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https://www.readbyqxmd.com/read/29342229/a-rapid-epistatic-mixed-model-association-analysis-by-linear-retransformations-of-genomic-estimated-values
#1
Chao Ning, Dan Wang, Huimin Kang, Raphael Mrode, Lei Zhou, Shizhong Xu, Jian-Feng Liu
Motivation: Epistasis provides a feasible way for probing potential genetic mechanism of complex traits. However, time-consuming computation challenges successful detection of interaction in practice, especially when linear mixed model (LMM) is used to control type I error in the presence of population structure and cryptic relatedness. Results: A rapid epistatic mixed-model association analysis (REMMA) method was developed to overcome computational limitation. This method first estimates individuals' epistatic effects by an extended genomic best linear unbiased prediction (EG-BLUP) model with additive and epistatic kinship matrix, then pairwise interaction effects are obtained by linear retransformations of individuals' epistatic effects...
January 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29341455/microsatellite-markers-for-evaluating-the-diversity-of-the-natural-killer-complex-and-major-histocompatibility-complex-genomic-regions-in-domestic-horses
#2
C Horecky, E Horecka, J Futas, E Janova, P Horin, A Knoll
Genotyping microsatellite markers represents a standard, relatively easy and inexpensive method of assessing genetic diversity of complex genomic regions in various animal species, such as the major histocompatibility complex (MHC) and/or natural killer cell receptor (NKR) genes. MHC-linked microsatellite markers have been identified and some of them were used for characterizing MHC polymorphism in various species, including horses. However, most of those were MHC class II markers, while MHC class I and III sub-regions were less well covered...
January 17, 2018: HLA
https://www.readbyqxmd.com/read/29340708/molecular-recognition-of-microbial-lipid-based-antigens-by-t-cells
#3
REVIEW
Stephanie Gras, Ildiko Van Rhijn, Adam Shahine, Jérôme Le Nours
The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells leading to antigen-specific activation...
January 16, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29339738/dna-methyltransferase-inhibition-upregulates-mhc-i-to-potentiate-cytotoxic-t-lymphocyte-responses-in-breast-cancer
#4
Na Luo, Mellissa J Nixon, Paula I Gonzalez-Ericsson, Violeta Sanchez, Susan R Opalenik, Huili Li, Cynthia A Zahnow, Michael L Nickels, Fei Liu, Mohammed N Tantawy, Melinda E Sanders, H Charles Manning, Justin M Balko
Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339521/immunogenetic-novelty-confers-a-selective-advantage-in-host-pathogen-coevolution
#5
Karl P Phillips, Joanne Cable, Ryan S Mohammed, Magdalena Herdegen-Radwan, Jarosław Raubic, Karolina J Przesmycka, Cock van Oosterhout, Jacek Radwan
The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins host-pathogen "Red Queen" coevolution, it has not been demonstrated in the context of natural MHC diversity...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29335408/escape-from-thymic-deletion-and-anti-leukemic-effects-of-t-cells-specific-for-hematopoietic-cell-restricted-antigen
#6
Ji-Min Ju, Min Ho Jung, Giri Nam, Woojin Kim, Sehwa Oh, Hyun Duk Kim, Joo Young Kim, Jun Chang, Sung Hak Lee, Gyeong Sin Park, Chang-Ki Min, Dong-Sup Lee, Moon Gyo Kim, Kyungho Choi, Eun Young Choi
Whether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion. This incomplete thymic deletion occurs to the T cells developing de novo in the thymus of H60-positive recipients in H60-mismatched bone marrow transplantation (BMT)...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334553/post-treatment-controllers-after-treatment-interruption-in-chronically-hiv-infected-patients
#7
Franco Maggiolo, Elisa Di Filippo, Laura Comi, Annapaola Callegaro
OBJECTIVE: Control HIV replication requires continuous combined antiretroviral therapy (cART) as discontinuation of cART results in a rapid viral rebound. However, a few individuals exist who took cART for several years and did not show the expected viral rebound after treatment cessation. Most post-treatment controllers (PTCs) are early treated individuals. We report three cases who started cART during chronic infection. DESIGN: Patients were treated and monitored according to Italian guidelines...
January 13, 2018: AIDS
https://www.readbyqxmd.com/read/29334412/stallion-semen-quality-depends-on-mhc-matching-to-teaser-mare
#8
E Jeannerat, E Marti, C Berney, F Janett, H Bollwein, H Sieme, D Burger, C Wedekind
The major histocompatibility complex (MHC) has repeatedly been found to influence mate choice of vertebrates, with MHC-dissimilar mates typically being preferred over MHC-similar mates. We used horses (Equus caballus) to test whether MHC matching also affects male investment into ejaculates after short exposure to a female. Semen characteristics varied much among stallions. Controlling for this variance with a full-factorial within-subject experimental design, we found that a short exposure to an MHC-dissimilar mare enhanced male plasma testosterone and led to ejaculates with elevated sperm numbers as compared to exposure to an MHC-similar mare...
January 15, 2018: Molecular Ecology
https://www.readbyqxmd.com/read/29332623/gene-expression-and-lymphocyte-population-at-the-fetal-maternal-interface-in-sheep-pregnancies-established-by-somatic-cell-nuclear-transfer
#9
Jason A Koroghli, Elizabeth Floyd, Misha Regouski, Kerry Rood, Kirsten Gash, Kip Panter, Rusty Stott, Christopher J Davies, Irina A Polejaeva, Heloisa M Rutigliano
The hypothesis of this study was that the leukocyte populations and expression levels of genes related to immune response, growth factors and apoptosis would be altered at the fetal-maternal interface in somatic cell nuclear transfer (SCNT)-generated sheep pregnancies. Placental and endometrial samples from sheep pregnancies established by SCNT and natural breeding (control) were collected at 45 days and at term. Expression of genes related to growth factors, apoptosis and immune response was examined using quantitative reverse transcription polymerase chain reaction...
January 15, 2018: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29332456/the-combined-antitumor-effects-of-125i-radioactive-particle-implantation-and-cytokine-induced-killer-cell-therapy-on-xenograft-hepatocellular-carcinoma-in-a-mouse-model
#10
Junyong Zhang, Nian Wu, Zhengrong Lian, Huyi Feng, Qing Jiang, Xianfeng Chen, Jianping Gong, Zhengrong Qiao
The combination of radiotherapy and immunotherapy has shown great promise in eradicating tumors. For example, 125I radioactive particle implantation and cytokine-induced killer cell therapies have demonstrated efficacy in treating hepatocellular carcinoma. However, the mechanism of this combination therapy remains unknown. In this study, we utilized cytokine-induced killer cells obtained from human peripheral blood mononuclear cells along with 125I radioactive particle implantation to treat subcutaneous hepatocellular carcinoma xenograft tumors in BALB/c nude mice...
December 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29330379/identification-of-shared-genetic-variants-between-schizophrenia-and-lung-cancer
#11
Verena Zuber, Erik G Jönsson, Oleksandr Frei, Aree Witoelar, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Yunpeng Wang, Srdjan Djurovic, Olav B Smeland, Ingrid Dieset, Ayman H Fanous, Rahul S Desikan, Sébastien Küry, Stéphane Bézieau, Anders M Dale, Ian G Mills, Ole A Andreassen
Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330111/soluble-major-histocompatibility-complex-class-i-related-chain-a-smica-levels-influence-graft-outcome-following-renal-transplantation
#12
Ajay K Baranwal, Sanjeev Goswami, Deepali K Bhat, Gurvinder Kaur, Sanjay K Agarwal, Narinder K Mehra
BACKGROUND: Since soluble isoforms of MICA play an important role in modulating the immune response, we evaluated a possible correlation between their levels and development of acute rejection following renal transplantation. METHODS: Serum samples collected at pre- and different time points posttransplant from 137 live related donor renal transplant recipients were evaluated retrospectively for sMICA levels and for the presence of MICA antibodies. Samples from 30 healthy volunteers were also tested as controls...
January 9, 2018: Human Immunology
https://www.readbyqxmd.com/read/29327813/computational-tools-for-the-identification-and-interpretation-of-sequence-motifs-in-immunopeptidomes
#13
REVIEW
Bruno Alvarez, Carolina Barra, Morten Nielsen, Massimo Andreatta
Recent advances in proteomics and mass-spectrometry have widely expanded the detectable peptide repertoire presented by major histocompatibility complex (MHC) molecules on the cell surface, collectively known as the immunopeptidome. Finely characterizing the immunopeptidome brings about important basic insights into the mechanisms of antigen presentation, but can also reveal promising targets for vaccine development and cancer immunotherapy. In this report, we describe a number of practical and efficient approaches to analyze immunopeptidomics data, discussing the identification of meaningful sequence motifs in various scenarios and considering current limitations...
January 12, 2018: Proteomics
https://www.readbyqxmd.com/read/29321349/analysis-of-two-susceptibility-snps-in-hla-region-and-evidence-of-interaction-between-rs6457617-in-hla-dqb1-and-hla-drb1-04-locus-on-tunisian-rheumatoid-arthritis
#14
Yosser Achour, Mariem Ben Hamad, Souhir Chaabane, Ahmed Rebai, Sameh Marzouk, Nadia Mahfoudh, Zouhir Bahloul, Leila Keskes, Abdellatif Maalej
Previous genomewide association studies (GWAS) and meta-analyses have enumerated several genes/loci in major histocompatibility complex region, which are consistently associated with rheumatoid arthritis (RA) in different ethnic populations. Given the genetic heterogeneity of the disease, it is necessary to replicate these susceptibility loci in other populations. In this case, we investigate the analysis of two SNPs, rs13192471 and rs6457617, from the human leukocyte antigen (HLA) region with the risk of RA in Tunisian population...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29321020/meta-analysis-of-human-gene-expression-in-response-to-mycobacterium-tuberculosis-infection-reveals-potential-therapeutic-targets
#15
Zhang Wang, Seda Arat, Michal Magid-Slav, James R Brown
BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection...
January 10, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29318745/tissue-distribution-of-some-immune-cells-in-bovine-reproductive-tract-during-follicular-and-luteal-phase
#16
Mehmet Erdem Akbalik, Narin Liman, Hakan Sagsoz, Berna Guney Saruhan
More recent studies indicate that immune cells which secrete their secretory products or cytokines play an important role in reproductive system. In our study, immune cell populations (CD8+ T lymphocytes, CD68+ macrophages, plasma cells, siderophages, eosinophils) and expression of major histocompatibility complex (MHC) class I and class II were examined in female reproductive tract during follicular (n = 13) and luteal phase (n = 10). Plasma cells and eosinophil granulocytes are present in few numbers in luminal epithelium, but abundant in longitudinal muscle layer of uterus, whereas siderophages are the dominant cell type in stroma...
January 10, 2018: Microscopy Research and Technique
https://www.readbyqxmd.com/read/29316044/global-transcriptome-profiling-of-mild-relapsing-remitting-versus-primary-progressive-multiple-sclerosis
#17
Marcus W Koch, Yaroslav Ilnytskyy, Andrey Golubov, Luanne M Metz, V Wee Yong, Olga Kovalchuk
BACKGROUND: Genetic research in MS mostly compares MS patients with healthy controls, but does not differentiate between MS disease courses. We compared peripheral blood gene expression patterns between extremes of MS phenotypes: patients with mild relapsing-remitting MS (mRRMS) and primary progressive MS (PPMS). METHODS: We analyzed global gene expression profiles of peripheral blood samples of age and gender matched patients with mRRMS and PPMS. Detailed bioinformatic and gene set enrichment analysis, pathway and principle component analyses were used to identify differentially expressed genes and pathways...
January 8, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29315598/improved-methods-for-predicting-peptide-binding-affinity-to-mhc-class-ii-molecules
#18
Kamilla Kjaergaard Jensen, Massimo Andreatta, Paolo Marcatili, Søren Buus, Jason A Greenbaum, Zhen Yan, Alessandro Sette, Bjoern Peters, Morten Nielsen
Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC class II peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan...
January 6, 2018: Immunology
https://www.readbyqxmd.com/read/29313971/in-vivo-antitumor-function-of-tumor-antigen-specific-ctls-generated-in-the-presence-of-ox40-co-stimulation-in-vitro
#19
Ngoc Pham Minh, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Masatsugu Kojima, Toru Miyake, Katsushi Takebayashi, Hirokazu Kodama, Eiji Mekata, Masaji Tani
Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29313952/how-to-consider-rare-genetic-variants-in-personalized-drug-therapy
#20
Volker M Lauschke, Magnus Ingelman-Sundberg
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME)...
January 5, 2018: Clinical Pharmacology and Therapeutics
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