1,060 research outputs found
Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events
Background: Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudo- palisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells.These âwavesâ of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBMâs spread and invasion, the recreation of these structures in vitro has remained challenging.
Methods: Here we present a new microfluidic model of GBM that mimics the dynamics of pseudopalisade forma- tion.To do this, we embedded U-251 MG cells within a collagen hydrogel in a custom-designed microfluidic device. By controlling the medium flow through lateral microchannels, we can mimic and control blood-vessel obstruction events associated with this disease.
Results: Through the use of this new system, we show that nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation in vitro.These results validate the hypothesis of pseudo- palisade formation and show an excellent agreement with a systems-biology model based on a hypoxia-driven phenomenon.
Conclusions: This paper shows the potential of microfluidic devices as advanced artificial systems capable of mod- eling in vivo nutrient and oxygen gradients during tumor evolution
Alt a 1 from Alternaria interacts with PR5 thaumatin-like proteins
Alt a 1 is a protein found in Alternaria alternata spores related to virulence and pathogenicity and considered to be responsible for chronic asthma in children. We found that spores of Alternaria inoculated on the outer surface of kiwifruits did not develop hyphae. Nevertheless, the expression of Alt a 1 gene was upregulated, and the protein was detected in the pulp where it co-localized with kiwi PR5. Pull-down assays demonstrated experimentally that the two proteins interact in such a way that Alt a 1 inhibits the enzymatic activity of PR5. These results are relevant not only for plant defense, but also for human health as patients with chronic asthma could suffer from an allergic reaction when they eat fruit contaminated with Alternaria
Smoking and age-related macular degeneration: review and update
Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health
Highlights from the Pierre Auger Observatory
The Pierre Auger Observatory is the world's largest cosmic ray observatory.
Our current exposure reaches nearly 40,000 km str and provides us with an
unprecedented quality data set. The performance and stability of the detectors
and their enhancements are described. Data analyses have led to a number of
major breakthroughs. Among these we discuss the energy spectrum and the
searches for large-scale anisotropies. We present analyses of our X
data and show how it can be interpreted in terms of mass composition. We also
describe some new analyses that extract mass sensitive parameters from the 100%
duty cycle SD data. A coherent interpretation of all these recent results opens
new directions. The consequences regarding the cosmic ray composition and the
properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray
Conference, Rio de Janeiro 201
Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer
Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkbl alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1(K781), was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination
A search for point sources of EeV photons
Measurements of air showers made using the hybrid technique developed with
the fluorescence and surface detectors of the Pierre Auger Observatory allow a
sensitive search for point sources of EeV photons anywhere in the exposed sky.
A multivariate analysis reduces the background of hadronic cosmic rays. The
search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an
energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been
detected. An upper limit on the photon flux has been derived for every
direction. The mean value of the energy flux limit that results from this,
assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial
direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in
which EeV cosmic ray protons are emitted by non-transient sources in the
Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical
Journa
Reconstruction of inclined air showers detected with the Pierre Auger Observatory
We describe the method devised to reconstruct inclined cosmic-ray air showers
with zenith angles greater than detected with the surface array of
the Pierre Auger Observatory. The measured signals at the ground level are
fitted to muon density distributions predicted with atmospheric cascade models
to obtain the relative shower size as an overall normalization parameter. The
method is evaluated using simulated showers to test its performance. The energy
of the cosmic rays is calibrated using a sub-sample of events reconstructed
with both the fluorescence and surface array techniques. The reconstruction
method described here provides the basis of complementary analyses including an
independent measurement of the energy spectrum of ultra-high energy cosmic rays
using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of
Cosmology and Astroparticle Physics (JCAP
Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory
The Pierre Auger Collaboration has reported evidence for anisotropy in the
distribution of arrival directions of the cosmic rays with energies
eV. These show a correlation with the distribution
of nearby extragalactic objects, including an apparent excess around the
direction of Centaurus A. If the particles responsible for these excesses at
are heavy nuclei with charge , the proton component of the
sources should lead to excesses in the same regions at energies . We here
report the lack of anisotropies in these directions at energies above
(for illustrative values of ). If the anisotropies
above are due to nuclei with charge , and under reasonable
assumptions about the acceleration process, these observations imply stringent
constraints on the allowed proton fraction at the lower energies
The Pierre Auger Observatory III: Other Astrophysical Observations
Astrophysical observations of ultra-high-energy cosmic rays with the Pierre
Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference,
Beijing, China, August 201
Measurement of the Depth of Maximum of Extensive Air Showers above 10^18 eV
We describe the measurement of the depth of maximum, Xmax, of the
longitudinal development of air showers induced by cosmic rays. Almost four
thousand events above 10^18 eV observed by the fluorescence detector of the
Pierre Auger Observatory in coincidence with at least one surface detector
station are selected for the analysis. The average shower maximum was found to
evolve with energy at a rate of (106 +35/-21) g/cm^2/decade below 10^(18.24 +/-
0.05) eV and (24 +/- 3) g/cm^2/decade above this energy. The measured
shower-to-shower fluctuations decrease from about 55 to 26 g/cm^2. The
interpretation of these results in terms of the cosmic ray mass composition is
briefly discussed.Comment: Accepted for publication by PR
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