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Human protein 4

Francesca Megiorni, Simona Camero, Simona Ceccarelli, Heather P McDowell, Olga Mannarino, Francesco Marampon, Barry Pizer, Rajeev Shukla, Antonio Pizzuti, Cinzia Marchese, Anna Clerico, Carlo Dominici
Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27...
October 15, 2016: Oncotarget
Daniela D'Arcangelo, Francesco Facchiano, Giovanni Nassa, Andrea Stancato, Annalisa Antonini, Stefania Rossi, Cinzia Senatore, Martina Cordella, Claudio Tabolacci, Annamaria Salvati, Roberta Tarallo, Alessandro Weisz, Angelo M Facchiano, Antonio Facchiano
Melanoma is the most aggressive skin-cancer, showing high mortality at advanced stages. Platelet Derived Growth Factor Receptor-alpha (PDGFR-alpha) potently inhibits melanoma- and endothelium-proliferation and its expression is significantly reduced in melanoma-biopsies, suggesting that melanoma progression eliminates cells expressing PDGFR-alpha. In the present study transient overexpression of PDGFR-alpha in endothelial (HUVEC) and melanoma (SKMel-28, A375, Preyer) human-cells shows strong anti-proliferative effects, with profound transcriptome and miRNome deregulation...
October 13, 2016: Oncotarget
Toshiaki Okada, Md Rafiqul Islam, Nargiza A Tsiferova, Yasunobu Okada, Ravshan Z Sabirov
The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of four other types of anion channel activated by acid, Ca(2+), patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells...
October 20, 2016: Channels
Ke Ren, Wei Zhang, Xiaoqing Chen, Yingyu Ma, Yue Dai, Yimei Fan, Yayi Hou, Ren Xiang Tan, Erguang Li
The human HSV-1 and -2 are common pathogens of human diseases. Both host and viral factors are involved in HSV lytic infection, although detailed mechanisms remain elusive. By screening a chemical library of epigenetic regulation, we identified bromodomain-containing protein 4 (BRD4) as a critical player in HSV infection. We show that treatment with pan BD domain inhibitor enhanced both HSV infection. Using JQ1 as a probe, we found that JQ1, a defined BD1 inhibitor, acts through BRD4 protein since knockdown of BRD4 expression ablated JQ1 effect on HSV infection...
October 2016: PLoS Pathogens
Jessica A Flynn, Eberhard Durr, Ryan Swoyer, Pedro J Cejas, Melanie S Horton, Jennifer D Galli, Scott A Cosmi, Amy S Espeseth, Andrew J Bett, Lan Zhang
Infection with Respiratory Syncytial Virus (RSV) causes both upper and lower respiratory tract disease in humans, leading to significant morbidity and mortality in both young children and older adults. Currently, there is no licensed vaccine available, and therapeutic options are limited. During the infection process, the type I viral fusion (F) glycoprotein on the surface of the RSV particle rearranges from a metastable prefusion conformation to a highly stable postfusion form. In people naturally infected with RSV, most potent neutralizing antibodies are directed to the prefusion form of the F protein...
2016: PloS One
Fujiko Mitsumoto-Kaseida, Masayuki Murata, Kazuya Ura, Koji Takayama, Satoshi Hiramine, Motohiro Shimizu, Kazuhiro Toyoda, Eiichi Ogawa, Norihiro Furusyo
CD64 is an Fc-gamma-receptor type 1. The expression level of neutrophil CD64 (nCD64) is a known bacterial infection marker, and it also increases in viral infections. We examined the absolute nCD64 before and after the initiation of antiretroviral therapy (ART) to determine its role as an infection and inflammation marker of human immunodeficiency virus (HIV) infection. In this prospective observational study, ninety-four HIV infected patients were enrolled and classified into ART (n=62), ART naive (n=24), and acute/early phase groups (n=8)...
October 20, 2016: AIDS Research and Human Retroviruses
Éva Sivadó, Sabrina Lareure, Valérie Attuil-Audenis, Saïd El Alaoui, Vincent Thomas
Tissue transglutaminase (tTG) belongs to the multigene transglutaminase family of Ca(2+)-dependent protein cross-linking enzymes. There is a strong evidence that tTG is involved in pathology, such as neurodegenerative diseases, cancer, and celiac disease. To study physiopathological implication of tTG, a sandwich immunoassay has been developed with a new monoclonal antibody for the capture and polyclonal antibody both generated in house. Using this ready to use assay, the tTG protein level can be measured in human tissue homogenates and cells extracts easily in about 4 h...
October 19, 2016: Amino Acids
Riccardo Bientinesi, Cesare Mancuso, Maria Martire, Pier Francesco Bassi, Emilio Sacco, Diego Currò
Voltage-gated type 7 K(+) (KV7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of KV7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of KV7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective KV7 channel blocker, concentration-dependently contracted the human detrusor; mean EC50 and Emax of XE-991-induced concentration-response curve were 14...
October 19, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Tara M Newcomb, Kevin M Flanigan
The cloning of the DMD gene, and the identifications of mutations in it as the cause of Duchenne muscular dystrophy (DMD), makes a compelling story that is aptly told elsewhere.(1) The locus-the largest in the human genome-consists of 79 exons, distributed over 2.5 million nucleotides on the X chromosome, which are assembled into a complementary DNA (cDNA) of around 14 kb encoding the predominant muscle isoform of the dystrophin protein.(2) The size of the gene, and the number of exons, had historically made mutation analysis challenging...
October 2016: Neurology. Genetics
Ying Yang, Min Chen, Zongwei Li, Abdullah M S Al-Hatmi, Sybren de Hoog, Weihua Pan, Qiang Ye, Xiaochen Bo, Zhen Li, Shengqi Wang, Junzhi Wang, Huipeng Chen, Wanqing Liao
Penicillium capsulatum is a rare Penicillium species used in paper manufacturing, but recently it has been reported to cause invasive infection. To research the pathogenicity of the clinical Penicillium strain, we sequenced the genomes and transcriptomes of the clinical and environmental strains of P. capsulatum. Comparative analyses of these two P. capsulatum strains and close related strains belonging to Eurotiales were performed. The assembled genome sizes of P. capsulatum are approximately 34.4 Mbp in length and encode 11,080 predicted genes...
2016: Frontiers in Microbiology
Awa Diop, Saber Khelaifia, Nicholas Armstrong, Noémie Labas, Pierre-Edouard Fournier, Didier Raoult, Matthieu Million
BACKGROUND: Microbial culturomics represents an ongoing revolution in the characterization of environmental and human microbiome. METHODS: By using three media containing high salt concentration (100, 150, and 200 g/L), the halophilic microbial culturome of a commercial table salt was determined. RESULTS: Eighteen species belonging to the Terrabacteria group were isolated including eight moderate halophilic and 10 halotolerant bacteria. Gracilibacillus massiliensis sp...
2016: Microbial Ecology in Health and Disease
J L Dentis, N B Schreiber, A M Burress, L J Spicer
Angiogenin is a member of the ribonuclease A superfamily of proteins that has been implicated in stimulating angiogenesis but whether angiogenin can directly affect ovarian granulosa or theca cell function is unknown. Therefore, the objective of these studies was to determine the effect of angiogenin on proliferation and steroidogenesis of bovine granulosa and theca cells. In experiments 1 and 2, granulosa cells from small (1 to 5 mm diameter) follicles and theca cells from large (8 to 22 mm diameter) follicles were cultured to evaluate the dose-response effect of recombinant human angiogenin on steroidogenesis...
October 20, 2016: Animal: An International Journal of Animal Bioscience
Nathan J Hare, Ling Y Lee, Ian Loke, Warwick J Britton, Bernadette M Saunders, Morten Thaysen-Andersen
Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of front-line alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M...
October 19, 2016: Journal of Proteome Research
K R Vogel, G R Ainslie, E E W Jansen, G S Salomons, K M Gibson
Aldehyde dehydrogenase 5a1-deficient (aldh5a1(-/-)) mice, the murine orthologue of human succinic semialdehyde dehydrogenase deficiency (SSADHD), manifest increased GABA (4-aminobutyric acid) that disrupts autophagy, increases mitochondria number, and induces oxidative stress, all mitigated with the mTOR (mechanistic target of rapamycin) inhibitor rapamycin [1]. Because GABA regulates mTOR, we tested the hypothesis that aldh5a1(-/-) mice would show altered levels of mRNA for genes associated with mTOR signaling and oxidative stress that could be mitigated by inhibiting mTOR...
October 16, 2016: Biochimica et Biophysica Acta
Yong-Chao Ma, Zhi-Xin Wang, Shao-Ju Jin, Yan-Xin Zhang, Guo-Qiang Hu, Dong-Tao Cui, Jiang-Shuan Wang, Min Wang, Fu-Qing Wang, Zhi-Jun Zhao
Both tyrosine kinase and topoisomerase II (TopII) are important anticancer targets, and their respective inhibitors are widely used in cancer therapy. However, some combinations of anticancer drugs could exhibit mutually antagonistic actions and drug resistance, which further limit their therapeutic efficacy. Here, we report that HMNE3, a novel bis-fluoroquinolone chalcone-like derivative that targets both tyrosine kinase and TopII, induces tumor cell proliferation and growth inhibition. The viabilities of 6 different cancer cell lines treated with a range of HMNE3 doses were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay...
2016: PloS One
Hanseol Kim, Jihye Ryu, Chaeyoung Lee
A genome-wide association study was conducted to identify expression quantitative trait loci (eQTL) for human telomerase.We tested the genetic associations of nucleotide variants with expression of the genes encoding human telomerase reverse transcriptase (hTERT) and telomerase RNA components (TERC) in lymphoblastoid cell lines derived from 373 Europeans.Our results revealed 6 eQTLs associated with hTERT (P < 5 × 10). One eQTL (rs17755753) was located in the intron 1 of the gene encoding R-spondin-3 (RSPO3), a well-known Wnt signaling regulator...
October 2016: Medicine (Baltimore)
Mitsutoshi Asakura, Fumika Karaki, Hideaki Fujii, Koichiro Atsuda, Tomoo Itoh, Ryoichi Fujiwara
Vildagliptin is a potent, orally active inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus. It has been reported that vildagliptin can cause hepatic dysfunction in patients. However, the molecular-mechanism of vildagliptin-induced liver dysfunction has not been elucidated. In this study, we employed an expression microarray to determine hepatic genes that were highly regulated by vildagliptin in mice. We found that pro-inflammatory S100 calcium-binding protein (S100) a8 and S100a9 were induced more than 5-fold by vildagliptin in the mouse liver...
October 19, 2016: Scientific Reports
Katrin Lorenz, Sabine Beck, Munir M Keilani, Joanna Wasielica-Poslednik, Norbert Pfeiffer, Franz H Grus
BACKGROUND: The aim of our current investigation was to analyze the autoantibody -reactivities of patients after acute angle closure glaucoma (AACG) by means of a protein microarray approach to identify intraocular pressure (IOP)-dependent antibodies. METHODS: Collected sera from different study time points (AACG n = 6, 0, 2, 4 and 12 weeks) and control group (CTRL n = 11, 0 and 12 weeks) were analyzed. Protein-microarrays were incubated with sera and occurring immunoreactivities were visualized with fluorescence labeled anti-human-IgG antibodies...
October 18, 2016: Clinical & Experimental Ophthalmology
Tao Song, Hui Xu, Congchong Wei, Tengfei Jiang, Shishang Qin, Weijia Zhang, Yu Cao, Chao Hu, Fan Zhang, Dairong Qiao, Yi Cao
Seaweed is receiving an increasing amount of attention as a "sea vegetable". The microbiota of coastal populations may acquire seaweed associated enzymes through marine food. Several agarases have been found in non-marine environments; however, their origin is unknown. In this study, a hypothetical protein, Aga1, was identified as an agarase from an inland soil agar-degrading bacterium, Paenibacillus sp. SSG-1.Having low similarity to known glycoside hydrolases, Aga1 may be a distant member of the glycoside hydrolase family 86...
October 19, 2016: Scientific Reports
Xuhao Zhang, Shan Zhu, Tete Li, Yong-Jun Liu, Wei Chen, Jingtao Chen
Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the body's anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered "immune privileged" and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma...
October 16, 2016: Oncotarget
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