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https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#1
Erika Della Mina, Alessandro Borghesi, Hao Zhou, Salim Bougarn, Sabri Boughorbel, Laura Israel, Ilaria Meloni, Maya Chrabieh, Yun Ling, Yuval Itan, Alessandra Renieri, Iolanda Mazzucchelli, Sabrina Basso, Piero Pavone, Raffaele Falsaperla, Roberto Ciccone, Rosa Maria Cerbo, Mauro Stronati, Capucine Picard, Orsetta Zuffardi, Laurent Abel, Damien Chaussabel, Nico Marr, Xiaoxia Li, Jean-Laurent Casanova, Anne Puel
Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28056837/vaccination-with-toxofilin-dna-in-combination-with-an-alum-monophosphoryl-lipid-a-mixed-adjuvant-induces-significant-protective-immunity-against-toxoplasma-gondii
#2
Pengxia Song, Shenyi He, Aihua Zhou, Gang Lv, Jingjing Guo, Jian Zhou, Yali Han, Huaiyu Zhou, Zhen Hao, Hua Cong
BACKGROUND: A widely prevalent disease, toxoplasmosis poses serious health threats to both humans and animals; therefore, development of an ideal DNA vaccine against Toxoplasma gondii is needed eagerly. The purpose of the present study is to assess the protective efficacy of a DNA vaccine encoding the T. gondii toxofilin gene (pEGFP-toxofilin). In addition, toxofilin DNA vaccine combined with the individual adjuvants, alum or monophosphoryl lipid A (MPLA), or a mixture of alum-MPLA adjuvant were screened for their ability to enhance antibody responses...
January 5, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28053314/comparative-transcriptome-profiles-of-human-blood-in-response-to-the-toll-like-receptor-4-ligands-lipopolysaccharide-and-monophosphoryl-lipid-a
#3
Liming Luan, Naeem K Patil, Yin Guo, Antonio Hernandez, Julia K Bohannon, Benjamin A Fensterheim, Jingbin Wang, Yaomin Xu, Perenlei Enkhbaatar, Ryan Stark, Edward R Sherwood
Monophosphoryl lipid A (MPLA), a less toxic derivative of lipopolysaccharide (LPS), is employed as a vaccine adjuvant and is under investigation as a non-specific immunomodulator. However, the differential response of human leukocytes to MPLA and LPS has not been well characterized. The goal of this study was to compare the differential transcriptomic response of human blood to LPS and MPLA. Venous blood from human volunteers was stimulated with LPS, MPLA or vehicle. Gene expression was determined using microarray analysis...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28048733/mo-de-201-02-self-awareness
#4
J Johnson
: Medical physicists possess technical knowledge and problem solving skills required to deliver high quality diagnosis and treatment in the clinic, to provide excellence in research, or to transfer expertise in industrial or regulatory environments. As the healthcare industry rapidly evolves, medical physicists must make a case for ensuring recognition of their value. One of many ways the AAPM is working to ensure stewardship of the profession is through development of the Medical Physics Leadership Academy (MPLA)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048232/mo-de-201-00-medical-physics-leadership-academy
#5
Jessica Clements
: Medical physicists possess technical knowledge and problem solving skills required to deliver high quality diagnosis and treatment in the clinic, to provide excellence in research, or to transfer expertise in industrial or regulatory environments. As the healthcare industry rapidly evolves, medical physicists must make a case for ensuring recognition of their value. One of many ways the AAPM is working to ensure stewardship of the profession is through development of the Medical Physics Leadership Academy (MPLA)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048074/mo-de-201-03-empathy
#6
E Ritenour
: Medical physicists possess technical knowledge and problem solving skills required to deliver high quality diagnosis and treatment in the clinic, to provide excellence in research, or to transfer expertise in industrial or regulatory environments. As the healthcare industry rapidly evolves, medical physicists must make a case for ensuring recognition of their value. One of many ways the AAPM is working to ensure stewardship of the profession is through development of the Medical Physics Leadership Academy (MPLA)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047584/mo-de-201-01-introduction-to-the-mpla-and-emotional-competencies
#7
J Clements
: Medical physicists possess technical knowledge and problem solving skills required to deliver high quality diagnosis and treatment in the clinic, to provide excellence in research, or to transfer expertise in industrial or regulatory environments. As the healthcare industry rapidly evolves, medical physicists must make a case for ensuring recognition of their value. One of many ways the AAPM is working to ensure stewardship of the profession is through development of the Medical Physics Leadership Academy (MPLA)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047416/mo-de-201-04-skits-and-panel-discussion
#8
R Miller
: Medical physicists possess technical knowledge and problem solving skills required to deliver high quality diagnosis and treatment in the clinic, to provide excellence in research, or to transfer expertise in industrial or regulatory environments. As the healthcare industry rapidly evolves, medical physicists must make a case for ensuring recognition of their value. One of many ways the AAPM is working to ensure stewardship of the profession is through development of the Medical Physics Leadership Academy (MPLA)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/27997339/toll-like-receptor-3-adjuvant-in-combination-with-virus-like-particles-elicit-a-humoral-response-against-hiv
#9
Ethan Poteet, Phoebe Lewis, Changyi Chen, Sam On Ho, Thai Do, SuMing Chiang, Celia Labranche, David Montefiori, Gary Fujii, Qizhi Yao
Human Immunodeficiency Virus (HIV) Virus-Like Particles (VLPs) composed of HIVIIIB Gag and HIVBaL gp120/gp41 envelope are a pseudovirion vaccine capable of presenting antigens in their native conformations. To enhance the immunogenicity of the HIV Env antigen, VLPs were coupled to VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) containing one of four toll-like-receptor (TLR) ligands, each activating a receptor with distinct cellular localization and downstream pathways. C57BL/6 mice were vaccinated by intranasal prime followed by two sub-cheek boosts and their sera immunoglobulin and neutralizing potency were measured over a duration of 3months after vaccination...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27927165/innate-immunity-based-cancer-immunotherapy-b16-f10-murine-melanoma-model
#10
Veronika Caisová, Andra Vieru, Zuzana Kumžáková, Simona Glaserová, Hana Husníková, Nikol Vácová, Gabriela Krejčová, Lucie Paďouková, Ivana Jochmanová, Katherine I Wolf, Jindřich Chmelař, Jan Kopecký, Jan Ženka
BACKGROUND: Using killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19(th) century. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans. METHODS: B16-F10 murine melanoma model was used...
December 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27906673/multiplex-ligation-dependent-probe-amplification-assay-identifies-additional-copy-number-changes-compared-with-r-band-karyotype-and-provide-more-accuracy-prognostic-information-in-myelodysplastic-syndromes
#11
Jingya Wang, Xiaofei Ai, Tiejun Qin, Zefeng Xu, Yue Zhang, Jinqin Liu, Bing Li, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Shiqiang Qu, Wenyu Cai, Kun Ru, Yujiao Jia, Gang Huang, Zhijian Xiao
Cytogenetic analysis provides important diagnostic and prognostic information for patients with Myelodysplastic syndromes (MDS) and plays an essential role in the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R). Multiplex ligation-dependent probe amplification (MLPA) assay is a recently developed technique to identify targeted cytogenetic aberrations in MDS patients. In the present study, we evaluated the results obtained using an MLPA assay in 437 patients with MDS to determine the efficacy of MLPA analysis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896542/immunomodulatory-effects-of-adjuvants-cpg-mpla-and-bcg-on-the-derp2-induced-acute-asthma-at-early-life-in-an-animal-model-of-balb-c-mice
#12
V Mohammadi-Shahrokhi, A Rezaei, A Andalib, A Rahnama, A Jafarzadeh, N Eskandari
The Th1- and Treg cell-related immune responses play key roles in the modulation of Th2 cell-related allergic disorders. The aim was to evaluate the effects of CPG, MPLA, and BCG on the number of Th1-, Th2-, and Treg cell-related parameters in an animal model of asthma. BALB/c mice were divided into five groups and immunized subcutaneously (SC) on days 1, 15, and 22 with allergen Derp2. Three groups of mice were pretreated SC on days 0, 14, and 21 with CPG, CPG + MPLA, or CPG + BCG. All mice were then challenged intranasally with Derp2 on days 28-37...
November 28, 2016: Inflammation
https://www.readbyqxmd.com/read/27835636/in-vitro-evaluation-of-the-biological-responses-of-canine-macrophages-challenged-with-plga-nanoparticles-containing-monophosphoryl-lipid-a
#13
Delphine Guldner, Julianne K Hwang, Maria Clara D Cardieri, Meaghan Eren, Parissa Ziaei, M Grant Norton, Cleverson D Souza
Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been considerably studied as a promising biodegradable delivery system to induce effective immune responses and to improve stability, safety, and cost effectiveness of vaccines. The study aimed at evaluating early inflammatory effects and cellular safety of PLGA NPs, co-encapsulating ovalbumin (PLGA/OVA NPs), as a model antigen and the adjuvant monophosphoryl lipid A (PLGA/MPLA NPs) as an adjuvant, on primary canine macrophages. The PLGA NPs constructs were prepared following the emulsion-solvent evaporation technique and further physic-chemically characterized...
2016: PloS One
https://www.readbyqxmd.com/read/27826300/treatment-with-dexamethasone-and-monophosphoryl-lipid-a-removes-disease-associated-transcriptional-signatures-in-monocyte-derived-dendritic-cells-from-rheumatoid-arthritis-patients-and-confers-tolerogenic-features
#14
Paulina A García-González, Katina Schinnerling, Alejandro Sepúlveda-Gutiérrez, Jaxaira Maggi, Lorena Hoyos, Rodrigo A Morales, Ahmed M Mehdi, Hendrik J Nel, Lilian Soto, Bárbara Pesce, María Carmen Molina, Miguel Cuchacovich, Milton L Larrondo, Óscar Neira, Diego Francisco Catalán, Catharien M Hilkens, Ranjeny Thomas, Ricardo A Verdugo, Juan C Aguillón
Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27793335/role-of-heterogeneous-cell-population-on-modulation-of-dendritic-cell-phenotype-and-activation-of-cd8-t-cells-for-use-in-cell-based-immunotherapies
#15
Hannah Frizzell, Jaehyung Park, Natacha Comandante Lou, Kim A Woodrow
Dendritic cell (DC)-based immunotherapies have much utility in their ability to prime antigen-specific adaptive immune responses. However, there does not yet exist a consensus standard to how DCs should be primed. In this study, we aimed to determine the role of heterogeneous co-cultures, composed of both CD11c+ (DCs) and CD11c- cells, in combination with monophosphoryl lipid A (MPLA) stimulation on DC phenotype and function. Upon DC priming in different co-culture ratios, we observed reduced expression of MHCII and CD86 and increased antigen uptake among CD11c+ cells in a CD11c- dependent manner...
January 2017: Cellular Immunology
https://www.readbyqxmd.com/read/27761933/immunogenicity-and-protective-efficacy-of-recombinant-iron-superoxide-dismutase-protein-from-bordetella-pertussis-in-mice-models
#16
Çiğdem Yılmaz, Aycan Apak, Erkan Özcengiz, Gülay Özcengiz
Whooping cough (pertussis) is a highly contagious respiratory infection caused by Bordetella pertussis. Although availability of effective pertussis vaccines reportedly decreases the incidence of the disease, B. pertussis circulation in populations has not been eliminated. Thus, it is necessary to find new protein candidates with greater immune protective capacities than the currently available acellular pertussis vaccines. In this study, iron superoxide dismutase (FeSOD) gene (sodB) was cloned, expressed in Escherichia coli and recombinant FeSOD protein thence purified...
November 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27737611/cysteine-mutagenesis-improves-the-production-without-abrogating-antigenicity-of-a-recombinant-protein-vaccine-candidate-for-human-chagas-disease
#17
Christopher A Seid, Kathryn M Jones, Jeroen Pollet, Brian Keegan, Elissa Hudspeth, Molly Hammond, Junfei Wei, C Patrick McAtee, Leroy Versteeg, Amanda Gutierrez, Zhuyun Liu, Bin Zhan, Jonathan L Respress, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez
A therapeutic vaccine for human Chagas disease is under development by the Sabin Vaccine Institute Product Development Partnership. The aim of the vaccine is to significantly reduce the parasite burden of Trypanosoma cruzi in humans, either as a standalone product or in combination with conventional chemotherapy. Vaccination of mice with Tc24 formulated with monophosphoryl-lipid A (MPLA) adjuvant results in a Th1 skewed immune response with elevated IgG2a and IFNγ levels and a statistically significant decrease in parasitemia following T...
October 13, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27698654/dexamethasone-and-monophosphoryl-lipid-a-modulated-dendritic-cells-promote-antigen-specific-tolerogenic-properties-on-naive-and-memory-cd4-t-cells
#18
Jaxaira Maggi, Katina Schinnerling, Bárbara Pesce, Catharien M Hilkens, Diego Catalán, Juan C Aguillón
Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated autoimmunity. Here, we evaluate the ability of dexamethasone-modulated and monophosphoryl lipid A (MPLA)-activated DCs [MPLA-tolerogenic DCs (tDCs)] to exert immunomodulatory effects on naive and memory CD4(+) T cells in an antigen-specific manner. For this purpose, MPLA-tDCs were loaded with purified protein derivative (PPD) as antigen and co-cultured with autologous naive or memory CD4(+) T cells. Lymphocytes were re-challenged with autologous PPD-pulsed mature DCs (mDCs), evaluating proliferation and cytokine production by flow cytometry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27671946/injectable-and-pathogen-mimicking-hydrogels-for-enhanced-protective-immunity-against-emerging-and-highly-pathogenic-influenza-virus
#19
Hyun Jong Noh, Young-Woock Noh, Min Beom Heo, Eun-Ha Kim, Su-Jin Park, Young-Il Kim, Young Ki Choi, Yong Taik Lim
Seasonal emerging infectious diseases such as influenza A impose substantial risk and need new translational strategies to achieve active immunomodulation. Here, a novel injectable pathogen-mimicking hydrogel (iPMH) that can enhance both cellular and humoral immune responses is suggested. By the help of poly(γ-glutamic acid) that has abundant carboxylate groups and dispersion helper function, hydrophobic immunostimulatory 3-O-desacyl-4'-monophosphoryl lipid A (MPLA) molecules and viral antigens (PR8, W150) can be successfully combined as pathogen-mimicking adjuvants...
December 2016: Small
https://www.readbyqxmd.com/read/27650574/norharmane-matrix-enhances-detection-of-endotoxin-by-maldi-ms-for-simultaneous-profiling-of-pathogen-host-and-vector-systems
#20
Alison J Scott, Bryn Flinders, Joanna Cappell, Tao Liang, Rebecca S Pelc, Bao Tran, David P A Kilgour, Ron M A Heeren, David R Goodlett, Robert K Ernst
The discovery of novel pathogenic mechanisms engaged during bacterial infections requires the evolution of advanced techniques. Here, we evaluate the dual polarity matrix norharmane (NRM) to improve detection of bacterial lipid A (endotoxin), from host and vector tissues infected with Francisella novicida (Fn). We evaluated NRM for improved detection and characterization of a wide range of lipids in both positive and negative polarities, including lipid A and phospholipids across a range of matrix assisted laser desorption-ionization (MALDI)-coupled applications...
September 19, 2016: Pathogens and Disease
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