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Robert Ringseis, Wilhelm Windisch, Klaus Eder
In the present study, transcript profiling was carried out in liver biopsies from high-yielding dairy cows at week 5 of lactation in order to identify genes and pathways regulated by feeding rumen-protected conjugated linoleic acid (CLA) during the transition period. Analysis of a bovine whole genome microarray revealed a total number of 130 annotated differentially expressed genes (DEGs) in the liver between cows of the CLA group and the control group (filter: P < 0.05 and fold change (FC) ≥ 1.3 or ≤- 1...
December 2016: Genomics Data
Yanfen Fang, Yannan Kong, Jianbei Xi, Mengli Zhu, Tong Zhu, Tongtong Jiang, Wenhao Hu, Mingliang Ma, Xiongwen Zhang
NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affinity by docking simulations study. MBM-5 potently inhibited NEK2 kinase activity in vitro in a concentration-dependent manner. MBM-5 also suppressed cellular NEK2 kinase activity, as evidenced by the decreased phosphorylation of its substrate Hec1 on S165 in a concentration- and time-dependent manner...
October 15, 2016: Oncotarget
Britta Unruhe-Knauf, Shirley K Knauer
The chromosomal passenger complex (CPC) is a key regulator of cell division. Its proper localization during the different phases of mitosis and cytokinesis is crucial for the exertion of its various functions. HDACi treatment has been demonstrated to disturb the centromeric localization of the CPC in tumor cells, thus leading to severe mitotic defects often followed by apoptosis. In this chapter, we describe how HDACi-induced changes of the CPC localization can be analyzed by indirect immunofluorescence using CPC-specific primary and fluorophore-coupled secondary antibodies followed by confocal microscopy...
2017: Methods in Molecular Biology
Kriti Sethi, Saravanan Palani, Juan C G Cortés, Mamiko Sato, Mayalagu Sevugan, Mariona Ramos, Shruthi Vijaykumar, Masako Osumi, Naweed I Naqvi, Juan Carlos Ribas, Mohan Balasubramanian
Cytokinesis in many organisms requires a plasma membrane anchored actomyosin ring, whose contraction facilitates cell division. In yeast and fungi, actomyosin ring constriction is also coordinated with division septum assembly. How the actomyosin ring interacts with the plasma membrane and the plasma membrane-localized septum synthesizing machinery remains poorly understood. In Schizosaccharomyces pombe, an attractive model organism to study cytokinesis, the β-1,3-glucan synthase Cps1p / Bgs1p, an integral membrane protein, localizes to the plasma membrane overlying the actomyosin ring and is required for primary septum synthesis...
October 2016: PLoS Genetics
M Wu, M Hamaker, L Li, D Small, A S Duffield
The FMS-like tyrosine kinase-3 (FLT3) gene is the most commonly mutated gene in acute myeloid leukemia (AML), and patients carrying internal tandem duplication (ITD) mutations have a poor prognosis. Long-term inhibition of FLT3 activity in these patients has been elusive. To provide a more complete understanding of FLT3 biology, a mass spectroscopy-based screen was performed to search for FLT3-interacting proteins. The screen identified dedicator of cytokinesis 2 (DOCK2), which is a guanine nucleotide exchange factor for Rho GTPases, and its expression is limited to hematolymphoid cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Anita Roy, Larissa Lordier, Stefania Mazzi, Yunhua Chang, Valérie Lapierre, Jérome Larghero, Najet Debili, Hana Raslova, William Vainchenker
Megakaryocyte polyploidy is characterized by cytokinesis failure due to defects in contractile forces at the cleavage furrow. Although immature megakaryocytes express two nonmuscle myosin II isoforms (NMIIA and NMIIB); only NMIIB localizes at the cleavage furrow and its subsequent absence contributes to polyploidy. In this study, we tried to understand why the abundant NMIIA does not localize at the furrow by focusing on RhoA/ROCK pathway that has a low activity in polyploid megakaryocytes. We observed that under low RhoA activity, NMII isoforms presented different activity that determined their localization...
October 13, 2016: Blood
Junqi Huang, Ting Gang Chew, Ying Gu, Saravanan Palani, Anton Kamnev, Douglas S Martin, Nicholas J Carter, Robert Anthony Cross, Snezhana Oliferenko, Mohan K Balasubramanian
Many eukaryotes assemble a ring-shaped actomyosin network that contracts to drive cytokinesis. Unlike actomyosin in sarcomeres, which cycles through contraction and relaxation, the cytokinetic ring disassembles during contraction through an unknown mechanism. Here we find in Schizosaccharomyces japonicus and Schizosaccharomyces pombe that, during actomyosin ring contraction, actin filaments associated with actomyosin rings are expelled as micron-scale bundles containing multiple actomyosin ring proteins. Using functional isolated actomyosin rings we show that expulsion of actin bundles does not require continuous presence of cytoplasm...
October 13, 2016: ELife
Mai Takagi, Takuya Sakamoto, Ritsuko Suzuki, Keiichirou Nemoto, Takeshi Obayashi, Takeshi Hirakawa, Tomoko M Matsunaga, Daisuke Kurihara, Yuko Nariai, Takeshi Urano, Tatsuya Sawasaki, Sachihiro Matsunaga
Aurora kinase (AUR) is a well-known mitotic serine/threonine kinase that regulates centromere formation, chromosome segregation, and cytokinesis in eukaryotes. In addition to regulating mitotic events, AUR has been shown to regulate protein dynamics during interphase in animal cells. In contrast, there has been no identification and characterization of substrates and/or interacting proteins during interphase in plants. The Arabidopsis thaliana genome encodes three AUR paralogues, AtAUR1, AtAUR2, and AtAUR3...
October 12, 2016: Journal of Plant Research
Mauricio Toro-Nahuelpan, Frank D Müller, Stefan Klumpp, Jürgen M Plitzko, Marc Bramkamp, Dirk Schüler
BACKGROUND: The navigation of magnetotactic bacteria relies on specific intracellular organelles, the magnetosomes, which are membrane-enclosed crystals of magnetite aligned into a linear chain. The magnetosome chain acts as a cellular compass, aligning the cells in the geomagnetic field in order to search for suitable environmental conditions in chemically stratified water columns and sediments. During cytokinesis, magnetosome chains have to be properly positioned, cleaved and separated in order to be evenly passed into daughter cells...
October 12, 2016: BMC Biology
M Moazzem Hossain, Guangyi Zhao, Moon-Sook Woo, James H-C Wang, Jian-Ping Jin
Cell traction force (CTF) plays a critical role in controlling cell shape, enabling cell motility, and maintaining cellular homeostasis in many biological processes such as angiogenesis, development, wound healing, and cancer metastasis. Calponin is an actin filament-associated cytoskeletal protein in smooth muscles and multiple types of non-muscle cells. An established biochemical function of calponin is the inhibition of myosin ATPase in smooth muscle cells. Vertebrates have three calponin isoforms. Among them, calponin 2 is expressed in epithelial cells, endothelial cells, macrophages, myoblasts and fibroblasts, and plays a role in regulating cytoskeleton activities such as cell adhesion, migration and cytokinesis...
October 13, 2016: Biochemistry
Karin Blomqvist, Christen DiPetrillo, Vincent A Streva, Stewart Pine, Jeffrey D Dvorin
Emerging resistance to current anti-malarials necessitates a more detailed understanding of the biological processes of Plasmodium falciparum proliferation, thus allowing identification of new drug targets. The well-conserved protein Receptor for Activated C-Kinase 1 (RACK1) was originally identified in mammalian cells as an anchoring protein for protein kinase C (PKC) and has since been shown to be important for cell migration, cytokinesis, transcription, epigenetics, and protein translation. The P. falciparum ortholog, PfRACK1, is expressed in blood stages of the parasite and is diffusely localized in the parasite cytoplasm...
October 11, 2016: Molecular and Biochemical Parasitology
Anne-Cecile Reymann, Fabio Staniscia, Anna Erzberger, Guillaume Salbreux, Stephan W Grill
Cytokinesis in eukaryotic cells is often accompanied by actomyosin cortical flow. Over 30 years ago, Borisy and White proposed that cortical flow converging upon the cell equator compresses the actomyosin network to mechanically align actin filaments. However, actin filaments also align via search-and-capture, and to what extent compression by flow or active alignment drive furrow formation remains unclear. Here we quantify the dynamical organization of actin filaments at the onset of ring assembly in the C...
October 10, 2016: ELife
Johannes Schöneberg, Il-Hyung Lee, Janet H Iwasa, James H Hurley
The narrow membrane necks formed during viral, exosomal and intra-endosomal budding from membranes, as well as during cytokinesis and related processes, have interiors that are contiguous with the cytosol. Severing these necks involves action from the opposite face of the membrane as occurs during the well-characterized formation of coated vesicles. This 'reverse' (or 'inverse')-topology membrane scission is carried out by the endosomal sorting complex required for transport (ESCRT) proteins, which form filaments, flat spirals, tubes and conical funnels that are thought to direct membrane remodelling and scission...
October 5, 2016: Nature Reviews. Molecular Cell Biology
Ching Man Chan, Jacqueline T M Aw, Sarah E Webb, Andrew L Miller
In zebrafish embryos, distinct Ca2+ transients are localized to the early cleavage furrows during the first few cell division cycles. These transients are generated mainly by release via IP3Rs in the endoplasmic reticulum, and they are necessary for furrow positioning, propagation, deepening and apposition. We previously showed, via the use of inhibitors, that store-operated Ca2+ entry (SOCE) also appears to be essential for maintaining the IP3R-mediated elevated levels of [Ca2+]i for the extended periods required for the completion of successful furrow deepening and daughter cell apposition in these large embryonic cells...
October 5, 2016: Zygote: the Biology of Gametes and Early Embryos
Asker Y Khapchaev, Olga A Kazakova, Mikhail V Samsonov, Maria V Sidorova, Valery N Bushuev, Elena L Vilitkevich, Andrey A Az'muko, Alexander S Molokoedov, Zhanna D Bespalova, Vladimir P Shirinsky
Myosin light chain kinase (MLCK) is a key regulator of various forms of cell motility including smooth muscle contraction, cell migration, cytokinesis, receptor capping, secretion, etc. Inhibition of MLCK activity in endothelial and epithelial monolayers using cell-permeant peptide Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys (PIK, Peptide Inhibitor of Kinase) allows protecting the barrier capacity, suggesting a potential medical use of PIK. However, low stability of L-PIK in a biological milieu prompts for development of more stable L-PIK analogues for use as experimental tools in basic and drug-oriented biomedical research...
October 4, 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
Xiong Liu, Shi Shu, Neil Billington, Chad D Williamson, Shuhua Yu, Hanna Brzeska, Julie G Donaldson, James R Sellers, Edward D Korn
Mammalian cells express three Class II nonmuscle myosins (NM): NM2A, NM2B and NM2C. The three NM2s have well-established essential roles in cell motility, adhesion and cytokinesis, and less well defined roles in vesicle transport and other processes that would require association of NM2s with cell membranes. Previous evidence for the mechanism of NM2-membrane association includes direct interaction of NM2s with membrane lipids and indirect interaction by association of NM2s with membrane-bound F-actin or peripheral membrane proteins...
October 3, 2016: Journal of Biological Chemistry
Mohsen Cheki, Alireza Shirazi, Aziz Mahmoudzadeh, Javad Tavakkoly Bazzaz, Seyed Jalal Hosseinimehr
Metformin is a widely prescribed drug used in the treatment of patients with type 2 diabetes. In this study, the radioprotective effect of metformin was investigated against cytotoxicity and genotoxicity induced by ionizing radiation (IR) in human peripheral blood lymphocytes. Human lymphocytes were treated with metformin at concentrations 10 and 50μM for 2h and irradiated with 6MV X-rays. The radiation antagonistic potential of metformin was assessed by MTT [3-(4,5-dimethyl-2-thiaozolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, chromosomal aberration (CA) analysis, cytokinesis blocked micronucleus (CBMN) assay, and flow cytometry...
October 2016: Mutation Research
Michael D Stubenvoll, Jeffrey C Medley, Miranda Irwin, Mi Hye Song
Centrosomes are critical sites for orchestrating microtubule dynamics, and exhibit dynamic changes in size during the cell cycle. As cells progress to mitosis, centrosomes recruit more microtubules (MT) to form mitotic bipolar spindles that ensure proper chromosome segregation. We report a new role for ATX-2, a C. elegans ortholog of Human Ataxin-2, in regulating centrosome size and MT dynamics. ATX-2, an RNA-binding protein, forms a complex with SZY-20 in an RNA-independent fashion. Depleting ATX-2 results in embryonic lethality and cytokinesis failure, and restores centrosome duplication to zyg-1 mutants...
September 2016: PLoS Genetics
X L Li, Q F Deng, X Zhang, T Wang, Z W Chen, Y S Bai, S H Wang, T C Wu, H Guo
Objective: To investigate the association and interaction of heat shock proteins B1(HSPB1)gene rs2868371 and tumor-suppressor protein p53(TP53)gene rs1042522 polymorphisms with chromosome damage levels among coke oven workers. Methods: We recruited 1 333 male workers from a state-run coke oven plant in Wuhan in September-October 2010. Among them, 949 who had worked in coke oven workplaces, including auxiliary facilities and bottom, side, and top ovens, were nominated as coke oven workers(i.e., exposed), and 384 administrative or medical staff whose workplaces were offices were used as controls...
October 6, 2016: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Chung-Ching Wang, Wei-Liang Chen, Chia-Ni Hsiung, Sheng-Ta Chiang, Ying-Chuan Wang, Ching-Hui Loh, I-Shen Lin, Hong-I Chen, Saou-Hsing Liou
OBJECTIVES: We investigated the relationship between 4,4'-methylene-bis(2-chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4). METHODS: We divided the study population into an exposed group (n=44 with total urine MBOCA ≥20 μg/g creatinine) and a control group (n=47 with total urine MBOCA <20 μg/g creatinine). Lymphocyte MN frequency (MNF) and micronucleated cell (MNC) frequency were measured by the cytokinesis-block MN assay method...
September 27, 2016: Occupational and Environmental Medicine
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