•We suggested a privacy-preserving data-publishing model to balance data utility and privacy preservation.•The model is based on surrogate vectors.•The model is applicable on grid environments.•The ...model also protects the private location information of individuals.•The model satisfies ε-differential privacy.
As smart devices and cloud services are rapidly expanding, a large amount of location information can easily be gathered. However, there is a conflict between collecting location data and protecting personal data since obtaining and utilizing the data may be restricted due to privacy concerns. Various methods for anonymity and on the original location data have been studied, but these methods have excessively reduced data utility while stressing highly on privacy preservation. In this article, we suggest a novel model to overcome this fundamental dilemma via a surrogate vector based on the grid environment. Compared to the existing approaches, our model shows a new theoretical advancement in privacy protection, and outstanding performance with respect to time complexity and data utility has been achieved.
In many water distribution systems, a significant amount of water is lost because of leakage during transit from the water treatment plant to consumers. As a result, water leakage detection and ...localization have been a consistent focus of research. Typically, diagnosis or detection systems based on sensor signals incur significant computational and time costs, whereas the system performance depends on the features selected as input to the classifier. In this paper, to solve this problem, we propose a novel, fast, and accurate water leakage detection system with an adaptive design that fuses a one-dimensional convolutional neural network and a support vector machine. We also propose a graph-based localization algorithm to determine the leakage location. An actual water pipeline network is represented by a graph network and it is assumed that leakage events occur at virtual points on the graph. The leakage location at which costs are minimized is estimated by comparing the actual measured signals with the virtually generated signals. The performance was validated on a wireless sensor network based test bed, deployed on an actual WDS. Our proposed methods achieved 99.3% leakage detection accuracy and a localization error of less than 3 m.
The oxysterol-binding protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans, and implicated in the regulation of lipid homeostasis and in signaling pathways. Saccharomyces ...cerevisiae has seven ORPs (Osh1–Osh7) that share one unknown essential function. Here, we report the 1.5–2.3 Å structures of the PH domain and ORD (OSBP-related domain) of yeast Osh3 in apo-form or in complex with phosphatidylinositol 4-phosphate (PI4P). Osh3 recognizes PI(4)P by the highly conserved residues in the tunnel of ORD whereas it lacks sterol binding due to the narrow hydrophobic tunnel. Yeast complementation tests suggest that PI(4)P binding to PH and ORD is essential for function. This study suggests that the unifying feature in all ORP homologs is the binding of PI(4)P to ORD and sterol binding is additional to certain homologs. Structural modeling of full-length Osh3 is consistent with the concept that Osh3 is a lipid transfer protein or regulator in membrane contact sites.
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•Structures reveal conservation of PI(4)P binding to ORD in all ORPs•PI(4)P binding is essential for ORP function•Osh3 homolog lacks sterol binding activity•This study redefines the major roles of ORPs as phosphoinositide-binding proteins
Yeast oxysterol-binding protein related proteins (ORPs) are implicated in the regulation of lipid homeostasis and signaling. Structural work by Tong et al. reveals that Osh3 binds PI(4)P while lacking sterol binding. The study suggests that PI(4)P binding might be the unifying feature in all yeast ORPs.
Abstract Angiogenesis is an important phenomenon involved in normal growth and wound healing processes. An imbalance of the growth factors involved in this process, however, causes the acceleration ...of several diseases including malignant, ocular, and inflammatory diseases. Inhibiting angiogenesis through interfering in its pathway is a promising methodology to hinder the progression of these diseases. The function and mechanism of silver nanoparticles (Ag-NPs) in angiogenesis have not been elucidated to date. PEDF is suggested to be a potent anti-angiogenic agent. In this study, we postulated that Ag-NPs might have the ability to inhibit angiogenesis, the pivotal step in tumor growth, invasiveness, and metastasis. We have demonstrated that Ag-NPs could also inhibit vascular endothelial growth factor (VEGF) induced cell proliferation, migration, and capillary-like tube formation of bovine retinal endothelial cells like PEDF. In addition, Ag-NPs effectively inhibited the formation of new blood microvessels induced by VEGF in the mouse Matrigel plug assay. To understand the underlying mechanism of Ag-NPs on the inhibitory effect of angiogenesis, we showed that Ag-NPs could inhibit the activation of PI3K/Akt. Together, our results indicate that Ag-NPs can act as an anti-angiogenic molecule by targeting the activation of PI3K/Akt signaling pathways.
The application of nanoscale materials and structures, usually ranging from 1 to 100 nanometers (nm), is an emerging area of nanoscience and nanotechnology. Nanomaterials may provide solutions to ...technological and environmental challenges in the areas of solar energy conversion, catalysis, medicine, and water-treatment. The development of techniques for the controlled synthesis of nanoparticles of well-defined size, shape and composition, to be used in the biomedical field and areas such as optics and electronics, has become a big challenge. Development of reliable and eco-friendly processes for synthesis of metallic nanoparticles is an important step in the field of application of nanotechnology. One of the options to achieve this objective is to use ‘natural factories’ such as biological systems. This study reports the optimal conditions for maximum synthesis of silver nanoparticles (AgNPs) through reduction of Ag
+ ions by the culture supernatant of
Escherichia coli. The synthesized silver nanoparticles were purified by using sucrose density gradient centrifugation. The purified sample was further characterized by UV–vis spectra, fluorescence spectroscopy and TEM. The purified solution yielded the maximum absorbance peak at 420
nm and the TEM characterization showed a uniform distribution of nanoparticles, with an average size of 50
nm. X-ray diffraction (XRD) spectrum of the silver nanoparticles exhibited 2
θ values corresponding to the silver nanocrystal. The size-distribution of nanoparticles was determined using a particle-size analyzer and the average particle size was found to be 50
nm. This study also demonstrates that particle size could be controlled by varying the parameters such as temperature, pH and concentration of AgNO
3.
RATIONALE:SERCA2a, sarco-endoplasmic reticulum Ca-ATPase, is a critical determinant of cardiac function. Reduced level and activity of SERCA2a are major features of heart failure. Accordingly, ...intensive efforts have been made to develop efficient modalities for SERCA2a activation. We showed that the activity of SERCA2a is enhanced by post-translational modification with SUMO1 (small ubiquitin-like modifier 1). However, the roles of other post-translational modifications on SERCA2a are still unknown.
OBJECTIVE:In this study, we aim to assess the role of lysine acetylation on SERCA2a function and determine whether inhibition of lysine acetylation can improve cardiac function in the setting of heart failure.
METHODS AND RESULTS:The acetylation of SERCA2a was significantly increased in failing hearts of humans, mice, and pigs, which is associated with the reduced level of SIRT1 (sirtuin 1), a class III histone deacetylase. Downregulation of SIRT1 increased the SERCA2a acetylation, which in turn led to SERCA2a dysfunction and cardiac defects at baseline. In contrast, pharmacological activation of SIRT1 reduced the SERCA2a acetylation, which was accompanied by recovery of SERCA2a function and cardiac defects in failing hearts. Lysine 492 (K492) was of critical importance for the regulation of SERCA2a activity via acetylation. Acetylation at K492 significantly reduced the SERCA2a activity, presumably through interfering with the binding of ATP to SERCA2a. In failing hearts, acetylation at K492 appeared to be mediated by p300 (histone acetyltransferase p300), a histone acetyltransferase.
CONCLUSIONS:These results indicate that acetylation/deacetylation at K492, which is regulated by SIRT1 and p300, is critical for the regulation of SERCA2a activity in hearts. Pharmacological activation of SIRT1 can restore SERCA2a activity through deacetylation at K492. These findings might provide a novel strategy for the treatment of heart failure.
Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to intestinal microbes in an individual with a genetic predisposition. Therefore, alleviation of ...inflammation is very important to treat IBD. Mesenchymal stem cells (MSCs) have been highlighted as new candidates for treating autoimmune disease based on their immunomodulatory properties. In this study, we investigated the anti-inflammatory mechanism and therapeutic effects of adipose tissue-derived MSCs (ASCs) using THP-1 macrophages and dextran sodium sulfate (DSS)-induced mice with chronic colitis. LPS-treated THP-1 cells expressed mRNA of CD11b, an M1 macrophage marker, at day 2. However, THP-1 co-cultured with ASCs expressed mRNA of CD206, CD68, CCL18, legumain, and IL-10, markers of M2 macrophages. In THP-1 cells co-cultured with ASCs, precursor (pro)-IL-1β, Cox-2, and NLRP3 increased dramatically compared to LPS-treated THP-1 cells. Secretion of IL-1β and IL-18 was significantly inhibited by ASCs, but PGE2 production was highly increased in co-culture conditions of THP-1 and ASCs. IL-18 secretion was inhibited by PGE2 treatment, and PGE2 inhibited inflammasome complex (ASC/Cas-1/NLRP3) formation in THP-1 cells. In the DSS-induced chronic colitis model, ASCs ameliorated colitis by decreasing the total number of macrophages and the M1 macrophage population. Our results suggest that ASCs can suppress the inflammatory response by controlling the macrophage population, and ASCs may be therapeutically useful for the treatment of IBD.
•PGE2 was remarkably increased in conditioned media from THP-1 co-cultured with ASCs.•ASCs induced M1 to M2 macrophage transition through PGE2.•ASCs suppressed secretion of inflammatory IL-1β and IL-18 through PGE2.•ASCs ameliorated colitis by decreasing the total number of macrophages.•ASCs relieved inflammation by decreasing the M1 macrophage population.
•Expression of FGF-2, FGF-4, EGF, and HGF decreased during long-term culture of BMSCs.•Loss of growth factors induced autophagy, senescence and decrease of stemness.•FGF-2 increased proliferation ...potential via AKT and ERK activation in BMSCs.•FGF-2 suppressed LC3-II expression and down-regulated senescence of BMSCs.•HGF was important in maintenance of the differentiation potential of BMSCs.
Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2month) cultures. Taken together, depletion of growth factors during serial passage could induce autophagy, senescence and down-regulation of stemness (proliferation via FGF-2/-4 and differentiation via HGF) through suppression of AKT and ERK signaling.
Angiogenesis, the growth of new blood vessels from pre-existing vasculature is of physiological and pathological importance. We have investigated the anti-angiogenic potential of silver ...nanoparticles, produced by
Bacillus licheniformis. Bovine retinal endothelial cells (BRECs) were treated with the different concentrations of silver nanoparticles for 24
h in the presence and absence of vascular endothelial growth factor (VEGF), where 500
nM (IC
50) of silver nanoparticle concentration, was able to block the proliferation and migration of BRECs. The cells showed a clear enhancement in caspase-3 activity and formation of DNA ladders, evidence of induction of apoptosis. Here we report for the first time that silver nanoparticles inhibit cell survival via PI3K/Akt dependent pathway in Bovine retinal endothelial cells.
Protein functions are often revealed by their localization to specialized cellular sites. Recent reports demonstrated that swiprosin-1 is found together with actin and actin-binding proteins in the ...cytoskeleton fraction of human mast cells and NK-like cells. However, direct evidence of whether swiprosin-1 regulates actin dynamics is currently lacking. We found that swiprosin-1 localizes to microvilli-like membrane protrusions and lamellipodia and exhibits actin-binding activity. Overexpression of swiprosin-1 enhanced lamellipodia formation and cell spreading. In contrast, swiprosin-1 knockdown showed reduced cell spreading and migration. Swiprosin-1 induced actin bundling in the presence of Ca(2+), and deletion of the EF-hand motifs partially reduced bundling activity. Swiprosin-1 dimerized in the presence of Ca(2+) via its coiled-coil domain, and a lysine (Lys)-rich region in the coiled-coil domain was essential for regulation of actin bundling. Consistent with these observations, mutations of the EF-hand motifs and coiled-coil region significantly reduced cell spreading and lamellipodia formation. We provide new evidence of how swiprosin-1 influences cytoskeleton reorganization and cell spreading.
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