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https://www.readbyqxmd.com/read/29151219/implementation-of-the-nmr-chemical-shift-covariance-analysis-chesca-a-chemical-biologist-s-approach-to-allostery
#1
Stephen Boulton, Rajeevan Selvaratnam, Rashik Ahmed, Giuseppe Melacini
Mapping allosteric sites is emerging as one of the central challenges in physiology, pathology, and pharmacology. Nuclear Magnetic Resonance (NMR) spectroscopy is ideally suited to map allosteric sites, given its ability to sense at atomic resolution the dynamics underlying allostery. Here, we focus specifically on the NMR CHEmical Shift Covariance Analysis (CHESCA), in which allosteric systems are interrogated through a targeted library of perturbations (e.g., mutations and/or analogs of the allosteric effector ligand)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29150961/modulation-of-igg1-immunoeffector-function-by-glycoengineering-of-the-gdp-fucose-biosynthesis-pathway
#2
Ronan M Kelly, Ronald L Kowle, Zhirui Lian, Beth A Strifler, Derrick R Witcher, Bhavin S Parekh, Tongtong Wang, Christopher C Frye
Cross-linking of the Fcγ receptors expressed on the surface of hematopoietic cells by IgG immune complexes triggers the activation of key immune effector mechanisms, including antibody-dependent cell mediated cytotoxicity (ADCC). A conserved N-glycan positioned at the N-terminal region of the IgG CH 2 domain is critical in maintaining the quaternary structure of the molecule for Fcγ receptor engagement. The removal of a single core fucose residue from the N-glycan results in a considerable increase in affinity for FcγRIIIa leading to an enhanced receptor-mediated immunoeffector function...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150633/ketamine-s-antidepressant-effect-is-mediated-by-energy-metabolism-and-antioxidant-defense-system
#3
Katja Weckmann, Michael J Deery, Julie A Howard, Renata Feret, John M Asara, Frederik Dethloff, Michaela D Filiou, Jamie Iannace, Christiana Labermaier, Giuseppina Maccarrone, Christian Webhofer, Larysa Teplytska, Kathryn Lilley, Marianne B Müller, Christoph W Turck
Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150602/tlr7-mediated-viral-recognition-results-in-focal-type-i-interferon-secretion-by-dendritic-cells
#4
Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150566/the-loss-of-tet2-promotes-cd8-t-cell-memory-differentiation
#5
Shannon A Carty, Mercy Gohil, Lauren B Banks, Renee M Cotton, Matthew E Johnson, Erietta Stelekati, Andrew D Wells, E John Wherry, Gary A Koretzky, Martha S Jordan
T cell differentiation requires appropriate regulation of DNA methylation. In this article, we demonstrate that the methylcytosine dioxygenase ten-eleven translocation (TET)2 regulates CD8(+) T cell differentiation. In a murine model of acute viral infection, TET2 loss promotes early acquisition of a memory CD8(+) T cell fate in a cell-intrinsic manner without disrupting Ag-driven cell expansion or effector function. Upon secondary recall, TET2-deficient memory CD8(+) T cells demonstrate superior pathogen control...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150563/nfat5-regulated-macrophage-polarization-supports-the-proinflammatory-function-of-macrophages-and-t-lymphocytes
#6
Mónica Tellechea, Maria Buxadé, Sonia Tejedor, Jose Aramburu, Cristina López-Rodríguez
Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150546/differential-regulation-of-two-tiered-plant-immunity-and-sexual-reproduction-by-anxur-receptor-like-kinases
#7
Hyunggon Mang, Baomin Feng, Zhangjian Hu, Aurelien Boisson-Dernier, Christina Franck, Xiangzong Meng, Yanyan Huang, Jinggeng Zhou, Guangyuan Xu, Taotao Wang, Libo Shan, Ping He
Plants have evolved two tiers of immune receptors to detect infections: cell surface-resident pattern recognition receptors (PRRs) that sense microbial signatures and intracellular nucleotide-binding domain leucine-rich repeat (NLR) proteins that recognize pathogen effectors. How PRRs and NLRs interconnect and activate the specific and overlapping plant immune responses remains elusive. A genetic screen for components controlling plant immunity identified ANXUR1 (ANX1), a malectin-like domain-containing receptor-like kinase, together with its homolog ANX2, as important negative regulators of both PRR- and NLR-mediated immunity in Arabidopsis thaliana...
November 17, 2017: Plant Cell
https://www.readbyqxmd.com/read/29150501/glna-truncation-in-salmonella-enterica-results-in-a-small-colony-variant-phenotype-attenuated-host-cell-entry-and-reduced-expression-of-flagellin-and-spi-1-associated-effector-genes
#8
Philipp Aurass, Juliane Düvel, Susanne Karste, Ulrich Nübel, Wolfgang Rabsch, Antje Flieger
Many pathogenic bacteria use sophisticated survival strategies to overcome harsh environmental conditions. One is the formation of slow-growing subpopulations termed small colony variants (SCVs). Here we characterize an SCV, which spontaneously emerged from an axenic Salmonella enterica serovar Typhimurium water culture. We found that the SCV harbors a frameshift mutation in the glutamine synthetase gene glnA leading to a ∼90% truncation of the corresponding protein. Glutamine synthetase, a central enzyme in nitrogen assimilation, converts glutamate and ammonia to glutamine...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150361/post-translational-mechanisms-of-host-subversion-by-bacterial-effectors
#9
REVIEW
Nichollas E Scott, Elizabeth L Hartland
Bacterial effector proteins are a specialized class of secreted proteins that are translocated directly into the host cytoplasm by bacterial pathogens. Effector proteins have diverse activities and targets, and many mediate post-translational modifications of host proteins. Effector proteins offer potential in novel biotechnological and medical applications as enzymes that may modify human proteins. Here, we discuss the mechanisms used by effectors to subvert the human host through blocking, blunting, or subverting immune mechanisms...
November 14, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29150278/a-hypothetical-role-for-notch-signaling-pathway-in-immunopathogenesis-of-leprosy
#10
Héctor Serrano-Coll, Liliana Acevedo-Saenz, Nora Cardona-Castro
Leprosy is a chronic infectious disease caused by Mycobacterium leprae mainly affecting skin and peripheral nerves. Leprosy has a broad range of clinical manifestations that range from mild (tuberculoid leprosy) to severe (lepromatous leprosy) forms, and are highly dependent on the host's immune response. Among the immune response elements involved in the pathogenesis of leprosy are the Toll-like receptors (TLRs), vitamin D receptor (VDR), natural killer cells (NK), and T cells. These innate and adaptive immune response elements may be related to the Notch signaling pathway, which is involved in immune cell growth, differentiation, and proliferation...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150026/regulatory-t-cells-friends-or-foe-in-human-mycobacterium-leprae-infection
#11
Ana T Chaves, Atvaldo F Ribeiro-Junior, Sandra Lyon, Nayara I Medeiros, Fábio Cassirer-Costa, Karina S Paula, Edilamar S Alecrim, Cristiane A S Menezes, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes
Regulatory T cells (Tregs) are known to control immune responses by suppressing the antigen-presenting and effector T cells. Some mechanisms adopted by Tregs in combating Mycobacterium infections have been proposed. Nevertheless, in M. leprae infection, also known as leprosy or Hansen's disease, the role of Tregs has not been completely elucidated. Using multicolor flow cytometry, we evaluated the expression of different cell surface and intracellular molecules present in Tregs from peripheral blood samples of leprosy patients...
November 13, 2017: Immunobiology
https://www.readbyqxmd.com/read/29149940/immune-activation-in-sepsis
#12
REVIEW
Andrew Conway-Morris, Julie Wilson, Manu Shankar-Hari
Sepsis is caused by a dysregulated host response to infection. Immune responses determine the characteristics of sepsis. The body's protection against infection involves danger signal surveillance and recognition from nonself, effector functions in response to sensing danger signals, homeostatic regulation, and generation of immunologic memory. During sepsis, the immune system is activated by pathogen-associated and host-derived molecular patterns. Detecting these molecular patterns generates multisystem responses...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#13
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29149101/how-does-p53-induce-apoptosis-and-how-does-this-relate-to-p53-mediated-tumour-suppression
#14
REVIEW
Brandon J Aubrey, Gemma L Kelly, Ana Janic, Marco J Herold, Andreas Strasser
The tumour suppressor gene TP53 is mutated in ~50% of human cancers. In addition to its function in tumour suppression, p53 also plays a major role in the response of malignant as well as nontransformed cells to many anticancer therapeutics, particularly those that cause DNA damage. P53 forms a homotetrameric transcription factor that is reported to directly regulate ~500 target genes, thereby controlling a broad range of cellular processes, including cell cycle arrest, cell senescence, DNA repair, metabolic adaptation and cell death...
November 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29148970/autophagic-cell-death-is-dependent-on-lysosomal-membrane-permeability-through-bax-and-bak
#15
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisciak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and in a previous eLIFE paper, Karch et al., 2013 showed that these 2 effectors are also needed for mitochondrial-dependent cellular necrosis. Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29148265/resveratrol-ameliorates-the-severity-of-fibrogenesis-in-mice-with-experimental-chronic-pancreatitis
#16
Yixuan Xia, Hai-Tao Xiao, Kanglun Liu, Hong-Jie Zhang, Siu Wai Tsang
SCOPE: Resveratrol is generally considered beneficial to health-span and longevity since this dietary stilbenoid has been scrutinized for its activating property on the "rescue gene" sirtuin-1 that promotes cellular survival under stress. In addition to its antiaging property, our previous in vitro studies revealed that resveratrol notably inhibited the production of extracellular matrix (ECM) proteins in pancreatic stellate cells (PSCs), the classic effector cells against pancreatic injury...
November 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29147628/trial-watch-adoptively-transferred-cells-for-anticancer-immunotherapy
#17
REVIEW
Carole Fournier, François Martin, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi, Lionel Apetoh
Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147626/functional-t-cells-targeting-tumor-associated-antigens-are-predictive-for-recurrence-free-survival-of-patients-with-radically-operated-non-small-cell-lung-cancer
#18
Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147609/tumor-immunology-meets%C3%A2-immunology-modified-cancer-cells-as-professional-apc-for-priming-na%C3%A3-ve-tumor-specific-cd4-t-cells
#19
REVIEW
Farah Bou Nasser Eddine, Elise Ramia, Giovanna Tosi, Greta Forlani, Roberto S Accolla
Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147008/the-transcription-factor-batf3-inhibits-the-differentiation-of-regulatory-t-cells-in-the-periphery
#20
Wonyong Lee, Hyeong Su Kim, Soo Seok Hwang, Gap Ryol Lee
Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation...
November 17, 2017: Experimental & Molecular Medicine
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