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https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#1
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28637323/evolution-of-transcription-activator-like-effectors-in-xanthomonas-oryzae
#2
Annett Erkes, Maik Reschke, Jens Boch, Jan Grau
Transcription activator-like effectors (TALEs) are secreted by plant-pathogenic Xanthomonas bacteria into plant cells where they act as transcriptional activators and, hence, are major drivers in reprogramming the plant for the benefit of the pathogen. TALEs possess a highly repetitive DNA-binding domain of typically 34 amino acid tandem repeats, where amino acid 12 and 13, termed repeat variable di-residue (RVD), determine target specificity. Different Xanthomonas strains possess different repertoires of TALEs...
June 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28636592/quantifiable-predictive-features-define-epitope-specific-t-cell-receptor-repertoires
#3
Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi H O Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas
T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10(15) (ref. 1) to as high as 10(61) (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#4
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28635326/encapsulins-molecular-biology-of-the-shell
#5
Robert J Nichols, Caleb Cassidy-Amstutz, Thawatchai Chaijarasphong, David F Savage
Compartmentalization is both a fundamental principle of cellular organization and an emerging theme in prokaryotic biology. Work in the past few decades has shown that protein-based organelles called microcompartments enhance the function of encapsulated cargo proteins. More recently, the repertoire of known prokaryotic organelles has expanded beyond microcompartments to include a new class of smaller proteinaceous compartments, termed nanocompartments (also known as encapsulins). Nanocompartments are icosahedral capsids that are smaller and less complex than microcompartments...
June 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28635107/new-space-time-metaphors-foster-new-nonlinguistic-representations
#6
Rose K Hendricks, Lera Boroditsky
What is the role of language in constructing knowledge? In this article, we ask whether learning new relational language can create new ways of thinking. In Experiment 1, we taught English speakers to talk about time using new vertical linguistic metaphors, saying things like "breakfast is above dinner" or "breakfast is below dinner" (depending on condition). In Experiment 2, rather than teaching people new metaphors, we relied on the left-right representations of time that our American college student participants have already internalized through a lifetime of visuospatial experience reading and writing text from left to right...
June 21, 2017: Topics in Cognitive Science
https://www.readbyqxmd.com/read/28634692/crispr-cas-orthologues-and-variants-optimizing-the-repertoire-specificity-and-delivery-of-genome-engineering-tools
#7
Alberto Cebrian-Serrano, Benjamin Davies
Robust and cost-effective genome editing in a diverse array of cells and model organisms is now possible thanks to the discovery of the RNA-guided endonucleases of the CRISPR-Cas system. The commonly used Cas9 of Streptococcus pyogenes shows high levels of activity but, depending on the application, has been associated with some shortcomings. Firstly, the enzyme has been shown to cause mutagenesis at genomic sequences resembling the target sequence. Secondly, the stringent requirement for a specific motif adjacent to the selected target site can limit the target range of this enzyme...
June 20, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28634433/the-draft-genome-of-the-non-host-associated-methanobrevibacter-arboriphilus-strain-dh1-encodes-a-large-repertoire-of-adhesin-like-proteins
#8
Anja Poehlein, Rolf Daniel, Henning Seedorf
Methanobrevibacter arboriphilus strain DH1 is an autotrophic methanogen that was isolated from the wetwood of methane-emitting trees. This species has been of considerable interest for its unusual oxygen tolerance and has been studied as a model organism for more than four decades. Strain DH1 is closely related to other host-associated Methanobrevibacter species from intestinal tracts of animals and the rumen, making this strain an interesting candidate for comparative analysis to identify factors important for colonizing intestinal environments...
2017: Archaea: An International Microbiological Journal
https://www.readbyqxmd.com/read/28632991/uncovering-the-repertoire-of-fungal-secondary-metabolites-from-fleming-s-lab-to-the-international-space-station
#9
Tomasz Boruta
Fungi produce a variety of secondary metabolites (SMs), low-molecular weight compounds associated with many potentially useful biological activities. The examples of biotechnologically relevant fungal metabolites include penicillin, a beta-lactam antibiotic, and lovastatin, a cholesterol-lowering drug. The discovery of pharmaceutical lead compounds within the microbial metabolic pools relies on the selection and biochemical characterization of promising strains. Not all SMs are produced under standard cultivation conditions, hence the uncovering of chemical potential of investigated strains often requires the use of induction strategies to awake the associated biosynthetic genes...
June 20, 2017: Bioengineered
https://www.readbyqxmd.com/read/28632705/targeting-the-n-terminus-for-site-selective-protein-modification
#10
Christian B Rosen, Matthew B Francis
The formation of well-defined protein bioconjugates is critical for many studies and technologies in chemical biology. Tried-and-true methods for accomplishing this typically involve the targeting of cysteine residues, but the rapid growth of contemporary bioconjugate applications has required an expanded repertoire of modification techniques. One very powerful set of strategies involves the modification of proteins at their N termini, as these positions are typically solvent exposed and provide chemically distinct sites for many protein targets...
July 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28631377/state-of-the-art-technologies-to-explore-long-non-coding-rnas-in-cancer
#11
REVIEW
Saeede Salehi, Mohammad Naser Taheri, Negar Azarpira, Abdolhossein Zare, Abbas Behzad-Behbahani
Long non-coding RNAs (lncRNAs) comprise a vast repertoire of RNAs playing a wide variety of crucial roles in tissue physiology in a cell-specific manner. Despite being engaged in myriads of regulatory mechanisms, many lncRNAs have still remained to be assigned any functions. A constellation of experimental techniques including single-molecule RNA in situ hybridization (sm-RNA FISH), cross-linking and immunoprecipitation (CLIP), RNA interference (RNAi), Clustered regularly interspaced short palindromic repeats (CRISPR) and so forth has been employed to shed light on lncRNA cellular localization, structure, interaction networks and functions...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28630873/an-integrative-developmental-genomics-and-systems-biology-approach-to-identify-an-in-vivo-sox-trio-mediated-gene-regulatory-network-in-murine-embryos
#12
Wenqing Jean Lee, Sumantra Chatterjee, Sook Peng Yap, Siew Lan Lim, Xing Xing, Petra Kraus, Wenjie Sun, Xiaoming Hu, V Sivakamasundari, Hsiao Yun Chan, Prasanna R Kolatkar, Shyam Prabhakar, Thomas Lufkin
Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the Sox trio, namely, Sox5, Sox6, and Sox9, which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process. A developmental genomics and systems biology approach offers to complement the reductionist methodology of current developmental biology and provide a more comprehensive and integrated view of the interrelationships of complex regulatory networks that occur during organogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28630816/the-effects-of-an-auditory-matching-ipad-app-on-three-preschoolers-echoic-and-listener-responses
#13
Lin Du, Jeanne Speckman, Megan Medina, Michelle Cole-Hatchard
We investigated the effects of an auditory match-to-sample protocol on three preschoolers' accurate echoics to 100 English words and advanced listener responses. The protocol was presented by using an iPad app Sounds the same: an app to target listening and speaking clearly. We used a combination of a multiple probe design (for echoic responses) and a delayed multiple probe design (for advanced listener literacy responses) with a time-lagged baseline across participants to test the effectiveness of the protocol...
June 2017: Behavior Analysis in Practice
https://www.readbyqxmd.com/read/28630303/how-members-of-the-human-gut-microbiota-overcome-the-sulfation-problem-posed-by-glycosaminoglycans
#14
Alan Cartmell, Elisabeth C Lowe, Arnaud Baslé, Susan J Firbank, Didier A Ndeh, Heath Murray, Nicolas Terrapon, Vincent Lombard, Bernard Henrissat, Jeremy E Turnbull, Mirjam Czjzek, Harry J Gilbert, David N Bolam
The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630124/the-dna-repair-repertoire-of-mycobacterium-smegmatis-fena-includes-the-incision-of-dna-5-flaps-and-the-removal-of-5-adenylylated-products-of-aborted-nick-ligation
#15
Maria Loressa Uson, Shreya Ghosh, Stewart Shuman
We characterize Mycobacterium smegmatis FenA as a manganese-dependent 5' -flap endonuclease homologous to the 5' -exonuclease of DNA polymerase I. FenA incises a nicked 5' flap between the first and second nucleotides of the duplex segment to yield a 1-nucleotide gapped DNA, which is then further resected in dinucleotide steps. Initial FenA cleavage at a Y-flap or nick occurs between the first and second nucleotides of the duplex. However, when the template 3' -single-strand is eliminated to create a 5' -tailed duplex, FenA incision shifts to between the second and third nucleotides...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28630092/characterization-of-high-avidity-cytomegalovirus-specific-t-cells-with-differential-tetramer-binding-coappearing-after-allogeneic-stem-cell-transplantation
#16
Justyna Ogonek, Kriti Verma, Christian Schultze-Florey, Pavankumar Varanasi, Susanne Luther, Patrick Schweier, Wolfgang Kühnau, Gudrun Göhring, Elke Dammann, Michael Stadler, Arnold Ganser, Ulrike Koehl, Christian Koenecke, Eva M Weissinger, Lothar Hambach
CMV reactivation is a major complication after allogeneic stem cell transplantation (SCT). Immune reconstitution of CMV-specific CTLs (CMV-CTLs) is essential for virus control. During CMV-CTL monitoring using mutated HLA/CMV tetramers selectively detecting high-avidity T cells, we observed coappearance of CMV-CTLs with low (CMV tet(low) CTLs) and high tetramer binding (CMV tet(high) CTLs) in 53/115 CMV IgG(+) patients stem cell transplanted from CMV IgG(+) donors. However, the relevance of these coappearing differentially tetramer binding ("dual") CMV-CTLs was unclear...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28629934/recent-advances-in-leishmania-reverse-genetics-manipulating-a-manipulative-parasite
#17
REVIEW
Samuel M Duncan, Nathaniel G Jones, Jeremy C Mottram
In this review we describe the expanding repertoire of molecular tools with which to study gene function in Leishmania. Specifically we review the tools available for studying functions of essential genes, such as plasmid shuffle and DiCre, as well as the rapidly expanding portfolio of available CRISPR/Cas9 approaches for large scale gene knockout and endogenous tagging. We include detail on approaches that allow the direct manipulation of RNA using RNAi and protein levels via Tet or DiCre induced overexpression and destabilization domain mediated degradation...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28629772/impact-of-the-cardiovascular-system-associated-adipose-tissue-on-atherosclerotic-pathology
#18
REVIEW
Dimitry A Chistiakov, Andrey V Grechko, Veronika A Myasoedova, Alexandra A Melnichenko, Alexander N Orekhov
Cardiac obesity makes an important contribution to the pathogenesis of cardiovascular disease. One of the important pathways of this contribution is the inflammatory process that takes place in the adipose tissue. In this review, we consider the role of the cardiovascular system-associated fat in atherosclerotic cardiovascular pathology and a non-atherosclerotic cause of coronary artery disease, such as atrial fibrillation. Cardiovascular system-associated fat not only serves as the energy store, but also releases adipokines that control local and systemic metabolism, heart/vascular function and vessel tone, and a number of vasodilating and anti-inflammatory substances...
June 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28629751/unique-influenza-a-crossreactive-memory-cd8-tcr-repertoire-has-a-potential-to-protect-against-epstein-barr-virus-seroconversion
#19
Levi B Watkin, Rabinarayan Mishra, Anna Gil, Nuray Aslan, Dario Ghersi, Katherine Luzuriaga, Liisa K Selin
No abstract text is available yet for this article.
June 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28629124/microbial-diseases-of-bivalve-mollusks-infections-immunology-and-antimicrobial-defense
#20
REVIEW
Carla Zannella, Francesco Mosca, Francesca Mariani, Gianluigi Franci, Veronica Folliero, Marilena Galdiero, Pietro Giorgio Tiscar, Massimiliano Galdiero
A variety of bivalve mollusks (phylum Mollusca, class Bivalvia) constitute a prominent commodity in fisheries and aquacultures, but are also crucial in order to preserve our ecosystem's complexity and function. Bivalve mollusks, such as clams, mussels, oysters and scallops, are relevant bred species, and their global farming maintains a high incremental annual growth rate, representing a considerable proportion of the overall fishery activities. Bivalve mollusks are filter feeders; therefore by filtering a great quantity of water, they may bioaccumulate in their tissues a high number of microorganisms that can be considered infectious for humans and higher vertebrates...
June 17, 2017: Marine Drugs
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