121 research outputs found
Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex
Connective-tissue growth factor (CTGF) is a member of the CCN family of secreted proteins. CCN family members contain four characteristic domains and exhibit multiple activities: they associate with the extracellular matrix, they can mediate cell adhesion, cell migration and chemotaxis, and they can modulate the activities of peptide growth factors. Many of the effects of CTGF are thought to be mediated by binding to integrins, whereas others may be because of its recently identified ability to interact with BMP4 and TGF?. We demonstrate, using Xenopus embryos, that CTGF also regulates signalling through the Wnt pathway, in accord with its ability to bind to the Wnt co-receptor LDL receptor-related protein 6 (LRP6). This interaction is likely to occur through the C-terminal (CT) domain of CTGF, which is distinct from the BMP- and TGF?-interacting domain. Our results define new activities of CTGF and add to the variety of routes through which cells regulate growth factor activity in development, disease and tissue homeostasis
An Investigation of Counterfactual Thinking in Individuals Diagnoses with Diabetes
Diabetes affects both the physical and emotional well-being of over 29 million Americans. Thus, it is important to investigate the psychological factors that can influence appropriate diabetes self-care. The present study investigates whether counterfactual thoughts might be related to how an individual copes with diabetes. The study utilizes a mixed-methods approach consisting of a quantitative survey assessing psychosocial factors, and a qualitative interview with the participant. The interview includes questions about the participantâs thoughts and feelings with their experience of diabetes, noting when participants spontaneously generate counterfactual thoughts about how things might be different if they hadnât been diagnosed with diabetes. Currently, 31 people have completed the protocol (11 males and 20 females). These preliminary results suggest that an increase in counterfactual thinking is marginally associated with higher levels of guilt (r(29) = .326, p = .085). Further, these higher levels of guilt are strongly associated with the maladaptive coping mechanisms of self-blame (r(29) = .671, p \u3c .001) and behavioral disengagement (r(29) = .541, p = .002). Notably, high levels of self-blame and behavioral disengagement were marginally associated with lower levels of diabetes self-efficacy (r(29) = -.303, p = .104, and r(29) = -.331, p =.074, respectively). Appropriate diabetes self-care is essential to the prevention of serious complications like blindness and amputation. This preliminary evidence suggests that certain types of counterfactual thoughts may undermine appropriate diabetes self-care. Further research on counterfactual thinking may assist in the design of educational initiatives to encourage successful diabetes self-care
Noble Metal Nanoparticles Networks Stabilized by RodâLike Organometallic Bifunctional Thiols
od-like organometallic dithiol containing square-planar Pt(II) centers, i. e., trans,trans- [(H3COCS)Pt(PBu3)2(CïżœC C6H4 C6H4 CïżœC)(PBu3)2Pt(SCOCH3)] was used as bifunctional stabilizing agent for the synthesis of Pd-, Au-, and AgNPs (MNPs). All the MNPs showed diameters of about 4 nm, which can be controlled by carefully modulating the synthesis parameters. Covalent MNPs stabilization occurred through a single S bridge between Pt(II) and the noble metal nanocluster surfaces, leading to a network of regularly spaced NPs with the formation of dyads, as supported by SR-XPS data
and by TEM imaging analysis. The chemical nature of NPs systems was also confirmed by EDS and NMR. Comparison between SR-XPS data of MNPs and self-assembled monolayers and multilayers of pristine rod-like dithiols deposited onto polycrystalline gold surfaces revealed an electronic interaction between Pt(II) centers and biphenyl moieties of adjacent ligands, stabilizing the organic structure of the network. The possibility to obtain networks of regularly spaced MNPs opens outstanding perspectives in optoelectronics
3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different
substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of
colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812
and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically
expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. Compound 10 minimally
affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase
inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing
G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in
human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML
The Contribution of Halos with Different Mass Ratios to the Overall Growth of Cluster-Sized Halos
We provide a new observational test for a key prediction of the \Lambda CDM
cosmological model: the contributions of mergers with different
halo-to-main-cluster mass ratios to cluster-sized halo growth. We perform this
test by dynamically analyzing seven galaxy clusters, spanning the redshift
range and caustic mass range M, with an average of 293 spectroscopically-confirmed
bound galaxies to each cluster. The large radial coverage (a few virial radii),
which covers the whole infall region, with a high number of spectroscopically
identified galaxies enables this new study. For each cluster, we identify bound
galaxies. Out of these galaxies, we identify infalling and accreted halos and
estimate their masses and their dynamical states. Using the estimated masses,
we derive the contribution of different mass ratios to cluster-sized halo
growth. For mass ratios between ~0.2 and ~0.7, we find a ~1 agreement
with \Lambda CDM expectations based on the Millennium simulations I and II. At
low mass ratios, , our derived contribution is underestimated
since the detection efficiency decreases at low masses,
M. At large mass ratios, , we do not
detect halos probably because our sample, which was chosen to be quite X-ray
relaxed, is biased against large mass ratios. Therefore, at large mass ratios,
the derived contribution is also underestimated.Comment: 25 pages, 16 figures, 6 tables, 2 machine readable tables, accepted
for publication in ApJ, updated acknowledgements and data table format
modifications mad
CLASH: Mass Distribution in and around MACS J1206.2-0847 from a Full Cluster Lensing Analysis
We derive an accurate mass distribution of the galaxy cluster MACS
J1206.2-0847 (z=0.439) from a combined weak-lensing distortion, magnification,
and strong-lensing analysis of wide-field Subaru BVRIz' imaging and our recent
16-band Hubble Space Telescope observations taken as part of the Cluster
Lensing And Supernova survey with Hubble (CLASH) program. We find good
agreement in the regions of overlap between several weak and strong lensing
mass reconstructions using a wide variety of modeling methods, ensuring
consistency. The Subaru data reveal the presence of a surrounding large scale
structure with the major axis running approximately north-west south-east
(NW-SE), aligned with the cluster and its brightest galaxy shapes, showing
elongation with a \sim 2:1 axis ratio in the plane of the sky. Our full-lensing
mass profile exhibits a shallow profile slope dln\Sigma/dlnR\sim -1 at cluster
outskirts (R>1Mpc/h), whereas the mass distribution excluding the NW-SE excess
regions steepens further out, well described by the Navarro-Frenk-White form.
Assuming a spherical halo, we obtain a virial mass M_{vir}=(1.1\pm 0.2\pm
0.1)\times 10^{15} M_{sun}/h and a halo concentration c_{vir} = 6.9\pm 1.0\pm
1.2 (\sim 5.7 when the central 50kpc/h is excluded), which falls in the range
4 <7 of average c(M,z) predictions for relaxed clusters from recent Lambda
cold dark matter simulations. Our full lensing results are found to be in
agreement with X-ray mass measurements where the data overlap, and when
combined with Chandra gas mass measurements, yield a cumulative gas mass
fraction of 13.7^{+4.5}_{-3.0}% at 0.7Mpc/h (\approx 1.7r_{2500}), a typical
value observed for high mass clusters.Comment: Accepted by ApJ (30 pages, 17 figures), one new figure (Figure 10)
added, minor text changes; a version with high resolution figures available
at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/MACS1206/ms_highreso.pd
The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation
Feline leukemia virus subgroup C receptor 1 (FLVCR1) is a cell membrane heme exporter that maintains the balance between heme levels and globin synthesis in erythroid precursors. It was previously shown that Flvcr1-null mice died in utero due to a failure of erythropoiesis. Here, we identify Flvcr1b, a mitochondrial Flvcr1 isoform that promotes heme efflux into the cytoplasm. Flvcr1b overexpression promoted heme synthesis and in vitro erythroid differentiation, whereas silencing of Flvcr1b caused mitochondrial heme accumulation and termination of erythroid differentiation. Furthermore, mice lacking the plasma membrane isoform (Flvcr1a) but expressing Flvcr1b had normal erythropoiesis, but exhibited hemorrhages, edema, and skeletal abnormalities. Thus, FLVCR1b regulates erythropoiesis by controlling mitochondrial heme efflux, whereas FLVCR1a expression is required to prevent hemorrhages and edema. The aberrant expression of Flvcr1 isoforms may play a role in the pathogenesis of disorders characterized by an imbalance between heme and globin synthesis
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