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https://www.readbyqxmd.com/read/28179539/smoking-reduces-circulating-cd26-hi-cd161-hi-mait-cells-in-healthy-individuals-and-patients-with-multiple-sclerosis
#1
Cecilie Ammitzbøll, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Birgitte Romme Nielsen, Helle B Søndergaard, Marina R von Essen, Finn Sellebjerg
Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI)...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28166248/characterization-of-three-dimensional-cancer-cell-migration-in-mixed-collagen-matrigel-scaffolds-using-microfluidics-and-image-analysis
#2
María Anguiano, Carlos Castilla, Martin Maška, Cristina Ederra, Rafael Peláez, Xabier Morales, Gorka Muñoz-Arrieta, Maite Mujika, Michal Kozubek, Arrate Muñoz-Barrutia, Ana Rouzaut, Sergio Arana, José Manuel Garcia-Aznar, Carlos Ortiz-de-Solorzano
Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28166217/drugs-and-drug-like-molecules-can-modulate-the-function-of-mucosal-associated-invariant-t-cells
#3
Andrew N Keller, Sidonia B G Eckle, Weijun Xu, Ligong Liu, Victoria A Hughes, Jeffrey Y W Mak, Bronwyn S Meehan, Troi Pediongco, Richard W Birkinshaw, Zhenjun Chen, Huimeng Wang, Criselle D'Souza, Lars Kjer-Nielsen, Nicholas A Gherardin, Dale I Godfrey, Lyudmila Kostenko, Alexandra J Corbett, Anthony W Purcell, David P Fairlie, James McCluskey, Jamie Rossjohn
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists...
February 6, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28164306/amustaline-s-303-treatment-inactivates-high-levels-of-zika-virus-in-red-blood-cell-components
#4
Andrew Laughhunn, Felicia Santa Maria, Julien Broult, Marion C Lanteri, Adonis Stassinopoulos, Didier Musso, Maite Aubry
BACKGROUND: The potential for Zika virus (ZIKV) transmission by blood transfusion (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH)...
February 5, 2017: Transfusion
https://www.readbyqxmd.com/read/28158203/silymarin-suppresses-basal-and-stimulus-induced-activation-exhaustion-differentiation-and-inflammatory-markers-in-primary-human-immune-cells
#5
Erica S Lovelace, Nicholas J Maurice, Hannah W Miller, Chloe K Slichter, Robert Harrington, Amalia Magaret, Martin Prlic, Stephen De Rosa, Stephen J Polyak
Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28137756/endocytic-turnover-of-rab8-controls-cell-polarization
#6
Maite Vidal-Quadras, Mikkel R Holst, Monika K Francis, Elin Larsson, Mariam Hachimi, Wai Lok Yau, Johan Peränen, Fernando Martín-Belmonte, Richard Lundmark
Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endo- and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1), a regulator of clathrin independent endocytosis...
January 30, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28119353/fibroblast-growth-factor-15-19-fgf15-19-protects-from-diet-induced-hepatic-steatosis-development-of-an-fgf19-based-chimeric-molecule-to-promote-fatty-liver-regeneration
#7
Gloria Alvarez-Sola, Iker Uriarte, M Ujue Latasa, Maite G Fernandez-Barrena, Raquel Urtasun, Maria Elizalde, Marina Barcena-Varela, Maddalen Jiménez, Haisul C Chang, Roberto Barbero, Victoria Catalán, Amaia Rodríguez, Gema Frühbeck, José M Gallego-Escuredo, Aleix Gavaldà-Navarro, Francesc Villarroya, Carlos M Rodriguez-Ortigosa, Fernando J Corrales, Jesus Prieto, Pedro Berraondo, Carmen Berasain, Matias A Avila
OBJECTIVE: Fibroblast growth factor 15/19 (FGF15/19), an enterokine that regulates synthesis of hepatic bile acids (BA), has been proposed to influence fat metabolism. Without FGF15/19, mouse liver regeneration after partial hepatectomy (PH) is severely impaired. We studied the role of FGF15/19 in response to a high fat diet (HFD) and its regulation by saturated fatty acids. We developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration...
January 24, 2017: Gut
https://www.readbyqxmd.com/read/28119072/invariant-natural-killer-t-cells-and-mucosal-associated-invariant-t-cells-in-multiple-sclerosis
#8
REVIEW
Elena Bianchini, Sara De Biasi, Anna Maria Simone, Diana Ferraro, Patrizia Sola, Andrea Cossarizza, Marcello Pinti
Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disorder of the central nervous system, and in several countries is a leading cause of permanent neurological disability in young adults, particularly women. MS is considered an autoimmune disease, caused by an aberrant immune response to environmental triggers in genetically susceptible subjects. However, the contribution of the innate or of the adaptive immune system to the development and progression of the disease has not yet been fully elucidated...
January 21, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28089359/transient-and-long-time-kinetic-responses-of-the-cadaveric-leg-during-internal-and-external-foot-rotation
#9
Alexander R Mait, Adwait Mane, Jason L Forman, John Paul Donlon, Bingbing Nie, Richard W Kent
The purpose of this study was to determine the long-time and transient characteristics of the moment generated by external (ER) and internal (IR) rotation of the calcaneus with respect to the tibia. Two human cadaver legs were disarticulated at the knee joint while maintaining the connective tissue between the tibia and fibula. An axial rotation of 21° was applied to the proximal tibia to generate either ER or IR while the fibula was unconstrained and the calcaneus was permitted to translate in the transverse plane...
January 7, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28089353/cerebrospinal-fluid-mitochondrial-dna-in-the-alzheimer-s-disease-continuum
#10
Laura Cervera-Carles, Daniel Alcolea, Ainara Estanga, Mirian Ecay-Torres, Andrea Izagirre, Montserrat Clerigué, Maite García-Sebastián, Jorge Villanúa, Clàudia Escalas, Rafael Blesa, Pablo Martínez-Lage, Alberto Lleó, Juan Fortea, Jordi Clarimón
Low levels of cell-free mitochondrial DNA (mtDNA) in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients have been identified and proposed as a novel biomarker for the disease. The lack of validation studies of previous results prompted us to replicate this finding in a comprehensive series of patients and controls. We applied droplet digital polymerase chain reaction in CSF specimens from 124 patients representing the AD spectrum and 140 neurologically healthy controls. The following preanalytical and analytical parameters were evaluated: the effect of freeze-thaw cycles on mtDNA, the linearity of mtDNA load across serial dilutions, and the mtDNA levels in the diagnostic groups...
December 22, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28069799/ikbke-is-required-during-kras-induced-pancreatic-tumorigenesis
#11
Mihir Rajurkar, Kyvan Dang, Maite G Fernandez-Barrena, Xiangfan Liu, Martin E Fernandez-Zapico, Brian C Lewis, Junhao Mao
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies lacking effective therapeutic strategies. Here, we show that the noncanonical IκB-related kinase, IKBKE, is a critical oncogenic effector during KRAS-induced pancreatic transformation. Loss of IKBKE inhibits the initiation and progression of pancreatic tumors in mice carrying pancreatic-specific KRAS activation. Mechanistically, we demonstrate that this protumoral effect of IKBKE involves the activation of GLI1 and AKT signaling and is independent of the levels of activity of the NF-κB pathway...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28062719/characteristics-in-limbic-encephalitis-with-anti-adenylate-kinase-5-autoantibodies
#12
Le-Duy Do, Eve Chanson, Virginie Desestret, Bastien Joubert, François Ducray, Sabine Brugière, Yohann Couté, Maité Formaglio, Veronique Rogemond, Catherine Thomas-Antérion, Laura Borrega, Brice Laurens, Francois Tison, Jonathan Curot, Thomas De Brouker, Christine Lebrun-Frenay, Jean-Yves Delattre, Jean-Christophe Antoine, Jerome Honnorat
OBJECTIVE: To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs). METHODS: We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay. RESULTS: AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57-80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances...
January 6, 2017: Neurology
https://www.readbyqxmd.com/read/28049488/intracellular-trafficking-and-cellular-uptake-mechanism-of-phbv-nanoparticles-for-targeted-delivery-in-epithelial-cell-lines
#13
Juan P Peñaloza, Valeria Márquez-Miranda, Mauricio Cabaña-Brunod, Rodrigo Reyes-Ramírez, Felipe M Llancalahuen, Cristian Vilos, Fernanda Maldonado-Biermann, Luis A Velásquez, Juan A Fuentes, Fernando D González-Nilo, Maité Rodríguez-Díaz, Carolina Otero
BACKGROUND: Nanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3)...
January 3, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28032215/a-driver-role-for-gaba-metabolism-in-controlling-stem-and-proliferative-cell-state-through-ghb-production-in-glioma
#14
Elias A El-Habr, Luiz G Dubois, Fanny Burel-Vandenbos, Alexandra Bogeas, Joanna Lipecka, Laurent Turchi, François-Xavier Lejeune, Paulo Lucas Cerqueira Coehlo, Tomohiro Yamaki, Bryan M Wittmann, Mohamed Fareh, Emna Mahfoudhi, Maxime Janin, Ashwin Narayanan, Ghislaine Morvan-Dubois, Charlotte Schmitt, Maité Verreault, Lisa Oliver, Ariane Sharif, Johan Pallud, Bertrand Devaux, Stéphanie Puget, Penelope Korkolopoulou, Pascale Varlet, Chris Ottolenghi, Isabelle Plo, Vivaldo Moura-Neto, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation...
December 28, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28011187/mucosal-associated-invariant-t-cells-are-depleted-and-functionally-altered-in-patients-with-common-variable-immunodeficiency
#15
Serena Arduini, Jean Dunne, Niall Conlon, Conleth Feighery, Derek G Doherty
Common variable immunodeficiency (CVID) is a primary immunoglobulin deficiency characterized by recurrent infections and complications, including autoimmunity, enteropathy, polyclonal lymphocytic infiltration or lymphoid malignancy. Innate T cells can support B cell maturation and antibody production. We investigated the numbers, phenotypes and functions of circulating B cell, γδ T cell, invariant natural killer T (iNKT) cell and mucosal-associated invariant T (MAIT) cell subsets in 23 CVID patients and 27 healthy controls...
December 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28010156/bacillus-calmette-gu%C3%A3-rin-infection-and-cytotoxicity-in-the-retinal-pigment-epithelium
#16
Victor Llorenç, Marina Mesquida, Blanca Molins, Julian Gonzalez-Martín, Maite Sainz de la Maza, Alfredo Adán
PURPOSE: To investigate bacillus Calmette-Guérin (BCG) infective capability and cytotoxicity in ARPE-19 cells. METHODS: BCG inoculum was dispensed at a MOI 100:1 for 3 h in 90% confluent ARPE-19 cells. Infection rates at different time points were determined by colony forming units (CFU) count and, in parallel, by the number of microscopically infected cells. WST-1 reagent was used for cytotoxicity assays. RESULTS: A 67-year-old man previously treated with intravesical BCG for bladder carcinoma presented with chronic, refractory, bilateral uveitis with macular edema...
December 23, 2016: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/27983470/single-cell-studies-of-ifn-%C3%AE-promoter-activation-by-wildtype-and-ns1-defective-influenza-a-viruses
#17
Marian J Killip, David Jackson, Maite Pérez-Cidoncha, Ervin Fodor, Richard E Randall
Deletion or truncation of NS1, the principal interferon (IFN) antagonist of influenza viruses, leads to increased IFN induction during influenza virus infection. We have studied activation of the IFN induction cascade by both wildtype and NS1-defective viruses at the single-cell level using a cell line expressing GFP under the control of the IFN-β promoter and by examining MxA expression. The IFN-β promoter was not activated in all infected cells, even during NS1-defective virus infections. Loss of NS1 expression is therefore by itself insufficient to induce IFN in an infected cell, and factors besides NS1 expression status must dictate whether the IFN response is activated...
December 15, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27866852/ompa-a-flexible-clamp-for-bacterial-cell-wall-attachment
#18
Firdaus Samsudin, Maite L Ortiz-Suarez, Thomas J Piggot, Peter J Bond, Syma Khalid
The envelope of Gram-negative bacteria is highly complex, containing separate outer and inner membranes and an intervening periplasmic space encompassing a peptidoglycan (PGN) cell wall. The PGN scaffold is anchored non-covalently to the outer membrane via globular OmpA-like domains of various proteins. We report atomically detailed simulations of PGN bound to OmpA in three different states, including the isolated C-terminal domain (CTD), the full-length monomer, or the complete full-length dimeric form. Comparative analysis of dynamics of OmpA CTD from different bacteria helped to identify a conserved PGN-binding mode...
December 6, 2016: Structure
https://www.readbyqxmd.com/read/27852037/placental-immune-editing-switch-pies-learning-about-immunomodulatory-pathways-from-a-unique-case-report
#19
Miguel H Bronchud, Francesc Tresserra, Wenjie Xu, Sarah Warren, Maite Cusido, Bernat Zantop, Ana Claudia Zenclussen, Alessandra Cesano
The hypothesis of this work is that, in order to escape the natural immune surveillance mechanisms, cancer cells and the surrounding microenvironment might express ectopically genes that are physiologically present in the placenta to mediate fetal immune-tolerance. These natural "placental immune-editing switch" mechanisms (PIES) may represent the result of millions of years of mammalian evolution developed to allow materno-fetal tolerance. Here, we introduce genes of the immune regulatory pathways that are either similarly over- or under-expressed in tumor vs normal tissue...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27849057/cell-senescence-is-an-antiviral-defense-mechanism
#20
Maite Baz-Martínez, Sabela Da Silva-Álvarez, Estefanía Rodríguez, Jorge Guerra, Ahmed El Motiam, Anxo Vidal, Tomás García-Caballero, Miguel González-Barcia, Laura Sánchez, César Muñoz-Fontela, Manuel Collado, Carmen Rivas
Cellular senescence is often considered a protection mechanism triggered by conditions that impose cellular stress. Continuous proliferation, DNA damaging agents or activated oncogenes are well-known activators of cell senescence. Apart from a characteristic stable cell cycle arrest, this response also involves a proinflammatory phenotype known as senescence-associated secretory phenotype (SASP). This, together with the widely known interference with senescence pathways by some oncoviruses, had led to the hypothesis that senescence may also be part of the host cell response to fight virus...
November 16, 2016: Scientific Reports
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