Differential expression of CCN family members CYR611, CTGF and NOV in gastric cancer and their association with disease progression

CCN is an acronym for cysteine-rich protein 61 (CYR61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (NOV). Aberrations of certain CCN members including CYR61, CTGF, Wnt1-inducible signalling pathway protein (WISP)-1 and -3 have been reported in gastric cancer. The present study aimed to examine the clinical relevance of NOV along with CYR61 and CTGF in gastric cancer by analysing their transcript levels. CYR61, CTGF and NOV transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues were determined using real-time quantitative PCR and the results were statistically analysed against patient clinicopathological data using SPSS software. NOV mRNA levels in gastric cancer tissues were significantly elevated when compared with levels in their paired adjacent non-cancerous tissues. Local advanced tumours with invasive expansion (T3 and T4) expressed higher levels of NOV (p=0.013) compared with the less invasive tumours (T1 and T2). CYR61 transcript levels were also significantly increased in gastric cancers compared with levels in the adjacent non cancerous tissues. Kaplan-Meier survival curves revealed that patients with CYR61-low transcript levels had longer overall survival (OS) (p=0.018) and disease-free survival (DFS) (p=0.015). NOV overexpression promoted the in vitro proliferation of AGS cells while the knockdown resulted in a reduced proliferation of HGC27 cells. A similar effect was observed for the invasion of these two gastric cancer cell lines. NOV expression was increased in gastric cancer which was associated with local invasion and distant metastases. Taken together, the expression of NOV and CYR61 was increased in gastric cancer. The elevated expression of CYR61 was associated with poorer survival. NOV promoted proliferation and invasion of gastric cancer cells. Further investigations may highlight their predictive and therapeutic potential in gastric cancer.Cancer Research Wales; Chinese Medical Research Scholarship of Cardiff UniversitySCI(E)[email protected]; [email protected]

From particles to orbits: precise dark matter density profiles using dynamical information

We introduce a new method to calculate dark matter halo density profiles from simulations. Each particle is ‘smeared’ over its orbit to obtain a dynamical profile that is averaged over a dynamical time, in contrast to the traditional approach of binning particles based on their instantaneous positions. The dynamical and binned profiles are in good agreement, with the dynamical approach showing a significant reduction in Poisson noise in the innermost regions. We find that the inner cusps of the new dynamical profiles continue inward all the way to the softening radius, reproducing the central density profile of higher resolution simulations within the 95 per cent confidence intervals, for haloes in virial equilibrium. Folding in dynamical information thus provides a new approach to improve the precision of dark matter density profiles at small radii, for minimal computational cost. Our technique makes two key assumptions that the halo is in equilibrium (phase mixed) and the potential is spherically symmetric. We discuss why the method is successful despite strong violations of spherical symmetry in the centres of haloes, and explore how substructures disturb equilibrium at large radii

Multiple uncertainty relation for accelerated quantum information

The uncertainty principle, first introduced by Heisenberg in inertial frames, clearly distinguishes quantum theories from classical mechanics. In non-inertial frames, its information-theoretic expressions, namely entropic uncertainty relations, have been extensively studied through delocalized quantum fields, and localization of the quantum fields were discussed as well. However, infeasibility of measurements applied on a delocalized quantum field due to the finite size of measurement apparatuses is left unexplained. Therefore, physical clarification of a quantum protocol revealing entropic uncertainty relations still needs investigation. Building on advances in quantum field theories and theoretical developments in entropic uncertainty relations, we demonstrate a relativistic protocol of an uncertainty game in the presence of localized fermionic quantum fields inside cavities. Moreover, a novel lower bound for entropic uncertainty relations with multiple quantum memories is given in terms of the Holevo quantity, which implies how acceleration affects uncertainty relations.Comment: 9 pages, 3 figure

Ram pressure stripping in elliptical galaxies: I. the impact of the interstellar medium turbulence

Elliptical galaxies contain X-ray emitting gas that is subject to continuous ram pressure stripping over timescales comparable to cluster ages. The gas in these galaxies is not in perfect hydrostatic equilibrium. Supernova feedback, stellar winds, or active galactic nuclei (AGN) feedback can significantly perturb the interstellar medium (ISM). Using hydrodynamical simulations, we investigate the effect of subsonic turbulence in the hot ISM on the ram pressure stripping process in early-type galaxies. We find that galaxies with more turbulent ISM produce longer, wider, and more smoothly distributed tails of the stripped ISM than those characterised by weaker ISM turbulence. Our main conclusion is that even very weak internal turbulence, at the level of <15% of the average ISM sound speed, can significantly accelerate the gas removal from galaxies via ram pressure stripping. The magnitude of this effect increases sharply with the strength of turbulence. As most of the gas stripping takes place near the boundary between the ISM and the intraclustermedium (ICM), the boost in the ISM stripping rate is due to the "random walk" of the ISM from the central regions of the galactic potential well to larger distances, where the ram pressure is able to permanently remove the gas from galaxies. The ICM can be temporarily trapped inside the galactic potential well due to the mixing of the turbulent ISM with the ICM. The galaxies with more turbulent ISM, yet still characterised by very weak turbulence, can hold larger amounts of the ICM. [Abridged]Comment: 12 pages, 11 figures, 2 tables; accepted for publication in MNRA

Use of Aripiprazole in Clozapine Induced Enuresis: Report of Two Cases

This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately

Flat Central Density Profile and Constant DM Surface Density in Galaxies from Scalar Field Dark Matter

The scalar field dark matter (SFDM) model proposes that galaxies form by condensation of a scalar field (SF) very early in the universe forming Bose-Einstein Condensates (BEC) drops, i.e., in this model haloes of galaxies are gigantic drops of SF. Here big structures form like in the LCDM model, by hierarchy, thus all the predictions of the LCDM model at big scales are reproduced by SFDM. This model predicts that all galaxies must be very similar and exist for bigger redshifts than in the LCDM model. In this work we show that BEC dark matter haloes fit high-resolution rotation curves of a sample of thirteen low surface brightness galaxies. We compare our fits to those obtained using a Navarro-Frenk-White and Pseudo-Isothermal (PI) profiles and found a better agreement with the SFDM and PI profiles. The mean value of the logarithmic inner density slopes is -0.27 +/- 0.18. As a second result we find a natural way to define the core radius with the advantage of being model-independent. Using this new definition in the BEC density profile we find that the recent observation of the constant dark matter central surface density can be reproduced. We conclude that in light of the difficulties that the standard model is currently facing the SFDM model can be a worthy alternative to keep exploring further.Comment: Submitted to MNRAS, 9 pages, 32 Figures, 2 Tables.The paper with better resolution figures can be downloaded at "http://estudiantes.fis.cinvestav.mx/vrobles/SFDMfile.pd

Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells

The insulin/IGF-1 (insulin-like growth factor 1)-activated protein kinase Akt (also known as protein kinase B) phosphorylates Ser(487) in the ‘ST loop’ (serine/threonine-rich loop) within the C-terminal domain of AMPK-α1 (AMP-activated protein kinase-α1), leading to inhibition of phosphorylation by upstream kinases at the activating site, Thr(172). Surprisingly, the equivalent site on AMPK-α2, Ser(491), is not an Akt target and is modified instead by autophosphorylation. Stimulation of HEK (human embryonic kidney)-293 cells with IGF-1 caused reduced subsequent Thr(172) phosphorylation and activation of AMPK-α1 in response to the activator A769662 and the Ca(2+) ionophore A23187, effects we show to be dependent on Akt activation and Ser(487) phosphorylation. Consistent with this, in three PTEN (phosphatase and tensin homologue deleted on chromosome 10)-null tumour cell lines (in which the lipid phosphatase PTEN that normally restrains the Akt pathway is absent and Akt is thus hyperactivated), AMPK was resistant to activation by A769662. However, full AMPK activation could be restored by pharmacological inhibition of Akt, or by re-expression of active PTEN. We also show that inhibition of Thr(172) phosphorylation is due to interaction of the phosphorylated ST loop with basic side chains within the αC-helix of the kinase domain. Our findings reveal that a previously unrecognized effect of hyperactivation of Akt in tumour cells is to restrain activation of the LKB1 (liver kinase B1)–AMPK pathway, which would otherwise inhibit cell growth and proliferation

Dihalohydration of Alkynols: A Versatile Approach to Diverse Halogenated Molecules

In this paper we outline how dihalohydration reactions of propargylic alcohols can be used to access a wide variety of useful halogenated building blocks. A novel procedure for dibromohydration of alkynes has been developed, and a selection of dichloro and dibromo diols and cyclic ethers were synthesized. The dihalohydration of homo‐propargylic alcohols provides a useful route to 3‐halofurans, which were shown to readily undergo cycloaddition reactions under mild conditions. Finally, a novel ring‐expansion of propargylic alcohols containing a cyclopropylalkyne provides access to halogenated alkenylcyclobutanes

TfR1 binding with H-ferritin nanocarrier achieves prognostic diagnosis and enhances the therapeutic efficacy in clinical gastric cancer

H-ferritin (HFn) nanocarrier is emerging as a promising theranostic platform for tumor diagnosis and therapy, which can specifically target tumor cells via binding transferrin receptor 1 (TfR1). This led us to investigate the therapeutic function of TfR1 in GC. The clinical significance of TfR1 was assessed in 178 GC tissues by using a magneto-HFn nanoparticle-based immunohistochemistry method. The therapeutic effects of doxorubicin-loaded HFn nanocarriers (HFn-Dox) were evaluated on TfR1-positive GC patient-derived xenograft (GC-PDX) models. The biological function of TfR1 was investigated through in vitro and in vivo assays. TfR1 was upregulated (73.03%) in GC tissues, and reversely correlated with patient outcome. TfR1-negative sorted cells exhibited tumor-initiating features, which enhanced tumor formation and migration/invasion, whereas TfR1-positive sorted cells showed significant proliferation ability. Knockout of TfR1 in GC cells also enhanced cell invasion. TfR1-deficient cells displayed immune escape by upregulating PD-L1, CXCL9, and CXCL10, when disposed with IFN-γ. Western blot results demonstrated that TfR1-knockout GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1-positive GC-PDX models, the HFn-Dox group significantly inhibited tumor growth, and increased mouse survival, compared with that of free-Dox group. TfR1 could be a potential prognostic and therapeutic biomarker for GC: (i) TfR1 reversely correlated with patient outcome, and its negative cells possessed tumor-aggressive features; (ii) TfR1-positive cells can be killed by HFn drug nanocarrier. Given the heterogeneity of GC, HFn drug nanocarrier combined with other therapies toward TfR1-negative cells (such as small molecules or immunotherapy) will be a new option for GC treatment