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Shoji Sugano, Satoru Maeda, Nagao Hayashi, Hideyuki Kajiwara, Haruhiko Inoue, Chang-Jie Jiang, Hiroshi Takatsuji, Masaki Mori
Plants have evolved many receptor-like cytoplasmic kinases (RLCKs) to modulate their growth, development, and innate immunity. Broad-Spectrum Resistance 1 (BSR1) encodes a rice RLCK whose overexpression confers resistance to multiple diseases, including fungal rice blast and bacterial leaf blight; however, the mechanisms underlying the resistance remain largely unknown. In the present study, we report that BSR1 is a functional protein kinase that autophosphorylates and transphosphorylates an artificial substrate, in vitro...
September 17, 2018: Plant Journal: for Cell and Molecular Biology
Daiki Muko, Takanori Ikenaga, Masanori Kasai, Janice B Rabor, Atsushi Nishitani, Yasuro Niidome
For analysis of low abundance peptides in a tissue section, immunohistochemical staining through antibody-antigen interaction is a usual technique. The antibody is conjugated with a probe moiety that aids in highly sensitive detection. Gold nanoparticles, which show excellent chemical stability and variation of surface modifications, are expected to act as a sensitive mass probe to desorb gold ions (Au+ , Au2 + , Au3 + ) that are distinguishable from fragment ions from organic molecules. Here, green fluorescent proteins (GFP) in a tissue section of a transgenic zebrafish was detected by the gold mass probe conjugated with antibodies...
September 17, 2018: Journal of Mass Spectrometry: JMS
Shenglan Dai, Xiaohua Chen, Yongsheng Yu, Guoqing Zang, Zhenghao Tang
Hepatitis B virus (HBV) infection is a global public health problem. T helper (Th)1‑associated cytokines are involved in HBV clearance during acute and persistent infection. In our previous study, it was demonstrated that lentiviral vectors encoding ubiquitinated hepatitis B core antigen (LV‑Ub‑HBcAg) effectively transduced dendritic cells (DCs) to induce maturation, which promoted T cell polarization to Th1 and generated HBcAg‑specific cytotoxic T lymphocytes (CTLs) ex vivo. In the present study, HBV transgenic mice were immunized with LV‑Ub‑HBcAg‑transduced DCs and HBcAg‑specific immune responses were evaluated...
September 14, 2018: Molecular Medicine Reports
Shi-Jiang Yu, Qi Pan, Ren Luo, Cui-Lun Wang, Lu-Yan Cheng, Juan-Sheng Yang, Hao-Nan Zhou, Dong-Yuan Hou, Hao-Qiang Liu, Chun Ran
BACKGROUND: Dialeurodes citri is an important pest in citrus-producing areas of the world. Lecanicillium attenuatum parasitizes D. citri and kills it, suggesting a potential approach for the biological control of pests. However, the low virulence of the fungus and its slow rate of killing have limited its commercial competitiveness. The objective reason for these disadvantages is immunological rejection by the host. Our strategy was to use fungi to express the dsRNA of the host immune genes...
September 16, 2018: Pest Management Science
Laura E Johnson, Dirk Brockstedt, Meredith Leong, Peter Lauer, Erin Theisen, John-Demian Sauer, Douglas G McNeel
Background . Sipuleucel T, an autologous cell-based vaccine targeting prostatic acid phosphatase (PAP), has demonstrated efficacy for the treatment of advanced prostate cancer. DNA vaccines encoding PAP and live attenuated Listeria vaccines have entered clinical trials for patients with prostate cancer, and have advantages in terms of eliciting predominantly Th1-biased immunity. In this study, we investigated whether the immunogenicity and anti-tumor efficacy of a DNA and Listeria vaccine, each encoding PAP, could be enhanced by using them in a heterologous prime/boost approach...
2018: Oncoimmunology
Annika J Kettenburg, Jan Hanspach, David J Abson, Joern Fischer
Transgenic Golden Rice has been hailed as a practical solution to vitamin A deficiency, but has also been heavily criticized. To facilitate a balanced view on this polarized debate, we investigated existing arguments for and against Golden Rice from a sustainability science perspective. In a structured literature review of peer-reviewed publications on Golden Rice, we assessed to what extent 64 articles addressed 70 questions covering different aspects of sustainability. Using cluster analysis, we grouped the literature into two major branches, containing two clusters each...
2018: Sustainability science
Cheng-Mao Lin, Paul M Titchenell, Jason M Keil, Adolfo Garcia-Ocaña, Mark T Bolinger, Steven F Abcouwer, David A Antonetti
Changes in permeability of retinal blood vessels contribute to macular edema and the pathophysiology of numerous ocular diseases, including diabetic retinopathy, retinal vein occlusions, and macular degeneration. Vascular endothelial growth factor (VEGF) induces retinal permeability and macular thickening in these diseases. However, inflammatory agents, such as tumor necrosis factor-α (TNF-α), also may drive vascular permeability, specifically in patients unresponsive to anti-VEGF therapy. Recent evidence suggests VEGF and TNF-α induce permeability through distinct mechanisms; however, both require the activation of atypical protein kinase C (aPKC)...
September 12, 2018: American Journal of Pathology
Ho-Jae Lee, Young-Min Han, Jeong Min An, Eun A Kang, Yong Jin Park, Ji-Young Cha, Ki Baik Hahm
Although inflammation is defensive and healing process that maintains organ homeostasis, unresolved inflammation can lead to diseases. Polyunsaturated fatty acids (PUFAs), especially n-6 PUFAs abundant in Western diet, are precursors of pro-inflammatory mediators, whereas n-3 PUFAs possess anti-inflammatory properties. Therefore, interest in the cancer-preventive effect of n-3 PUFAs is increasing. Areas covered: We have observed significant reductions of gastrointestinal (GI) tumorigenesis in the Fat-1 transgenic mouse as evidenced that the decrease in Helicobacter pylori-infected gastric tumorigenesis, colon, biliary and pancreatic cancer was seen in Fat-1 mice producing n-3 PUFAs...
September 17, 2018: Expert Review of Anticancer Therapy
Iris F Macheleidt, Priya S Dalvi, So-Young Lim, Sonja Meemboor, Lydia Meder, Olivia Käsgen, Marion Müller, Karolin Kleemann, Lingyu Wang, Peter Nürnberg, Vanessa Rüsseler, Stephan C Schäfer, Esther Mahabir, Reinhard Büttner, Margarete Odenthal
Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Despite the development of novel targeted and immune therapies, the five-year survival rate is still only 21%, necessitating more efficient treatment regimens. Lysine-specific demethylase 1 (LSD1) is an epigenetic eraser which modifies histone 3 methylation status, and is highly overexpressed in LUAD. Using representative human cell culture systems and two autochthonous transgenic mouse models, we investigated inhibition of LSD1 as a novel therapeutic option to treat LUAD...
September 16, 2018: Molecular Oncology
Nicholas D Bonawitz, W Michael Ainley, Asuka Itaya, Sivarama R Chennareddy, Tobias Cicak, Katherine Effinger, Ke Jiang, Tejinder Kumar Mall, Pradeep Reddy Marri, J Pon Samuel, Nagesh Sardesai, Matthew Simpson, Otto Folkerts, Rodrigo Sarria, Steven R Webb, Delkin O Gonzalez, Daina H Simmonds, Dayakar R Pareddy
Emerging genome editing technologies hold great promise for the improvement of agricultural crops. Several related genome editing methods currently in development utilize engineered, sequence-specific endonucleases to generate DNA double strand breaks (DSBs) at user-specified genomic loci. These DSBs subsequently result in small insertions/deletions (indels), base substitutions, or incorporation of exogenous donor sequences at the target site, depending on the application. Targeted mutagenesis in soybean (Glycine max) via non-homologous end joining (NHEJ)-mediated repair of such DSBs has been previously demonstrated with multiple nucleases, as has homology-directed repair (HDR)-mediated integration of a single transgene into target endogenous soybean loci using CRISPR/Cas9...
September 16, 2018: Plant Biotechnology Journal
Shun Zhang, Xiang Shu, Jinji Yang, Jinyue Shi, Xiaomei Guan, Jianrong Jiang, Yingming Wei, Chan Luo, Deshun Shi, Fenghua Lu
The present study explored a suitable parthenogenetic activation (PA) procedure for rabbit oocytes and investigated the developmental potential of somatic cell nuclear transfer (SCNT) embryos using rabbit fetal fibroblasts (RFFs). The electrical activation had the optimal rate of blastocyst (14.06%) when oocytes were activated by three direct current (DC) pulses (40 V/mm, 20 μs each) followed by 6-dimethylaminopurine (6-DMAP) and cycloheximide (CHX) treatment; the blastocyst rate of ionomycin (ION)+6-DMAP+CHX (12...
September 16, 2018: Reproduction in Domestic Animals, Zuchthygiene
Adriana Marcelo, Filipa Brito, Sara Carmo-Silva, Carlos A Matos, João Alves-Cruzeiro, Ana Vasconcelos-Ferreira, Rebekah Koppenol, Liliana Mendonça, Luís Pereira Almeida, Clévio Nóbrega
Machado-Joseph disease (MJD) is a neurodegenerative disorder, caused by an abnormal expansion of CAG trinucleotide repeats in the disease-causing gene. This mutation leads to an abnormal polyglutamine tract in the protein ataxin-3, resulting in formation of mutant ataxin-3 aggregates. Despite several attempts to develop a therapeutic option for MJD, currently there are no available therapies capable of delaying or stopping disease progression. Recently, our group reported that reducing the expression levels of mutant ataxin-3 lead to a mitigation of several MJD-related behavior and neuropathological abnormalities...
September 13, 2018: Human Molecular Genetics
Huyen Trang Ha Thi, Hye-Youn Kim, Young-Jae Lee, Seong-Jin Kim, Suntaek Hong
SMAD7 is a general inhibitor of transforming growth factor β (TGF-β) signaling that acts through interaction and degradation of TGF-β receptors. SMAD7 has been demonstrated to be transcriptionally upregulated in chemical-induced skin tumors and TGF-β-treated normal keratinocytes. To evaluate the function of SMAD7 in skin carcinogenesis in vivo, Smad7 transgenic mice that specifically express either wild-type SMAD7 (TG-Smad7-WT) or mutant SMAD7 (TG-Smad7-MT) in keratinocytes, as well as Smad7 keratinocyte-specific knockout (Smad72f/2f-K14Cre) mice were subjected to chemical-induced skin carcinogenesis...
September 14, 2018: Carcinogenesis
Ying Liu, Ghislaine Charpin-El Hamri, Haifeng Ye, Martin Fussenegger
Trigger-inducible transgene expression systems are utilized in biopharmaceutical manufacturing and also to enable controlled release of therapeutic agents in vivo. We considered that free fatty acids (FFAs), which are dietary components, signaling molecules and important biomarkers, would be attractive candidates as triggers for novel transgene switches with many potential applications, e.g. in future gene- and cell-based therapies. To develop such a switch, we rewired the signal pathway of human G-protein coupled receptor 40 to a chimeric promoter triggering gene expression through an increase of intracellular calcium concentration...
September 14, 2018: Nucleic Acids Research
Qinshuo Zhao, Jingqiu Huang, Dong Wang, Liang Chen, Dating Sun, Chunxia Zhao
BACKGROUND: Myocardial infarction (MI) contributes to the development of cardiac remodeling and heart failure. Insufficient post-MI myocardial angiogenesis has been identified as a non-negligible event which precipitates heart failure progression. Previous studies reported that cytochrome P450 epoxygenase and its metabolites exerted beneficial effects on cardiovascular diseases. However, the role of cytochrome P450 2J2 (CYP2J2) in post-MI heart failure is incompletely understood. METHODS AND RESULTS: First, western blot and real-time PCR analyses showed that CYP2J2 expression increased clearly in patients with acute MI and old MI, compared to control...
September 13, 2018: Journal of Molecular and Cellular Cardiology
Rebecca K Carrell, Rebecca A Stanton, Stephen P Ethier, Amanda C LaRue, Adam C Soloff
Cellular immunity established via immunotherapy holds the potential to eliminate solid tumors. Yet, cancer vaccines have failed to induce tumor-reactive T cells of sufficient quality to control disease. The inducible T cell costimulator (ICOS) pathway has been implicated in both the selective induction of immunity over tolerance as well as licensing of IL-17-polarized cellular immunity. Herein, we evaluated the ability of ICOS ligand (ICOSL) to augment the immunogenicity of adenoviral-based vaccination targeting the unglycosylated MUC1 peptide antigen...
September 12, 2018: Vaccine
Ben R Dickie, Matthias Vandesquille, José Ulloa, Hervé Boutin, Laura M Parkes, Geoff J M Parker
Blood-brain barrier (BBB) breakdown has been hypothesized to play a key role in the onset and progression of Alzheimer's disease (AD). However, the question of whether AD itself contributes to loss of BBB integrity is still uncertain, as many in-vivo studies have failed to detect signs of AD-related BBB breakdown. We hypothesize AD-related BBB damage is subtle, and that these negative results arise from a lack of measurement sensitivity. With the aim of developing a more sensitive measure of BBB breakdown, we have designed a novel MRI scanning protocol to quantify the trans-BBB exchange of endogenous water...
September 13, 2018: NeuroImage
Yan Wu, Liu Liu, Chunxiang Bian, Qingchun Diao, Muhammad Farrukh Nisar, Xuemei Jiang, Jörg W Bartsch, Maojiao Zhong, Xiangyu Hu, Julia Li Zhong
BACKGROUND: The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documented. However, in order for this information to be useful in therapeutic manipulation of miRNA levels, it is essential that detailed functional mechanisms are elucidated. This study aimed to explore the effects of IL-6 targeting by let-7b and ERK1/2 mediated signaling on keratinocyte differentiation in psoriasis. METHODS: Following imiquimod cream (IMQ) application to let-7bTG (keratinocyte-specific let-7b overexpression mouse) and control mice for 7 days, we analyzed erythema, scaling and thickening of skin...
September 15, 2018: Cell Communication and Signaling: CCS
Najiba Mammadova, Corey M Summers, Robyn D Kokemuller, Qing He, Shaowei Ding, Thierry Baron, Chenxu Yu, Rudy J Valentine, Donald S Sakaguchi, Anumantha G Kanthasamy, Justin J Greenlee, M Heather West Greenlee
Parkinson's disease (PD) is a neurodegenerative disorder characterized by accumulation of misfolded α-synuclein within the central nervous system (CNS). Visual problems in PD patients are common, although retinal pathology associated with PD is not well understood. The purpose of this study was to investigate retinal pathology in a transgenic mouse model (TgM83) expressing the human A53T α-synuclein mutation and assess the effect of α-synuclein "seeding" on the development of retinal pathology...
September 12, 2018: Neurobiology of Disease
Panos Zanos, Helen Keyworth, Polymnia Georgiou, Ian Kitchen, Andreas Zimmer, Alexis Bailey
Nicotine dependence and schizophrenia are two mental health disorders with remarkably high comorbidity. Cigarette smoking is particularly prevalent among schizophrenic patients and it is hypothesized to comprise a form of self-medication for relieving cognitive deficits in these patients. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin in the modulation of drug addiction, as well as schizophrenia symptomology; however, the underlying mechanism remains unclear. Therefore, we sought to investigate the effects of chronic nicotine administration on oxytocin receptor (OTR) binding in the brain of a transgenic mouse model of schizophrenia that carries a bacterial artificial chromosome of the human G72/G30 locus (G72Tg)...
September 15, 2018: European Journal of Neuroscience
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