bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome Network Analysis Identifies CXCL13-CXCR5 Signaling Modules in the Prostate Tumor Immune Microenvironment
Authors: Ohandjo Adaugo Q. , Liu Zongzhi , Dammer Eric B. , Dill Courtney D. , Griffen Tiara L. , Carey Kaylin M. , Hinton Denise E. , Meller Robert , Lillard James W. 
Published: October 2019

AbstractThe tumor immune microenvironment (TIME) consists of multiple cell types that contribute to the heterogeneity and complexity of prostate cancer (PCa). In this study, we sought to understand the gene-expression signature of patients with primary prostate tumors by investigating the co-expression profiles of patient samples and their corresponding clinical outcomes, in particular “disease-free months” and “disease reoccurrence”. We tested the hypothesis that the CXCL13-CXCR5 axis is co-expressed with factors supporting TIME and PCa progression. Gene expression counts, with clinical attributes from PCa patients, were acquired from TCGA. Profiles of PCa patients were used to identify key drivers that influence or regulate CXCL13-CXCR5 signaling. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expression patterns among CXCL13-CXCR5, associated genes, and key genetic drivers within the CXCL13-CXCR5 signaling pathway. The processing of downloaded data files began with quality checks using NOISeq, followed by WGCNA. Our results confirmed the quality of the TCGA transcriptome data, identified 12 co-expression networks, and demonstrated that CXCL13, CXCR5 and associated genes are members of signaling networks (modules) associated with G protein coupled receptor (GPCR) responsiveness, invasion/migration, immune checkpoint, and innate immunity. We also identified top canonical pathways and upstream regulators associated with CXCL13-CXCR5 expression and function.
C60 ions of 1 MeV are slow but elongate nanoparticles like swift heavy ions of hundreds MeV
Authors: Amekura H. , Narumi K. , Chiba A. , Hirano Y. , Yamada K. , Tsuya D. , Yamamoto S. , Okubo N. , Ishikawa N. , Saitoh Y. 
Published: October 2019

AbstractThis study reports that high fluence fullerene ion (C60+) irradiation of 1–6 MeV, which was made possible by a new-type of high-flux ion source, elongates metal nanoparticles (NPs) in amorphous SiO2 as efficiently as swift heavy ions (SHIs) of 200 MeV Xe14+, i.e., two orders of the magnitude higher energy ions. Comparing the irradiation effects induced by both the beams, the stopping processes of C60 ions in SiO2 are discussed in this paper. Despite of having almost the same elongation efficiency, the C60+ irradiation induced ~10 times more efficient sputtering due to the clustering enhancement and/or the synergy effect. Ion tracks of ~10.4 nm in diameter and 60–80 nm in length were observed in crystalline SiO2 under 4 MeV C60 irradiation. While the track diameter was comparable to those by SHIs of the same electronic stopping, much shorter track lengths than those predicted by a rigid C60 molecule model indicates that the fragmentation occurred due to nuclear collisions. The elongation of the metal NPs was induced only down to the depth where the tracks were observed but not beyond.
Macrofluidic recirculating model of skeletal metastasis
Authors: Osawa Takahiro , Wang Wenchu , Dai Jinlu , Keller Evan T. 
Published: October 2019

AbstractWhile microfluidic systems model aspects of metastasis, they are limited to artificially created tissues of limited complexity. We set out to develop an in vitro model of tumor cell migration from a primary tumor to a distant site that allows use of tissue. Accordingly, we created a macrofluidic model using culture plate wells connected with type I collagen-coated large bore tubing and has recirculating media. Green fluorescent protein-positive prostate carcinoma cells in a hydrogel or excised tumor xenografts from mice were placed into primary tumor sites and either human bone stromal cells (HS-5) in a hydrogel or human-derived bone chips were seeded into metastatic sites. Cells from the primary sites migrated to and grew in metastatic sites. Bone enhanced growth at metastatic sites and established a CXCL12 gradient that was higher in metastatic versus primary sites. AMD3100-mediated inhibition of CXCL12 function reduced the number of cells targeting the bone at the metastatic sites. In summary, we have developed a macrofluidic metastasis model that allows incorporation of tumor and metastatic microenvironment tissues and models chemotaxis. This system allows for incorporation of tumor heterogeneity and inclusion of an intact microenvironment. These features will facilitate identification of mechanisms and therapeutics for bone metastasis.
Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells
Authors: Raymond Aaron C. , Gao Boning , Girard Luc , Minna John D. , Gomika Udugamasooriya D. 
Published: October 2019

AbstractTumors often contain a small subset of drug-resisting, self-renewing, and highly metastatic cells called tumor initiating cells or cancer stem cells (CSCs). To develop new approaches to detecting and targeting lung cancer CSCs, we applied an “unbiased” peptoid combinatorial cell screen to identify highly specific ligands that bind a CSC subpopulation of non-small cell lung cancer cells (defined by Aldefluor positivity), but not the remaining aldefluor negative cancer cells from the same preclinical model. One of the ‘hit’ peptoids bound to plectin, a structural protein, predominantly expressed intracellularly, but whose localization on the cell surface is linked to tumor invasion and metastasis. Our studies show both genotypic and phenotypic correlations between plectin and lung CSCs, as well as association of high plectin mRNA expression with poor patient survival in lung adenocarcinoma, potentially identifying plectin as a biomarker for lung CSCs.
Flying Drosophila show sex-specific attraction to fly-labelled food
Authors: Cazalé-Debat Laurie , Houot Benjamin , Farine Jean-Pierre , Everaerts Claude , Ferveur Jean-François 
Published: October 2019

AbstractAnimals searching for food and sexual partners often use odourant mixtures combining food-derived molecules and pheromones. For orientation, the vinegar fly Drosophila melanogaster uses three types of chemical cues: (i) the male volatile pheromone 11-cis-vaccenyl acetate (cVA), (ii) sex-specific cuticular hydrocarbons (CHs; and CH-derived compounds), and (iii) food-derived molecules resulting from microbiota activity. To evaluate the effects of these chemicals on odour-tracking behaviour, we tested Drosophila individuals in a wind tunnel. Upwind flight and food preference were measured in individual control males and females presented with a choice of two food sources labelled by fly lines producing varying amounts of CHs and/or cVA. The flies originated from different species or strains, or their microbiota was manipulated. We found that (i) fly-labelled food could attract—but never repel—flies; (ii) the landing frequency on fly-labelled food was positively correlated with an increased flight duration; (iii) male—but not female or non-sex-specific—CHs tended to increase the landing frequency on fly-labelled food; (iv) cVA increased female—but not male—preference for cVA-rich food; and (v) microbiota-derived compounds only affected male upwind flight latency. Therefore, sex pheromones interact with food volatile chemicals to induce sex-specific flight responses in Drosophila.
Variations in growth, water consumption and economic benefit of transplanted cotton after winter wheat harvest subjected to different irrigation methods
Authors: Zhang Hao , Liu Hao , Wang Shunsheng , Guo Xuan , Ge Lu , Sun Jingsheng 
Published: October 2019

AbstractIn the North China Plain (NCP), the utilization efficiency of cultivated land can be improved by transplanted cotton after winter wheat harvest (TCWWH). To understand the growth, water consumption and economic benefit of TCWWH under different irrigation methods, an irrigation experiment was carried out during 2013–2015 to explore the effects of border irrigation (BI), surface drip irrigation (SDI) and micro-sprinkling hose irrigation (MHI) on the plant development, water use efficiency (WUE) and economic benefit of TCWWH. The results showed that the survival rate of cotton seedlings in the SDI treatment was 12% and 7% larger than that in the BI and the MHI treatments, respectively. SDI increased plant height by 19% and 8% and increased leaf area index (LAI) by 24% and 17%, compared with BI and MHI, respectively. The highest seed cotton yield and better fibre quality were obtained in the SDI treatment, compared to the BI and the MHI treatments. Compared with BI and MHI, SDI reduced the soil evaporation and evapotranspiration (ET) in the field, and resulted in the largest WUE. The net profit generated by the SDI treatment exceeded that of the BI and the MHI treatments by 183% and 23%, respectively. Therefore, SDI can promote the growth of TCWWH and can increase the WUE and the economic benefit of TCWWH, compared with BI and MHI.
Hematopoietic Npc1 mutation shifts gut microbiota composition in Ldlr−/− mice on a high-fat, high-cholesterol diet
Authors: Houben Tom , Penders John , Oligschlaeger Yvonne , dos Reis Inês A. Magro , Bonder Marc-Jan , Koonen Debby P. , Fu Jingyuan , Hofker Marten H. , Shiri-Sverdlov Ronit 
Published: October 2019

AbstractWhile the link between diet-induced changes in gut microbiota and lipid metabolism in metabolic syndrome (MetS) has been established, the contribution of host genetics is rather unexplored. As several findings suggested a role for the lysosomal lipid transporter Niemann-Pick type C1 (NPC1) in macrophages during MetS, we here explored whether a hematopoietic Npc1 mutation, induced via bone marrow transplantation, influences gut microbiota composition in low-density lipoprotein receptor knockout (Ldlr−/−) mice fed a high-fat, high-cholesterol (HFC) diet for 12 weeks. Ldlr−/− mice fed a HFC diet mimic a human plasma lipoprotein profile and show features of MetS, providing a model to explore the role of host genetics on gut microbiota under MetS conditions. Fecal samples were used to profile the microbial composition by 16 s ribosomal RNA gene sequencing. The hematopoietic Npc1 mutation shifted the gut microbiota composition and increased microbial richness and diversity. Variations in plasma lipid levels correlated with microbial diversity and richness as well as with several bacterial genera. This study suggests that host genetic influences on lipid metabolism affect the gut microbiome under MetS conditions. Future research investigating the role of host genetics on gut microbiota might therefore lead to identification of diagnostic and therapeutic targets for MetS.
Evaluation of Small Molecule Drug Uptake in Patient-Derived Prostate Cancer Explants by Mass Spectrometry
Authors: Mutuku Shadrack M. , Trim Paul J. , Prabhala Bala K. , Irani Swati , Bremert Kayla L. , Logan Jessica M. , Brooks Douglas A. , Stahl Jürgen , Centenera Margaret M. , Snel Marten F. , Butler Lisa M. 
Published: October 2019

AbstractPatient-derived explant (PDE) culture of solid tumors is increasingly being applied to preclinical evaluation of novel therapeutics and for biomarker discovery. In this technique, treatments are added to culture medium and penetrate the tissue via a gelatin sponge scaffold. However, the penetration profile and final concentrations of small molecule drugs achieved have not been determined to date. Here, we determined the extent of absorption of the clinical androgen receptor antagonist, enzalutamide, into prostate PDEs, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matrix-assisted laser/desorption ionisation (MALDI) mass spectrometry imaging (MSI). In a cohort of 11 PDE tissues from eight individual patients, LC-MS/MS quantification of PDE homogenates confirmed enzalutamide (10 µM) uptake by all PDEs, which reached maximal average tissue concentration of 0.24–0.50 ng/µg protein after 48 h culture. Time dependent uptake of enzalutamide (50 µM) in PDEs was visualized using MALDI MSI over 24–48 h, with complete penetration throughout tissues evident by 6 h of culture. Drug signal intensity was not homogeneous throughout the tissues but had areas of markedly high signal that corresponded to drug target (androgen receptor)-rich epithelial regions of tissue. In conclusion, application of MS-based drug quantification and visualization in PDEs, and potentially other 3-dimensional model systems, can provide a more robust basis for experimental study design and interpretation of pharmacodynamic data.
Causes of large projected increases in hurricane precipitation rates with global warming
Authors: Liu Maofeng , Vecchi Gabriel A. , Smith James A. , Knutson Thomas R. 
Published: October 2019

AbstractRecent climate modeling studies point to an increase in tropical cyclone rainfall rates in response to climate warming. These studies indicate that the percentage increase in tropical cyclone rainfall rates often outpaces the increase in saturation specific humidity expected from the Clausius-Clapeyron relation (~7% °C−1). We explore the change in tropical cyclone rainfall rates over all oceans under global warming using a high-resolution climate model with the ability to simulate the entire intensity spectrum of tropical cyclones. Consistent with previous results, we find a robust increase of tropical cyclone rainfall rates. The percentage increase for inner-core tropical cyclone rainfall rates in our model is markedly larger than the Clausius-Clapeyron rate. However, when the impact of storm intensity is excluded, the rainfall rate increase shows a much better match with the Clausius-Clapeyron rate, suggesting that the “super Clausius-Clapeyron” scaling of rainfall rates with temperature increase is due to the warming-induced increase of tropical cyclone intensity. The increase of tropical cyclone intensity and environmental water vapor, in combination, explain the tropical cyclone rainfall rate increase under global warming.
The repurposing of type I-E CRISPR-Cascade for gene activation in plants
Authors: Young Joshua K. , Gasior Stephen L. , Jones Spencer , Wang Lijuan , Navarro Pedro , Vickroy Becca , Barrangou Rodolphe 
Published: October 2019

AbstractCRISPR-Cas systems are robust and facile tools for manipulating the genome, epigenome and transcriptome of eukaryotic organisms. Most groups use class 2 effectors, such as Cas9 and Cas12a, however, other CRISPR-Cas systems may provide unique opportunities for genome engineering. Indeed, the multi-subunit composition of class 1 systems offers to expand the number of domains and functionalities that may be recruited to a genomic target. Here we report DNA targeting in Zea mays using a class 1 type I-E CRISPR-Cas system from S. thermophilus. First, we engineer its Cascade complex to modulate gene expression by tethering a plant transcriptional activation domain to 3 different subunits. Next, using an immunofluorescent assay, we confirm Cascade cellular complex formation and observe enhanced gene activation when multiple subunits tagged with the transcriptional activator are combined. Finally, we examine Cascade mediated gene activation at chromosomal DNA targets by reprogramming Zea mays cells to change color.
Wavelength-decoupled geometric metasurfaces by arbitrary dispersion control
Authors: Yoon Gwanho , Kim Jeonghyun , Mun Jungho , Lee Dasol , Nam Ki Tae , Rho Junsuk 
Published: October 2019

AbstractConventional multicolor metaholograms suffer from the fundamental limitations of low resolution and irreducible noise because the unit structure functionality is still confined to a single wavelength. Here, we propose wavelength-decoupled metasurfaces that enables to control chromatic phase responses independently in a full range from 0 to 2π for each wavelength. The propagation phase associated with the geometric phase of rectangular dielectric nanostructures plays a critical role to embed a dual phase response into a single nanostructure. A multicolor metahologram is also demonstrated to verify the feasibility of our method that breaks through the fundamental constraints of conventional multicolor metaholograms. Our approach can be extended to achieve complete control of chromatic phase responses in the visible for general dual-wavelength diffractive optical elements.
Cu(ii) phenanthroline–phenazine complexes dysregulate mitochondrial function and stimulate apoptosis
Authors: Rochford Garret , Molphy Zara , Kavanagh Kevin , McCann Malachy , Devereux Michael , Kellett Andrew , Howe Orla 
Published: October 2019

Abstract
Herein we report an in-depth study on the cytotoxic mechanism of action of four developmental cytotoxic copper(ii) complexes: [Cu(phen)2]2+ (Cu-Phen); [Cu(DPQ)(Phen)]2+ (Cu-DPQ-Phen); [Cu(DPPZ)(Phen)]2+; and [Cu(DPPN)(Phen)]2+ (where Phen = 1,10-phenanthroline, DPQ = dipyrido[3,2-f:2′,3′-h]quinoxaline, DPPZ = dipyrido[3,2-a:2′,3′-c]phenazine, and DPPN = benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine). This complex class is known for its DNA intercalative properties and recent evidence—derived from an in vivo proteomic study—supports the potential targeting of mitochondrial function. Therefore, we focused on mitochondrial-mediated apoptosis related to cytotoxic activity and the potential impact these agents have on mitochondrial function. The Cu(ii) complexes demonstrated superior activity regardless of aromatic extension within the phenazine ligand to the previously demonstrated activity of cisplatin. Unique toxicity mechanisms were also identified in prior demonstrated cisplatin sensitive and resistant cell lines. Double strand breaks in genomic DNA, quantified by γH2AX foci formation, were then coupled with apoptotic gene expression to elucidate the mechanisms of cell death. These results indicate that while DNA damage-induced apoptosis by BAX, XIAP and caspase-9 and -3 expression is moderate for the Cu(ii) complexes when compared to cisplatin, protein targets independent of DNA exert a multimodal mechanistic effect. Significantly, mitochondrial gene expression of oxidative stress, protease expression, and fission/fusion processes—upregulated HMOX, DRP1 and LON, respectively—indicated an increased oxidative damage associated with compromised mitochondrial health upon exposure to these agents. These data support a unique mode of action by these complexes and provide valuable evidence of the developmental potential of these therapeutic inorganic complexes.
Silencing of lncRNA EZR-AS1 inhibits proliferation, invasion, and migration of colorectal cancer cells through blocking transforming growth factor β signaling
Authors: Liu Zhenhua , Wang Ning , Wang Feiqing , Zhang Shuaimin , Ding Jie 
Published: October 2019

Abstract
Long non-coding RNA (lncRNA) plays a key regulatory role in the pathogenesis of colorectal cancer (CRC). In the present study, the specific regulatory role of lncRNA ezrin antisense RNA 1 (EZR-AS1) on CRC was investigated. The expression of lncRNA EZR-AS1 was significantly up-regulated in CRC cell lines (HCT8, HCT116, HT29, and SW620 cells), which was significantly different from that of normal human fetal colonic mucosa cells (FHC cells) (P&lt;0.01). HCT116 and HT29 cells were then transfected with EZR-AS1 shRNA (sh-EZR-AS1) to silence lncRNA EZR-AS1 (P&lt;0.01). When compared with the Control, after transfection of SH-EZR-AS1, E-cadherin was up-regulated, Vimentin was down-regulated, the apoptosis rate was increased, the cell viability, wound healing rate, and the number of invasive cells were decreased in HCT116 and HT29 cells (P&lt;0.05). Silencing of lncRNA EZR-AS also significantly reduced the tumor volume and weight in mice injected with sh-EZR-AS1-transfected HCT116 and HT29 cells (P&lt;0.05). The regulatory relationship between lncRNA EZR-AS1 and transforming growth factor β (TGF-β) signaling was further identified in CRC cells. Silencing of lncRNA EZR-AS1 significantly down-regulated TGF-β, Smad2, and α-SMA expression in HCT116 and HT29 cells at the protein level (P&lt;0.05). The intervention of SB431542 (a TGF-β receptor blocker) and silencing of Smad2 both significantly down-regulated lncRNA EZR-AS1 expression in HCT116 and HT29 cells (P&lt;0.01). In conclusion, silencing of lncRNA EZR-AS1 inhibited the proliferation, invasion, migration, and epithelial–mesenchymal transition, and promoted the apoptosis of CRC cells through blocking TGF-β signaling.
Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions
Authors: Cheng Nan , Zhang Zheng , Guo Yue , Qiu Zhuo-Lin , Du Jing-Yi , Hei Zi-Qing , Li Xiang 
Published: October 2019

AbstractNeuropathic pain is a common, debilitating clinical issue. Here, the weighted gene co-expression network analysis (WGCNA) was used to identify the specific modules and hub genes that are related to neuropathic pain. The microarray dataset of a neuropathic rat model induced by tibial nerve transection (TNT), including dorsal root ganglion (DRG) tissues from TNT model (n=7) and sham (n=8) rats, was downloaded from the ArrayExpress database (E-MTAB-2260). The co-expression network modules were identified by the WGCNA package. The protein–protein interaction (PPI) network was constructed, and the node with highest level of connectivity in the network were identified as the hub gene. A total of 1739 genes and seven modules were identified. The most significant module was the brown module, which contained 215 genes that were primarily associated with the biological process (BP) of the defense response and molecular function of calcium ion binding. Furthermore, C–C motif chemokine ligand 2 (Ccl2), Fos and tissue inhibitor of metalloproteinase 1 (Timp1) which were identified as the hub genes in the PPI network and two subnetworks separately. The in vivo studies validated that mRNA and protein levels of Ccl2, Fos and Timp1 were up-regulated in DRG and spinal cord tissues after TNT. The present study offers novel insights into the molecular mechanisms of neuropathic pain in the context of peripheral nerve injury.
Association between dectin-1 gene single nucleotide polymorphisms and fungal infection: a systemic review and meta-analysis
Authors: Zhou Peiru , Xie Yufei , Yan Zhimin , Liu Xiaosong , Hua Hong 
Published: October 2019

Abstract
Objectives: To investigate the association between dectin-1 gene single nucleotide polymorphisms (SNPs) and susceptibility to fungal infection (FI). Methods: Databases were searched electronically and manually to identify case–control studies concerning dectin-1 SNPs and FI, which were published up to 12 November 2018. The Newcastle–Ottawa Quality Assessment Scale was used to determine the study quality and bias. The SNP frequencies of the B (the variant or minor allele) and A (the wild or major allele) alleles of the dectin-1 gene in both cases and controls were analyzed with regard to FI susceptibility. Results: Eight high-quality studies were included in the review. Systemic review of the included studies demonstrated that dectin-1 SNPs rs3901533 and rs7309123 might be associated with susceptibility to invasive pulmonary aspergillosis infection; moreover, rs16910527 SNP can possibly increase the susceptibility to oropharyngeal candidiasis in HIV-positive patients. The meta-analysis identified significant associations between dectin-1 SNPs and overall FI risk in the homozygote model (pooled odds ratio (OR) 1.77, P=0.04). When classified by subtypes, significant associations were also found for deep FI in the homozygote model (pooled OR 2.46, P=0.01) and the recessive model (pooled OR 2.85, P=0.002). There appeared to be no significant association between dectin-1 SNPs and superficial FI. Conclusion: Systemic review of the included studies suggested that dectin-1 SNPs rs3901533, rs7309123, and rs16910527 might play a role in FI susceptibility. The meta-analysis provided convincing evidence that dectin-1 SNPs might have an important role in FI susceptibility, especially for deep FI.