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https://www.readbyqxmd.com/read/29054116/t-cell-epitope-content-comparison-epicc-of-swine-h1-influenza-a-virus-hemagglutinin
#1
Andres H Gutiérrez, Vicki Rapp-Gabrielson, Frances E Terry, Crystal Loving, Leonard Moise, William D Martin, Anne S De Groot
BACKGROUND: Predicting vaccine efficacy against emerging pathogen strains is a significant problem in human and animal vaccine design. T cell epitope cross-conservation may play an important role in cross-strain vaccine efficacy. While influenza A virus (IAV) hemagglutination inhibition (HI) antibody titers are widely used to predict protective efficacy of one IAV vaccine against new strains, no similar correlate of protection has been identified for T cell epitopes. OBJECTIVE: We developed a computational method (EpiCC) that facilitates pairwise comparison of protein sequences based on an immunological property - T cell epitope content - rather than sequence identity, and evaluated its ability to classify swine IAV strain relatedness to estimate cross-protective potential of a vaccine strain for circulating viruses...
October 20, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/29053971/a-gut-microbial-mimic-that-hijacks-diabetogenic-autoreactivity-to-suppress-colitis
#2
Roopa Hebbandi Nanjundappa, Francesca Ronchi, Jinguo Wang, Xavier Clemente-Casares, Jun Yamanouchi, Channakeshava Sokke Umeshappa, Yang Yang, Jesús Blanco, Helena Bassolas-Molina, Azucena Salas, Hamza Khan, Robyn M Slattery, Madeleine Wyss, Catherine Mooser, Andrew J Macpherson, Laura K Sycuro, Pau Serra, Derek M McKay, Kathy D McCoy, Pere Santamaria
The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic β cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053960/a-general-strategy-for-discovery-of-inhibitors-and-activators-of-ring-and-u-box-e3-ligases-with-ubiquitin-variants
#3
Mads Gabrielsen, Lori Buetow, Mark A Nakasone, Syed Feroj Ahmed, Gary J Sibbet, Brian O Smith, Wei Zhang, Sachdev S Sidhu, Danny T Huang
RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2∼Ub binding site...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29053706/solea-senegalensis-sperm-cryopreservation-new-insights-on-sperm-quality
#4
Marta F Riesco, Catarina Oliveira, Florbela Soares, Paulo J Gavaia, María T Dinis, Elsa Cabrita
Cryopreservation of Senegalese sole sperm can represent an alternative to overcome some reproductive problems of this species. However, it is important to guarantee the safe use of cryopreserved sperm by selecting an appropriate protocol according to a high demand quality need to be ensured. It has been demonstrated that traditional assays such as motility and viability do not provide enough information to identify specific damage caused by cryopreservation process (freezing and thawing). Specific tests, including lipid peroxidation and DNA damage, should be performed...
2017: PloS One
https://www.readbyqxmd.com/read/29053579/stem-cells-as-potential-candidates-for-psoriasis-cell-replacement-therapy
#5
REVIEW
Agnieszka Owczarczyk-Saczonek, Magdalena Krajewska-Włodarczyk, Anna Kruszewska, Waldemar Placek, Wojciech Maksymowicz, Joanna Wojtkiewicz
Recent years have seen considerable progress in explaining the mechanisms of the pathogenesis of psoriasis, with a significant role played in it by the hyper-reactivity of Th1 and Th17 cells, Treg function disorder, as well as complex relationships between immune cells, keratinocytes, and vascular endothelium. The effect of stem cells in the epidermis and stem cells on T cells has been identified and the dysfunction of various types of stem cells may be a prime cause of dysregulation of the inflammatory response in psoriasis...
October 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29053396/embryonic-stem-cell-secreted-factors-decrease-invasiveness-of-triple-negative-breast-cancer-cells-through-regulome-modulation
#6
Elizabeth Tarasewicz, Robert S Oakes, Misael O Aviles, Joelle Straehla, Kathryn M Chilton, Joseph T Decker, Jia Wu, Lonnie D Shea, Jacqueline S Jeruss
Stem cell microenvironments decrease the invasiveness of cancer cells, and elucidating the mechanisms associated with disease regression could further the development of targeted therapies for aggressive cancer subtypes. To this end, we applied an emerging technology, TRanscriptional Activity CEll aRray (TRACER), to investigate the reprogramming of triple-negative breast cancer (TNBC) cells in conditions that promoted a less aggressive phenotype. The repressive environment was established through exposure to mouse embryonic stem cell conditioned media (mESC CM)...
October 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29053157/current-applications-of-multiparameter-flow-cytometry-in-plasma-cell-disorders
#7
REVIEW
T Jelinek, R Bezdekova, M Zatopkova, L Burgos, M Simicek, T Sevcikova, B Paiva, R Hajek
Multiparameter flow cytometry (MFC) has become standard in the management of patients with plasma cell (PC) dyscrasias, and could be considered mandatory in specific areas of routine clinical practice. It plays a significant role during the differential diagnostic work-up because of its fast and conclusive readout of PC clonality, and simultaneously provides prognostic information in most monoclonal gammopathies. Recent advances in the treatment and outcomes of multiple myeloma led to the implementation of new response criteria, including minimal residual disease (MRD) status as one of the most relevant clinical endpoints with the potential to act as surrogate for survival...
October 20, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/29053133/-ophthalmic-disorders-as-a-manifestation-of-parkinson-s-disease
#8
N B Chesnokova, T A Pavlenko, M V Ugrumov
Parkinson's disease is a severe neurodegenerative disease accompanied with the degeneration of dopaminergic neurons in the central and peripheral nervous system. The diagnosis of Parkinson's disease can still be made only on the stage of irreversible and nearly total degeneration of the nigrostriatum dopaminergic system and exhaustion of brain compensatory mechanisms that explains the low efficacy of therapy. Ophthalmic pathology is one of the nonmotor symptoms of Parkinson's disease. This can be explained firstly by the fact that eye is a 'peripheral part of brain' and secondly by the involvement of dopaminergic neurons (dopamine-producing cells) that are subject to the selective degeneration during Parkinson's disease in the regulation of visual function in the eye and brain...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#9
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052750/impact-of-a-cd4-gene-haplotype-on-the-immune-response-in-minipigs
#10
Fany Blanc, Françoise Créchet, Nicolas Bruneau, Guillaume Piton, Jean-Jacques Leplat, Fabrice Andréoletti, Giorgia Egidy, Silvia Vincent-Naulleau, Emmanuelle Bourneuf
The cluster of differentiation 4 (CD4) molecule functions as a co-receptor for MHC class II binding to TCR in T helper cells. A CD4 epitope deficiency was identified in the swine MeLiM (melanoblastoma-bearing Libechov minipig) strain, a model for spontaneous cutaneous melanoma development and regression. Extensive sequencing revealed a high genetic variability of CD4 and the existence of several haplotypes segregating in MeLiM. Forty polymorphisms were identified in the coding sequence, out of which 20 correspond to non-synonymous variants and 10 are located in the 3'UTR of CD4 transcripts...
October 20, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29052609/neuro-ophthalmic-side-effects-of-molecularly-targeted-cancer-drugs
#11
REVIEW
M T Bhatti, A K S Salama
The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity...
October 20, 2017: Eye
https://www.readbyqxmd.com/read/29052596/t-6-11-renal-cell-carcinoma-a-study-of-seven-cases-including-two-with-aggressive-behavior-and-utility-of-cd68-pg-m1-in-the-differential-diagnosis-with-pure-epithelioid-pecoma-epithelioid-angiomyolipoma
#12
Anna Caliò, Matteo Brunelli, Diego Segala, Serena Pedron, Regina Tardanico, Andrea Remo, Stefano Gobbo, Emanuela Meneghelli, Claudio Doglioni, Ondrej Hes, Claudia Zampini, Pedram Argani, Guido Martignoni
Renal cell carcinomas with t(6;11) chromosome translocation involving the TFEB gene are indolent neoplasms which often occur in young patients. In this study, we report seven cases of renal cell carcinoma with TFEB rearrangement, two of whom had histologically proven metastasis. Patients (4F, 3M) ranged in age from 19 to 55 years (mean 37). One patient developed paratracheal and pleural metastases 24 months after surgery and died of disease after 46 months; another one recurred with neoplastic nodules in the perinephric fat and pelvic soft tissue...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29052520/upregulation-of-dars2-by-hbv-promotes-hepatocarcinogenesis-through-the-mir-30e-5p-mapk-nfat5-pathway
#13
Xian Qin, Changsheng Li, Tao Guo, Jing Chen, Hai-Tao Wang, Yi-Tao Wang, Yu-Sha Xiao, Jun Li, Pengpeng Liu, Zhi-Su Liu, Quan-Yan Liu
BACKGROUND: Infection with the hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). The osmoregulatory transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown to play an important role in the development of many types of human cancers. The role of NFAT5 in HBV-associated HCC has never previously been investigated. METHODS: We compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC samples, adjacent nontumor tissues and different hepatoma cell lines by quantitative real-time polymerase chain reaction and /or Western blot...
October 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29052324/effect-of-heat-stress-during-in-vitro-maturation-on-developmental-competence-of-vitrified-bovine-oocytes
#14
M Vendrell-Flotats, N Arcarons, E Barau, M López-Béjar, T Mogas
Heat-shock protein 70 (HSP70) plays a crucial role as intracellular cytoprotectant and molecular chaperone. A phenomenon of heat stress (HS) leads to production of these proteins that could be beneficial to cells during cryopreservation, which is also a stressful process for the cell. This study aimed to evaluate the protective effect of exposure of bovine oocytes to moderate HS during in vitro maturation (IVM) prior vitrification. First, oocytes were subjected to HS (41.5°C for 1 hr) at 0, 4, 8, 12 or 16 of IVM...
October 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29052321/coenzyme-q10-supplementation-during-in-vitro-maturation-of-bovine-oocytes-bos-taurus-helps-to-preserve-oocyte-integrity-after-vitrification
#15
M Ruiz-Conca, M Vendrell, M Sabés-Alsina, T Mogas, M Lopez-Bejar
Oocyte vitrification causes less cell stress than slow cooling, but cytoskeletal and spindle alterations may occur affecting the oocyte competence. In vitro maturation (IVM) supplementation with different antioxidant molecules has been performed to attenuate this harmful stress. Coenzyme Q10 (CoQ10 ) supplementation has previously shown to have positive effects in bovine and mouse in vitro embryo development. The aim of this study was to evaluate the effects of CoQ10 during bovine oocyte IVM and vitrification...
October 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29052136/human-t-cell-leukemia-virus-type-1-infection-and-adult-t-cell-leukemia
#16
Chi-Ping Chan, Kin-Hang Kok, Dong-Yan Jin
Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus discovered to cause adult T-cell leukemia (ATL), a highly aggressive blood cancer. HTLV-1 research in the past 35 years has been most revealing in the mechanisms of viral oncogenesis. HTLV-1 establishes a lifelong persistent infection in CD4(+) T lymphocytes. The infection outcome is governed by host immunity. ATL develops in 2-5% of infected individuals 30-50 years after initial exposure. HTLV-1 encodes two oncoproteins Tax and HBZ, which are required for initiation of cellular transformation and maintenance of cell proliferation, respectively...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29051764/polyfunctional-cd4-t-cells-as-targets-for-tuberculosis-vaccination
#17
REVIEW
Deborah A Lewinsohn, David M Lewinsohn, Thomas J Scriba
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of morbidity and mortality worldwide, despite the widespread use of the only licensed vaccine, Bacille Calmette Guerin (BCG). Eradication of TB will require a more effective vaccine, yet evaluation of new vaccine candidates is hampered by lack of defined correlates of protection. Animal and human studies of intracellular pathogens have extensively evaluated polyfunctional CD4(+) T cells producing multiple pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) as a possible correlate of protection from infection and disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29051577/de-novo-mutations-of-tuba3d-are-associated-with-keratoconus
#18
Xiao-Dan Hao, Peng Chen, Yang-Yang Zhang, Su-Xia Li, Wei-Yun Shi, Hua Gao
Keratoconus (KC) is a common degenerative corneal disease, and heredity plays a key role in its development. Although few genes are known to cause KC, a large proportion of disease-causing genes remain to be revealed. Here, we report the identification of TUBA3D as a novel gene linked to KC. Using whole-exome sequencing of a twins pedigree, a novel de novo mutation (c.31 C > T, p.Gln11stop) in TUBA3D gene was identified. A screening performed in 200 additional unrelated patients with KC revealed another two mutations (c...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051323/epithelial-to-mesenchymal-transition-antagonizes-response-to-targeted-therapies-in-lung-cancer-by-suppressing-bim
#19
Anthony C Faber, Kyung-A Song, Matthew J Niederst, Timothy L Lochmann, Aaron N Hata, Hidenori Kitai, Jungoh Ham, Konstantinos V Floros, Mark A Hicks, Haichuan Hu, Hillary E Mulvey, Yotam Drier, Daniel A R Heisey, Mark T Hughes, Neha U Patel, Elizabeth Lockerman, Angel R Garcia, Shawn Gillepsie, Hannah L Archibald, Maria Gomez-Caraballo, Tara J Nulton, Brad Windle, Zofia Piotrowska, Sinem E Sahingur, Shirley M Taylor, Mikhail G Dozmorov, Lecia V Sequist, Bradley E Bernstein, Hiromichi Ebi, Jeffrey A Engelman
PURPOSE: Epithelial-to-mesenchymal transition (EMT) confers resistance to a number of targeted therapies and chemotherapies. However, it has been unclear why EMT promotes resistance, thereby impairing progress to overcome it. EXPERIMENTAL DESIGN: We have developed several models of EMT-mediated resistance to EGFR inhibitors (EGFRi) in EGFR mutant lung cancers to evaluate a novel mechanism of EMT-mediated resistance. Results: We observed that mesenchymal EGFR mutant lung cancers are resistant to EGFRi-induced apoptosis via insufficient expression of BIM, preventing cell death despite potent suppression of oncogenic signaling following EGFRi treatment...
October 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29051183/development-of-t-cell-immunotherapy-for-hematopoietic-stem-cell-transplantation-recipients-at-risk-of-leukemia-relapse
#20
Robson G Dossa, Tanya Cunningham, Daniel Sommermeyer, Indira Medina-Rodriguez, Melinda A Biernacki, Kimberly Foster, Marie Bleakley
Leukemia relapse remains the major cause of allogeneic hematopoietic stem cell transplantation (HCT) failure and the prognosis for patients with post-HCT relapse is poor. There is compelling evidence that potent selective anti-leukemic effects can be delivered by donor T cells specific for particular minor histocompatibility (H) antigens. Thus, T cell receptors (TCR) isolated from minor H antigen-specific T cells represent an untapped resource for developing targeted T cell immunotherapy to manage post-HCT leukemic relapse...
October 19, 2017: Blood
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