173 research outputs found
Deconstructing the DGAT1 enzyme: membrane interactions at substrate binding sites
Diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in the triacylglyceride synthesis pathway. Bovine DGAT1 is an endoplasmic reticulum membrane-bound protein associated with the regulation of fat content in milk and meat. The aim of this study was to evaluate the interaction of DGAT1 peptides corresponding to putative substrate binding sites with different types of model membranes. Whilst these peptides are predicted to be located in an extramembranous loop of the membrane-bound protein, their hydrophobic substrates are membrane-bound molecules. In this study, peptides corresponding to the binding sites of the two substrates involved in the reaction were examined in the presence of model membranes in order to probe potential interactions between them that might influence the subsequent binding of the substrates. Whilst the conformation of one of the peptides changed upon binding several types of micelles regardless of their surface charge, suggesting binding to hydrophobic domains, the other peptide bound strongly to negatively-charged model membranes. This binding was accompanied by a change in conformation, and produced leakage of the liposome-entrapped dye calcein. The different hydrophobic and electrostatic interactions observed suggest the peptides may be involved in the interactions of the enzyme with membrane surfaces, facilitating access of the catalytic histidine to the triacylglycerol substrates
Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene
Measurement of Beam-Spin Asymmetries for Deep Inelastic Electroproduction
We report the first evidence for a non-zero beam-spin azimuthal asymmetry in
the electroproduction of positive pions in the deep-inelastic region. Data have
been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector
at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of
the modulation increases with the momentum of the pion relative to
the virtual photon, , with an average amplitude of for range.Comment: 5 pages, RevTEX4, 3 figures, 2 table
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured in the resonance region at and 0.65
GeV. Data for the reaction were taken at Jefferson Lab
with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally
polarized electrons at an energy of 1.515 GeV. For the first time a complete
angular distribution was measured, permitting the separation of different
non-resonant amplitudes using a partial wave analysis. Comparison with previous
beam asymmetry measurements at MAMI indicate a deviation from the predicted
dependence of using recent phenomenological
models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid
Communications. Version 2 has revised Q^2 analysi
Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n
We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic
range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c)
peaks where two nucleons each have 20% or less, and the third nucleon has most
of the transferred energy. These fast pp and pn pairs are back-to-back with
little momentum along the three-momentum transfer, indicating that they are
spectators. Experimental and theoretical evidence indicates that we have
measured distorted two-nucleon momentum distributions by striking the third
nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR
Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12
Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using
2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12
targets in the CLAS detector. A_LT' is related to the imaginary part of the
longitudinal-transverse interference and in quasifree nucleon knockout it
provides an unambiguous signature for final state interactions (FSI).
Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3%
for data with good statistical precision. Optical Model in Eikonal
Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation
(RMSGA) calculations are shown to be consistent with the measured asymmetries.Comment: 9 pages, 5 figure
Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma
Invasion of ovarian cancer cells is induced by PITX2-mediated activation of TGF-β and Activin-A
Background:Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer.
Methods: The status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The
expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR)
and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological
effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and
activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells.
Results: Human ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced
expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling
pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1
and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted
as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in
loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells.
Conclusions: Overall, our findings suggest a significant contributory role of PITX2 in promoting invasive
behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future
First Measurement of Transferred Polarization in the Exclusive e p --> e' K+ Lambda Reaction
The first measurements of the transferred polarization for the exclusive ep
--> e'K+ Lambda reaction have been performed in Hall B at the Thomas Jefferson
National Accelerator Facility using the CLAS spectrometer. A 2.567 GeV electron
beam was used to measure the hyperon polarization over a range of Q2 from 0.3
to 1.5 (GeV/c)2, W from 1.6 to 2.15 GeV, and over the full center-of-mass
angular range of the K+ meson. Comparison with predictions of hadrodynamic
models indicates strong sensitivity to the underlying resonance contributions.
A non-relativistic quark model interpretation of our data suggests that the
s-sbar quark pair is produced with spins predominantly anti-aligned.
Implications for the validity of the widely used 3P0 quark-pair creation
operator are discussed.Comment: 6 pages, 4 figure
Single pi+ Electroproduction on the Proton in the First and Second Resonance Regions at 0.25GeV^2 < Q^2 < 0.65GeV^2 Using CLAS
The ep -> e'pi^+n reaction was studied in the first and second nucleon
resonance regions in the 0.25 GeV^2 < Q^2 < 0.65 GeV^2 range using the CLAS
detector at Thomas Jefferson National Accelerator Facility. For the first time
the absolute cross sections were measured covering nearly the full angular
range in the hadronic center-of-mass frame. The structure functions sigma_TL,
sigma_TT and the linear combination sigma_T+epsilon*sigma_L were extracted by
fitting the phi-dependence of the measured cross sections, and were compared to
the MAID and Sato-Lee models.Comment: Accepted for publication in PR
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