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https://www.readbyqxmd.com/read/29342287/to-the-brain-and-back-migratory-paths-of-dendritic-cells-in-multiple-sclerosis
#1
Maxime De Laere, Zwi N Berneman, Nathalie Cools
Migration of dendritic cells (DC) to the central nervous system (CNS) is a critical event in the pathogenesis of multiple sclerosis (MS). While up until now, research has mainly focused on the transmigration of DC through the blood-brain barrier, experimental evidence points out that also the choroid plexus and meningeal vessels represent important gateways to the CNS, especially in early disease stages. On the other hand, DC can exit the CNS to maintain immunological tolerance to patterns expressed in the CNS, a process that is perturbed in MS...
January 12, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29341790/postnatal-tendon-growth-and-remodeling-requires-platelet-derived-growth-factor-receptor-signaling
#2
Kristoffer B Sugg, James F Markworth, Nathaniel P Disser, Andrew M Rizzi, Jeffrey R Talarek, Dylan C Sarver, Susan V Brooks, Christopher L Mendias
Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response...
December 13, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29339490/structural-basis-of-sterol-recognition-and-nonvesicular-transport-by-lipid-transfer-proteins-anchored-at-membrane-contact-sites
#3
Junsen Tong, Mohammad Kawsar Manik, Young Jun Im
Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339412/the-sequence-specific-peptide-binding-activity-of-the-protein-sulfide-isomerase-agr2-directs-its-stable-binding-to-the-oncogenic-receptor-epcam
#4
M Aiman Mohtar, Lenka Hernychova, Robert O'Neill, Melanie Lawrence, Euan Murray, Borek Vojtesek, Ted R Hupp
AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide isomerase. AGR2 protein has a relatively unique property for a chaperone in that it can bind sequence-specifically to a specific peptide motif (TTIYY). A synthetic TTIYY-containing peptide column was used to affinity-purify AGR2 from crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen-deuterium exchange mass spectrometry localized the dominant region in AGR2 that interacts with the TTIYY peptide to within a structural loop from amino acids 131-135 (VDPSL)...
January 16, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29339384/a-novel-inhibitor-of-the-lolcde-abc-transporter-essential-for-lipoprotein-trafficking-in-gram-negative-bacteria
#5
Nicholas N Nickerson, Christine C Jao, Yiming Xu, John Quinn, Elizabeth Skippington, Mary Kate Alexander, Anh Miu, Nicholas Skelton, Jessica V Hankins, Michael S Lopez, Christopher M Koth, Steven Rutherford, Mireille Nishiyama
The outer membrane is an essential structural component of Gram-negative bacteria that is composed of lipoproteins, lipopolysaccharides, phospholipids, and integral β-barrel membrane proteins. A dedicated machinery, called the Lol system, ensures proper trafficking of lipoproteins from the inner to the outer membrane. The LolCDE ABC transporter is the inner membrane component, which is essential for bacterial viability. Here, we report a novel pyrrolopyrimidinedione compound, G0507, which was identified in a phenotypic screen for inhibitors of E...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29338048/ebola-virus-requires-a-host-scramblase-for-externalization-of-phosphatidylserine-on-the-surface-of-viral-particles
#6
Asuka Nanbo, Junki Maruyama, Masaki Imai, Michiko Ujie, Yoichiro Fujioka, Shinya Nishide, Ayato Takada, Yusuke Ohba, Yoshihiro Kawaoka
Cell surface receptors for phosphatidylserine contribute to the entry of Ebola virus (EBOV) particles, indicating that the presence of phosphatidylserine in the envelope of EBOV is important for the internalization of EBOV particles. Phosphatidylserine is typically distributed in the inner layer of the plasma membrane in normal cells. Progeny virions bud from the plasma membrane of infected cells, suggesting that phosphatidylserine is likely flipped to the outer leaflet of the plasma membrane in infected cells for EBOV virions to acquire it...
January 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29337303/pd-l1-on-host-cells-is-essential-for-pd-l1-blockade-mediated-tumor-regression
#7
Haidong Tang, Yong Liang, Robert A Anders, Janis M Taube, Xiangyan Qiu, Aditi Mulgaonkar, Xin Liu, Susan M Harrington, Jingya Guo, Yangchun Xin, Yahong Xiong, Kien Nham, William Silvers, Guiyang Hao, Xiankai Sun, Mingyi Chen, Raquibul Hannan, Jian Qiao, Haidong Dong, Hua Peng, Yang-Xin Fu
Programmed death-ligand 1 (PD-L1) expression on tumor cells is essential for T cell impairment, and PD-L1 blockade therapy has shown unprecedented durable responses in several clinical studies. Although higher expression of PD-L1 on tumor cells is associated with a better immune response after Ab blockade, some PD-L1-negative patients also respond to this therapy. In the current study, we explored whether PD-L1 on tumor or host cells was essential for anti-PD-L1-mediated therapy in 2 different murine tumor models...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337241/differential-effects-of-alzheimer-s-disease-a%C3%AE-40-and-42-on-endocytosis-and-intraneuronal-trafficking
#8
Rajesh S Omtri, Kevin Thompson, Xiojia Tang, Chaitanya C Gali, Ute Panzenboeck, Michael W Davidson, Krishna R Kalari, Karunya K Kadimalla
Anomalous neuronal accumulation of Aβ peptides was shown to affect synaptic transmission and contribute to neurodegeneration in Alzheimer's disease (AD) brain. Neuronal cells internalize amyloid beta (Aβ) peptides from the brain extracellular space even under normal physiological conditions, and these endocytotic pathways go awry during AD progression. We hypothesized that exposure to toxic Aβ species accumulating in AD brain contribute to perturbations in neuronal endocytosis. We have shown substantial down-regulation of KEGG endocytotic pathway genes in AD patient brain regions that accumulate Aβ compared to those in non-demented individuals...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29337164/identification-of-novel-antivirals-inhibiting-recognition-of-venezuelan-equine-encephalitis-virus-capsid-protein-by-the-importin-%C3%AE-%C3%AE-1-heterodimer-through-high-throughput-screening
#9
David R Thomas, Lindsay Lundberg, Chelsea Pinkham, Sharon Shechter, Aaron Debono, Jonathan Baell, Kylie M Wagstaff, Caroline A Hick, Kylene Kehn-Hall, David A Jans
Although the alphavirus Venezuelan equine encephalitis virus (VEEV) has been the cause of multiple outbreaks resulting in extensive human and equine mortality and morbidity, there are currently no anti-VEEV therapeutics available. VEEV pathogenicity is largely dependent on targeting of the viral capsid protein (CP) to the host cell nucleus through the nuclear transporting importin (Imp) α/β1 heterodimer. Here we perform a high-throughput screen, combined with nested counterscreens to identify small molecules able to inhibit the Impα/β1:CP interaction for the first time...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29336668/safety-and-biodistribution-of-sulfated-archaeal-glycolipid-archaeosomes-as-vaccine-adjuvants
#10
Bassel Akache, Felicity C Stark, Umar Iqbal, Wangxue Chen, Yimei Jia, Lakshmi Krishnan, Michael J McCluskie
Archaeosomes are liposomes comprised of ether lipids derived from various archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high pH and thermal stability. As adjuvants, archaeosomes can induce robust, long-lasting humoral and cell-mediated immune responses and enhance protection in murine models of infectious disease and cancer. Archaeosomes constituted with total polar lipids (TPL) of various archaea are relatively complex, comprising >10 different lipid compounds. Archaeosomes can be constituted with semi-synthetic glycerolipids built on ether-linked isoprenoid phytanyl cores with varied synthetic glycol- and amino-head groups...
January 16, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29336505/signalling-transduction-events-involved-in-agonist-induced-pge2-ep4-receptor-externalization-in-cultured-rat-dorsal-root-ganglion-neurons
#11
W Ma, B St-Jacques
BACKGROUND: Prostaglandin E2 (PGE2) enriched in inflamed tissues contributes to chronic pain by sensitizing nociceptive dorsal root ganglion (DRG) neurons (nociceptors). Of four PGE2 receptors (EP1-4), EP4 plays a major role in PGE2-induced nociceptor sensitization. We have previously reported that PGE2 or EP4 agonists stimulated EP4 externalization in cultured DRG neurons and this event contributes to nociceptor sensitization. However, the signalling transduction events governing this event remain unknown...
January 16, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29336451/the-uptake-retention-and-clearance-of-drug-loaded-dendrimer-nanoparticles-in-astrocytes-electrophysiological-quantification
#12
Helena H Chowdhury, Susana R Cerqueira, Nuno Sousa, Joaquim M Oliveira, Rui L Reis, Robert Zorec
Nanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with a lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. The cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high-resolution membrane capacitance measurements...
January 16, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29336357/distinctive-roles-of-rac1-and-rab29-in-lrrk2-mediatedmembrane-trafficking-and-neurite-outgrowth
#13
Min Feng, Xin Hu, Na Li, Fan Hu, Fei Chang, Hong-Fei Xu, Yong-Jian Liu
Parkinson's disease (PD) associated leucine-rich repeat kinase 2 (LRRK2) mutants have shown pathogenic effects on variety of subcellular processes.Two small GTPases Rac1 and Rab29 have been indicated as possible downstream effectors participating in LRRK2 signaling but their detail mechanisms remain unclear. In this study, we have used biochemical and cell biology approaches to address whether two GTPases interact with LRRK2 and hence function differently in LRRK2 mediated pathogenesis.Here we show thatRac1 and Rab29 specifically interact with LRRK2with higher affinity for Rab29and with different preference in functional domain binding...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29335590/direct-observation-of-the-effects-of-cellulose-synthesis-inhibitors-using-live-cell-imaging-of-cellulose-synthase-cesa-in-physcomitrella-patens
#14
Mai L Tran, Thomas W McCarthy, Hao Sun, Shu-Zon Wu, Joanna H Norris, Magdalena Bezanilla, Luis Vidali, Charles T Anderson, Alison W Roberts
Results from live cell imaging of fluorescently tagged Cellulose Synthase (CESA) proteins in Cellulose Synthesis Complexes (CSCs) have enhanced our understanding of cellulose biosynthesis, including the mechanisms of action of cellulose synthesis inhibitors. However, this method has been applied only in Arabidopsis thaliana and Brachypodium distachyon thus far. Results from freeze fracture electron microscopy of protonemal filaments of the moss Funaria hygrometrica indicate that a cellulose synthesis inhibitor, 2,6-dichlorobenzonitrile (DCB), fragments CSCs and clears them from the plasma membrane...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334180/nitric-oxide-dependent-degradation-of-polyethylene-glycol-modified-single-walled-carbon-nanotubes-implications-for-intra-articular-delivery
#15
Kunal Bhattacharya, Cristiano Sacchetti, Pedro M Costa, Jens Sommertune, Birgit D Brandner, Andrea Magrini, Nicola Rosato, Nunzio Bottini, Massimo Bottini, Bengt Fadeel
Polyethylene glycol (PEG)-modified carbon nanotubes have been successfully employed for intra-articular delivery in mice without systemic or local toxicity. However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG-modified single-walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra-articular injection into the knee-joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee-joint and are found to either egress from the synovial cavity or undergo biodegradation over a period of 3 weeks...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29332538/role-of-infiltrating-monocytes-in-the-development-of-radiation-induced-pulmonary-fibrosis
#16
Angela M Groves, Carl J Johnston, Jacqueline P Williams, Jacob N Finkelstein
Lung exposure to radiation induces an injury response that includes the release of cytokines and chemotactic mediators; these signals recruit immune cells to execute inflammatory and wound-healing processes. However, radiation alters the pulmonary microenvironment, dysregulating the immune responses and preventing a return to homeostasis. Importantly, dysregulation is observed as a chronic inflammation, which can progress into pneumonitis and promote pulmonary fibrosis; inflammatory monocytes, which are bone marrow derived and express CCR2, have been shown to migrate into the lung after radiation exposure...
January 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29331806/unifying-in%C3%A2-vitro-and-in%C3%A2-vivo-ivt-mrna-expression-discrepancies-in-skeletal-muscle-via-mechanotransduction
#17
Sushma M Bhosle, Kristin H Loomis, Jonathan L Kirschman, Emmeline L Blanchard, Daryll A Vanover, Chiara Zurla, Damien Habrant, Darin Edwards, Patrick Baumhof, Bruno Pitard, Philip J Santangelo
The translational efficiency of an in vitro transcribed (IVT) mRNA was measured upon delivery to primary skeletal muscle cells and to a mouse model system, towards the development of a predictive in vitro assay for the screening and validation of intramuscular mRNA-based vaccines. When IVT mRNA was delivered either naked or complexed with novel aminoglycoside-based delivery vehicles, significant differences in protein expression in vitro and in vivo were observed. We hypothesized that this previously anticipated discrepancy was due to differences in the mechanism of IVT mRNA endosomal entry and release following delivery...
January 6, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331581/identification-and-characterization-of-arginine-finger-like-motifs-and-endosome-lysosome-basolateral-sorting-signals-within-ectopically-expressed-cira-a-coxiella-burnetii-type-iv-secreted-effector-protein
#18
Mary M Weber, Robert Faris, Erin J van Schaik, James E Samuel
Coxiella burnetii is an obligate intracellular pathogen that replicates in an endolysosome-like compartment termed the Coxiella-containing vacuole (CCV). Formation of this unique replicative niche requires delivery of bacterial effector proteins into the host cytosol where they mediate crucial interactions with the host. We previously identified an essential Dot/Icm effector, CirA that is required for intracellular replication and CCV formation. Furthermore, CirA was shown to stimulate the GTPase activity of RhoA in vitro...
January 10, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29331508/compartmentalized-crosstalk-of-cftr-and-tmem16a-ano1-through-epac1-and-adcy1
#19
Joana Lérias, Madalena Pinto, Roberta Benedetto, Rainer Schreiber, Margarida Amaral, Massimo Aureli, Karl Kunzelmann
Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29331069/cellular-membrane-trafficking-machineries-utilized-by-the-hepatitis-viruses
#20
REVIEW
Jun Inoue, Masashi Ninomiya, Tooru Shimosegawa, Mark A McNiven
While the life cycles of hepatitis viruses (hepatitis A, B, C, D, and E viruses) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses 'hijack' the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are well known as a leading cause of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating HCV patients have recently been made, patients with HBV continue to require life-long treatment, which makes a thorough understanding of the HBV life cycle essential...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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