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Repertoire Sequencing

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https://www.readbyqxmd.com/read/28823056/exploiting-non-canonical-translation-to-identify-new-targets-for-t-cell-based-cancer-immunotherapy
#1
REVIEW
Céline M Laumont, Claude Perreault
Cryptic MHC I-associated peptides (MAPs) are produced via two mechanisms: translation of protein-coding genes in non-canonical reading frames and translation of allegedly non-coding sequences. In general, cryptic MAPs are coded by relatively short open reading frames whose translation can be regulated at the level of initiation, elongation or termination. In contrast to conventional MAPs, the processing of cryptic MAPs is frequently proteasome independent. The existence of cryptic MAPs derived from allegedly non-coding regions enlarges the scope of CD8 T cell immunosurveillance from a mere ~2% to as much as ~75% of the human genome...
August 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28819830/identification-and-characterization-of-tyrosine-kinases-in-anole-lizard-indicate-the-conserved-tyrosine-kinase-repertoire-in-vertebrates
#2
Ake Liu, Funan He, Xun Gu
The tyrosine kinases (TKs) play principal roles in regulation of multicellular aspects of the organism and are implicated in many cancer types and congenital disorders. The anole lizard has recently been introduced as a model organism for laboratory-based studies of organismal function and field studies of ecology and evolution. However, the TK family of anole lizard has not been systematically identified and characterized yet. In this study, we identified 82 TK-encoding genes in the anole lizard genome and classified them into 28 subfamilies through phylogenetic analysis, with no member from ROS and STYK1 subfamilies identified...
August 17, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#3
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28813462/a-comprehensive-profiling-of-t-and-b-lymphocyte-receptor-repertoires-from-a-chinese-origin-rhesus-macaque-by-high-throughput-sequencing
#4
Longfei Fu, Xinyang Li, Wei Zhang, Changxi Wang, Jinghua Wu, Huanming Yang, Jian Wang, Xiao Liu
Due to the close genetic background, high similarity of physiology, and susceptibility to infectious and metabolic diseases with humans, rhesus macaques have been widely used as an important animal model in biomedical research, especially in the study of vaccine development and human immune-related diseases. In recent years, high-throughput sequencing based immune repertoire sequencing (IR-SEQ) has become a powerful tool to study the dynamic adaptive immune responses. Several previous studies had analyzed the responses of B cells to HIV-1 trimer vaccine or T cell repertoire of rhesus macaques using this technique, however, there are little studies that had performed a comprehensive analysis of immune repertoire of rhesus macaques, including T and B lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28812732/genome-of-the-pitcher-plant-cephalotus-reveals-genetic-changes-associated-with-carnivory
#5
Kenji Fukushima, Xiaodong Fang, David Alvarez-Ponce, Huimin Cai, Lorenzo Carretero-Paulet, Cui Chen, Tien-Hao Chang, Kimberly M Farr, Tomomichi Fujita, Yuji Hiwatashi, Yoshikazu Hoshi, Takamasa Imai, Masahiro Kasahara, Pablo Librado, Likai Mao, Hitoshi Mori, Tomoaki Nishiyama, Masafumi Nozawa, Gergő Pálfalvi, Stephen T Pollard, Julio Rozas, Alejandro Sánchez-Gracia, David Sankoff, Tomoko F Shibata, Shuji Shigenobu, Naomi Sumikawa, Taketoshi Uzawa, Meiying Xie, Chunfang Zheng, David D Pollock, Victor A Albert, Shuaicheng Li, Mitsuyasu Hasebe
Carnivorous plants exploit animals as a nutritional source and have inspired long-standing questions about the origin and evolution of carnivory-related traits. To investigate the molecular bases of carnivory, we sequenced the genome of the heterophyllous pitcher plant Cephalotus follicularis, in which we succeeded in regulating the developmental switch between carnivorous and non-carnivorous leaves. Transcriptome comparison of the two leaf types and gene repertoire analysis identified genetic changes associated with prey attraction, capture, digestion and nutrient absorption...
February 6, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28811963/characterization-of-the-cryoablation-induced-immune-response-in-kidney-cancer-patients
#6
Taigo Kato, Tomoyuki Iwasaki, Motohide Uemura, Akira Nagahara, Hiroki Higashihara, Keigo Osuga, Yuji Ikeda, Kazuma Kiyotani, Jae-Hyun Park, Norio Nonomura, Yusuke Nakamura
Cryoablation is one of treatment modalities for kidney cancer and is expected to induce strong local immune responses as well as systemic T-cell-mediated immune reactions that may lead to the regression of distant metastatic lesions. Thus, the characterization of T cell repertoire and immune environment in tumors before and after treatment should contribute to the better understanding of the cryoablation-induced anticancer immune responses. In this study, we collected tumor tissues from 22 kidney cancer patients, before cryoablation and at 3 mo after cryoablation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810143/genomic-evolution-of-breast-cancer-metastasis-and-relapse
#7
Lucy R Yates, Stian Knappskog, David Wedge, James H R Farmery, Santiago Gonzalez, Inigo Martincorena, Ludmil B Alexandrov, Peter Van Loo, Hans Kristian Haugland, Peer Kaare Lilleng, Gunes Gundem, Moritz Gerstung, Elli Pappaemmanuil, Patrycja Gazinska, Shriram G Bhosle, David Jones, Keiran Raine, Laura Mudie, Calli Latimer, Elinor Sawyer, Christine Desmedt, Christos Sotiriou, Michael R Stratton, Anieta M Sieuwerts, Andy G Lynch, John W Martens, Andrea L Richardson, Andrew Tutt, Per Eystein Lønning, Peter J Campbell
Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#8
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28801904/constructing-strong-cell-type-specific-promoters-through-informed-design
#9
Adam J Brown, David C James
Promoter functionality is highly context dependent, as exemplified by gene-specific expression profiles across different tissues and cell types. Cell type-specific promoter regulation is a function of each cell's unique complement of transcriptional machinery components. Accordingly, to achieve high levels of transcriptional activity within a particular cell type, synthetic promoters must be specifically designed to harness those cells discrete repertoire of available transcription factors . Here, we describe a method for constructing very strong cell type-specific synthetic promoters for use in any given mammalian host cell...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28798737/complete-genome-analysis-of-thermus-parvatiensis-and-comparative-genomics-of-thermus-spp-provide-insights-into-genetic-variability-and-evolution-of-natural-competence-as-strategic-survival-attributes
#10
Charu Tripathi, Harshita Mishra, Himani Khurana, Vatsala Dwivedi, Komal Kamra, Ram K Negi, Rup Lal
Thermophilic environments represent an interesting niche. Among thermophiles, the genus Thermus is among the most studied genera. In this study, we have sequenced the genome of Thermus parvatiensis strain RL, a thermophile isolated from Himalayan hot water springs (temperature >96°C) using PacBio RSII SMRT technique. The small genome (2.01 Mbp) comprises a chromosome (1.87 Mbp) and a plasmid (143 Kbp), designated in this study as pTP143. Annotation revealed a high number of repair genes, a squeezed genome but containing highly plastic plasmid with transposases, integrases, mobile elements and hypothetical proteins (44%)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28798410/a-novel-signature-for-stratifying-the-molecular-heterogeneity-of-the-tissue-infiltrating-t-cell-receptor-repertoire-reflects-gastric-cancer-prognosis
#11
Manchao Kuang, Jieyao Cheng, Chengli Zhang, Lin Feng, Xue Xu, Yajing Zhang, Ming Zu, Jianfang Cui, Hang Yu, Kaitai Zhang, Aiming Yang, Shujun Cheng
Many basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791748/evolution-of-the-ige-and-igg-repertoire-to-a-comprehensive-array-of-allergen-molecules-in-the-first-decade-of-life
#12
Xinyuan Huang, Olympia Tsilochristou, Serena Perna, Stephanie Hofmaier, Antonio Cappella, Carl-Peter Bauer, Ute Hoffman, Johannes Forster, Fred Zepp, Antje Schuster, Raffaele D'Amelio, Ulrich Wahn, Thomas Keil, Susanne Lau, Paolo Maria Matricardi
BACKGROUND: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood. OBJECTIVE: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10yrs. METHODS: We examined the sera collected between birth and age 10yrs from participants in the German Multicentre Allergy Study, a birth cohort born in 1990...
August 8, 2017: Allergy
https://www.readbyqxmd.com/read/28791254/transcriptional-profiling-defines-histone-acetylation-as-a-regulator-of-gene-expression-during-human-to-mosquito-transmission-of-the-malaria-parasite-plasmodium-falciparum
#13
Che J Ngwa, Meike J Kiesow, Olga Papst, Lindsey M Orchard, Michael Filarsky, Alina N Rosinski, Till S Voss, Manuel Llinás, Gabriele Pradel
Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28791028/trna-derived-smallrnas-smallrnas-repertoire-has-yet-to-be-decoded-in-plants
#14
Gaurav Sablok, Kun Yang, Rui Chen, Xiaopeng Wen
Among several smallRNAs classes, microRNAs play an important role in controlling the post-transcriptional events. Next generation sequencing has played a major role in extending the landscape of miRNAs and revealing their spatio-temporal roles in development and abiotic stress. Lateral evolution of these smallRNAs classes have widely been seen with the recently emerging knowledge on tRNA derived smallRNAs. In the present perspective, we discussed classification, identification and roles of tRNA derived smallRNAs across plants and their potential involvement in abiotic and biotic stresses...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28790414/modelling-the-evolution-of-transcription-factor-binding-preferences-in-complex-eukaryotes
#15
Antonio Rosanova, Alberto Colliva, Matteo Osella, Michele Caselle
Transcription factors (TFs) exert their regulatory action by binding to DNA with specific sequence preferences. However, different TFs can partially share their binding sequences due to their common evolutionary origin. This "redundancy" of binding defines a way of organizing TFs in "motif families" by grouping TFs with similar binding preferences. Since these ultimately define the TF target genes, the motif family organization entails information about the structure of transcriptional regulation as it has been shaped by evolution...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790026/dominant-b-cell-receptor-clones-in-peripheral-blood-predict-onset-of-arthritis-in-individuals-at-risk-for-rheumatoid-arthritis
#16
Paul P Tak, Marieke E Doorenspleet, Maria J H de Hair, Paul L Klarenbeek, Marian H van Beers-Tas, Antoine H C van Kampen, Dirkjan van Schaardenburg, Danielle M Gerlag, Frank Baas, Niek de Vries
BACKGROUND: The onset of seropositive rheumatoid arthritis (RA) is preceded by the presence of specific autoantibodies in the absence of synovial inflammation. Only a subset of these at-risk individuals will develop clinical disease. This impedes efforts to implement early interventions that may prevent onset of clinically manifest disease. Here we analyse whether clonal changes in the B cell receptor (BCR) repertoire can reliably predict onset of signs and symptoms. METHODS: In a prospective cohort study in 21 individuals at risk for RA based on the presence of autoantibodies, the BCR repertoire of paired peripheral blood and synovial tissue samples was analysed using next-generation BCR sequencing...
August 8, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28783761/classification-of-the-pospiviroidae-based-on-their-structural-hallmarks
#17
Tamara Giguère, Jean-Pierre Perreault
The simplest known plant pathogens are the viroids. Because of their non-coding single-stranded circular RNA genome, they depend on both their sequence and their structure for both a successful infection and their replication. In the recent years, important progress in the elucidation of their structures was achieved using an adaptation of the selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) protocol in order to probe viroid structures in solution. Previously, SHAPE has been adapted to elucidate the structures of all of the members of the family Avsunviroidae, as well as those of a few members of the family Pospiviroidae...
2017: PloS One
https://www.readbyqxmd.com/read/28783691/characterization-of-t-and-b-cell-repertoire-diversity-in-patients-with-rag-deficiency
#18
Yu Nee Lee, Francesco Frugoni, Kerry Dobbs, Irit Tirosh, Likun Du, Francesca A Ververs, Heng Ru, Lisa Ott de Bruin, Mehdi Adeli, Jacob H Bleesing, David Buchbinder, Manish J Butte, Caterina Cancrini, Karin Chen, Sharon Choo, Reem A Elfeky, Andrea Finocchi, Ramsay L Fuleihan, Andrew R Gennery, Dalia H El-Ghoneimy, Lauren A Henderson, Waleed Al-Herz, Elham Hossny, Robert P Nelson, Sung-Yun Pai, Niraj C Patel, Shereen M Reda, Pere Soler-Palacin, Raz Somech, Paolo Palma, Hao Wu, Silvia Giliani, Jolan E Walter, Luigi D Notarangelo
Recombination-activating genes 1 and 2 (RAG1 and RAG2) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome (n = 5), leaky SCID (n = 3), or CID-G/AI (n = 4)...
December 16, 2016: Science Immunology
https://www.readbyqxmd.com/read/28782508/circulating-and-tissue-resident-cd4-t-cells-with-reactivity-to-intestinal-microbiota-are-abundant-in-healthy-individuals-and-function-is-altered-during-inflammation
#19
Ahmed N Hegazy, Nathaniel R West, Michael J T Stubbington, Emily Wendt, Kim I M Suijker, Angeliki Datsi, Sebastien This, Camille Danne, Suzanne Campion, Sylvia H Duncan, Benjamin M J Owens, Holm H Uhlig, Andrew McMichael, Andreas Bergthaler, Sarah A Teichmann, Satish Keshav, Fiona Powrie
BACKGROUND & AIMS: Interactions between commensal microbes and the immune system are tightly regulated and maintain intestinal homeostasis, but little is known about these interactions in humans. We investigated responses of human CD4(+) T cells to the intestinal microbiota. We measured the abundance of T cells in circulation and intestinal tissues that respond to intestinal microbes and determined their clonal diversity. We also assessed their functional phenotypes and effects on intestinal resident cell populations, and studied alterations in microbe-reactive T cells in patients with chronic intestinal inflammation...
August 3, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28774779/extensive-and-functional-overlap-of-the-stat6-and-rxr-cistromes-in-the-active-enhancer-repertoire-of-human-cd14-monocyte-derived-differentiating-macrophages
#20
REVIEW
Zsolt Czimmerer, Zsuzsanna S Nagy, Gergely Nagy, Attila Horvath, Timea Silye-Cseh, Agnes Kriston, David Jonas, Sascha Sauer, Laszlo Steiner, Bence Daniel, Jean-Francois Deleuze, Laszlo Nagy
Macrophages are able to differentiate into classically polarized (M1) or alternatively polarized (M2) states upon encountering pro-inflammatory cytokines such as interferon (IFN) γ or anti-inflammatory cytokines such as interleukin (IL) -4/IL-13, respectively. Moreover, macrophages are known to regulate lipid metabolism via multiple members of the nuclear hormone receptor family, including the retinoid X receptors (RXR). It has been also documented that cytokines are able to modulate macrophage responses to lipid signals but the nature of these interactions and the underlying mechanisms of these processes especially at the level of the chromatinized genome are not well understood...
July 31, 2017: Molecular and Cellular Endocrinology
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