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https://www.readbyqxmd.com/read/28101591/functions-of-cancer-derived-extracellular-vesicles-in-immunosuppression
#1
REVIEW
Liliana Czernek, Markus Düchler
Extracellular vesicles, including exosomes, constitute an important element of intercellular communication by carrying a variety of molecules from producer to target cells. The transport of mRNA and miRNA can directly modulate gene expression in the target cells. The miRNA content in exosomes is characteristic for the cell from which the vesicles were derived enabling the usage of exosomes as biomarkers for the diagnosis various diseases, including cancer. Cancer-derived exosomes support the survival and progression of tumors in many ways and also contribute to the neutralization of the anti-cancer immune response...
January 18, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28101527/regulation-of-physical-microglia-neuron-interactions-by-fractalkine-signaling-after-status-epilepticus
#2
Ukpong B Eyo, Jiyun Peng, Madhuvika Murugan, Mingshu Mo, Almin Lalani, Ping Xie, Pingyi Xu, David J Margolis, Long-Jun Wu
Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28101520/an-observational-study-of-alemtuzumab-following-fingolimod-for-multiple-sclerosis
#3
Mark Willis, Owen Pearson, Zsolt Illes, Tobias Sejbaek, Christian Nielsen, Martin Duddy, Kate Petheram, Caspar van Munster, Joep Killestein, Clas Malmeström, Emma Tallantyre, Neil Robertson
OBJECTIVE: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. METHODS: Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers. RESULTS: Nine patients were identified...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28100648/multi-scale-structural-analysis-of-plant-er-pm-contact-sites
#4
Heather E McFarlane, Eun Kyoung Lee, Laura S van Bezouwen, Bradford Ross, Abel Rosado, A Lacey Samuels
Membrane contact sites (MCS) are recognized across eukaryotic systems as important nanostructures. Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (EPCS) are involved in excitation-contraction coupling, signalling, and plant responses to stress. In this report, we perform a multi-scale structural analysis of Arabidopsis EPCS that combine live cell imaging, quantitative transmission electron microscopy (TEM), and electron tomography over a developmental gradient. To place EPCS in the context of the entire cortical ER, we examined GFP-HDEL in living cells over a developmental gradient, then SYT1-GFP was used as a specific marker of EPCS...
January 18, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28100644/multicellular-hypothesis-for-the-pathogenesis-of-alzheimer-s-disease
#5
Edward J Goetzl, Bruce L Miller
Extensive abnormal interactions among microglia, astrocytes, and neurons of the CNS have been observed in proteinopathic neurodegenerative dementias of the elderly. These multicellular interactions are initiated by insoluble tangles of phosphorylated tau protein and plaques of amyloid peptides. Most research has focused on these neurotoxic proteins, but much less is known about the pathogenic roles of the responding resident and recruited neural cells. Principal interactions among the major 3 sets of CNS cells are herein considered at several levels in relation to cellular phenotypic alterations, mechanisms of cellular communication, and extent of involvement in the pathogenesis of Alzheimer's disease and related proteinopathic dementias...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28100454/gene-therapy-targeting-oligodendrocytes-provides-therapeutic-benefit-in-a-leukodystrophy-model
#6
Elena Georgiou, Kyriaki Sidiropoulou, Jan Richter, Christos Papaneophytou, Irene Sargiannidou, Alexia Kagiava, Georg von Jonquieres, Christina Christodoulou, Matthias Klugmann, Kleopas A Kleopa
Pelizaeus-Merzbacher-like disease or hypomyelinating leukodystrophy-2 is an autosomal recessively inherited leukodystrophy with childhood onset resulting from mutations in the gene encoding the gap junction protein connexin 47 (Cx47, encoded by GJC2). Cx47 is expressed specifically in oligodendrocytes and is crucial for gap junctional communication throughout the central nervous system. Previous studies confirmed that a cell autonomous loss-of-function mechanism underlies hypomyelinating leukodystrophy-2 and that transgenic oligodendrocyte-specific expression of another connexin, Cx32 (GJB1), can restore gap junctions in oligodendrocytes to achieve correction of the pathology in a disease model...
January 18, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28100105/inventing-a-co-axial-atomic-resolution-patch-clamp-to-study-a-single-resonating-protein-complex-and-ultra-low-power-communication-deep-inside-a-living-neuron-cell
#7
Subrata Ghosh, Satyajit Sahu, Lokesh Agrawal, Takashi Shiga, Anirban Bandyopadhyay
To read the signals of single molecules in vitro on a surface, or inside a living cell or organ, we introduce a coaxial atom tip (coat) and a coaxial atomic patch clamp (COAPAP). The metal-insulator-metal cavity of these probes extends to the atomic scale (0.1[Formula: see text]nm), it eliminates the cellular or environmental noise with a S/N ratio 10(5). Five ac signals are simultaneously applied during a measurement by COAT and COAPAP to shield a true signal under environmental noise in five unique ways. The electromagnetic drive in the triaxial atomic tips is specifically designed to sense anharmonic vibrational and transmission signals for any systems between 0...
January 18, 2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/28099413/communication-between-viruses-guides-lysis-lysogeny-decisions
#8
Zohar Erez, Ida Steinberger-Levy, Maya Shamir, Shany Doron, Avigail Stokar-Avihail, Yoav Peleg, Sarah Melamed, Azita Leavitt, Alon Savidor, Shira Albeck, Gil Amitai, Rotem Sorek
Temperate viruses can become dormant in their host cells, a process called lysogeny. In every infection, such viruses decide between the lytic and the lysogenic cycles, that is, whether to replicate and lyse their host or to lysogenize and keep the host viable. Here we show that viruses (phages) of the SPbeta group use a small-molecule communication system to coordinate lysis-lysogeny decisions. During infection of its Bacillus host cell, the phage produces a six amino-acids-long communication peptide that is released into the medium...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28099001/conformational-dynamics-in-penicillin-binding-protein-2a-of-methicillin-resistant-staphylococcus-aureus-allosteric-communication-network-and-enablement-of-catalysis
#9
Kiran V Mahasenan, Rafael Molina, Renee Bouley, Maria T Batuecas, Jed F Fisher, Juan A Hermoso, Mayland Chang, Shahriar Mobashery
The mechanism of the β-lactam antibacterials is the functionally irreversible acylation of the enzymes that catalyze the cross-linking steps in the biosynthesis of their peptidoglycan cell wall. The Gram-positive pathogen Staphylococcus aureus uses one primary resistance mechanism. An enzyme, called penicillin-binding protein 2a (PBP2a), is brought into this biosynthetic pathway to complete the cross-linking. PBP2a effectively discriminates against the β-lactam antibiotics as potential inhibitors, and in favor of the peptidoglycan substrate...
January 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28098880/the-role-of-gap-junctions-in-inflammatory-and-neoplastic-disorders-review
#10
Pui Wong, Victoria Laxton, Saurabh Srivastava, Yin Wah Fiona Chan, Gary Tse
Gap junctions are intercellular channels made of connexin proteins, mediating both electrical and biochemical signals between cells. The ability of gap junction proteins to regulate immune responses, cell proliferation, migration, apoptosis and carcinogenesis makes them attractive therapeutic targets for treating inflammatory and neoplastic disorders in different organ systems. Alterations in gap junction profile and expression levels are observed in hyperproliferative skin disorders, lymphatic vessel diseases, inflammatory lung diseases, liver injury and neoplastic disorders...
January 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28098821/tumor-microenvironment-modulation-via-gold-nanoparticles-targeting-malicious-exosomes-implications-for-cancer-diagnostics-and-therapy
#11
REVIEW
Catarina Roma-Rodrigues, Luís R Raposo, Rita Cabral, Fabiana Paradinha, Pedro V Baptista, Alexandra R Fernandes
Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development...
January 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098558/platelet-derived-growth-factor-pdgf-signaling-directs-cardiomyocyte-movement-toward-the-midline-during-heart-tube-assembly
#12
Joshua Bloomekatz, Reena Singh, Owen Wj Prall, Ariel C Dunn, Megan Vaughan, Chin-San Loo, Richard P Harvey, Deborah Yelon
Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28096541/the-mucosal-immune-system-master-regulator-of-bidirectional-gut-brain-communications
#13
REVIEW
Nick Powell, Marjorie M Walker, Nicholas J Talley
Communication between the brain and gut is not one-way, but a bidirectional highway whereby reciprocal signals between the two organ systems are exchanged to coordinate function. The messengers of this complex dialogue include neural, metabolic, endocrine and immune mediators responsive to diverse environmental cues, including nutrients and components of the intestinal microbiota (microbiota-gut-brain axis). We are now starting to understand how perturbation of these systems affects transition between health and disease...
January 18, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28096472/myosin-vi-facilitates-connexin-43-gap-junction-accretion
#14
Bennett Waxse, Prabuddha Sengupta, Geoffrey G Hesketh, Jennifer Lippincott-Schwartz, Folma Buss
In this study, we demonstrate myosin VI enrichment at Cx43 gap junctions in heart tissue, primary cardiomyocytes and cell culture models. The loss of myosin VI via siRNA-mediated knock down or isolation of primary cardiac tissue and fibroblasts from the myosin VI-null mouse results in reduced GJ plaque size with a concomitant reduction in intercellular communication as shown by FRAP and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable in the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28095652/exosomal-trafficking-in-xenopus-development
#15
REVIEW
Michael Danilchik, Tess Tumarkin
Exosomes are small extracellular vesicles (EVs) secreted by many cell types in both normal and pathogenic circumstances. Because EVs, particularly exosomes, are known to transfer biologically active proteins, RNAs and lipids between cells, they have recently become the focus of intense interest as potential mediators of cell-cell communication, particularly in long-range and juxtacrine signaling events associated with adaptive immune function and progression of cancer. Among the EVs, exosomes appear particularly adapted for long-range delivery of cargoes between cells...
January 17, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28095365/barreloid-borders-and-neuronal-activity-shape-panglial-gap-junction-coupled-networks-in-the-mouse-thalamus
#16
Lena Claus, Camille Philippot, Stephanie Griemsmann, Aline Timmermann, Ronald Jabs, Christian Henneberger, Helmut Kettenmann, Christian Steinhäuser
The ventral posterior nucleus of the thalamus plays an important role in somatosensory information processing. It contains elongated cellular domains called barreloids, which are the structural basis for the somatotopic organization of vibrissae representation. So far, the organization of glial networks in these barreloid structures and its modulation by neuronal activity has not been studied. We have developed a method to visualize thalamic barreloid fields in acute slices. Combining electrophysiology, immunohistochemistry, and electroporation in transgenic mice with cell type-specific fluorescence labeling, we provide the first structure-function analyses of barreloidal glial gap junction networks...
November 24, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/28094788/electronic-control-of-gene-expression-and-cell-behaviour-in-escherichia-coli-through-redox-signalling
#17
Tanya Tschirhart, Eunkyoung Kim, Ryan McKay, Hana Ueda, Hsuan-Chen Wu, Alex Eli Pottash, Amin Zargar, Alejandro Negrete, Joseph Shiloach, Gregory F Payne, William E Bentley
The ability to interconvert information between electronic and ionic modalities has transformed our ability to record and actuate biological function. Synthetic biology offers the potential to expand communication 'bandwidth' by using biomolecules and providing electrochemical access to redox-based cell signals and behaviours. While engineered cells have transmitted molecular information to electronic devices, the potential for bidirectional communication stands largely untapped. Here we present a simple electrogenetic device that uses redox biomolecules to carry electronic information to engineered bacterial cells in order to control transcription from a simple synthetic gene circuit...
January 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28094758/exosomes-isolated-from-serum-of-systemic-sclerosis-patients-display-alterations-in-their-content-of-profibrotic-and-antifibrotic-microrna-and-induce-a-profibrotic-phenotype-in-cultured-normal-dermal-fibroblasts
#18
Peter J Wermuth, Piera-Velazquez Sonsoles, Sergio A Jimenez
OBJECTIVES: Exosomes are lipid bilayer-bound microvesicles containing various macromolecules including numerous microRNA (miRNA). Exosomes mediate intercellular communication by fusing and releasing their macromolecular content into target cells. Here, we analysed the content of profibrotic and antifibrotic miRNAs in exosomes isolated from the serum of systemic sclerosis (SSc) patients and tested their ability to induce a profibrotic phenotype in normal human dermal fibroblasts in vitro...
January 13, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28094501/artificial-cells-synthetic-compartments-with-life-like-functionality-and-adaptivity
#19
Bastiaan C Buddingh', Jan C M van Hest
Cells are highly advanced microreactors that form the basis of all life. Their fascinating complexity has inspired scientists to create analogs from synthetic and natural components using a bottom-up approach. The ultimate goal here is to assemble a fully man-made cell that displays functionality and adaptivity as advanced as that found in nature, which will not only provide insight into the fundamental processes in natural cells but also pave the way for new applications of such artificial cells. In this Account, we highlight our recent work and that of others on the construction of artificial cells...
January 17, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28093986/antimicrobial-polymers-mimicking-amino-acid-functionality-sequence-control-and-three-dimensional-structure-of-host-defense-peptides
#20
Matthias Hartlieb, Elizabeth G L Williams, Agnès Kuroki, Sébastien Perrier, Katherine E S Locock
Peptides and proteins control and direct all aspects of cellular function and communication. Having been honed by nature for millions of years, they also typically display an unsurpassed specificity for their biological targets. This underlies the continued focus on peptides as promising drug candidates. However, the development of peptides into viable drugs is hampered by their lack of chemical and pharmacokinetic stability and the cost of large scale production. One method to overcome such hindrances is to develop polymer systems that are able to retain the important structural features of these biologically active peptides, while being cheaper and easier to produce and manipulate chemically...
January 16, 2017: Current Medicinal Chemistry
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