bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression
Authors: Rokavec Matjaz , Kaller Markus , Horst David , Hermeking Heiko 
Published: June 2017

AbstractEpithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. A comprehensive, bioinformatics analysis of CCLE and TCGA datasets of seven tumor types allowed us to identify a novel pan-cancer EMT-associated gene expression signature consisting of 16 epithelial and 4 mesenchymal state-associated mRNAs. Among the identified epithelial cell state-associated factors, down-regulation of the RBM47 (RNA binding motif protein 47) mRNA displayed the most significant association with metastasis and poor survival in multiple cohorts of colorectal cancer (CRC) patients. Moreover, decreased RBM47 protein expression was associated with metastasis in a cohort of primary CRCs. RBM47 was directly suppressed during EMT induced by IL6-activated STAT3 or ectopic SNAIL and SLUG expression via conserved binding motifs of these factors within the RBM47 promoter. Moreover, RNAi-mediated down-regulation of RBM47 in CRC lines resulted in increased cell migration, invasion and metastases formation. As demonstrated by the example of RBM47, the EMT-associated signature characterized here allows to identify biomarkers for predicting clinical outcome of CRC and presumably other cancer entities. In addition, our functional analysis of RBM47 shows that the down-regulation of RBM47 during CRC progression may promote EMT and metastasis.
Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
Authors: An Jiayin , Zhang Yin , He Jiaojiang , Zang Zhenle , Zhou Zheng , Pei Xiangdong , Zheng Xin , Zhang Weihua , Yang Hui , Li Song 
Published: June 2017

AbstractLactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in invasive PA samples, and positively correlated with higher Ki-67 index. Overexpression of LDHA in a PA cell line (GH3) promoted glucose uptake through the upregulation of glucose transporter-1 (Glut1), lactate secretion and induced cellular invasion by upregulation of matrix metalloproteinase2 (MMP2). LDHA also promoted GH3 cell proliferation through induction of cell cycle progression via activation of the Akt-GSK-3β-cyclinD1 pathway. Accordingly, oxamate-induced inhibition of LDHA suppressed glucose uptake, lactate secretion, invasion and proliferation in GH3 cells via down regulation of Glut1 and MMP2 expression and inhibition of the Akt-GSK-3β-cyclinD1 pathway. Moreover, oxamate induced GH3 cell apoptosis by increasing mitochondrial reactive oxygen species (ROS) generation. In vivo, LDHA overexpression promoted tumor growth, and oxamate delayed tumor growth. In primary PA cell cultures, oxamate also effectively suppressed invasion and proliferation. Our data indicate that LDHA is involved in promoting the progression of PA, and oxamate might be a promising therapeutic agent for the treatment of PA.
DFT-inspired methods for quantum thermodynamics
Authors: Herrera Marcela , Serra Roberto M. , D’Amico Irene 
Published: June 2017

AbstractIn the framework of quantum thermodynamics, we propose a method to quantitatively describe thermodynamic quantities for out-of-equilibrium interacting many-body systems. The method is articulated in various approximation protocols which allow to achieve increasing levels of accuracy, it is relatively simple to implement even for medium and large number of interactive particles, and uses tools and concepts from density functional theory. We test the method on the driven Hubbard dimer at half filling, and compare exact and approximate results. We show that the proposed method reproduces the average quantum work to high accuracy: for a very large region of parameter space (which cuts across all dynamical regimes) estimates are within 10% of the exact results.
Developmental validation of a 6-dye typing system with 27 loci and application in Han population of China
Authors: Liu Yaju , Guo Lihong , Jin Haiying , Li Zheng , Bai Rufeng , Shi Meisen , Ma Shuhua 
Published: June 2017

AbstractIn this study, a novel 27-locus system (now known as the SureID PanGlobal system), including 24 autosomal STRs (D3S1358, TH01, D21S11, D18S51, Penta E, D12S391, D6S1043, D2S1338, D1S1656, D2S441, D5S818, D13S317, D7S820, D19S433, CSF1PO, Penta D, vWA, D8S1179, TPOX, FGA, D16S539, D22S1045, SE33, D10S1248), two Y-chromosome markers (DYS391 and Y-indel) and the sex determining marker, Amelogenin was developed with six fluorescent dyes labeling. The included STR loci belonged to the core loci in the Combined DNA Index System (CODIS) and the European Standard Set (ESS) as well as some additional loci commonly used in commercial kits and national DNA databases. This paper describes the validation studies conducted with the SureID PanGlobal system using Applied Biosystems 3500 XL Genetic Analyzer for fragment length detection that included the analysis of the following parameters and aspects: PCR conditions, sensitivity, species specificity, inhibition, precision, stutter, DNA mixtures, and stability studies with crime scene samples. The studies demonstrated that the SureID PanGlobal system is reproducible, accurate, sensitive and robust for forensic application and databasing. Additionally, the whole cycling time of the system can finish within 65 minutes, which was developed specifically for rapid and reliable generation of DNA profiles obtained from blood, buccal swabs and forensic stains.
Liver Fat, Hepatic Enzymes, Alkaline Phosphatase and the Risk of Incident Type 2 Diabetes: A Prospective Study of 132,377 Adults
Authors: Chen Sean Chun-Chang , Tsai Shan Pou , Jhao Jing-Yun , Jiang Wun-Kai , Tsao Chwen Keng , Chang Ly-Yun 
Published: June 2017

AbstractPrevious studies have reported inconsistent results of the associations of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) with incident type 2 diabetes (diabetes hereafter). We aimed to resolve the controversy by taking nonalcoholic fatty liver disease (NAFLD) into account. The study population comprised 132,377 non-diabetic individuals (64,875 men and 67,502 women) aged 35–79 who had two or more health examinations during 1996–2014. A total of 6,555 incident diabetes (3,734 men and 2,821 women) were identified, on average, over 5.8 years of follow-up. Cox regression was used to calculate the hazard ratio (HR) for incident diabetes, adjusting for classical confounders. The risk of incident diabetes was significantly associated with NAFLD [HR = 2.08 (men) and 2.65 (women)]. Elevated ALT, AST, GGT and ALP were also significantly associated with the increased risk of diabetes, with HRs of 1.27, 1.23, 1.58 and 1.37, respectively, in men, and 1.56, 1.18, 1.48 and 1.44, respectively in women. Our results suggest that NAFLD, ALT, AST, GGT and ALP are independent predictors for incident diabetes in both men and women.
Synergistic cellular effects including mitochondrial destabilization, autophagy and apoptosis following low-level exposure to a mixture of lipophilic persistent organic pollutants
Authors: Rainey Nathan E. , Saric Ana , Leberre Alexandre , Dewailly Etienne , Slomianny Christian , Vial Guillaume , Zeliger Harold I. , Petit Patrice X. 
Published: June 2017

AbstractHumans are exposed to multiple exogenous environmental pollutants. Many of these compounds are parts of mixtures that can exacerbate harmful effects of the individual mixture components. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is primarily produced via industrial processes including incineration and the manufacture of herbicides. Both endosulfan and TCDD are persistent organic pollutants which elicit cytotoxic effects by inducing reactive oxygen species generation. Sublethal concentrations of mixtures of TCDD and endosulfan increase oxidative stress, as well as mitochondrial homeostasis disruption, which is preceded by a calcium rise and, in fine, induce cell death. TCDD+Endosulfan elicit a complex signaling sequence involving reticulum endoplasmic destalilization which leads to Ca2+ rise, superoxide anion production, ATP drop and late NADP(H) depletion associated with a mitochondrial induced apoptosis concomitant early autophagic processes. The ROS scavenger, N-acetyl-cysteine, blocks both the mixture-induced autophagy and death. Calcium chelators act similarly and mitochondrially targeted anti-oxidants also abrogate these effects. Inhibition of the autophagic fluxes with 3-methyladenine, increases mixture-induced cell death. These findings show that subchronic doses of pollutants may act synergistically. They also reveal that the onset of autophagy might serve as a protective mechanism against ROS-triggered cytotoxic effects of a cocktail of pollutants in Caco-2 cells and increase their tumorigenicity.
Screening Specific Biomarkers of Herbs Using a Metabolomics Approach: A Case Study of Panax ginseng
Authors: Wang Hong-ping , Liu Yan , Chen Chang , Xiao Hong-bin 
Published: June 2017

AbstractMedicinal herbs belonging to the same genus are always easily confused due to their extremely similar morphology and metabolites. Previously, to differentiate them, inherently specific biomarkers were screened out via intuitive comparison of their metabolite profiles. Unfortunately, the selected biomarkers have worked only partially. Most significant specific biomarkers have been neglected. Herein, a novel method for screening specific biomarkers of medicinal herbs using a metabolomics technique was developed. Firstly, the profiles of a group of easily confused herbs belonging to the same genus were analyzed by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry to detect all components, including low-response metabolites. Then, all components were compared between the different samples, and specific biomarkers were extracted by the metabolomics techniques of alignment, normalization, defining the sample sets, filtering by frequency and Venn diagram analysis with Mass Profiler Professional (MPP) software. Thirdly, the correlations of these biomarkers were investigated via partial correlational analysis to obtain the most representative specific biomarkers. As an example, selection of specific biomarkers for ginseng (Panax ginseng) was performed, and three specific biomarkers including chikusetsusaponin IVa, ginsenoside Rf and ginsenoside Rc were finally selected and verified as the most representative specific biomarkers of Panax ginseng.
The discovery of novel heat-stable keratinases from Meiothermus taiwanensis WR-220 and other extremophiles
Authors: Wu Wan-Ling , Chen Mei-Yi , Tu I-Fan , Lin Yu-Ching , EswarKumar Nadendla , Chen Ming-Yi , Ho Meng-Chiao , Wu Shih-Hsiung 
Published: June 2017

AbstractBillions of tons of keratin bio-wastes are generated by poultry industry annually but discarded that result in serious environmental pollution. Keratinase is a broad spectrum protease with the unique ability to degrade keratin, providing an eco-friendly way to convert keratin wastes to valuable amino acids. In this report, a feather-degrading thermophilic bacterium,Meiothermus taiwanensisWR-220, was investigated due to its ability to apparently complete feather decay at 65 °C in two days. By genomics, proteomics, and biochemical approaches, the extracellular heat-stable keratinase (MtaKer) fromM. taiwanensisWR-220 was identified. The recombinant MtaKer (rMtaKer) possesses keratinolytic activities at temperatures ranging from 25 to 75 °C and pH from 4 to 11, with a maximum keratinolytic activity at 65 °C and pH 10. The phylogenetic and structural analysis revealed that MtaKer shares low sequence identity but high structural similarity with known keratinases. Accordingly, our findings have enabled the discovery of more keratinases from other extremophiles,ThermusandDeinococcus. Proteins encoded in the extremophiles shall be evolved to be functional in the extreme conditions. Hence, our study expands the current boundary of hunting keratinases that can tolerate extreme conditions for keratin wastes biorecycle and other industrial applications.
Challenging the Wigglesworthia, Sodalis, Wolbachia symbiosis dogma in tsetse flies: Spiroplasma is present in both laboratory and natural populations
Authors: Doudoumis V. , Blow F. , Saridaki A. , Augustinos A. , Dyer N. A. , Goodhead I. , Solano P. , Rayaisse J.-B. , Takac P. , Mekonnen S. , Parker A. G. , Abd-Alla A. M. M. , Darby A. , Bourtzis K. , Tsiamis G. 
Published: June 2017

AbstractProfiling of wild and laboratory tsetse populations using 16S rRNA gene amplicon sequencing allowed us to examine whether the “Wigglesworthia-Sodalis-Wolbachia dogma” operates across species and populations. The most abundant taxa, in wild and laboratory populations, were Wigglesworthia (the primary endosymbiont), Sodalis and Wolbachia as previously characterized. The species richness of the microbiota was greater in wild than laboratory populations. Spiroplasma was identified as a new symbiont exclusively in Glossina fuscipes fuscipes and G. tachinoides, members of the palpalis sub-group, and the infection prevalence in several laboratory and natural populations was surveyed. Multi locus sequencing typing (MLST) analysis identified two strains of tsetse-associated Spiroplasma, present in G. f. fuscipes and G. tachinoides. Spiroplasma density in G. f. fuscipes larva guts was significantly higher than in guts from teneral and 15-day old male and female adults. In gonads of teneral and 15-day old insects, Spiroplasma density was higher in testes than ovaries, and was significantly higher density in live versus prematurely deceased females indicating a potentially mutualistic association. Higher Spiroplasma density in testes than in ovaries was also detected by fluorescent in situ hybridization in G. f. fuscipes.
BsmR degrades c-di-GMP to modulate biofilm formation of nosocomial pathogen Stenotrophomonas maltophilia
Authors: Liu Wei , Tian Xiu-Qi , Wei Jin-Wei , Ding Li-Li , Qian Wei , Liu Zhong , Wang Fang-Fang 
Published: June 2017

Abstractc-di-GMP is a cellular second messenger that regulates diverse bacterial processes, including swimming, biofilm formation and virulence. However, in Stenotrophomonas maltophilia, a nosocomial pathogen that frequently infects immunodeficient or immunoincompetent patients, the regulatory function of c-di-GMP remains unclear. Here we show that BsmR is a negative regulator of biofilm development that degrades c-di-GMP through its EAL domain. Increasing BsmR expression resulted in significant increase in bacterial swimming and decrease in cell aggregation. BsmR regulates the expression of at least 349 genes. Among them, 34 involved in flagellar assembly and a flagellar-assembly-related transcription factor (fsnR) are positively regulated. Although BsmR is a response regulator of the two-component signaling system, its role in biofilm formation depends on the expression level of its respective gene (bsmR), not on the protein’s phosphorylation level. A transcription factor, BsmT, whose coding gene is located in the same tetra-cistronic operon as bsmR, was shown to directly bind to the promoter region of the operon and, through a positive regulatory loop, modulate bsmR transcription. Thus, our results revealed that the c-di-GMP signaling pathway controls biofilm formation and swimming in S. maltophilia, suggesting c-di-GMP signaling as a target in the development of novel antibacterial agents to resist this pathogen.
Seasonal and daily protandry in a cyprinid fish
Authors: Šmejkal Marek , Ricard Daniel , Vejřík Lukáš , Mrkvička Tomáš , Vebrová Lucie , Baran Roman , Blabolil Petr , Sajdlová Zuzana , Vejříková Ivana , Prchalová Marie , Kubečka Jan 
Published: June 2017

AbstractIn polygynandrous mating systems, in which females limit reproductive success, males can increase their success by investing in courtship. Earlier arrival at the spawning ground compared to when females arrive may increase their opportunities in competitive mating systems. In this study, we used passive telemetry to test whether a male minnow known as the asp, Leuciscus aspius, times its arrival at spawning grounds relative to the arrival of females. Males arrived in a model stream approximately five days earlier than females on average and left four to five days later than females over two years. Both sexes performed a daily migration between a staging ground (standing water, low energy costs) and the fluvial spawning ground (high energy costs). Fish abundance peaked twice a day, with a major peak at sunset and a minor peak at sunrise and with the evening peak abundance for males occurring 1 hour 40 minutes earlier than that of females. The number of females on the spawning ground never exceeded the number of males. While the degree of protandry is hypothesized to be influenced by the operational sex ratio (ranging from 0.5 to 1 in our study), our data did not support this theory.
Peptides derived from the knuckle epitope of BMP-9 induce the cholinergic differentiation and inactivate GSk3beta in human SH-SY5Y neuroblastoma cells
Authors: Lauzon Marc-Antoine , Drevelle Olivier , Faucheux Nathalie 
Published: June 2017

AbstractThe incidence of brain degenerative disorders like Alzheimer’s disease (AD) will increase as the world population ages. While there is presently no known cure for AD and current treatments having only a transient effect, an increasing number of publications indicate that growth factors (GF) may be used to treat AD. GFs like the bone morphogenetic proteins (BMPs), especially BMP-9, affect many aspects of AD. However, BMP-9 is a big protein that cannot readily cross the blood-brain barrier. We have therefore studied the effects of two small peptides derived from BMP-9 (pBMP-9 and SpBMP-9). We investigated their capacity to differentiate SH-SY5Y human neuroblastoma cells into neurons with or without retinoic acid (RA). Both peptides induced Smad 1/5 phosphorylation and their nuclear translocation. They increased the number and length of neurites and the expression of neuronal markers MAP-2, NeuN and NSE better than did BMP-9. They also promoted differentiation to the cholinergic phenotype more actively than BMP-9, SpBMP-9 being the most effective as shown by increases in intracellular acetylcholine, ChAT and VAchT. Finally, both peptides activated the PI3K/Akt pathway and inhibited GSK3beta, a current AD therapeutic target. BMP-9-derived peptides, especially SpBMP-9, with or without RA, are promising molecules that warrant further investigation.
Surface chemistry for cytosolic gene delivery and photothermal transgene expression by gold nanorods
Authors: Nakatsuji Hirotaka , Kawabata Galbraith Kelly , Kurisu Junko , Imahori Hiroshi , Murakami Tatsuya , Kengaku Mineko 
Published: June 2017

AbstractLight-inducible gene regulation has great potential for remote and noninvasive control of the fate and function of target cells. One method to achieve such control is delivery of heat shock protein (HSP) promoter-driven protein expression vectors and photothermal heaters into the cells, followed by activation by illumination. In this study, we show that gold nanorods (AuNRs) functionalized with two conventional lipids, oleate and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), are capable of efficient transfection and quick photoactivation of the HSP promoter. Use of our AuNRs (DOTAP-AuNRs) was comparable to Lipofectamine 2000 in terms of transfection efficiency, while lower in cytotoxicity. Subsequent near-infrared laser (NIR) illumination of the cells transfected by DOTAP-AuNRs for 10 s induced time- and site-specific transgene expression without significant phototoxicity, to a degree similar to that of heating the entire culture dish for 30 min. Our mechanistic studies suggest that efficient transfection and quick photoactivation of the HSP promoter (HSP70b’) are due to the promoted endosomal escape of DOTAP-AuNRs. We propose a novel protocol for NIR-inducible, site-directed gene expression using an unprecedented complex of the three conventional components capable of both transfection and photothermal heating.
Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients
Authors: Raj V. Stalin , Hundie Gadissa Bedada , Schürch Anita C. , Smits Saskia L. , Pas Suzan D. , Le Pogam Sophie , Janssen Harry L. A. , de Knegt Rob J. , Osterhaus Albert D. M. E. , Najera Isabel , Boucher Charles A. , Haagmans Bart L. 
Published: June 2017

AbstractCurrent standard-of-care treatment of chronically infected hepatitis C virus (HCV) patients involves direct-acting antivirals (DAA). However, concerns exist regarding the emergence of drug -resistant variants and subsequent treatment failure. In this study, we investigate potential natural drug-resistance mutations in the NS5B gene of HCV genotype 1b from treatment-naïve patients. Population-based sequencing and 454 deep sequencing of NS5B gene were performed on plasma and liver samples obtained from 18 treatment- naïve patients. The quasispecies distribution in plasma and liver samples showed a remarkable overlap in each patient. Although unique sequences in plasma or liver were observed, in the majority of cases the most dominant sequences were shown to be identical in both compartments. Neither in plasma nor in the liver codon changes were detected at position 282 that cause resistance to nucleos(t)ide analogues. However, in 10 patients the V321I change conferring resistance to nucleos(t)ide NS5B polymerase inhibitors and in 16 patients the C316N/Y/H non-nucleoside inhibitors were found mainly in liver samples. In conclusion, 454-deep sequencing of liver and plasma compartments in treatment naïve patients provides insight into viral quasispecies and the pre-existence of some drug-resistant variants in the liver, which are not necessarily present in plasma.
Altered interhemispheric functional connectivity in remitted bipolar disorder: A Resting State fMRI Study
Authors: Zhao Lianping , Wang Ying , Jia Yanbin , Zhong Shuming , Sun Yao , Qi Zhangzhang , Zhang Zhongping , Huang Li 
Published: June 2017

AbstractAbnormalities in structural and functional brain connectivity have been increasingly reported in patients with bipolar disorder (BD). However, alterations of remitted BD (RBD) in functional connectivity between the cerebral hemispheres are still not well understood. This study was designed to analyze the pattern of the interhemispheric functional connectivity of the whole brain in patients with remitted BD during resting state. Twenty patients with RBD and 38 healthy controls (HC) underwent the resting-state functional magnetic resonance imaging. The functional connectivity between any pair of symmetrical interhemispheric voxels (i.e., functional homotopy) was measured by voxel-mirrored homotopic connectivity (VMHC). The patients with RBD showed lower VMHC than HC in the middle frontal gyrus and precentral gyrus. No regions of increased VMHC were detected in the RBD patients. There were no significant correlations between the VMHC values in these regions and the clinical variables. These findings suggest substantial impairment of interhemispheric coordination in RBD and they may represent trait, rather than state, neurobiological feature of brain function in BD.