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https://www.readbyqxmd.com/read/28641133/abc-transporters-in-megakaryopoiesis-and-platelet-activity
#1
REVIEW
Wei Wang, Lorena Buitrago, Ying Wang
ATP-binding cassette (ABC) is a family of transporters that facilitates the translocation of substrates across cell membrane using its ATPase subunit. These transporters have key roles in multidrug resistance, lipid homeostasis, antigen processing, immunity, cell proliferation and hematopoiesis. Some ABC transporters are selectively expressed on megakaryocyte progenitor, megakaryocyte and its cellular fragment platelet. However, the role of ABC transporters in hemostasis and thrombosis were not well explored until recently...
June 14, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28641125/an-altered-redox-environment-assisted-by-over-expression-of-fetal-hemoglobins-protects-from-inflammatory-colitis-and-reduces-inflammatory-cytokine-expression
#2
R M Gorczynski, C Alexander, K Brandenburg, Z Chen, A Heini, D Neumann, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, Kai Yu, U Zahringer, I Khatri
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents...
June 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#3
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28641094/emerging-concepts-in-cytomegalovirus-infection-following-hematopoietic-stem-cell-transplantation
#4
REVIEW
Jose F Camargo, Krishna V Komanduri
Despite the refinements in molecular methods for the detection of cytomegalovirus (CMV) and the advent of highly effective preemptive strategies, CMV remains a leading cause of morbidity and mortality in hematopoietic cell transplant (HCT) recipients. CMV can cause tissue-invasive disease including pneumonia, hepatitis, colitis, retinitis, and encephalitis. Mortality in HCT recipients with CMV disease can be as high as 60%. CMV infection has been associated with increased risk of secondary bacterial and fungal infections, increased risk of graft-versus-host disease, and high rates of nonrelapse mortality following HCT...
June 14, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28640974/resistance-to-powdery-mildew8-1-boosts-pattern-triggered-immunity-against-multiple-pathogens-in-arabidopsis-and-rice
#5
Yan Li, Yong Zhang, Qing-Xia Wang, Ting-Ting Wang, Xiao-Long Cao, Zhi-Xue Zhao, Sheng-Li Zhao, Yong-Ju Xu, Zhi-Yuan Xiao, Jin-Lu Li, Jing Fan, Hui Yang, Fu Huang, Shunyuan Xiao, Wen-Ming Wang
The Arabidopsis gene RESISTANCE TO POWDERY MILDEW8.1 (RPW8.1) confers resistance to virulent fungal and oomycete pathogens that cause powdery mildew and downy mildew, respectively. However, the underlying mechanism remains unclear. Here, we show that ectopic expression of RPW8.1 boosts pattern-triggered immunity (PTI) resulting in enhanced resistance against different pathogens in both Arabidopsis and rice. In Arabidopsis, transcriptome analysis revealed that ectopic expression of RPW8.1-YFP constitutively up-regulates expression of many pathogen-associated molecular pattern-(PAMP-) inducible genes...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28640898/competition-between-influenza-a-virus-subtypes-through-heterosubtypic-immunity-modulates-re-infection-and-antibody-dynamics-in-the-mallard-duck
#6
Neus Latorre-Margalef, Justin D Brown, Alinde Fojtik, Rebecca L Poulson, Deborah Carter, Monique Franca, David E Stallknecht
Our overall hypothesis is that host population immunity directed at multiple antigens will influence the prevalence, diversity and evolution of influenza A virus (IAV) in avian populations where the vast subtype diversity is maintained. To investigate how initial infection influences the outcome of later infections with homologous or heterologous IAV subtypes and how viruses interact through host immune responses, we carried out experimental infections in mallard ducks (Anas platyrhynchos). Mallards were pre-challenged with an H3N8 low-pathogenic IAV and were divided into six groups...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640810/lassim-a-network-inference-toolbox-for-genome-wide-mechanistic-modeling
#7
Rasmus Magnusson, Guido Pio Mariotti, Mattias Köpsén, William Lövfors, Danuta R Gawel, Rebecka Jörnsten, Jörg Linde, Torbjörn Nordling, Elin Nyman, Sylvie Schulze, Colm E Nestor, Huan Zhang, Gunnar Cedersund, Mikael Benson, Andreas Tjärnberg, Mika Gustafsson
Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28637300/commercial-rodent-diets-differentially-regulate-autoimmune-glomerulonephritis-epigenetics-and-microbiota-in-mrl-lpr-mice
#8
Michael R Edwards, Rujuan Dai, Bettina Heid, Thomas E Cecere, Deena Khan, Qinghui Mu, Catharine Cowan, Xin M Luo, S Ansar Ahmed
The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone rich soy and alfalfa, Harlan 2018 isoflavone rich soy-based diet, or ResearchDiets Inc...
June 15, 2017: International Immunology
https://www.readbyqxmd.com/read/28637001/a-novel-method-to-generate-salmonella-typhi-ty21a-ghosts-exploiting-the-%C3%AE-phage-holin-endolysin-system
#9
Gayeon Won, Boram Kim, John Hwa Lee
Human typhoid fever caused by Salmonella Typhi still poses a severe global disease burden in developing countries despite the availability of commercial vaccines. In this study, we constructed a non-living S. Typhi Ty21a vaccine candidate by employing a lambda (λ) phage-derived holin-endolysin system to efficiently construct bacterial ghosts. The lysis plasmid pJHL464 harbors an R lysis cassette that is stringently regulated by dual promoters containing cI857/λPR and ParaBAD/araC components. The plasmid was introduced into an asd gene-deleted S...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636960/mechanisms-and-therapeutic-relevance-of-neuro-immune-communication
#10
REVIEW
Sangeeta S Chavan, Valentin A Pavlov, Kevin J Tracey
Active research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity. Molecular mechanistic insights into the inflammatory reflex and other neuro-immune interactions have greatly advanced our understanding of immunity and identified new therapeutic possibilities in inflammatory and autoimmune diseases. Recent successful clinical trials using bioelectronic devices that modulate the inflammatory reflex to significantly ameliorate rheumatoid arthritis and inflammatory bowel disease provide a path for using electrons as a therapeutic modality for targeting molecular mechanisms of immunity...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636952/human-leukocyte-antigen-f-presents-peptides-and-regulates-immunity-through-interactions-with-nk-cell-receptors
#11
Charles L Dulberger, Curtis P McMurtrey, Angelique Hölzemer, Karlynn E Neu, Victor Liu, Adriana M Steinbach, Wilfredo F Garcia-Beltran, Michael Sulak, Bana Jabri, Vincent J Lynch, Marcus Altfeld, William H Hildebrand, Erin J Adams
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636945/pkn1-directs-polarized-rab21-vesicle-trafficking-via-rph3a-and-is-important-for-neutrophil-adhesion-and-ischemia-reperfusion-injury
#12
Qianying Yuan, Chunguang Ren, Wenwen Xu, Björn Petri, Jiasheng Zhang, Yong Zhang, Paul Kubes, Dianqing Wu, Wenwen Tang
Polarized vesicle transport plays an important role in cell polarization, but the mechanisms underlying this process and its role in innate immune responses are not well understood. Here, we describe a phosphorylation-regulated polarization mechanism that is important for neutrophil adhesion to endothelial cells during inflammatory responses. We show that the protein kinase PKN1 phosphorylates RPH3A, which enhances binding of RPH3A to guanosine triphosphate (GTP)-bound RAB21. These interactions are important for polarized localization of RAB21 and RPH3A in neutrophils, which leads to PIP5K1C90 polarization...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636560/lipocalin-2-regulates-intestine-bacterial-survival-by-interplaying-with-siderophore-in-a-weaned-piglet-model-of-escherichia-coli-infection
#13
Bing-Xiu Guo, Qian-Qian Wang, Jia-Hui Li, Zhen-Shun Gan, Xiao-Feng Zhang, Yi-Zhen Wang, Hua-Hua Du
Iron is an essential nutrient that facilitates cell proliferation and growth, which plays a pivotal role in modulating the battle for survival between mammalian hosts and their pathogens. Pathogenic bacteria secrete siderophores to acquire iron from the host. However, lipocalin 2 (Lcn2), a siderophore-binding antimicrobial protein, binds to siderophores to prevent bacterial uptake of iron, which is critical for the control of systemic infection with Escherichia coli (E. coli). But few studies focus on the anti-infective response of Lcn2 in the intestines by inhibiting bacterial proliferation based on microbial iron metabolism...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636394/synthesis-of-rna-5-azides-from-2-o-pivaloyloxymethyl-protected-rnas-and-their-reactivity-in-azide-alkyne-cycloaddition-reactions
#14
Marcin Warminski, Joanna Kowalska, Jacek Jemielity
Commercially available 2'-O-pivaloyloxymethyl (PivOM) phosphoramidites were employed in an SPS protocol for RNA 5' azides. The utility of the N3-RNAs in CuAAC and SPAAC was demonstrated by RNA 5' labeling, chemical ligation including fragment joining and cyclization, and bioconjugation. As a result, several new RNA conjugates that may be valuable tools for studies on biological events such as innate immune response (cyclic dinucleotides), post-transcriptional gene regulation (circular RNAs), or mRNA turnover (m(7)G capped RNAs) were obtained...
June 21, 2017: Organic Letters
https://www.readbyqxmd.com/read/28636161/infinity-sperm-storage-the-gift-that-keeps-on-giving
#15
Gauthier Schang, Beatriz Fernandez-Fuertes, Samantha C Lean, Alexandra L Nguyen, Osvaldo Bogado Pascottini
Female Drosophila retain sperm for up to two weeks post-copulation in a network of storage organs includng the bursa, the seminal receptacle, and the spermathecae. This image shows the seminal receptacle of a Drosophila melanogaster female, 2-hrs post-copulation between a LHM (wild-type) female with a Protamine B (green), β-Tubulin (blue) fluorescently tagged male, whose sperm can be visualized within the female. This 'infinity' structure of the seminal receptacle resembles the tubular coil that allows for the storage of very long sperm relative to female body size -up to 20 times the length of the female in some Drosophila species...
June 21, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#16
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635669/modulation-of-human-%C3%AE-defensin-1-production-by-viruses
#17
REVIEW
Lisa Kathleen Ryan, Gill Diamond
While initially identified as a broad-spectrum antimicrobial peptide, constitutively expressed in epithelia, human β-defensin (hBD)-1 is now recognized to have a more complex pattern of expression of its gene, DEFB1, as well as activities that extend beyond direct antimicrobial. These observations suggest a complex role for hBD-1 in the host defense against viral infections, as evidenced by its expression in cells involved in viral defense, and its gene regulation in response to viral challenge. This regulation is observed both in vitro and in vivo in humans, as well as with the murine homolog, mBD-1...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28635668/the-role-of-cccdna-in-hbv-maintenance
#18
REVIEW
Lena Allweiss, Maura Dandri
Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide; it can cause various degrees of liver damage and is strongly associated with the development of liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms determining HBV persistence are not fully understood, but these appear to be multifactorial and the unique replication strategy employed by HBV enables its maintenance in infected hepatocytes. Both the stability of the HBV genome, which forms a stable minichromosome, the covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, and the inability of the immune system to resolve chronic HBV infection are believed to be key mechanisms of HBV chronicity...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28635660/diverse-regulation-of-vitamin-d-receptor-gene-expression-by-1-25-dihydroxyvitamin-d-and-atra-in-murine-and-human-blood-cells-at-early-stages-of-their-differentiation
#19
Sylwia Janik, Urszula Nowak, Agnieszka Łaszkiewicz, Anastasiia Satyr, Michał Majkowski, Aleksandra Marchwicka, Łukasz Śnieżewski, Klaudia Berkowska, Marian Gabryś, Małgorzata Cebrat, Ewa Marcinkowska
Vitamin D receptor (VDR) is present in multiple blood cells, and the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is essential for the proper functioning of the immune system. The role of retinoic acid receptor α (RARα) in hematopoiesis is very important, as the fusion of RARα gene with PML gene initiates acute promyelocytic leukemia where differentiation of the myeloid lineage is blocked, followed by an uncontrolled proliferation of leukemic blasts. RARα takes part in regulation of VDR transcription, and unliganded RARα acts as a transcriptional repressor to VDR gene in acute myeloid leukemia (AML) cells...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#20
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
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