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https://www.readbyqxmd.com/read/29339380/negative-regulation-of-the-keap1-nrf2-pathway-by-a-p62-sqstm1-splicing-variant
#1
Shun Kageyama, Tetsuya Saito, Miki Obata, Ryo-Hei Koide, Yoshinobu Ichimura, Masaaki Komatsu
A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via multiple mechanisms, including gene expression, post-translational modifications such as ubiquitination and phosphorylation, and autophagic degradation of p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl database search and subsequent biochemical analyses in mice revealed the presence of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region (KIR), which is essential for the interaction with Keap1...
January 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29330418/hla-b-hla-c-and-kir-improve-the-predictive-value-of-ifnl3-for-hepatitis-c-spontaneous-clearance
#2
Mario Frias, Antonio Rivero-Juárez, Diego Rodriguez-Cano, Ángela Camacho, Pedro López-López, María Ángeles Risalde, Bárbara Manzanares-Martín, Teresa Brieva, Isabel Machuca, Antonio Rivero
IFNL3 is the strongest predictor of spontaneous resolution (SR) of hepatitis C virus (HCV), however, consideration of IFNL3 genotype alone is of limited clinical value for the prediction of SR or chronic HCV infection. The objective of this study was to analyze the impact of HLA-B, HLA-C and KIRs on SR, as well as their additive effects on the predictive value of the IFNL3 genotype. We conducted a retrospective study of HIV patients that included both SR and chronic HCV patients. In our study, 61.6% of patients with IFNL3 CC achieved SR, and 81...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329284/identification-of-an-elaborate-nk-specific-system-regulating-hla-c-expression
#3
Hongchuan Li, Martin A Ivarsson, Victoria E Walker-Sperling, Jeff Subleski, Jenna K Johnson, Paul W Wright, Mary Carrington, Niklas K Björkström, Daniel W McVicar, Stephen K Anderson
The HLA-C gene appears to have evolved in higher primates to serve as a dominant source of ligands for the KIR2D family of inhibitory MHC class I receptors. The expression of NK cell-intrinsic MHC class I has been shown to regulate the murine Ly49 family of MHC class I receptors due to the interaction of these receptors with NK cell MHC in cis. However, cis interactions have not been demonstrated for the human KIR and HLA proteins. We report the discovery of an elaborate NK cell-specific system regulating HLA-C expression, indicating an important role for HLA-C in the development and function of NK cells...
January 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#4
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29326855/all-types-of-age-related-macular-degeneration-in-one-patient
#5
Zafer Cebeci, Nur Kır
Herein, we describe a neovascular age-related macular degeneration patient with retinal angiomatous proliferation (RAP) and polypoidal choroidal vasculopathy (PCV) coexisting in the same eye at the time of diagnosis. A 55-year-old woman presented with a history of decreased vision in her left eye. Fundoscopy, fluorescein and indocyanine green angiography, and optical coherence tomography imaging revealed RAP and PCV lesions in her left eye at first diagnosis. The patient received intravitreal ranibizumab therapy but developed tachyphylaxis after the first dose despite having three monthly doses...
December 2017: Turkish Journal of Ophthalmology
https://www.readbyqxmd.com/read/29322425/production-of-recombinant-killer-immunoglobulin-like-receptors-for-crystallography-and-luminex-based-assays
#6
Phillip Pymm, Julian P Vivian
The killer immunoglobulin-like receptors (KIR) are a highly diverse family of cell-surface receptors that are of importance to the effector function of Natural Killer cells. KIR have been implicated in the detection and clearance of malignantly transformed cells and in the immune-control of viruses including HIV, HCV and CMV. Recently, the mismatching of donor and recipient KIR has been demonstrated to improve success of hematopoietic stem cell transplantation treatments of leukemias. Due to the high degree of diversity amongst the KIR, a number of strategies are required for the production of recombinant protein for medical, biochemical and structural applications...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29320699/lret-determination-of-molecular-distances-during-ph-gating-of-the-mammalian-inward-rectifier-kir1-1b
#7
Mikheil Nanazashvili, Jorge E Sánchez-Rodríguez, Ben Fosque, Francisco Bezanilla, Henry Sackin
Gating of the mammalian inward rectifier Kir1.1 at the helix bundle crossing (HBC) by intracellular pH is believed to be mediated by conformational changes in the C-terminal domain (CTD). However, the exact motion of the CTD during Kir gating remains controversial. Crystal structures and single-molecule fluorescence resonance energy transfer of KirBac channels have implied a rigid body rotation and/or a contraction of the CTD as possible triggers for opening of the HBC gate. In our study, we used lanthanide-based resonance energy transfer on single-Cys dimeric constructs of the mammalian renal inward rectifier, Kir1...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29317494/hydrogen-sulfide-inhibits-kir2-and-kir3-channels-by-decreasing-sensitivity-to-the-phospholipid-pip2
#8
Junghoon Ha, Yu Xu, Takeharu Kawano, Tyler Hendon, Lia Baki, Sumanta Garai, Andreas Papapetropoulos, Ganesh Thakur, Leigh D Plant, Diomedes E Logothetis
Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain and other peripheral tissues. Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. The gasotransmitter carbon monoxide has been shown to regulate Kir channel activity by altering channel-PIP2 interactions.  Here, we tested in two cellular models the effects and mechanism of action of another gasotransmitter, hydrogen sulfide (H2S), thought to play a key role in cellular responses under ischemic conditions...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29307888/high-resolution-hla-analysis-reveals-independent-class-i-haplotypes-and-amino-acid-motifs-protective-for-multiple-sclerosis
#9
Steven J Mack, Julia Udell, Franziska Cohen, Kazutoyo Osoegawa, Sharon K Hawbecker, David A Noonan, Martha B Ladner, Damian Goodridge, Elizabeth A Trachtenberg, Jorge R Oksenberg, Henry A Erlich
We investigated association between HLA class I and class II alleles and haplotypes, and KIR loci and their HLA class I ligands, with multiple sclerosis (MS) in 419 European American MS patients and 412 ethnically matched controls, using next-generation sequencing. The DRB1*15:01~DQB1*06:02 haplotype was highly predisposing (odds ratio (OR) = 3.98; 95% confidence interval (CI) = 3-5.31; p-value (p) = 2.22E-16), as was DRB1*03:01~DQB1*02:01 (OR = 1.63; CI = 1.19-2.24; p = 1.41E-03). Hardy-Weinberg (HW) analysis in MS patients revealed a significant DRB1*03:01~DQB1*02:01 homozyote excess (15 observed; 8...
January 8, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29273355/what-is-the-most-important-for-elite-control-genetic-background-of-patient-genetic-background-of-partner-both-or-neither-description-of-complete-natural-history-within-a-couple-of-msm
#10
M Bendenoun, A Samri, V Avettand-Fènoël, S Cardinaud, B Descours, G Carcelain, M-C Mazeron, J-F Bergmann, A Urrutia, A Moris, C Rouzioux, F Simon, P Andre, M Pocard, X Dray, T Mourez, V Vieillard, B Autran, F Barin, P Sellier
BACKGROUND: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background. METHODS: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined. FINDINGS: Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay...
December 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29247781/kir-ligand-mismatch-in-donor-vs-recipient-direction-provides-better-graft-versus-tumor-effect-in-patients-with-hematological-malignancies-undergoing-allogeneic-t-replete-haploidentical-transplantation-followed-by-post-transplant-cyclophosphamide
#11
Anne Wanquet, Stephania Bramanti, Samia Harbi, Sabine Fürst, Faezeh Legrand, Catherine Faucher, Angela Granata, Boris Calmels, Claude Lemarie, Christophe Picard, Christian Chabannon, Pierre-Jean Weiller, Luca Castagna, Didier Blaise, Raynier Devillier
We evaluated the impact of unidirectional donor vs. recipient killer-cell immunoglobulin-like receptor (KIR)-ligand mismatch (KIR-Lmm) on the outcomes of T-replete Haplo-SCT with post-transplant cyclophosphamide (PT-Cy) in a cohort of 144 patients treated for various hematological diseases. We separately analyzed 81 patients in complete remission (CR group) and 63 with active disease (no CR group) at the time of Haplo-SCT. One-third of patients in each group had KIR-Lmm. In the no CR group, KIR-Lmm was associated with a significantly lower incidence of relapse (hazard ratio (HR) = 0...
December 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29247515/intrahepatic-and-peripheral-blood-phenotypes-of-nk-and-t-cells-differential-surface-expression-of-kir-receptors
#12
Ariel Podhorzer, Andrés Machicote, Santiago Belen, Leandro Lauferman, Oscar Imventarza, Silvina Montal, Sebastián Marciano, Omar Galdame, Luis G Podesta, Leonardo Fainboim
Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood NK, NKT and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activatory marker NKp44...
December 16, 2017: Immunology
https://www.readbyqxmd.com/read/29237245/molecular-mechanisms-and-physiological-relevance-of-rgk-proteins-in-the-heart
#13
REVIEW
U Meza, D Beqollari, R A Bannister
The primary route of Ca2+ entry into cardiac myocytes is via 1,4-dihydropyridine-sensitive, voltage-gated L-type Ca2+ channels. Ca2+ influx through these channels influences duration of action potential and engages excitation-contraction (EC) coupling in both the atria and the myocardium. Members of the RGK (Rad, Rem, Rem2 and Gem/Kir) family of small GTP-binding proteins are potent, endogenously expressed inhibitors of cardiac L-type channels. Although much work has focused on the molecular mechanisms by which RGK proteins inhibit the CaV 1...
December 13, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29222435/long-term-maintenance-of-peripheral-blood-derived-human-nk-cells-in-a-novel-human-il-15-transgenic-nog-mouse
#14
Ikumi Katano, Chiyoko Nishime, Ryoji Ito, Tsutomu Kamisako, Takuma Mizusawa, Yuyo Ka, Tomoyuki Ogura, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
We generated a novel mouse strain expressing transgenic human interleukin-15 (IL-15) using the severe immunodeficient NOD/Shi-scid-IL-2Rγ null (NOG) mouse genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from the peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. In addition, the cell number increased, and the hu-PB-NK cells persisted for 3 months without signs of xenogeneic graft versus host diseases (xGVHD). These in vivo-expanded hu-PB-NK cells maintained the original expression patterns of various surface antigens, including NK receptors and killer cell immunoglobulin-like receptor (KIR) molecules...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211322/perivascular-adipose-tissue-and-the-dynamic-regulation-of-kv-7-and-kir-channels-implications-to-resistant-hypertension
#15
Maik Gollasch, Donald G Welsh, Rudolf Schubert
Resistant hypertension is defined as high blood pressure that remains uncontrolled despite treatment with at least three antihypertensive drugs at adequate doses. Resistant hypertension is an increasingly common clinical problem in older age, obesity, diabetes, sleep apnea, and chronic kidney disease. Although the direct vasodilator minoxidil was introduced in the early 1970s, only recently has this drug been shown to be particularly effective in a subgroup of patients with treatment-resistant or uncontrolled hypertension...
December 6, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29205356/molecular-and-functional-characterization-of-inwardly-rectifying-k-currents-in-murine-proximal-colon
#16
Xu Huang, Si Hyung Lee, Hongli Lu, Kenton M Sanders, Sang Don Koh
Membrane potentials of gastrointestinal (GI) muscles are important because voltage dependent Ca2+ channels in smooth muscle cells (SMC) provide the Ca2+ that triggers contraction. Regulation of membrane potential is complicated because SMC are electrically coupled to interstitial cells of Cajal (ICC) and PDGFRα+ cells. Activation of conductances in any of these cells affects the excitability of the syncytium. We explored the role of inward rectifier K+ conductances in colonic ICC that might contribute to regulation of membrane potential...
December 3, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29201919/dynamics-of-insulin-secretion-from-endoc-%C3%AE-h1-%C3%AE-cell-pseudoislets-in-response-to-glucose-and-other-nutrient-and-nonnutrient-secretagogues
#17
Hiroki Teraoku, Sigurd Lenzen
The dynamics of insulin secretion were characterized in response to a variety of physiological and pharmacological stimulators and other compounds in perifused pseudoislets generated from cells of the EndoC-βH1 β-cell line. Perifusion of EndoC-βH1 pseudoislets with the physiological stimulus glucose (16.7 mM) induced sustained insulin secretion, which was inhibited by mannoheptulose. The adenylate cyclase activators IBMX and forskolin strongly potentiated this secretion. Glibenclamide, a Kir 6.2 potassium channel blocker, and Bay K 8644, an opener of the voltage-sensitive Ca2+ channel, also potentiated glucose-induced insulin secretion...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29197675/homozygous-hla-c1-is-associated-with-reduced-risk-of-relapse-after-hla-matched-transplantation-in-patients-with-myeloid-leukemia
#18
Nobuyoshi Arima, Junya Kanda, Junji Tanaka, Toshio Yabe, Yasuo Morishima, Sung-Won Kim, Yuho Najima, Yukiyasu Ozawa, Tetsuya Eto, Heiwa Kanamori, Takehiko Mori, Naoki Kobayashi, Tadakazu Kondo, Hirohisa Nakamae, Naoyuki Uchida, Masami Inoue, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry...
December 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29194614/immunomodulatory-effects-of-foreskin-mesenchymal-stromal-cells-fsk-mscs-on-natural-killer-nk-cells
#19
Mehdi Najar, Mohammad Fayyad-Kazan, Nathalie Meuleman, Dominique Bron, Hussein Fayyad-Kazan, Laurence Lagneaux
Foreskin-mesenchymal stromal cells (FSK-MSCs) are immune-privileged thus making them valuable immunotherapeutic cell product. Characterization of the relationship between FSK-MSCs and natural killer (NK) cells is essential to improve cell-based therapy. In the present study, we studied for the first time FSK-MSCs-NK interaction and showed that the result of such cross talk was robustly dependent on the type of cytokines (IL-2, IL-12, IL-15 and IL-21) employed to activate NK cells. Distinctly activated-NK cells showed uneven cytotoxicity against FSK-MSCs, triggering their death in fine...
December 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29192147/protein-crowding-and-lipid-complexity-influence-the-nanoscale-dynamic-organization-of-ion-channels-in-cell-membranes
#20
Anna L Duncan, Tyler Reddy, Heidi Koldsø, Jean Hélie, Philip W Fowler, Matthieu Chavent, Mark S P Sansom
Cell membranes are crowded and complex environments. To investigate the effect of protein-lipid interactions on dynamic organization in mammalian cell membranes, we have performed coarse-grained molecular dynamics simulations containing >100 copies of an inwardly rectifying potassium (Kir) channel which forms specific interactions with the regulatory lipid phosphatidylinositol 4,5-bisphosphate (PIP2). The tendency of protein molecules to cluster has the effect of organizing the membrane into dynamic compartments...
November 30, 2017: Scientific Reports
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