bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mito-priming as a method to engineer Bcl-2 addiction
Authors: Lopez Jonathan , Bessou Margaux , Riley Joel S. , Giampazolias Evangelos , Todt Franziska , Rochegüe Tony , Oberst Andrew , Green Douglas R. , Edlich Frank , Ichim Gabriel , Tait Stephen W. G. 
Published: February 2016

AbstractMost apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis.
Lack of association between IL-10 and IL-18 gene promoter polymorphisms and Parkinson’s disease with cognitive impairment in a Chinese population
Authors: Liu Zhenhua , Guo Jifeng , Wang Yaqin , Li Kai , Kang Jifeng , Wei Yang , Sun Qiying , Xu Qian , Xu Changshui , Yan Xinxiang , Tang Beisha 
Published: February 2016

AbstractInflammatory processes have been implicated in the pathogenesis of Parkinson’s disease (PD), including the development of PD-associated cognitive impairment. Whether genetic variants of inflammatory cytokine genes influence the risk of cognitive impairment in PD is unknown. In this study, we investigated single nucleotide polymorphisms (SNPs) in the IL-10 promoter (rs1800871 and rs1800872) and in the IL-18 promoter (rs1946518 and rs187238) in a Han Chinese cohort (N = 933). PD patients (N = 460) and controls (N = 473) were genotyped. Additionally, 268 PD patients were divided into three subgroups [cognitively normal (PD-NC), mild cognitive impairment (PD-MCI) and with dementia (PD-D)] on the basis of their performance on a battery of neuropsychological tests. No associations were found between the aforementioned polymorphisms and cognitive impairment in PD; thus no confirmatory evidence for the hypothesis of IL-10 and IL-18 alleles modulating the risk of cognitive impairment in Chinese PD patients was obtained.
Under the hood of statistical learning: A statistical MMN reflects the magnitude of transitional probabilities in auditory sequences
Authors: Koelsch Stefan , Busch Tobias , Jentschke Sebastian , Rohrmeier Martin 
Published: February 2016

AbstractWithin the framework of statistical learning, many behavioural studies investigated the processing of unpredicted events. However, surprisingly few neurophysiological studies are available on this topic and no statistical learning experiment has investigated electroencephalographic (EEG) correlates of processing events with different transition probabilities. We carried out an EEG study with a novel variant of the established statistical learning paradigm. Timbres were presented in isochronous sequences of triplets. The first two sounds of all triplets were equiprobable, while the third sound occurred with either low (10%), intermediate (30%), or high (60%) probability. Thus, the occurrence probability of the third item of each triplet (given the first two items) was varied. Compared to high-probability triplet endings, endings with low and intermediate probability elicited an early anterior negativity that had an onset around 100 ms and was maximal at around 180 ms. This effect was larger for events with low than for events with intermediate probability. Our results reveal that, when predictions are based on statistical learning, events that do not match a prediction evoke an early anterior negativity, with the amplitude of this mismatch response being inversely related to the probability of such events. Thus, we report a statistical mismatch negativity (sMMN) that reflects statistical learning of transitional probability distributions that go beyond auditory sensory memory capabilities.
The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization
Authors: Liu Lei , Zhao Yan , Jia Jia , Chen Hui , Bai Wei , Yang Man , Yin Zhanxin , He Chuangye , Zhang Lei , Guo Wengang , Niu Jing , Yuan Jie , Cai Hongwei , Xia Jielai , Fan Daiming , Han Guohong 
Published: February 2016

AbstractThis retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2–66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24–3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15–2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy.
Molecular mechanisms of ionic liquid cytotoxicity probed by an integrated experimental and computational approach
Authors: Yoo Brian , Jing Benxin , Jones Stuart E. , Lamberti Gary A. , Zhu Yingxi , Shah Jindal K. , Maginn Edward J. 
Published: February 2016

AbstractIonic liquids (ILs) are salts that remain liquid down to low temperatures and sometimes well below room temperature. ILs have been called “green solvents” because of their extraordinarily low vapor pressure and excellent solvation power, but ecotoxicology studies have shown that some ILs exhibit greater toxicity than traditional solvents. A fundamental understanding of the molecular mechanisms responsible for IL toxicity remains elusive. Here we show that one mode of IL toxicity on unicellular organisms is driven by swelling of the cell membrane. Cytotoxicity assays, confocal laser scanning microscopy and molecular simulations reveal that IL cations nucleate morphological defects in the microbial cell membrane at concentrations near the half maximal effective concentration (EC50) of several microorganisms. Cytotoxicity increases with increasing alkyl chain length of the cation due to the ability of the longer alkyl chain to more easily embed in and ultimately disrupt, the cell membrane.
Effective pore size and radius of capture for K+ ions in K-channels
Authors: Moldenhauer Hans , Díaz-Franulic Ignacio , González-Nilo Fernando , Naranjo David 
Published: February 2016

AbstractReconciling protein functional data with crystal structure is arduous because rare conformations or crystallization artifacts occur. Here we present a tool to validate the dimensions of open pore structures of potassium-selective ion channels. We used freely available algorithms to calculate the molecular contour of the pore to determine the effective internal pore radius (rE) in several K-channel crystal structures. rE was operationally defined as the radius of the biggest sphere able to enter the pore from the cytosolic side. We obtained consistent rE estimates for MthK and Kv1.2/2.1 structures, with rE = 5.3–5.9 Å and rE = 4.5–5.2 Å, respectively. We compared these structural estimates with functional assessments of the internal mouth radii of capture (rC) for two electrophysiological counterparts, the large conductance calcium activated K-channel (rC = 2.2 Å) and the Shaker Kv-channel (rC = 0.8 Å), for MthK and Kv1.2/2.1 structures, respectively. Calculating the difference between rE and rC, produced consistent size radii of 3.1–3.7 Å and 3.6–4.4 Å for hydrated K+ ions. These hydrated K+ estimates harmonize with others obtained with diverse experimental and theoretical methods. Thus, these findings validate MthK and the Kv1.2/2.1 structures as templates for open BK and Kv-channels, respectively.
Real Time Imaging of Deuterium in a Duplex Stainless Steel Microstructure by Time-of-Flight SIMS
Authors: Sobol O. , Straub F. , Wirth Th. , Holzlechner G. , Boellinghaus Th. , Unger W. E. S. 
Published: February 2016

AbstractFor more than one century, hydrogen assisted degradation of metallic microstructures has been identified as origin for severe technical component failures but the mechanisms behind have not yet been completely understood so far. Any in-situ observation of hydrogen transport phenomena in microstructures will provide more details for further elucidation of these degradation mechanisms. A novel experiment is presented which is designed to elucidate the permeation behaviour of deuterium in a microstructure of duplex stainless steel (DSS). A hydrogen permeation cell within a TOF-SIMS instrument enables electrochemical charging with deuterium through the inner surface of the cell made from DSS. The outer surface of the DSS permeation cell exposed to the vacuum has been imaged by TOF-SIMS vs. increasing time of charging with subsequent chemometric treatment of image data. This in-situ experiment showed evidently that deuterium is permeating much faster through the ferrite phase than through the austenite phase. Moreover, a direct proof for deuterium enrichment at the austenite-ferrite interface has been found.
Selection preserves Ubiquitin Specific Protease 4 alternative exon skipping in therian mammals
Authors: Vlasschaert Caitlyn , Xia Xuhua , Gray Douglas A. 
Published: February 2016

AbstractUbiquitin specific protease 4 (USP4) is a highly networked deubiquitinating enzyme with reported roles in cancer, innate immunity and RNA splicing. In mammals it has two dominant isoforms arising from inclusion or skipping of exon 7 (E7). We evaluated two plausible mechanisms for the generation of these isoforms: (A) E7 skipping due to a long upstream intron and (B) E7 skipping due to inefficient 5′ splice sites (5′SS) and/or branchpoint sites (BPS). We then assessed whether E7 alternative splicing is maintained by selective pressure or arose from genetic drift. Both transcript variants were generated from a USP4-E7 minigene construct with short flanking introns, an observation consistent with the second mechanism whereby differential splice signal strengths are the basis of E7 skipping. Optimization of the downstream 5′SS eliminated E7 skipping. Experimental validation of the correlation between 5′SS identity and exon skipping in vertebrates pinpointed the +6 site as the key splicing determinant. Therian mammals invariably display a 5′SS configuration favouring alternative splicing and the resulting isoforms have distinct subcellular localizations. We conclude that alternative splicing of mammalian USP4 is under selective maintenance and that long and short USP4 isoforms may target substrates in various cellular compartments.
Multivariate multiscale complex network analysis of vertical upward oil-water two-phase flow in a small diameter pipe
Authors: Gao Zhong-Ke , Yang Yu-Xuan , Zhai Lu-Sheng , Dang Wei-Dong , Yu Jia-Liang , Jin Ning-De 
Published: February 2016

AbstractHigh water cut and low velocity vertical upward oil-water two-phase flow is a typical complex system with the features of multiscale, unstable and non-homogenous. We first measure local flow information by using distributed conductance sensor and then develop a multivariate multiscale complex network (MMCN) to reveal the dispersed oil-in-water local flow behavior. Specifically, we infer complex networks at different scales from multi-channel measurements for three typical vertical oil-in-water flow patterns. Then we characterize the generated multiscale complex networks in terms of network clustering measure. The results suggest that the clustering coefficient entropy from the MMCN not only allows indicating the oil-in-water flow pattern transition but also enables to probe the dynamical flow behavior governing the transitions of vertical oil-water two-phase flow.
Digital detection of endonuclease mediated gene disruption in the HIV provirus
Authors: Sedlak Ruth Hall , Liang Shu , Niyonzima Nixon , De Silva Feelixge Harshana S. , Roychoudhury Pavitra , Greninger Alexander L. , Weber Nicholas D. , Boissel Sandrine , Scharenberg Andrew M. , Cheng Anqi , Magaret Amalia , Bumgarner Roger , Stone Daniel , Jerome Keith R. 
Published: February 2016

AbstractGenome editing by designer nucleases is a rapidly evolving technology utilized in a highly diverse set of research fields. Among all fields, the T7 endonuclease mismatch cleavage assay, or Surveyor assay, is the most commonly used tool to assess genomic editing by designer nucleases. This assay, while relatively easy to perform, provides only a semi-quantitative measure of mutation efficiency that lacks sensitivity and accuracy. We demonstrate a simple droplet digital PCR assay that quickly quantitates a range of indel mutations with detection as low as 0.02% mutant in a wild type background and precision (≤6%CV) and accuracy superior to either mismatch cleavage assay or clonal sequencing when compared to next-generation sequencing. The precision and simplicity of this assay will facilitate comparison of gene editing approaches and their optimization, accelerating progress in this rapidly-moving field.
Comparative three-dimensional connectome map of motor cortical projections in the mouse brain
Authors: Jeong Minju , Kim Yongsoo , Kim Jeongjin , Ferrante Daniel D. , Mitra Partha P. , Osten Pavel , Kim Daesoo 
Published: February 2016

AbstractThe motor cortex orchestrates simple to complex motor behaviors through its output projections to target areas. The primary (MOp) and secondary (MOs) motor cortices are known to produce specific output projections that are targeted to both similar and different target areas. These projections are further divided into layer 5 and 6 neuronal outputs, thereby producing four cortical outputs that may target other areas in a combinatorial manner. However, the precise network structure that integrates these four projections remains poorly understood. Here, we constructed a whole-brain, three-dimensional (3D) map showing the tract pathways and targeting locations of these four motor cortical outputs in mice. Remarkably, these motor cortical projections showed unique and separate tract pathways despite targeting similar areas. Within target areas, various combinations of these four projections were defined based on specific 3D spatial patterns, reflecting anterior-posterior, dorsal-ventral and core-capsular relationships. This 3D topographic map ultimately provides evidence for the relevance of comparative connectomics: motor cortical projections known to be convergent are actually segregated in many target areas with unique targeting patterns, a finding that has anatomical value for revealing functional subdomains that have not been classified by conventional methods.
Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10
Authors: Mao Zhigang , Wu Jeffrey H. , Dong Tingting , Wu Mei X. 
Published: February 2016

AbstractDiabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient and merits further clinical study.
The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients with advanced renal cell carcinoma
Authors: Qin Chao , Cao Qiang , Li Pu , Wang Shangqian , Wang Jian , Wang Meilin , Chu Haiyan , Zhou Liqun , Li Xuesong , Ye Dingwei , Zhang Hailiang , Huang Yiran , Dong Baijun , Sun Xiaofeng , Zou Qing , Cai Hongzhou , Sun Lijiang , Zhu Jian , Liu Fade , Ji Junbiao , Cui Li , Wang Xiaoxiang , Zhou Hai , Zhao Hu , Wu Bin , Chen Jianchun , Jiang Minjun , Zhang Zhengdong , Shao Pengfei , Ju Xiaobing , Yin Changjun 
Published: February 2016

AbstractThe purpose of the present study was to investigate whether genetic variants that influence angiogenesis and sorafenib pharmacokinetics are associated with clinical outcomes and toxic effects in advanced renal cell carcinoma patients treated with this drug. One hundred patients with advanced renal cell carcinoma were enrolled. Forty-two polymorphisms in 15 genes were selected for genotyping and analyzed for associations with progression-free survival, overall survival and toxic effects. We found that rs1570360 in VEGF and rs2239702 in VEGFR2 were significantly associated with progression-free. Specifically, patients carrying the variant genotypes (AG + AA) of these two polymorphisms both had an unfavorable progression-free. In addition, compared with those with the rs2239702 GG genotype, patients with the AG + AA genotype suffered an unfavorable OS. We found that the VEGF rs2010963 CG + GG genotypes had a significantly increased risk of hand-foot syndrome and the ABCB1 rs1045642 CT + TT genotypes had an increased risk of high blood pressure. Our results suggest that polymorphisms in VEGF and VEGFR2 are associated with sorafenib clinical outcomes and polymorphisms in VEGF and ABCB1 are associated with sorafenib-related toxicities. Larger studies are warranted to validate our findings.
Preparation of Aluminum Nanomesh Thin Films from an Anodic Aluminum Oxide Template as Transparent Conductive Electrodes
Authors: Li Yiwen , Chen Yulong , Qiu Mingxia , Yu Hongyu , Zhang Xinhai , Sun Xiao Wei , Chen Rui 
Published: February 2016

AbstractWe have employed anodic aluminum oxide as a template to prepare ultrathin, transparent and conducting Al films with a unique nanomesh structure for transparent conductive electrodes. The anodic aluminum oxide template is obtained through direct anodization of a sputtered Al layer on a glass substrate and subsequent wet etching creates the nanomesh metallic film. The optical and conductive properties are greatly influenced by experimental conditions. By tuning the anodizing time, transparent electrodes with appropriate optical transmittance and sheet resistance have been obtained. The results demonstrate that our proposed strategy can serve as a potential method to fabricate low-cost TCEs to replace conventional indium tin oxide materials.
In Situ Study of Strain-Dependent Ion Conductivity of Stretchable Polyethylene Oxide Electrolyte
Authors: Kelly Taylor , Ghadi Bahar Moradi , Berg Sean , Ardebili Haleh 
Published: February 2016

AbstractThere is a strong need in developing stretchable batteries that can accommodate stretchable or irregularly shaped applications including medical implants, wearable devices and stretchable electronics. Stretchable solid polymer electrolytes are ideal candidates for creating fully stretchable lithium ion batteries mainly due to their mechanical and electrochemical stability, thin-film manufacturability and enhanced safety. However, the characteristics of ion conductivity of polymer electrolytes during tensile deformation are not well understood. Here, we investigate the effects of tensile strain on the ion conductivity of thin-film polyethylene oxide (PEO) through an in situ study. The results of this investigation demonstrate that both in-plane and through-plane ion conductivities of PEO undergo steady and linear growths with respect to the tensile strain. The coefficients of strain-dependent ion conductivity enhancement (CSDICE) for in-plane and through-plane conduction were found to be 28.5 and 27.2, respectively. Tensile stress-strain curves and polarization light microscopy (PLM) of the polymer electrolyte film reveal critical insights on the microstructural transformation of stretched PEO and the potential consequences on ionic conductivity.
Unexpected Giant-Gap Quantum Spin Hall Insulator in Chemically Decorated Plumbene Monolayer
Authors: Zhao Hui , Zhang Chang-wen , Ji Wei-xiao , Zhang Run-wu , Li Sheng-shi , Yan Shi-shen , Zhang Bao-min , Li Ping , Wang Pei-ji 
Published: February 2016

AbstractQuantum spin Hall (QSH) effect of two-dimensional (2D) materials features edge states that are topologically protected from backscattering by time-reversal symmetry. However, the major obstacles to the application for QSH effect are the lack of suitable QSH insulators with a large bulk gap. Here, we predict a novel class of 2D QSH insulators in X-decorated plumbene monolayers (PbX; X = H, F, Cl, Br, I) with extraordinarily giant bulk gaps from 1.03 eV to a record value of 1.34 eV. The topological characteristic of PbX mainly originates from s-px,y band inversion related to the lattice symmetry, while the effect of spin-orbital coupling (SOC) is only to open up a giant gap. Their QSH states are identified by nontrivial topological invariant Z2 = 1, as well as a single pair of topologically protected helical edge states locating inside the bulk gap. Noticeably, the QSH gaps of PbX are tunable and robust via external strain. We also propose high-dielectric-constant BN as an ideal substrate for the experimental realization of PbX, maintaining its nontrivial topology. These novel QSH insulators with giant gaps are a promising platform to enrich topological phenomena and expand potential applications at high temperature.