bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating the Intestine with Oral ApoA-I Mimetic Tg6F Reduces Tumor Burden in Mouse Models of Metastatic Lung Cancer
Authors: Chattopadhyay Arnab , Yang Xinying , Mukherjee Pallavi , Sulaiman Dawoud , Fogelman Hannah R. , Grijalva Victor , Dubinett Steven , Wasler Tonya C. , Paul Manash K. , Salehi-Rad Ramin , Mack Julia J. , Iruela-Arispe M. Luisa , Navab Mohamad , Fogelman Alan M. , Reddy Srinivasa T. 
Published: June 2018

AbstractHaving demonstrated that apolipoprotein A-I (apoA-I) mimetic peptides ameliorate cancer in mouse models, we sought to determine the mechanism for the anti-tumorigenic function of these peptides. CT-26 cells (colon cancer cells that implant and grow into tumors in the lungs) were injected into wild-type BALB/c mice. The day after injection, mice were either continued on chow or switched to chow containing 0.06% of a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F). After four weeks, the number of lung tumors was significantly lower in Tg6F-fed mice. Gene expression array analyses of jejunum and lung identified Notch pathway genes significantly upregulated, whereas osteopontin (Spp1) was significantly downregulated by Tg6F in both jejunum and lung. In jejunum, Tg6F increased protein levels for Notch1, Notch2, Dll1, and Dll4. In lung, Tg6F increased protein levels for Notch1 and Dll4 and decreased Spp1. Tg6F reduced oxidized phospholipid levels (E06 immunoreactivity) and reduced 25-hydroxycholesterol (25-OHC) levels, which are known to inhibit Notch1 and induce Spp1, respectively. Notch pathway promotes anti-tumorigenic patrolling monocytes, while Spp1 facilitates pro-tumorigenic myeloid derived suppressor cells (MDSCs) formation. Tg6F-fed mice had higher numbers of patrolling monocytes in jejunum and in lung (p < 0.02), and lower plasma levels of Spp1 with reduced numbers of MDSCs in jejunum and in lung (p < 0.03). We conclude that Tg6F alters levels of specific oxidized lipids and 25-OHC to modulate Notch pathways and Spp1, which alter small intestine immune cells, leading to similar changes in lung that reduce tumor burden.
(−)-Gochnatiolide B, synthesized from dehydrocostuslactone, exhibits potent anti-bladder cancer activity in vitro and in vivo
Authors: Chen Yuwen , Li Wenhua , Zeng Zhongqiu , Tang Yaxiong 
Published: June 2018

AbstractWith limited success achieved in bladder cancer patient management, novel agents are in urgent need for the purpose of therapy and prevention. As a sesquiterpenoid dimmer isolated from Gochnatia pomculat, (−)-gochnatiolide B has been bio-mimetically synthesized in multiple steps with a poor yield, which heavily limited the further research and clinical application. Herein, (−)-gochnatiolide B was synthesized beginning with dehydrocostuslactone in four steps with a total yield of 26%. MTT assays showed that (−)-gochnatiolide B inhibited the growth of vast majority of human cancer cells especially bladder cancer cells. Mechanistically, (−)-gochnatiolide B induced the increased expression of pro-apoptotic proteins and the decreased expression of anti-apoptosis proteins and further resulted in apoptosis of T24 cells. (−)-Gochnatiolide B induced G1 arrest which associated with SKP2 downregulation, leading to p27/Kip1 accumulation and downregulation of cyclin D1 in T24 cells. Furthermore, in vivo studies showed that (−)-gochnatiolide B remarkably inhibited tumor growth by 81% compared with vehicle control. Taken together, (−)-gochnatiolide B exhibits inhibitory activity against bladder cancer cells both in vitro and in vivo by inducing apoptosis, which suggests that (−)-gochnatiolide B could be an important candidate compound for prevention and treatment of bladder cancer.
Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica
Authors: Varet Hugo , Shaulov Yana , Sismeiro Odile , Trebicz-Geffen Meirav , Legendre Rachel , Coppée Jean-Yves , Ankri Serge , Guillen Nancy 
Published: June 2018

AbstractOxidative stress is one of the strongest toxic factors in nature: it can harm or even kill cells. Cellular means of subverting the toxicity of oxidative stress are important for the success of infectious diseases. Many types of bacterium inhabit the intestine, where they can encounter pathogens. During oxidative stress, we analyzed the interplay between an intestinal parasite (the pathogenic amoeba Entamoeba histolytica - the agent of amoebiasis) and enteric bacteria (microbiome residents, pathogens and probiotics). We found that live enteric bacteria protectedE. histolyticaagainst oxidative stress. By high-throughput RNA sequencing, two amoebic regulatory modes were observed with enteric bacteria but not with probiotics. The first controls essential elements of homeostasis, and the second the levels of factors required for amoeba survival. Characteristic genes of both modes have been acquired by the amoebic genome through lateral transfer from the bacterial kingdom (e.g. glycolytic enzymes and leucine-rich proteins). Members of the leucine-rich are homologous to proteins from anti-bacterial innate immune such as Toll-like receptors. The factors identified here suggest that despite its old age in evolutionary terms, the protozoanE. histolyticadisplays key characteristics of higher eukaryotes’ innate immune systems indicating that components of innate immunity existed in the common ancestor of plants and animals.
Facile preparation and adsorption performance of graphene oxide-manganese oxide composite for uranium
Authors: Yang Aili , Zhu Yukuan , Huang C. P. 
Published: June 2018

AbstractTo overcome the limits of low adsorption capacity and the separation difficulty of solid from liquid phase for graphene oxide (GO), a novel nanocomposite graphene oxide-manganese oxide (GOMO) was facilely fabricated under ultrasonic radiation. The structures and micro-morphology of the products were characterized by fourier transform infrared (FT-IR) spectroscopy, raman shift spectroscopy, X-ray diffraction (XRD) pattern and scanning electron microscopy (SEM). The effect of solution pH, adsorbent dose, contact time, initial uranium concentration, ionic strength and temperature on uranium removal efficiency was studied by batch adsorption experiments. The product GOMO was used to examine the feasibility of the removal of high salt content in uranium-containing wastewater. The adsorption results were fitted using the Langmuir and Freundlich isotherm models. The kinetic parameters in the adsorption process were measured and fitted. Five adsorption/desorption cycles were performed using 3 M HNO3 as the regenerant in order to evaluate the reuse of GOMO.
Clinical significance of CCR7+CD8+ T cells in kidney transplant recipients with allograft rejection
Authors: Kim Kyoung Woon , Kim Bo-Mi , Doh Kyoung Chan , Cho Mi-La , Yang Chul Woo , Chung Byung Ha 
Published: June 2018

AbstractThe regulatory function of CCR7+CD8+ T cells against effector T-cells involved in T-cell mediated rejection (TCMR) in kidney transplant recipients was investigated. In vitro experiments explored the ability of CCR7+CD8+ T cells to suppress T-cell proliferation under T-cell activation conditions or during coculture with human renal proximal tubular epithelial cells (HRPTEpiC). In an ex vivo experiment, the proportion of CCR7+/CD8+, FOXP3+/CCR7+CD8+ T and effector T-cell subsets were compared between the normal biopsy control (NC, n = 17) and TCMR group (n = 17). The CCR7+CD8+ T cells significantly suppressed the proliferation of CD4+ T cells and significantly decreased the proportion of IFN-γ+ and IL-17+/CD4+ T cells and inflammatory cytokine levels (all p < 0.05). After coculturing with HRPTEpiC, CCR7+CD8+ T cells also suppressed T-cell differentiation into IL-2+, IFN-γ+, and IL-17+/CD4+ T cells (all p < 0.05). The TCMR group had significantly fewer CCR7+/CD8+ and FOXP3+/CCR7+CD8+ T in comparison with the NC group, but the proportions of all three effector T-cell subsets were increased in the TCMR group (all p < 0.05). The proportion of CCR7+/CD8+ T was inversely correlated with those of effector T-cell subsets. The results indicate that CCR7+CD8+ T cells may regulate effector T-cells involved in TCMR in an in vitro and in an ex vivo transplant model.
Microstructural Insights into Natural Silver Wires
Authors: Boellinghaus Th. , Lüders V. , Nolze G. 
Published: June 2018

AbstractDue to the increasing global demand for pure silver, native wire silver aggregates in very high purities are gaining more industrial attention. Up to the present, no substantial metallurgical investigation of natural wire silver exists in the accessible literature. To convey urgently needed cross-disciplinary fundamental knowledge for geoscientists and metallurgical engineers, twenty natural wire silver specimens from eight different ore deposits have been investigated in detail for the first time by EBSD (Electron Back Scattering Diffraction), supported by light microscopy and micro-probe analyses. The improved understanding of the natural silver wire microstructure provides additional information regarding the growth of natural silver aggregates in comparison to undesired artificial growth on electronic devices. Clear evidence is provided that natural silver curls and hairs exhibit a polycrystalline face-centered cubic microstructure associated with significant twinning. Although the investigated natural wire silver samples have relatively high purity (Ag > 99.7 wt.-%), they contain a variety of trace elements such as, S, Cu, Mn, Ni, Zn, Co and Bi, As and Sb. Additionally, Vickers micro-hardness measurements are provided for the first time which revealed that natural silver wires and curls are softer than it might be expected from conversion of the general Mohs hardness of 2.7.
PYRE insertion within HIV-1 subtype C p6-Gag functions as an ALIX-dependent late domain
Authors: Chaturbhuj Devidas , Patil Ajit , Gangakhedkar Raman 
Published: June 2018

AbstractALG-2 interacting protein X (ALIX) links HIV-1 Gag to the components of ESCRT-III. HIV-1 engages the ALIX via its nucleocapsid and LYPXnL motif in p6. Overexpression of ALIX corrects the release defect of PTAP deleted HIV-1 via LYPXnL/ALIX pathway. However, HIV-1 subtype C lacks the LYPXnL motif and hence cannot employ LYPXnL/ALIX mechanism. Though the preferential occurrences of PYXE insertion in HIV-1 C p6 is predicted to restore the ALIX binding site there is no functional proof to support these observations. In this study we show that HIV-1 construct with subtype C p6 having PTAP deletion and PYRE insertion (pNL-INp6ΔPTAP/PYRE) could respond to ALIX overexpression. Notably, conserved Phenyl alanine residue (F676) in ALIX was critical for ALIX mediated release of pNL-INp6ΔPTAP/PYRE implying the critical role of this hydrophobic patch in ALIX recruitment. In addition, we show that Nedd4-1 could also correct the release defect of pNL-INp6ΔPTAP/PYRE. Moreover, Nedd4-1 was more robust compared to ALIX in its ability to stimulate the release of pNL-INp6ΔPTAP/PYRE. Replication kinetic data highlights the positive effect of PYRE insertion on virus replication. In summary, our data reveals the functional role of PYRE insertion towards the cooperative mechanism of ALIX/Nedd4-1 in virus release in the absence of PTAP/Tsg101 pathway.
Investigating the viral ecology of global bee communities with high-throughput metagenomics
Authors: Galbraith David A. , Fuller Zachary L. , Ray Allyson M. , Brockmann Axel , Frazier Maryann , Gikungu Mary W. , Martinez J. Francisco Iturralde , Kapheim Karen M. , Kerby Jeffrey T. , Kocher Sarah D. , Losyev Oleksiy , Muli Elliud , Patch Harland M. , Rosa Cristina , Sakamoto Joyce M. , Stanley Scott , Vaudo Anthony D. , Grozinger Christina M. 
Published: June 2018

AbstractBee viral ecology is a fascinating emerging area of research: viruses exert a range of effects on their hosts, exacerbate impacts of other environmental stressors, and, importantly, are readily shared across multiple bee species in a community. However, our understanding of bee viral communities is limited, as it is primarily derived from studies of North American and European Apis mellifera populations. Here, we examined viruses in populations of A. mellifera and 11 other bee species from 9 countries, across 4 continents and Oceania. We developed a novel pipeline to rapidly and inexpensively screen for bee viruses. This pipeline includes purification of encapsulated RNA/DNA viruses, sequence-independent amplification, high throughput sequencing, integrated assembly of contigs, and filtering to identify contigs specifically corresponding to viral sequences. We identified sequences for (+)ssRNA, (−)ssRNA, dsRNA, and ssDNA viruses. Overall, we found 127 contigs corresponding to novel viruses (i.e. previously not observed in bees), with 27 represented by >0.1% of the reads in a given sample, and 7 contained an RdRp or replicase sequence which could be used for robust phylogenetic analysis. This study provides a sequence-independent pipeline for viral metagenomics analysis, and greatly expands our understanding of the diversity of viruses found in bee communities.
Interleukin-6/STAT3 signalling regulates adipocyte induced epithelial-mesenchymal transition in breast cancer cells
Authors: Gyamfi Jones , Lee Yun-Hee , Eom Minseob , Choi Junjeong 
Published: June 2018

AbstractThe tumour microenvironment is a key regulators of tumour progression through the secretion of growth factors that activate epithelial-mesenchymal transition (EMT). Induction of EMT is a key step for transition from a benign state to a metastatic tumour. Adipose tissue forms a bulk portion of the breast cancer microenvironment, emerging evidence indicates the potential for adipocytes to influence tumour progression through the secretion of adipokines that can induce EMT. The molecular mechanisms underlying how adipocytes enhance breast cancer progression is largely unknown. We hypothesized that paracrine signalling by adipocytes can activate EMT and results in increased migration and invasion characteristics of breast cancer cells. We found that IL-6 secreted by adipocytes induce EMT in breast cancer cells. The effect of IL-6 expression on EMT is mediated through activation of the signal transducer and activated of transcription 3 (STAT3). Blocking of IL-6 signalling in breast cancer cells and adipocytes, decreased proliferation, migration and invasion capabilities and altered the expression of genes regulating EMT. Together, our results suggest that matured human adipocytes can enhance the aggressive behaviour of breast cancer cells and induce an EMT-phenotype through paracrine IL-6/STAT3 signalling.
Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema
Authors: Rashid Kahkashan , Sundar Isaac K. , Gerloff Janice , Li Dongmei , Rahman Irfan 
Published: June 2018

AbstractCigarette smoke (CS) induces lung cellular senescence that plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). How aging influences cellular senescence and other molecular hallmarks, and increases the risk of CS-induced damage remains unknown. We hypothesized that aging-associated changes in lungs worsen the COPD/emphysema by CS exposure. Younger and older groups of C57BL/6J mice were exposed to chronic CS for 6 months with respective age-matched air-exposed controls. CS caused a decline in lung function and affected the lung structure of both groups of mice. No alterations were observed in the induction of inflammatory mediators between the air-exposed younger and older controls, but aging increased the severity of CS-induced lung inflammation. Aging per se increased lung cellular senescence and significant changes in damage-associated molecular patterns marker S100A8. Gene transcript analysis using the nanoString nCounter showed a significant upregulation of key pro-senescence targets by CS (Mmp12, Ccl2, Cdkn2a, Tert, Wrn, and Bub1b). Aging independently influenced lung function and structure, as well as increased susceptibility to CS-induced inflammation in emphysema, but had a negligible effect on cellular senescence. Thus, aging solely does not contribute to the induction of cellular senescence by CS in a mouse model of COPD/emphysema.
Thermally Activated Delayed Fluorescence Host for High Performance Organic Light-Emitting Diodes
Authors: Zhang Lu , Cheah Kok Wai 
Published: June 2018

AbstractThermally activated delayed florescence (TADF) materials can be an efficient host in organic LED (OLED). It is because it is possible to couple energetically the emission energy level of a dopant to the energy levels in the TADF material. In this work fluorescent emitters 2,3,6,7-tetrahydro-1,1,7,7,-tetramethyl-1H,5 H,11H-10-(2-benzothiazolyl)quinolizino-9,9a,1gh coumarin (c545t) and 5,6,11,12-tetraphenyltetracene (rubrene) were used as dopants in a blended TADF host; tris(4-carbazoyl-9-ylphenyl)amine (TCTA) with 2,4,6-tris(3′-(pyridin-3-yl)biphenyl-3-yl)-1,3,5-triazine (Tm3PyBPZ). The blended TADF host has an energy difference between the singlet and triplet excited states (ΔEST) around 27 meV with the yield of reverse intersystem crossing (ФRISC) nearly 100%. This high ФRISC yield enhances the OLED performance with the c545t doped OLED having 11.9% external quantum efficiency and 10% for the rubrene doped OLED.
Selective binding of facial features reveals dynamic expression fragments
Authors: Harrison Charlotte , Binetti Nicola , Mareschal Isabelle , Johnston Alan 
Published: June 2018

AbstractThe temporal correspondence between two arbitrarily chosen pairs of alternating features can generally be reported for rates up to 3–4 Hz. This limit is however surpassed for specialised visual mechanisms that encode conjunctions of features. Here we show that this 3–4 Hz limit is exceeded for eye gaze and eyebrow pairing, but not for eye gaze and mouth pairing, suggesting combined eye and eyebrow motion constitutes a dynamic expression fragment; a building block of superordinate facial actions.
The relative contribution of causal factors in the transition from infection to clinical chlamydial disease
Authors: Quigley Bonnie L. , Carver Scott , Hanger Jon , Vidgen Miranda E. , Timms Peter 
Published: June 2018

AbstractChlamydia is a major bacterial pathogen in humans and animals globally. Yet 80% of infections never progress to clinical disease. Decades of research have generated an interconnected network linking pathogen, host, and environmental factors to disease expression, but the relative importance of these and whether they account for disease progression remains unknown. To address this, we used structural equation modeling to evaluate putative factors likely to contribute to urogenital and ocular chlamydial disease in the koala (Phascolarctos cinereus). These factors include Chlamydia detection, load, and ompA genotype; urogenital and ocular microbiomes; host sex, age, weight, body condition; breading season, time of year; location; retrovirus co-infection; and major histocompatibility complex class II (MHCII) alleles. We show different microbiological processes underpin disease progression at urogenital and ocular sites. From each category of factors, urogenital disease was most strongly predicted by chlamydial PCR detection and load, koala body condition and environmental location. In contrast, ocular disease was most strongly predicted by phylum-level Chlamydiae microbiome proportions, sampling during breeding season and co-infection with koala retrovirus subtype B. Host MHCII alleles also contributed predictive power to both disease models. Our results also show considerable uncertainty remains, suggesting major causal mechanisms are yet to be discovered.
A data mining paradigm for identifying key factors in biological processes using gene expression data
Authors: Li Jin , Zheng Le , Uchiyama Akihiko , Bin Lianghua , Mauro Theodora M. , Elias Peter M. , Pawelczyk Tadeusz , Sakowicz-Burkiewicz Monika , Trzeciak Magdalena , Leung Donald Y. M. , Morasso Maria I. , Yu Peng 
Published: June 2018

AbstractA large volume of biological data is being generated for studying mechanisms of various biological processes. These precious data enable large-scale computational analyses to gain biological insights. However, it remains a challenge to mine the data efficiently for knowledge discovery. The heterogeneity of these data makes it difficult to consistently integrate them, slowing down the process of biological discovery. We introduce a data processing paradigm to identify key factors in biological processes via systematic collection of gene expression datasets, primary analysis of data, and evaluation of consistent signals. To demonstrate its effectiveness, our paradigm was applied to epidermal development and identified many genes that play a potential role in this process. Besides the known epidermal development genes, a substantial proportion of the identified genes are still not supported by gain- or loss-of-function studies, yielding many novel genes for future studies. Among them, we selected a top gene for loss-of-function experimental validation and confirmed its function in epidermal differentiation, proving the ability of this paradigm to identify new factors in biological processes. In addition, this paradigm revealed many key genes in cold-induced thermogenesis using data from cold-challenged tissues, demonstrating its generalizability. This paradigm can lead to fruitful results for studying molecular mechanisms in an era of explosive accumulation of publicly available biological data.
Significance of NS5B Substitutions in Genotype 1b Hepatitis C Virus Evaluated by Bioinformatics Analysis
Authors: Uchida Yoshihito , Nakamura Shugo , Kouyama Jun-Ichi , Naiki Kayoko , Motoya Daisuke , Sugawara Kayoko , Inao Mie , Imai Yukinori , Nakayama Nobuaki , Tomiya Tomoaki , Hedskog Charlotte , Brainard Diana , Mo Hongmei , Mochida Satoshi 
Published: June 2018

AbstractTo evaluate the effects of HCV NS5B amino acid substitutions on treatment outcome in Ledipasvir (LDV)/Sofosbuvir (SOF) for Japanese patients with genotype 1b HCV infection, NS5B sequences were examined in i) seven patients experiencing virologic failure after LDV/SOF in real-world practice, ii) 109 SOF-naïve patients, iii) 165 patients enrolled in Phase-3 LDV/SOF trial. A218S and C316N were detected in all patients with viral relapse; the percentages of these substitutions in SOF-naïve patients were 64.2% and 55.0%, respectively. Genotype 1b HCV strains with NS5B-C316N mutation were located in the leaves different from those in which HCV strains without such substitutions were present on the phylogenetic tree. Structural modeling revealed that amino acid 218 was located on the surface of the NTP tunnel. Free energy analysis based on molecular dynamics simulations demonstrated that the free energy required to pass through the tunnel was larger for triphosphate SOF than for UTP in NS5B polymerase carrying A218S, but not in wild-type. However, no susceptibility change was observed for these substitutions to SOF in replicon assay. Furthermore, the SVR rate was 100% in patients enrolled the Phase-3 trial. In conclusion, NS5B A218S and C316N were detected in all patients who relapsed following LDV/SOF in real-world practice. These substitutions did not impact the overall SVR rate after LDV/SOF, however, further studies are needed to elucidate the impact of these substitutions.