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https://www.readbyqxmd.com/read/28738408/cgas-surveillance-of-micronuclei-links-genome-instability-to-innate-immunity
#1
Karen J Mackenzie, Paula Carroll, Carol-Anne Martin, Olga Murina, Adeline Fluteau, Daniel J Simpson, Nelly Olova, Hannah Sutcliffe, Jacqueline K Rainger, Andrea Leitch, Ruby T Osborn, Ann P Wheeler, Marcin Nowotny, Nick Gilbert, Tamir Chandra, Martin A M Reijns, Andrew P Jackson
DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane...
July 24, 2017: Nature
https://www.readbyqxmd.com/read/28738373/neuroprogression-in-schizophrenia-and-psychotic-disorders-the-possible-role-of-inflammation
#2
Norbert Müller
Schizophrenia is a disorder that shows a progressive course in 30-50% of the people concerned. The biology of chronification and progression is unclear. Genetic aspects may play a role, but details are unresolved. The fact that immune-mediated and autoimmune disorders such as rheumatoid arthritis or multiple sclerosis have a very similar course as schizophrenia has focused the interest on the immunopathogenesis of schizophrenia. A clear immune marker for neuroprogression in schizophrenia or psychosis could not be identified up to now, but a proinflammatory immune state (increased markers of cellular immunity) is regularly found in schizophrenia, e...
July 24, 2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28737932/ins-and-outs-in-environmental-and-occupational-safety-studies-of-asthma-and-engineered-nanomaterials
#3
Marina A Dobrovolskaia, Michael R Shurin, Valerian E Kagan, Anna A Shvedova
According to the Centers for Disease Control and Prevention, approximately 25 million Americans suffer from asthma. The disease total annual cost is about $56 billion and includes both the direct and indirect costs of medications, hospital stays, missed work, and decreased productivity. Air pollution with xenobiotics, bacterial agents, and industrial nanomaterials, such as carbon nanotubes, contribute to the exacerbation of this condition and are a point of particular attention in environmental toxicology as well as in occupational health and safety research...
July 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/28737722/induction-of-a-regulatory-phenotype-in-cd3-cd4-hla-dr-t-cells-after-allogeneic-mixed-lymphocyte-culture-indications-of-both-contact-dependent-and-independent-activation
#4
Anne Louise Schacht Revenfeld, Rikke Bæk, Malene Møller Jørgensen, Kim Varming, Allan Stensballe
Although the observation of major histocompatibility complex II (MHCII) receptors on T cells is longstanding, the explanation for this occurrence remains enigmatic. Reports of an inducible, endogenous expression exist, as do studies demonstrating a protein acquisition from other cells by mechanisms including vesicle transfer. Irrespective of origin, the presence of the human MHCII isotype, human leukocyte antigen DR (HLA-DR), potentially identifies a regulatory T cell population. Using an allogeneic mixed lymphocyte culture (MLC) to induce an antigen-specific immune response, the role of antigen-presenting cells (APCs) for the presence of HLA-DR on cluster of differentiation 3(CD3)+ CD4+ T cells was evaluated...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28737721/pyranopyran-1-8-dione-an-active-compound-from-vitices-fructus-attenuates-cigarette-smoke-induced-lung-inflammation-in-mice
#5
Gihyun Lee, Kyung-Hwa Jung, Eun Seok Ji, Hyunsu Bae
Previously, we isolated and identified pyranopyran-1,8-dione (PPY) from Viticis Fructus, as a bioactive compound possessing anti-inflammatory properties. The present study was aimed to evaluate the preventive benefit of PPY on cigarette-smoke (CS)-induced lung inflammation. C57BL/6 mice were exposed to CS for 2 weeks while PPY was administrated by oral injection 2 h before CS exposure. To validate the anti-inflammatory effects of PPY, the numbers of immune cells in the bronchoalveolar lavage fluid were counted...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28737557/human-and-autologous-adipose-derived-stromal-cells-increase-flap-survival-in-rats-independently-of-host-immune-response
#6
Navid Mohamadpour Toyserkani, Charlotte Harken Jensen, Ditte Caroline Andersen, Søren Paludan Sheikh, Jens Ahm Sørensen
INTRODUCTION: There is a rising interest in adipose-derived stromal cells for clinical use; however, it is unknown whether freshly isolated stromal cells (SVF) or culture-expanded cells (ASCs) are more efficacious. We therefore aimed to compare the 2 cellular therapies in an in vivo model of angiogenesis, the ischemic flap in rats, which induces acute ischemia. We also aimed to determine the importance of cell presence and the host immune response. METHODS: A total of 96 rats (n = 12 in each group) were used, and in each rat, a caudally based random flap measuring 2 × 7 cm was made...
July 22, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28737116/apoptotic-induction-induces-leishmania-aethiopica-and-l-mexicana-spreading-in-terminally-differentiated-thp-1-cells
#7
Rajeev Rai, Paul Dyer, Simon Richardson, Laurence Harbige, Giulia Getti
Leishmaniasis develops after parasites establish themselves as amastigotes inside mammalian cells and start replicating. As relatively few parasites survive the innate immune defence, intracellular amastigotes spreading towards uninfected cells is instrumental to disease progression. Nevertheless the mechanism of Leishmania dissemination remains unclear, mostly due to the lack of a reliable model of infection spreading. Here, an in vitro model representing the dissemination of Leishmania amastigotes between human macrophages has been developed...
July 24, 2017: Parasitology
https://www.readbyqxmd.com/read/28736767/activation-of-mosquito-complement-antiplasmodial-response-requires-cellular-immunity
#8
Julio César Castillo, Ana Beatriz Barletta Ferreira, Nathanie Trisnadi, Carolina Barillas-Mury
The mosquito complement-like system is a major defense mechanism that limits Plasmodium infection. Ookinete midgut invasion results in irreversible damage to invaded cells and triggers epithelial nitration and complement activation. Several lines of evidence suggest that hemocytes participate in early antiplasmodial responses that target ookinetes, but their role remains unclear. The fate of hemocytes in response to Plasmodium infection was investigated by labeling this cell population in vivo. We found that midgut nitration triggers the local release of hemocyte-derived microvesicles (HdMv) into the basal labyrinth of the midgut...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28736435/extracellular-vesicles-in-renal-disease
#9
REVIEW
Diana Karpman, Anne-Lie Ståhl, Ida Arvidsson
Extracellular vesicles, such as exosomes and microvesicles, are host cell-derived packages of information that allow cell-cell communication and enable cells to rid themselves of unwanted substances. The release and uptake of extracellular vesicles has important physiological functions and may also contribute to the development and propagation of inflammatory, vascular, malignant, infectious and neurodegenerative diseases. This Review describes the different types of extracellular vesicles, how they are detected and the mechanisms by which they communicate with cells and transfer information...
July 24, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28736297/1%C3%AE-hydroxy-derivatives-of-7-dehydrocholesterol-are-selective-liver-x-receptor-modulators
#10
Kaori Endo-Umeda, Atsushi Aoyama, Masato Shimizu, Minoru Ishikawa, Yuichi Hashimoto, Sachiko Yamada, Makoto Makishima
The nuclear receptors liver X receptor (LXR) α and LXRβ are involved in the regulation of lipid metabolism, inflammation, immunity, cellular proliferation, and apoptosis. Oxysterols are endogenous LXR ligands, and also interact with other nuclear and membrane receptors. We previously reported that a phytosterol derivative with a 1α-hydroxy group acts as a potent LXR agonist with intestine-selective action and that 25-hydroxy and 26/27-hydroxy metabolites of 7-dehydrocholsterol (7-DHC) exhibit partial LXR agonism...
July 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28736117/modulation-of-dendritic-cell-and-t-cell-cross-talk-during-aging-the-potential-role-of-checkpoint-inhibitory-molecules
#11
REVIEW
Joanne K Gardner, Cyril D S Mamotte, Connie Jackaman, Delia J Nelson
Dendritic cells (DCs) undergo continuous changes throughout life, and there is evidence that elderly DCs have a reduced capacity to stimulate T cells, which may contribute to impaired anti-tumour immune responses in elderly people with cancer. Changes in checkpoint inhibitory molecules/pathways during aging may be one mechanism that impairs the ability of elderly DCs to activate T cells. However, little is currently known regarding the combined effects of aging and cancer on DC and T cell inhibitory molecules/pathways...
July 20, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28735964/bovine-a20-gene-overexpression-during-bovine-viral-diarrhea-virus-1-infection-blocks-nf-%C3%AE%C2%BAb-pathway-in-mdbk-cells
#12
Melina Villalba, Nivia Canales, Nicolas Maldonado, Carola Otth, Fernanda Fredericksen, Pablo Garcés, Cristopher Stepke, Valentina Arriagada, Víctor H Olavarría
Viruses have developed cellular strategies to ensure progeny survival. One of the most interesting is immune camouflage, where the virus triggers a controlled-intensity immune response that prevents total destruction of the infected cell, thus "winning time" for the virus. This study explored the regulatory contexts of the bovine A20 gene during bovine viral diarrhea virus (BVDV)-1 infection, using IL-8 as an immune-response sentinel molecule. Assessments were conducted through RT-qPCR, Western blotting, gene silencing/overexpression, luciferase assays, and the use of pharmacological inhibitors, among other approaches...
July 20, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28735164/vesicle-trafficking-in-plant-immunity
#13
REVIEW
Hye Sup Yun, Chian Kwon
To defend against extracellular pathogens, plants primarily depend on cell-autonomous innate immunity due to the lack of the circulatory immune system including mobile immune cells. To extracellularly restrict or kill the pathogens, plant cells dump out antimicrobials. However, since antimicrobials are also toxic to plant cells themselves, they have to be safely delivered to the target sites in a separate vesicular compartment. In addition, because immune responses often requires energy otherwise used for the other metabolic processes, it is very important to properly control the duration and strength of immune responses depending on pathogen types...
July 20, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28734795/monoclonal-antibodies-in-multiple-myeloma-a-new-wave-of-the-future
#14
REVIEW
Daniel W Sherbenou, Tomer M Mark, Peter Forsberg
In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity...
June 27, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28734132/high-dimensional-single-cell-mapping-of-cerium-distribution-in-the-lung-immune-microenvironment-of-an-active-smoker
#15
Adeeb H Rahman, Yonit Lavin, Soma Kobayashi, Andrew Leader, Miriam Merad
BACKGROUND: Mass cytometry leverages inductively coupled mass spectrometry to perform high dimensional single cell analyses using antibodies tagged with rare earth isotopes that are considered to be largely absent in biological samples. We have recently noted an unusual exception to this rule while analyzing tissue samples from patients undergoing surgical resection for early stage lung cancer, and here we present a detailed cytometric characterization of cerium in a clinical patient sample...
July 22, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28733594/cd56-is-a-pathogen-recognition-receptor-on-human-natural-killer-cells
#16
Sabrina Ziegler, Esther Weiss, Anna-Lena Schmitt, Jan Schlegel, Anne Burgert, Ulrich Terpitz, Markus Sauer, Lorenzo Moretta, Simona Sivori, Ines Leonhardt, Oliver Kurzai, Hermann Einsele, Juergen Loeffler
Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733487/the-stat4-mll1-epigenetic-axis-regulates-the-antimicrobial-functions-of-murine-macrophages
#17
William F Carson, Karen A Cavassani, Elyara M Soares, Soichiro Hirai, Nicolai A Kittan, Matthew A Schaller, Melissa M Scola, Amrita Joshi, Akihiro Matsukawa, David M Aronoff, Craig N Johnson, Yali Dou, Katherine A Gallagher, Steven L Kunkel
Macrophages are critical immune cells for the clearance of microbial pathogens and cellular debris from peripheral tissues. Macrophage inflammatory responses are governed by gene expression patterns, and these patterns are often subject to epigenetic control. Chromatin modifications, such as histone methylation, regulate gene accessibility in macrophages, and macrophage polarization is governed in part by the expression and function of chromatin-modifying enzymes. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) preferentially modifies lysine residue 4 on the unstructured protein tail of histone H3...
July 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#18
Jocelyn T Kim, Yarong Liu, Rajan P Kulkarni, Kevin K Lee, Bingbing Dai, Geoffrey Lovely, Yong Ouyang, Pin Wang, Lili Yang, David Baltimore
Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733429/proteogenomic-analysis-and-discovery-of-immune-antigens-in-mycobacterium-vaccae
#19
Jianhua Zheng, Lihong Chen, Liguo Liu, Haifeng Li, Bo Liu, Dandan Zheng, Tao Liu, Jie Dong, Lilian Sun, Yafang Zhu, Jian Yang, Xiaobing Zhang, Qi Jin
Tuberculosis (TB) is one of the leading causes of death worldwide, especially in developing countries. Neonatal BCG vaccination occurs in various regions, but the level of protection varies in different populations. Recently, Mycobacterium vaccae is found to be an immunomodulating therapeutic agent that could confer a significant level of protection against TB. It is the only vaccine in a phase III trial from WHO to assess its efficacy and safety in preventing TB disease in people with latent TB infection. However, the mechanism of immunotherapy of M...
July 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28733031/mkk4-activates-non-canonical-nf%C3%AE%C2%BAb-signaling-by-promoting-nf%C3%AE%C2%BAb2-p100-processing
#20
Jeong Seon Kim, Eun Ju Kim, Hee-Sun Kim, Jonathan M Kurie, Young-Ho Ahn
The NFκB family of transcription factors is crucial for innate or adaptive immunity, inflammation, and diseases including cancer. The two NFκB signaling pathways (canonical and non-canonical) differ from each other in extracellular signals, membrane receptors, signaling adaptors, and dimer subunits. The p52 (NFκB2) subunit, which participates in the non-canonical pathway, is generated by ubiquitin-mediated processing of the p100 precursor. Here, we found that NFκB2 processing and activation were mediated by mitogen-activated protein kinase kinase-4 (MKK4) and its substrate c-Jun N-terminal kinase (JNK)...
July 18, 2017: Biochemical and Biophysical Research Communications
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