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Human antigen r

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https://www.readbyqxmd.com/read/28747530/sequence-intrinsic-somatic-mutation-mechanisms-contribute-to-affinity-maturation-of-vrc01-class-hiv-1-broadly-neutralizing-antibodies
#1
Joyce K Hwang, Chong Wang, Zhou Du, Robin M Meyers, Thomas B Kepler, Donna Neuberg, Peter D Kwong, John R Mascola, M Gordon Joyce, Mattia Bonsignori, Barton F Haynes, Leng-Siew Yeap, Frederick W Alt
Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR1 and CDR2 encoded by the V segment and CDR3 encoded by the V(D)J junction region. Antigen-stimulated germinal center (GC) B cells undergo somatic hypermutation (SHM) of V(D)J exons followed by selection for SHMs that increase antigen-binding affinity...
July 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28747496/parainfluenza-virus-5-piv5-expressing-wild-type-or-pre-fusion-respiratory-syncytial-virus-rsv-fusion-protein-protect-mice-and-cotton-rats-from-rsv-challenge
#2
Shannon I Phan, James R Zengel, Huiling Wei, Zhuo Li, Dai Wang, Biao He
Human respiratory syncytial virus (RSV) is the leading cause of pediatric bronchiolitis and hospitalizations. RSV can also cause severe complications in elderly and immunocompromised individuals. There is no licensed vaccine. We previously generated a PIV5-vectored vaccine candidate expressing the RSV fusion protein (F) that was immunogenic and protective in mice. In this work, our goal was to improve the original vaccine candidate by modifying the PIV5 vector or by modifying the RSV-F antigen. We previously demonstrated that inserting a foreign gene at the PIV5 SH-HN junction or deleting PIV5 SH increased vaccine efficacy...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28744670/rna-binding-protein-hur-enhances-mineralocorticoid-signaling-in-renal-kc3ac1-cells-under-hypotonicity
#3
Ingrid Lema, Larbi Amazit, Khadija Lamribet, Jérôme Fagart, Anne Blanchard, Marc Lombès, Nadia Cherradi, Say Viengchareun
Mineralocorticoid receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron. Herein, we decipher mechanisms by which hypotonicity increases MR expression in renal principal cells. We identify HuR (human antigen R), an mRNA-stabilizing protein, as an important posttranscriptional regulator of MR expression. Hypotonicity triggers a rapid and reversible nuclear export of HuR in renal KC3AC1 cells, as quantified by high-throughput microscopy. We also identify a key hairpin motif in the 3'-untranslated region of MR transcript, pivotal for the interaction with HuR and its stabilizing function...
July 25, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28742141/bruton-s-tyrosine-kinase-inhibitor-bms-986142-in-experimental-models-of-rheumatoid-arthritis-enhances-efficacy-of-agents-representing-clinical-standard-of-care
#4
Kathleen M Gillooly, Claudine Pulicicchio, Mark A Pattoli, Lihong Cheng, Stacey Skala, Elizabeth M Heimrich, Kim W McIntyre, Tracy L Taylor, Daniel W Kukral, Shailesh Dudhgaonkar, Jignesh Nagar, Dana Banas, Scott H Watterson, Joseph A Tino, Aberra Fura, James R Burke
Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune disorders. BMS-986142 is a potent and highly selective reversible small molecule inhibitor of BTK currently being investigated in clinical trials for the treatment of both RA and primary Sjögren's syndrome. In the present report, we detail the in vitro and in vivo pharmacology of BMS-986142 and show this agent provides potent and selective inhibition of BTK (IC50 = 0...
2017: PloS One
https://www.readbyqxmd.com/read/28740731/comparing-new-generation-candidate-vaccines-against-human-orthopoxvirus-infections
#5
R A Maksyutov, S N Yakubitskyi, I V Kolosova, S N Shchelkunov
The lack of immunity to the variola virus in the population, increasingly more frequent cases of human orthopoxvirus infection, and increased risk of the use of the variola virus (VARV) as a bioterrorism agent call for the development of modern, safe vaccines against orthopoxvirus infections. We previously developed a polyvalent DNA vaccine based on five VARV antigens and an attenuated variant of the vaccinia virus (VACV) with targeted deletion of six genes (VACΔ6). Independent experiments demonstrated that triple immunization with a DNA vaccine and double immunization with VACΔ6 provide protection to mice against a lethal dose (10 LD50) of the ectromelia virus (ECTV), which is highly pathogenic for mice...
April 2017: Acta Naturae
https://www.readbyqxmd.com/read/28739603/novel-in-vitro-booster-vaccination-to-rapidly-generate-antigen-specific-human-monoclonal-antibodies
#6
Irene Sanjuan Nandin, Carol Fong, Cecilia Deantonio, Juan A Torreno-Pina, Simone Pecetta, Paula Maldonado, Francesca Gasparrini, Jose Ordovas-Montanes, Samuel W Kazer, Svend Kjaer, Daryl W Borley, Usha Nair, Julia A Coleman, Daniel Lingwood, Alex K Shalek, Eric Meffre, Pascal Poignard, Dennis R Burton, Facundo D Batista
Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9...
July 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28734965/enhanced-immunostimulatory-activity-of-in-silico-discovered-agonists-of-toll-like-receptor-2-tlr2
#7
M S Murgueitio, S Ebner, P Hörtnagl, C Rakers, R Bruckner, P Henneke, G Wolber, S Santos-Sierra
BACKGROUND: Emergent therapies in anticancer vaccination use Toll-like receptors (TLRs) agonists as dendritic cell (DC) vaccine adjuvants. DCs from the patient are isolated, stimulated with TLR agonists and tumor antigens ex vivo and then infused back into the patient. Although some TLR ligands have been tested in clinical trials, novel TLR agonists with improved immunomodulatory properties are essential to optimize treatment success. We report on the discovery of small-molecule TLR2 agonists, with favorable properties as synthetic adjuvants...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28733900/the-putative-role-of-environmental-mercury-in-the-pathogenesis-and-pathophysiology-of-autism-spectrum-disorders-and-subtypes
#8
REVIEW
G Morris, B K Puri, R E Frye, M Maes
Exposure to organic forms of mercury has the theoretical capacity to generate a range of immune abnormalities coupled with chronic nitro-oxidative stress seen in children with autism spectrum disorder (ASD). The paper discusses possible mechanisms explaining the neurotoxic effects of mercury and possible associations between mercury exposure and ASD subtypes. Environmental mercury is neurotoxic at doses well below the current reference levels considered to be safe, with evidence of neurotoxicity in children exposed to environmental sources including fish consumption and ethylmercury-containing vaccines...
July 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28733290/us-feral-swine-were-exposed-to-both-avian-and-swine-influenza-a-viruses
#9
Brigitte E Martin, Hailiang Sun, Margaret Carrel, Fred L Cunningham, John A Baroch, Katie C Hanson-Dorr, Sean G Young, Brandon Schmit, Jacqueline M Nolting, Kyoung-Jin Yoon, Mark W Lutman, Kerri Pedersen, Kelly Lager, Andrew S Bowman, Richard D Slemons, David R Smith, Thomas DeLiberto, Xiu-Feng Wan
Influenza A viruses (IAVs) in swine can cause sporadic infections and pandemic outbreaks among humans, but how avian IAV emerges in swine is still unclear. Unlike domestic swine, feral swine are free ranging and have many opportunities for IAV exposure through contacts with various habitats and animals, including migratory waterfowl, a natural reservoir for IAVs. During 2010--2013, 8,239 serum samples were collected from feral swine across 35 US states and tested against 45 contemporary antigenic variants of avian, swine, and human IAVs; of these, 406 (4...
July 21, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28731588/human-leukocyte-antigen-distribution-and-genomic-ancestry-in-brazilian-patients-with-sickle-cell-disease
#10
M C F da Silva-Malta, P S Rodrigues, L W Zuccherato, F C B de Souza, E M F L Domingues, V R Souza, E Tarazona-Santos, M L Martins
Hematopoietic stem-cell transplantation (HSCT) is currently the only established curative treatment for sickle cell disease (SCD), but is limited by donor availability. Ethnicity is thought to have an impact on the complications experienced by patients that undergo HSCT and on the likelihood of identifying an HLA matched donor. In the present study, we investigated the genomic ancestry and the distribution of HLA allele groups in Brazilian patients with SCD, compared these HLA profiles to worldwide populations and evaluate the availability of HLA-matched donors...
July 21, 2017: HLA
https://www.readbyqxmd.com/read/28728276/-the-role-of-hur-in-mediating-snail-expression-in-human-small-airway-epithelium-induced-by-cigarette-smoke-extract
#11
X M Gu, X G Wang, J Sun, N Wang, S J Jiang
Objective: To investigate the abundance of human antigen R (HuR) in small airway epithelial cells stimulated by cigarette smoke extract (CSE) as well as the role of HuR in mediating snail which is recognized as a key transcription factor in regulating epithelial-mesenchymal transition (EMT). Methods: Human small airway epithelial cells (HSAEpiC) cultured in vitro were exposed to cigarette smoke extract (CSE) to model COPD status. Real-time PCR and western blotting analysis were used in detecting HuR protein and mRNA expression in cells with CSE which were divided into 5 groups: a control group, a 1%-24 h group, a 3%-24 h group, a 1%-48 h group and a 3%-48 h group...
July 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28726771/rapid-elicitation-of-broadly-neutralizing-antibodies-to-hiv-by-immunization-in-cows
#12
Devin Sok, Khoa M Le, Melissa Vadnais, Karen Saye-Francisco, Joseph G Jardine, Jonathan Torres, Zachary T Berndsen, Leopold Kong, Robyn Stanfield, Jennifer Ruiz, Alejandra Ramos, Chi-Hui Liang, Patricia L Chen, Michael F Criscitiello, Waithaka Mwangi, Ian A Wilson, Andrew B Ward, Vaughn V Smider, Dennis R Burton
No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens (BG505 SOSIP) that antigenically mimic the HIV envelope glycoprotein (Env)(1) have improved the elicitation of potent isolate-specific antibody responses in rabbits(2) and macaques(3), but so far failed to induce broadly neutralizing antibodies. One possible contributor to this failure is that the relevant antibody repertoires are poorly suited to target somewhat occluded conserved epitope regions on Env relative to exposed variable epitopes...
July 20, 2017: Nature
https://www.readbyqxmd.com/read/28726109/the-study-of-immunogenicity-of-the-antigenic-protein-of-high-risk-oncogenic-type-of-the-human-papillomavirus-hpv16-l1-produced-in-the-plant-expression-system-on-the-base-of-transgenic-tomato
#13
R K Salyaev, N I Rekoslavskaya, A S Stolbikov, A V Tretyakova
The immunogenicity of plant-made peroral vaccine against cervical cancer was studied in mice during 342 days after vaccination with the material of tomato fruits genetically transformed with HPV16 L1 Ώ 5'UTR TMV. The immune response was found on day 4 after vaccination in blood serum of vaccinated mice. On days 90-100, the rise to maximum value of the level of antibodies to HPV16 L1 was in the range of 500 ng of the standard antibodies to HPV16 L1 (Santa Cruz Biotechnology, United States). This level of antibodies was retained until the end of the study...
May 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28724967/a-balancing-act-rna-binding-protein-hur-ttp-axis-in-endometriosis-patients
#14
Kasra Khalaj, Soo Hyun Ahn, Mallikarjun Bidarimath, Yasmin Nasirzadeh, Sukhbir S Singh, Asgerally T Fazleabas, Steven L Young, Bruce A Lessey, Madhuri Koti, Chandrakant Tayade
Endometriosis, a major reproductive pathology affecting 8-10% of women is characterized by chronic inflammation and immune dysfunction. Human antigen R (HuR) and Tristetraprolin (TTP) are RNA binding proteins that competitively bind to cytokines involved in inflammation including: tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) among others, and stabilize and destabilize them, respectively. The aim of this study was to examine RNA binding protein (RNABP) HuR/TTP axis in endometriosis patients compared to menstrual stage matched healthy fertile controls in hopes of better understanding their contribution to the pathogenesis of endometriosis...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#15
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#16
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28716800/relationship-between-vascular-resistance-and-sympathetic-nerve-fiber-density-in-arterial-vessels-in-children-with-sleep-disordered-breathing
#17
Anna Kontos, Kurt Lushington, James Martin, Quenten Schwarz, Ryan Green, David Wabnitz, Xiangjun Xu, Elke M Sokoya, Scott Willoughby, Mathias Baumert, Antonio Ferrante, Melissa La Forgia, Declan Kennedy
BACKGROUND: Sleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is recognized to promote vascular remodeling. Importantly, increased vascular sympathetic nerve fiber density and innervation in early life plays a key role in the development of early-onset hypertension in animal models...
July 17, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28716370/a-systematic-review-and-framework-for-the-use-of-hormone-therapy-with-salvage-radiation-therapy-for-recurrent-prostate-cancer
#18
REVIEW
Daniel E Spratt, Robert T Dess, Zachary S Zumsteg, Daniel W Lin, Phuoc T Tran, Todd M Morgan, Emmanuel S Antonarakis, Paul L Nguyen, Charles J Ryan, Howard M Sandler, Matthew R Cooperberg, Edwin Posadas, Felix Y Feng
CONTEXT: Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results. OBJECTIVE: To perform a systematic review of randomized phase III trials of the use of SRT ± HT and generate a framework for the use of HT with SRT. EVIDENCE ACQUISITION: Systematic literature searches were conducted on February 15, 2017 in three databases (MEDLINE [via PubMed], EMBASE, and ClinicalTrials...
July 14, 2017: European Urology
https://www.readbyqxmd.com/read/28716099/xenoantigenicity-of-porcine-decellularized-valves
#19
Meghana R K Helder, Nicholas J Stoyles, Brandon J Tefft, Ryan S Hennessy, Rebecca R C Hennessy, Roy Dyer, Tyra Witt, Robert D Simari, Amir Lerman
BACKGROUND: The xenoantigenicity of porcine bioprosthetic valves is implicated as an etiology leading to calcification and subsequent valve failure. Decellularization of porcine valves theoretically could erase the antigenicity of the tissue leading to more durable prosthetic valves, but the effectiveness of decellularization protocols in regard to completely removing antigens has yet to be verified. Our hypothesis was that decellularization would remove the more abundant α-gal antigens but not remove all the non α-gal antigens, which could mount a response...
July 17, 2017: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/28713239/increased-white-matter-inflammation-in-aging-and-alzheimer-s-disease-brain
#20
Divya Raj, Zhuoran Yin, Marjolein Breur, Janine Doorduin, Inge R Holtman, Marta Olah, Ietje J Mantingh-Otter, Debby Van Dam, Peter P De Deyn, Wilfred den Dunnen, Bart J L Eggen, Sandra Amor, Erik Boddeke
Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis...
2017: Frontiers in Molecular Neuroscience
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