121 research outputs found
Reduced Expression of miRNA-27a Modulates Cisplatin Resistance in Bladder Cancer by Targeting the Cystine/Glutamate Exchanger SLC7A11
Purpose: Resistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs (miRNA) that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug-resistant phenotype, and how this resistance might be overcome.
Experimental Design: miRNA expression in paired cisplatin-resistant and -sensitive cell lines was measured. Dysregulated miRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin-resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione (GSH). Candidate miRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and miRNA-27a were quantified in patient tumor material.
Results: A panel of miRNAs were found to be dysregulated in cisplatin-resistant cells. miRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of GSH biosynthesis. In patients, SLC7A11 expression was inversely related to miRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring miRNA-27a expression or reducing SLC7A11 activity with siRNA or with sulfasalazine.
Conclusion: Our findings indicate that miRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease
Quantum suppression of shot noise in field emitters
We have analyzed the shot noise of electron emission under strong applied
electric fields within the Landauer-Buttiker scheme. In contrast to the
previous studies of vacuum-tube emitters, we show that in new generation
electron emitters, scaled down to the nanometer dimensions, shot noise much
smaller than the Schottky noise is observable. Carbon nanotube field emitters
are among possible candidates to observe the effect of shot-noise suppression
caused by quantum partitioning.Comment: 5 pages, 1 fig, minor changes, published versio
Effects of Pore Walls and Randomness on Phase Transitions in Porous Media
We study spin models within the mean field approximation to elucidate the
topology of the phase diagrams of systems modeling the liquid-vapor transition
and the separation of He--He mixtures in periodic porous media. These
topologies are found to be identical to those of the corresponding random field
and random anisotropy spin systems with a bimodal distribution of the
randomness. Our results suggest that the presence of walls (periodic or
otherwise) are a key factor determining the nature of the phase diagram in
porous media.Comment: REVTeX, 11 eps figures, to appear in Phys. Rev.
Dynamic nuclear polarization and spin-diffusion in non-conducting solids
There has been much renewed interest in dynamic nuclear polarization (DNP),
particularly in the context of solid state biomolecular NMR and more recently
dissolution DNP techniques for liquids. This paper reviews the role of spin
diffusion in polarizing nuclear spins and discusses the role of the spin
diffusion barrier, before going on to discuss some recent results.Comment: submitted to Applied Magnetic Resonance. The article should appear in
a special issue that is being published in connection with the DNP Symposium
help in Nottingham in August 200
Active Galactic Nuclei at the Crossroads of Astrophysics
Over the last five decades, AGN studies have produced a number of spectacular
examples of synergies and multifaceted approaches in astrophysics. The field of
AGN research now spans the entire spectral range and covers more than twelve
orders of magnitude in the spatial and temporal domains. The next generation of
astrophysical facilities will open up new possibilities for AGN studies,
especially in the areas of high-resolution and high-fidelity imaging and
spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These
studies will address in detail a number of critical issues in AGN research such
as processes in the immediate vicinity of supermassive black holes, physical
conditions of broad-line and narrow-line regions, formation and evolution of
accretion disks and relativistic outflows, and the connection between nuclear
activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic
Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical
Symposia Serie
D* Production in Deep Inelastic Scattering at HERA
This paper presents measurements of D^{*\pm} production in deep inelastic
scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The
data have been taken with the ZEUS detector at HERA. The decay channel
(+ c.c.) has been used in the study. The
cross section for inclusive D^{*\pm} production with
and is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region
{ GeV and }. Differential cross
sections as functions of p_T(D^{*\pm}), and are
compared with next-to-leading order QCD calculations based on the photon-gluon
fusion production mechanism. After an extrapolation of the cross section to the
full kinematic region in p_T(D^{*\pm}) and (D^{*\pm}), the charm
contribution to the proton structure function is
determined for Bjorken between 2 10 and 5 10.Comment: 17 pages including 4 figure
Observation of Scaling Violations in Scaled Momentum Distributions at HERA
Charged particle production has been measured in deep inelastic scattering
(DIS) events over a large range of and using the ZEUS detector. The
evolution of the scaled momentum, , with in the range 10 to 1280
, has been investigated in the current fragmentation region of the Breit
frame. The results show clear evidence, in a single experiment, for scaling
violations in scaled momenta as a function of .Comment: 21 pages including 4 figures, to be published in Physics Letters B.
Two references adde
Heavy flavor properties of jets produced in interactions at 1.8 TeV
We present a detailed examination of the heavy flavor properties of jets
produced at the Fermilab Tevatron collider. The data set, collected with the
Collider Detector at Fermilab, consists of events with two or more jets with
transverse energy GeV and pseudo-rapidity . The
heavy flavor content of the data set is enriched by requiring that at least one
of the jets (lepton-jet) contains a lepton with transverse momentum larger than
8 GeV/c. Jets containing hadrons with heavy flavor are selected via the
identification of secondary vertices.
The parton-level cross sections predicted by the {\sc herwig} Monte Carlo
generator program are tuned within theoretical and experimental uncertainties
to reproduce the secondary-vertex rates in the data.
The tuned simulation provides new information on the origin of the
discrepancy between the cross section measurements at the Tevatron
and the next-to-leading order QCD prediction. We also compare the rate of
away-jets (jets recoiling against the lepton-jet) containing a soft lepton
( GeV/c) in the data to that in the tuned simulation.
We find that this rate is larger than what is expected for the conventional
production and semileptonic decay of pairs of hadrons with heavy flavor.Comment: 65 pages, 14 tables, 14 figures. To be submitted to Phys. Rev.
NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics
Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
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