bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural modification of P-glycoprotein induced by OH radicals: Insights from atomistic simulations
Authors: Khosravian N. , Kamaraj B. , Neyts E. C. , Bogaerts A. 
Published: February 2016

AbstractThis study reports on the possible effects of OH radical impact on the transmembrane domain 6 of P-glycoprotein, TM6, which plays a crucial role in drug binding in human cells. For the first time, we employ molecular dynamics (MD) simulations based on the self-consistent charge density functional tight binding (SCC-DFTB) method to elucidate the potential sites of fragmentation and mutation in this domain upon impact of OH radicals and to obtain fundamental information about the underlying reaction mechanisms. Furthermore, we apply non-reactive MD simulations to investigate the long-term effect of this mutation, with possible implications for drug binding. Our simulations indicate that the interaction of OH radicals with TM6 might lead to the breaking of C-C and C-N peptide bonds, which eventually cause fragmentation of TM6. Moreover, according to our simulations, the OH radicals can yield mutation in the aromatic ring of phenylalanine in TM6, which in turn affects its structure. As TM6 plays an important role in the binding of a range of cytotoxic drugs with P-glycoprotein, any changes in its structure are likely to affect the response of the tumor cell in chemotherapy. This is crucial for cancer therapies based on reactive oxygen species, such as plasma treatment.
Bio-Source of di-n-butyl phthalate production by filamentous fungi
Authors: Tian Congkui , Ni Jinren , Chang Fang , Liu Sitong , Xu Nan , Sun Weiling , Xie Yuan , Guo Yongzhao , Ma Yanrong , Yang Zhenxing , Dang Chenyuan , Huang Yuefei , Tian Zhexian , Wang Yiping 
Published: February 2016

AbstractAlthough DBP (di-n-butyl phthalate) is commonly encountered as an artificially-synthesized plasticizer with potential to impair fertility, we confirm that it can also be biosynthesized as microbial secondary metabolites from naturally occurring filamentous fungi strains cultured either in an artificial medium or natural water. Using the excreted crude enzyme from the fungi for catalyzing a variety of substrates, we found that the fungal generation of DBP was largely through shikimic acid pathway, which was assembled by phthalic acid with butyl alcohol through esterification. The DBP production ability of the fungi was primarily influenced by fungal spore density and incubation temperature. This study indicates an important alternative natural waterborne source of DBP in addition to artificial synthesis, which implied fungal contribution must be highlighted for future source control and risk management of DBP.
Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats
Authors: Song Shangxin , Hooiveld Guido J. , Li Mengjie , Zhao Fan , Zhang Wei , Xu Xinglian , Muller Michael , Li Chunbao , Zhou Guanghong 
Published: February 2016

AbstractThis study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets.
Continuous quantification of HER2 expression by microfluidic precision immunofluorescence estimates HER2 gene amplification in breast cancer
Authors: Dupouy Diego G. , Ciftlik Ata Tuna , Fiche Maryse , Heintze Déborah , Bisig Bettina , de Leval Laurence , Gijs Martin A. M. 
Published: February 2016

AbstractChromogenic immunohistochemistry (IHC) is omnipresent in cancer diagnosis, but has also been criticized for its technical limit in quantifying the level of protein expression on tissue sections, thus potentially masking clinically relevant data. Shifting from qualitative to quantitative, immunofluorescence (IF) has recently gained attention, yet the question of how precisely IF can quantify antigen expression remains unanswered, regarding in particular its technical limitations and applicability to multiple markers. Here we introduce microfluidic precision IF, which accurately quantifies the target expression level in a continuous scale based on microfluidic IF staining of standard tissue sections and low-complexity automated image analysis. We show that the level of HER2 protein expression, as continuously quantified using microfluidic precision IF in 25 breast cancer cases, including several cases with equivocal IHC result, can predict the number of HER2 gene copies as assessed by fluorescence in situ hybridization (FISH). Finally, we demonstrate that the working principle of this technology is not restricted to HER2 but can be extended to other biomarkers. We anticipate that our method has the potential of providing automated, fast and high-quality quantitative in situ biomarker data using low-cost immunofluorescence assays, as increasingly required in the era of individually tailored cancer therapy.
Dictyocaulus viviparus genome, variome and transcriptome elucidate lungworm biology and support future intervention
Authors: McNulty Samantha N. , Strübe Christina , Rosa Bruce A. , Martin John C. , Tyagi Rahul , Choi Young-Jun , Wang Qi , Hallsworth Pepin Kymberlie , Zhang Xu , Ozersky Philip , Wilson Richard K. , Sternberg Paul W. , Gasser Robin B. , Mitreva Makedonka 
Published: February 2016

AbstractThe bovine lungworm, Dictyocaulus viviparus (order Strongylida), is an important parasite of livestock that causes substantial economic and production losses worldwide. Here we report the draft genome, variome and developmental transcriptome of D. viviparus. The genome (161 Mb) is smaller than those of related bursate nematodes and encodes fewer proteins (14,171 total). In the first genome-wide assessment of genomic variation in any parasitic nematode, we found a high degree of sequence variability in proteins predicted to be involved host-parasite interactions. Next, we used extensive RNA sequence data to track gene transcription across the life cycle of D. viviparus and identified genes that might be important in nematode development and parasitism. Finally, we predicted genes that could be vital in host-parasite interactions, genes that could serve as drug targets and putative RNAi effectors with a view to developing functional genomic tools. This extensive, well-curated dataset should provide a basis for developing new anthelmintics, vaccines and improved diagnostic tests and serve as a platform for future investigations of drug resistance and epidemiology of the bovine lungworm and related nematodes.
Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains
Authors: Nakagawa Akifumi , Adams Curtis E. , Huang Yinshi , Hamarneh Sulaiman R. , Liu Wei , Von Alt Kate N. , Mino-Kenudson Mari , Hodin Richard A. , Lillemoe Keith D. , Fernández-del Castillo Carlos , Warshaw Andrew L. , Liss Andrew S. 
Published: February 2016

AbstractAbsorptive and secretory cells of the small intestine are derived from a single population of Lgr5-expressing stem cells. While key genetic pathways required for differentiation into specific lineages have been defined, epigenetic programs contributing to this process remain poorly characterized. Members of the BET family of chromatin adaptors contain tandem bromodomains that mediate binding to acetylated lysines on target proteins to regulate gene expression. In this study, we demonstrate that mice treated with a small molecule inhibitor of BET bromodomains, CPI203, exhibit greater than 90% decrease in tuft and enteroendocrine cells in both crypts and villi of the small intestine, with no changes observed in goblet or Paneth cells. BET bromodomain inhibition did not alter the abundance of Lgr5-expressing stem cells in crypts, but rather exerted its effects on intermediate progenitors, in part through regulation of Ngn3 expression. When BET bromodomain inhibition was combined with the chemotherapeutic gemcitabine, pervasive apoptosis was observed in intestinal crypts, revealing an important role for BET bromodomain activity in intestinal homeostasis. Pharmacological targeting of BET bromodomains defines a novel pathway required for tuft and enteroendocrine differentiation and provides an important tool to further dissect the progression from stem cell to terminally differentiated secretory cell.
Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts
Authors: Zhao Lei , Shao Qianqian , Zhang Yun , Zhang Lin , He Ying , Wang Lijie , Kong Beihua , Qu Xun 
Published: February 2016

AbstractMaternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal–placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN+CD14+CD1a− phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4+CD25+Foxp3+ Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal–fetal interface.
Selective plasmon-driven catalysis for para-nitroaniline in aqueous environments
Authors: Cui Lin , Wang Peijie , Li Yuanzuo , Sun Mengtao 
Published: February 2016

AbstractThe plasmon-driven oxidation of amine (−NH2) groups and the reduction of nitro (−NO2) groups on a nanostructured metal surface in an aqueous environment have been reported experimentally and theoretically. The question of which process occurs first in the aqueous environment is an interesting question in the field of plasmon-related photochemistry. Para-nitroaniline (PNA), with both nitro (−NO2) and amine (−NH2) groups, is the best candidate for studying the priority of the plasmon-driven oxidation and the reduction reactions in an aqueous environment. Using surface-enhanced Raman scattering (SERS) spectroscopy, our experimental results and theoretical simulations reveal that PNA is selectively catalyzed to 4,4′-diaminoazobenzene (DAAB) through the plasmon-assisted dimerization of the nitro (−NO2) group into an azo group in an aqueous environment. This indicates that the plasmon-driven reduction of the nitro (−NO2) group clearly occurs before the oxidation of the amine (−NH2) group in an aqueous environment. The plasmon-driven reduction of PNA to DAAB is a selective surface catalytic reduced reaction in aqueous environment.
Small-molecule inhibition of PTPRZ reduces tumor growth in a rat model of glioblastoma
Authors: Fujikawa Akihiro , Nagahira Asako , Sugawara Hajime , Ishii Kentaro , Imajo Seiichi , Matsumoto Masahito , Kuboyama Kazuya , Suzuki Ryoko , Tanga Naomi , Noda Masanori , Uchiyama Susumu , Tomoo Toshiyuki , Ogata Atsuto , Masumura Makoto , Noda Masaharu 
Published: February 2016

AbstractProtein tyrosine phosphatase receptor-type Z (PTPRZ) is aberrantly over-expressed in glioblastoma and a causative factor for its malignancy. However, small molecules that selectively inhibit the catalytic activity of PTPRZ have not been discovered. We herein performed an in vitro screening of a chemical library and identified SCB4380 as the first potent inhibitor for PTPRZ. The stoichiometric binding of SCB4380 to the catalytic pocket was demonstrated by biochemical and mass spectrometric analyses. We determined the crystal structure of the catalytic domain of PTPRZ and the structural basis of the binding of SCB4380 elucidated by a molecular docking method was validated by site-directed mutagenesis studies. The intracellular delivery of SCB4380 by liposome carriers inhibited PTPRZ activity in C6 glioblastoma cells and thereby suppressed their migration and proliferation in vitro and tumor growth in a rat allograft model. Therefore, selective inhibition of PTPRZ represents a promising approach for glioma therapy.
The Biosynthesis of Infrared-Emitting Quantum Dots in Allium Fistulosum
Authors: Green M. , Haigh S. J. , Lewis E. A. , Sandiford L. , Burkitt-Gray M. , Fleck R. , Vizcay-Barrena G. , Jensen L. , Mirzai H. , Curry R. J. , Dailey L.-A. 
Published: February 2016

AbstractThe development of simple routes to emissive solid-state materials is of paramount interest and in this report we describe the biosynthesis of infrared emitting quantum dots in a living plant via a mutual antagonistic reaction. Exposure of common Allium fistulosum to mercury and tellurium salts under ambient conditions resulted in the expulsion of crystalline, non-passivated HgTe quantum dots that exhibited emissive characteristics in the near-infrared spectral region, a wavelength range that is important in telecommunications and solar energy conversion.
Lanthanum and Neodymium Doped Barium Ferrite-TiO2/MCNTs/poly(3-methyl thiophene) Composites with Nest Structures: Preparation, Characterization and Electromagnetic Microwave Absorption Properties
Authors: Zhao Jie , Yu Jian , Xie Yu , Le Zhanggao , Hong Xiaowei , Ci Suqin , Chen Junhong , Qing Xiaoyan , Xie Weijie , Wen Zhenhai 
Published: February 2016

AbstractWe report herein the synthesis of a novel nest structured electromagnetic composite through in-situ chemical polymerization of 3-methyl thiophene (3MT) in the presence of the BaFe11.92(LaNd)0.04O19-TiO2 (BFTO) nanoparticles and MCNTs. As an absorbing material, the BFTO/MCNTs/P3MT/wax composites were prepared at various loadings of BFTO/MCNTs/P3MT (0.2:0.10:1.0 ~ 0.2:0.30:1.0) and they exhibited strong microwave absorption properties in the range of 1.0–18 GHz. When the loading of BFTO/MCNTs/P3MT is 0.2:0.30:1.0, the composite has a strongest absorbing peak at 11.04 GHz and achieves a maximum absorbing value of −21.56 dB. The absorbing peak position moves to higher frequencies with the increase of MCNTs content. The mechanism for microwave absorption of these composites has been explained in detail.
Quantitative assessment of radiation force effect at the dielectric air-liquid interface
Authors: Capeloto Otávio Augusto , Zanuto Vitor Santaella , Malacarne Luis Carlos , Baesso Mauro Luciano , Lukasievicz Gustavo Vinicius Bassi , Bialkowski Stephen Edward , Astrath Nelson Guilherme Castelli 
Published: February 2016

AbstractWe induce nanometer-scale surface deformation by exploiting momentum conservation of the interaction between laser light and dielectric liquids. The effect of radiation force at the air-liquid interface is quantitatively assessed for fluids with different density, viscosity and surface tension. The imparted pressure on the liquids by continuous or pulsed laser light excitation is fully described by the Helmholtz electromagnetic force density.
The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells
Authors: Sharma Dileep , Hamlet Stephen Mark , Petcu Eugen Bogdan , Ivanovski Saso 
Published: February 2016

AbstractThe contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).
TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis
Authors: Qin Xing , Yan Ming , Zhang Jianjun , Wang Xu , Shen Zongze , Lv Zhongjing , Li Zhihui , Wei Wenyi , Chen Wantao 
Published: February 2016

AbstractThe matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer-associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-β3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-β3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target.
Gold nanoparticle-assisted all optical localized stimulation and monitoring of Ca2+ signaling in neurons
Authors: Lavoie-Cardinal Flavie , Salesse Charleen , Bergeron Éric , Meunier Michel , De Koninck Paul 
Published: February 2016

AbstractLight-assisted manipulation of cells to control membrane activity or intracellular signaling has become a major avenue in life sciences. However, the ability to perform subcellular light stimulation to investigate localized signaling has been limited. Here, we introduce an all optical method for the stimulation and the monitoring of localized Ca2+ signaling in neurons that takes advantage of plasmonic excitation of gold nanoparticles (AuNPs). We show with confocal microscopy that 800 nm laser pulse application onto a neuron decorated with a few AuNPs triggers a transient increase in free Ca2+, measured optically with GCaMP6s. We show that action potentials, measured electrophysiologically, can be induced with this approach. We demonstrate activation of local Ca2+ transients and Ca2+ signaling via CaMKII in dendritic domains, by illuminating a single or few functionalized AuNPs specifically targeting genetically-modified neurons. This NP-Assisted Localized Optical Stimulation (NALOS) provides a new complement to light-dependent methods for controlling neuronal activity and cell signaling.
Spatial Electron-hole Separation in a One Dimensional Hybrid Organic–Inorganic Lead Iodide
Authors: Savory Christopher N. , Palgrave Robert G. , Bronstein Hugo , Scanlon David O. 
Published: February 2016

AbstractThe increasing efficiency of the inorganic-organic hybrid halides has revolutionised photovoltaic research. Despite this rapid progress, the significant issues of poor stability and toxicity have yet to be suitably overcome. In this article, we use Density Functional Theory to examine (Pb2I6) · (H2DPNDI) · (H2O) · (NMP), an alternative lead-based hybrid inorganic-organic solar absorber based on a photoactive organic cation. Our results demonstrate that optical properties suitable for photovoltaic applications, in addition to spatial electron-hole separation, are possible but efficient charge transport may be a limiting factor.
Sorting nexin 10 acting as a novel regulator of macrophage polarization mediates inflammatory response in experimental mouse colitis
Authors: You Yan , Zhou Chun , Li Dong , Cao Zhong-Lian , Shen Weixing , Li Wan-Zhen , Zhang Sulin , Hu Bin , Shen Xiaoyan 
Published: February 2016

AbstractIn response to changes in microenvironment, macrophages polarize into functionally distinct phenotypes, playing a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the effects of sorting nexin 10 (SNX10), a protein involved in endosomal trafficking and osteoclast maturation, on regulation of macrophage polarization and progression of mouse colitis. Our results revealed that SNX10 deficiency increased the population of M2-type monocytes/macrophages and protected against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). By in vitro study, we showed that deficiency of SNX10 polarized macrophages derived from mouse bone marrow or human peripheral blood mononuclear cells (PBMCs) towards an anti-inflammatory M2 phenotype, which partially reversed by SNX10 plasmid transfection. Adoptive transfer of SNX10−/− macrophages ameliorated colitis in WT mice. However, transfer of WT macrophages exacerbated colitis in SNX10−/− mice. Our data disclose a crucial role and novel function for SNX10 in macrophage polarization. Loss of SNX10 function may be a potential promising therapeutic strategy for IBD.