853 research outputs found
Signaling network map of the aryl hydrocarbon receptor
We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics, Bangalore. We thank the “Infosys Foundation” for research support to the Institute of Bioinformatics. We thank UK India Education and Research Initiative (UKIERI) for generous grant support. SDY is a recipient of DST-INSPIRE Senior Research Fellowship from Department of Science and Technology (DST), Government of India. AR and JA are recipients of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. RR is a recipient of Research Associateship from Department of Biotechnology, Government of India
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis
Following Mitochondrial Footprints through a Long Mucosal Path to Lung Cancer
BACKGROUND:Mitochondrial DNA (mtDNA) mutations are reported in different tumors. However, there is no information on the temporal development of the mtDNA mutations/content alteration and their extent in normal and abnormal mucosa continuously exposed to tobacco smoke in lung cancer patients. METHODOLOGY:We examined the pattern of mtDNA alteration (mtDNA mutation and content index) in 25 airway mucosal biopsies, corresponding tumors and normal lymph nodes obtained from three patients with primary lung cancers. In addition, we examined the pattern of mtDNA mutation in corresponding tumors and normal lymph nodes obtained from eight other patients with primary lung cancers. The entire 16.5 kb mitochondrial genome was sequenced on Affymetrix Mitochip v2.0 sequencing platform in every sample. To examine mtDNA content index, we performed real-time PCR analysis. PRINCIPAL FINDINGS:The airway mucosal biopsies obtained from three lung cancer patients were histopathologically negative but exhibited multiple clonal mtDNA mutations detectable in the corresponding tumors. One of the patients was operated twice for the removal of tumor from the right upper and left lower lobe respectively within a span of two years. Both of these tumors exhibited twenty identical mtDNA mutations. MtDNA content increased significantly (P<0.001) in the lung cancer and all the histologically negative mucosal biopsies except one compared to the control lymph node. CONCLUSIONS/SIGNIFICANCE:Our results document the extent of massive clonal patches that develop in lifetime smokers and ultimately give rise to clinically significant cancers. These observations shed light on the extent of disease in the airway of smokers traceable through mtDNA mutation. MtDNA mutation could be a reliable tool for molecular assessment of respiratory epithelium exposed to continuous smoke as well as disease detection and monitoring. Functional analysis of the pathogenic mtDNA mutations may be useful to understand their role in lung tumorigenesis
Modeling of Electromagnetic NDE of Civil Structures
The inspection of civil structures, such as bridge decks, roadways and masonry is becoming an increasingly important area for the application of NDE methodologies. A variety of methods have been used for detecting flaws, cracks and voids as well as locating structural features such as reinforcing bars and tensioning cables. The large size of civil structures necessitates the use of an NDE technique that is capable of rapid inspection of large areas with good penetration. A candidate approach for such inspection is the microwave NDT method. Microwave energy penetrates dielectric materials such as those encountered in civil structures and consequently inspection can be accomplished using noncontact devices mounted on a fast scanning mechanism. The paper presents a numerical model for simulating electromagnetic scattering from two and three dimensional objects embedded in large structures. Such models are useful in the design and development of systems required for microwave imaging of civil structures.</p
Appearance of fluctuating stripes at the onset of the pseudogap in the high-Tc Superconductor Bi2Sr2CaCu2O8+x
Doped Mott insulators have been shown to have a strong propensity to form
patterns of holes and spins often referred to as stripes. In copper-oxides,
doping also gives rise to the pseudogap state, which transforms into a high
temperature superconductor with sufficient doping or by reducing the
temperature. A long standing question has been the interplay between pseudogap,
which is generic to all hole-doped cuprates, and stripes, whose static form
occurs in only one family of cuprates over a narrow range of the phase diagram.
Here we examine the spatial reorganization of electronic states with the onset
of the pseudogap state at T* in the high-temperature superconductor
Bi2Sr2CaCu2O8+x using spectroscopic mapping with the scanning tunneling
microscope (STM). We find that the onset of the pseudogap phase coincides with
the appearance of electronic patterns that have the predicted characteristics
of fluctuating stripes. As expected, the stripe patterns are strongest when the
hole concentration in the CuO2 planes is close to 1/8 (per Cu). While
demonstrating that the fluctuating stripes emerge with the onset of the
pseudogap state and occur over a large part of the cuprate phase diagram, our
experiments indicate that they are a consequence of pseudogap behavior rather
than its cause.Comment: preprint version, 25 pages including supplementary informatio
Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay
We reconstruct the rare decays , , and in a data sample
corresponding to collected in collisions at
by the CDF II detector at the Fermilab Tevatron
Collider. Using and decays we report the branching ratios. In addition, we report
the measurement of the differential branching ratio and the muon
forward-backward asymmetry in the and decay modes, and the
longitudinal polarization in the decay mode with respect to the squared
dimuon mass. These are consistent with the theoretical prediction from the
standard model, and most recent determinations from other experiments and of
comparable accuracy. We also report the first observation of the {\mathcal{B}}(B^0_s \to
\phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}27 \pm 6B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let
Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons
We report measurements of the resonance properties of Lambda_c(2595)+ and
Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as
Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+
pi+/- final states. These measurements are performed using data corresponding
to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV,
collected with the CDF II detector at the Fermilab Tevatron. Exploiting the
largest available charmed baryon sample, we measure masses and decay widths
with uncertainties comparable to the world averages for Sigma_c states, and
significantly smaller uncertainties than the world averages for excited
Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17
pages, 15 figure
Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV
We present a search for a new heavy charged vector boson decaying
to an electron-neutrino pair in collisions at a center-of-mass
energy of 1.96\unit{TeV}. The data were collected with the CDF II detector
and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No
significant excess above the standard model expectation is observed and we set
upper limits on . Assuming standard
model couplings to fermions and the neutrino from the boson decay to
be light, we exclude a boson with mass less than
1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer
<p>Abstract</p> <p>Background</p> <p>In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas.</p> <p>Methods</p> <p>We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750) in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (<it>MT-ATP6, MT-CO1, MT-CYB, MT-ND1</it>, <it>MT-ND6</it>, and <it>MT-RNR1</it>) were quantified in 62 cancer tissues by real-time RT-PCR.</p> <p>Results</p> <p>Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene <it>RNR1 </it>might be used as a predictor of tumour sensitivity to chemotherapy.</p> <p>Conclusion</p> <p>In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.</p
Elastin Peptides Signaling Relies on Neuraminidase-1-Dependent Lactosylceramide Generation
The sialidase activity of neuraminidase-1 (Neu-1) is responsible for ERK 1/2 pathway activation following binding of elastin peptide on the elastin receptor complex. In this work, we demonstrate that the receptor and lipid rafts colocalize at the plasma membrane. We also show that the disruption of these microdomains as well as their depletion in glycolipids blocks the receptor signaling. Following elastin peptide treatment, the cellular GM3 level decreases while lactosylceramide (LacCer) content increases consistently with a GM3/LacCer conversion. The use of lactose or Neu-1 siRNA blocks this process suggesting that the elastin receptor complex is responsible for this lipid conversion. Flow cytometry analysis confirms this elastin peptide-driven LacCer generation. Further, the use of a monoclonal anti-GM3 blocking antibody shows that GM3 is required for signaling. In conclusion, our data strongly suggest that Neu-1-dependent GM3/LacCer conversion is the key event leading to signaling by the elastin receptor complex. As a consequence, we propose that LacCer is an early messenger for this receptor
- …