bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy
Authors: Kim Eun Kyung , Kwon Jeong-Eun , Lee Seon-Young , Lee Eun-Jung , Kim Da Som , Moon Su-Jin , Lee Jennifer , Kwok Seung-Ki , Park Sung-Hwan , Cho Mi-La 
Published: January 2017

AbstractFibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades cartilage and bone in rheumatoid arthritis (RA). FLS resistance to apoptosis is a major characteristic of RA. The aims of this study were to investigate the effects of interleukin-17 (IL-17) and IL-17-producing T helper (Th17) cells on resistance to apoptosis in FLSs from RA patients (RA FLSs) and their roles in mitochondrial dysfunction and autophagy. Mitochondrial function was assessed in RA FLSs and FLSs from osteoarthritis patients (OA FLSs). FLSs were treated with IL-17 and their morphological features, respiratory level and mitochondrial gene expression were measured. The effects of IL-17 and Th17 cells on the relationship between autophagy and apoptosis were evaluated by measuring the expression of apoptosis-related genes using sodium nitroprusside or 3-methyladenine. The mitochondria of FLSs isolated from RA and osteoarthritis patients displayed different morphological and physiological features. RA FLSs exhibited greater autophagosome formation and greater dysfunction of mitochondrial respiration compared with OA FLSs. IL-17 induced mitochondrial dysfunction and autophagosome formation in RA FLSs, suggesting that they were resistant to apoptosis. Autophagy-related antiapoptosis induced by IL-17 was restored by inhibition of autophagy, suggesting a relationship between mitochondrial dysfunction and cell survival in RA FLSs. Th17 cells and IL-17 increased autophagy of RA FLSs by causing mitochondrial dysfunction. Our findings suggest that, in RA, interactions between RA FLSs and Th17 cells may be involved in the tumorous growth of FLSs and the formation of pannus in joints.
Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression
Authors: Huang Chongbiao , Li Na , Li Zengxun , Chang Antao , Chen Yanan , Zhao Tiansuo , Li Yang , Wang Xiuchao , Zhang Wei , Wang Zhimin , Luo Lin , Shi Jingjing , Yang Shengyu , Ren He , Hao Jihui 
Published: January 2017

AbstractInterleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation. Mechanistically, IL-35 promotesICAM1overexpression through a GP130-STAT1 signalling pathway, which facilitates endothelial adhesion and transendothelial migration via an ICAM1–fibrinogen–ICAM1 bridge. In an orthotopic xenograft model, IL-35 promotes spontaneous pancreatic cancer metastasis in anICAM1-dependent manner. Together, our results indicate additional functions of IL-35 in promoting PDAC metastasis through mediatingICAM1expression.
Shape-dependent ordering of gold nanocrystals into large-scale superlattices
Authors: Gong Jianxiao , Newman Richmond S. , Engel Michael , Zhao Man , Bian Fenggang , Glotzer Sharon C. , Tang Zhiyong 
Published: January 2017

AbstractSelf-assembly of individual building blocks into highly ordered structures, analogous to spontaneous growth of crystals from atoms, is a promising approach to realize the collective properties of nanocrystals. Yet the ability to reliably produce macroscopic assemblies is unavailable and key factors determining assembly quality/yield are not understood. Here we report the formation of highly ordered superlattice films, with single crystalline domains of up to half a millimetre in two dimensions and thickness of up to several microns from nanocrystals with tens of nanometres in diameter. Combining experimental and computational results for gold nanocrystals in the shapes of spheres, cubes, octahedra and rhombic dodecahedra, we investigate the entire self-assembly process from disordered suspensions to large-scale ordered superlattices induced by nanocrystal sedimentation and eventual solvent evaporation. Our findings reveal that the ultimate coherence length of superlattices strongly depends on nanocrystal shape. Factors inhibiting the formation of high-quality large-scale superlattices are explored in detail.
The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells
Authors: Gambardella Gennaro , Carissimo Annamaria , Chen Amy , Cutillo Luisa , Nowakowski Tomasz J. , di Bernardo Diego , Blelloch Robert 
Published: January 2017

AbstractMicroRNAs act posttranscriptionally to suppress multiple target genes within a cell population. To what extent this multi-target suppression occurs in individual cells and how it impacts transcriptional heterogeneity and gene co-expression remains unknown. Here we used single-cell sequencing combined with introduction of individual microRNAs. miR-294 and let-7c were introduced into otherwise microRNA-deficient Dgcr8 knockout mouse embryonic stem cells. Both microRNAs induce suppression and correlated expression of their respective gene targets. The two microRNAs had opposing effects on transcriptional heterogeneity within the cell population, with let-7c increasing and miR-294 decreasing the heterogeneity between cells. Furthermore, let-7c promotes, whereas miR-294 suppresses, the phasing of cell cycle genes. These results show at the individual cell level how a microRNA simultaneously has impacts on its many targets and how that in turn can influence a population of cells. The findings have important implications in the understanding of how microRNAs influence the co-expression of genes and pathways, and thus ultimately cell fate.
The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes
Authors: Wu Vin-Cent , Wang Shuo-Meng , Chueh Shih-Chieh Jeff , Yang Shao-Yu , Huang Kuo-How , Lin Yen-Hung , Wang Jian-Jhong , Connolly Rory , Hu Ya-Hui , Gomez-Sanchez Celso E. , Peng Kang-Yung , Wu Kwan-Dun 
Published: January 2017

AbstractConstitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboringCTNNB1mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harboredKCNJ5mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) hadCTNNB1mutations. Patients with APAs harboringCTNNB1mutations were older and had shorter duration of hypertension. After adrenalectomy,CTNNB1mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboringCTNNB1mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests thatCTNNB1mutations may be more related to tumorigenesis rather than excessive aldosterone production.
WHSC1L1-mediated EGFR mono-methylation enhances the cytoplasmic and nuclear oncogenic activity of EGFR in head and neck cancer
Authors: Saloura Vassiliki , Vougiouklakis Theodore , Zewde Makda , Deng Xiaolan , Kiyotani Kazuma , Park Jae-Hyun , Matsuo Yo , Lingen Mark , Suzuki Takehiro , Dohmae Naoshi , Hamamoto Ryuji , Nakamura Yusuke 
Published: January 2017

AbstractWhile multiple post-translational modifications have been reported to regulate the function of epidermal growth factor receptor (EGFR), the effect of protein methylation on its function has not been well characterized. In this study, we show that WHSC1L1 mono-methylates lysine 721 in the tyrosine kinase domain of EGFR, and that this methylation leads to enhanced activation of its downstream ERK cascade without EGF stimulation. We also show that EGFR K721 mono-methylation not only affects the function of cytoplasmic EGFR, but also that of nuclear EGFR. WHSC1L1-mediated methylation of EGFR in the nucleus enhanced its interaction with PCNA in squamous cell carcinoma of the head and neck (SCCHN) cells and resulted in enhanced DNA synthesis and cell cycle progression. Overall, our study demonstrates the multifaceted oncogenic function of the protein lysine methyltransferase WHSC1L1 in SCCHN, which is mediated through direct non-histone methylation of the EGFR protein with effects both in its cytoplasmic and nuclear functions.
Chelerythrine down regulates expression of VEGFA, BCL2 and KRAS by arresting G-Quadruplex structures at their promoter regions
Authors: Jana Jagannath , Mondal Soma , Bhattacharjee Payel , Sengupta Pallabi , Roychowdhury Tanaya , Saha Pranay , Kundu Pallob , Chatterjee Subhrangsu 
Published: January 2017

AbstractA putative anticancer plant alkaloid, Chelerythrine binds to G-quadruplexes at promoters of VEGFA, BCL2 and KRAS genes and down regulates their expression. The association of Chelerythrine to G-quadruplex at the promoters of these oncogenes were monitored using UV absorption spectroscopy, fluorescence anisotropy, circular dichroism spectroscopy, CD melting, isothermal titration calorimetry, molecular dynamics simulation and quantitative RT-PCR technique. The pronounced hypochromism accompanied by red shifts in UV absorption spectroscopy in conjunction with ethidium bromide displacement assay indicates end stacking mode of interaction of Chelerythrine with the corresponding G-quadruplex structures. An increase in fluorescence anisotropy and CD melting temperature of Chelerythrine-quadruplex complex revealed the formation of stable Chelerythrine-quadruplex complex. Isothermal titration calorimetry data confirmed that Chelerythrine-quadruplex complex formation is thermodynamically favourable. Results of quantative RT-PCR experiment in combination with luciferase assay showed that Chelerythrine treatment to MCF7 breast cancer cells effectively down regulated transcript level of all three genes, suggesting that Chelerythrine efficiently binds toin celluloquadruplex motifs. MD simulation provides the molecular picture showing interaction between Chelerythrine and G-quadruplex. Binding of Chelerythrine with BCL2, VEGFA and KRAS genes involved in evasion, angiogenesis and self sufficiency of cancer cells provides a new insight for the development of future therapeutics against cancer.
Super-strong materials for temperatures exceeding 2000 °C
Authors: Silvestroni Laura , Kleebe Hans-Joachim , Fahrenholtz William G. , Watts Jeremy 
Published: January 2017

AbstractCeramics based on group IV-V transition metal borides and carbides possess melting points above 3000 °C, are ablation resistant and are, therefore, candidates for the design of components of next generation space vehicles, rocket nozzle inserts, and nose cones or leading edges for hypersonic aerospace vehicles. As such, they will have to bear high thermo-mechanical loads, which makes strength at high temperature of great importance. While testing of these materials above 2000 °C is necessary to prove their capabilities at anticipated operating temperatures, literature reports are quite limited. Reported strength values for zirconium diboride (ZrB2) ceramics can exceed 1 GPa at room temperature, but these values rapidly decrease, with all previously reported strengths being less than 340 MPa at 1500 °C or above. Here, we show how the strength of ZrB2ceramics can be increased to more than 800 MPa at temperatures in the range of 1500–2100 °C. These exceptional strengths are due to a core-shell microstructure, which leads toin-situtoughening and sub-grain refinement at elevated temperatures. Our findings promise to open a new avenue to designing materials that are super-strong at ultra-high temperatures.
Tracking of Mesenchymal Stem Cells with Fluorescence Endomicroscopy Imaging in Radiotherapy-Induced Lung Injury
Authors: Perez Jessica R. , Ybarra Norma , Chagnon Frederic , Serban Monica , Lee Sangkyu , Seuntjens Jan , Lesur Olivier , El Naqa Issam 
Published: January 2017

AbstractMesenchymal stem cells (MSCs) have potential for reducing inflammation and promoting organ repair. However, limitations in available techniques to track them and assess this potential for lung repair have hindered their applicability. In this work, we proposed, implemented and evaluated the use of fluorescence endomicroscopy as a novel imaging tool to track MSCs in vivo. MSCs were fluorescently labeled and injected into a rat model of radiation-induced lung injury via endotracheal (ET) or intravascular (IV) administration. Our results show that MSCs were visible in the lungs with fluorescence endomicroscopy. Moreover, we developed an automatic cell counting algorithm to quantify the number of detected cells in each condition. We observed a significantly higher number of detected cells in ET injection compared to IV and a slight increase in the mean number of detected cells in irradiated lungs compared to control, although the latter did not reach statistical significance. Fluorescence endomicroscopy imaging is a powerful new minimally invasive and translatable tool that can be used to track and quantify MSCs in the lungs and help assess their potential in organ repair.
Dynamic modeling of uteroplacental blood flow in IUGR indicates vortices and elevated pressure in the intervillous space – a pilot study
Authors: Roth Christian J. , Haeussner Eva , Ruebelmann Tanja , Koch Franz v. , Schmitz Christoph , Frank Hans-Georg , Wall Wolfgang A. 
Published: January 2017

AbstractIschemic placental disease is a concept that links intrauterine growth retardation (IUGR) and preeclampsia (PE) back to insufficient remodeling of uterine spiral arteries. The rheological consequences of insufficient remodeling of uterine spiral arteries were hypothesized to mediate the considerably later manifestation of obstetric disease. However, the micro-rheology in the intervillous space (IVS) cannot be examined clinically and rheological animal models of the human IVS do not exist. Thus, an in silico approach was implemented to provide in vivo inaccessible data. The morphology of a spiral artery and the inflow region of the IVS were three-dimensionally reconstructed to provide a morphological stage for the simulations. Advanced high-end supercomputing resources were used to provide blood flow simulations at high spatial resolution. Our simulations revealed turbulent blood flow (high-velocity jets and vortices) combined with elevated blood pressure in the IVS and increased wall shear stress at the villous surface in conjunction with insufficient spiral artery remodeling only. Post-hoc histological analysis of uterine veins showed evidence of increased trophoblast shedding in an IUGR placenta. Our data support that rheological alteration in the IVS is a relevant mechanism linking ischemic placental disease to altered structural integrity and function of the placenta.
New insights into fetal mammary gland morphogenesis: differential effects of natural and environmental estrogens
Authors: Speroni Lucia , Voutilainen Maria , Mikkola Marja L. , Klager Skylar A. , Schaeberle Cheryl M. , Sonnenschein Carlos , Soto Ana M. 
Published: January 2017

AbstractAn increased breast cancer risk during adulthood has been linked to estrogen exposure during fetal life. However, the impossibility of removing estrogens from the feto-maternal unit has hindered the testing of estrogen’s direct effect on mammary gland organogenesis. To overcome this limitation, we developed an ex vivo culture method of the mammary gland where the direct action of estrogens can be tested during embryonic days (E)14 to 19. Mouse mammary buds dissected at E14 and cultured for 5 days showed that estrogens directly altered fetal mammary gland development. Exposure to 0.1 pM, 10 pM, and 1 nM 17 β-estradiol (E2) resulted in monotonic inhibition of mammary buds ductal growth. In contrast, Bisphenol-A (BPA) elicited a non-monotonic response. At environmentally relevant doses (1 nM), BPA significantly increased ductal growth, as previously observed in vivo, while 1 μM BPA significantly inhibited ductal growth. Ductal branching followed the same pattern. This effect of BPA was blocked by Fulvestrant, a full estrogen antagonist, while the effect of estradiol was not. This method may be used to study the hormonal regulation of mammary gland development, and to test newly synthesized chemicals that are released into the environment without proper assessment of their hormonal action on critical targets like the mammary gland.
Viral microRNAs Target a Gene Network, Inhibit STAT Activation, and Suppress Interferon Responses
Authors: Ramalingam Dhivya , Ziegelbauer Joseph M. 
Published: January 2017

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs during latency that are processed to yield ~25 mature microRNAs (miRNAs). We were interested in identifying cellular networks that were targeted by KSHV-miRNAs and employed network building strategies using validated KSHV miRNA targets. Here, we report the identification of a gene network centering on the transcription factor- signal transducer and activator of transcription 3 (STAT3) that is targeted by KSHV miRNAs. KSHV miRNAs suppressed STAT3 and STAT5 activation and inhibited STAT3-dependent reporter activation upon IL6-treatment. KSHV miRNAs also repressed the induction of antiviral interferon-stimulated genes upon IFNα- treatment. Finally, we observed increased lytic reactivation of KSHV from latently infected cells upon STAT3 repression with siRNAs or a small molecule inhibitor. Our data suggest that treatment of infected cells with a STAT3 inhibitor and a viral replication inhibitor, ganciclovir, represents a possible strategy to eliminate latently infected cells without increasing virion production. Together, we show that KSHV miRNAs suppress a network of targets associated with STAT3, deregulate cytokine-mediated gene activation, suppress an interferon response, and influence the transition into the lytic phase of viral replication.
Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio
Authors: Li Jia-Min , Li Ling-Yu , Qin Xuan , Ning Li-Jun , Lu Dong-Liang , Li Dong-Liang , Zhang Mei-Ling , Wang Xin , Du Zhen-Yu 
Published: January 2017

AbstractExcess fat accumulation has been observed widely in farmed fish; therefore, efficient lipid-lowering factors have obtained high attention in the current fish nutrition studies. Dietary L-carnitine can increase fatty acid β-oxidation in mammals, but has produced contradictory results in different fish species. To date, the mechanisms of metabolic regulation of L-carnitine in fish have not been fully determined. The present study used zebrafish to investigate the systemic regulation of nutrient metabolism by dietary L-carnitine supplementation. L-carnitine significantly decreased the lipid content in liver and muscle, accompanied by increased concentrations of total and free carnitine in tissues. Meanwhile, L-carnitine enhanced mitochondrial β-oxidation activities and the expression of carnitine palmitoyltransferase 1 mRNA significantly, whereas it depressed the mRNA expression of adipogenesis-related genes. In addition, L-carnitine caused higher glycogen deposition in the fasting state, and increased and decreased the mRNA expressions of gluconeogenesis-related and glycolysis-related genes, respectively. L-carnitine also increased the hepatic expression of mTOR in the feeding state. Taken together, dietary L-carnitine supplementation decreased lipid deposition by increasing mitochondrial fatty acid β-oxidation, and is likely to promote protein synthesis. However, the L-carnitine-enhanced lipid catabolism would cause a decrease in glucose utilization. Therefore, L-carnitine has comprehensive effects on nutrient metabolism in fish.
Temporal Topic Modeling to Assess Associations between News Trends and Infectious Disease Outbreaks
Authors: Ghosh Saurav , Chakraborty Prithwish , Nsoesie Elaine O. , Cohn Emily , Mekaru Sumiko R. , Brownstein John S. , Ramakrishnan Naren 
Published: January 2017

AbstractIn retrospective assessments, internet news reports have been shown to capture early reports of unknown infectious disease transmission prior to official laboratory confirmation. In general, media interest and reporting peaks and wanes during the course of an outbreak. In this study, we quantify the extent to which media interest during infectious disease outbreaks is indicative of trends of reported incidence. We introduce an approach that uses supervised temporal topic models to transform large corpora of news articles into temporal topic trends. The key advantages of this approach include: applicability to a wide range of diseases and ability to capture disease dynamics, including seasonality, abrupt peaks and troughs. We evaluated the method using data from multiple infectious disease outbreaks reported in the United States of America (U.S.), China, and India. We demonstrate that temporal topic trends extracted from disease-related news reports successfully capture the dynamics of multiple outbreaks such as whooping cough in U.S. (2012), dengue outbreaks in India (2013) and China (2014). Our observations also suggest that, when news coverage is uniform, efficient modeling of temporal topic trends using time-series regression techniques can estimate disease case counts with increased precision before official reports by health organizations.
Structure and membrane interactions of the homodimeric antibiotic peptide homotarsinin
Authors: Verly Rodrigo M. , Resende Jarbas M. , Junior Eduardo F. C. , de Magalhães Mariana T. Q. , Guimarães Carlos F. C. R. , Munhoz Victor H. O. , Bemquerer Marcelo Porto , Almeida Fábio C. L. , Santoro Marcelo M. , Piló-Veloso Dorila , Bechinger Burkhard 
Published: January 2017

AbstractAntimicrobial peptides (AMPs) from amphibian skin are valuable template structures to find new treatments against bacterial infections. This work describes for the first time the structure and membrane interactions of a homodimeric AMP. Homotarsinin, which was found in Phyllomedusa tarsius anurans, consists of two identical cystine-linked polypeptide chains each of 24 amino acid residues. The high-resolution structures of the monomeric and dimeric peptides were determined in aqueous buffers. The dimer exhibits a tightly packed coiled coil three-dimensional structure, keeping the hydrophobic residues screened from the aqueous environment. An overall cationic surface of the dimer assures enhanced interactions with negatively charged membranes. An extensive set of biophysical data allowed us to establish structure-function correlations with antimicrobial assays against Gram-positive and Gram-negative bacteria. Although both peptides present considerable antimicrobial activity, the dimer is significantly more effective in both antibacterial and membrane biophysical assays.