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https://www.readbyqxmd.com/read/27910888/microtubule-stabilising-peptides-rescue-tau-phenotypes-in-vivo
#1
Shmma Quraishe, Megan Sealey, Louise Cranfield, Amritpal Mudher
The microtubule cytoskeleton is a highly dynamic, filamentous network underpinning cellular structure and function. In Alzheimer's disease, the microtubule cytoskeleton is compromised, leading to neuronal dysfunction and eventually cell death. There are currently no disease-modifying therapies to slow down or halt disease progression. However, microtubule stabilisation is a promising therapeutic strategy that is being explored. We previously investigated the disease-modifying potential of a microtubule-stabilising peptide NAP (NAPVSIPQ) in a well-established Drosophila model of tauopathy characterised by microtubule breakdown and axonal transport deficits...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909046/capping-protein-modulates-actin-remodeling-in-response-to-ros-during-plant-innate-immunity
#2
Jiejie Li, Lingyan Cao, Christopher J Staiger
Plants perceive microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs) to activate innate immune signaling events, such as bursts of reactive oxygen species (ROS). The actin cytoskeleton remodels during the first five minutes of innate immune signaling in Arabidopsis epidermal cells; however, the immune signals that impinge on actin cytoskeleton and its response regulators remain largely unknown. Here, we demonstrate that rapid actin remodeling upon elicitation with diverse MAMPs and DAMPs represents a conserved plant immune response...
December 1, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27908613/sparc-interacts-with-actin-in-skeletal-muscle-in%C3%A2-vitro-and-in%C3%A2-vivo
#3
Louise H Jørgensen, Pia Lørup Jepsen, Anders Boysen, Line B Dalgaard, Lars G Hvid, Niels Ørtenblad, Dea Ravn, Jeeva Sellathurai, Jakob Møller-Jensen, Hanns Lochmüller, Henrik D Schrøder
The cytoskeleton is an integral part of skeletal muscle structure, and reorganization of the cytoskeleton occurs during various modes of remodeling. We previously found that the extracellular matrix protein secreted protein acidic and rich in cysteine (SPARC) is up-regulated and expressed intracellularly in developing muscle, during regeneration and in myopathies, which together suggests that SPARC might serve a specific role within muscle cells. Using co-immunoprecipitation combined with mass spectrometry and verified by staining for direct protein-protein interaction, we find that SPARC binds to actin...
November 28, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27906134/tumour-suppressor-micrornas-regulate-ovarian-cancer-cell-physical-properties-and-invasive-behaviour
#4
Clara K Chan, Yinghong Pan, Kendra Nyberg, Marco A Marra, Emilia L Lim, Steven J M Jones, Dianna Maar, Ewan A Gibb, Preethi H Gunaratne, A Gordon Robertson, Amy C Rowat
The activities of pathways that regulate malignant transformation can be influenced by microRNAs (miRs). Recently, we showed that increased expression of five tumour-suppressor miRs, miR-508-3p, miR-508-5p, miR-509-3p, miR-509-5p and miR-130b-3p, correlate with improved clinical outcomes in human ovarian cancer patients, and that miR-509-3p attenuates invasion of ovarian cancer cell lines. Here, we investigate the mechanism underlying this reduced invasive potential by assessing the impact of these five miRs on the physical properties of cells...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27906101/characterization-of-a-dmd-egfp-reporter-mouse-as-a-tool-to-investigate-dystrophin-expression
#5
Mina V Petkova, Susanne Morales-Gonzales, Karima Relizani, Esther Gill, Franziska Seifert, Josefine Radke, Werner Stenzel, Luis Garcia, Helge Amthor, Markus Schuelke
BACKGROUND: Dystrophin is a rod-shaped cytoplasmic protein that provides sarcolemmal stability as a structural link between the cytoskeleton and the extracellular matrix via the dystrophin-associated protein complex (DAPC). Mutations in the dystrophin-encoding DMD gene cause X-linked dystrophinopathies with variable phenotypes, the most severe being Duchenne muscular dystrophy (DMD) characterized by progressive muscle wasting and fibrosis. However, dystrophin deficiency does not only impair the function of skeletal and heart muscle but may also affect other organ systems such as the brain, eye, and gastrointestinal tract...
July 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27902484/depletion-of-mitochondrial-reactive-oxygen-species-downregulates-epithelial-to-mesenchymal-transition-in-cervical-cancer-cells
#6
Galina Shagieva, Lidiya Domnina, Olga Makarevich, Boris Chernyak, Vladimir Skulachev, Vera Dugina
In the course of cancer progression, epithelial cells often acquire morphological and functional characteristics of mesenchymal cells, a process known as epithelial-to-mesenchymal transition (EMT). EMT provides epithelial cells with migratory, invasive, and stem cell capabilities. Reactive oxygen species produced by mitochondria (mtROS) could be of special importance for pro-tumorigenic signaling and EMT.In our study, we used mitochondria-targeted antioxidant SkQ1 to lower the mtROS level and analyze their role in the regulation of the actin cytoskeleton, adhesion junctions, and signaling pathways critical for tumorigenesis of cervical carcinomas...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901489/membrane-bound-icam-1-contributes-to-the-onset-of-proinvasive-tumor-stroma-by-controlling-acto-myosin-contractility-in-carcinoma-associated-fibroblasts
#7
Stephanie Bonan, Jean Albrengues, Eloise Grasset, Sanya-Eduarda Kuzet, Nicolas Nottet, Isabelle Bourget, Thomas Bertero, Bernard Mari, Guerrino Meneguzzi, Cedric Gaggioli
Acto-myosin contractility in carcinoma-associated fibroblasts leads to assembly of the tumor extracellular matrix. The pro-inflammatory cytokine LIF governs fibroblast activation in cancer by regulating the myosin light chain 2 activity. So far, however, how LIF mediates cytoskeleton contractility remains unknown. Using phenotypic screening assays based on knock-down of LIF-dependent genes in fibroblasts, we identified the glycoprotein ICAM-1 as a crucial regulator of stroma fibroblast proinvasive matrix remodeling...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901125/rab14-specifies-the-apical-membrane-through-arf6-mediated-regulation-of-lipid-domains-and-cdc42
#8
Ruifeng Lu, Jean M Wilson
The generation of cell polarity is essential for the development of multi-cellular organisms as well as for the function of epithelial organs in the mature animal. Small GTPases regulate the establishment and maintenance of polarity through effects on cytoskeleton, membrane trafficking, and signaling. Using short-term 3-dimensional culture of MDCK cells, we find that the small GTPase Rab14 is required for apical membrane specification. Rab14 knockdown results in disruption of polarized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical membrane...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900823/high-frequency-mechanostimulation-of-cell-adhesion
#9
Laith F Kadem, K Grace Suana, Michelle Holz, Wei Wang, Hannes Westerhaus, Rainer Herges, Christine Selhuber-Unkel
Cell adhesion is regulated by molecularly defined protein interactions and by mechanical forces, which can activate a dynamic restructuring of adhesion sites. Previous attempts to explore the response of cell adhesion to forces have been limited to applying mechanical stimuli that involve the cytoskeleton. In contrast, we here apply a new, oscillatory type of stimulus through push-pull azobenzenes. Push-pull azobenzenes perform a high-frequency, molecular oscillation upon irradiation with visible light that has frequently been applied in polymer surface relief grating...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27900754/ezrin-and-moesin-expression-in-canine-and-feline-osteosarcoma
#10
Juraj Hlavaty, Birgitt Wolfesberger, Marlene Hauck, Barbara Obermayer-Pietsch, Andrea Fuchs-Baumgartinger, Ingrid Miller, Ingrid Walter
Biological features of canine osteosarcomas (OS) differ markedly from those found in feline and resemble more human osteosarcomas, in particular for their high rate of metastasis and poor prognosis. Ezrin, radixin and moesin are members of the ERM protein family and link the actin cytoskeleton with the cell membrane. Ezrin and moesin have been shown to be of prognostic significance in tumor progression due to their role in the metastatic process. The objective of this study was to analyze ezrin and moesin protein expression in a series of dog (n = 16) and cat (n = 8) osteosarcoma samples using immunohistochemistry and western blot techniques...
November 30, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27899144/hypoxia-induced-responses-by-endothelial-colony-forming-cells-are-modulated-by-placental-growth-factor
#11
Michelle B Hookham, Imran H A Ali, Christina L O'Neill, Emer Hackett, Melanie H Lambe, Tina Schmidt, Reinhold J Medina, Sara Chamney, Bharathi Rao, Eibhlin McLoone, David Sweet, Alan W Stitt, Derek P Brazil
BACKGROUND: Endothelial colony-forming cells (ECFCs), also termed late outgrowth endothelial cells, are a well-defined circulating endothelial progenitor cell type with an established role in vascular repair. ECFCs have clear potential for cell therapy to treat ischaemic disease, although the precise mechanism(s) underlying their response to hypoxia remains ill-defined. METHODS: In this study, we isolated ECFCs from umbilical cord blood and cultured them on collagen...
November 29, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27898103/glyoxalase-1-knockdown-in-human-aortic-endothelial-cells-effect-on-the-proteome-and-endothelial-function-estimates
#12
Bernd Stratmann, Britta Engelbrecht, Britta C Espelage, Nadine Klusmeier, Janina Tiemann, Thomas Gawlowski, Yvonne Mattern, Martin Eisenacher, Helmut E Meyer, Naila Rabbani, Paul J Thornalley, Diethelm Tschoepe, Gereon Poschmann, Kai Stühler
Methylglyoxal (MG), an arginine-directed glycating agent, is implicated in diabetic late complications. MG is detoxified by glyoxalase 1 (GLO1) of the cytosolic glyoxalase system. The aim was to investigate the effects of MG accumulation by GLO1-knockdown under hyperglycaemic conditions in human aortic endothelial cells (HAECs) hypothesizing that the accumulation of MG accounts for the deleterious effects on vascular function. SiRNA-mediated knockdown of GLO1 was performed and MG concentrations were determined...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895171/impairment-of-ccr6-and-cxcr3-th-cell-migration-in-hiv-1-infection-is-rescued-by-modulating-actin-polymerization
#13
Valentina Cecchinato, Enos Bernasconi, Roberto F Speck, Michele Proietti, Ulrike Sauermann, Gianluca D'Agostino, Gabriela Danelon, Tanja Rezzonico Jost, Fabio Grassi, Lorenzo Raeli, Franziska Schöni-Affolter, Christiane Stahl-Hennig, Mariagrazia Uguccioni
CD4(+) T cell repopulation of the gut is rarely achieved in HIV-1-infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6(+) and CXCR3(+) Th cells accumulate in the blood of aviremic HIV-1-infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895123/addressing-the-functional-determinants-of-fak-during-ciliogenesis-in-multiciliated-cells
#14
Ioanna Antoniades, Panayiota Stylianou, Neophytos Christodoulou, Paris A Skourides
We have previously identified FAK as an important regulator of ciliogenesis in multiciliated cells. FAK and other focal adhesion (FA) proteins associate with the basal bodies and their striated rootlets and form complexes named ciliary adhesions (CAs). CAs display similarities with FAs but are established in an integrin independent fashion and are responsible for anchoring basal bodies to the actin cytoskeleton during ciliogenesis, as well as in mature multiciliated cells. FAK downregulation leads to aberrant ciliogenesis due to impaired association between the basal bodies and the actin cytoskeleton, suggesting that FAK is an important regulator of the CA complex...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27894934/mir-142-is-required-for-staphylococcus-aureus-clearance-at-skin-wound-sites-via-small-gtpase-mediated-regulation-of-the-neutrophil-actin-cytoskeleton
#15
Katsuya Tanaka, Sang Eun Kim, Hiroki Yano, Gaku Matsumoto, Ryoma Ohuchida, Yuhoko Ishikura, Masatake Araki, Kimi Araki, Seongjoon Park, Toshimitsu Komatsu, Hiroko Hayashi, Kazuya Ikematsu, Katsumi Tanaka, Akiyoshi Hirano, Paul Martin, Isao Shimokawa, Ryoichi Mori
MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein translation by binding to complementary target mRNAs. We previously identified two mature members of the miR-142 family, miR-142-5p and miR-142-3p, as inflammation-related miRNAs with potential roles in wound healing. Here, we demonstrated that these two miRNAs are prominently expressed in wound-infiltrated neutrophils and macrophages and play central roles in wound healing. We generated miR-142(-/-) mice using the exchangeable gene-trap method and showed that healing of Staphylococcus aureus-infected skin wounds was significantly delayed in miR-142(-/-) mice compared with that in wild-type mice...
November 25, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27894594/alterations-of-golgi-organization-in-alzheimer-s-disease-a-cause-or-a-consequence
#16
REVIEW
Inmaculada Ayala, Antonino Colanzi
The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized in polarized manner, which are interconnected by membrane tubules to constitute the Golgi ribbon, located in the proximity of the centrosome. Besides the processing and transport of cargo, the Golgi complex is actively involved in the regulation of mitotic entry, cytoskeleton organization and dynamics, calcium homeostasis, and apoptosis, representing a signalling platform for the control of several cellular functions, including signalling initiated by receptors located at the plasma membrane...
November 19, 2016: Tissue & Cell
https://www.readbyqxmd.com/read/27891552/enteric-glial-cells-are-susceptible-to-clostridium-difficile-toxin-b
#17
Katia Fettucciari, Pamela Ponsini, Davide Gioè, Lara Macchioni, Camilla Palumbo, Elisabetta Antonelli, Stefano Coaccioli, Vincenzo Villanacci, Lanfranco Corazzi, Pierfrancesco Marconi, Gabrio Bassotti
Clostridium difficile causes nosocomial/antibiotic-associated diarrhoea and pseudomembranous colitis. The major virulence factors are toxin A and toxin B (TcdB), which inactivate GTPases by monoglucosylation, leading to cytopathic (cytoskeleton alteration, cell rounding) and cytotoxic effects (cell-cycle arrest, apoptosis). C. difficile toxins breaching the intestinal epithelial barrier can act on underlying cells, enterocytes, colonocytes, and enteric neurons, as described in vitro and in vivo, but until now no data have been available on enteric glial cell (EGC) susceptibility...
November 28, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27890731/mechanisms-of-cdc42-mediated-rat-msc-differentiation-on-micro-nano-textured-topography
#18
Guangwen Li, Yanyan Song, Mengqi Shi, Yuanhong Du, Wei Wang, Yumei Zhang
Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/ β -catenin is the underlying mechanism...
November 24, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27889644/delineating-the-role-of-%C3%AE-iv-tubulins-in-pancreatic-cancer-%C3%AE-ivb-tubulin-inhibition-sensitizes-pancreatic-cancer-cells-to-vinca-alkaloids
#19
G Sharbeen, J McCarroll, J Liu, J Youkhana, L F Limbri, A V Biankin, A Johns, M Kavallaris, D Goldstein, P A Phillips
Pancreatic cancer (PC) is a lethal disease which is characterized by chemoresistance. Components of the cell cytoskeleton are therapeutic targets in cancer. βIV-tubulin is one such component that has two isotypes-βIVa and βIVb. βIVa and βIVb isotypes only differ in two amino acids at their C-terminus. Studies have implicated βIVa-tubulin or βIVb-tubulin expression with chemoresistance in prostate, breast, ovarian and lung cancer. However, no studies have examined the role of βIV-tubulin in PC or attempted to identify isotype specific roles in regulating cancer cell growth and chemosensitivity...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27889578/molecular-neurobiology-of-mtor
#20
REVIEW
Katarzyna Switon, Katarzyna Kotulska, Aleksandra Janusz-Kaminska, Justyna Zmorzynska, Jacek Jaworski
Mammalian/mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that controls several important aspects of mammalian cell function. mTOR activity is modulated by various intra- and extracellular factors; in turn, mTOR changes rates of translation, transcription, protein degradation, cell signaling, metabolism, and cytoskeleton dynamics. mTOR has been repeatedly shown to participate in neuronal development and the proper functioning of mature neurons. Changes in mTOR activity are often observed in nervous system diseases, including genetic diseases (e...
November 23, 2016: Neuroscience
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