bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout
Authors: Lee Hye Eun , Yang Gabsik , Kim Nam Doo , Jeong Seongkeun , Jung Yunjin , Choi Jae Young , Park Hyun Ho , Lee Joo Young 
Published: December 2016

AbstractGouty arthritis is caused by the deposition of uric acid crystals, which induce the activation of NOD-like receptor family, pyrin domain containing 3(NLRP3) inflammasome. The NLRP3 inflammasome, composed of NLRP3, the adaptor protein ASC, and caspase-1, is closely linked to the pathogenesis of various metabolic diseases including gouty arthritis. We investigated whether an orally administrable inhibitor of NLRP3 inflammasome was effective for alleviating the pathological symptoms of gouty arthritis and what was the underlying mechanism. In primary mouse macrophages, caffeic acid phenethyl ester(CAPE) blocked caspase-1 activation and IL-1β production induced by MSU crystals, showing that CAPE suppresses NLRP3 inflammasome activation. In mouse gouty arthritis models, oral administration of CAPE suppressed MSU crystals-induced caspase-1 activation and IL-1β production in the air pouch exudates and the foot tissues, correlating with attenuation of inflammatory symptoms. CAPE directly associated with ASC as shown by SPR analysis and co-precipitation, resulting in blockade of NLRP3-ASC interaction induced by MSU crystals. Our findings provide a novel regulatory mechanism by which small molecules harness the activation of NLRP3 inflammasome by presenting ASC as a new target. Furthermore, the results suggest the preventive or therapeutic strategy for NLRP3-related inflammatory diseases such as gouty arthritis using orally available small molecules.
A Predictive Model for Toxicity Effects Assessment of Biotransformed Hepatic Drugs Using Iterative Sampling Method
Authors: Tharwat Alaa , Moemen Yasmine S. , Hassanien Aboul Ella 
Published: December 2016

AbstractMeasuring toxicity is one of the main steps in drug development. Hence, there is a high demand for computational models to predict the toxicity effects of the potential drugs. In this study, we used a dataset, which consists of four toxicity effects:mutagenic, tumorigenic, irritant and reproductive effects. The proposed model consists of three phases. In the first phase, rough set-based methods are used to select the most discriminative features for reducing the classification time and improving the classification performance. Due to the imbalanced class distribution, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. ITerative Sampling (ITS) method is proposed to avoid the limitations of those methods. ITS method has two steps. The first step (sampling step) iteratively modifies the prior distribution of the minority and majority classes. In the second step, a data cleaning method is used to remove the overlapping that is produced from the first step. In the third phase, Bagging classifier is used to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed model performed well in classifying the unknown samples according to all toxic effects in the imbalanced datasets.
Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid
Authors: Zhan Honglei , Liang Jun F. 
Published: December 2016

AbstractNon-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 < 5.0 μg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field.
Use of polyvinylpyrrolidone-iodine solution for sterilisation and preservation improves mechanical properties and osteogenesis of allografts
Authors: Zhao Yantao , Hu Xiantong , Li Zhonghai , Wang Fuli , Xia Yang , Hou Shuxun , Zhong Hongbin , Zhang Feimin , Gu Ning 
Published: December 2016

AbstractAllografts eliminate the disadvantages associated with autografts and synthetic scaffolds but are associated with a disease-transmission risk. Therefore, allograft sterilisation is crucial. We aimed to determine whether polyvinylpyrrolidone-iodine (PVP-I) can be used for sterilisation and as a new wet-preservation method. PVP-I–sterilised and preserved allografts demonstrated improved mechanical property, osteogenesis, and excellent microbial inhibition. A thigh muscle pouch model of nude mice showed that PVP-I–preserved allografts demonstrated better ectopic formation than Co60-sterilised allografts (control) in vivo (P < 0.05). Furthermore, the PVP-I–preserved group showed no difference between 24 h and 12 weeks of allograft preservation (P > 0.05). PVP-I–preserved allografts showed more hydrophilic surfaces and PVP-I–sterilised tendons showed higher mechanical strength than Co60-sterilised tendons (P < 0.05). The level of residual PVP-I was higher without washing and with prolonged preservation (P < 0.05). In vitro cellular tests showed that appropriate PVP-I concentration was nontoxic to preosteoblast cells, and cellular differentiation measured by alkaline phosphatase activity and osteogenic gene markers was enhanced (P < 0.05). Therefore, the improved biological performance of implanted allografts may be attributable to better surface properties and residual PVP-I, and PVP-I immersion can be a simple, easy method for allograft sterilisation and preservation.
Mitigate Cascading Failures on Networks using a Memetic Algorithm
Authors: Tang Xianglong , Liu Jing , Hao Xingxing 
Published: December 2016

AbstractResearch concerning cascading failures in complex networks has become a hot topic. However, most of the existing studies have focused on modelling the cascading phenomenon on networks and analysing network robustness from a theoretical point of view, which considers only the damage incurred by the failure of one or several nodes. However, such a theoretical approach may not be useful in practical situation. Thus, we first design a much more practical measure to evaluate the robustness of networks against cascading failures, termedRcf. Then, adoptingRcfas the objective function, we propose a new memetic algorithm (MA) named MA-Rcfto enhance network the robustness against cascading failures. Moreover, we design a new local search operator that considers the characteristics of cascading failures and operates by connecting nodes with a high probability of having similar loads. In experiments, both synthetic scale-free networks and real-world networks are used to test the efficiency and effectiveness of the MA-Rcf. We systematically investigate the effects of parameters on the performance of the MA-Rcfand validate the performance of the newly designed local search operator. The results show that the local search operator is effective, that MA-Rcfcan enhance network robustness against cascading failures efficiently, and that it outperforms existing algorithms.
Global water cycle amplifying at less than the Clausius-Clapeyron rate
Authors: Skliris Nikolaos , Zika Jan D. , Nurser George , Josey Simon A. , Marsh Robert 
Published: December 2016

AbstractA change in the cycle of water from dry to wet regions of the globe would have far reaching impact on humanity. As air warms, its capacity to hold water increases at the Clausius-Clapeyron rate (CC, approximately 7% °C−1). Surface ocean salinity observations have suggested the water cycle has amplified at close to CC following recent global warming, a result that was found to be at odds with state-of the art climate models. Here we employ a method based on water mass transformation theory for inferring changes in the water cycle from changes in three-dimensional salinity. Using full depth salinity observations we infer a water cycle amplification of 3.0 ± 1.6% °C−1 over 1950–2010. Climate models agree with observations in terms of a water cycle amplification (4.3 ± 2.0% °C−1) substantially less than CC adding confidence to projections of total water cycle change under greenhouse gas emission scenarios.
Thyroid hormone suppresses expression of stathmin and associated tumor growth in hepatocellular carcinoma
Authors: Tseng Yi-Hsin , Huang Ya-Hui , Lin Tzu-Kang , Wu Sheng-Ming , Chi Hsiang-Cheng , Tsai Chung-Ying , Tsai Ming-Ming , Lin Yang-Hsiang , Chang Wei-Chun , Chang Ya-Ting , Chen Wei-Jan , Lin Kwang-Huei 
Published: December 2016

AbstractStathmin (STMN1), a recognized oncoprotein upregulated in various solid tumors, promotes microtubule disassembly and modulates tumor growth and migration activity. However, the mechanisms underlying the genetic regulation of STMN1 have yet to be elucidated. In the current study, we report that thyroid hormone receptor (THR) expression is negatively correlated with STMN1 expression in a subset of clinical hepatocellular carcinoma (HCC) specimens. We further identified the STMN1 gene as a target of thyroid hormone (T3) in the HepG2 hepatoma cell line. An analysis of STMN1 expression profile and mechanism of transcriptional regulation revealed that T3 significantly suppressed STMN1 mRNA and protein expression, and further showed that THR directly targeted the STMN1 upstream element to regulate STMN1 transcriptional activity. Specific knockdown of STMN1 suppressed cell proliferation and xenograft tumor growth in mice. In addition, T3 regulation of cell growth arrest and cell cycle distribution were attenuated by overexpression of STMN1. Our results suggest that the oncogene STMN1 is transcriptionally downregulated by T3 in the liver. This T3-mediated suppression of STMN1 supports the theory that T3 plays an inhibitory role in HCC tumor growth, and suggests that the lack of normal THR function leads to elevated STMN1 expression and malignant growth.
Co-delivery of docetaxel and palmitoyl ascorbate by liposome for enhanced synergistic antitumor efficacy
Authors: Li Junxiu , Guo Chaorui , Feng Fan , Fan Ali , Dai Yu , Li Ning , Zhao Di , Chen Xijing , Lu Yang 
Published: December 2016

AbstractPalmitoyl ascorbate (PA) as an antioxidant has the potential for the treatment of cancer. In the present study, a nanocarrier system was developed for co-delivery of docetaxel (DOC) with palmitoyl ascorbate and the therapeutic efficacy of a combination drug regimen was investigated. For this purpose, different ratios of docetaxel and palmitoyl ascorbate were co-encapsulated in a liposome and they all showed high encapsulation efficiency. The average diameters of the liposomes ranged from 140 to 170 nm. Negative zeta potential values were observed for all systems, ranged from −40 mV to −56 mV. Studies on drug release and cellular uptake of the co-delivery system demonstrated that both drugs were effectively taken up by the cells and released slowly. Moreover, the liposome loading drugs with DOC/PA concentration ratio of 1:200 showed the highest anti-tumor activity to three different types of tumor cells. The higher in vivo therapeutic efficacy with lower systemic toxicity of the DOC-PA200-LPs was also verified by the H22 tumor bearing mice model. Our results showed that such co-loaded delivery systems could serve as a promising therapeutic approach to improve clinical outcomes against hepatic carcinoma.
Characterization of the first double-stranded RNA bacteriophage infecting Pseudomonas aeruginosa
Authors: Yang Yuhui , Lu Shuguang , Shen Wei , Zhao Xia , Shen Mengyu , Tan Yinling , Li Gang , Li Ming , Wang Jing , Hu Fuquan , Le Shuai 
Published: December 2016

AbstractBacteriophages (phages) are widely distributed in the biosphere and play a key role in modulating microbial ecology in the soil, ocean, and humans. Although the role of DNA bacteriophages is well described, the biology of RNA bacteriophages is poorly understood. More than 1900 phage genomes are currently deposited in NCBI, but only 6 dsRNA bacteriophages and 12 ssRNA bacteriophages genome sequences are reported. The 6 dsRNA bacteriophages were isolated from legume samples or lakes with Pseudomonas syringae as the host. Here, we report the first Pseudomonas aeruginosa phage phiYY with a three-segmented dsRNA genome. phiYY was isolated from hospital sewage in China with the clinical P. aeruginosa strain, PAO38, as a host. Moreover, the dsRNA phage phiYY has a broad host range, which infects 99 out of 233 clinical P. aeruginosa strains isolated from four provinces in China. This work presented a detailed characterization of the dsRNA bacteriophage infecting P. aeruginosa.
The defining DNA methylation signature of Floating-Harbor Syndrome
Authors: Hood Rebecca L. , Schenkel Laila C. , Nikkel Sarah M. , Ainsworth Peter J. , Pare Guillaume , Boycott Kym M. , Bulman Dennis E. , Sadikovic Bekim 
Published: December 2016

AbstractFloating-Harbor syndrome (FHS) is an autosomal dominant genetic condition characterized by short stature, delayed osseous maturation, expressive language impairment, and unique facial dysmorphology. We previously identified mutations in the chromatin remodeling protein SRCAP (SNF2-related CBP Activator Protein) as the cause of FHS. SRCAP has multiple roles in chromatin and transcriptional regulation; however, specific epigenetic consequences of SRCAP mutations remain to be described. Using high resolution genome-wide DNA methylation analysis, we identified a unique and highly specific DNA methylation “epi-signature” in the peripheral blood of individuals with FHS. Both hyper and hypomethylated loci are distributed across the genome, preferentially occurring in CpG islands. Clonal bisulfite sequencing of two hypermethylated (FIGN and STPG2) and two hypomethylated (MYO1F and RASIP1) genes confirmed these findings. The identification of a unique methylation signature in FHS provides further insight into the biological function of SRCAP and provides a unique biomarker for this disorder.
Long Duration of Ground Motion in the Paradigmatic Valley of Mexico
Authors: Cruz-Atienza V. M. , Tago J. , Sanabria-Gómez J. D. , Chaljub E. , Etienne V. , Virieux J. , Quintanar L. 
Published: December 2016

AbstractBuilt-up on top of ancient lake deposits, Mexico City experiences some of the largest seismic site effects worldwide. Besides the extreme amplification of seismic waves, duration of intense ground motion from large subduction earthquakes exceeds three minutes in the lake-bed zone of the basin, where hundreds of buildings collapsed or were seriously damaged during the magnitude 8.0 Michoacán earthquake in 1985. Different mechanisms contribute to the long lasting motions, such as the regional dispersion and multiple-scattering of the incoming wavefield from the coast, more than 300 km away the city. By means of high performance computational modeling we show that, despite the highly dissipative basin deposits, seismic energy can propagate long distances in the deep structure of the valley, promoting also a large elongation of motion. Our simulations reveal that the seismic response of the basin is dominated by surface-waves overtones, and that this mechanism increases the duration of ground motion by more than 170% and 290% of the incoming wavefield duration at 0.5 and 0.3 Hz, respectively, which are two frequencies with the largest observed amplification. This conclusion contradicts what has been previously stated from observational and modeling investigations, where the basin itself has been discarded as a preponderant factor promoting long and devastating shaking in Mexico City.
Overexpression of Glucocorticoid-induced Leucine Zipper (GILZ) increases susceptibility to Imiquimod-induced psoriasis and involves cutaneous activation of TGF-β1
Authors: Carceller Elena , Ballegeer Marlies , Deckers Julie , Riccardi Carlo , Bruscoli Stefano , Hochepied Tino , Libert Claude , Pérez Paloma 
Published: December 2016

AbstractPsoriasis vulgaris is a chronic inflammatory skin disease affecting millions of people. Its pathophysiology is complex and involves a skin compartment with epidermal and immune cells which produce cytokines, e.g. belonging to the IL-23–Th17-cell axis. Glucocorticoids (GCs) are the most common therapeutics used in cutaneous inflammatory disorders and GC-induced leucine zipper (GILZ) has emerged as a mediator of GCs due to its anti-inflammatory actions, theoretically lacking GC side-effects. We evaluated whether GILZ may provide a better therapeutic index in comparison to GCs during the onset and progression of psoriasis by generating and characterizing a mouse model with generalized overexpression of this protein (GILZ-Tg mice) and the imiquimod (IMQ) psoriasis model. Unexpectedly, in GILZ-Tg mice, the severity of IMQ-induced psoriasis-like skin lesions as well as induction of cytokines commonly up-regulated in human psoriasis (Il-17, Il-22, Il-23, Il-6, S100a8/a9, and Stat3) was significantly more pronounced relative to GILZ-Wt mice. The increased susceptibility to IMQ-induced psoriasis of GILZ-Tg mice was significantly associated with skin-specific over-activation of TGF-β1-mediated signaling via SMAD2/3. Our findings demonstrate that GILZ may behave as pro-inflammatory protein in certain tissues and that, similar to prolonged GC therapy, GILZ as an alternative treatment for psoriasis may also have adverse effects.
Sensitisation of an Azole-Resistant Aspergillus fumigatus Strain containing the Cyp51A-Related Mutation by Deleting the SrbA Gene
Authors: Hagiwara Daisuke , Watanabe Akira , Kamei Katsuhiko 
Published: December 2016

AbstractAzoles are widely used for controlling fungal growth in both agricultural and medical settings. The target protein of azoles is CYP51, a lanosterol 14-α-demethylase involved in the biosynthesis of ergosterol. Recently, a novel azole resistance mechanism has arisen in pathogenic fungal species Aspergillus fumigatus. Resistant strains contain a 34-bp or 46-bp tandem repeat (TR) in the promoter of cyp51A, and have disseminated globally in a short period of time. In this study, we investigated whether an azole-resistant strain with a 46-bp TR (TR46/Y121F/T289A) could be sensitised to azoles by deletion of srbA, encoding a direct regulator of cyp51A. The loss of SrbA did not affect colony growth or conidia production, but decreased expression of cyp51A. The srbA deletion strain showed hyper-susceptibility to medical azoles as well as azole fungicides, while its sensitivity to non-azole fungicides was unchanged. This is the first demonstration that deletion of a regulator of cyp51A can sensitise an azole-resistant A. fumigatus strain. This finding may assist in the development of new drugs to help combat life-threatening azole-resistant fungal pathogens.
Real-Time Optical Monitoring of Pt Catalyst Under the Potentiodynamic Conditions
Authors: Song Hyeon Don , Lee Minzae , Kim Gil-Pyo , Choi Inhee , Yi Jongheop 
Published: December 2016

AbstractIn situ monitoring of electrode materials reveals detailed physicochemical transition in electrochemical device. The key challenge is to explore the localized features of electrode surfaces, since the performance of an electrochemical device is determined by the summation of local architecture of the electrode material. Adaptive in situ techniques have been developed for numerous investigations; however, they require restricted measurement environments and provide limited information, which has impeded their widespread application. In this study, we realised an optics-based electrochemical in situ monitoring system by combining a dark-field micro/spectroscopy with an electrochemical workstation to investigate the physicochemical behaviours of Pt catalyst. We found that the localized plasmonic trait of a Pt-decorated Au nanoparticle as a model system varied in terms of its intensity and wavelength during the iterations of a cyclic voltammetry test. Furthermore, we show that morphological and compositional changes of the Pt catalyst can be traced in real time using changes in quantified plasmonic characteristics, which is a distinct advantage over the conventional electrochemistry-based in situ monitoring systems. These results indicate the substantial promise of online operando observation in a wide range of electrical energy conversion systems and electrochemical sensing areas.
The mechanism of a formaldehyde-sensing transcriptional regulator
Authors: Denby Katie J. , Iwig Jeffrey , Bisson Claudine , Westwood Jodie , Rolfe Matthew D. , Sedelnikova Svetlana E. , Higgins Khadine , Maroney Michael J. , Baker Patrick J. , Chivers Peter T. , Green Jeffrey 
Published: December 2016

AbstractMost organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. Therefore, biology has evolved systems to perceive and detoxify formaldehyde. The frmRA(B) operon that is present in many bacteria represents one such system. The FrmR protein is a transcriptional repressor that is specifically inactivated in the presence of formaldehyde, permitting expression of the formaldehyde detoxification machinery (FrmA and FrmB, when the latter is present). The X-ray structure of the formaldehyde-treated Escherichia coli FrmR (EcFrmR) protein reveals the formation of methylene bridges that link adjacent Pro2 and Cys35 residues in the EcFrmR tetramer. Methylene bridge formation has profound effects on the pattern of surface charge of EcFrmR and combined with biochemical/biophysical data suggests a mechanistic model for formaldehyde-sensing and derepression of frmRA(B) expression in numerous bacterial species.
Harmonic‐free and low cost delay‐locked loop with a 20–80% input duty cycle
Authors: Wei Xing , Chen Zhujia , Li Wei , Yang Haigang 
Published: December 2016

A low‐cost two‐step delay locked loop (DLL) with a 20–80% input duty cycle is presented. For eliminating harmonic and zero‐trap locking issues along the whole range of digital controlled delay line, a hierarchy phase detector (HPD) is proposed to compare the phase difference between input reference clock and two phase‐isotonic clocks generated by sharing a common delay line. By monitoring of HPD's output, state controller can solve harmonic and zero‐trap locking issues while being naturally immune to the wide range of input duty cycle. With an asymmetric edge combiner, high duty cycle correction accuracy can be achieved. The proposed DLL is implemented in 55 nm CMOS technology with a 0.00574 mm2 chip area. Simulation results show that the operation range of the proposed DLL is 0.3–1.6 GHz without the occurrence of harmonic and zero‐trap locking, and the range of input duty cycle is 20–80%. The power consumption is 0.76 mW at 1.6 GHz.