Cloud storage plays an important role in today’s cloud ecosystem. Increasingly clients tend to outsource their data to the cloud. In spite of its copious advantages, integrity has always been a ...significant issue. The audit method is commonly used to ensure integrity in cloud scenarios. However, traditional auditing schemes expect a third-party auditor (TPA), which is not always available in the real world. Also, the former scheme implies a limited pay-as-you-go service, as it requires the client to pay for the service in advance.
In this paper, we aim to address the aforementioned drawback by adopting blockchain to replace TPA and designing a blockchain-based fair payment smart contract for public cloud storage auditing. In our system, data owner and cloud service provider (CSP) will run a blockchain-based smart contract. The contract ensures that the CSP is required to submit data possession proof regularly. The CSP gets paid only if the verification is passed; otherwise, it gets no remuneration but has to pay the penalties. To reduce the number of interactions in the execution of contract, we present the notion of non-interactive public provable data possession and design a blockchain-based smart contract for public cloud storage auditing based on this primitive.
Dietary fat promotes pathological insulin resistance through chronic inflammation. The inactivation of inflammatory proteins produced by macrophages improves diet-induced diabetes, but how ...nutrient-dense diets induce diabetes is unknown. Membrane lipids affect the innate immune response, which requires domains that influence high-fat-diet-induced chronic inflammation and alter cell function based on phospholipid composition. Endogenous fatty acid synthesis, mediated by fatty acid synthase (FAS), affects membrane composition. Here we show that macrophage FAS is indispensable for diet-induced inflammation. Deleting Fasn in macrophages prevents diet-induced insulin resistance, recruitment of macrophages to adipose tissue and chronic inflammation in mice. We found that FAS deficiency alters membrane order and composition, impairing the retention of plasma membrane cholesterol and disrupting Rho GTPase trafficking-a process required for cell adhesion, migration and activation. Expression of a constitutively active Rho GTPase, however, restored inflammatory signalling. Exogenous palmitate was partitioned to different pools from endogenous lipids and did not rescue inflammatory signalling. However, exogenous cholesterol, as well as other planar sterols, did rescue signalling, with cholesterol restoring FAS-induced perturbations in membrane order. Our results show that the production of endogenous fat in macrophages is necessary for the development of exogenous-fat-induced insulin resistance through the creation of a receptive environment at the plasma membrane for the assembly of cholesterol-dependent signalling networks.
De novo lipogenesis, the production of fats from simple precursors, is often dismissed as irrelevant to the pathobiology of obesity caused by positive energy balance due to typical high fat diets. ...However, emerging data implicate de novo lipogenesis in the generation of metabolic signals that alter disease risk. Exploiting this signaling pathway represents lipoexpediency. Lipoexpediency is the concept of directing fats toward benefit even in the setting of lipid overload, and represents a strategy to complement efforts aimed at improving energy balance. Optimizing lipid signals initiated by key lipogenic enzymes such as fatty acid synthase might limit morbidity in people who are unlikely to abandon the lifestyle of the sedentary gourmand.
As Internet of Things (IoT) devices develop, an increasing number of images appear in our everyday lives. The emergence of massive amounts of image data has increased the burden on local IoT devices. ...As IoT owners try to outsource to the cloud server, privacy disclosure may occur during the outsourcing process. In this study, we designed a secure image-retrieval scheme that supports multiple sources. In our solution, we first encrypt the image features by improving a secure multiparty sum protocol, which can effectively support the similarity calculation of encrypted features gathered from multiple sources. Then, IoT owners store the feature vectors locally to avoid disclosing similarity information to the cloud. Finally, we created an index to improve search efficiency by locality-sensitive hashing. Security is analyzed to demonstrate that the privacy of images and matching results have been well protected against the cloud server. In addition, the performance analysis and experimental results show that the proposed scheme achieves highly competitive results on real datasets.
OBJECTIVE—Defects in insulin signaling are associated with abnormal endothelial cell function, which occurs commonly in cardiovascular disease. Targets of insulin signaling in endothelial cells are ...incompletely understood. Protein S-palmitoylation, the reversible modification of proteins by the lipid palmitate, is a post-translational process relevant to cell signaling, but little is known about the role of insulin in protein palmitoylation.
APPROACH AND RESULTS—To test the hypothesis that insulin alters protein palmitoylation in endothelial cells, we combined acyl-biotin exchange chemistry with stable isotope labeling by amino acids in cell culture to perform quantitative proteomic profiling of human endothelial cells. We identified ≈380 putative palmitoylated proteins, of which >200 were not known to be palmitoylated; ≈10% of the putative palmitoylated proteins were induced or suppressed by insulin. Of those potentially affected by insulin, <10 have been implicated in vascular function. For one, platelet-activating factor acetylhydrolase IB subunit gamma (PAFAH1b3; not previously known to be palmitoylated), we confirmed that insulin stimulated palmitoylation without affecting PAFAH1b3 protein abundance. Chemical inhibition of palmitoylation prevented insulin-induced angiogenesis in vitro; knockdown of PAFAH1b3 had the same effect. PAFAH1b3 knockdown also disrupted cell migration. Mutagenesis of cysteines at residues 56 and 206 prevented palmitoylation of PAFAH1b3, abolished its capacity to stimulate cell migration, and inhibited its association with detergent-resistant membranes, which are implicated in cell signaling. Insulin promoted the association of wild-type PAFAH1b3 with detergent-resistant membranes.
CONCLUSIONS—These findings provide proof of principle for using proteomics to identify novel insulin-inducible palmitoylation targets relevant to endothelial function.
The rapid development of online social media has significantly promoted product diffusion in online social networks (PDOSN). However, prior studies focusing on irrational behavior, such as ...overconfidence, in PDOSN are scarce. To investigate the effect of overconfidence on PDOSN, this study combined overconfidence and an evolutionary game to conduct a multiagent simulation on PDOSN. This combined method provided an effective reference to examine product diffusion in the context of irrational behavior. After careful consideration, this study identified three overconfidence scenarios, benefit, cost, and benefit and cost overconfidence, developed a multiagent simulation model for PDOSN using various overconfidence scenarios, and conducted a comparison with real-world cases to validate the model’s feasibility. The findings indicated that adoption benefits and betrayal penalties had a positive effect on the results in all models, while adoption costs had the opposite effect. When benefit and cost overconfidence occurred simultaneously, benefit overconfidence offset the negative effect of cost overconfidence. Moderate connectivity, a large number of core nodes, and high reconnection probability fully promoted product diffusion. Benefit overconfidence and cost overconfidence had a significant impact on the results in different networks. As such, this study combined psychological theory with simulation methods, providing insights for future research on product diffusion.
Dear Editor,
Receptor-like kinases （RLKs） constitute the major family of cell surface-associated receptors in plants and play essential roles in perceiving extracellular signals 1. Over two hundred ...members of the largest subfam- ily of RLKs that contain leucine-rich repeat extracellular domains （LRR-RLK） are found in Arabidopsis, among which BRIl-associated kinase 1 （BAK1） is one of the best studied. BAK1 was initially identified based on its association with the LRR-RLK BRI1, which perceives brassinosteroid, an important hormone that regulates a wide range of developmental and physiological processes in plants 2. BAK1 also serves as a co-receptor for sev- eral other LRR-RLKs that perceive pathogen-associated molecular patterns （PAMPs）, including flagellin-sensing 2 （FLS2） and elongation factor EF-Tu receptor 3, 4, and is therefore required for the innate immunity of plants. The reciprocal phosphorylation on the cytoplas- mic domains of BAK1 and the ligand-binding RLKs in the complex is a prerequisite for the full activation of the receptor kinase 5. The crystal structure of BAK1 com- plexed with AvrPtoB, which is an effector secreted by Pseudomonas syringae pv. Tomato to suppress PAMP- triggered immunity, recently revealed the mechanism by which BAK1 activity is inhibited 6. However, the mechanism for BAK1 activation, particularly the impact of phosphorylation of key residues on BAK1 activation, remains unclear.
Neutrophils are the first effectors of inflammatory response triggered by mastitis infection, and are important defense cells against pathogenic Escherichia coli (E. coli). DNA methylation, as a ...critical epigenetic mechanism for regulating gene function, is involved in bovine mastitis.
In this study, we sequenced the blood neutrophils of healthy and E. coli-infected mastitic half-sib cows for the overall DNA methylation levels using transcriptome sequencing and reduced representation bisulfite sequencing. The methylation levels in the mastitis cows (MCs) were decreased compared with healthy cows (HCs). A total of 494 differentially methylated regions were identified, among which 61 were up-methylated and 433 were down-methylated (MCs vs. HCs). The expression levels of 1094 differentially expressed genes were up-regulated, and 245 genes were down-regulated. Twenty-nine genes were found in methylation and transcription data, among which seven genes' promoter methylation levels were negatively correlated with expression levels, and 11 genes were differentially methylated in the exon regions. The bisulfite sequencing PCR and quantitative real-time PCR validation results demonstrated that the promoter methylation of CITED2 and SLC40A1 genes affected differential expression. The methylation of LGR4 exon 5 regulated its own alternative splicing. The promoter methylation of bta-miR-15a has an indirect effect on the expression of its target gene CD163. The CITED2, SLC40A1, and LGR4 genes can be used as candidates for E. coli-induced mastitis resistance.
This study explored the roles of DNA methylation in affecting transcription of protein-coding genes and miRNAs in E. coli-induced mastitis, thereby helping explain the function of DNA methylation in the pathogenesis of mastitis and provided new target genes and epigenetic markers for mastitis resistance breeding in dairy cattle.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fatty acid synthase (FAS) is altered in metabolic disorders and cancer. Conventional FAS null mice die in utero, so effects of whole-body inhibition of lipogenesis following development are unknown. ...Inducible global knockout of FAS (iFASKO) in mice was lethal due to a disrupted intestinal barrier and leukopenia. Conditional loss of FAS was associated with the selective suppression of granulopoiesis without disrupting granulocytic differentiation. Transplantation of iFASKO bone marrow into wild-type mice followed by Cre induction resulted in selective neutrophil depletion, but not death. Impaired lipogenesis increased ER stress and apoptosis in neutrophils by preferentially decreasing peroxisome-derived membrane phospholipids containing ether bonds. Inducible global knockout of PexRAP, a peroxisomal enzyme required for ether lipid synthesis, also produced neutropenia. FAS knockdown in neutrophil-like HL-60 cells caused cell loss that was partially rescued by ether lipids. Inhibiting ether lipid synthesis selectively constrains neutrophil development, revealing an unrecognized pathway in immunometabolism.
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•Fatty acid synthase (FAS)-mediated lipogenesis maintains neutrophil viability•FAS is required for granulopoiesis without affecting granulocytic differentiation•FAS regulates ether lipid synthesis to maintain neutrophil membrane composition•Inhibition of ether lipid synthesis recapitulates effects of FAS loss on neutropenia
Lodhi et al. demonstrate that a lipogenic pathway involving fatty acid synthase and the generation of ether lipids by peroxisomes is required for the maintenance of neutrophil homeostasis, findings potentially relevant to neutropenia as well as neoplastic and inflammatory states.
Acyl-protein thioesterases 1 and 2 (APT1 and APT2) reverse S-acylation, a potential regulator of systemic glucose metabolism in mammals. Palmitoylation proteomics in liver-specific knockout mice ...shows that APT1 predominates over APT2, primarily depalmitoylating mitochondrial proteins, including proteins linked to glutamine metabolism. miniTurbo-facilitated determination of the protein-protein proximity network of APT1 and APT2 in HepG2 cells reveals APT proximity networks encompassing mitochondrial proteins including the major translocases Tomm20 and Timm44. APT1 also interacts with Slc1a5 (ASCT2), the only glutamine transporter known to localize to mitochondria. High-fat-diet-fed male mice with dual (but not single) hepatic deletion of APT1 and APT2 have insulin resistance, fasting hyperglycemia, increased glutamine-driven gluconeogenesis, and decreased liver mass. These data suggest that APT1 and APT2 regulation of hepatic glucose metabolism and insulin signaling is functionally redundant. Identification of substrates and protein-protein proximity networks for APT1 and APT2 establishes a framework for defining mechanisms underlying metabolic disease.
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•APT1 and APT2 deacylate mitochondrial targets including mediators of glutamine metabolism•APT proximity networks include the major mitochondrial translocases Tomm20 and Timm44•High-fat-fed liver-specific APT1/APT2 knockout mice are insulin resistant•Glutamine-driven gluconeogenesis is increased in APT deficiency
Speck et al. use proteomics in mouse liver and miniTurbo constructs in HepG2 cells to identify substrates and the protein interactome for acyl-protein thioesterases 1 and 2. Regulation of hepatic glucose metabolism by these enzymes is found to be functionally redundant, in part through effects on acylation of mitochondrial proteins.
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