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Christine Gross, Veit Wiesmann, Sebastian Millen, Martina Kalmer, Thomas Wittenberg, Jan Gettemans, Andrea K Thoma-Kress
The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells...
October 2016: PLoS Pathogens
Mingyi Qu, Fang Fang, Xiaojing Zou, Quan Zeng, Zeng Fan, Lin Chen, Wen Yue, Xiaoyan Xie, Xuetao Pei
A better understanding of the mechanisms involved in megakaryocyte maturation will facilitate the generation of platelets in vitro and their clinical applications. A microRNA, miR-125b, has been suggested to have important roles in the self-renewal of megakaryocyte-erythroid progenitors and in platelet generation. However, miR-125b is also critical for hematopoietic stem cell self-renewal. Thus, the function of miR-125b and the complex signaling pathways regulating megakaryopoiesis remain to be elucidated. In this study, an attentive examination of the endogenous expression of miR-125b during megakaryocyte differentiation was performed...
October 20, 2016: Cell Death & Disease
Aysegül Kaymak, Holger Richly
In the present study we addressed the function of the transcriptional activator Zrf1 in the generation of the three germ layers during in vitro development. Currently, Zrf1 is rather regarded as a factor that drives the expression of neuronal genes. Here, we have employed mouse embryonic stem cells and P19 cells to understand the role of Zrf1 in the generation of mesoderm-derived tissues like adipocytes, cartilage and heart. Our data shows that Zrf1 is essential for the transcriptional activation of genes that give rise to mesoderm and in particular heart development...
October 18, 2016: Cell Cycle
Arif U Hasan, Koji Ohmori, Takeshi Hashimoto, Kazuyo Kamitori, Fuminori Yamaguchi, Kumi Konishi, Takahisa Noma, Junsuke Igarashi, Tetsuo Yamashita, Katsuya Hirano, Masaaki Tokuda, Tetsuo Minamino, Akira Nishiyama, Masakazu Kohno
Deterioration of adipocyte function due to increased oxidative stress predisposes patients to metabolic disorders in advanced age. However, the roles of tumor suppressors in such conditions remain largely unknown. Therefore, we aimed to address their dynamics in aged adipocytes using a long-term culture model. We compared 3T3-L1 adipocytes at 17-19 days (long-term) with those at 8-10 days (short-term) after initiation of adipogenic induction for mimicking 'aged' and 'young' adipocytes, respectively. H2O2 release and dihydroethidium (DHE) staining was increased, while superoxide dismutase (SOD) activity was reduced in long-term cultured adipocytes, which is suggestive of enhanced oxidative stress in this group...
October 12, 2016: Biogerontology
Alessandra Rossi, Karin J Ferrari, Andrea Piunti, SriGanesh Jammula, Fulvio Chiacchiera, Luca Mazzarella, Andrea Scelfo, Pier Giuseppe Pelicci, Diego Pasini
Leukemia is a complex heterogeneous disease often driven by the expression of oncogenic fusion proteins with different molecular and biochemical properties. Whereas several fusion proteins induce leukemogenesis by activating Hox gene expression (Hox-activating fusions), others impinge on different pathways that do not involve the activation of Hox genes (non-Hox-activating fusions). It has been postulated that one of the main oncogenic properties of the HOXA9 transcription factor is its ability to control the expression of the p16/p19 tumor suppressor locus (Cdkn2a), thereby compensating Polycomb-mediated repression, which is dispensable for leukemias induced by Hox-activating fusions...
October 2016: Science Advances
Michael Devos, Barbara Gilbert, Geertrui Denecker, Kirsten Leurs, Conor Mc Guire, Kelly Lemeire, Tino Hochepied, Marnik Vuylsteke, Jo Lambert, Caroline Van Den Broecke, Louis Libbrecht, Jody Haigh, Geert Berx, Saskia Lippens, Peter Vandenabeele, Wim Declercq
Unlike its family member p53, the p63 gene is rarely mutated in human cancer. However, ΔNp63α protein levels are often elevated in tumors of epithelial origin, such as squamous cell carcinoma and cholangiocarcinoma. In order to study the oncogenic properties of ΔNp63α in vivo, we generated transgenic mice overexpressing ΔNp63α from the Rosa26 locus promoter controlled by K5Cre. We found that these mice spontaneously develop epidermal cysts and ectopic ΔNp63α expression in the bile duct epithelium that leads to dilatation of the intrahepatic biliary ducts, to hepatic cyst formation and bile duct adenoma...
October 7, 2016: Journal of Investigative Dermatology
Wenwen Tu, Huijuan Cao, Long Zhang, Jianchun Bao, Xuhui Liu, Zhihui Dai
Using Au nanoparticles (NPs) decorated water-soluble ZnSe-COOH nanoflakes (NFs), an ultrasensitive photoelectrochemical (PEC) biosensing strategy based on the dual signal amplification was proposed. As a result of the localized surface plasmon resonance (SPR) of Au NPs, the ultraviolet-visible absorption spectrum of Au NPs overlapped with emission spectra of ZnSe-COOH NFs, which generated efficient resonant energy transfer (RET) between ZnSe-COOH NFs and Au NPs. The RET improved photoelectric conversion efficiency of ZnSe-COOH NFs and significantly amplified PEC signal...
October 10, 2016: Analytical Chemistry
Mohamed Salah I Abaza, Mohammad Afzal, Raja'a J Al-Attiyah, Radhika Guleri
BACKGROUND: Natural products are valuable sources for anticancer agents. In the present study, methylferulate (MF) was identified for the first time from Tamarix aucheriana. Spectral data were used for identification of MF. The potential of MF to control cell growth, cell cycle, apoptosis, generation of reactive oxygen species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding activity and proteasomal activities, as well as the enhancement of chemosensitivity in human colorectal cancer cells, were evaluated...
October 1, 2016: BMC Complementary and Alternative Medicine
Levente Kontra, Tibor Csorba, Mario Tavazza, Alessandra Lucioli, Raffaela Tavazza, Simon Moxon, Viktória Tisza, Anna Medzihradszky, Massimo Turina, József Burgyán
RNA silencing is one of the main defense mechanisms employed by plants to fight viruses. In change, viruses have evolved silencing suppressor proteins to neutralize antiviral silencing. Since the endogenous and antiviral functions of RNA silencing pathway rely on common components, it was suggested that viral suppressors interfere with endogenous silencing pathway contributing to viral symptom development. In this work, we aimed to understand the effects of the tombusviral p19 suppressor on endogenous and antiviral silencing during genuine virus infection...
October 2016: PLoS Pathogens
Michihiro Hashimoto, Azusa Asai, Hiroyuki Kawagishi, Ryuta Mikawa, Yuji Iwashita, Kazuki Kanayama, Kazushi Sugimoto, Tadashi Sato, Mitsuo Maruyama, Masataka Sugimoto
Senescent cells accumulate in many tissues as animals age and are considered to underlie several aging-associated pathologies. The tumor suppressors p19(ARF) and p16(INK4a), both of which are encoded in the CDKN2A locus, play critical roles in inducing and maintaining permanent cell cycle arrest during cellular senescence. Although the elimination of p16(INK4a)-expressing cells extends the life span of the mouse, it is unclear whether tissue function is restored by the elimination of senescent cells in aged animals and whether and how p19(ARF) contributes to tissue aging...
August 4, 2016: JCI Insight
Yanling Chen, David H Reese
Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo...
2016: PloS One
Beom Seok Kim, Chang-Hee Lee, Gyeong-Eon Chang, Eunji Cheong, Injae Shin
Sirtuin 1 (SIRT1) is known to suppress differentiation of pluripotent/multipotent cells and neural progenitor cells into neurons by blocking activation of transcription factors critical for neurogenesis. EX-527 is a highly selective and potent inhibitor against SIRT1 and has been used as a chemical probe that modulates SIRT1-associated biological processes. However, the effect of EX-527 on neuronal differentiation in pluripotent cells has not been well elucidated. Here, we report an examination of EX-527 effects on neurogenesis of pluripotent P19 cells...
September 29, 2016: Scientific Reports
Stephanie Azzopardi, Sharon Pang, David S Klimstra, Yi-Chieh Nancy Du
In human studies and mouse models, the contributions of p53 and p16(Ink4a)/p19(Arf) loss are well established in pancreatic ductal adenocarcinoma (PDAC). Although loss of functional p53 pathway and loss of Ink4a/Arf in human pancreatic acinar cell carcinoma (PACC) and pancreatic neuroendocrine tumor (PanNET) are identified, their direct roles in tumorigenesis of PACC and PanNET remain to be determined. Using transgenic mouse models expressing the viral oncogene polyoma middle T antigen (PyMT), we demonstrate that p53 loss in pancreatic Pdx1+ progenitor cells results in aggressive PACC, whereas Ink4a/Arf loss results in PanNETs...
October 2016: Neoplasia: An International Journal for Oncology Research
Lisa A Lesniewski, Douglas R Seals, Ashley E Walker, Grant D Henson, Mark W Blimline, Daniel W Trott, Gary C Bosshardt, Thomas J LaRocca, Brooke R Lawson, Melanie C Zigler, Anthony J Donato
Inhibition of mammalian target of rapamycin, mTOR, extends lifespan and reduces age-related disease. It is not known what role mTOR plays in the arterial aging phenotype or if mTOR inhibition by dietary rapamycin ameliorates age-related arterial dysfunction. To explore this, young (3.8 ± 0.6 months) and old (30.3 ± 0.2 months) male B6D2F1 mice were fed a rapamycin supplemented or control diet for 6-8 weeks. Although there were few other notable changes in animal characteristics after rapamycin treatment, we found that glucose tolerance improved in old mice, but was impaired in young mice, after rapamycin supplementation (both P < 0...
September 22, 2016: Aging Cell
Aidong Wang, Ming Cui, Hong Qu, Jiabo Di, Zaozao Wang, Jiadi Xing, Fan Wu, Wei Wu, Xicheng Wang, Lin Shen, Beihai Jiang, Xiangqian Su
The epidermal growth factor receptor (EGFR) is overexpressed in several epithelial tumors. Anti-EGFR humanized monoclonal antibodies, cetuximab and panitumumab, in combination with chemotherapy have improved the prognosis for patients with wild-type RAS tumors. To identify mimotopes of EGFR and develop mimotope-based EGFR vaccines, we screened a phage display peptide library with panitumumab. Two EGFR mimotopes P19 and P26, which could be recognized by panitumumab specifically, were isolated. To enhance the immune responses, we generated recombinant proteins of P19 or P26 fused to a heat-shock cognate protein 70 (Hsc70), and evaluated the efficacy of Hsc70-P19 and Hsc70-P26 as vaccines in vivo...
September 21, 2016: Oncotarget
Nansong Xia, Juan Cai, Feifei Wang, Baijun Dong, Song Liu, Fengling Chen, Jinke Cheng, Yong Zuo
Cell senescence can limit proliferative potential and prevent tumorigenesis. Bmi1 is a key regulator in cell senescence by suppressing the Ink4a/Arf locus. However, how to regulate Bmi1 activity in cell senescence is largely unknown. Here, we show that SENP1 plays an important role in cell senescence by regulating Bmi1 SUMOylation. Senp1(-/-) primary MEF cells show resistance to cell senescence induced by passaging or other senescence inducing signals. SENP1 deficiency also reduces oncogene H-Ras(V12)-induced senescence, and enhances H-Ras(V12)-induced cell transformation...
2016: Scientific Reports
Yingjiao Xu, Wenjie Pang, Jishun Lu, Aidong Shan, Yan Zhang
Mucin-type O-glycosylation is initiated by an evolutionarily conserved family of polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts). Previously, it was reported that ppGalNAc-T13 is restrictively expressed at a high level in brain. Here, we provide evidence for the critical role of ppGalNAc-T13 in neural differentiation. In detail, we show that the expression of ppGalNAc-T13 was dramatically up-regulated during early neurogenesis in mouse embryonic brains. Similar changes were also observed in the cell models of neuronal differentiation by using either the primary mouse cortical neural precursor cells or murine embryonal carcinoma P19 cells...
September 14, 2016: Journal of Biological Chemistry
Chia-Yuan Chang, Yi-Wen Chen, Tsu-Wei Wang, Wen-Sung Lai
Accumulating evidence implies that both AKT1 and GABAA receptor (GABAAR) subunit genes are involved in schizophrenia pathogenesis. Activated Akt promotes GABAergic neuron differentiation and increases GABAAR expression on the plasma membrane. To elucidate the role of Akt1 in modulating GABAergic functions and schizophrenia-related cognitive deficits, a set of 6 in vitro and in vivo experiments was conducted. First, an Akt1/2 inhibitor was applied to evaluate its effect on GABAergic neuron-like cell formation from P19 cells...
2016: Scientific Reports
Mateus R Amorim, Leni G H Bonagamba, George M P R Souza, Davi J A Moraes, Benedito H Machado
Sino-aortic denervated (SAD) rats present mean arterial pressure (MAP) similar to control rats. Since respiration modulates MAP, we hypothesized that conscious SAD rats present respiratory changes associated with the normal MAP. In this study we evaluated the cardiovascular and respiratory activities and arterial blood gases in control and SAD rats. Male juvenile Wistar rats (P19-P21) were submitted to SAD, sham surgery, or selective carotid bodies removal (CBX) and the three groups were evaluated 10 days after the surgery (SAD, n = 21, Sham, n = 18, CBX, n = 13)...
September 12, 2016: Experimental Physiology
Kazuo Kamemura, Hiromi Abe
Although Ewing sarcoma protein (EWS) is known to be glycosylated by O-linked β-N-acetylglucosamine (O-GlcNAc), the dynamics and stoichiometry of its glycosylation remain obscure. Here, we report a dynamic change in the glycosylation stoichiometry of EWS species during neuronal differentiation of embryonic carcinoma P19 cells. Our findings suggest that O-GlcNAc glycosylation participates in the regulation of EWS functions in neuronal cells.
September 8, 2016: Bioscience, Biotechnology, and Biochemistry
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