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Claudia Kruger, Susan J Burke, J Jason Collier, Trang-Tiffany Nguyen, J Michael Salbaum, Krisztian Stadler
Early podocyte loss is characteristic of chronic kidney diseases (CKD) in obesity and diabetes. Since treatments for hyperglycemia and hypertension do not prevent podocyte loss, there must be additional factors causing podocyte depletion. The role of oxidative stress has been implicated in CKD but it is not known how exactly free radicals affect podocyte physiology. To assess this relationship, we investigated the effects of lipid radicals on podocytes, as lipid peroxidation is a major form of oxidative stress in diabetes...
March 6, 2018: Redox Biology
Anna Szewczyk, Julie Gehl, Malgorzata Daczewska, Jolanta Saczko, Stine Krog Frandsen, Julita Kulbacka
Calcium electroporation (CaEP) describes the use of electric pulses (electroporation) to transiently permeabilize cells to allow supraphysiological doses of calcium to enter the cytosol. Calcium electroporation has successfully been investigated for treatment of cutaneous metastases in a clinical study. This preclinical study explores the possible use of calcium electroporation for treatment of sarcoma. A normal murine muscle cell line (C2C12), and a human rhabdomyosarcoma cell line (RD) were used in the undifferentiated and differentiated state...
February 20, 2018: Oncotarget
Xuechao Liu, Haibo Qiu, Peng Zhang, Xingyu Feng, Tao Chen, Yong Li, Kaixiong Tao, Guoxin Li, Xiaowei Sun, Zhiwei Zhou, On Behalf Of China Gastrointestinal Stromal Tumor Study Group Cn-Gist
Objective: We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors (GISTs). Methods: Data from 2,570 consecutive GIST patients from four medical centers in China (January 2001-December 2015) were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors. Results: Of the included patients, 1,375 (53...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Danuta Gutowska-Owsiak, Jorge Bernardino de La Serna, Marco Fritzsche, Aishath Naeem, Ewa I Podobas, Michael Leeming, Huw Colin-York, Ryan O'Shaughnessy, Christian Eggeling, Graham S Ogg
Epidermal stratification critically depends on keratinocyte differentiation and programmed death by cornification, leading to formation of a protective skin barrier. Cornification is dynamically controlled by the protein filaggrin, rapidly released from keratohyalin granules (KHGs). However, the mechanisms of cornification largely remain elusive, partly due to limitations of the observation techniques employed to study filaggrin organization in keratinocytes. Moreover, while the abundance of keratins within KHGs has been well described, it is not clear whether actin also contributes to their formation or fate...
March 15, 2018: Cell Death & Disease
Anthony J Kee, Jayshan Chagan, Jeng Yie Chan, Nicole S Bryce, Christine A Lucas, Jun Zeng, Jeff Hook, Herbert Treutlein, D Ross Laybutt, Justine R Stehn, Peter W Gunning, Edna C Hardeman
The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets...
March 15, 2018: Scientific Reports
Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-Ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa
BACKGROUND: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. METHODS: The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed...
March 15, 2018: Arthritis Research & Therapy
Oriane Blanquie, Frank Bradke
Recent years have seen cytoskeleton dynamics emerging as a key player in axon regeneration. The cytoskeleton, in particular microtubules and actin, ensures the growth of neuronal processes and maintains the singular, highly polarized shape of neurons. Following injury, adult central axons are tipped by a dystrophic structure, the retraction bulb, which prevents their regeneration. Abnormal cytoskeleton dynamics are responsible for the formation of this growth-incompetent structure but pharmacologically modulating cytoskeleton dynamics of injured axons can transform this structure into a growth-competent growth cone...
March 12, 2018: Current Opinion in Neurobiology
Yasmine Baktash, Anisha Madhav, Kelly E Coller, Glenn Randall
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms...
March 14, 2018: Cell Host & Microbe
Chaoqiong Liang, Jianjun Hao, Yan Meng, Laixin Luo, Jianqiang Li
Cucumber green mottle mosaic virus (CGMMV) is an economically important pathogen and causes significant reduction of both yield and quality of cucumber (Cucumis sativus). Currently, there were no satisfied strategies for controlling the disease. A better understanding of microRNA (miRNA) expression related to the regulation of plant-virus interactions and virus resistance would be of great assistance when developing control strategies for CGMMV. However, accurate expression analysis is highly dependent on robust and reliable reference gene used as an internal control for normalization of miRNA expression...
2018: PloS One
Natthanon Leelarasamee, Lei Zhang, Cynthia Gleason
Root-knot nematodes secrete effectors that manipulate their host plant cells so that the nematode can successfully establish feeding sites and complete its lifecycle. The root-knot nematode feeding structures, their "giant cells," undergo extensive cytoskeletal remodeling. Previous cytological studies have shown the cytoplasmic actin within the feeding sites looks diffuse. In an effort to study root-knot nematode effectors that are involved in giant cell organogenesis, we have identified a nematode effector called MiPFN3 (Meloidogyne incognita Profilin 3)...
March 15, 2018: PLoS Pathogens
Yoshinori Hirano, Yu Amano, Shigenobu Yonemura, Toshio Hakoshima
Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G...
March 15, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Thomas O Tolsma, Lena M Cuevas, Santiago M Di Pietro
Clathrin mediated endocytosis is a fundamental transport pathway that depends on numerous protein-protein interactions. Testing the importance of the adaptor protein-clathrin interaction for coat formation and progression of endocytosis in vivo has been difficult due to experimental constrains. Here we addressed this question using the yeast clathrin adaptor Sla1, which is unique in showing a cargo endocytosis defect upon substitution of three amino acids in its clathrin-binding motif (sla1AAA ) that disrupt clathrin binding...
March 15, 2018: Traffic
Istvan Bodi, Anastasios Giamouriadis, Naomi Sibtain, Ross Laxton, Andrew King, Francesco Vergani
Background: Primary CNS malignant rhabdoid tumors are very rare in adults and much less is known about their biological behavior than in children. Recently, two adult cases of SMARCB1 (also known as INI1)-deficient tumor with rhabdoid cells have been described, suggesting an emerging group of primary meningeal SMARCB1-deficient tumors. We have recently encountered a case of INI1-deficient tumor with similar histology and immunophenotype to the above cases, but with a superficial cerebral, yet apparent intra-axial origin...
2018: Surgical Neurology International
Liang Liang, Ming Zeng, Haixia Pan, Hao Liu, Yangke He
Previous studies have demonstrated that nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in a number of tumors. In the present study, it was demonstrated that the gene and protein levels of NNMT were significantly increased in gastric cancer cells. Furthermore, upregulation of NNMT significantly increased the expression of mesenchymal markers, including α-smooth muscle actin (SMA), vimentin and fibronectin, but decreased the levels of epithelial cadherin. Since transforming growth factor (TGF)-β1 may serve a key function in epithelial-mesenchymal transition (EMT), the effects of NNMT on the expression of TGF-β1 were investigated in BGC-823 cells...
April 2018: Oncology Letters
Alexis Bonfim-Melo, Éden R Ferreira, Renato A Mortara
This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups...
2018: Frontiers in Microbiology
Sho Sugawara, Yasutaka Yamada, Takayuki Arai, Atsushi Okato, Tetsuya Idichi, Mayuko Kato, Keiichi Koshizuka, Tomohiko Ichikawa, Naohiko Seki
Analyses of microRNA (miRNA) expression signatures obtained by RNA sequencing revealed that some passenger miRNAs (miR-144-5p, miR-145-3p, miR-149-3p, miR-150-3p, and miR-199a-3p) acted as anti-tumor miRNAs in several types of cancer cells. The involvement of passenger strands in the pathogenesis of human cancer is a novel concept. Based on the miRNA signature of bladder cancer (BC) obtained by RNA sequencing, we focused on both strands of the miR-223-duplex (miR-223-5p and miR-223-3p) and investigated their functional significance in BC cells...
March 14, 2018: Journal of Human Genetics
Dhivya Kumar, Rebecca T Thomason, Maya Yankova, Jonathan D Gitlin, Richard E Mains, Betty A Eipper, Stephen M King
The assembly of membranous extensions such as microvilli and cilia in polarized cells is a tightly regulated, yet poorly understood, process. Peptidylglycine α-amidating monooxygenase (PAM), a membrane enzyme essential for the synthesis of amidated bioactive peptides, was recently identified in motile and non-motile (primary) cilia and has an essential role in ciliogenesis in Chlamydomonas, Schmidtea and mouse. In mammalian cells, changes in PAM levels alter secretion and organization of the actin cytoskeleton...
March 14, 2018: Scientific Reports
Ryo Hatano, Ai Takeda, Yukiko Abe, Kotoku Kawaguchi, Itsuro Kazama, Mitsunobu Matsubara, Shinji Asano
Ezrin is highly expressed in glomerular podocytes and is reported to form a multi-protein complex with scaffold protein Na+ /H+ exchanger regulatory factor 2 (NHERF2) and podocalyxin, a major sialoprotein. Podocalyxin-knockout mice died within 24 h of birth with anuric renal failure, whereas NHERF2-knockout mice show no apparent changes in the glomerular functions. However, the physiological roles of ezrin in glomerular podocytes remain unclear. Here, we investigated the importance of ezrin in the regulation of glomerular podocyte function using ezrin-knockdown mice (Vil2kd/kd )...
March 14, 2018: Scientific Reports
Kuo-Fu Tseng, Pan Wang, Yuh-Ru Julie Lee, Joel Bowen, Allison M Gicking, Lijun Guo, Bo Liu, Weihong Qiu
In animals and fungi, cytoplasmic dynein is a processive minus-end-directed motor that plays dominant roles in various intracellular processes. In contrast, land plants lack cytoplasmic dynein but contain many minus-end-directed kinesin-14s. No plant kinesin-14 is known to produce processive motility as a homodimer. OsKCH2 is a plant-specific kinesin-14 with an N-terminal actin-binding domain and a central motor domain flanked by two predicted coiled-coils (CC1 and CC2). Here, we show that OsKCH2 specifically decorates preprophase band microtubules in vivo and transports actin filaments along microtubules in vitro...
March 14, 2018: Nature Communications
Nicla Porciello, Paola Grazioli, Antonio F Campese, Martina Kunkl, Silvana Caristi, Marta Mastrogiovanni, Michela Muscolini, Francesca Spadaro, Cédric Favre, Jacques A Nunès, Aldo Borroto, Balbino Alarcon, Isabella Screpanti, Loretta Tuosto
CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immunosuppressive regulatory T cells (Treg) in mice. However, pre-clinical trials assessing CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory response syndrome in humans, thereby implying the existence of distinct signalling abilities between human and mouse CD28. Here, we show that a single amino acid variant within the C-terminal proline-rich motif of human and mouse CD28 (P212 in human vs. A210 in mouse) regulates CD28-induced NF-κB activation and pro-inflammatory cytokine gene expression...
March 14, 2018: Nature Communications
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