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https://www.readbyqxmd.com/read/28649611/lrrk2-levels-in-immune-cells-are-increased-in-parkinson-s-disease
#1
D A Cook, G T Kannarkat, A F Cintron, Laura M Butkovich, Kyle B Fraser, J Chang, N Grigoryan, S A Factor, Andrew B West, J M Boss, M G Tansey
Mutations associated with leucine-rich repeat kinase 2 are the most common known cause of Parkinson's disease. The known expression of leucine-rich repeat kinase 2 in immune cells and its negative regulatory function of nuclear factor of activated T cells implicates leucine-rich repeat kinase 2 in the development of the inflammatory environment characteristic of Parkinson's disease. The aim of this study was to determine the expression pattern of leucine-rich repeat kinase 2 in immune cell subsets and correlate it with the immunophenotype of cells from Parkinson's disease and healthy subjects...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28647908/cmv-immune-evasion-and-manipulation-of-the-immune-system-with-aging
#2
REVIEW
Sarah E Jackson, Anke Redeker, Ramon Arens, Debbie van Baarle, Sara P H van den Berg, Chris A Benedict, Luka Čičin-Šain, Ann B Hill, Mark R Wills
Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response...
June 24, 2017: GeroScience
https://www.readbyqxmd.com/read/28646647/successful-maintenance-of-key-physiological-parameters-in-preterm-lambs-treated-with-ex%C3%A2-vivo-uterine-environment-therapy-for-a-period-of-1-week
#3
Haruo Usuda, Shimpei Watanabe, Yuichiro Miura, Masatoshi Saito, Gabrielle C Musk, Judith Rittenschober-Böhm, Hideyuki Ikeda, Shinichi Sato, Takushi Hanita, Tadashi Matsuda, Alan H Jobe, John P Newnham, Sarah J Stock, Matthew W Kemp
BACKGROUND: Extremely preterm infants born at the border of viability (22-24 weeks' gestation) have high rates of death and lasting disability. Ex vivo uterine environment therapy is an experimental neonatal intensive care strategy that provides gas exchange using parallel membranous oxygenators connected to the umbilical vessels, sparing the extremely preterm cardiopulmonary system from ventilation-derived injury. OBJECTIVE: In this study, we aimed to refine our ex vivo uterine environment therapy platform to eliminate fetal infection and inflammation, while simultaneously extending the duration of hemodynamically stable ex vivo uterine environment therapy to 1 week...
June 20, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28646096/heat-stress-causes-dysfunctional-autophagy-in-oxidative-skeletal-muscle
#4
Alexandra J Brownstein, Shanthi Ganesan, Corey M Summers, Sarah Pearce, Benjamin J Hale, Jason W Ross, Nicholas Gabler, Jacob T Seibert, Robert P Rhoads, Lance H Baumgard, Joshua T Selsby
We have previously established that 24 h of environmental hyperthermia causes oxidative stress and have implicated mitochondria as likely contributors to this process. Given this, we hypothesized that heat stress would lead to increased autophagy/mitophagy and a reduction in mitochondrial content. To address this hypothesis pigs were housed in thermoneutral (TN; 20°C) or heat stress (35°C) conditions for 1- (HS1) or 3- (HS3) days and the red and white portions of the semitendinosus collected. We did not detect differences in glycolytic muscle...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28640518/a-carborane-containing-fluorophore-as-a-stain-of-cellular-lipid-droplets
#5
Andrew Wu, Jacek L Kolanowski, Badwi B Boumelhem, Kylie Yang, Rebecca Lee, Amandeep Kaur, Stuart T Fraser, Elizabeth J New, Louis M Rendina
The use of fluorescent markers and probes greatly enhances biological investigations but relies on the provision of an array of fluorophores with diverse properties. Herein we report a novel carborane-containing coumarin, 5, which is sufficiently lipophilic to localise in cellular lipid droplets. In non-polar solvents which show comparable polarities to those of a lipid environment, compound 5 exhibits a fluorescence quantum yield two orders of magnitude greater than found in aqueous solvents, adding a further degree of selectivity to lipid droplet imaging...
June 22, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28638480/mouse-ip-10-gene-delivered-by-folate-modified-chitosan-nanoparticles-and-dendritic-tumor-cells-fusion-vaccine-effectively-inhibit-the-growth-of-hepatocellular-carcinoma-in-mice
#6
Zixi Hu, Jiaojiao Chen, Sufang Zhou, Nuo Yang, Siliang Duan, Zhenghua Zhang, Jing Su, Jian He, Zhiyong Zhang, Xiaoling Lu, Yongxiang Zhao
Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28638095/mitochondria-localization-induced-self-assembly-of-peptide-amphiphiles-for-cellular-dysfunction
#7
M T Jeena, L Palanikumar, Eun Min Go, Inhye Kim, Myoung Gyun Kang, Seonik Lee, Sooham Park, Huyeon Choi, Chaekyu Kim, Seon-Mi Jin, Sung Chul Bae, Hyun Woo Rhee, Eunji Lee, Sang Kyu Kwak, Ja-Hyoung Ryu
Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28637878/cd4-t-cell-and-nk-cell-interplay-key-to-regression-of-mhc-class-i-low-tumors-upon-tlr7-8-agonist-therapy
#8
Elien M Doorduijn, Marjolein Sluijter, Daniela C Salvatori, Serenella Silvestri, Saskia Maas, Ramon Arens, Ferry Ossendorp, Sjoerd H van der Burg, Thorbald van Hall
One of the next challenges in cancer immunotherapy is the resistance of tumors to T cell-based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4(+) T cells, whereas activated CD8(+) T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637471/enhanced-humoural-and-cellular-immune-responses-to-influenza-h7n9-antigen-ha1-2-fused-with-flagellin-in-chickens
#9
Li Song, Dan Xiong, Maozhi Hu, Xilong Kang, Zhiming Pan, Xinan Jiao
BACKGROUND: Sudden increases in the number of human A (H7N9) cases reported during December and January have been observed in previous years. Most reported infection cases are due to prior exposure to live poultry or potentially contaminated environments. Low pathogenicity of influenza A (H7N9) virus in avian species complicates timely discovery of infected birds. Therefore, there is a pressing need to develop safe and effective anti-H7N9 vaccines for poultry to reduce the risk of human infection and prevent the emergence of novel mutated strains...
June 21, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28636547/hnscc-subverts-pbmcs-to-secrete-soluble-products-that-promote-tumor-cell-proliferation
#10
Marcell Costa de Medeiros, Rajat Banerjee, Min Liu, Giovana Anovazzi, Nisha J D'Silva, Carlos Rossa Junior
The immune system detects shifts from homeostasis and eliminates altered cells. However, neoplastic cells can modulate the host response to escape immunosurveillance thereby allowing tumor progression. Head and neck squamous cell carcinoma (HNSCC) is one of the most immunosuppressive cancers but its role in co-opting the immune system to actively promote tumor growth has not been investigated. In this study, we investigated the influence of soluble factors secreted by HNSCC and non-neoplastic epithelial cells on proliferation, apoptosis, activation, cytokine gene expression and phenotypic polarization of immune cells of healthy donors...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636546/changes-of-peripheral-lymphocyte-subsets-and-cytokine-environment-during-ageing-and-deteriorating-gastrointestinal-tract-health-status
#11
Jing Wang, Guodong Yang, Dongfang Wang, Kuiliang Liu, Yongchao Ma, Hong Liu, Jing Wu, Min Fang
Human immune senescence accompanies with the physical and physiological frailty. The functional change and shift of NK, NKT and T cell subsets by ageing have been widely studied. However, it remains largely unclear how the ageing and disease conditions affect the distribution of lymphocytes. In the present study, 233 subjects with age range from 20 to 87 year old, including healthy people, people with chronic gastrointestinal tract disease or cancers were investigated. We found that the proportion of NK cells, CD8+ T cells and NKT cells remained relatively unchanged with ageing...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635615/topography-on-a-subcellular-scale-modulates-cellular-adhesions-and-actin-stress-fiber-dynamics-in-tumor-associated-fibroblasts
#12
Mikheil Azatov, Xiaoyu Sun, Alexandra Suberi, John T Fourkas, Arpita Upadhyaya
Cells can sense and adapt to mechanical properties of their environment. The local geometry of the extracellular matrix, such as its topography, has been shown to modulate cell morphology, migration, and proliferation. Here we investigate the effect of micro/nanotopography on the morphology and cytoskeletal dynamics of human pancreatic tumor-associated fibroblast cells (TAFs). We use arrays of parallel nanoridges with variable spacings on a subcellular scale to investigate the response of TAFs to the topography of their environment...
June 21, 2017: Physical Biology
https://www.readbyqxmd.com/read/28634161/oncolytic-adenovirus-expressing-bispecific-antibody-targets-t-cell-cytotoxicity-in-cancer-biopsies
#13
Joshua D Freedman, Joachim Hagel, Eleanor M Scott, Ioannis Psallidas, Avinash Gupta, Laura Spiers, Paul Miller, Nikolaos Kanellakis, Rebecca Ashfield, Kerry D Fisher, Margaret R Duffy, Leonard W Seymour
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication...
June 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28630322/tcte1-is-a-conserved-component-of-the-dynein-regulatory-complex-and-is-required-for-motility-and-metabolism-in-mouse-spermatozoa
#14
Julio M Castaneda, Rong Hua, Haruhiko Miyata, Asami Oji, Yueshuai Guo, Yiwei Cheng, Tao Zhou, Xuejiang Guo, Yiqiang Cui, Bin Shen, Zibin Wang, Zhibin Hu, Zuomin Zhou, Jiahao Sha, Renata Prunskaite-Hyyrylainen, Zhifeng Yu, Ramiro Ramirez-Solis, Masahito Ikawa, Martin M Matzuk, Mingxi Liu
Flagella and cilia are critical cellular organelles that provide a means for cells to sense and progress through their environment. The central component of flagella and cilia is the axoneme, which comprises the "9+2" microtubule arrangement, dynein arms, radial spokes, and the nexin-dynein regulatory complex (N-DRC). Failure to properly assemble components of the axoneme leads to defective flagella and in humans leads to a collection of diseases referred to as ciliopathies. Ciliopathies can manifest as severe syndromic diseases that affect lung and kidney function, central nervous system development, bone formation, visceral organ organization, and reproduction...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630108/inducing-mucosal-iga-a-challenge-for-vaccine-adjuvants-and-delivery-systems
#15
REVIEW
Prosper N Boyaka
Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and enzymes of host or microbial origin. Production of SIgA is finely regulated, and distinct T-independent and T-dependent mechanisms orchestrate Ig α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines...
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28629745/exposure-to-non-microbial-n-glycolylneuraminic-acid-protects-farmers-children-against-airway-inflammation-and-colitis
#16
Remo Frei, Ruth Ferstl, Caroline Roduit, Mario Ziegler Dipl-Ing, Elisa Schiavi, Weronika Barcik, Noelia Rodriguez-Perez, Oliver F Wirz, Marcin Wawrzyniak, Benoit Pugin, Dirk Nehrbass, Marek Jutel, Sylwia Smolinska, Patrycja Konieczna, Christian Bieli, Susanne Loeliger, Marco Waser, Göran Pershagen, Josef Riedler, Martin Depner, Bianca Schaub, Jon Genuneit, Harald Renz, Juha Pekkanen, Anne M Karvonen, Jean-Charles Dalphin, Marianne van Hage, Gert Doekes, Mübeccel Akdis, Charlotte Braun-Fahrländer, Cezmi A Akdis, Erika von Mutius, Liam O'Mahony, Roger P Lauener
BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether besides exposure to microbes also exposure to structures of non-microbial origin such as the sialic acid N-Glycolylneuraminic acid (Neu5Gc) may play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in the sera of children enrolled in two farm studies: the PARSIFAL study (n=299) and the PASTURE birth cohort (cord blood (n=836), 1 year (n=734), 4...
June 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28626582/fluorescent-flavonoids-for-endoplasmic-reticulum-cell-imaging
#17
Lucas McDonald, Bin Liu, Alexandra Taraboletti, Kyle Whiddon, Leah P Shriver, Michael Konopka, Qin Liu, Yi Pang
Visualization of subcellular organelles in vivo is critical for basic biomedical research and clinical applications. Two new flavonoids with an amide substituent were synthesized and characterized. The flavonoids were nearly non-fluorescent in aqueous environment, but exhibited two emission peaks (one λem at 495-536 nm and the other at 570-587 nm) in organic solvents, which were assigned to the excited normal (N(*)) and tautomer (T(*)) emission. When the dyes were examined on oligodendrocyte cells, they were found to selectively accumulate in the endoplasmic reticulum (ER), a eukaryotic organelle involved in lipid and protein synthesis, giving fluorescence turn-on...
December 28, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28625080/in-vivo-pet-imaging-of-the-activated-immune-environment-in-a-small-animal-model-of-inflammatory-arthritis
#18
Benjamin L Franc, Sam Goth, John MacKenzie, Xiaojuan Li, Joseph Blecha, Tina Lam, Salma Jivan, Randall A Hawkins, Henry VanBrocklin
BACKGROUND: Evolving immune-mediated therapeutic strategies for rheumatoid arthritis (RA) may benefit from an improved understanding of the complex role that T-cell activation plays in RA. This study assessed the potential of fluorine-18-labeled 9-β-d-arabinofuranosylguanine ([(18)F]F-AraG) positron emission tomography (PET) imaging to report immune activation in vivo in an adjuvant-induced arthritis (AIA) small animal model. METHODS: Using positron emission tomography-computed tomography imaging, uptake of [(18)F]F-AraG in the paws of mice affected by arthritis at 6 (acute) and 20 (chronic) days following AIA induction in a single paw was assessed and compared to uptake in contralateral control paws...
January 1, 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28624966/molecular-mechanisms-underlying-th1-like-treg-generation-and-function
#19
REVIEW
Alexandra Kitz, Margarita Dominguez-Villar
Since their 're-discovery' more than two decades ago, FOXP3(+) regulatory T cells (Tregs) have been an important subject of investigation in the biomedical field and our understanding of the mechanisms that drive their phenotype and function in health and disease has advanced tremendously. During the past few years it has become clear that Tregs are not a terminally differentiated population but show some degree of plasticity, and can, under specific environmental conditions, acquire the phenotype of effector T cells...
June 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28624612/human-mast-cells-present-antigen-to-autologous-cd4-t-cells
#20
Sahar Lotfi-Emran, Brant R Ward, Quang T Le, Andrea L Pozez, Masoud H Manjili, Judith Woodfolk, Lawrence B Schwartz
BACKGROUND: Mast cells (MCs), the primary effector cell of the atopic response, participate in immune defense at host/environment interfaces, yet the mechanisms by which they interact with CD4(+)-T cells has been controversial. OBJECTIVE: We utilize in situ-matured primary human MCs and matched CD4(+)-T cells to diligently assess the ability of MCs to act as antigen-presenting cells. METHODS: We examined mature human skin-derived MCs by flow cytometry for expression of antigen-presenting molecules; for their ability to stimulate CD4(+)-T cells to express CD25 and proliferate when exposed to superantigen or to CMV antigen using matched T cells and MCs from CMV seropositive or seronegative donors; and for uptake of antigens...
June 14, 2017: Journal of Allergy and Clinical Immunology
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