bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
Authors: Zhu Yafeng , Orre Lukas M. , Johansson Henrik J. , Huss Mikael , Boekel Jorrit , Vesterlund Mattias , Fernandez-Woodbridge Alejandro , Branca Rui M. M. , Lehtiö Janne 
Published: February 2018

AbstractProteogenomics enable the discovery of novel peptides (from unannotated genomic protein-coding loci) and single amino acid variant peptides (derived from single-nucleotide polymorphisms and mutations). Increasing the reliability of these identifications is crucial to ensure their usefulness for genome annotation and potential application as neoantigens in cancer immunotherapy. We here present integrated proteogenomics analysis workflow (IPAW), which combines peptide discovery, curation, and validation. IPAW includes the SpectrumAI tool for automated inspection of MS/MS spectra, eliminating false identifications of single-residue substitution peptides. We employ IPAW to analyze two proteomics data sets acquired from A431 cells and five normal human tissues using extended (pH range, 3–10) high-resolution isoelectric focusing (HiRIEF) pre-fractionation and TMT-based peptide quantitation. The IPAW results provide evidence for the translation of pseudogenes, lncRNAs, short ORFs, alternative ORFs, N-terminal extensions, and intronic sequences. Moreover, our quantitative analysis indicates that protein production from certain pseudogenes and lncRNAs is tissue specific.
Formation of size-dependent and conductive phase on lithium iron phosphate during carbon coating
Authors: Liu Yulong , Liu Jian , Wang Jiajun , Banis Mohammad Norouzi , Xiao Biwei , Lushington Andrew , Xiao Wei , Li Ruying , Sham Tsun-Kong , Liang Guoxian , Sun Xueliang 
Published: February 2018

AbstractCarbon coating is a commonly employed technique for improving the conductivity of active materials in lithium ion batteries. The carbon coating process involves pyrolysis of organic substance on lithium iron phosphate particles at elevated temperature to create a highly reducing atmosphere. This may trigger the formation of secondary phases in the active materials. Here, we observe a conductive phase during the carbon coating process of lithium iron phosphate and the phase content is size, temperature, and annealing atmosphere dependent. The formation of this phase is related to the reducing capability of the carbon coating process. This finding can guide us to control the phase composition of carbon-coated lithium iron phosphate and to tune its quality during the manufacturing process.
Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits
Authors: Wu Yang , Zeng Jian , Zhang Futao , Zhu Zhihong , Qi Ting , Zheng Zhili , Lloyd-Jones Luke R. , Marioni Riccardo E. , Martin Nicholas G. , Montgomery Grant W. , Deary Ian J. , Wray Naomi R. , Visscher Peter M. , McRae Allan F. , Yang Jian 
Published: February 2018

AbstractThe identification of genes and regulatory elements underlying the associations discovered by GWAS is essential to understanding the aetiology of complex traits (including diseases). Here, we demonstrate an analytical paradigm of prioritizing genes and regulatory elements at GWAS loci for follow-up functional studies. We perform an integrative analysis that uses summary-level SNP data from multi-omics studies to detect DNA methylation (DNAm) sites associated with gene expression and phenotype through shared genetic effects (i.e., pleiotropy). We identify pleiotropic associations between 7858 DNAm sites and 2733 genes. These DNAm sites are enriched in enhancers and promoters, and >40% of them are mapped to distal genes. Further pleiotropic association analyses, which link both the methylome and transcriptome to 12 complex traits, identify 149 DNAm sites and 66 genes, indicating a plausible mechanism whereby the effect of a genetic variant on phenotype is mediated by genetic regulation of transcription through DNAm.
Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
Authors: Yeh Chen-Hao , Nojima Takuya , Kuraoka Masayuki , Kelsoe Garnett 
Published: February 2018

AbstractB cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII+/+and MHCII+/−) that GC selection is insensitive to halving pMHCII density. Alone, both B cell types generate identical humoral responses; in competition, MHCII+/+B cells are preferentially recruited to early GCs but this advantage does not persist once GCs are established. During GC responses, competing MHCII+/+and MHCII+/−GC B cells comparably accumulate mutations and have indistinguishable rates of affinity maturation. We conclude that B-cell selection by pMHCII density is stringent in the establishment of GCs, but relaxed during GC responses.
Nitrogen-doped tungsten carbide nanoarray as an efficient bifunctional electrocatalyst for water splitting in acid
Authors: Han Nana , Yang Ke R. , Lu Zhiyi , Li Yingjie , Xu Wenwen , Gao Tengfei , Cai Zhao , Zhang Ying , Batista Victor S. , Liu Wen , Sun Xiaoming 
Published: February 2018

AbstractTungsten carbide is one of the most promising electrocatalysts for the hydrogen evolution reaction, although it exhibits sluggish kinetics due to a strong tungsten-hydrogen bond. In addition, tungsten carbide’s catalytic activity toward the oxygen evolution reaction has yet to be reported. Here, we introduce a superaerophobic nitrogen-doped tungsten carbide nanoarray electrode exhibiting high stability and activity toward hydrogen evolution reaction as well as driving oxygen evolution efficiently in acid. Nitrogen-doping and nanoarray structure accelerate hydrogen gas release from the electrode, realizing a current density of −200 mA cm−2at the potential of −190 mV vs. reversible hydrogen electrode, which manifest one of the best non-noble metal catalysts for hydrogen evolution reaction. Under acidic conditions (0.5 M sulfuric acid), water splitting catalyzed by nitrogen-doped tungsten carbide nanoarray starts from about 1.4 V, and outperforms most other water splitting catalysts.
Flexible quantum dot light-emitting diodes for next-generation displays
Authors: Choi Moon Kee , Yang Jiwoong , Hyeon Taeghwan , Kim Dae-Hyeong 
Published: February 2018

AbstractIn the future electronics, all device components will be connected wirelessly to displays that serve as information input and/or output ports. There is a growing demand of flexible and wearable displays, therefore, for information input/output of the next-generation consumer electronics. Among many kinds of light-emitting devices for these next-generation displays, quantum dot light-emitting diodes (QLEDs) exhibit unique advantages, such as wide color gamut, high color purity, high brightness with low turn-on voltage, and ultrathin form factor. Here, we review the recent progress on flexible QLEDs for the next-generation displays. First, the recent technological advances in device structure engineering, quantum-dot synthesis, and high-resolution full-color patterning are summarized. Then, the various device applications based on cutting-edge quantum dot technologies are described, including flexible white QLEDs, wearable QLEDs, and flexible transparent QLEDs. Finally, we showcase the integration of flexible QLEDs with wearable sensors, micro-controllers, and wireless communication units for the next-generation wearable electronics.
The Stress-Dependent Activation Parameters for Dislocation Nucleation in Molybdenum Nanoparticles
Authors: Chachamovitz Doron , Mordehai Dan 
Published: February 2018

AbstractMany specimens at the nanoscale are pristine of dislocations, line defects which are the main carriers of plasticity. As a result, they exhibit extremely high strengths which are dislocation-nucleation controlled. Since nucleation is a thermally activated process, it is essential to quantify the stress-dependent activation parameters for dislocation nucleation in order to study the strength of specimens at the nanoscale and its distribution. In this work, we calculate the strength of Mo nanoparticles in molecular dynamics simulations and we propose a method to extract the activation free-energy barrier for dislocation nucleation from the distribution of the results. We show that by deforming the nanoparticles at a constant strain rate, their strength distribution can be approximated by a normal distribution, from which the activation volumes at different stresses and temperatures are calculated directly. We found that the activation energy dependency on the stress near spontaneous nucleation conditions obeys a power-law with a critical exponent of approximately 3/2, which is in accordance with critical exponents found in other thermally activated processes but never for dislocation nucleation. Additionally, significant activation entropies were calculated. Finally, we generalize the approach to calculate the activation parameters for other driving-force dependent thermally activated processes.
Identifying inhibitors of the Leishmania inositol phosphorylceramide synthase with antiprotozoal activity using a yeast-based assay and ultra-high throughput screening platform
Authors: Norcliffe Jennifer L. , Mina John G. , Alvarez Emilio , Cantizani Juan , de Dios-Anton Francisco , Colmenarejo Gonzalo , Valle Silva Gonzalez-Del , Marco Maria , Fiandor José M. , Martin Julio J. , Steel Patrick G. , Denny Paul W. 
Published: February 2018

AbstractLeishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the world’s poorest, however vaccines are absent and drug therapy limited. Recently, public-private partnerships have developed to identify new modes of controlling leishmaniasis. Drug discovery is a significant part of these efforts and here we describe the development and utilization of a novel assay to identify antiprotozoal inhibitors of the Leishmania enzyme, inositol phosphorylceramide (IPC) synthase. IPC synthase is a membrane-bound protein with multiple transmembrane domains, meaning that a conventional in vitro assay using purified protein in solution is highly challenging. Therefore, we utilized Saccharomyces cerevisiae as a vehicle to facilitate ultra-high throughput screening of 1.8 million compounds. Antileishmanial benzazepanes were identified and shown to inhibit the enzyme at nanomolar concentrations. Further chemistry produced a benzazepane that demonstrated potent and specific inhibition of IPC synthase in the Leishmania cell.
Mahanine drives pancreatic adenocarcinoma cells into endoplasmic reticular stress-mediated apoptosis through modulating sialylation process and Ca2+-signaling
Authors: Sarkar Bhattacharya Sayantani , Mandal Chandan , Albiez Reinhard Schwartz , Samanta Suman Kumar , Mandal Chitra 
Published: February 2018

AbstractEndoplasmic reticulum (ER) stress results from protein unfolding/misfolding during cellular maturation, which requires a coordinated action of several chaperones and enzymes and Ca2+ signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insights into this complex signaling network are urgently needed. Here, we systematically analyzed the impact of ER stress-mediated unfolded protein response (UPR) and Ca2+-signaling cross-talk for the survival of pancreatic adenocarcinoma (PDAC) cells. We observed enhanced ER activity and initiation of UPR signaling induced by a carbazole alkaloid (mahanine). This event triggers a time-dependent increase of intracellular Ca2+ leakage from ER and subsequently Ca2+ signaling induced by enhanced reactive oxygen species (ROS) produced by this pro-oxidant agent. In addition, we observed an altered glycosylation, in particular with regard to reduced linkage-specific sialic acids possibly due to decreased sialyltransferase activity. Changes in sialylation entailed enhanced expression of the ganglioside GD3 in the treated cells. GD3, an inducer of apoptosis, inhibited pancreatic xenograft tumor. Taken together, our study describes a molecular scenario how PDAC cells are driven into apoptosis by mahanine by UPR-driven ER stress-associated and ROS-mediated calcium signaling and possibly defective sialylation.
Significance of risk polymorphisms for depression depends on stress exposure
Authors: Gonda Xenia , Hullam Gabor , Antal Peter , Eszlari Nora , Petschner Peter , Hökfelt Tomas GM , Anderson Ian Muir , Deakin John Francis William , Juhasz Gabriella , Bagdy Gyorgy 
Published: February 2018

AbstractDepression is a polygenic and multifactorial disorder where environmental effects exert a significant impact, yet most genetic studies do not consider the effect of stressors which may be one reason for the lack of replicable results in candidate gene studies, GWAS and between human studies and animal models. Relevance of functional polymorphisms in seven candidate genes previously implicated in animal and human studies on a depression-related phenotype given various recent stress exposure levels was assessed with Bayesian relevance analysis in 1682 subjects. This Bayesian analysis indicated a gene-environment interaction whose significance was also tested with a traditional multivariate analysis using general linear models. The investigated genetic factors were only relevant in the moderate and/or high stress exposure groups. Rank order of genes was GALR2 > BDNF > P2RX7 > HTR1A > SLC6A4 > CB1 > HTR2A, with strong relevance for the first four. Robust gene-gene-environment interaction was found between BDNF and HTR1A. Gene-environment interaction effect was confirmed, namely no main effect of genes, but a significant modulatory effect on environment-induced development of depression were found. Our data support the strong causative role of the environment modified by genetic factors, similar to animal models. Gene-environment interactions point to epigenetic factors associated with risk SNPs. Galanin-2 receptor, BDNF and X-type purin-7 receptor could be drug targets for new antidepressants.
Metformin-induced caveolin-1 expression promotes T-DM1 drug efficacy in breast cancer cells
Authors: Chung Yuan-Chiang , Chang Ching-Ming , Wei Wan-Chen , Chang Ting-Wei , Chang King-Jen , Chao Wei-Ting 
Published: February 2018

AbstractTrastuzumab emtansine (T-DM1) is an antibody drug conjugate (ADC) that was recently approved for the treatment of HER-2-positive metastatic breast cancer. The drug sensitivity of ADCs depends mainly on the internalization efficiency of the drug. Caveolin-1 was shown to promote T-DM1 internalization and enhance drug sensitivity. Whether caveolin-1 can be overexpressed to improve T-DM1 efficacy is interesting and has the potential for clinical application. In this study, diabetes drug metformin was investigated in terms of induction of caveolin-1 expression for increased efficacy of subsequent T-DM1 application. BT-474 cells were pretreated with metformin, followed by combined therapy with metformin and T-DM1. The T-DM1 internalization and drug efficacy were determined, and the protein expressions for signal transduction were also monitored. Caveolin-1 shRNA was applied to suppress endogenous caveolin-1 expression, and the ability of metformin to promote T-DM1 efficacy was investigated. Result showed that in BT-474 cells pretreated with metformin, cellular caveolin-1 overexpression was induced, which then promoted drug efficacy by enhancing T-DM1 internalization. As cellular caveolin-1 was suppressed by shRNA, the effect of metformin-enhanced T-DM1 cytotoxicity was decreased. This study demonstrated that metformin can be applied prior to T-DM1 treatment to improve the clinical efficacy of T-DM1 by enhancing caveolin-1-mediated endocytosis.
Computationally-Guided Development of a Stromal Inflammation Histologic Biomarker in Lung Squamous Cell Carcinoma
Authors: Xia Daniel , Casanova Ruben , Machiraju Devayani , McKee Trevor D. , Weder Walter , Beck Andrew H. , Soltermann Alex 
Published: February 2018

AbstractThe goal of this study is to use computational pathology to help guide the development of human-based prognostic H&E biomarker(s) suitable for research and potential clinical use in lung squamous cell carcinoma (SCC). We started with high-throughput computational image analysis with tissue microarrays (TMAs) to screen for histologic features associated with patient overall survival, and found that features related to stromal inflammation were the most strongly prognostic. Based on this, we developed an H&E stromal inflammation (SI) score. The prognostic value of the SI score was validated by two blinded human observers on two large cohorts from a single institution. The SI score was found to be reproducible on TMAs (Spearman rho = 0.88 between the two observers), and highly prognostic (e.g. hazard ratio = 0.32; 95% confidence interval: 0.19–0.54; p-value = 2.5 × 10−5 in multivariate analyses), particularly in comparison to established histologic biomarkers. Guided by downstream molecular/biomarker correlation studies starting with TCGA cases, we investigated the hypothesis that epithelial PD-L1 expression modified the prognostic value of SI. Our research demonstrates that computational pathology can be an efficient hypothesis generator for human pathology research, and support the histologic evaluation of SI as a prognostic biomarker in lung SCCs.
Central s-resistin deficiency ameliorates hypothalamic inflammation and increases whole body insulin sensitivity
Authors: Rodríguez María , Pintado Cristina , Moltó Eduardo , Gallardo Nilda , Fernández-Martos Carmen M. , López Virginia , Andrés Antonio , Arribas Carmen 
Published: February 2018

AbstractS-resistin, a non-secretable resistin isoform, acts as an intracrine factor that regulates adipocyte maduration, inflammatory and insulin response in 3T3-L1 cells. However, its intracellular function in vivo is still unknown. In this study, we analyze the central role of s-resistin, decreasing its hypothalamic expression using an intracerebroventricular injection of lentiviral RNAi. The data present herein support an improvement in the hypothalamic leptin and insulin signaling pathway upon s-resistin downregulation. Furthermore, hypothalamic levels of pro-inflammatory markers decrease, meanwhile those of the anti-inflammatory cytokine IL-10 increases. Interestingly, peripheral NEFA decreases alike circulating leptin and resistin levels. These data demonstrate that hypothalamic s-resistin controls fuel mobilization and adipokines secretion. Importantly, central s-resistin downregulation improves systemic insulin sensitivity, as demonstrated after an IPGTT. Interestingly, our data also indicate that s-resistin downregulation could improve hypothalamic inflammation in aged Wistar rats. Altogether, our findings suggest that hypothalamic s-resistin seems to be a key regulator of the brain-fat axis which links inflammation with metabolic homeostasis.
Exposure of Insects to Radio-Frequency Electromagnetic Fields from 2 to 120 GHz
Authors: Thielens Arno , Bell Duncan , Mortimore David B. , Greco Mark K. , Martens Luc , Joseph Wout 
Published: February 2018

AbstractInsects are continually exposed to Radio-Frequency (RF) electromagnetic fields at different frequencies. The range of frequencies used for wireless telecommunication systems will increase in the near future from below 6 GHz (2 G, 3 G, 4 G, and WiFi) to frequencies up to 120 GHz (5 G). This paper is the first to report the absorbed RF electromagnetic power in four different types of insects as a function of frequency from 2 GHz to 120 GHz. A set of insect models was obtained using novel Micro-CT (computer tomography) imaging. These models were used for the first time in finite-difference time-domain electromagnetic simulations. All insects showed a dependence of the absorbed power on the frequency. All insects showed a general increase in absorbed RF power at and above 6 GHz, in comparison to the absorbed RF power below 6 GHz. Our simulations showed that a shift of 10% of the incident power density to frequencies above 6 GHz would lead to an increase in absorbed power between 3–370%.
Structural and functional studies on Pseudomonas aeruginosa DspI: implications for its role in DSF biosynthesis
Authors: Liu Li , Li Tao , Cheng Xing-Jun , Peng Cui-Ting , Li Chang-Cheng , He Li-Hui , Ju Si-Min , Wang Ning-Yu , Ye Ting-Hong , Lian Mao , Xiao Qing-Jie , Song Ying-Jie , Zhu Yi-Bo , Yu Luo-Ting , Wang Zhen-Ling , Bao Rui 
Published: February 2018

AbstractDspI, a putative enoyl-coenzyme A (CoA) hydratase/isomerase, was proposed to be involved in the synthesis of cis-2-decenoic acid (CDA), a quorum sensing (QS) signal molecule in the pathogen Pseudomonas aeruginosa (P. aeruginosa). The present study provided a structural basis for the dehydration reaction mechanism of DspI during CDA synthesis. Structural analysis reveals that Glu126, Glu146, Cys127, Cys131 and Cys154 are important for its enzymatic function. Moreover, we show that the deletion of dspI results in a remarkable decreased in the pyoverdine production, flagella-dependent swarming motility, and biofilm dispersion as well as attenuated virulence in P. aeruginosa PA14. This study thus unravels the mechanism of DspI in diffusible signal factor (DSF) CDA biosynthesis, providing vital information for developing inhibitors that interfere with DSF associated pathogenicity in P. aeruginosa.
Mass spectrometry and multivariate analysis to classify cervical intraepithelial neoplasia from blood plasma: an untargeted lipidomic study
Authors: Neves Ana C. O. , Morais Camilo L. M. , Mendes Thais P. P. , Vaz Boniek G. , Lima Kássio M. G. 
Published: February 2018

AbstractCervical cancer is still an important issue of public health since it is the fourth most frequent type of cancer in women worldwide. Much effort has been dedicated to combating this cancer, in particular by the early detection of cervical pre-cancerous lesions. For this purpose, this paper reports the use of mass spectrometry coupled with multivariate analysis as an untargeted lipidomic approach to classifying 76 blood plasma samples into negative for intraepithelial lesion or malignancy (NILM, n = 42) and squamous intraepithelial lesion (SIL, n = 34). The crude lipid extract was directly analyzed with mass spectrometry for untargeted lipidomics, followed by multivariate analysis based on the principal component analysis (PCA) and genetic algorithm (GA) with support vector machines (SVM), linear (LDA) and quadratic (QDA) discriminant analysis. PCA-SVM models outperformed LDA and QDA results, achieving sensitivity and specificity values of 80.0% and 83.3%, respectively. Five types of lipids contributing to the distinction between NILM and SIL classes were identified, including prostaglandins, phospholipids, and sphingolipids for the former condition and Tetranor-PGFM and hydroperoxide lipid for the latter. These findings highlight the potentiality of using mass spectrometry associated with chemometrics to discriminate between healthy women and those suffering from cervical pre-cancerous lesions.