126 research outputs found
LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells
Melanoma cells steer out of tumours using self-generated lysophosphatidic acid (LPA) gradients. The cells break down LPA, which is present at high levels around the tumours, creating a dynamic gradient that is low in the tumour and high outside. They then also migrate up this gradient, creating a complex and evolving outward chemotactic stimulus. Here we introduce a new assay for self-generated chemotaxis, and show that raising LPA levels causes a delay in migration rather than loss of chemotactic efficiency. Knockdown of the lipid phosphatase LPP3 - but not its homologues LPP1 or LPP2 - diminishes the cell's ability to break down LPA. This is specific for chemotactically active LPAs, such as the 18:1 and 20:4 species. Inhibition of autotaxin-mediated LPA production does not diminish outward chemotaxis, but loss of LPP3-mediated LPA breakdown blocks it. Similarly, in both 2D and 3D invasion assays, knockdown of LPP3 diminishes melanoma cells' ability to invade. Our results demonstrate that LPP3 is the key enzyme in melanoma cells' breakdown of LPA, and confirm the importance of attractant breakdown in LPA-mediated cell steering
Effectiveness of interventions to support the early detection of skin cancer through skin self-examination: a systematic review and meta-analysis.
BACKGROUND: As skin cancer incidence rises, there is a need to evaluate early detection interventions by the public using skin self-examination (SSE); however, the literature focuses on primary prevention. No systematic reviews have evaluated the effectiveness of such SSE interventions. OBJECTIVES: To systematically examine, map, appraise and synthesize, qualitatively and quantitatively, studies evaluating the early detection of skin cancer, using SSE interventions. METHODS: This is a systematic review (narrative synthesis and meta-analysis) examining randomized controlled trials (RCTs) and quasiexperimental, observational and qualitative studies, published in English, using PRISMA and National Institute for Health and Care Excellence guidance. The MEDLINE, Embase and PsycINFO databases were searched through to April 2015 (updated in April 2018 using MEDLINE). Risk-of-bias assessment was conducted. RESULTS: Included studies (n = 18), totalling 6836 participants, were derived from 22 papers; these included 12 RCTs and five quasiexperiments and one complex-intervention development. More studies (n = 10) focused on targeting high-risk groups (surveillance) than those at no higher risk (screening) (n = 8). Ten (45%) study interventions were theoretically underpinned. All of the study outcomes were self-reported, behaviour related and nonclinical in nature. Meta-analysis demonstrated the impact of the intervention on the degree of SSE activity from five studies, especially in the short term (up to 4 months) (odds ratio 2·31, 95% confidence interval 1·90-2·82), but with small effect sizes. Risk-of-bias assessment indicated that 61% of the studies (n = 11) were of weak quality. CONCLUSIONS: Four RCTs and a quasiexperimental study indicate that some interventions can enhance SSE activity and so are more likely to aid early detection of skin cancer. However, the actual clinical impact remains unclear, and this is based on overall weak study (evidence) quality
Experimental phase function and degree of linear polarization curve of olivine and spinel and the origin of the Barbarian polarization behaviour
We explore experimentally possible explanations of the polarization curves of the sunlight reflected by the Barbarian asteroids. Their peculiar polarization curves are characterized by a large-inversion angle, around 30 degrees, which could be related to the presence of FeO-bearing spinel embedded in Calcium-Aluminum inclusions. In order to test this hypothesis, we have measured the phase function and degree of linear polarization of six samples of Mg-rich olivine and spinel. For each material, we have analysed the light scattering properties of a millimeter-sized grain and of two powdered samples with size distributions in the micrometer size range. The three spinel samples show a well-defined negative polarization branch with an inversion phase angle located around 24 degrees-30 degrees. In contrast, in the case of the olivine samples, the inversion angle is highly dependent on particle size and tends to decrease for larger sizes. We identify the macroscopic geometries as a possible explanation for the evident differences in the polarization curves between olivine and spinel millimeter samples. Although the polarization behaviour in near backscattering of the Barbara asteroid is similar to that of our spinel mm-sized sample in random orientation, this similarity could result in part from crystal retro-reflection rather than composition. This is part of an ongoing experimental project devoted to test separately several components of CV3-like meteorites, representative of the Barbarians composition, to disentangle their contributions to the polarization behaviour of these objects.Peer reviewe
Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.
The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient
Co-Transport of Polycyclic Aromatic Hydrocarbons by Motile Microorganisms Leads to Enhanced Mass Transfer under Diffusive Conditions.
The
environmental chemodynamics of hydrophobic organic chemicals
(HOCs) are often rate-limited by diffusion in stagnant boundary layers.
This study investigated whether motile microorganisms can act as microbial
carriers that enhance mass transfer of HOCs through diffusive boundary
layers. A new experimental system was developed that allows (1) generation
of concentration gradients of HOCs under the microscope, (2) exposure
and direct observation of microorganisms in such gradients, and (3)
quantification of HOC mass transfer. Silicone O-rings were integrated
into a Dunn chemotaxis chamber to serve as sink and source for polycyclic
aromatic hydrocarbons (PAHs). This resulted in stable concentration
gradients in water (>24 h). Adding the model organism <i>Tetrahymena
pyriformis</i> to the experimental system enhanced PAH mass transfer
up to hundred-fold (benzoÂ[a]Âpyrene). Increasing mass transfer enhancement
with hydrophobicity indicated PAH co-transport with the motile organisms.
Fluorescence microscopy confirmed such transport. The effective diffusivity
of <i>T. pyriformis</i>, determined by video imaging microscopy,
was found to exceed molecular diffusivities of the PAHs up to four-fold.
Cell-bound PAH fractions were determined to range from 28% (naphthalene)
to 92% (pyrene). Motile microorganisms can therefore function as effective
carriers for HOCs under diffusive conditions and might significantly
enhance mobility and availability of HOCs
Study of the chemotactic response of multicellular spheroids in a microfluidic device
YesWe report the first application of a microfluidic device to observe chemotactic migration in
multicellular spheroids. A microfluidic device was designed comprising a central microchamber
and two lateral channels through which reagents can be introduced. Multicellular
spheroids were embedded in collagen and introduced to the microchamber. A gradient of
fetal bovine serum (FBS) was established across the central chamber by addition of growth
media containing serum into one of the lateral channels. We observe that spheroids of oral
squamous carcinoma cells OSCâ19 invade collectively in the direction of the gradient of
FBS. This invasion is more directional and aggressive than that observed for individual cells
in the same experimental setup. In contrast to spheroids of OSCâ19, U87-MG multicellular
spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant
shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant
wave engulfs the spheroid before diffusing through it.This work has been supported by National Research Program of Spain (DPI2011-28262-c04-01) and by the project "MICROANGIOTHECAN" (CIBERBBN, IMIBIC and SEOM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines
yesWe describe a novel protocol to quantitatively and simultaneously compare the chemotactic responses of cells towards different chemokines. In this protocol, droplets of agarose gel containing different chemokines are applied onto the surface of a Petri dish, and then immersed under culture medium in which cells are suspended. As chemokine molecules diffuse away from the spot, a transient chemoattractant gradient is established across the spots. Cells expressing the corresponding cognate chemokine receptors migrate against this gradient by crawling under the agarose spots towards their centre. We show that this migration is chemokine-specific; meaning that only cells that express the cognate chemokine cell surface receptor, migrate under the spot containing its corresponding chemokine ligand. Furthermore, we show that migration under the agarose spot can be modulated by selective small molecule antagonists present in the cell culture medium
Gaia Early Data Release 3 Acceleration of the Solar System from Gaia astrometry
Context. Gaia Early Data Release 3 (Gaia EDR3) provides accurate astrometry for about 1.6 million compact (QSO-like) extragalactic sources, 1.2 million of which have the best-quality five-parameter astrometric solutions. Aims. The proper motions of QSO-like sources are used to reveal a systematic pattern due to the acceleration of the solar systembarycentre with respect to the rest frame of the Universe. Apart from being an important scientific result by itself, the acceleration measured in this way is a good quality indicator of the Gaia astrometric solution. Methods. Theeffect of the acceleration was obtained as a part of the general expansion of the vector field of proper motions in vector spherical harmonics (VSH). Various versions of the VSH fit and various subsets of the sources were tried and compared to get the most consistent result and a realistic estimate of its uncertainty. Additional tests with the Gaia astrometric solution were used to get a better idea of the possible systematic errors in the estimate. Results. Our best estimate of the acceleration based on Gaia EDR3 is (2.32 +/- 0.16) x 10(-10) m s(-2) (or 7.33 +/- 0.51 km s(-1) Myr-1) towards alpha = 269.1 degrees +/- 5.4 degrees, delta = -31.6 degrees +/- 4.1 degrees, corresponding to a proper motion amplitude of 5.05 +/- 0.35 mu as yr(-1). This is in good agreement with the acceleration expected from current models of the Galactic gravitational potential. We expect that future Gaia data releases will provide estimates of the acceleration with uncertainties substantially below 0.1 mu as yr(-1).Peer reviewe
Gaia Focused Product Release: A catalogue of sources around quasars to search for strongly lensed quasars
Context. Strongly lensed quasars are fundamental sources for cosmology. The
Gaia space mission covers the entire sky with the unprecedented resolution of
" in the optical, making it an ideal instrument to search for
gravitational lenses down to the limiting magnitude of 21. Nevertheless, the
previous Gaia Data Releases are known to be incomplete for small angular
separations such as those expected for most lenses. Aims. We present the Data
Processing and Analysis Consortium GravLens pipeline, which was built to
analyse all Gaia detections around quasars and to cluster them into sources,
thus producing a catalogue of secondary sources around each quasar. We analysed
the resulting catalogue to produce scores that indicate source configurations
that are compatible with strongly lensed quasars. Methods. GravLens uses the
DBSCAN unsupervised clustering algorithm to detect sources around quasars. The
resulting catalogue of multiplets is then analysed with several methods to
identify potential gravitational lenses. We developed and applied an outlier
scoring method, a comparison between the average BP and RP spectra of the
components, and we also used an extremely randomised tree algorithm. These
methods produce scores to identify the most probable configurations and to
establish a list of lens candidates. Results. We analysed the environment of 3
760 032 quasars. A total of 4 760 920 sources, including the quasars, were
found within 6" of the quasar positions. This list is given in the Gaia
archive. In 87\% of cases, the quasar remains a single source, and in 501 385
cases neighbouring sources were detected. We propose a list of 381 lensed
candidates, of which we identified 49 as the most promising. Beyond these
candidates, the associate tables in this Focused Product Release allow the
entire community to explore the unique Gaia data for strong lensing studies
further.Comment: 35 pages, 60 figures, accepted for publication by Astronomy and
Astrophysic
Gaia Early Data Release 3: Summary of the contents and survey properties
ABSTRACT: Context. We present the early installment of the third Gaia data release, Gaia EDR3, consisting of astrometry and photometry for 1.8 billion sources brighter than magnitude 21, complemented with the list of radial velocities from Gaia DR2.
Aims. A summary of the contents of Gaia EDR3 is presented, accompanied by a discussion on the differences with respect to Gaia DR2 and an overview of the main limitations which are present in the survey. Recommendations are made on the responsible use of Gaia EDR3 results.
Methods. The raw data collected with the Gaia instruments during the first 34 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium and turned into this early third data release, which represents a major advance with respect to Gaia DR2 in terms of astrometric and photometric precision, accuracy, and homogeneity.
Results. Gaia EDR3 contains celestial positions and the apparent brightness in G for approximately 1.8 billion sources. For 1.5 billion of those sources, parallaxes, proper motions, and the (GBP ? GRP) colour are also available. The passbands for G, GBP, and GRP are provided as part of the release. For ease of use, the 7 million radial velocities from Gaia DR2 are included in this release, after the removal of a small number of spurious values. New radial velocities will appear as part of Gaia DR3. Finally, Gaia EDR3 represents an updated materialisation of the celestial reference frame (CRF) in the optical, the Gaia-CRF3, which is based solely on extragalactic sources. The creation of the source list for Gaia EDR3 includes enhancements that make it more robust with respect to high proper motion stars, and the disturbing effects of spurious and partially resolved sources. The source list is largely the same as that for Gaia DR2, but it does feature new sources and there are some notable changes. The source list will not change for Gaia DR3. Conclusions. Gaia EDR3 represents a significant advance over Gaia DR2, with parallax precisions increased by 30 per cent, proper motion precisions increased by a factor of 2, and the systematic errors in the astrometry suppressed by 30-40% for the parallaxes and by a factor ~2.5 for the proper motions. The photometry also features increased precision, but above all much better homogeneity across colour, magnitude, and celestial position. A single passband for G, GBP, and GRP is valid over the entire magnitude and colour range, with no systematics above the 1% levelThe Gaia mission and data processing have financially been supported by ; the Spanish Ministry of Economy (MINECO/FEDER, UE) through grants ESP2016-80079-C2-1-R, ESP2016-80079-C2-2-R, RTI2018-095076-B-C21, RTI2018-095076-B-C22, BES-2016-078499, and BES-2017-083126 and the Juan de la Cierva formaciĂłn 2015 grant FJCI-2015-2671, the Spanish Ministry of Education, Culture, and Sports through grant FPU16/03827, the Spanish Ministry of Science and Innovation (MICINN) through grant
AYA2017-89841P for project âEstudio de las propiedades de los fĂłsiles estelares en el entorno del Grupo Localâ and through grant TIN2015-65316-P for project
âComputaciĂłn de Altas Prestaciones VII
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