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https://www.readbyqxmd.com/read/28643250/genome-editing-in-mouse-zygotes-and-embryonic-stem-cells-by-introducing-sgrna-cas9-expressing-plasmids
#1
Taichi Noda, Asami Oji, Masahito Ikawa
In mammalian cells, genome editing with the single guide RNA (sgRNA)/Cas9 complex allows for high targeting efficiency within a relatively short time frame with the added benefits of being low cost and easy to design. sgRNA/Cas9-mediated editing in mouse zygotes has accelerated the analysis of gene functions and the generation of mouse models of human diseases. Despite the benefits, this method still suffers from several problems, such as mosaicism in the founder generation which complicates genotyping and phenotypical analyses, and the low efficiency of more complicated genome editing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28642191/new-aspects-in-free-flap-surgery-mini-perforator-flaps-and-extracorporeal-flap-perfusion
#2
Klaus-Dietrich Wolff
BACKGROUND: The scope of microvascular tissue transfer in the Head and Neck reaches from coverage of simple soft tissue defects to complex 3-D reconstructions using multiple or chimeric flaps. This paper summarises the presentation given at the Congress of the French Society of Oral and Maxillofacial Surgery in Marseille 2017. It was the aim of our work to add further elements to this wide spectrum of reconstructive possibilities. METHODS: For patients with small intraoral soft tissue defects in whom the use of a radial forearm flap would not be justified because of its donor site morbidity, but who nevertheless would take a benefit from a small free flap, we used mini-perforator flaps from the lower leg...
June 19, 2017: Journal of Stomatology, Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28642103/chimeric-analogs-of-human-%C3%AE-defensin-1-and-%C3%AE-defensin-disrupt-pre-established-bacterial-biofilms
#3
Basil Mathew, Sudar Olli, Ankeeta Guru, Ramakrishanan Nagaraj
Antibiofilm activity of several human defensin analogs that have the ability to kill planktonic bacteria, against pre-established biofilms of Escherichia coli MG1655 and Staphylococcus aureus NCTC 8530 were examined. Linear and linear fatty acylated analogs did not show any activity while disulfide constrained analogs disrupted pre-established S. aureus biofilms. Chimeric analogs of human β-defensin 1 and θ-defensin, hBTD-1 and [d]hBTD-1 were highly active against S. aureus biofilms. Among the analogs tested, only the d-enantiomer [d]hBTD-1 showed activity against E...
June 12, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28641998/construction-of-a-hepatitis-b-virus-neutralizing-chimeric-monoclonal-antibody-recognizing-escape-mutants-of-the-viral-surface-antigen-hbsag
#4
Forough Golsaz-Shirazi, Mohammad Mehdi Amiri, Samira Farid, Motahareh Bahadori, Felix Bohne, Sebastian Altstetter, Lisa Wolff, Tohid Kazemi, Jalal Khoshnoodi, Mohammad Hojjat-Farsangi, Michael Chudy, Mahmood Jeddi-Tehrani, Ulrike Protzer, Fazel Shokri
Hepatitis B virus (HBV) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. Over 248 million patients are currently suffering from chronic HBV infection worldwide and annual mortality rate of this infection is 686000. The "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis B surface antigen (HBsAg), and antibodies against this region can neutralize the virus and are protective against all subtypes. We have recently generated a murine anti-HBs monoclonal antibody (4G4), which can neutralize HBV infection in HepaRG cells and recognize most of the escape mutant forms of HBsAg...
June 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28641074/development-of-novel-antigen-receptors-for-car-t-cell-therapy-directed-toward-solid-malignancies
#5
REVIEW
David Chen, James Yang
Development of chimeric antigen receptor (CAR) T cells have led to remarkable successes in the treatment of B-cell malignancies with anti-CD19 CAR. Here we discuss the development of novel antigen receptors for use in solid malignancies with respect to target antigens, receptor design, and T cell manipulations.
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28640745/the-amino-terminal-subdomain-of-glycoprotein-gc-of-schmallenberg-virus-disulfide-bonding-and-structural-determinants-of-neutralization
#6
Gleyder Roman-Sosa, Axel Karger, Franziska Kraatz, Andrea Aebischer, Kerstin Wernike, Pavlo Maksimov, Christopher H Lillig, Ilona Reimann, Emiliana Brocchi, Markus Keller, Martin Beer
Orthobunyaviruses are enveloped viruses that can cause human and animal diseases. A novel and major member is the Schmallenberg virus (SBV), the etiological agent of an emerging disease of ruminants that has been spreading all over Europe since 2011. The glycoproteins Gn and Gc of orthobunyaviruses mediate the viral entry, and specifically Gc is a major target for the humoral immune response. For example, the N terminal subdomain of the SBV glycoprotein Gc is targeted by neutralizing monoclonal antibodies that recognize conformational epitopes...
June 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28638381/anti-bovine-programmed-death-1-rat-bovine-chimeric-antibody-for-immunotherapy-of-bovine-leukemia-virus-infection-in-cattle
#7
Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Chie Nakajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1), is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat-bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28637755/seasonal-h3n2-and-2009-pandemic-h1n1-influenza-a-viruses-reassort-efficiently-but-produce-attenuated-progeny
#8
Kara L Phipps, Nicolle Marshall, Hui Tao, Shamika Danzy, Nina Onuoha, John Steel, Anice C Lowen
Reassortment of gene segments between co-infecting influenza A viruses (IAV) facilitates viral diversification and has significant epidemiological impact on seasonal and pandemic influenza. Since 1977, human IAVs of H1N1 and H3N2 subtypes have co-circulated with relatively few documented cases of reassortment. We evaluated the potential for viruses of the 2009 pandemic H1N1 (pH1N1) and seasonal H3N2 lineages to reassort under experimental conditions. Results of heterologous co-infections with pH1N1 and H3N2 viruses were compared to those obtained following co-infection with homologous, genetically tagged, pH1N1 viruses as a control...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637753/structural-mimicry-of-the-dengue-virus-envelope-glycoprotein-revealed-by-the-crystallographic-study-of-an-idiotype-anti-idiotype-fab-complex
#9
Yee Hwa Wong, Boon Chong Goh, She Yah Lim, En Wei Teo, Angeline P C Lim, Pete C Dedon, Brendon J Hanson, Paul A MacAry, Julien Lescar
A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic Flaviviruses such as Dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idiotype antibody (E1) specific for a potent, fully human DENV serotype 1-specific antibody termed HM14c10, derived from a recovered patient. The crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 provides the first detailed molecular comparison of an anti-idiotype paratope specific for a human antibody with its analogous epitope- a discontinuous quaternary structure located at the surface of the viral particle that spans adjacent envelope (E) proteins...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637688/fus-ddit3-fusion-protein-driven-igf-ir-signaling-is-a-therapeutic-target-in-myxoid-liposarcoma
#10
Marcel Trautmann, Jasmin Menzel, Christian Bertling, Magdalene Cyra, Ilka Isfort, Konrad Steinestel, Sandra Elges, Inga Grünewald, Bianca Altvater, Claudia Rossig, Stefan Fröhling, Susanne Hafner, Thomas Simmet, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann
Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS-DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS‑DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#11
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634848/erratum-to-towards-novel-cry-toxins-with-enhanced-toxicity-broader-a-new-chimeric-cry4ba-cry1ac-toxin
#12
Raida Zribi Zghal, Jihen Elleuch, Mamdouh Ben Ali, Frédéric Darriet, Ahmed Rebaï, Fabrice Chandre, Samir Jaoua, Slim Tounsi
No abstract text is available yet for this article.
June 20, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28634010/lamp-1-chimeric-dna-vaccines-enhance-the-antibody-response-in-japanese-flounder-paralichthys-olivaceus
#13
Iang Rondón-Barragán, Reiko Nozaki, Ikuo Hirono, Hidehiro Kondo
DNA vaccination is one method to protect farmed fish from viral and bacterial diseases. Chimeric antigens encoded by DNA vaccines have been shown to increase the resistance to viral diseases. Here, we sequenced the gene encoding lysosome-associated membrane protein-1 from Japanese flounder, Paralichthys olivaceus, (JfLAMP-1) and assessed its use in a chimeric DNA vaccine fused with the major capsule protein (MCP) from red seabream iridovirus (RSIV). JfLAMP-1 cDNA has a length of 1248 bp encoding 415 aa, which contains transmembrane and cytoplasmic domains...
June 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28633988/a-cross-clade-h5n1-influenza-a-virus-neutralizing-monoclonal-antibody-binds-to-a-novel-epitope-within-the-vestigial-esterase-domain-of-hemagglutinin
#14
Subha Sankar Paul, Chee-Keng Mok, Tze-Minn Mak, Oi-Wing Ng, James Odame Aboagye, Teddy John Wohlbold, Florian Krammer, Yee-Joo Tan
The sporadic outbreaks of highly pathogenic H5N1 avian influenza virus have raised public health concerns. Monoclonal antibodies (MAbs) against hemagglutinin (HA) have been increasingly used successfully for therapeutic purposes. Previously, MAb 9F4, generated against clade 1 H5N1 HA, was observed to have cross-clade neutralizing efficacy and inhibited viral entry by preventing the pH-mediated conformational change of HA. Furthermore, mouse-human chimeric MAb 9F4 was found to retain high degrees of neutralizing activity...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28632322/reduced-intensity-conditioning-allogeneic-transplantation-after-salvage-treatment-with-dt-pace-in-myeloma-patients-relapsing-early-after-autologous-transplant
#15
K Randall, M Kaparou, E Xenou, S Paneesha, B Kishore, A Kanellopoulos, R Lovell, K Holder, J Suhr, L Baker, L Ryan, E Nikolousis
OBJECTIVE: In this retrospective single center study we have looked into the transplant outcomes(overall survival OS, progression free survival PFS,GvHD) and the role of chimerism, DLI and pre-transplant characteristics in patients who had a suboptimal response (<12 months)to an autologous stem cell transplant for myeloma and underwent an Alemtuzumab T-cell depleted reduced intensity allograft(RIC). METHODS: 24 patients were salvaged with 2 cycles of DT-PACE and received a RIC transplant with Fludarabine, Melphalan and Alemtuzumab...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28631012/rapid-preparation-of-bioluminescent-tracers-for-relaxin-family-peptides-using-sortase-catalysed-ligation
#16
Jia-Hui Wang, Xiao-Xia Shao, Meng-Jun Hu, Dian Wei, Wei-Han Nie, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Relaxin family is a group of peptide hormones with a variety of biological functions by activating G protein-coupled receptors RXFP1-4. We recently developed bioluminescent tracers for their receptor-binding assays by chemical conjugation with the ultrasensitive NanoLuc reporter. To simplify preparation of the bioluminescent tracers, in the present study, we established a sortase-catalysed ligation approach using the chimeric R3/I5 as a model. Following catalysis by recombinant sortase A, a NanoLuc reporter carrying the LPETG sortase recognition motif at the C-terminus was efficiently ligated to an R3/I5 peptide carrying four successive Gly residues at the A-chain N-terminus, via the formation of a peptide bond between the C-terminal LPET sequence of NanoLuc and the A-chain N-terminal Gly residue of R3/I5...
June 19, 2017: Amino Acids
https://www.readbyqxmd.com/read/28630856/chimeric-genes-in-deletions-and-duplications-associated-with-intellectual-disability
#17
Sonia Mayo, Sandra Monfort, Mónica Roselló, Carmen Orellana, Silvestre Oltra, Alfonso Caro-Llopis, Francisco Martínez
We report on three nonrelated patients with intellectual disability and CNVs that give rise to three new chimeric genes. All the genes forming these fusion transcripts may have an important role in central nervous system development and/or in gene expression regulation, and therefore not only their deletion or duplication but also the resulting chimeric gene may contribute to the phenotype of the patients. Deletions and duplications are usually pathogenic when affecting dose-sensitive genes. Alternatively, a chimeric gene may also be pathogenic by different gain-of-function mechanisms that are not restricted to dose-sensitive genes: the emergence of a new polypeptide that combines functional domains from two different genes, the deregulated expression of any coding sequence by the promoter region of a neighboring gene, and/or a putative dominant-negative effect due to the preservation of functional domains of partially truncated proteins...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28630263/determination-of-the-residues-in-the-extracellular-domain-of-the-nicotinic-%C3%AE-subunit-required-for-the-actions-of-physostigmine-on-neuronal-nicotinic-receptors
#18
Xiaochun Jin, Allison L Germann, Daniel J Shin, Gustav Akk, Joseph H Steinbach
Physostigmine can potentiate and inhibit neuronal nicotinic receptors, in addition to inhibiting the activity of acetylcholinesterase. We found that receptors containing 3 copies of the α2 subunit are inhibited by low concentrations of physostigmine in contrast to receptors containing 3 copies of the α4 subunit that are potentiated. We exploited this observation to determine regions required for the actions of physostigmine. Chimeric constructs of the α2 and α4 subunits located two regions in the extracellular amino-terminal domain of the subunit: the E loop (a loop of the transmitter-binding domain) and a region closer to the amino-terminus that collectively could completely determine the different effects of physostigmine...
June 19, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28630092/characterization-of-high-avidity-cytomegalovirus-specific-t-cells-with-differential-tetramer-binding-coappearing-after-allogeneic-stem-cell-transplantation
#19
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/28629762/targeting-the-tumor-and-its-associated-stroma-one-and-one-can-make-three-in-adoptive-t-cell-therapy-of-solid-tumors
#20
Anna Mondino, Gerlanda Vella, Laura Icardi
Adoptive T cell therapy (ACT) has become a promising immunotherapeutic option for cancer patients. The proof for ACT therapeutic efficacy was first obtained with allogenic T cells and then reproduced with T cells isolated from patients' tumor samples (i.e. tumor-infiltrating lymphocytes). It is now clear that specificity of ACT products can be educated by genetically engineering T cells with classical T Cell Receptors (TCR) or chimeric antigen receptors (CAR). To date a poor accessibility of the tumor mass and a hostile microenvironment, influenced by genetic and epigenetic instability, mainly limit ACT therapeutic efficacy in the case of solid tumors...
June 15, 2017: Cytokine & Growth Factor Reviews
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