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Jiankai Liang, Li Guo, Kai Li, Xiao Xiao, Wenbo Zhu, Xiaoke Zheng, Jun Hu, Haipeng Zhang, Jing Cai, Yaya Yu, Yaqian Tan, Chuntao Li, Xincheng Liu, Cheng Hu, Ying Liu, Pengxin Qiu, Xingwen Su, Songmin He, Yuan Lin, Guangmei Yan
Oncolytic virus is an attractive anticancer agent that selectively lyses cancer through targeting cancer cells rather than normal cells. Although M1 virus is effective against several cancer types, certain cancer cells present low sensitivity to it. Here we identified that most of the components in the cholesterol biosynthesis pathway are downregulated after M1 virus infection. Further functional studies illustrate that mevalonate/protein farnesylation/ras homolog family member Q (RHOQ) axis inhibits M1 virus replication...
April 18, 2018: Nature Communications
Virginia Actis Dato, Rubén A Grosso, María C Sánchez, Claudio M Fader, Gustavo A Chiabrando
Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) is expressed in retinal Müller glial cells (MGCs) and regulates intracellular translocation to the plasma membrane (PM) of the membrane proteins involved in cellular motility and activity. Different functions of MGCs may be influenced by insulin, including the removal of extracellular glutamate in the retina. In the present work, we investigated whether insulin promotes LRP1 translocation to the PM in the Müller glial-derived cell line MIO-M1...
April 18, 2018: Biochemical Journal
Guendalina Rossi, Kelly Watson, Wade Kennedy, Patrick Brennwald
The tomosyn/Sro7 family is thought to play an important role in cell surface trafficking both as an effector of Rab family GTPases and as a regulator of plasma membrane SNARE function. Recent work has determined the binding site of GTP-bound Sec4 on Sro7. Here we examine the effect of mutations in Sro7 that block Sec4 binding to determine the role of this interaction in Sro7 function. Using an in vitro vesicle:vesicle tethering assay, we find that most of Sro7's ability to tether vesicles is blocked by mutations that disrupt binding to Sec4-GTP...
April 18, 2018: Molecular Biology of the Cell
Bipul Baibhav, Maheedhar Gedela, Michael Moulton, Gregory Pavlides, Vincent Pompili, Tanveer Rab, George Dangas, Deepak L Bhatt, Aleem Siddique, Yiannis S Chatzizisis
In patients with stable coronary artery disease, percutaneous coronary intervention is associated with improved outcomes if the lesion is deemed significant by invasive functional assessment using fractional flow reserve. Recent studies have shown that a revascularization strategy using instantaneous wave-free ratio is noninferior to fractional flow reserve in patients with intermediate-grade stenoses. The decision to perform coronary artery bypass grafting surgery is usually based on anatomic assessment of stenosis severity by coronary angiography...
April 17, 2018: Circulation
Subbaiah Chalivendra, Catherine DeRobertis, Jorge Reyes Pineda, Jong Hyun Ham, Kenneth Damann
The emergence of super-toxigenic strains by recombination is a risk from an intensive use of intraspecific aflatoxin (AF) biocontrol agents (BCAs). Periodical alternation with interspecific-BCAs will be safer since they preclude recombination. We are developing an AF-biocontrol system using rice-associated Bacilli reported previously (RABs). More than 50% of RABs inhibited the growth of multiple A. flavus strains, with RAB4R being the most inhibitory and RAB1 among the least. The fungistatic activity of RAB4R is associated with the lysis of A...
April 16, 2018: Toxins
Heron Werner, Maene Marcondes, Pedro Daltro, Tatiana Fazecas, Bianca Guedes Ribeiro, Renata Nogueira, Edward Araujo Júnior
OBJECTIVE: We aimed to compare three-dimensional (3D) fetal malformation images obtained using ultrasonography (US) and magnetic resonance imaging (MRI) on the same day during the third trimester of pregnancy. METHODS: Total 33 fetuses were selected from cases evaluated for malformations. Morphological abnormalities were first scanned using 3DUS . MRI was used to confirm the previous preliminary 3DUS findings, and diagnoses were confirmed postnatally. 3DUS scans were performed transabdominally using an Rab (4-8 L) probe, Voluson 730 Pro/Expert and E8 (General Electric, Healthcare, Zipf, Austria)...
April 15, 2018: Journal of Maternal-fetal & Neonatal Medicine
Robert P Law, Stephen J Atkinson, Paul Bamborough, Chun-Wa Chung, Emmanuel H Demont, Laurie J Gordon, Matthew Lindon, Rab K Prinjha, Allan J B Watson, David Jonathan Hirst
The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains, BRD2, BRD3, BRD4 and BRDT, each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but few reported inhibitors show selectivity within the BET family. Inhibitors with selectivity for the first or second bromodomain are desired to aid investigation of the biological function of these domains...
April 15, 2018: Journal of Medicinal Chemistry
Mary A Morse, Karla K Balogh, Sarah A Brendle, Colin A Campbell, Mao X Chen, Rebecca C Furze, Isobel L Harada, Ian D Holyer, Umesh Kumar, Kevin Lee, Rab K Prinjha, Martin Rüdiger, Jon Seal, Simon Taylor, Jason Witherington, Neil D Christensen
The DNA papillomaviruses infect squamous epithelium and can cause persistent, benign and sometimes malignant hyperproliferative lesions. Effective antiviral drugs to treat human papillomavirus (HPV) infection are lacking and here we investigate the anti-papillomavirus activity of novel epigenetic targeting drugs, BET bromodomain inhibitors. Bromodomain and Extra-Terminal domain (BET) proteins are host proteins which regulate gene transcription, they bind acetylated lysine residues in histones and non-histone proteins via bromodomains, functioning as scaffold proteins in the formation of transcriptional complexes at gene regulatory regions...
April 10, 2018: Antiviral Research
Tokuhiro Chano, Sofia Avnet
RAB39A is a Rab small GTPase that localizes at distinct subcellular compartments and regulates intracellular membrane trafficking pathways in vertebrate cells. RAB39A interacts with various molecules and modulates vesicular trafficking that regulates multiple biological pathways such as neuronal differentiation and/or autophagy. Among these pathways are Hippo and Notch signalings, microtubular organization, and mitophagy/autophagy. Although RAB39A has never been studied in cancer biology, it has been recently shown to promote cancer stemness and tumorigenesis...
April 10, 2018: Journal of Biochemistry
Pingbo Ouyang, Yun Li, Feng Zhang, Chengzhang Zhu, Beiji Zou, Jianlan Le, Lusi Zhang
Choroideremia is an X‑linked recessive chorioretinal degenerative disease that is characterized by progressive centripetal loss of the photoreceptor, retinal pigment epithelium (RPE), and choriocapillaris layers. The CHM gene [choroideremia (Rab escort protein 1)] has been identified as the pathogenic gene in choroideremia. The aim of the present study was to describe the clinical and genetic characteristics of a family with choroideremia family. In the present study, a family with choroideremia presenting with serious chorioretinal atrophy and pigment proliferation, shallow anterior chambers, angle closure and high intraocular pressure (IOP) were recruited...
April 5, 2018: Molecular Medicine Reports
Lina Yang, Xinrui Yang, Yiwei Tang, Defu Zhang, Lijie Zhu, Shengnan Wang, Bo Wang, Tao Ma
Non‑small cell lung cancer (NSCLC) is radioresistant to X‑rays due to powerful cellular DNA damage repair mechanisms. DNA‑dependent protein kinase (DNA‑PK) is a key enzyme involved in DNA damage repair and the phenomenon and molecular mechanism of NSCLC radionsensitivity were investigated following inhibition of DNA‑PK activity. In the present study A549 cells were treated with the DNA‑PK inhibitor NU7026 and/or siRNA directed against ataxia telangiectasia mutated (ATM), followed by exposure to 4 Gy X‑ray irradiation...
March 29, 2018: Molecular Medicine Reports
Xuewei Yang, Ni Ma, Le Yang, Yaqing Zheng, Zhengyi Zhen, Qing Li, Meihua Xie, Juan Li, Ke-Qin Zhang, Jinkui Yang
Rab GTPases are the largest group of the small GTPases family, which play a pivotal role in the secretion of proteins. Arthrobotrys oligospora is a representative nematode-trapping fungus that can produce adhesive networks to capture nematodes. In this study, the roles of two Rab GTPases AoRab-7A and AoRab-2 were characterized by gene knockout in the fungus A. oligospora. The disruption of AoRab-7A hindered the mycelial growth in different media, the conidiation of ΔAoRab-7A transformants was almost abolished, and the transcription of four sporulation-related genes (AbaA, FluG, Hyp1, and VosA) was downregulated compared to the wild-type strain (WT)...
April 3, 2018: Applied Microbiology and Biotechnology
Stephen Bruinsma, Declan J James, Melanie Quintana Serrano, Joseph Esquibel, Sang Su Woo, Elle Kielar-Grevstad, Ellen Crummy, Rehan Quraishi, Judy A Kowalchyk, Thomas F J Martin
Ca2+ -dependent secretory granule fusion with the plasma membrane is the final step for the exocytic release of inflammatory mediators, neuropeptides, and peptide hormones. Secretory cells use a similar protein machinery at late steps in the regulated secretory pathway employing protein isoforms from Rab, Sec1/Munc18, Munc13/CAPS, SNARE, and synaptotagmin protein families. However, no small molecule inhibitors of secretory granule exocytosis that target these proteins are currently available, but could have clinical utility...
April 3, 2018: Journal of Biological Chemistry
Irawan Cosphiadi, Tubagus D Atmakusumah, Nurjati C Siregar, Abdul Muthalib, Alida Harahap, Muchtarruddin Mansyur
BACKGROUND: Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM. PATIENTS AND METHODS: A total of 92 advanced breast cancer patients, including 46 patients with BM and 46 patients without BM, were identified for this study...
March 8, 2018: Clinical Breast Cancer
Emily K Herman, Moazzam Ali, Mark C Field, Joel B Dacks
Endocytosis is a crucial process in eukaryotic cells. The GTPases Rab 5, 21 and 22 that mediate endocytosis are ancient eukaryotic features and all available evidence suggests conserved function. In animals and fungi, these GTPases are regulated in part by proteins possessing Vps9 domains. However, the diversity, evolution and functions of Vps9 proteins beyond animals or fungi are poorly explored. Here we report a comprehensive analysis of the Vps9 family of GTPase regulators, combining molecular evolutionary data with functional characterization in the non-opisthokont model organism Trypanosoma brucei...
March 30, 2018: Traffic
Alexandr Sember, Jörg Bohlen, Vendula Šlechtová, Marie Altmanová, Šárka Pelikánová, Petr Ráb
Polyploidization has played an important role in the evolution of vertebrates, particularly at the base of Teleostei-an enormously successful ray-finned fish group with additional genome doublings on lower taxonomic levels. The investigation of post-polyploid genome dynamics might provide important clues about the evolution and ecology of respective species and can help to decipher the role of polyploidy per se on speciation. Few studies have attempted to investigate the dynamics of repetitive DNA sequences in the post-polyploid genome using molecular cytogenetic tools in fishes, though recent efforts demonstrated their usefulness...
2018: PloS One
Liu Yang, Hai Jiang, Meiling Yan, Xudong Xing, Xinyue Guo, Bingyou Yang, Qiuhong Wang, Haixue Kuang
An accurate and reliable method using ultra-high performance liquid chromatography combined with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) was established for simultaneous quantification of five major bioactive analytes in raw, wine-processed, and salt-processed Radix Achyranthis bidentatae (RAB). The results showed that this method exhibited desirable sensitivity, precision, stability, and repeatability. The overall intra-day and inter-day variations (RSD) were in the range of 1.57-2.46 and 1...
March 26, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
S P Fenemor, A R Homer, T L Perry, C M Skeaff, M C Peddie, N J Rehrer
AIMS: To quantify and compare energy utilization associated with prolonged sitting alone, or interrupted with regular activity breaks and/or an additional bout of continuous physical activity. METHODS AND RESULTS: Thirty six adults (11 males, BMI 24.1 ± 4.6) completed four interventions: (1) prolonged sitting (SIT), (2) sitting with 2-min of walking every 30 min (RAB), (3) prolonged sitting with 30-min of continuous walking at the end of the day (SIT + PA), (4) a combination of the activities in (2) and (3) above (RAB + PA)...
February 13, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Gabriela M Soares, Lucas Zangerolamo, Elis G Azevedo, Jose M Costa-Júnior, Everardo M Carneiro, Sara T Saad, Antonio C Boschero, Helena C Barbosa-Sampaio
GTPase activating proteins (GAPs) are ubiquitously expressed, and their role in cellular adhesion and membrane traffic processes have been well described. TBC1D1, which is a Rab-GAP, is necessary for adequate glucose uptake by muscle cells, whereas increased TCGAP, which is a Rho-GAP, decreases GLUT4 translocation, and consequently glucose uptake in adipocytes. Here, we assessed the possible involvement of ARHGAP21, a Rho-GAP protein, in glucose homeostasis. For this purpose, wild type mice and ARHGAP21 transgenic whole-body gene-deficiency mice (heterozygous mice, expressing approximately 50% of ARHGAP21) were fed either chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD)...
March 25, 2018: Journal of Cellular Physiology
Guillaume Kulakowski, Hugo Bousquet, Jean-Baptiste Manneville, Patricia Bassereau, Bruno Goud, Lena K Oesterlin
Specific intracellular localization of RAB GTPases has been reported to be dependent on protein factors but the contribution of the membrane physicochemical properties to this process has been poorly described. Here, we show that three RAB proteins (RAB1/RAB5/RAB6) preferentially bind in vitro to disordered and curved membranes, and that this feature is uniquely dependent on their prenyl group. Our results imply that the addition of a prenyl group confers to RAB proteins, and most probably also to other prenylated proteins, the ability to sense lipid packing defects induced by unsaturated conical-shaped lipids and curvature...
March 23, 2018: Traffic
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