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Repertoire Sequencing

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https://www.readbyqxmd.com/read/29242186/biased-igh-vdj-gene-repertoire-and-clonal-expansions-in-b-cells-of-chronically-hepatitis-c-virus-infected-individuals
#1
Felicia A Tucci, Simo Kitanovski, Patricia Johansson, Ludger Klein-Hitpass, Alisan Kahraman, Jan Dürig, Daniel Hoffmann, Ralf Küppers
Patients chronically infected with hepatitis C virus (HCV) frequently develop mixed cryoglobulinemia (MC), a monoclonal expansion of IgM+ autoreactive B cells, and also have an increased B cell lymphoma risk. Whether HCV infection also impacts the B cell compartment and the B cell receptor repertoire in patients not affected by MC or lymphomas is poorly understood. Flow cytometric analysis of peripheral blood B cells of 30 MC-negative HCV-infected patients and 15 healthy controls revealed that frequencies of class-switched memory B cells were increased in the patients, whereas frequencies of transitional and naive B cells were decreased...
December 14, 2017: Blood
https://www.readbyqxmd.com/read/29237773/a-subset-of-human-autoreactive-cd1c-restricted-t-cells-preferentially-expresses-trbv4-1-tcrs
#2
Tingxi Guo, Ming Yin Koo, Yuki Kagoya, Mark Anczurowski, Chung-Hsi Wang, Kayoko Saso, Marcus O Butler, Naoto Hirano
In humans, a substantial portion of T cells recognize lipids presented by the monomorphic CD1 proteins. Recent studies have revealed the molecular basis of mycobacterial lipid recognition by CD1c-restricted T cells. Subsets of CD1c-restricted T cells recognize self-lipids in addition to foreign lipids, which may have implications in human diseases involving autoimmunity and malignancy. However, the molecular identity of these self-reactive T cells remains largely elusive. In this study, using a novel CD1c+ artificial APC (aAPC)-based system, we isolated human CD1c-restricted autoreactive T cells and characterized them at the molecular level...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29227286/drug-perturbation-based-stratification-of-blood-cancer
#3
Sascha Dietrich, Małgorzata Oleś, Junyan Lu, Leopold Sellner, Simon Anders, Britta Velten, Bian Wu, Jennifer Hüllein, Michelle da Silva Liberio, Tatjana Walther, Lena Wagner, Sophie Rabe, Sonja Ghidelli-Disse, Marcus Bantscheff, Andrzej K Oleś, Mikołaj Słabicki, Andreas Mock, Christopher C Oakes, Shihui Wang, Sina Oppermann, Marina Lukas, Vladislav Kim, Martin Sill, Axel Benner, Anna Jauch, Lesley Ann Sutton, Emma Young, Richard Rosenquist, Xiyang Liu, Alexander Jethwa, Kwang Seok Lee, Joe Lewis, Kerstin Putzker, Christoph Lutz, Davide Rossi, Andriy Mokhir, Thomas Oellerich, Katja Zirlik, Marco Herling, Florence Nguyen-Khac, Christoph Plass, Emma Andersson, Satu Mustjoki, Christof von Kalle, Anthony D Ho, Manfred Hensel, Jan Dürig, Ingo Ringshausen, Marc Zapatka, Wolfgang Huber, Thorsten Zenz
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29227193/ddx5-p68-associated-lncrna-loc284454-is-differentially-expressed-in-human-cancers-and-modulates-gene-expression
#4
Monalisa Das, Arun Renganathan, Shrinivas Nivrutti Dighe, Utsa Bhaduri, Abhijith Shettar, Geetashree Mukherjee, Paturu Kondaiah, Manchanahalli R Satyanarayana Rao
Long non-coding RNAs (lncRNAs) are emerging as important players in regulation of gene expression in higher eukaryotes. DDX5/p68 RNA helicase protein which is involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells to identify the complete repertoire of DDX5/p68 interacting transcripts including 73 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the list of SE lncRNAs which we have characterized in detail for its molecular features and cellular functions...
December 11, 2017: RNA Biology
https://www.readbyqxmd.com/read/29226517/natural-selection-beyond-genes-identification-and-analyses-of-evolutionarily-conserved-elements-in-the-genome-of-the-collared-flycatcher-ficedula-albicollis
#5
Rory J Craig, Alexander Suh, Mi Wang, Hans Ellegren
It is becoming increasingly clear that a significant proportion of the functional sequence within eukaryotic genomes is noncoding. However, since the identification of conserved elements (CEs) has been restricted to a limited number of model organisms, the dynamics and evolutionary character of the genomic landscape of conserved, and hence likely functional, sequence is poorly understood in most species. Moreover, identification and analysis of the full suite of functional sequence is particularly important for the understanding of the genetic basis of trait loci identified in genome scans or quantitative trait locus mapping efforts...
December 11, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29225728/the-complete-genome-sequence-of-the-rumen-bacterium-butyrivibrio-hungatei-mb2003
#6
Nikola Palevich, William J Kelly, Sinead C Leahy, Eric Altermann, Jasna Rakonjac, Graeme T Attwood
Butyrivibrio hungatei MB2003 was isolated from the plant-adherent fraction of rumen contents from a pasture-grazed New Zealand dairy cow, and was selected for genome sequencing in order to examine its ability to degrade plant polysaccharides. The genome of MB2003 is 3.39 Mb and consists of four replicons; a chromosome, a secondary chromosome or chromid, a megaplasmid and a small plasmid. The genome has an average G + C content of 39.7%, and encodes 2983 putative protein-coding genes. MB2003 is able to use a variety of monosaccharide substrates for growth, with acetate, butyrate and formate as the principal fermentation end-products, and the genes encoding these metabolic pathways have been identified...
2017: Standards in Genomic Sciences
https://www.readbyqxmd.com/read/29224093/sex-effects-at-the-ramparts-nutrient-and-microbe-mediated-regulation-of-the-immune-metabolic-interface
#7
Nyrie Israelian, Jayne S Danska
The relationships between dietary compounds, derivative metabolites, and host metabolism and immunity are controlled by diverse molecular mechanisms. Essential contributions to these dynamics come from the community of microbes (the microbiome) inhabiting the human digestive tract. The composition and function of the microbiome are shaped by available nutrients, and reciprocally, these organisms produce an as yet poorly defined repertoire of molecules that communicate with the epithelial barrier and the mucosal immune system...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29222257/is-molecular-remission-the-goal-of-multiple-myeloma-therapy
#8
REVIEW
Faith E Davies
The increased number of effective therapies and the wider use of combinations that give deeper remissions have resulted in a reassessment of the goals of myeloma therapy. With the advent of new therapeutic strategies and diagnostic tools, achievement of minimal residual disease (MRD)-negative status has become increasingly important, with some even considering it as the primary endpoint for therapy. The level of MRD that is aimed for is a continuous, rather than an absolute variable, with studies in both transplant-eligible and -noneligible patients showing that the level of MRD achieved is predictive of progression-free survival and overall survival, with an improvement in survival of approximately 1 year for each log-depletion in MRD level...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29220521/trypanosomatid-mitochondrial-rna-editing-dramatically-complex-transcript-repertoires-revealed-with-a-dedicated-mapping-tool
#9
Evgeny S Gerasimov, Anna A Gasparyan, Iosif Kaurov, Boris Tichý, Maria D Logacheva, Alexander A Kolesnikov, Julius Lukeš, Vyacheslav Yurchenko, Sara L Zimmer, Pavel Flegontov
RNA editing by targeted insertion and deletion of uridine is crucial to generate translatable mRNAs from the cryptogenes of the mitochondrial genome of kinetoplastids. This type of editing consists of a stepwise cascade of reactions generally proceeding from 3' to 5' on a transcript, resulting in a population of partially edited as well as pre-edited and completely edited molecules for each mitochondrial cryptogene of these protozoans. Often, the number of uridines inserted and deleted exceed the number of nucleotides that are genome-encoded...
December 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29219730/a-comprehensive-profile-of-circulating-rnas-in-human-serum
#10
Sinan Uğur Umu, Hilde Langseth, Cecilie Bucher-Johannessen, Bastian Fromm, Andreas Keller, Eckart Meese, Marianne Lauritzen, Magnus Leithaug, Robert Lyle, Trine B Rounge
Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion Illumina reads from 477 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). We found that the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi-interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA)...
December 8, 2017: RNA Biology
https://www.readbyqxmd.com/read/29217783/somatic-stat3-mutations-in-the-felty-syndrome-an-implication-for-a-common-pathogenesis-with-large-granular-lymphocyte-leukemia
#11
Paula Savola, Oscar Brück, Thomas Olson, Tiina Kelkka, Markku J Kauppi, Panu E Kovanen, Soili Kytölä, Tuulikki Sokka-Isler, Thomas P Loughran, Marjatta Leirisalo-Repo, Satu Mustjoki
Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. We now aimed to study whether these mutations can also be detected in Felty syndrome, which would imply for a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty syndrome patients who were monitored at the rheumatology outpatient clinic for Felty syndrome...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29211135/longitudinal-evaluation-of-humoral-immune-response-and-merozoite-surface-antigen-diversity-in-calves-naturally-infected-with-babesia-bovis-in-s%C3%A3-o-paulo-brazil
#12
Carlos António Matos, Luiz Ricardo Gonçalves, Dasiel Obregón Alvarez, Carla Roberta Freschi, Jenevaldo Barbosa da Silva, Silvana Pompeia Val-Moraes, Natalia Serra Mendes, Marcos Rogério André, Rosangela Zacarias Machado
Babesiosis is an economically important infectious disease affecting cattle worldwide. In order to longitudinally evaluate the humoral immune response against Babesia bovis and the merozoite surface antigen diversity of B. bovis among naturally infected calves in Taiaçu, Brazil, serum and DNA samples from 15 calves were obtained quarterly, from their birth to 12 months of age. Anti-B. bovis IgG antibodies were detected by means of the indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA)...
October 2017: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
https://www.readbyqxmd.com/read/29209563/comparative-immunologic-characterization-of-autoimmune-giant-cell-myocarditis-with-ipilimumab
#13
Alexandre Reuben, Mariana Petaccia de Macedo, Jennifer McQuade, Aron Joon, Zhiyong Ren, Tiffany Calderone, Brandy Conner, Khalida Wani, Zachary A Cooper, Hussein Tawbi, Michael T Tetzlaff, Robert F Padera, Jean-Bernard Durand, Alexander J Lazar, Jennifer A Wargo, Michael A Davies
Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding of this complication, we performed immune profiling on post-mortem tissue from a patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myocarditis, and shrinking lung metastases after ipilimumab treatment. Histological analysis of heart tissue demonstrated findings consistent with giant cell myocarditis (GCM). The immune infiltrate in the heart was largely comprised of CD4+ T cells, whereas the liver had very few T cells, and CD8+ T cells were predominant in the responding lung metastases...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29204143/local-chromatin-features-including-pu-1-and-ikaros-binding-and-h3k4-methylation-shape-the-repertoire-of-immunoglobulin-kappa-genes-chosen-for-v-d-j-recombination
#14
Louise S Matheson, Daniel J Bolland, Peter Chovanec, Felix Krueger, Simon Andrews, Hashem Koohy, Anne E Corcoran
V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igκ) light chain recombination follows immunoglobulin heavy chain (Igh) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29203177/characterisation-analysis-of-expression-and-localisation-of-the-opsin-gene-repertoire-from-the-perspective-of-photoperiodism-in-the-aphid-acyrthosiphon-pisum
#15
Jorge Mariano Collantes-Alegre, Florian Mattenberger, Miquel Barberà, David Martínez-Torres
Organisms exhibit a wide range of seasonal responses as adaptions to predictable annual changes in their environment. These changes are originally caused by the effect of the Earth's cycles around the sun and its axial tilt. Examples of seasonal responses include floration, migration, reproduction and diapause. In temperate climate zones, the most robust variable to predict seasons is the length of the day (i.e. the photoperiod). The first step to trigger photoperiodic driven responses involves measuring the duration of the light-dark phases, but the molecular clockwork performing this task is poorly characterized...
December 1, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/29202449/clonal-relationships-of-csf-b-cells-in-treatment-naive-multiple-sclerosis-patients
#16
Erica L Eggers, Brady A Michel, Hao Wu, Sheng-Zhi Wang, Carolyn J Bevan, Aya Abounasr, Natalie S Pierson, Antje Bischof, Max Kazer, Elizabeth Leitner, Ariele L Greenfield, Stanislas Demuth, Michael R Wilson, Roland G Henry, Bruce Ac Cree, Stephen L Hauser, H-Christian von Büdingen
A role of B cells in multiple sclerosis (MS) is well established, but there is limited understanding of their involvement during active disease. Here, we examined cerebrospinal fluid (CSF) and peripheral blood (PB) B cells in treatment-naive patients with MS or high-risk clinically isolated syndrome. Using flow cytometry, we found increased CSF lymphocytes with a disproportionate increase of B cells compared with T cells in patients with gadolinium-enhancing (Gd+) lesions on brain MRI. Ig gene heavy chain variable region (Ig-VH) repertoire sequencing of CSF and PB B cells revealed clonal relationships between intrathecal and peripheral B cell populations, which could be consistent with migration of B cells to and activation in the CNS in active MS...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29200193/immunogenetic-factors-driving-formation-of-ultralong-vh-cdr3-in-bos-taurus-antibodies
#17
Thaddeus C Deiss, Melissa Vadnais, Feng Wang, Patricia L Chen, Ali Torkamani, Waithaka Mwangi, Marie-Paule Lefranc, Michael F Criscitiello, Vaughn V Smider
The antibody repertoire of Bos taurus is characterized by a subset of variable heavy (VH) chain regions with ultralong third complementarity determining regions (CDR3) which, compared to other species, can provide a potent response to challenging antigens like HIV env. These unusual CDR3 can range to over seventy highly diverse amino acids in length and form unique β-ribbon 'stalk' and disulfide bonded 'knob' structures, far from the typical antigen binding site. The genetic components and processes for forming these unusual cattle antibody VH CDR3 are not well understood...
December 4, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29197474/venomics-reveals-novel-ion-transport-peptide-likes-itpls-from-the-parasitoid-wasp-tetrastichus-brontispae
#18
Nai-Yong Liu, Zhi-Wen Xu, Wei Yan, Xue-Min Ren, Zhi-Quan Zhang, Jia-Ying Zhu
Despite substantial advances in uncovering constituents of parasitoid venoms due to their potential applications as insecticides and pharmaceuticals, most of these studies are primarily restricted to braconid and ichneumonid wasps. Little information is available regarding virulent factors from venom of Eulophidae. In order to provide insight into the venom components of this family and parasitoid venom evolution, a venom protein repertoire (venomics) of the endoparasitoid wasp, Tetrastichus brontispae was deciphered using a proteomic approach...
November 29, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29196413/the-fungal-snornaome
#19
Sebastian Canzler, Peter F Stadler, Jana Schoor
Small nucleolar RNAs (snoRNAs) are essential players in the rRNA biogenesis due to their involvement in the nucleolytic processing of the precursor and the subsequent guidance of nucleoside modifications. Within the kingdom Fungi, merely a few species-specific surveys have explored their snoRNA repertoire. However, the wide range of the snoRNA landscape spanning all major fungal lineages has not been mapped so far, mainly because of missing tools for automatized snoRNA detection and functional analysis. For the first time, we report here a comprehensive inventory of fungal snoRNAs together with a functional analysis and an in-depth investigation of their evolutionary history including innovations, deletions, and target switches...
December 1, 2017: RNA
https://www.readbyqxmd.com/read/29194033/immunoproteomic-analysis-of-the-protein-repertoire-of-unsporulated-eimeria-tenella-oocysts
#20
Zhenchao Zhang, Shuai Wang, Charles Li, Liheng Liu
The apicomplexan protozoans Eimeria spp. cause coccidioses, the most common intestinal diseases in chickens. Coccidiosis is associated with significant animal welfare issues and has a high economic impact on the poultry industry. Lack of a full understanding of immunogenic molecules and their precise functions involved in the Eimeria life cycles may limit development of effective vaccines and drug therapies. In this study, immunoproteomic approaches were used to define the antigenic protein repertoire from the total proteins of unsporulated Eimeria tenella oocysts...
2017: Parasite: Journal de la Société Française de Parasitologie
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