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https://www.readbyqxmd.com/read/29159928/the-immunogenetics-of-neurological-disease
#1
REVIEW
Maneesh K Misra, Vincent Damotte, Jill A Hollenbach
Genes encoding antigen-presenting molecules within the human major histocompatibility complex (MHC) account for the highest component of genetic risk for many neurological diseases, such as multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. Myriad genetic, immunological and environmental factors may contribute to an individual's susceptibility to neurological disease. Here, we review and discuss the decades long research on the influence of genetic variation at the MHC locus and the role of immunogenetic killer cell immunoglobulin-like receptor (KIR) loci in neurological diseases, including multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis...
November 21, 2017: Immunology
https://www.readbyqxmd.com/read/29159903/soluble-mhc-molecules-in-immune-regulation-highlighting-class-ii-antigens
#2
REVIEW
Katerina Bakela, Irene Athanassakis
The involvement of Major histocompatibility complex (MHC) antigens in the development and regulation of immune response has been well defined over the years, starting from maturation, antigenic peptide loading, migration to the cell membrane for recognition by the T cell receptor and recycling for immune response cessation. During this intracellular trafficking, MHC antigens find a way to be excreted by the cells, since they can be found as soluble MHC class I (sMHCI) and class II (sMHCII) molecules in all body fluids...
November 21, 2017: Immunology
https://www.readbyqxmd.com/read/29158528/fine-mapping-of-genetic-loci-driving-spontaneous-clearance-of-hepatitis-c-virus-infection
#3
Hailiang Huang, Priya Duggal, Chloe L Thio, Rachel Latanich, James J Goedert, Alessandra Mangia, Andrea L Cox, Gregory D Kirk, Shruti Mehta, Jasneet Aneja, Laurent Alric, Sharyne M Donfield, Matthew E Cramp, Salim I Khakoo, Leslie H Tobler, Michael Busch, Graeme J Alexander, Hugo R Rosen, Brian R Edlin, Florencia P Segal, Georg M Lauer, David L Thomas, Mark J Daly, Raymond T Chung, Arthur Y Kim
Approximately three quarters of acute hepatitis C (HCV) infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using ImmunoChip in European and African ancestries. We confirmed two previously reported significant associations, in the IL28B/IFNL4 and the major histocompatibility complex (MHC) regions, with spontaneous clearance in the European population...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158167/clc-3-chloride-channel-is-involved-in-isoprenaline-induced-cardiac-hypertrophy
#4
Chunmei Li, Dan Huang, Jing Tang, Mengqing Chen, Qun Lu, He Li, Mengzhen Zhang, Bin Xu, Jianwen Mao
Isoprenaline, an activator of β-adrenergic receptor, has been found to induce cardiac hypertrophy in vivo and in vitro, but the exact mechanism is still unclear. ClC-3 is a member of the chloride channel family and is highly expressed in mammalian myocardium. In the present study, the role of ClC-3 in isopronaline-induced cardiac hypertrophy was investigated. We found that ClC-3 expression was reduced in isoprenaline-induced hypertrophic H9c2 cells, primary rat neonatal cardiomyocytes and myocardium of C57/BL/6 mice, and this reduction was prevented by the pretreatment of propranolol...
November 17, 2017: Gene
https://www.readbyqxmd.com/read/29157986/lncrna-myocardial-infarction-associated-transcript-miat-contributed-to-cardiac-hypertrophy-by-regulating-tlr4-via-mir-93
#5
Yunwei Li, Juan Wang, Lili Sun, Shengnan Zhu
It has been reported that lncRNA myocardial infarction-associated transcript (MIAT) facilitated the pathological development in angiotensin II (AngII)-induced cardiac hypertrophy. Nevertheless, the underlying mechanism of MIAT involved in cardiac hypertrophy is largely unknown. In this study, AngII-treated cardiomyocytes were applied as a cardiac hypertrophy model in vitro. The expressions of MIAT and miR-93 were detected by qRT-PCR. The protein levels of toll-like receptor 4 (TLR4), atrial natriuretic factor (ANF), beta-myosin heavy chain (β-MHC), phosphoinositide-3 kinase (PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) were determined by western blot...
November 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29157448/ab-initio-conformational-epitope-structure-prediction-using-genetic-algorithm-and-svm-for-vaccine-design
#6
Basem Ameen Moghram, Emad Nabil, Amr Badr
BACKGROUND AND OBJECTIVE: T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i...
January 2018: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29157306/a-pilot-study-of-the-immunogenicity-of-a-9-peptide-breast-cancer-vaccine-plus-poly-iclc-in-early-stage-breast-cancer
#7
Patrick M Dillon, Gina R Petroni, Mark E Smolkin, David R Brenin, Kimberly A Chianese-Bullock, Kelly T Smith, Walter C Olson, Ibrahim S Fanous, Carmel J Nail, Christiana M Brenin, Emily H Hall, Craig L Slingluff
BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157299/the-similarities-between-smdcs-and-regdcs-in-alleviating-the-immune-injury-caused-by-transplantation-of-hepatocytes-differentiated-from-escs
#8
Cheng Zhang, Wenwei Liao, Bing Cai, Furong Liu, Qiong Ke, Xiaofeng Zhu, Xiaoshun He, Anbin Hu
BACKGROUND: This study aimed to investigate the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and to confirm the low immunogenicity of hepatocytes differentiated from ESCs. METHODS: Green fluorescent protein-labeled ESCs collected from 129 mice were cultured to differentiate into hepatocytes. smDCs and regDCs were cultured in vitro...
November 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29156562/biodegradable-chitosan-decreases-the-immune-response-to-trichinella-spiralis-in-mice
#9
Klaudia Brodaczewska, Natalia Wolaniuk, Katarzyna Lewandowska, Katarzyna Donskow-Łysoniewska, Maria Doligalska
The purpose of this study was to evaluate the potential of chitosan units released during natural degradation of the polymer to activate the immune system against T. spiralis infection. High molecular weight chitosan was injected intraperitoneally into C57BL/6 mice. Flow cytometry and cytokine concentration, measured by ELISA, were used to characterize peritoneal cell populations during T. spiralis infection. The strong chemo-attractive properties of chitosan caused considerable infiltration into the peritoneal cavity of CD11b⁺ cells, with reduced expression of MHC class II, CD80, CD86, Dectin-1 or CD23 receptors in comparison to T...
November 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#10
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29155786/isolation-and-cultivation-of-adult-rat-cardiomyocytes
#11
Franziska Nippert, Rolf Schreckenberg, Klaus-Dieter Schlüter
In an intact heart, adjacent cells influence adult cardiomyocytes. With the method of isolation and cultivation of adult cardiomyocytes, a precise investigation of the behavior of these cells under specific treatments and environments is possible. This manuscript presents a protocol for successful isolation and cultivation of adult rat ventricular cardiomyocytes (ARVC). The rat is sacrificed by cervical dislocation under deep anesthesia. Then, the heart is extracted and the aorta is uncovered. Subsequently, perfusion on the Langendorff perfusion system with calcium depletion and collagenase treatment is performed...
October 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29152228/cd1-from-molecules-to-diseases
#12
REVIEW
D Branch Moody, Sara Suliman
The human cluster of differentiation (CD)1 system for antigen display is comprised of four types of antigen-presenting molecules, each with a distinct functional niche: CD1a, CD1b, CD1c, and CD1d. Whereas CD1 proteins were thought solely to influence T-cell responses through display of amphipathic lipids, recent studies emphasize the role of direct contacts between the T-cell receptor and CD1 itself. Moving from molecules to diseases, new research approaches emphasize human CD1-transgenic mouse models and the study of human polyclonal T cells in vivo or ex vivo in disease states...
2017: F1000Research
https://www.readbyqxmd.com/read/29151718/achievement-of-adequate-glycemic-control-in-patients-with-type-2-diabetes-and-comorbid-mental-health-conditions-treated-in-a-primary-care-setting
#13
Kaitlyn Brown, Katherine Fortenberry, Lisa Gren, Karen Gunning, Carrie McAdam-Marx
Objective: This study investigated the association between the presence of a mental health condition (MHC) diagnosis and glycemic control in patients with type 2 diabetes in a primary care clinic network. Methods: This retrospective cross-sectional study compared adequate glycemic control (A1C <8.0%) in patients with type 2 diabetes with and without any MHC, as well as by MHC subtypes of depression or anxiety, bipolar or schizophrenia disorders, and substance use disorder...
November 2017: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29151581/human-pbmc-transferred-murine-mhc-class-i-ii-deficient-nog-mice-enable-long-term-evaluation-of-human-immune-responses
#14
Tomonori Yaguchi, Asuka Kobayashi, Takashi Inozume, Kenji Morii, Haruna Nagumo, Hiroshi Nishio, Takashi Iwata, Yuyo Ka, Ikumi Katano, Ryoji Ito, Mamoru Ito, Yutaka Kawakami
Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg(null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD...
November 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29151514/a-case-of-dermatomyositis-complicated-by-digital-ischemia-and-lung-adenocarcinoma-in-a-patient-with-positive-anti-signal-recognition-particle-antibodies
#15
Takashi Nawata, Makoto Kubo, Hitomi Mitsui, Keiji Oishi, Masatoshi Omoto, Takashi Kanda, Masafumi Yano
A 58-year-old Japanese woman was diagnosed with anti-signal recognition particle (SRP)-positive dermatomyositis associated with Sjögren's syndrome, rheumatoid arthritis and lung adenocarcinoma. She presented with cutaneous lesions, including ulceration of her right middle finger. Tissue specimens obtained from her right deltoid muscle were positive for CD4(+) T-cell infiltration and the sarcolemma showed the upregulation of major histocompatibility complex (MHC) class I antigens. The present case suggests that overlapping autoimmune diseases or complications of malignancy may result in an atypical clinical presentations and histological findings in patients with anti-SRP antibody-positive dermatomyositis...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29150769/changes-in-expression-of-the-membrane-receptors-cd14-mhc-ii-sr-a-and-tlr4-in-tissue-specific-monocytes-macrophages-following-porphyromonas-gingivalis-lps-stimulation
#16
Chunfang Wu, Chongwu Liu, Kai Luo, Yanfen Li, Jun Jiang, Fuhua Yan
The aim of the study was to provide a theoretical foundation for understanding the relationship between periodontal diseases and systemic diseases by examining the inflammatory effect of Porphyromonas gingivalis lipopolysaccharide (LPS) on monocytes/macrophages isolated from tissues distinct from the oral cavity in normal and hyperlipidemic New Zealand white rabbits. Macrophages were isolated from four separate tissues (mononuclear cells from blood, alveolar macrophages, peritoneal macrophages, and Kupffer cells) from both normal and hyperlipidemic New Zealand white rabbits...
November 18, 2017: Inflammation
https://www.readbyqxmd.com/read/29150562/the-role-of-mhc-e-in-t-cell-immunity-is-conserved-among-humans-rhesus-macaques-and-cynomolgus-macaques
#17
Helen L Wu, Roger W Wiseman, Colette M Hughes, Gabriela M Webb, Shaheed A Abdulhaqq, Benjamin N Bimber, Katherine B Hammond, Jason S Reed, Lina Gao, Benjamin J Burwitz, Justin M Greene, Fidel Ferrer, Alfred W Legasse, Michael K Axthelm, Byung S Park, Simon Brackenridge, Nicholas J Maness, Andrew J McMichael, Louis J Picker, David H O'Connor, Scott G Hansen, Jonah B Sacha
MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8(+) T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#18
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29148973/the-somatically-generated-portion-of-the-t-cell-receptor-cdr3%C3%AE-contributes-to-the-mhc-allele-specificity-of-the-t-cell-receptor
#19
Philippa Marrack, Sai Harsha Krovi, Daniel Silberman, Janice White, Eleanor Kushnir, Maki Nakayama, James Crooks, Thomas Danhorn, Sonia Leach, Randy Anselment, James Scott-Browne, Laurent Gapin, John Kappler
Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29148051/mechanical-parameters-of-the-molecular-motor-myosin-ii-determined-in-permeabilised-fibres-from-slow-and-fast-skeletal-muscles-of-the-rabbit
#20
Valentina Percario, Simona Boncompagni, Feliciano Protasi, Irene Pertici, Francesca Pinzauti, Marco Caremani
The skeletal muscle exhibits large functional differences depending on the myosin heavy chain (MHC) isoform expressed in its molecular motor myosin II. The differences in the mechanical features of force generation by myosin isoforms are investigated in situ by using fast sarcomere-level mechanical methods in permeabilised fibres (sarcomere length 2.4 μm, temperature 12°C, 4% dextran T-500) from the slow (soleus, containing the MHC-1 isoform) and the fast (psoas, containing the MHC-2X isoform) skeletal muscle of the rabbit...
November 17, 2017: Journal of Physiology
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