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https://www.readbyqxmd.com/read/28109042/expression-and-characterization-of-a-codon-optimized-blood-coagulation-factor-viii
#1
S A Shestopal, J-J Hao, E Karnaukhova, Y Liang, M V Ovanesov, M Lin, J H Kurasawa, T K Lee, J H McVey, A G Sarafanov
BACKGROUND: Production of recombinant factor VIII (FVIII) is challenging due to its low expression. It was previously shown that codon-optimization of a B domain-deleted FVIII (BDD-FVIII) cDNA resulted in increased protein expression. However, it is well-recognized that synonymous mutations may affect the protein structure and function. OBJECTIVES: To compare biochemical properties of a BDD-FVIII expressed from codon-optimized (CO) and the wild-type (WT) cDNAs. METHODS: Each variant of the BDD-FVIII was expressed in several independent CHO cell lines, generated using a lentiviral platform...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28109028/breadth-of-t-cell-responses-after-immunization-with-adenovirus-vectors-encoding-ancestral-antigens-or-polyvalent-papillomavirus-antigens
#2
Emeline Ragonnaud, Anders Gorm Pedersen, Peter Johannes Holst
Oncogenic human papillomaviruses (HPVs) are in most cases eliminated by intervention of T cells. As many other pathogens, these oncogenic HPVs belong to an ancient and diverse virus family. Therefore, we found it relevant to investigate the potential and limitations of inducing a broad response - either by inducing cross-reactive T cells or by administering a polyvalent vaccine. To test these strategies, we designed 3 ancestral and 2 circulating sequences based on the two domains of the E1 and E2 proteins of papillomaviruses (PVs) that exhibit the highest degree of conservation in comparison to the other PV proteins...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#3
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28109003/eradication-of-hcv-and-non-liver-related-non-aids-related-events-in-hiv-hcv-coinfection
#4
Juan Berenguer, Elena Rodríguez-Castellano, Ana Carrero, Miguel A Von Wichmann, Marta Montero, María J Galindo, Josep Mallolas, Manuel Crespo, María J Téllez, Carmen Quereda, José Sanz, Carlos Barros, Cristina Tural, Ignacio Santos, Federico Pulido, Josep M Guardiola, Rafael Rubio, Enrique Ortega, María L Montes, Juan J Jusdado, Gabriel Gaspar, Herminia Esteban, José M Bellón, Juan González-García
: We assessed non-liver-related non-AIDS-related (NLR-NAR) events and mortality in a cohort of HIV/HCV-coinfected patients treated with interferon and ribavirin between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and non-responders. Fine and Gray regression analysis was conducted to determine the adjusted sub-hazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk...
January 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28108952/transcriptional-regulators-dictate-innate-lymphoid-cell-fates
#5
REVIEW
Chao Zhong, Jinfang Zhu
Research on innate lymphoid cells (ILC) has recently been a fast paced topic of immunological research. As ILCs are able to produce signature Th cytokine, ILCs have garnered considerable attention and have been described to represent the innate counterpart of the CD4(+) T helper (Th) cells. The development and function of ILCs are precisely regulated by a network of crucial transcription factors, which are also involved in the development or differentiation of conventional natural killer (cNK) cells and T cells...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108559/antigen-processing-in-the-endoplasmic-reticulum-is-monitored-by-semi-invariant-%C3%AE-%C3%AE-tcrs-specific-for-a-conserved-peptide-qa-1b-mhc-class-ib-ligand
#6
Jian Guan, Soo Jung Yang, Federico Gonzalez, Yuxin Yin, Nilabh Shastri
Ag processing in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP) is central to presentation of a normal peptide-MHC class I (MHC I) repertoire. Alternations in ERAAP function cause dramatic changes in the MHC I-presented peptides, which elicit potent immune responses. An unusual subset of CD8(+) T cells monitor normal Ag processing by responding to a highly conserved FL9 peptide that is presented by Qa-1(b), a nonclassical MHC Ib molecule (QFL) in ERAAP-deficient cells...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108558/irf4-expression-in-thymic-epithelium-is-critical-for-thymic-regulatory-t-cell-homeostasis
#7
Uku Haljasorg, James Dooley, Martti Laan, Kai Kisand, Rudolf Bichele, Adrian Liston, Pärt Peterson
The thymus is a primary lymphoid organ required for the induction and maintenance of central tolerance. The main function of the thymus is to generate an immunocompetent set of T cells not reactive to self. During negative selection in the thymus, thymocytes with autoreactive potential are either deleted or differentiated into regulatory T cells (Tregs). The molecular basis by which the thymus allows high-efficiency Treg induction remains largely unknown. In this study, we report that IFN regulatory factor 4 (Irf4) is highly expressed in murine thymic epithelium and is required to prime thymic epithelial cells (TEC) for effective Treg induction...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108557/low-level-mhc-class-ii-expression-leads-to-suboptimal-th-cell-response-increased-autoaggression-and-heightened-cytokine-inducibility
#8
Yi-Ting Chen, Yu-Chia Su, Mei-Ling Chang, Pi-Fang Tsai, John T Kung
The development and activation of MHC class II (MHC-II)-restricted CD4(+) T cells are distinct immunological processes that are strictly MHC-II-dependent. To address their relative dependence on MHC-II, we established a novel ENU-induced mutant mouse on the C57BL/6 background, named I-A(12%), with ∼8-fold reduced I-A expression on the surface of B cells, dendritic cells, cortical thymic epithelial cells, and medullary thymic epithelial cells. I-A(100%) and I-A(12%) mice are highly similar with respect to the numbers of double-positive thymocytes, CD4(+)CD8(-) T cells, regulatory T cells, CD4(+) T cell marker expression, lifespan, and Th/regulatory T cell function...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108509/differential-pi3k%C3%AE-signaling-in-cd4-t-cell-subsets-enables-selective-targeting-of-t-regulatory-cells-to-enhance-cancer-immunotherapy
#9
Samir N Khleif, Shamim Ahmad, Rasha Abu Eid, Rajeev K Shrimali, Mason Webb, Vivek Verma, Atbin Doroodchi, Zuzana Berrong, Raed N Samara, Paulo C Rodriguez, Mikayel Mkrtichyan
To modulate T cell function for cancer therapy one challenge is to selectively attenuate regulatory but not conventional CD4+ T cell subsets (Treg and Tconv). In this study we show how a functional dichotomy in Class IA PI3K isoforms in these two subsets of CD4+ T cells be exploited to target Treg while leaving Tconv intact. Studies employing isoform-specific PI3K inhibitors and a PI3Kδ-deficient mouse strain revealed that PI3Kα and PI3Kβ were functionally redundant with PI3Kδ in Tconv. Conversely, PI3Kδ was functionally critical in Treg, acting there to control TCR signaling, cell proliferation and survival...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108460/enhancer-remodeling-during-adaptive-bypass-to-mek-inhibition-is-attenuated-by-pharmacological-targeting-of-the-p-tefb-complex
#10
Jon S Zawistowski, Samantha M Bevill, Daniel R Goulet, Timothy J Stuhlmiller, Adriana S Beltran, Jose F Olivares-Quintero, Darshan Singh, Noah Sciaky, Joel S Parker, Naim U Rashid, Xin Chen, James S Duncan, Martin C Whittle, Steven P Angus, Sara Hanna Velarde, Brian T Golitz, Xiaping He, Charlene Santos, David B Darr, Kristalyn Gallagher, Lee M Graves, Charles M Perou, Lisa A Carey, H Shelton Earp, Gary L Johnson
Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment...
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28108419/regulation-of-protein-kinase-c-related-kinase-prk-signalling-by-the-tp%C3%AE-and-tp%C3%AE-isoforms-of-the-human-thromboxane-a2-receptor-implications-for-thromboxane-and-androgen-dependent-neoplastic-and-epigenetic-responses-in-prostate-cancer
#11
Aine G O'Sullivan, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX) A2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA2/TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA2-TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108285/rifampin-suppresses-osteoclastogenesis-and-titanium-particle-induced-osteolysis-via-modulating-rankl-signaling-pathways
#12
Liang Zhu, Hui Kang, Chang-An Guo, Wen-Shuai Fan, Yi-Ming Wang, Lian-Fu Deng, Zuo-Qin Yan
BACKGROUND: Wear particles liberated from the surface of prostheses are considered to be main reason for osteoclast bone resorption and that extensive osteoclastogenesis leads to peri-implant osteolysis and subsequent prosthetic loosening. The aim of this study was to assess the effect of rifampin on osteoclastogenesis and titanium (Ti) particle-induced osteolysis. METHODS: The Ti particle-induced osteolysis mouse calvarial model and bone marrow-derived macrophages (BMMs) were used...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28108243/tpx2-as-a-prognostic-indicator-and-potential-therapeutic-target-in-clear-cell-renal-cell-carcinoma
#13
Zachary A Glaser, Harold D Love, Shunhua Guo, Lan Gellert, Sam S Chang, Stanley Duke Herrell, Daniel A Barocas, David F Penson, Michael S Cookson, Peter E Clark
OBJECTIVES: Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA). METHODS: Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist...
January 17, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28108239/preoperative-ultrasonography-for-evaluation-of-clinically-n0-neck-in-oral-cavity-carcinoma
#14
Angel Rollon-Mayordomo, Teresa Creo-Martinez, Yolanda Marin-Lapeira, Juan-Andres Rodriguez-Ruiz, Pedro Infante-Cossio
The aim of this study was to evaluate preoperative ultrasound criteria to detect lymph node (LN) cervical metastasis in patients with clinically node-negative neck (cN0) oral cavity squamous cell carcinoma (OCSCC). A prospective, single-center, observational study was conducted in 90 patients undergoing cancer excision with or without elective neck dissection (END) between 2005 and 2012. A surgeon and an experienced radiologist performed preoperative cervical ultrasonography in all cases. The primary objective was to obtain an a priori sensitivity of 90% and specificity >50% in cN0 OCSCC staging...
December 21, 2016: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28108221/sirtuin-1-independent-effects-of-resveratrol-in-ins-1e-%C3%AE-cells
#15
Cihan S Erdogan, Mathias Mørup-Lendal, Louise T Dalgaard, Ole Vang
Resveratrol (Resv), a natural polyphenol, is suggested to have various health benefits including improved insulin sensitivity. Resv activates Sirtuin (Sirt1) in several species and tissues. Sirt1 is a protein deacetylase with an important role in ageing, metabolism and β-cell function. In insulinoma β-cells (INS-1E), Resv is previously shown to improve glucose-stimulated insulin secretion in a Sirt1-dependent mechanism and to protect against β-cell dedifferentiation in non-human primates, while inducing hypertrophy in myoblasts...
January 17, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28108192/epidemiology-and-pathophysiology-of-childhood-narcolepsy
#16
REVIEW
Thomas J Dye, Neepa Gurbani, Narong Simakajornboon
It is now recognized that there are two types of narcolepsy. Narcolepsy type I or Narcolepsy with cataplexy is caused by the loss of hypocretin or orexin neurons. Narcolepsy type II or narcolepsy without cataplexy has normal hypocretin and the etiology is unknown. Hypocretin is a neuropeptide produced by neurons in the lateral hypothalamus. Both genetic and environmental factors play a crucial role in the pathogenesis of narcolepsy. Most patients with narcolepsy type I and half of patients with narcolepsy type II carry HLA-DQB1*0602...
December 21, 2016: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28108186/editing-the-trypanosoma-cruzi-genome-with-zinc-finger-nucleases
#17
Gabriela Assis Burle-Caldas, Viviane Grazielle-Silva, Melissa Soares-Simões, Gabriela Schumann Burkard, Isabel Roditi, Wanderson Duarte DaRocha, Santuza M Teixeira
Gene function studies in Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, have been hindered by the lack of efficient genetic manipulation protocols. In most organisms, insertion and deletion of DNA fragments in the genome are dependent on the generation of double-stranded DNA break (DSB) and repair. By inducing a site-specific DSB, zinc finger nucleases (ZFNs) have proven to be useful to enhance gene editing in many cell types. Using a pair of ZFNs targeted to the T. cruzi gp72 gene, we were able to generate gp72 knockout parasites with improved efficiency compared to the conventional gene knockout protocol...
January 17, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28108028/comparison-of-ca-2-puffs-evoked-by-extracellular-agonists-and-photoreleased-ip3
#18
REVIEW
Jeffrey T Lock, Ian F Smith, Ian Parker
The inositol trisphosphate (IP3) signaling pathway evokes local Ca(2+) signals (Ca(2+) puffs) that arise from the concerted openings of clustered IP3 receptor/channels in the ER membrane. Physiological activation is triggered by binding of agonists to G-protein-coupled receptors (GPCRs) on the cell surface, leading to cleavage of phosphatidyl inositol bisphosphate and release of IP3 into the cytosol. Photorelease of IP3 from a caged precursor provides a convenient and widely employed means to study the final stage of IP3-mediated Ca(2+) liberation, bypassing upstream signaling events to enable more precise control of the timing and relative concentration of cytosolic IP3...
December 5, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28107608/the-increased-expression-of-tcf3-is-correlated-with-poor-prognosis-in-chinese-patients-with-nasopharyngeal-carcinoma
#19
Xiaohe Shen, Jizhao Yuan, Mengjie Zhang, Wenhua Li, Bing Ni, Yuzhang Wu, Li Jiang, Weiping Fan, Zhiqiang Tian
OBJECTIVES: Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote cancer growth and progression. B-cell-specific transcription factor 3 (TCF3/E2A) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family that is central to regulating epidermal and embryonic stem cell identity. It has been reported that TCF3 was connected with the development and progression of a number of human cancers...
January 20, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28107375/narcolepsy-type-1-is-associated-with-a-systemic-increase-and-activation-of-regulatory-t-cells-and-with-a-systemic-activation-of-global-t-cells
#20
Michel Lecendreux, Guillaume Churlaud, Fabien Pitoiset, Armelle Regnault, Tu Anh Tran, Roland Liblau, David Klatzmann, Michelle Rosenzwajg
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination...
2017: PloS One
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