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T cell sensitivity

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https://www.readbyqxmd.com/read/29352186/glycolysis-promotes-caspase-3-activation-in-lipid-rafts-in-t-cells
#1
Michael A Secinaro, Karen A Fortner, Oliver Dienz, Angela Logan, Michael P Murphy, Vikas Anathy, Jonathan E Boyson, Ralph C Budd
Resting T cells undergo a rapid metabolic shift to glycolysis upon activation in the presence of interleukin (IL)-2, in contrast to oxidative mitochondrial respiration with IL-15. Paralleling these different metabolic states are striking differences in susceptibility to restimulation-induced cell death (RICD); glycolytic effector T cells are highly sensitive to RICD, whereas non-glycolytic T cells are resistant. It is unclear whether the metabolic state of a T cell is linked to its susceptibility to RICD. Our findings reveal that IL-2-driven glycolysis promotes caspase-3 activity and increases sensitivity to RICD...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352088/an-archaeal-fluoride-responsive-riboswitch-provides-an-inducible-expression-system-for-hyperthermophiles
#2
Michael Clayton Speed, Brett W Burkhart, Jonathan W Picking, Thomas J Santangelo
Robust genetic systems for the hyperthermophilic Thermococcales have facilitated overexpression of native genes, allowed for the addition of sequences encoding secretion signals, epitope, and affinity tags to coding regions, and permitted the introduction of sequences encoding new proteins in these fast growing fermentative heterotrophs. Tightly controlled and easily manipulated systems permitting regulated gene expression are however limited for these hosts. Here we describe an alternative method for regulatory control reliant on a cis-encoded functional riboswitch in the model archaeon Thermococcus kodakarensis Despite the hyperthermophilic growth temperatures, the proposed structure of the riboswitch conforms to a fluoride-responsive riboswitch encoded in many bacteria, and similarly functions to regulate a component conserved fluoride export pathway...
January 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29351998/detection-of-experimental-and-clinical-immune-complexes-by-measuring-ship-1-recruitment-to-the-inhibitory-fc%C3%AE-riib
#3
Richard J Stopforth, Robert J Oldham, Alison L Tutt, Patrick Duriez, H T Claude Chan, Brock F Binkowski, Chad Zimprich, Dun Li, Philip G Hargreaves, Mei Cong, Venkat Reddy, Maria J Leandro, Geraldine Cambridge, Anja Lux, Falk Nimmerjahn, Mark S Cragg
Fc γ receptors (FcγR) are involved in multiple aspects of immune cell regulation, are central to the success of mAb therapeutics, and underpin the pathology of several autoimmune diseases. However, reliable assays capable of accurately measuring FcγR interactions with their physiological ligands, IgG immune complexes (IC), are limited. A method to study and detect IC interactions with FcγRs was therefore developed. This method, designed to model the signaling pathway of the inhibitory FcγRIIB (CD32B), used NanoLuc Binary Interaction Technology to measure recruitment of the Src homology 2 domain-containing inositol phosphatase 1 to the ITIM of this receptor...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351883/titanium-dioxide-nanoparticle-exposure-reduces-algal-biomass-and-alters-algal-assemblage-composition-in-wastewater-effluent-dominated-stream-mesocosms
#4
Moncie V Wright, Cole W Matson, Leanne S Baker, Benjamin T Castellon, Preston S Watkins, Ryan S King
A 5-week mesocosm experiment was conducted to investigate the toxicity of titanium dioxide nanoparticles (TiO2NPs) to periphytic algae in an environmentally-realistic scenario. We used outdoor experimental streams to simulate the characteristics of central Texas streams receiving large discharges of wastewater treatment plant effluent during prolonged periods of drought. The streams were continually dosed and maintained at two concentrations. The first represents an environmentally relevant concentration of 0...
January 16, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29350807/mait-cells-and-viruses
#5
James E Ussher, Christian B Willberg, Paul Klenerman
Mucosal associated invariant T cells (MAIT cells) bear a T cell receptor (TCR) that specifically targets microbially-derived metabolites. Functionally they respond to bacteria and yeasts, which possess the riboflavin pathway, essential for production of such metabolites and which are presented on MR1. Viruses cannot generate these ligands, so a priori, they should not be recognized by MAIT cells and indeed this is true when considering recognition through the TCR. However, MAIT cells are distinctive in another respect, since they respond quite sensitively to non-TCR signals, especially in the form of inflammatory cytokines...
January 19, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29350437/diffusion-tensor-imaging-mri-of-sickle-cell-kidney-disease-initial-results-and-comparison-with-iron-deposition
#6
Shannon B Donnola, Connie M Piccone, Lan Lu, Joshua Batesole, Jane Little, Katherine M Dell, Chris A Flask
Chronic kidney disease (CKD) occurs in over one-third of patients with sickle cell disease (SCD) and can progress to end-stage renal disease. Unfortunately, current clinical assessments of kidney function are insensitive to early-stage CKD. Previous studies have shown that diffusion magnetic resonance imaging (MRI) can sensitively detect regional renal microstructural changes associated with early-stage CKD. However, previous MRI studies in patients with SCD have been largely limited to the detection of renal iron deposition assessed by T2 * relaxometry...
January 19, 2018: NMR in Biomedicine
https://www.readbyqxmd.com/read/29348365/detection-and-localization-of-surgically-resectable-cancers-with-a-multi-analyte-blood-test
#7
Joshua D Cohen, Lu Li, Yuxuan Wang, Christopher Thoburn, Bahman Afsari, Ludmila Danilova, Christopher Douville, Ammar A Javed, Fay Wong, Austin Mattox, Ralph H Hruban, Christopher L Wolfgang, Michael G Goggins, Marco Dal Molin, Tian-Li Wang, Richard Roden, Alison P Klein, Janine Ptak, Lisa Dobbyn, Joy Schaefer, Natalie Silliman, Maria Popoli, Joshua T Vogelstein, James D Browne, Robert E Schoen, Randall E Brand, Jeanne Tie, Peter Gibbs, Hui-Li Wong, Aaron S Mansfield, Jin Jen, Samir M Hanash, Massimo Falconi, Peter J Allen, Shibin Zhou, Chetan Bettegowda, Luis Diaz, Cristian Tomasetti, Kenneth W Kinzler, Bert Vogelstein, Anne Marie Lennon, Nickolas Papadopoulos
Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with non-metastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29348127/murine-chronic-graft-versus-host-disease-proteome-profiling-discovers-ccl15-as-a-novel-biomarker-in-patients
#8
Jing Du, Ryan Flynn, Katelyn Paz, Hong-Gang Ren, Yuko Ogata, Qing Zhang, Philip R Gafken, Barry E Storer, Nathan H Roy, Janis K Burkhardt, Wendy Mathews, Jakub Tolar, Stephanie J Lee, Bruce R Blazar, Sophie Paczesny
Improved diagnostic and treatment methods are needed for chronic graft-versus-host disease (cGVHD), the leading cause of late non-relapse mortality (NRM) in long-term survivors of allogenic hematopoietic cell transplantation (allo-HCT). Validated biomarkers that facilitate disease diagnosis, and classification generally are lacking in cGVHD. Here, we conducted whole serum proteomics analysis of a well-established murine multi-organ system cGVHD model. We discovered 4 up-regulated proteins during cGVHD that are targetable by genetic ablation or blocking antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8 and CCL9 chemokines...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29347185/balancing-specificity-sensitivity-and-speed-of-ligand-discrimination-by-zero-order-ultraspecificity
#9
Masashi K Kajita, Kazuyuki Aihara, Tetsuya J Kobayashi
Specific interactions between receptors and their target ligands in the presence of nontarget ligands are crucial for biological processes such as T cell ligand discrimination. To discriminate between the target and nontarget ligands, cells have to increase specificity to the target ligands by amplifying the small differences in affinity among ligands. In addition, sensitivity to the ligand concentration and quick discrimination are also important to detect low amounts of target ligands and facilitate fast cellular decision making after ligand recognition...
July 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346757/p53-suppresses-metabolic-stress-induced-ferroptosis-in-cancer-cells
#10
Amy Tarangelo, Leslie Magtanong, Kathryn T Bieging-Rolett, Yang Li, Jiangbin Ye, Laura D Attardi, Scott J Dixon
How cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, and high-resolution, time-lapse imaging, we find that stabilization of wild-type p53 delays the onset of ferroptosis in response to cystine deprivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346274/irf4-mediates-the-oncogenic-effects-of-stat3-in-anaplastic-large-cell-lymphomas
#11
Cecilia Bandini, Aldi Pupuleku, Elisa Spaccarotella, Elisa Pellegrino, Rui Wang, Nicoletta Vitale, Carlotta Duval, Daniela Cantarella, Andrea Rinaldi, Paolo Provero, Ferdinando Di Cunto, Enzo Medico, Francesco Bertoni, Giorgio Inghirami, Roberto Piva
Systemic anaplastic large cell lymphomas (ALCL) are a category of T-cell non-Hodgkin's lymphomas which can be divided into anaplastic lymphoma kinase (ALK) positive and ALK negative subgroups, based on ALK gene rearrangements. Among several pathways aberrantly activated in ALCL, the constitutive activation of signal transducer and activator of transcription 3 (STAT3) is shared by all ALK positive ALCL and has been detected in a subgroup of ALK negative ALCL. To discover essential mediators of STAT3 oncogenic activity that may represent feasible targets for ALCL therapies, we combined gene expression profiling analysis and RNA interference functional approaches...
January 18, 2018: Cancers
https://www.readbyqxmd.com/read/29345051/mir-595-suppresses-the-cellular-uptake-and-cytotoxic-effects-of-methotrexate-by-targeting-slc19a1-in-cem-c1-cells
#12
Shu-Mei Wang, Lu-Lu Sun, Wan-Shui Wu, Dan Yan
The human solute carrier family 19 member 1 (SLC19A1) is the gene coding for reduced folate carrier 1 (RFC1). In our previous work, we showed that the miR-595-related polymorphism, rs1051296 G>T, which was located in the 3'-untranslated region (3'-UTR) of SLC19A1, was associated with high methotrexate (MTX) plasma concentrations in pediatric acute lymphoblastic leukaemia (ALL) patients. The present study aimed to investigate the role of miR-595 in the regulation of SLC19A1 expression and its effects on the cellular uptake and cytotoxicity of MTX in ALL CEM/C1 cells...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29344299/enhanced-synergism-of-thermo-chemotherapy-for-liver-cancer-with-magnetothermally-responsive-nanocarriers
#13
Minghua Li, Wenbo Bu, Jie Ren, Jianbo Li, Li Deng, Mingyuan Gao, Xiaolong Gao, Peijun Wang
A combination of magnetic hyperthermia and magnetothermally-facilitated drug release system was developed as a promising strategy for liver cancer therapy. The thermosensitive copolymer, 6sPCL-b-P(MEO2MA-co-OEGMA) shows a good temperature-controlled drug release response. Mn-Zn ferrite magnetic nanoparticles (MZF-MNPs) exhibit a strong magnetic thermal effect with an alternating magnetic field (AMF). Owing to its high magnetic sensitivity, the magnetothermally-responsive nanocarrier/doxorubicin (MTRN/DOX) can be concentrated in the tumor site efficiently through magnetic targeting...
2018: Theranostics
https://www.readbyqxmd.com/read/29343825/a-survey-of-validation-strategies-for-crispr-cas9-editing
#14
Monica F Sentmanat, Samuel T Peters, Colin P Florian, Jon P Connelly, Shondra M Pruett-Miller
The T7 endonuclease 1 (T7E1) mismatch detection assay is a widely used method for evaluating the activity of site-specific nucleases, such as the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system. To determine the accuracy and sensitivity of this assay, we compared the editing estimates derived by the T7E1 assay with that of targeted next-generation sequencing (NGS) in pools of edited mammalian cells. Here, we report that estimates of nuclease activity determined by T7E1 most often do not accurately reflect the activity observed in edited cells...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343807/house-dust-mite-induced-allergic-airway-disease-is-attenuated-in-cd11ccreil-4r%C3%AE-l%C3%A2-x-mice
#15
Natalie Eva Nieuwenhuizen, Frank Kirstein, Jennifer Claire Hoving, Frank Brombacher
The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c+ cells influences allergen-induced Th2 responses in mice. CD11ccreIL-4Rα-/l°x mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα-/l°x littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite. Cytokine responses, eosinophil and neutrophil infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were evaluated after allergen challenge...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343689/a-novel-%C3%AE-conopeptide-eu1-6-inhibits-n-type-cav2-2-calcium-channels-and-exhibits-potent-analgesic-activity
#16
Zhuguo Liu, Peter Bartels, Mahsa Sadeghi, Tianpeng Du, Qing Dai, Cui Zhu, Shuo Yu, Shuo Wang, Mingxin Dong, Ting Sun, Jiabin Guo, Shuangqing Peng, Ling Jiang, David J Adams, Qiuyun Dai
We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343642/mechanogenetics-for-the-remote-and-noninvasive-control-of-cancer-immunotherapy
#17
Yijia Pan, Sangpil Yoon, Jie Sun, Ziliang Huang, Changyang Lee, Molly Allen, Yiqian Wu, Ya-Ju Chang, Michel Sadelain, K Kirk Shung, Shu Chien, Yingxiao Wang
While cell-based immunotherapy, especially chimeric antigen receptor (CAR)-expressing T cells, is becoming a paradigm-shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and noninvasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that is activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK293T cells to convert the ultrasound-activated Piezo1 into transcriptional activities...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343578/a-new-quinoline-brd4-inhibitor-targets-a-distinct-latent-hiv-1-reservoir-for-re-activation-from-other-shock-drugs
#18
Erik Abner, Mateusz Stoszko, Lei Zeng, Heng-Chang Chen, Andrea Izquierdo-Bouldstridge, Tsuyoshi Konuma, Eduard Zorita, Elisa Fanunza, Qiang Zhang, Tokameh Mahmoudi, Ming-Ming Zhou, Guillaume J Filion, Albert Jordan
Upon HIV-1 infection, a reservoir of latently infected resting T cells prevents the eradication of the virus from patients. To achieve complete depletion, the existing virus-suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. We previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol) that is able to reactivate viral transcription in several models of HIV latency including J-Lat cells through an unknown mechanism. MMQO potentiates the activity of known latency-reversing agents (LRAs) or 'shock' drugs such as PKC agonists or HDAC inhibitors...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343554/biased-generation-and-in-situ-activation-of-lung-tissue-resident-memory-cd4-t-cells-in-the-pathogenesis-of-allergic-asthma
#19
Damian L Turner, Monica Goldklang, Filip Cvetkovski, Daniel Paik, Jordis Trischler, Josselyn Barahona, Minwei Cao, Ronak Dave, Nicole Tanna, Jeanine M D'Armiento, Donna L Farber
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells that promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRMs) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. In this study, we used a mouse model of chronic exposure to intranasal house dust mite (HDM) extract to dissect how lung TRMs are generated and function in the persistence and pathogenesis of allergic airway disease...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29342997/-x-linked-inhibitor-of-apoptosis-deficiency-manifested-as-crohn-s-disease-a-case-report-and-literature-review
#20
L J Xu, Y Y Luo, J D Yu, J G Lou, Y H Fang, J Chen
Objective: To analyze the clinical characteristics of X-linked inhibitor of apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's disease. Methods: Clinical manifestations, laboratory investigations, genetic testing and therapeutic interventions of one case of XIAP deficiency who was admitted to Department of Gastroenterology in Children's Hospital, Zhejiang University School of Medicine in May 2016 were summarized. PubMed and Chinese database for articles published from January 2016 to June 2017 were searched using the key words of'Crohn's disease'and'XIAP', and the relevant literature was reviewed...
January 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
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