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https://www.readbyqxmd.com/read/28527894/hfe-genotype-affects-exosome-phenotype-in-cancer
#1
Oliver D Mrowczynski, A B Madhankumar, Becky Slagle-Webb, Sang Y Lee, Brad E Zacharia, James R Connor
Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28525262/serum-protein-adsorption-enhances-active-leukemia-stem-cell-targeting-of-mesoporous-silica-nanoparticles
#2
Michaela Beck, Tamoghna Mandal, Christian Buske, Mika Lindén
The functionalization of nanoparticles with a ligand targeting receptors overexpressed by the target cells is a commonly used strategy when aiming at nanoparticle-based, cell type-specific drug delivery. However, the influence of particle surface chemistry on the targetability has received much less attention. The surface charge is known to directly or indirectly affect the nanoparticle cellular uptake kinetics by influencing serum protein adsorption. Thus, it is fair to assume that both the specificity and cellular uptake kinetics of targeted nanoparticles are influenced by the nanoparticle charge, both of which are important parameters for controlling cell-specific drug delivery efficiency...
May 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28525259/biodegradable-smart-polyphosphazenes-with-intrinsic-multi-functionality-as-intracellular-protein-delivery-vehicles
#3
Andre P Martinez, Bareera Qamar, Thomas R Fuerst, Silvia Muro, Alexander K Andrianov
A series of biodegradable drug delivery polymers with intrinsic multifunctionality have been designed and synthesized utilizing polyphosphazene macromolecular engineering approach. Novel water-soluble polymers, which contain carboxylic acid and pyrrolidone moieties attached to inorganic phosphorus-nitrogen backbone, were characterized by a suite of physico-chemical methods to confirm their structure, composition, and molecular sizes. All synthesized polyphosphazenes displayed composition dependent hydrolytic degradability in aqueous solutions at neutral pH...
May 19, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28524820/chemical-structure-guided-design-of-dynapyrazoles-potent-cell-permeable-dynein-inhibitors-with-a-unique-mode-of-action
#4
Jonathan Baruch Steinman, Cristina C Santarossa, Rand M Miller, Lola S Yu, Anna S Serpinskaya, Hideki Furukawa, Sachie Morimoto, Yuta Tanaka, Mitsuyoshi Nishitani, Moriteru Asano, Ruta Zalyte, Alison E Ondrus, Alex G Johnson, Fan Ye, Maxence V Nachury, Yoshiyuki Fukase, Kazuyoshi Aso, Michael A Foley, Vladimir I Gelfand, James K Chen, Andrew P Carter, Tarun M Kapoor
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that power transport of cellular cargos towards microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally-constrained isosteres...
May 19, 2017: ELife
https://www.readbyqxmd.com/read/28524544/enzymatic-engineering-of-live-bacterial-cell-surface-using-butelase-1
#5
Xiaobao Bi, Juan Yin, Giang K T Nguyen, Chang Rao, Nurashikin Bte Abdul Halim, Xinya Hemu, James P Tam, Chuan-Fa Liu
We show that butelase-mediated ligation (BML) can be used to modify live bacterial cell surfaces with diverse cargo molecules. Surface-displayed butelase recognition motif NHV was first introduced at the C-terminal end of the anchoring protein OmpA on E. coli cells. This then served as a handle of BML for the functionalization of E. coli cell surfaces with fluorescein and biotin tags, a tumor-associated monoglycosylated peptide and mCherry protein. The cell-surface ligation reaction was achieved at low concentrations of butelase and the labeling substrates...
May 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28515232/the-nuclear-export-factor-crm1-controls-juxta-nuclear-microtubule-dependent-virus-transport
#6
I-Hsuan Wang, Christoph J Burckhardt, Artur Yakimovich, Matthias K Morf, Urs F Greber
Transport of large cargo through the cytoplasm requires motor proteins and polarized filaments. Viruses that replicate in the nucleus of post-mitotic cells use microtubules and the dynein/dynactin motor to traffic to the nuclear membrane, and deliver their genome through nuclear pore complexes (NPCs) into the nucleus. How virus particles (virions) or cellular cargo are transferred from microtubules to the NPC is unknown. Here, we analyzed trafficking of incoming cytoplasmic adenoviruses by single particle tracking and super-resolution microscopy...
May 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28511536/biomimetic-silica-nanocapsules-for-tunable-sustained-release-and-cargo-protection
#7
Guang-Ze Yang, David Wibowo, Jung-Ho Yun, Lianzhou Wang, Anton Peter J Middelberg, Chun-Xia Zhao
Silica nanocapsules have attracted tremendous interest for encapsulation, protection and controlled release of various cargoes due to their unique hierarchical core-shell structure. However, it remains challenging to synthesize silica nanocapsules having high cargo-loading capacity and cargo-protection capability without compromising process simplicity and biocompatibility properties. Here, we synthesized oil-core silica-shell nanocapsules under environmentally friendly conditions by a novel emulsion and biomimetic dual-templating approach using a dual-functional protein, in lieu of petrochemical surfactants, thus avoiding the necessities for the removal of toxic components...
May 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28507101/human-myosin-viia-is-a-very-slow-processive-motor-protein-on-various-cellular-actin-structures
#8
Osamu Sato, Satoshi Komatsu, Tsuyoshi Sakai, Yoshikazu Tsukasaki, Ryosuke Tanaka, Takeomi Mizutani, Tomonobu M Watanabe, Reiko Ikebe, Mitsuo Ikebe
Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human Usher syndrome (USH) type 1B, which causes human congenital hearing and visual loss. While it has been thought that the role of human myosin VIIa is critical for USH1 protein tethering with actin and transportation along actin bundles in inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we studied the motor function of the tail-truncated human myosin VIIa dimer (HM7AΔTail/LZ) at the single-molecule level...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28507098/cargo-engagement-protects-protease-adaptors-from-degradation-in-a-substrate-specific-manner
#9
Kamal Kishore Joshi, Madeleine Sutherland, Peter Chien
Protein degradation in bacteria is a highly controlled process involving proteolytic adaptors that regulate protein degradation during cell cycle progression or during stress responses. Many adaptors work as scaffolds that selectively bind cargo and tether substrates to their cognate proteases to promote substrate destruction, while others primarily activate the target protease. Because adaptors must bind their cognate protease, all adaptors run the risk of being recognized by the protease as substrates themselves, a process that could limit their effectiveness...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28506891/viral-mechanisms-for-docking-and-delivering-at-nuclear-pore-complexes
#10
REVIEW
Justin W Flatt, Urs F Greber
Some viruses possess the remarkable ability to transport their genomes across nuclear pore complexes (NPCs) for replication inside the host cell's intact nuclear compartment. Viral mechanisms for crossing the restrictive NPC passageway are highly complex and astonishingly diverse, requiring in each case stepwise interaction between incoming virus particles and components of the nuclear transport machinery. Exactly how a large viral genome loaded with accessory proteins is able to pass through the relatively narrow central channel of the NPC without causing catastrophic structural damage is not yet fully understood...
May 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28506890/biomechanics-of-the-transport-barrier-in-the-nuclear-pore-complex
#11
REVIEW
George J Stanley, Ariberto Fassati, Bart W Hoogenboom
The nuclear pore complex (NPC) is the selective gateway through which all molecules must pass when entering or exiting the nucleus. It is a cog in the gene expression pathway, an entrance to the nucleus exploited by viruses, and a highly-tuned nanoscale filter. The NPC is a large proteinaceous assembly with a central lumen occluded by natively disordered proteins, known as FG-nucleoporins (or FG-nups). These FG-nups, along with a family of soluble proteins known as nuclear transport receptors (NTRs), form the selective transport barrier...
May 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28505371/the-arm-domain-of-armadillo-repeat-kinesin-1-is-not-required-for-microtubule-catastrophe-but-can-negatively-regulate-nima-related-kinase-6-in-arabidopsis-thaliana
#12
Ryan C Eng, Laryssa S Halat, Samuel J Livingston, Tatsuya Sakai, Hiroyasu Motose, Geoffrey Wasteneys
Microtubules are dynamic filaments, the assembly and disassembly of which are under precise control of various associated proteins, including motor proteins and regulatory enzymes. In Arabidopsis thaliana, two such proteins are the ARMADILLO-REPEAT KINESIN 1 (ARK1), which promotes microtubule disassembly, and the NIMA-RELATED KINASE 6 (NEK6), which has a role in organizing microtubule arrays. Previous yeast 2-hybrid and in vitro pull-down assays determined that NEK6 can interact with ARK1 through the latter protein's Armadillo-repeat (ARM) cargo domain...
May 13, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28505322/exosomes-in-toxicology-relevance-to-chemical-exposure-and-pathogenesis-of-environmentally-linked-diseases
#13
Dilshan S Harischandra, Shivani Ghaisas, Dharmin Rokad, Anumantha G Kanthasamy
Chronic exposure to environmental toxins has been known to initiate or aggravate various neurological disorders, carcinomas and other adverse health effects. Uptake by naïve cells of pathogenic factors such as danger-associated molecules, mRNAs, miRNAs or aggregated proteins leads to disruption in cellular homeostasis further resulting in inflammation and disease propagation. While early research tended to focus solely on exosomal removal of unwanted cellular contents, more recent reports indicate that these nano-vesicles play an active role in intercellular signaling...
May 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28500756/sphingomyelin-metabolism-controls-the-shape-and-function-of-the-golgi-cisternae
#14
Felix Campelo, Josse van Galen, Gabriele Turacchio, Seetharaman Parashuraman, Michael M Kozlov, María García-Parajo, Vivek Malhotra
The flat Golgi cisterna is a highly conserved feature of eukaryotic cells, but how is this morphology achieved and is it related to its function in cargo sorting and export? A physical model of cisterna morphology led us to propose that sphingomyelin (SM) metabolism at the trans-Golgi membranes in mammalian cells essentially controls the structural features of a Golgi cisterna by regulating its association to curvature-generating proteins. An experimental test of this hypothesis revealed that affecting SM homeostasis converted flat cisternae into highly curled membranes with a concomitant dissociation of membrane curvature-generating proteins...
May 13, 2017: ELife
https://www.readbyqxmd.com/read/28500324/labeling-extracellular-vesicles-for-nanoscale-flow-cytometry
#15
Aizea Morales-Kastresana, Bill Telford, Thomas A Musich, Katherine McKinnon, Cassandra Clayborne, Zach Braig, Ari Rosner, Thorsten Demberg, Dionysios C Watson, Tatiana S Karpova, Gordon J Freeman, Rosemarie H DeKruyff, George N Pavlakis, Masaki Terabe, Marjorie Robert-Guroff, Jay A Berzofsky, Jennifer C Jones
Extracellular vesicles (EVs), including exosomes and microvesicles, are 30-800 nm vesicles that are released by most cell types, as biological packages for intercellular communication. Their importance in cancer and inflammation makes EVs and their cargo promising biomarkers of disease and cell-free therapeutic agents. Emerging high-resolution cytometric methods have created a pressing need for efficient fluorescent labeling procedures to visualize and detect EVs. Suitable labels must be bright enough for one EV to be detected without the generation of label-associated artifacts...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28500182/upr-transducer-bbf2h7-allows-export-of-type-ii-collagen-in-a-cargo-and-developmental-stage-specific-manner
#16
Tokiro Ishikawa, Takuya Toyama, Yuki Nakamura, Kentaro Tamada, Hitomi Shimizu, Satoshi Ninagawa, Tetsuya Okada, Yasuhiro Kamei, Tomoko Ishikawa-Fujiwara, Takeshi Todo, Eriko Aoyama, Masaharu Takigawa, Akihiro Harada, Kazutoshi Mori
The unfolded protein response (UPR) handles unfolded/misfolded proteins accumulated in the endoplasmic reticulum (ER). However, it is unclear how vertebrates correctly use the total of ten UPR transducers. We have found that ER stress occurs physiologically during early embryonic development in medaka fish and that the smooth alignment of notochord cells requires ATF6 as a UPR transducer, which induces ER chaperones for folding of type VIII (short-chain) collagen. After secretion of hedgehog for tissue patterning, notochord cells differentiate into sheath cells, which synthesize type II collagen...
May 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28499870/fibronectin-on-extracellular-vesicles-from-microvascular-endothelial-cells-is-involved-in-the-vesicle-uptake-into-oligodendrocyte-precursor-cells
#17
Sho Osawa, Masashi Kurachi, Hanako Yamamoto, Yuhei Yoshimoto, Yasuki Ishizaki
We previously reported transplantation of brain microvascular endothelial cells (MVECs) into cerebral white matter infarction model improved the animal's behavioral outcome by increasing the number of oligodendrocyte precursor cells (OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted survival and proliferation of OPCs in vitro. In this study, we investigated the mechanism how EVs derived from MVECs contribute to OPC survival and proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay revealed fibronectin was abundant on the surface of EVs from MVECs...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28497202/exosomes-and-their-application-in-biomedical-field-difficulties-and-advantages
#18
REVIEW
Jafar Rezaie, Saeed Ajezi, Çığır Biray Avci, Mohammad Karimipour, Mohammad Hossein Geranmayeh, Alireza Nourazarian, Emel Sokullu, Aysa Rezabakhsh, Reza Rahbarghazi
The science of gene therapy has experienced a controversial history. At first, the initial concept that various disorders become curable by gene transferring was very exciting and challengeable. However, the problems and difficulties related to emerging techniques and unwanted side effects seen in some patients who have undergone gene therapy make some questions against the safety of novel molecular medicine approach. In line with this statement, discovery and developing a good bio-vector possessing low toxicity and high efficiency rate are the most important issues in gene therapy field...
May 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28495747/reticulon-3-dependent-er-pm-contact-sites-control-egfr-nonclathrin-endocytosis
#19
Giusi Caldieri, Elisa Barbieri, Gilda Nappo, Andrea Raimondi, Massimo Bonora, Alexia Conte, Lisette G G C Verhoef, Stefano Confalonieri, Maria Grazia Malabarba, Fabrizio Bianchi, Alessandro Cuomo, Tiziana Bonaldi, Emanuele Martini, Davide Mazza, Paolo Pinton, Carlo Tacchetti, Simona Polo, Pier Paolo Di Fiore, Sara Sigismund
The integration of endocytic routes is critical to regulate receptor signaling. A nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor (EGFR) is activated at high ligand concentrations and targets receptors to degradation, attenuating signaling. Here we performed an unbiased molecular characterization of EGFR-NCE. We identified NCE-specific regulators, including the endoplasmic reticulum (ER)-resident protein reticulon 3 (RTN3) and a specific cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)-ER contact sites that were required for the formation and/or maturation of NCE invaginations...
May 12, 2017: Science
https://www.readbyqxmd.com/read/28491287/linking-cortical-microtubule-attachment-and-exocytosis
#20
REVIEW
Ivar Noordstra, Anna Akhmanova
Exocytosis is a fundamental cellular process whereby secreted molecules are packaged into vesicles that move along cytoskeletal filaments and fuse with the plasma membrane. To function optimally, cells are strongly dependent on precisely controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve as major tracks for vesicle transport by motor proteins, and thus microtubule organization is important for targeted delivery of secretory carriers. Over the years, multiple microtubule-associated and cortical proteins have been discovered that facilitate the interaction between the microtubule plus ends and the cell cortex...
2017: F1000Research
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