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https://www.readbyqxmd.com/read/28812547/lung-epithelial-cells-therapeutically-inducible-effectors-of-antimicrobial-defense
#1
REVIEW
M M Leiva-Juárez, J K Kolls, S E Evans
Lung epithelial cells are increasingly recognized to be active effectors of microbial defense, contributing to both innate and adaptive immune function in the lower respiratory tract. As immune sentinels, lung epithelial cells detect diverse pathogens through an ample repertoire of membrane-bound, endosomal, and cytosolic pattern-recognition receptors (PRRs). The highly plastic epithelial barrier responds to detected threats via modulation of paracellular flux, intercellular communications, mucin production, and periciliary fluid composition...
August 16, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28811263/the-role-of-escrt-during-development-and-functioning-of-the-nervous-system
#2
REVIEW
Rémy Sadoul, Marine H Laporte, Romain Chassefeyre, Yves Goldberg, Christine Chatellard, Fiona J Hemming, Sandrine Fraboulet
The endosomal sorting complex required for transport (ESCRT) is made of subcomplexes (ESCRT I-III), crucial to membrane remodelling at endosomes, nuclear envelope and cell surface. ESCRT-III shapes membranes and in most cases cooperates with the ATPase VPS4 to mediate fission of membrane necks from the inside. The first ESCRT complexes mainly serve to catalyse the formation of ESCRT-III but can be bypassed by accessory proteins like the Alg-2 interacting protein-X (ALIX). In the nervous system, ALIX/ESCRT controls the survival of embryonic neural progenitors and later on the outgrowth and pruning of axons and dendrites, all necessary steps to establish a functional brain...
August 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28809539/polymersomes-with-endosomal-ph-induced-vesicle-to-micelle-morphology-transition-and-a-potential-application-for-controlled-doxorubicin-delivery
#3
Turgay Yildirim, Anja Traeger, Pelin Sungur, Stephanie Hoeppener, Carolin Kellner, Ilknur Yildirim, David Pretzel, Stephanie Schubert, Ulrich S Schubert
A series of pH responsive block copolymers were synthesized via the reversible addition-fragmentation chain transfer (RAFT) polymerization of 3,4-dihydro-2H-pyran (DHP) protected 2-hydroxyethyl methacrylate (HEMA) (2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl methacrylate (THP-HEMA)) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) using p(THP-HEMA) as a macro chain transfer agent (mCTA). The degree of polymerization (DP) of the p(THP-HEMA) block was fixed to 35, whereas the DP of the p(DMAEMA) block was systematically varied from 21 to 50...
August 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28809098/interfacially-engineered-pyridinium-pseudo-gemini-surfactants-as-versatile-and-efficient-supramolecular-delivery-systems-for-dna-sirna-and-mrna
#4
Uttam Satyal, Bogdan Draghici, Lisa L Dragic, Qiangnan Zhang, Kyle Norris, Muniswamy Madesh, Eugen Brailoiu, Marc A Ilies
The article presents the synthesis, self-assembling and biological activity as transfection agents for pDNA, siRNA and mRNA of novel pyridinium pseudo-gemini surfactants, interfacially-engineered from the most efficient gemini surfactants and lipids generated in our amphiphile research program. Formulation of novel amphiphiles in water revealed supramolecular properties very similar to gemini surfactants, despite their lipid-like charge/mass ratio. This dual character was found to also enhance endosomal escape and significantly increase the transfection efficiency...
August 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28808191/shunts-channels-and-lipoprotein-endosomal-traffic-a-new-model-of-cholesterol-homeostasis-in-the-hepatocyte
#5
Robert Scott Kiss, Allan Sniderman
The liver directs cholesterol metabolism in the organism. All the major fluxes of cholesterol within the body involve the liver: dietary cholesterol is directed to the liver; cholesterol from peripheral cells goes to the liver; the liver is a major site of cholesterol synthesis for the organism; cholesterol is secreted from the liver within the bile, within apoB lipoproteins and translocated to nascent HDL. The conventional model of cholesterol homeostasis posits that cholesterol from any source enters a common, rapidly exchangeable pool within the cell, which is in equilibrium with a regulatory pool...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808134/vps9a-activates-the-rab5-gtpase-ara7-to-confer-distinct-pre-and-post-invasive-plant-innate-immunity
#6
Mads Eggert Nielsen, Gerd Jürgens, Hans Thordal-Christensen
Plant innate immunity can effectively prevent the proliferation of filamentous pathogens. Papilla formation at the site of attack is essential for pre-invasive immunity; in post-invasive immunity the encasement of pathogen structures inside host cells can hamper disease. Whereas papillae are highly dependent on transcytosis of premade material, little is known about encasement formation. Here we show that endosome-associated VPS9a, the conserved guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against a non-adapted powdery mildew fungus (Blumeria graminis f...
August 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28807885/biogenesis-and-function-of-escrt-dependent-extracellular-vesicles
#7
REVIEW
Thomas Juan, Maximilian Fürthauer
From bacteria to humans, cells secrete a large variety of membrane-bound extracellular vesicles. Only relatively recently has it however started to become clear that the exovesicular transport of proteins and RNAs is important for normal physiology and numerous pathological conditions. Extracellular vesicles can be formed through the release of the intralumenal vesicles of multivesicular endosomes as so-called exosomes, or through direct, ectosomal, budding from the cell surface. Through their ability to promote the bending of membranes away from the cytoplasm, the components of the Endosomal Sorting Complex Required for Transport (ESCRT) have been implicated in both exo- and ectosomal biogenesis...
August 11, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28807884/escrt-and-autophagies-endosomal-functions-and-beyond
#8
REVIEW
Christophe Lefebvre, Renaud Legouis, Emmanuel Culetto
ESCRT (endosomal sorting complex required for transport) machinery has been initially identified for its role during endocytosis, which allows membrane proteins and lipids to be degraded in the lysosome. ESCRT function is required to form intraluminal vesicles permitting internalization of cytosolic components or membrane embedded cargoes and promoting endosome maturation. ESCRT machinery also contributes to multiple key cell mechanisms in which it reshapes membranes. In addition, ESCRT actively participates in different types of autophagy processes for degrading cytosolic components, such as endosomal microautophagy and macroautophagy...
August 11, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28806752/the-escrt-iii-pathway-facilitates-cardiomyocyte-release-of-cbin1-containing-microparticles
#9
Bing Xu, Ying Fu, Yan Liu, Sosse Agvanian, Robert C Wirka, Rachel Baum, Kang Zhou, Robin M Shaw, TingTing Hong
Microparticles (MPs) are cell-cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold- generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus...
August 14, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#10
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28804598/a-rigorous-method-to-enrich-for-exosomes-from-brain-tissue
#11
Laura J Vella, Benjamin J Scicluna, Lesley Cheng, Emma G Bawden, Colin L Masters, Ching-Seng Ang, Nicholas Willamson, Catriona McLean, Kevin J Barnham, Andrew F Hill
Extracellular vesicles, including exosomes, are released by all cells, including those of the nervous system. Capable of delivering lipid, protein and nucleic acids to both nearby and distal cells, exosomes have been hypothesized to play a role in progression of many diseases of the nervous system. To date, most analyses on the role of these vesicles in the healthy and diseased state have relied on studying vesicles from in vitro sources, such as conditioned cell culture media, or body fluids. Here we have taken a critical approach to the enrichment and characterization of exosomes from human frontal cortex...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28802715/elucidating-virus-entry-using-a-tetracysteine-tagged-virus
#12
REVIEW
Bjorn-Patrick Mohl, Polly Roy
Fluorescent tags constitute an invaluable tool in facilitating a deeper understanding of the mechanistic processes governing virus-host interactions. However, when selecting a fluorescent tag for in vivo imaging of cells, a number of parameters and aspects must be considered. These include whether the tag may affect and interfere with protein conformation or localization, cell toxicity, spectral overlap, photo-stability and background. Cumulatively, these constitute challenges to be overcome. Bluetongue virus (BTV), a member of the Orbivirus genus in the Reoviridae family, is a non-enveloped virus that is comprised of two architecturally complex capsids...
August 9, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28802408/down-regulation-of-malate-synthase-in-mycobacterium-tuberculosis-h37ra-leads-to-reduced-stress-tolerance-persistence-and-survival-in-macrophages
#13
Kumar Sachin Singh, Rishabh Sharma, Deepa Keshari, Nirbhay Singh, Sudheer Kumar Singh
Malate synthase is a condensing enzyme responsible for conversion of glyoxylate to malate in the presence of acetyl-CoA. This reaction helps in bypassing the TCA cycle reactions involving carbon loss and leads to diverting some of the carbon skeletons to gluconeogenic events while rest can continue to provide TCA cycle intermediates. Malate synthase (GlcB) is encoded by MRA_1848 of Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a knockdown (KD) Mtb-Ra strain by down-regulating GlcB. The survival studies suggested increased susceptibility to oxidative and nitrosative stress as well as to rifampicin...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802158/lipidation-increases-antiviral-activities-of-coronavirus-fusion-inhibiting-peptides
#14
Jung-Eun Park, Tom Gallagher
Coronaviruses (CoVs) can cause life-threatening respiratory diseases. Their infectious entry requires viral spike (S) proteins, which attach to cell receptors, undergo proteolytic cleavage, and then refold in a process that catalyzes virus-cell membrane fusion. Fusion-inhibiting peptides bind to S proteins, interfere with refolding, and prevent infection. Here we conjugated fusion-inhibiting peptides to various lipids, expecting this to secure peptides onto cell membranes and thereby increase antiviral potencies...
August 9, 2017: Virology
https://www.readbyqxmd.com/read/28800156/quantitative-dextran-trafficking-to-the-coxiella-burnetii-parasitophorous-vacuole
#15
Seth Winfree, Stacey D Gilk
The gram-negative bacterium Coxiella burnetii causes human Q fever, a disease characterized by a debilitating flu-like illness in acute cases and endocarditis in chronic patients. An obligate intracellular pathogen, Coxiella burnetii survives within a large, lysosome-like vacuole inside the host cell. A unique feature of the Coxiella parasitophorous vacuole (PV) is high levels of fusion with the host endocytic pathway, with PV-endosome fusion critical for Coxiella survival within the host cell. This unit describes quantitating PV-endosome fusion by measuring delivery of the fluid phase endosome marker dextran to the PV using live cell imaging...
August 11, 2017: Current Protocols in Microbiology
https://www.readbyqxmd.com/read/28799168/small-scaffolds-big-potential-developing-miniature-proteins-as-therapeutic-agents
#16
Justin M Holub
Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs...
August 10, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28799085/dimerization-leads-to-changes-in-app-amyloid-precursor-protein-trafficking-mediated-by-lrp1-and-sorla
#17
Simone Eggert, A C Gonzalez, C Thomas, S Schilling, S M Schwarz, C Tischer, V Adam, P Strecker, V Schmidt, T E Willnow, G Hermey, C U Pietrzik, E H Koo, Stefan Kins
Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization...
August 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28798148/ubiquitination-of-basal-vegfr2-regulates-signal-transduction-and-endothelial-function
#18
Gina A Smith, Gareth W Fearnley, Izma Abdul-Zani, Stephen B Wheatcroft, Darren C Tomlinson, Michael A Harrison, Sreenivasan Ponnambalam
Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulates signal transduction and angiogenesis but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated response by endothelial cells...
August 10, 2017: Biology Open
https://www.readbyqxmd.com/read/28797971/modified-pamam-dendrimer-with-4-carbomethoxypyrrolidone-surface-groups-its-uptake-efflux-and-location-in-a-cell
#19
Anna Janaszewska, Maciej Studzian, Johannes F Petersen, Mario Ficker, Valentina Paolucci, Jørn B Christensen, Donald A Tomalia, Barbara Klajnert-Maculewicz
Traditional amine terminated PAMAM dendrimers may be readily surface engineered by a facile one-pot conversion with dialkyl itaconate esters into 4-carbomethoxypyrrolidone terminated PAMAM (G=0-4) dendrimers. These terminated dendrimers are uniquely characterized by exhibiting blue fluorescence emissions (λexc=370nm, λmaxem=440nm). Thanks to this property they can be directly analyzed by confocal microscopy and flow cytometry without additional fluorescence labeling, treatment of dendrimers with chemicals or adjusting pH...
July 29, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28797838/escrt-dependent-cargo-sorting-at-multivesicular-endosomes
#20
REVIEW
E B Frankel, Anjon Audhya
The endosomal sorting complex required for transport (ESCRT) machinery is composed of five multi-subunit protein complexes, which act cooperatively at specialized endosomes to facilitate the movement of specific cargoes from the limiting membrane into vesicles that bud into the endosome lumen. Over the past decade, numerous proteins, lipids, and RNAs have been shown to be incorporated into intralumenal vesicles (ILVs), but the mechanisms by which these unique cargoes are captured are only now becoming better understood...
August 7, 2017: Seminars in Cell & Developmental Biology
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