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https://www.readbyqxmd.com/read/28324664/limited-understanding-of-the-functional-diversity-of-n-linked-glycans-as-a-major-gap-of-prion-biology
#1
Ilia V Baskakov
Among a broad range of hypotheses on the molecular nature of transmissible spongiform encephalopathy or scrapie agents discussed in 1960s was a hypothesis of self-replicating polysaccharides. While the studies of the past 40 years provided unambiguous proof that this is not the case, emerging evidence suggests that carbohydrates in the form of sialylated N-linked glycans, which are a constitutive part of mammalian prions or PrP(Sc), are essential in determining prion fate in an organism. The current extra-view article discusses recent advancements on the role of N-linked glycans and specifically their sialylation status in controlling prion fate...
March 21, 2017: Prion
https://www.readbyqxmd.com/read/28323873/a-three-monoclonal-antibody-combination-potently-neutralizes-multiple-botulinum-neurotoxin-serotype-f-subtypes
#2
Yongfeng Fan, Consuelo Garcia-Rodriguez, Jianlong Lou, Weihua Wen, Fraser Conrad, Wenwu Zhai, Theresa J Smith, Leonard A Smith, James D Marks
Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4...
2017: PloS One
https://www.readbyqxmd.com/read/28319871/autoantibodies-and-immune-complexes-to-oxidation-specific-epitopes-and-progression-of-aortic-stenosis-results-from-the-astronomer-trial
#3
Romain Capoulade, Kwan L Chan, Patrick Mathieu, Yohan Bossé, Jean G Dumesnil, James W Tam, Koon K Teo, Xiaohong Yang, Joseph L Witztum, Benoit J Arsenault, Jean-Pierre Després, Philippe Pibarot, Sotirios Tsimikas
BACKGROUND AND AIMS: Elevated levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict the progression of pre-existing mild-to-moderate calcific aortic valve stenosis (CAVS). Whether indirect markers of oxidation-specific epitopes (OSE) are also predictive is not known. The association between IgG and IgM autoantibodies and malondialdehyde-modified low density lipoprotein (MDA-LDL) and IgG and IgM apolipoprotein B immune complexes (apoB-IC), and the hemodynamic progression rate of CAVS was determined in the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin, NCT00800800) trial...
March 9, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28319811/protein-epitope-mimetic-macrocycles-as-biopharmaceuticals
#4
REVIEW
Anatol Luther, Kerstin Moehle, Eric Chevalier, Glenn Dale, Daniel Obrecht
Fully synthetic medium-sized macrocyclic peptides mimicking the key β-hairpin and α-helical protein epitopes relevant in many protein-protein interactions have emerged as a novel class of drugs with the potential to fill an important gap between small molecules and proteins. Conformationally stabilized macrocyclic scaffolds represent ideal templates for medicinal chemists to incorporate bioactive peptide and protein pharmacophores in order to generate novel drugs to treat diseases with high unmet medical need...
March 5, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28319404/encapsulation-of-an-ep67-conjugated-ctl-peptide-vaccine-in-nanoscale-biodegradable-particles-increases-the-efficacy-of-respiratory-immunization-and-affects-the-magnitude-and-memory-subsets-of-vaccine-generated-mucosal-and-systemic-cd8-t-cells-in-a-diameter
#5
Bala Vamsi Krishna Karuturi, Shailendra B Tallapaka, Pravin Yeapuri, Stephen M Curran, Sam D Sanderson, Joseph A Vetro
The diameter of biodegradable particles used to co-encapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8(+) T cells generated by systemic immunization. Possible effects on the magnitude of CD8(+) T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles...
March 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28319150/high-throughput-transformation-of-saccharomyces-cerevisiae-using-liquid-handling-robots
#6
Guangbo Liu, Clayton Lanham, J Ross Buchan, Matthew E Kaplan
Saccharomyces cerevisiae (budding yeast) is a powerful eukaryotic model organism ideally suited to high-throughput genetic analyses, which time and again has yielded insights that further our understanding of cell biology processes conserved in humans. Lithium Acetate (LiAc) transformation of yeast with DNA for the purposes of exogenous protein expression (e.g., plasmids) or genome mutation (e.g., gene mutation, deletion, epitope tagging) is a useful and long established method. However, a reliable and optimized high throughput transformation protocol that runs almost no risk of human error has not been described in the literature...
2017: PloS One
https://www.readbyqxmd.com/read/28318435/determining-zebrafish-epitope-reactivity-to-commercially-available-antibodies
#7
Michael A Villarreal, Nicole M Biediger, Natalie A Bonner, Jennifer N Miller, Samantha K Zepeda, Benjamin J Ricard, Dana M García, Karen A Lewis
Antibodies raised against mammalian proteins may exhibit cross-reactivity with zebrafish proteins, making these antibodies useful for fish studies. However, zebrafish may express multiple paralogues of similar sequence and size, making them difficult to distinguish by traditional Western blot analysis. To identify the zebrafish proteins that are recognized by an antimammalian antibody, we developed a system to screen putative epitopes by cloning the sequences between the yeast SUMO protein and a C-terminal 6xHis tag...
March 20, 2017: Zebrafish
https://www.readbyqxmd.com/read/28317992/synthetic-glycoconjugates-characterize-the-fine-specificity-of-brucella-a-and-m-monoclonal-antibodies
#8
Satadru Sekhar Mandal, N Vijaya Ganesh, Joanna M Sadowska, David R Bundle
The dominant cell wall antigen of Brucella bacteria is the O-polysaccharide component of the smooth lipopolysaccharide. Infection by various Brucella biovars causes abortions and infertility in a wide range of domestic and wild animals and debilitating disease in humans. Diagnosis relies on the detection of antibodies to the A and M antigens expressed in the O-polysaccharide. This molecule is a homopolymer of the rare monosaccharide, 4-formamido-4,6-dideoxy-d-mannopyranose (Rha4NFo). The A epitope is created by a uniform α1,2 linked internal polymeric sequence capped by a distinct tetrasaccharide sequence defining the M antigen...
March 20, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28317937/identification-of-cancer-associated-missense-mutations-in-hace1-that-impair-cell-growth-control-and-rac1-ubiquitylation
#9
Emilie Andrio, Romain Lotte, Daniel Hamaoui, Jacqueline Cherfils, Anne Doye, Mads Daugaard, Poul H Sorensen, Frédéric Bost, Raymond Ruimy, Amel Mettouchi, Emmanuel Lemichez
The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317093/non-neutralizing-epitopes-induce-robust-hcv-specific-antibody-dependent-cd56-nk-cell-responses-in-chronic-hcv-infected-patients
#10
Lu Long, Manxue Jia, Xueying Fan, Hua Liang, Jiahua Wang, Liyan Zhu, Zhe Xie, Tao Shen
NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC) is of considerable interest in viral infection. However, little is known about NK-ADCC responses in chronic hepatitis C virus (HCV) infection. In this study, impaired nonspecific antibody-dependent CD56(+) NK cell responses were observed in chronic HCV infection, as shown by decreased degranulation (extracellular CD107a expression) and IFN-γ production in response to antibody-bound P815 cells. A peptide pool composed of epitopes recognized by anti-HCV-E1/E2 antibodies could induce pronounced HCV-specific antibody-dependent NK cell responses in sera from approximately half of the chronic HCV carriers...
March 20, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28315936/peptide-binding-motifs-of-two-common-equine-class-i-mhc-molecules-in-thoroughbred-horses
#11
Tobias Bergmann, Mikaela Lindvall, Erin Moore, Eugene Moore, John Sidney, Donald Miller, Rebecca L Tallmadge, Paisley T Myers, Stacy A Malaker, Jeffrey Shabanowitz, Nikolaus Osterrieder, Bjoern Peters, Donald F Hunt, Douglas F Antczak, Alessandro Sette
Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201...
March 18, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28315476/comparative-analysis-of-protein-evolution-in-the-genome-of-pre-epidemic-and-epidemic-zika-virus
#12
Arunachalam Ramaiah, Lei Dai, Deisy Contreras, Sanjeev Sinha, Ren Sun, Vaithilingaraja Arumugaswami
Zika virus (ZIKV) causes microcephaly in congenital infection, neurological disorders, and poor pregnancy outcome and no vaccine is available for use in humans or approved. Although ZIKV was first discovered in 1947, the exact mechanism of virus replication and pathogenesis remains unknown. Recent outbreaks of Zika virus in the Americas clearly suggest a human-mosquito cycle or urban cycle of transmission. Understanding the conserved and adaptive features in the evolution of ZIKV genome will provide a hint on the mechanism of ZIKV adaptation to a new cycle of transmission...
March 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28315224/an-overview-of-bioinformatics-tools-and-resources-in-allergy
#13
Zhiyan Fu, Jing Lin
The rapidly increasing number of characterized allergens has created huge demands for advanced information storage, retrieval, and analysis. Bioinformatics and machine learning approaches provide useful tools for the study of allergens and epitopes prediction, which greatly complement traditional laboratory techniques. The specific applications mainly include identification of B- and T-cell epitopes, and assessment of allergenicity and cross-reactivity. In order to facilitate the work of clinical and basic researchers who are not familiar with bioinformatics, we review in this chapter the most important databases, bioinformatic tools, and methods with relevance to the study of allergens...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315223/t-cell-epitope-prediction
#14
George N Konstantinou
An epitope is a part of an immunogenic protein that can be recognized by the immune system. The peptides that can be recognized by the T-cell receptors after a particular antigen has been intracellularly processed, bound to at least one MHC molecule and expressed on the surface of the antigen presenting cell as a MHC-peptide complex, are called a T-cell epitope. Individuals who have at least one MHC molecule able to most avidly bind to allergenic amino acid sequences from an allergen, and at the same time have the appropriate T-cell clone that can recognize this MHC-peptide complex, are expected to be genetically prone to allergic reactions against that allergen...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315222/tetramer-guided-epitope-mapping-a-rapid-approach-to-identify-hla-restricted-t-cell-epitopes-from-composite-allergens
#15
Luis L Diego Archila, William W Kwok
Tetramer-guided epitope mapping (TGEM) is a technique in immunology that permits the rapid identification of allergenic epitopes through peptide screening procedures utilizing human lymphocyte antigen (HLA) class II tetramers as staining reagents for detection. The identification of allergenic epitopes is a prerequisite for the accurate characterization of allergen-specific CD4(+) T cells without in vitro stimulation. Additionally, these MHC-II/peptide complexes that interact with T-cell receptors (TCR) of pathogenic CD4(+) T cells are compatible with a different number of assays like Intracelullar Cytokine Staining (ICS), and Carboxyfluorescein succinimidyl ester (CFSE) making it a robust technology to study the functionality of allergen-specific CD4(+) T cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315221/t-cell-proliferation-assay-determination-of-immunodominant-t-cell-epitopes-of-food-allergens
#16
Madhan Masilamani, Mariona Pascal, Hugh A Sampson
Characterization of allergen-specific T cells is critical to understand their contribution to disease pathogenesis. The identification of immunodominant T-cell epitopes is crucial for development of T-cell-based vaccines. Peptide-specific T-cell proliferation studies are usually performed in a library of short synthetic peptides (15mer or 20mer) with 3 or 5 offset spanning the entire length of the allergen. T-cell peptide epitopes lack the primary and tertiary structure of the native protein to cross-link IgE, but retain the ability to stimulate T cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315220/ige-epitope-mapping-using-peptide-microarray-immunoassay
#17
Jing Lin, Hugh A Sampson
IgE epitope mapping has the potential to become an additional tool for food allergy diagnosis/prognosis and to lead to a better understanding of the pathogenesis and tolerance induction of food allergy. Due to its ability to screen thousands of targets in parallel using small volumes of sample, peptide microarray has greatly facilitated large-scale IgE epitope mapping. In the past 10 years, we have developed and optimized a reliable and sensitive peptide microarray immunoassay, which has been successfully applied for IgE epitope mapping of many food allergens in our lab...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315209/recombinant-allergen-production-in-e-coli
#18
Changqi Liu, LeAnna N Willison, Shridhar K Sathe
Recombinant protein allergens have been used in allergy studies, allergy diagnosis, and epitope mapping. Messenger RNAs (mRNAs) are isolated from tissues of interest for complementary DNA (cDNA) library construction. Subsequently, the allergen gene is amplified by polymerase chain reaction (PCR) and sequenced. The amplified gene is then cloned into an expression vector, expressed in Escherichia coli cells, and purified from the cell lysate. This chapter describes the protocols for recombinant allergen production...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315001/ltb-syn-a-recombinant-immunogen-for-the-development-of-plant-made-vaccines-against-synucleinopathies
#19
Jaime I Arevalo-Villalobos, Dania O Govea-Alonso, Elizabeth Monreal-Escalante, Sergio Zarazúa, Sergio Rosales-Mendoza
A recombinant antigen targeting α-synuclein was produced in the plant cell rendering an immunogenic protein capable to induce humoral responses in mice upon oral administration. Synucleinopathies are neurodegenerative diseases characterized by the abnormal accumulation of α-synuclein (α-Syn, a 140 amino acid protein that normally plays various neurophysiologic roles) aggregates. Parkinson's disease (PD) is the synucleinopathy with the highest epidemiologic impact and although its etiology remains unknown, α-Syn aggregation during disease progression pointed out α-Syn as target in the development of immunotherapies...
March 17, 2017: Planta
https://www.readbyqxmd.com/read/28314956/evolution-of-mhc-based-technologies-used-for-detection-of-antigen-responsive-t-cells
#20
REVIEW
Amalie Kai Bentzen, Sine Reker Hadrup
T cell-mediated recognition of peptide-major histocompatibility complex (pMHC) class I and II molecules is crucial for the control of intracellular pathogens and cancer, as well as for stimulation and maintenance of efficient cytotoxic responses. Such interactions may also play a role in the development of autoimmune diseases. Novel insights into this mechanism are crucial to understanding disease development and establishing new treatment strategies. MHC multimers have been used for detection of antigen-responsive T cells since the first report by Altman et al...
March 17, 2017: Cancer Immunology, Immunotherapy: CII
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