578 research outputs found
Elucidation of the Roles of Tumor Integrin 1 in the Extravasation Stage of the Metastasis Cascade
Tumor integrin β1 (ITGB1) contributes to primary tumor growth and metastasis, but its specific roles in extravasation have not yet been clearly elucidated. In this study, we engineered a three-dimensional microfluidic model of the human microvasculature to recapitulate the environment wherein extravasation takes place and assess the consequences of β1 depletion in cancer cells. Combined with confocal imaging, these tools allowed us to decipher the detailed morphology of transmigrating tumor cells and associated endothelial cells in vitro at high spatio-temporal resolution not easily achieved in conventional transmigration assays. Dynamic imaging revealed that β1-depleted cells lacked the ability to sustain protrusions into the subendothelial matrix in contrast with control cells. Specifically, adhesion via α3β1 and α6β1 to subendothelial laminin was a critical prerequisite for successful transmigration. β1 was required to invade past the endothelial basement membrane, whereas its attenuation in a syngeneic tumor model resulted in reduced metastatic colonization of the lung, an effect not observed upon depletion of other integrin alpha and beta subunits. Collectively, our findings in this novel model of the extravasation microenvironment revealed a critical requirement for β1 in several steps of extravasation, providing new insights into the mechanisms underlying metastasis.National Cancer Institute (U.S.) (Grant 1U01CA202177-01
Post-Collision Interaction with Wannier electrons
A theory of the Post-Collision Interaction (PCI) is developed for the case
when an electron atom impact results in creation of two low-energy Wannier
electrons and an ion excited into an autoionizing state. The following
autoionization decay exposes the Wannier pair to the influence of PCI resulting
in variation of the shape of the line in the autoionization spectrum. An
explicit dependence of the autoionization profile on the wave function of the
Wannier pair is found. PCI provides an opportunity to study this wave function
for a wide area of distancesComment: 33 pages, Latex, IOP style, and 3 figures fig1.ps, fig2.ps, fig3.p
Inflamed neutrophils sequestered at entrapped tumor cells via chemotactic confinement promote tumor cell extravasation
Systemic inflammation occurring around the course of tumor progression and treatment are often correlated with adverse oncological outcomes. As such, it is suspected that neutrophils, the first line of defense against infection, may play important roles in linking inflammation and metastatic seeding. To decipher the dynamic roles of inflamed neutrophils during hematogenous dissemination, we employ a multiplexed microfluidic model of the human microvasculature enabling physiologically relevant transport of circulating cells combined with real-time, high spatial resolution observation of heterotypic cell–cell interactions. LPS-stimulated neutrophils (PMNs) and tumor cells (TCs) form heterotypic aggregates under flow, and arrest due to both mechanical trapping and neutrophil–endothelial adhesions. Surprisingly, PMNs are not static following aggregation, but exhibit a confined migration pattern near TC–PMN clusters. We discover that PMNs are chemotactically confined by self-secreted IL-8 and tumor-derived CXCL-1, which are immobilized by the endothelial glycocalyx. This results in significant neutrophil sequestration with arrested tumor cells, leading to the spatial localization of neutrophil-derived IL-8, which also contributes to increasing the extravasation potential of adjacent tumor cells through modulation of the endothelial barrier. Strikingly similar migration patterns and extravasation behaviors were also observed in an in vivo zebrafish model upon PMN–tumor cell coinjection into the embryo vasculature. These insights into the temporal dynamics of intravascular tumor–PMN interactions elucidate the mechanisms through which inflamed neutrophils can exert proextravasation effects at the distant metastatic site. Keywords: metastasis; inflammation; neutrophils; extravasation; cell migratio
Towards the conversion of carbohydrate biomass feedstocks to biofuels via hydroxylmethylfurfural
This review appraises the chemical conversion processes recently reported for the production of
hydroxylmethylfurfural (HMF), a key biorefining intermediate, from carbohydrate biomass
feedstocks. Catalytic sites or groups required for the efficient and selective conversion of hexose
substrates to HMF are examined. The principle of concerted catalysis was used to rationalise the
dehydration of fructose and glucose to HMF in non-aqueous media. A survey of reported reaction
routes to diesel-range biofuel intermediates from HMF or furfural is presented and self-condensation
reaction routes for linking two or more HMF and furfural units together toward obtaining kerosene and diesel-range biofuel intermediates are highlighted. The reaction routes include: benzoin condensation, condensation of furfuryl alcohols, hetero Diels–Alder reaction and ketonisation
reaction. These reaction routes are yet to be exploited despite their potential for obtaining kerosene and diesel-range biofuel intermediates exclusively from furfural or hydroxylmethylfurfural
Direct constraint on the distance of y2 Velorum from AMBER/VLTI observations
In this work, we present the first AMBER observations, of the Wolf-Rayet and
O (WR+O) star binary system y2 Velorum. The AMBER instrument was used with the
telescopes UT2, UT3, and UT4 on baselines ranging from 46m to 85m. It delivered
spectrally dispersed visibilities, as well as differential and closure phases,
with a resolution R = 1500 in the spectral band 1.95-2.17 micron. We interpret
these data in the context of a binary system with unresolved components,
neglecting in a first approximation the wind-wind collision zone flux
contribution. We show that the AMBER observables result primarily from the
contribution of the individual components of the WR+O binary system. We discuss
several interpretations of the residuals, and speculate on the detection of an
additional continuum component, originating from the free-free emission
associated with the wind-wind collision zone (WWCZ), and contributing at most
to the observed K-band flux at the 5% level. The expected absolute separation
and position angle at the time of observations were 5.1±0.9mas and
66±15° respectively. However, we infer a separation of
3.62+0.11-0.30 mas and a position angle of 73+9-11°. Our analysis thus
implies that the binary system lies at a distance of 368+38-13 pc, in agreement
with recent spectrophotometric estimates, but significantly larger than the
Hipparcos value of 258+41-31 pc
Near-Infrared interferometry of Eta Carinae with high spatial and spectral resolution using the VLTI and the AMBER instrument
We present the first NIR spectro-interferometry of the LBV Eta Carinae. The K
band observations were performed with the AMBER instrument of the ESO Very
Large Telescope Interferometer using three 8.2m Unit Telescopes with baselines
from 42 to 89m. The aim of this work is to study the wavelength dependence of
Eta Car's optically thick wind region with a high spatial resolution of 5 mas
(11 AU) and high spectral resolution. The medium spectral resolution
observations (R=1,500) were performed in the wavelength range around both the
HeI 2.059 micron and the Br gamma 2.166 micron emission lines, the high
spectral resolution observations (R=12,000) only in the Br gamma line region.
In the K-band continuum, a diameter of 4.0 +/-0.2 mas (Gaussian FWHM, fit range
28-89m) was measured for Eta Car's optically thick wind region. If we fit
Hillier et al. (2001) model visibilities to the observed AMBER visibilities, we
obtain 50 % encircled-energy diameters of 4.2, 6.5 and 9.6mas in the 2.17
micron continuum, the HeI, and the Br gamma emission lines, respectively. In
the continuum near the Br gamma line, an elongation along a position angle of
120+/-15 degrees was found, consistent with previous VLTI/VINCI measurements by
van Boekel et al. (2003). We compare the measured visibilities with predictions
of the radiative transfer model of Hillier et al. (2001), finding good
agreement. Furthermore, we discuss the detectability of the hypothetical hot
binary companion. For the interpretation of the non-zero differential and
closure phases measured within the Br gamma line, we present a simple geometric
model of an inclined, latitude-dependent wind zone. Our observations support
theoretical models of anisotropic winds from fast-rotating, luminous hot stars
with enhanced high-velocity mass loss near the polar regions.Comment: 22 pages, 14 figures, 2 tables; A&A in pres
The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.
The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects
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