bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Does the L884P Mutation Confer Resistance to Type-II Inhibitors of JAK2 Kinase: A Comprehensive Molecular Modeling Study
Authors: Kong Xiaotian , Sun Huiyong , Pan Peichen , Li Dan , Zhu Feng , Chang Shan , Xu Lei , Li Youyong , Hou Tingjun 
Published: August 2017

AbstractJanus kinase 2 (JAK2) has been regarded as an essential target for the treatment of myeloproliferative neoplasms (MPNs). BBT594 and CHZ868, Type-II inhibitors of JAK2, illustrate satisfactory efficacy in preclinical MPNs and acute lymphoblastic leukemia (ALL) models. However, the L884P mutation of JAK2 abrogates the suppressive effects of BBT594 and CHZ868. In this study, conventional molecular dynamics (MD) simulations, umbrella sampling (US) simulations and MM/GBSA free energy calculations were employed to explore how the L884P mutation affects the binding of BBT594 and CHZ868 to JAK2 and uncover the resistance mechanism induced by the L884P mutation. The results provided by the US and MD simulations illustrate that the L884P mutation enhances the flexibility of the allosteric pocket and alters their conformations, which amplify the conformational entropy change (−TΔS) and weaken the interactions between the inhibitors and target. Additionally, the structural analyses of BBT594 and CHZ868 in complex with the WT JAK2 illustrate that the drug tail with strong electronegativity and small size located in the allosteric pocket of JAK2 may enhance anti-resistance capability. In summary, our results highlight that both of the changes of the conformational entropies and enthalpies contribute to the L884P-induced resistance in the binding of two Type-II inhibitors into JAK2 kinase.
Liprin-α-1 is a novel component of the murine neuromuscular junction and is involved in the organization of the postsynaptic machinery
Authors: Bernadzki Krzysztof M. , Gawor Marta , Pęziński Marcin , Mazurek Paula , Niewiadomski Paweł , Rędowicz Maria J. , Prószyński Tomasz J. 
Published: August 2017

AbstractNeuromuscular junctions (NMJs) are specialized synapses that connect motor neurons to skeletal muscle fibers and orchestrate proper signal transmission from the nervous system to muscles. The efficient formation and maintenance of the postsynaptic machinery that contains acetylcholine receptors (AChR) are indispensable for proper NMJ function. Abnormalities in the organization of synaptic components often cause severe neuromuscular disorders, such as muscular dystrophy. The dystrophin-associated glycoprotein complex (DGC) was shown to play an important role in NMJ development. We recently identified liprin-α-1 as a novel binding partner for one of the cytoplasmic DGC components, α-dystrobrevin-1. In the present study, we performed a detailed analysis of localization and function of liprin-α-1 at the murine NMJ. We showed that liprin-α-1 localizes to both pre- and postsynaptic compartments at the NMJ, and its synaptic enrichment depends on the presence of the nerve. Using cultured muscle cells, we found that liprin-α-1 plays an important role in AChR clustering and the organization of cortical microtubules. Our studies provide novel insights into the function of liprin-α-1 at vertebrate neuromuscular synapses.
Peritoneal Dialysis Catheter Emplacement by Advanced Laparoscopy: 8-year Experience from a Medical Center of China
Authors: Mo Min , Ju Yongle , Hu Haitang , Zhang Wei , Pan Jianyi , Zheng Qingkun , Chen Jinzhong , Su Lijuan , Dou Xianrui 
Published: August 2017

AbstractLaparoscopic experience and relevant reports about PD catheter emplacement in Chinese patients are seldom. In this study, we described our experience with advanced laparoscopy for PD catheter implantation in Chinese patients. There were one hundred and thirty Chinese patients accepted advanced laparoscopic approach for PD catheter emplacement in this study. Six of 26 patients with prior abdominal operations had abdominal adhesion, while six of 104 patients without prior abdominal surgeries showed abdominal adhesion. Operation time required 10 to 180 minutes. During a mean follow-up time of 26.46 months, the catheter complications were shown as outflow obstruction (n = 6, 4.62%), pericatheter leaking (n = 3, 2.31%), hydrocele of tunica vaginalis (n = 1, 0.77% in all), and umbilical hernia (n = 2, 1.54%). Cumulative revision-free survival probability for catheter loss from mechanical complications at 8 years was 0.95. During the postoperative follow-up ranged between 6 and 106 months, 98 patients (75.38%) were still on CAPD, 17 patients (13.08%) died, 8 patients (6.15%) were transferred to hemodialysis, 6 patients (4.62%) received kidney transplantation, and 1 patient (0.77%) showed improved renal function. These results showed that PD catheter placement with advanced laparoscopy is a safe and effective approach in Chinese patients with or without prior abdominal surgeries.
Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy
Authors: Jun Ikhyun , Lee Joon Suk , Lee Ji Hwan , Lee Christopher Seungkyu , Choi Seung-il , Gee Heon Yung , Lee Min Goo , Kim Eung Kweon 
Published: August 2017

AbstractAdult-onset vitelliform macular dystrophy (AVMD) is a common and benign macular degeneration which can be caused by BEST1 mutation. Here, we investigated the clinical characteristics associated with a newly identified BEST1 mutation, p.Ile38Ser and confirmed the associated physiological functional defects. The 51-year-old patient presented bilateral small subretinal yellow deposits. Consistent with AVMD, the corresponding lesions showed hyperautofluorescence, late staining in fluorescein angiography, and subretinal hyper-reflective materials in spectral-domain optical coherence tomography. Genetic analysis demonstrated that the patient presented with a heterozygous p.Ile38Ser BEST1 mutation. Surface biotinylation and patch clamp experiments were performed in transfected HEK293T cells. Although, the identified BEST1 mutant maintains normal membrane expression, p.Ile38Ser mutant showed significantly smaller currents than wild type (WT). However, it showed larger currents than other BEST1 mutants, p.Trp93Cys, causing autosomal dominant best vitelliform macular dystrophy (BVMD), and p.Ala195Val, causing autosomal recessive bestrophinopathy (ARB). The cells expressing both WT and each BEST1 mutant showed that the functional defect of p.Ile38ser was milder than that of p.Trp93Cys, whereas combination of p.Ala195Val with WT showed good current. We identified and described the phenotype and in vitro functions of a novel BEST1 mutation causing AVMD. AVMD induced by p.Ile38Ser BEST1 mutation is a mild form of BVMD.
Cyclocarya paliurus tea leaves enhances pancreatic β cell preservation through inhibition of apoptosis
Authors: Xiao Hai-tao , Wen Bo , Ning Zi-wan , Zhai Li-xiang , Liao Cheng-hui , Lin Cheng-yuan , Mu Huai-xue , Bian Zhao-xiang 
Published: August 2017

AbstractLeaves of Cyclocarya paliurus are a sweet tea traditionally used to treat obesity and diabetes in China. However, its protective mechanisms against hyperglycemia remains unclear. Here, we demonstrate that the extract of C. paliurus leaves significantly decreased body loss, food intake and blood glucose level, and increased blood insulin level, β-cell number and insulin-producing β cells in high-fat diet-low dose STZ-induced diabetic mice. In vivo and in vitro studies also showed the extract of C. paliurus leaves significantly inhibited pancreatic β cell apoptosis by suppressing the expression of caspase 8, caspase 9 and cleaved caspase-3, as well as Bax/Bcl-2 ratio, down-regulating p38, ERK and JNK phosphorylation, and up-regulating Akt phosphorylation. These effects were significantly enhanced by inhibitor p-38 or ERK or JNK, and counteracted by inhibitor of PI3K. In addition, the extract of C. paliurus leaves also significantly improved hepatic steatosis, nephropathy and cardiac hypertrophy of diabetic mice. Taken together, these results provide the insight into the effects of C. paliurus leaves on pancreatic β cell preservation in standing glucolipotoxicity. Therefore, C. paliurus tea leaves may be used as a new remedy for diabetes through enhancing pancreatic β cell preservation by inhibiting β cell apoptosis.
Fungal lifestyle reflected in serine protease repertoire
Authors: Muszewska Anna , Stepniewska-Dziubinska Marta M. , Steczkiewicz Kamil , Pawlowska Julia , Dziedzic Agata , Ginalski Krzysztof 
Published: August 2017

AbstractFungi are able to switch between different lifestyles in order to adapt to environmental changes. Their ecological strategy is connected to their secretome as fungi obtain nutrients by secreting hydrolytic enzymes to their surrounding and acquiring the digested molecules. We focus on fungal serine proteases (SPs), the phylogenetic distribution of which is barely described so far. In order to collect a complete set of fungal proteases, we searched over 600 fungal proteomes. Obtained results suggest that serine proteases are more ubiquitous than expected. From 54 SP families described in MEROPS Peptidase Database, 21 are present in fungi. Interestingly, 14 of them are also present in Metazoa and Viridiplantae – this suggests that, except one (S64), all fungal SP families evolved before plants and fungi diverged. Most representatives of sequenced eukaryotic lineages encode a set of 13–16 SP families. The number of SPs from each family varies among the analysed taxa. The most abundant are S8 proteases. In order to verify hypotheses linking lifestyle and expansions of particular SP, we performed statistical analyses and revealed previously undescribed associations. Here, we present a comprehensive evolutionary history of fungal SP families in the context of fungal ecology and fungal tree of life.
BHX, a novel pyrazoline derivative, inhibits breast cancer cell invasion by reversing the epithelial-mesenchymal transition and down-regulating Wnt/β-catenin signalling
Authors: Bao Hanmei , Zhang Qing , Zhu Zhongling , Xu Hui , Ding Fengxia , Wang Meisa , Du Shuangshuang , Du Yibo , Yan Zhao 
Published: August 2017

AbstractThe novel pyrazoline derivative, BHX, has recently been shown to exhibit potent anti-tumour activity by blocking the Wnt/β-catenin signalling pathway. However, its effect on breast cancer growth and invasion are unknown. Our results show that BHX suppresses MDA-MB-231 cell viability and colony formation in a dose-dependent manner, and induces apoptosis and G0/G1 phase arrest. BHX-treated breast cancer cells showed morphological characteristics of cells undergoing apoptosis. Furthermore, BHX inhibited cell migration and invasion, which was associated with increased E-cadherin mRNA and protein expression, and down-regulation of SNAIL and vimentin. In addition, BHX induced the generation of intracellular ROS and decreased β-catenin protein and mRNA expression. We used a mouse xenograft model to investigate the effects of BHX in vivo, where the growth of MDA-MB-231 xenografted tumours was suppressed in nude mice treated continuously with BHX for 21 days. Finally, the rat plasma concentration of BHX was measured by ultra-performance liquid-chromatography tandem mass spectrometry and the pharmacokinetic parameters of BHX were processed by non-compartmental analysis. In conclusion, BHX merits further study as a novel therapeutic small molecule for the treatment of breast cancer.
Differential neurophysiological correlates of information processing in Internet gaming disorder and alcohol use disorder measured by event-related potentials
Authors: Park Minkyung , Kim Yeon Jin , Kim Dai Jin , Choi Jung-Seok 
Published: August 2017

AbstractInternet gaming disorder (IGD) shares clinical and neuropsychological features with alcohol use disorder (AUD), but few studies have identified the neurophysiological characteristics of IGD. We investigated the N100 and P300 event-related potentials (ERPs) in patients with IGD to compare them with those of patients with AUD and healthy controls (HCs). Twenty-six patients with IGD, 22 patients with AUD, and 29 HCs participated in this study. ERPs were acquired from young male adults during an auditory oddball task. Between-group differences in N100 and P300 were investigated separately using repeated-measures analysis of variance. Correlations between the ERP values and neurocognitive functioning of each group were examined. Both the IGD and AUD groups showed reduced P300 amplitudes at the midline central and parietal area compared with the HCs. The IGD exhibited reduced N100 amplitudes at the midline frontal area compared with the HCs. The reduced P300 were correlated with a higher spatial span error rate in the IGD. The reduced N100 and P300 were not correlated with Internet addiction severity scores in the IGD. These results indicate that IGD have abnormalities in the P300 comparable to those in AUD. Moreover, the reduction in N100 could be considered a candidate trait marker for IGD.
Study on Physio-chemical Properties of plasma polymerization in C2H2/N2 plasma and Their Impact on COL X
Authors: Ghafouri Samaneh , Abdijahed Sara , Farivar Shirin , Hosseini Seyed Iman , Rezaei Fatemeh , Ardeshirylajimi Abdolreza , Shokri Babak 
Published: August 2017

AbstractNitrogen-containing plasma polymerization is of considerable interest for tissue engineering due to their properties on cell adhesion and mesenchymal stem cells (MSCs) response. In this study, low-pressure RF plasma of acetylene and nitrogen was used to deposit nitrogen-containing plasma polymerized coatings on several substrates. Deposition kinetics and surface characteristics of coatings were investigated in terms of RF power and gas flow ratio. OES was used to monitor the plasma process and investigate the relation between the film structure and plasma species. Presence of several bonds and low concentration of amine functional groups were determined using FTIR and Colorimetric methods. Contact angle goniometry results indicated about 30% increase in surface hydrophilicity. Stability of coatings in air and two different liquid environments was examined by repeating surface free energy measurements. Deposited films exhibited acceptable stability during the storage duration. Surface roughness measured by AFM was found to decrease with growing concentration of nitrogen. The deposition rate increased with increasing RF power and decreased with growing concentration of nitrogen. Zeta potential measurements of coatings revealed the negative potential on the surface of the thin films. Temporary suppression of collagen X in the presence of plasma coatings was confirmed by RT-PCR results.
Condition-dependence of pheomelanin-based coloration in nuthatches Sitta europaea suggests a detoxifying function: implications for the evolution of juvenile plumage patterns
Authors: Galván Ismael 
Published: August 2017

AbstractAdult-like juvenile plumage patterns often signal genotypic quality to parents. During adulthood, the same patterns often signal quality to mates. This has led to assume that adult-like juvenile plumage is a developmental consequence of sexual selection operating in adults. Many of these patterns are produced by the pigment pheomelanin, whose synthesis may help remove toxic excess cysteine. Excess cysteine is likely to arise under conditions of relatively low stress, such as those experienced by nestling birds. Thus, adult-like plumage may be advantageous for juveniles if produced by pheomelanin. In the Eurasian nuthatch Sitta europaea, juveniles are sexually dichromatic and identical to adults. Nestling nuthatches in poorer condition develop more intense pheomelanin-based feathers, indicating greater pigment production. The same is not observed in adults. This is contrary to a function related to signaling quality and instead suggests that, at least in the Eurasian nuthatch, adult-like juvenile plumage has evolved because of the detoxifying function of pheomelanin-based pigmentation. Given the prevalence of colors typically conferred by pheomelanin in juvenile plumage patterns, the detoxifying capacity of pheomelanin under low stress levels should be considered as an explanation for the evolution of both adult-like and distinctively juvenile plumage patterns.
Research on the control strategy of distributed energy resources inverter based on improved virtual synchronous generator
Authors: Gao Changwei , Liu Xiaoming , Chen Hai 
Published: August 2017

AbstractThis paper focus on the power fluctuations of the virtual synchronous generator(VSG) during the transition process. An improved virtual synchronous generator(IVSG) control strategy based on feed-forward compensation is proposed. Adjustable parameter of the compensation section can be modified to achieve the goal of reducing the order of the system. It can effectively suppress the power fluctuations of the VSG in transient process. To verify the effectiveness of the proposed control strategy for distributed energy resources inverter, the simulation model is set up in MATLAB/SIMULINK platform and physical experiment platform is established. Simulation and experiment results demonstrate the effectiveness of the proposed IVSG control strategy.
Magnetic Nanoparticle Assisted Self-assembly of Cell Penetrating Peptides-Oligonucleotides Complexes for Gene Delivery
Authors: Dowaidar Moataz , Abdelhamid Hani Nasser , Hällbrink Mattias , Freimann Krista , Kurrikoff Kaido , Zou Xiaodong , Langel Ülo 
Published: August 2017

AbstractMagnetic nanoparticles (MNPs, Fe3O4) incorporated into the complexes of cell penetrating peptides (CPPs)-oligonucleotides (ONs) promoted the cell transfection for plasmid transfection, splice correction, and gene silencing efficiencies. Six types of cell penetrating peptides (CPPs; PeptFect220 (denoted PF220), PF221, PF222, PF223, PF224 and PF14) and three types of gene therapeutic agents (plasmid (pGL3), splicing correcting oligonucleotides (SCO), and small interfering RNA (siRNA) were investigated. Magnetic nanoparticles incorporated into the complexes of CPPs-pGL3, CPPs-SCO, and CPPs-siRNA showed high cell biocompatibility and efficiently transfected the investigated cells with pGL3, SCO, and siRNA, respectively. Gene transfer vectors formed among PF14, SCO, and MNPs (PF14-SCO-MNPs) showed a superior transfection efficiency (up to 4-fold) compared to the noncovalent PF14-SCO complex, which was previously reported with a higher efficiency compared to commercial vector called Lipofectamine™2000. The high transfection efficiency of the new complexes (CPPs-SCO-MNPs) may be attributed to the morphology, low cytotoxicity, and the synergistic effect of MNPs and CPPs. PF14-pDNA-MNPs is an efficient complex for in vivo gene delivery upon systemic administration. The conjugation of CPPs-ONs with inorganic magnetic nanoparticles (Fe3O4) may open new venues for selective and efficient gene therapy.
Assembly of a functional and responsive microstructure by heat bonding of DNA-grafted colloidal brick
Authors: Sakamoto Yuki , Toyabe Shoichi 
Published: August 2017

AbstractA micromachine constructed to possess various chemical and mechanical functions is one of the ultimate targets of technology. Conventional lithographic processes can be used to form complicated structures. However, they are basically limited to rigid and static structures with poor surface properties. Here, we demonstrate a novel method for assembling responsive and functional microstructures from diverse particles modified with DNA strands. The DNA strands are designed to form hairpins at room temperature and denature when heated. Structures are assembled through the simultaneous manipulation and heating of particles with “hot” optical tweezers, which incorporates the particles one by one. The flexible connection formed by DNA strands allows the responsive deformation of the structures with local controllability of the structural flexibility. We assembled a microscopic robot arm actuated by an external magnet, a hinge structure with a locally controlled connection flexibility and a three-dimensional double helix structure. The method is simple and can also be applied to build complex biological tissues from cells.
Enhanced photoelectrochemical performance of anatase TiO2 for water splitting via surface codoping
Authors: Wang Jiajun , Huang Jing , Meng Jie , Li Qunxiang , Yang Jinlong 
Published: August 2017

We explore the (Rh + F) surface codoping effect on anatase TiO2 (101) and (001) facets for solar water splitting by performing extensive density functional theory calculations.
Novel approach for sleep disorder monitoring using a finite‐state machine for localities lacking specialist physicians
Authors: Swetapadma Aleena 
Published: August 2017

This study proposes a novel method for sleep disorder monitoring based on a finite‐state machine (FSM) from various bio‐signals, namely electroencephalography (EEG), electro‐oculography (EOG) and electromyography (EMG) signals. The sleep signals have been obtained from physionet sleep repository, which includes horizontal EOG, submental‐EMG and EEG sampled at 100 Hz sampling frequency. Inputs given to the FSM‐based module are the processed signals from EMG, EEG and EOG signals. The FSM module for sleep analysis is composed of different states and the conditions to flow from one state to another state. In this study, two FSM modules are designed, one for sleep wave and another for sleep stage identification. Based on the outputs obtained from the above two FSM modules, the sleep disorder can be monitored. The accuracy of the proposed method has been calculated with percentage accuracy, false acceptance rate and false rejection ratio. The average classification accuracy of the finite‐state automaton (FSA)‐based method is up to 99% for all the tested fault cases. The proposed FSA method suggests a novel method and can be put to effective use in the rural areas for primary analysis.
Structure and ferromagnetism properties of leaf‐like ZnO nanostructures
Authors: Lijun Li 
Published: August 2017

Leaf‐like macroscopic ZnO nanostructures have been synthesised via a conventional thermal evaporation method at 950°C, using a mixture of graphite, zinc oxide and CuO powders as a source material. The effect of CuO in a relevant growth mechanism was discussed. Its crystal structure properties were determined using X‐ray diffraction, scanning electron microscopy and high resolution transmission electron microscopy. Photoluminescence spectra of the sample exhibit emission peaks centred at about 382, 525, 542 and 767 nm, respectively. The room temperature ferromagnetism was observed using a physical property measurement system.
Effects of various hydrogenated temperatures on photocatalytic activity of mesoporous titanium dioxide
Authors: Soo Chan Wai , Lai Chin Wei , Pan Guan‐Ting , Yang Thomas Chung‐Kuang , Lee Kian Mun , Yusop Rahimi Muhammad , Juan Joon Ching 
Published: August 2017

Hydrogenated titanium dioxide (H‐TiO2) has drawn much research attention in the photocatalysis society since it has significantly improved solar absorption and enhanced photocatalytic activity. Nevertheless, the key factor that leads to the enhanced photocatalytic performance of H‐TiO2 is still debatable. To clarify this issue, the structural properties of H‐TiO2 and its effects on photogenerated charges are investigated. Mesoporous H‐TiO2 was subjected to different hydrogenation temperatures rate under the flow of purified H2 gas and its photocatalytic activities are evaluated by reactive black 5 photodegradation. The H‐TiO2 pretreated at different temperatures seems to have a detrimental effect on photocatalytic activity as compared with that of untreated H‐TiO2. Further investigations reveal that H‐TiO2 treated at high temperature can cause the formation of less photoactive rutile phase and agglomeration that leads to the inhibition of their photocatalytic activity.