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Rafaella Paola Meneguete Dos Guimarães-Peixoto, Paulo Sérgio de Arruda Pinto, Marcus Rebouças Santos, Marcelo Depólo Polêto, Letícia Ferreira da Silva, Abelardo Silva Júnior
Bovine cysticercosis is a zoonotic infection widely spread throughout Brazil, creating a burden on hygiene maintenance and the economy. Diagnosis of cysticercosis usually relies on post mortem inspection of carcasses in slaughterhouses. This detection method provides only low sensitivity. Recent advancements have improved the performance of serologic tests, such as ELISA, providing greater sensitivity and specificity. The objective of the current study was to identify and evaluate a synthetic peptide derived from the Taenia saginata 18kDa oncospheric surface protein for the diagnosis of bovine cysticercosis in ELISA...
October 16, 2016: Acta Tropica
Liang Chen, Lijuan Zhao, Frederick W Alt, Michael S Krangel
Chromatin looping mediated by the CCCTC binding factor (CTCF) regulates V(D)J recombination at Ag receptor loci. CTCF-mediated looping can influence recombination signal sequence (RSS) accessibility by regulating enhancer activation of germline promoters. CTCF-mediated looping has also been shown to limit directional tracking of the RAG recombinase along chromatin, and to regulate long-distance interactions between RSSs, independent of the RAG recombinase. However, in all prior instances in which CTCF-mediated looping was shown to influence V(D)J recombination, it was not possible to fully resolve the relative contributions to the V(D)J recombination phenotype of changes in accessibility, RAG tracking, and RAG-independent long-distance interactions...
September 9, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yangbo Yue, Stanley G Leung, Yueyong Liu, Yurong Huang, Kirsten Grundt, Anne-Carine Østvold, Kuang-Yu Jen, David Schild, Jian-Hua Mao, Claudia Wiese
NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo...
August 16, 2016: Oncotarget
Sohei Arase, Yohei Watanabe, Hiromi Setoyama, Noriko Nagaoka, Mitsuhisa Kawai, Satoshi Matsumoto
Psychological stress can exacerbate inflammatory bowel disease. However, the mechanisms underlying how psychological stress affects gut inflammation remain unclear. Here, we focused on the relationship between changes in the microbial community of mucosa-associated commensal bacteria (MACB) and mucosal immune responses induced by chronic psychological stress in a murine model of ulcerative colitis. Furthermore, we examined the effect of probiotic treatment on exacerbated colitis and MACB composition changes induced by chronic psychological stress...
2016: PloS One
Anna Pasetto, Alena Gros, Paul F Robbins, Drew C Deniger, Todd D Prickett, Rodrigo Matus-Nicodemos, Daniel C Douek, Bryan Howie, Harlan Robins, Maria R Parkhurst, Jared Gartner, Katarzyna Trebska-McGowan, Jessica S Crystal, Steven A Rosenberg
Adoptive transfer of T cells with engineered T-cell receptor (TCR) genes that target tumor-specific antigens can mediate cancer regression. Accumulating evidence suggests that the clinical success of many immunotherapies is mediated by T cells targeting mutated neoantigens unique to the patient. We hypothesized that the most frequent TCR clonotypes infiltrating the tumor were reactive against tumor antigens. To test this hypothesis, we developed a multistep strategy that involved TCRB deep sequencing of the CD8(+)PD-1(+) T-cell subset, matching of TCRA-TCRB pairs by pairSEQ and single-cell RT-PCR, followed by testing of the TCRs for tumor-antigen specificity...
September 2, 2016: Cancer Immunology Research
H Cordero, A Cuesta, J Meseguer, M A Esteban
Lymphocystis or lymphocystis disease virus (LCDV) is distributed worldwide and affects many fresh and marine water fish species. LCDV is commonly found in aquaria fish species but also in farmed fish species, among them the gilthead seabream (Sparus aurata L.). The immune status of gilthead seabream (S. aurata) specimens under a natural outbreak of LCDV was studied. The replication of the virus was demonstrated in infected fish, but not in control fish. The results showed decreased total serum IgM levels and increased innate cellular immune response (peroxidase and respiratory burst activities) of head kidney leucocytes in LCDV-infected fish, compared to the values obtained in uninfected specimens...
May 2, 2016: Journal of Fish Diseases
Ai-Zhen Liu, Hong-Guo Zhao, Ying Gao, Ming Liu, Bao-Zhi Guo
Intrauterine adhesion (IUA), also known as Asherman's syndrome, is a common disease for among women. The extent of adhesion and pre-surgery hormone therapy greatly affects the function of uterine cavity. This current study investigates the association of different doses of estrogen before transcervical resection of adhesions (TCRA) surgery and clinical outcome in serious IUA. About 120 newly diagnostic serious IUA patients who underwent TCRA were randomly divided into three study groups: Estradiol valerate (progynova) 3 or 9 mg per diet before surgery and the control group...
March 16, 2016: Gynecological Endocrinology
X Wang, H Duan
OBJECTIVE: To evaluate the effect of amniotic products after transcervical resection of uterine adhesions (TCRA). METHODS: This study was carried out in 57 patients with intensive degree of intrauterine adhesions (IUA) who had been treated by TCRA between Jun. 2013 to Jun. 2014. These patients were devided into two groups randomly. In group amnion, 29 patients were placed amniontic scaffold balloon after TCRA; in group balloon, 28 patients were placed Foley's balloon after TCRA...
January 2016: Zhonghua Fu Chan Ke za Zhi
Cielito C Reyes-Gibby, Jian Wang, Mary Rose T Silvas, Robert Yu, Sai-Ching J Yeung, Sanjay Shete
BACKGROUND: Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC). RESULTS: We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search...
2016: BMC Genetics
Lichen Jing, Kerry J Laing, Lichun Dong, Ronnie M Russell, Russell S Barlow, Juergen G Haas, Meena S Ramchandani, Christine Johnston, Soren Buus, Alec J Redwood, Katie D White, Simon A Mallal, Elizabeth J Phillips, Christine M Posavad, Anna Wald, David M Koelle
The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity...
March 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Anna Stengel, Wolfgang Kern, Melanie Zenger, Karolína Perglerová, Susanne Schnittger, Torsten Haferlach, Claudia Haferlach
T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data are available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis...
January 2016: Genes, Chromosomes & Cancer
Bryan Howie, Anna M Sherwood, Ashley D Berkebile, Jan Berka, Ryan O Emerson, David W Williamson, Ilan Kirsch, Marissa Vignali, Mark J Rieder, Christopher S Carlson, Harlan S Robins
The T cell receptor (TCR) protein is a heterodimer composed of an α chain and a β chain. TCR genes undergo somatic DNA rearrangements to generate the diversity of T cell binding specificities needed for effective immunity. Recently, high-throughput immunosequencing methods have been developed to profile the TCR α (TCRA) and TCR β (TCRB) repertoires. However, these methods cannot determine which TCRA and TCRB chains combine to form a specific TCR, which is essential for many functional and therapeutic applications...
August 19, 2015: Science Translational Medicine
Liang Chen, Zachary Carico, Han-Yu Shih, Michael S Krangel
The locus encoding the T cell antigen receptor (TCR) α-chain and δ-chain (Tcra-Tcrd) undergoes recombination of its variable-diversity-joining (V(D)J) segments in CD4(-)CD8(-) double-negative thymocytes and CD4(+)CD8(+) double-positive thymocytes to generate diverse TCRδ repertoires and TCRα repertoires, respectively. Here we identified a chromatin-interaction network in the Tcra-Tcrd locus in double-negative thymocytes that was formed by interactions between binding elements for the transcription factor CTCF...
October 2015: Nature Immunology
Cristina Hernández-Munain
Tcra/Tcrd includes 2 genes with distinct developmental programs controlled by 2 distant enhancers, Eα and Eδ. These enhancers work as a developmental switch during thymocyte development and they are essential for generation of αβ and γδ T-lymphocytes. Tcra and Tcrd transit from an unrearranged configuration to a rearranged configuration during T-cell development. Eα and Eδ are responsible for transcription of their respective unrearranged genes in thymocytes but are dispensable for such functions in the context of the rearranged genes in mature T-cells...
2015: Transcription
Tanya Parish
Two-component regulatory systems (2CRSs) are widely used by bacteria to sense and respond to environmental stimuli with coordinated changes in gene expression. Systems are normally comprised of a sensory kinase protein that activates a transcriptional regulator by phosphorylation. Mycobacteria have few 2CRSs, but they are of key importance for bacterial survival and play important roles in pathogenicity. Mycobacterium tuberculosis has 12 paired two-component regulatory systems (which include a system with two regulators and one sensor, and a split sensor system), as well as four orphan regulators...
February 2014: Microbiology Spectrum
P Y Yew, H Alachkar, R Yamaguchi, K Kiyotani, H Fang, K L Yap, H T Liu, A Wickrema, A Artz, K van Besien, S Imoto, S Miyano, M R Bishop, W Stock, Y Nakamura
Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach...
September 2015: Bone Marrow Transplantation
Hongwei Shao, Yanmei Lin, Teng Wang, Yusheng Ou, Han Shen, Changli Tao, Fenglin Wu, Wenfeng Zhang, Huaben Bo, Hui Wang, Shulin Huang
Identification of TCR genes specific for tumor-associated antigens (TAAs) is necessary for TCR gene modification of T cells, which is applied in anti-tumor adoptive T cell therapy (ACT). The usual identification methods are based on isolating single peptide-responding T cells and cloning the TCR gene by in vitro expansion or by single-cell RT-PCR. However, the long and exacting in vitro culture period and demanding operational requirements restrict the application of these methods. Immunoscope is an effective tool that profiles a repertoire of TCRs and identifies significantly expanded clones through CDR3 length analysis...
July 10, 2015: Cancer Letters
Bingtao Hao, Abani Kanta Naik, Akiko Watanabe, Hirokazu Tanaka, Liang Chen, Hunter W Richards, Motonari Kondo, Ichiro Taniuchi, Yoshinori Kohwi, Terumi Kohwi-Shigematsu, Michael S Krangel
Rag1 and Rag2 gene expression in CD4(+)CD8(+) double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here, we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements...
May 4, 2015: Journal of Experimental Medicine
Beatriz del Blanco, Úrsula Angulo, Michael S Krangel, Cristina Hernández-Munain
The Tcra enhancer (Eα) is essential for Tcra locus germ-line transcription and primary Vα-to-Jα recombination during thymocyte development. We found that Eα is inhibited late during thymocyte differentiation and in αβ T lymphocytes, indicating that it is not required to drive transcription of rearranged Tcra genes. Eα inactivation resulted in the disruption of functional long-range enhancer-promoter interactions and was associated with loss of Eα-dependent histone modifications at promoter and enhancer regions, and reduced expression and recruitment of E2A to the Eα enhanceosome in T cells...
April 7, 2015: Proceedings of the National Academy of Sciences of the United States of America
Mitsuo Hashimoto, Haruhiko Yanagisawa, Shunsuke Minagawa, Debasish Sen, Amanda Goodsell, Royce Ma, Catherine Moermans, Kate J McKnelly, Jody L Baron, Matthew F Krummel, Stephen L Nishimura
Chronic airway inflammation and fibrosis, known as airway remodeling, are defining features of chronic obstructive pulmonary disease and are refractory to current treatments. How and whether chronic inflammation contributes to airway fibrosis remain controversial. In this study, we use a model of chronic obstructive pulmonary disease airway disease utilizing adenoviral delivery of IL-1β to determine that adaptive T cell immunity is required for airway remodeling because mice deficient in α/β T cells (tcra(-/-)) are protected...
April 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
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