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https://www.readbyqxmd.com/read/29454215/effect-based-trigger-values-for-in-vitro-and-in-vivo-bioassays-performed-on-surface-water-extracts-supporting-the-environmental-quality-standards-eqs-of-the-european-water-framework-directive
#1
Beate I Escher, Selim Aїt-Aїssa, Peter A Behnisch, Werner Brack, François Brion, Abraham Brouwer, Sebastian Buchinger, Sarah E Crawford, David Du Pasquier, Timo Hamers, Karina Hettwer, Klára Hilscherová, Henner Hollert, Robert Kase, Cornelia Kienle, Andrew J Tindall, Jochen Tuerk, Ron van der Oost, Etienne Vermeirssen, Peta A Neale
Effect-based methods including cell-based bioassays, reporter gene assays and whole-organism assays have been applied for decades in water quality monitoring and testing of enriched solid-phase extracts. There is no common EU-wide agreement on what level of bioassay response in water extracts is acceptable. At present, bioassay results are only benchmarked against each other but not against a consented measure of chemical water quality. The EU environmental quality standards (EQS) differentiate between acceptable and unacceptable surface water concentrations for individual chemicals but cannot capture the thousands of chemicals in water and their biological action as mixtures...
February 14, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29454096/jak-stat-inhibitors-and-other-small-molecule-cytokine-antagonists-for-the-treatment-of-allergic-disease
#2
REVIEW
Michael D Howell, Carolyn Fitzsimons, Paul Smith
OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their utilization in atopic dermatitis (AD), asthma, and allergic rhinitis (AR)...
February 14, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29454012/immunologic-effects-of-chronic-administration-of-tofacitinib-a-janus-kinase-inhibitor-in-cynomolgus-monkeys-and-rats-comparison-of-juvenile-and-adult-responses
#3
Mark Collinge, Douglas J Ball, Christopher J Bowman, Andrea L Nilson, Zaher A Radi, W Mark Vogel
Tofacitinib, an oral Janus kinase (JAK) inhibitor for treatment of rheumatoid arthritis, targets JAK1, JAK3, and to a lesser extent JAK2 and TYK2. JAK1/3 inhibition impairs gamma common chain cytokine receptor signaling, important in lymphocyte development, homeostasis and function. Adult and juvenile cynomolgus monkey and rat studies were conducted and the impact of tofacitinib on immune parameters (lymphoid tissues and lymphocyte subsets) and function (T-dependent antibody response (TDAR), mitogen-induced T cell proliferation) assessed...
February 14, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29454004/identification-and-analysis-of-peanut-specific-t-effector-and-t-regulatory-cells-in-children-allergic-and-tolerant-to-peanut
#4
Katherine A Weissler, Marjohn Rasooly, Tom DiMaggio, Hyejeong Bolan, Daly Cantave, David Martino, Melanie R Neeland, Mimi Lk Tang, Thanh D Dang, Katrina J Allen, Pamela A Frischmeyer-Guerrerio
BACKGROUND: Peanut allergy is potentially life-threatening and generally persists lifelong. Recent data suggests the skin may be an important route of initial sensitization to peanut, while early oral exposure to peanut is protective. In mice, T regulatory cells (Tregs) are central to development of tolerance to food, but their contribution to the pathogenesis of food allergy in humans is less clear. OBJECTIVE: We sought to quantify and phenotype peanut-specific CD4+ T effector (ps-Teff) and ps-Tregs in children with and without peanut allergy or sensitization...
February 14, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29453899/the-role-of-dna-pk-in-aging-and-energy-metabolism
#5
REVIEW
Jay H Chung
DNA-dependent protein kinase (DNA-PK) is a very large holoenzyme comprised of the p470 kDa DNA-PK catalytic subunit (DNA-PK cs ) and the Ku heterodimer consisting of the p86 (Ku 80) and p70 (Ku 70) subunits. It is best known for its non-homologous end joining (NHEJ) activity, which repairs double-strand DNA (dsDNA) breaks (DSBs). As expected, the absence of DNA-PK activity results in sensitivity to ionizing radiation, which generates DSBs and defect in lymphocyte development, which requires NHEJ of the V(D)J region in the immunoglobulin and T cell receptor loci...
February 17, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29453894/organisation-of-lymphocytic-infiltrates-inanca-associated-glomerulonephritis
#6
Silke R Brix, Mercedes Noriega, Elisabeth M Herden, Birgit Goldmann, Ulrike Langbehn, Martin Busch, Wolfram J Jabs, Oliver M Steinmetz, Ulf Panzer, Tobias B Huber, Rolf A K Stahl, Thorsten Wiech
AIMS: Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis contributes to significant morbidity and mortality in patients. In chronic inflammation, B cells are recruited to the inflamed tissue and organised lymphoid structures have been described in several autoimmune diseases. Aim of this study was to correlate the lymphoid organisation in renal biopsies with renal outcome in ANCA-associated glomerulonephritis (GN). METHODS AND RESULTS: We investigated 112 renal biopsies from patients with newly diagnosed ANCA-associated necrotizing GN...
February 17, 2018: Histopathology
https://www.readbyqxmd.com/read/29453746/effect-of-aerobic-exercise-on-treg-and-th17-of-rats-with-ischemic-cardiomyopathy
#7
Zhisong Chen, Wenwen Yan, Yu Mao, Yi Ni, Lin Zhou, Haoming Song, Wenjun Xu, Leming Wang, Yuqin Shen
Immune activation and inflammation participate in the progression of chronic heart failure (CHF). Th17 cells and CD4+CD25+ regulatory T (Treg) cells both come from naive Th cells and share reciprocal development pathways but exhibit opposite effects. We hypothesized that the Th17/Treg balance was impaired in patients with CHF, and exercise can improve it. Rats with ischemic cardiomyopathy were prepared by ligaturing the left anterior descending branch of the left coronary artery. Rats in training group were trained with treadmill; Th17 cells increased significantly while Treg cells significantly decreased in s by flow cytometry, and the peripheral blood level of IL-6, IL-17, and TNF-α was obviously elevated by ELISA assay...
February 16, 2018: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/29453553/-microbiome-atopic-eczema-and-blockade-of-type-2-immunity
#8
REVIEW
M Köberle, T Biedermann
Atopic dermatitis affects roughly 20% of children and 3% of adults in Germany and other industrial countries, with an increasing prevalence. Its causality has still not been conclusively clarified but a type‑2 T‑helper cell mediated immunity reaction (type 2 immunity) dominates cutaneous inflammation. In the quest for the underlying pathogenic mechanisms and the development of improved prevention and treatment options, attention is also increasingly being paid to the influence of microbial colonization...
February 16, 2018: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/29453518/chimeric-antigen-receptors-with-human-scfvs-preferentially-induce-t-cell-anti-tumor-activity-against-tumors-with-high-b7h6-expression
#9
Albert T Gacerez, Casey K Hua, Margaret E Ackerman, Charles L Sentman
B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29453398/host-defense-against-oral-microbiota-by-bone-damaging-t-cells
#10
Masayuki Tsukasaki, Noriko Komatsu, Kazuki Nagashima, Takeshi Nitta, Warunee Pluemsakunthai, Chisa Shukunami, Yoichiro Iwakura, Tomoki Nakashima, Kazuo Okamoto, Hiroshi Takayanagi
The immune system evolved to efficiently eradicate invading bacteria and terminate inflammation through balancing inflammatory and regulatory T-cell responses. In autoimmune arthritis, pathogenic T H 17 cells induce bone destruction and autoimmune inflammation. However, whether a beneficial function of T-cell-induced bone damage exists is unclear. Here, we show that bone-damaging T cells have a critical function in the eradication of bacteria in a mouse model of periodontitis, which is the most common infectious disease...
February 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#11
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453292/clonal-selection-drives-protective-memory-b-cell-responses-in-controlled-human-malaria-infection
#12
Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa, Gemma Pidelaserra Martí, Katharina Imkeller, Christian E Busse, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, Elena A Levashina, Peter G Kremsner, Benjamin Mordmüller, Thomas Höfer, Hedda Wardemann
Affinity maturation, the clonal selection and expansion of antigen-activated B cells expressing somatically mutated antibody variants that develop during T cell-dependent germinal center reactions, is considered pivotal for efficient development of protective B cell memory responses to infection and vaccination. Repeated antigen exposure promotes affinity maturation but each time also recruits antigen-reactive naïve B cells into the response. Here, we determined the relative impact of affinity maturation versus antigen-mediated clonal selection of naïve B cells to mount potent B cell memory responses in humans after repeated exposure to a complex pathogen, the malaria parasite Plasmodium falciparum (Pf)...
February 16, 2018: Science Immunology
https://www.readbyqxmd.com/read/29453284/structural-and-compositional-diversity-of-fibrillin-microfibrils-in-human-tissues
#13
Alexander Eckersley, Kieran T Mellody, Suzanne M Pilkington, Christopher Em Griffiths, Rachel E B Watson, Ronan O'Cualain, Clair Baldock, David Knight, Michael J Sherratt
Elastic fibres comprising fibrillin microfibrils and elastin are present in many tissues, including the skin, lung, and arteries where they confer elasticity and resilience. Although fibrillin microfibrils play distinct and tissue-specific functional roles, it is unclear whether their ultrastructure and composition differ between elastin-rich (skin) and elastin-poor (ciliary body and zonule) organs or after in vitro synthesis by cultured cells. Here, we used atomic force microscopy, which revealed that the bead morphology of fibrillin microfibrils isolated from the human eye differs from those isolated from the skin...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29453278/molecular-signatures-of-circulating-melanoma-cells-for-monitoring-early-response-to-immune-checkpoint-therapy
#14
Xin Hong, Ryan J Sullivan, Mark Kalinich, Tanya Todorova Kwan, Anita Giobbie-Hurder, Shiwei Pan, Joseph A LiCausi, John D Milner, Linda T Nieman, Ben S Wittner, Uyen Ho, Tianqi Chen, Ravi Kapur, Donald P Lawrence, Keith T Flaherty, Lecia V Sequist, Sridhar Ramaswamy, David T Miyamoto, Michael Lawrence, Mehmet Toner, Kurt J Isselbacher, Shyamala Maheswaran, Daniel A Haber
A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29453262/insights-into-the-fundamental-physiology-of-the-uncultured-fe-oxidizing-bacterium-leptothrix-ochracea
#15
E J Fleming, T Woyke, A R Donatello, M M M Kuypers, A Sczyrba, S Littmann, D Emerson
Leptothrix ochracea is known for producing large volumes of iron-oxyhydroxide sheaths that alter wetland biogeochemistry. For over a century, these delicate structures have fascinated microbiologists and geoscientists. Because L. ochracea still resists long-term in vitro culture, the debate regarding its metabolic classification dates back to 1885. We developed a novel culturing technique for L. ochracea using in situ natural waters, and coupled this with single cell genomics and nanoscale secondary ion mass spectrophotometry (nanoSIMS) to probe L...
February 16, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29453127/generation-of-d1-1-talen-isogenic-control-cell-line-from-dravet-syndrome-patient-ipscs-using-talen-mediated-editing-of-the-scn1a-gene
#16
Yasuyoshi Tanaka, Takefumi Sone, Norimichi Higurashi, Tetsushi Sakuma, Sadafumi Suzuki, Mitsuru Ishikawa, Takashi Yamamoto, Jun Mitsui, Hitomi Tsuji, Hideyuki Okano, Shinichi Hirose
Dravet syndrome (DS) is an infantile epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene encoding the α1 subunit of the voltage-gated sodium channel Na v 1.1. As an in vitro model of this disease, we previously generated an induced pluripotent stem cell (iPSC) line from a patient with DS carrying a c.4933C>T (p.R1645*) substitution in SCN1A. Here, we describe developing a genome-edited control cell line from this DS iPSC line by substituting the point mutation with the wild-type residue...
February 2, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29453041/microrna-signature-of-regulatory-t-cells-in-health-and-autoimmunity
#17
REVIEW
Mehdi Soltanzadeh-Yamchi, Mehdi Shahbazi, Saeed Aslani, Mousa Mohammadnia-Afrouzi
MicroRNAs (miRNAs) are small RNA molecules with regulatory functions on the expression of genes through binding directly to target messenger RNA (mRNA) transcripts, eventuating in gene expression suppression via translational hindrance and/or target mRNA cleavage. These molecules have been established to participate in numerous critical cellular settings, including differentiation, development, and function of immune cells. As an important suppressor cell of immune system, regulatory T cells (Tregs) are important in modulating the immune homeostasis as well as tolerance to self-antigens...
February 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29452963/chemical-sensing-in-development-and-function-of-intestinal-lymphocytes
#18
REVIEW
Luisa Cervantes-Barragan, Marco Colonna
The immune system of the intestinal tract has the challenging task of recognizing and eliminating intestinal pathogens while maintaining tolerance to dietary and commensal antigens; therefore, it must be able to sense environmental cues within the intestine and mount suitable responses dictated by their pathogenic or nonpathogenic nature. The aryl hydrocarbon receptor (AHR) was originally characterized as a chemical sensor of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [12]. More recently, AHR has emerged as a major chemical sensor expressed in many intestinal immune cells that enables them to distinguish nutritional and microbial cues and is, therefore, important for development, maintenance and function of the intestinal immune system...
February 13, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29452960/traditionally-practiced-medicinal-plant-extracts-inhibit-the-ergosterol-biosynthesis-of-clinically-isolated-dermatophytic-pathogens
#19
M Chellappandian, M Saravanan, P Pandikumar, P Harikrishnan, K Thirugnanasambantham, S Subramanian, V I Hairul-Islam, S Ignacimuthu
OBJECTIVE: Dermatophytes are resistant to some available antibiotics. Development of new plant drugs to control drug resistant microbes is urgently needed. This study evaluates the antidermatophytic potential of 18 selected medicinal plants used by traditional healers in Theni and Virudhunagar Districts of Tamil Nadu, India. MATERIALS AND METHODS: Selected plant parts were collected, shade dried and powdered. Plant powders were extracted with ethanol and their antifungal potency was investigated against and clinical dermatophytes...
February 13, 2018: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/29452898/transcriptional-and-epigenetic-regulation-of-innate-like-t-lymphocyte-development
#20
REVIEW
Mihalis Verykokakis, Barbara L Kee
Invariant Natural Killer T (iNKT) cells are a heterogeneous innate T cell population that recognizes lipid antigens. Despite the monospecific nature of their T cell receptor, iNKT cells differentiate into stable sublineages during thymic development, before foreign antigen encounter. How iNKT cell subsets acquire and maintain their functional programs is a central question in innate lymphocyte biology. Global transcriptional and epigenetic profiling of iNKT subsets has provided insights into the internal wiring of these subsets that defines their identity...
February 13, 2018: Current Opinion in Immunology
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