods</p> <p>Data from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression.</p> <p>Results</p> <p>Ninety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D.</p> <p>Conclusion</p> <p>The CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates.</p

    HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

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    Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation

    Electric dipole moments and the search for new physics

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    Static electric dipole moments of nondegenerate systems probe mass scales for physics beyond the Standard Model well beyond those reached directly at high energy colliders. Discrimination between different physics models, however, requires complementary searches in atomic-molecular-and-optical, nuclear and particle physics. In this report, we discuss the current status and prospects in the near future for a compelling suite of such experiments, along with developments needed in the encompassing theoretical framework.Comment: Contribution to Snowmass 2021; updated with community edits and endorsement
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