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Nicolas Unsain, Genevieve Dorval, JaeHyung Sheen, Philip A Barker
The Neurotrophin receptor associated death domain gene (Nradd/Nrh2/Plaidd) is a type I transmembrane protein with a unique and short N-terminal extracellular domain and a transmembrane and intracellular domain that bears high similarity to the p75 neurotrophin receptor (p75NTR/Ngfr). Initial studies suggested that NRADD regulates neurotrophin signaling but very little is known about its physiological roles. We have generated and characterized NRADD conditional and germ-line null mouse lines. These mice are viable and fertile and dońt show evident abnormalities...
October 24, 2016: Genesis: the Journal of Genetics and Development
Alice Brandli, Daniel M Johnstone, Jonathan Stone
Purpose: To test whether remote ischemic preconditioning (RIP) is protective to photoreceptors, in a light damage model, and to identify mechanisms involved. Methods: A pressure cuff was used to induce ischemia (2 × 5 minutes) in one hind limb of 4- to 6-month-old albino Sprague-Dawley rats raised in dim, cyclic light (12 hours 5 lux, 12 hours dark). Immediately following the ischemia, rats were exposed to bright continuous light (1000 lux) for 24 hours. After 7-day survival in dim, cyclic light conditions, retinal function was assessed using the flash electroretinogram (ERG) and retinal structure was examined for photoreceptor survival and death, as well as for stress...
October 1, 2016: Investigative Ophthalmology & Visual Science
Chen Chen, June Ho Shin, Joshua T Eggold, Man Ki Chung, Luhua H Zhang, Jeremy Lee, John B Sunwoo
Oral squamous cell carcinoma (OSCC) is a highly invasive and metastatic malignancy. The nerve growth factor receptor (NGFR) has been observed to be expressed on a subset of cells in OSCC, and NGFR+ cells have greater tumor-initiating capacity in vivo. Further, inhibition of NGFR reduces tumor growth, indicating a functional role of this receptor; however, the mechanisms by which NGFR confers enhanced tumor formation are not known. Here, we used an established murine model of OSCC and gene expression array analysis to identify ESM1 as a downstream target gene of NGFR, critical for tumor invasion and metastasis...
September 23, 2016: Oncotarget
Reka Chakravarthy, Katarzyna Mnich, Adrienne M Gorman
Triple negative breast cancer [TNBC] cells are reported to secrete the neurotrophin nerve growth factor [NGF] and express its receptors, p75 neurotrophin receptor [p75(NTR)] and TrkA, leading to NGF-activated pro-survival autocrine signaling. This provides a rationale for NGF as a potential therapeutic target for TNBC. Here we show that exposure of TNBC cells to NGF leads to increased levels of p75(NTR), which was diminished by NGF-neutralizing antibody or NGF inhibitors [Ro 08-2750 and Y1086]. NGF-mediated increase in p75(NTR) levels were partly due to increased transcription and partly due to inhibition of proteolytic processing of p75(NTR)...
September 30, 2016: Biochemical and Biophysical Research Communications
Akimasa Seno, Tomonari Kasai, Masashi Ikeda, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Hiroshi Murakami, Tetsuya Ishikawa, Masaharu Seno
We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7...
2016: Cancer Informatics
Zhenhui Li, Ming Zheng, Bahareldin Ali Abdalla, Zhe Zhang, Zhenqiang Xu, Qiao Ye, Haiping Xu, Wei Luo, Qinghua Nie, Xiquan Zhang
In the poultry industry, aggressive behaviour is a large animal welfare issue all over the world. To date, little is known about the underlying genetics of the aggressive behaviour. Here, we performed a genome-wide association study (GWAS) to explore the genetic mechanism associated with aggressive behaviour in chickens. The GWAS results showed that a total of 33 SNPs were associated with aggressive behaviour traits (P < 4.6E-6). rs312463697 on chromosome 4 was significantly associated with aggression (P = 2...
2016: Scientific Reports
Samantha E Boyle, Clare G Fedele, Vincent Corbin, Elisha Wybacz, Pacman Szeto, Jeremy Lewin, Richard J Young, Annie Wong, Robert Fuller, John Spillane, David Speakman, Simon Donahoe, Miklos Pohl, David Gyorki, Michael A Henderson, Ricky W Johnstone, Anthony T Papenfuss, Mark Shackleton
The stability of markers that identify cancer cells that propagate disease is important to the outcomes of targeted therapy strategies. In human melanoma, conflicting data exist as to whether hierarchical expression of CD271/p75/NGFR (nerve growth factor receptor) marks cells with enriched tumorigenicity, which would compel their specific targeting in therapy. To test whether these discrepancies relate to differences among groups in assay approaches, we undertook side-by-side testing of published methods of patient-derived melanoma xenografting (PDX), including comparisons of tissue digestion procedures or coinjected Matrigel formulations...
July 1, 2016: Cancer Research
Xiang Zhou, Qian Hao, Peng Liao, Shiwen Luo, Minhong Zhang, Guohui Hu, Hongbing Liu, Yiwei Zhang, Bo Cao, Melody Baddoo, Erik K Flemington, Shelya X Zeng, Hua Lu
Cancer develops and progresses often by inactivating p53. Here, we unveil nerve growth factor receptor (NGFR, p75NTR or CD271) as a novel p53 inactivator. p53 activates NGFR transcription, whereas NGFR inactivates p53 by promoting its MDM2-mediated ubiquitin-dependent proteolysis and by directly binding to its central DNA binding domain and preventing its DNA-binding activity. Inversely, NGFR ablation activates p53, consequently inducing apoptosis, attenuating survival, and reducing clonogenic capability of cancer cells, as well as sensitizing human cancer cells to chemotherapeutic agents that induce p53 and suppressing mouse xenograft tumor growth...
2016: ELife
Darilang Mawrie, Atul Kumar, Damaris Magdalene, Jina Bhattacharyya, Bithiah Grace Jaganathan
Mesenchymal stem cells (MSC) have been proposed as suitable candidates for cell therapy for neurological disorderssince they exhibit good neuronal differentiation capacity. However, for better therapeutic outcomes, it is necessary to isolate MSC from a suitable tissue sourcethat posses high neuronal differentiation. In this context, we isolated MSC from extra ocular muscle (EOM) tissue and tested the in vitro neuronal differentiation potential. In the current study, EOM tissue derived MSC were characterized and compared with bone marrow derived MSC...
2016: PloS One
Catherine Do, Charles F Lang, John Lin, Huferesh Darbary, Izabela Krupska, Aulona Gaba, Lynn Petukhova, Jean-Paul Vonsattel, Mary P Gallagher, Robin S Goland, Raphael A Clynes, Andrew Dwork, John G Kral, Catherine Monk, Angela M Christiano, Benjamin Tycko
Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-Seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported...
May 5, 2016: American Journal of Human Genetics
Caroline E Gargett, Shanti Gurung
No abstract text is available yet for this article.
June 2016: Biology of Reproduction
M Maranesi, F Parillo, L Leonardi, P G Rebollar, B Alonso, L Petrucci, A Gobbetti, C Boiti, J Arruda-Alencar, A Moura, M Zerani
The aim of the present study was to evaluate: (1) the presence of nerve growth factor (NGF), neurotrophic tyrosine kinase receptor 1 (NTRK1), and nerve growth factor receptor (NGFR) in the rabbit uterus; and (2) the in vitro effects of NGF on PGF2α and PGE2 synthesis and on the PGE2-9-ketoreductase (PGE2-9-K) activity by the rabbit uterus. Nerve growth factor, NTRK1, and NGFR were immunolocalized in the luminal and glandular epithelium and stroma cells of the endometrium. reverse transcriptase polymerase chain reaction indicated the presence of messenger RNA for NGF, NTRK1, and NGFR in the uterus...
July 2016: Domestic Animal Endocrinology
Sándor Nardai, Arpád Dobolyi, Judit Skopál, Kinga Lakatos, Béla Merkely, Zoltán Nagy
Matrix metalloproteinase (MMP) inhibition can potentially prevent hemorrhagic transformation following cerebral infarction; however, delayed-phase MMP activity is also necessary for functional recovery after experimental stroke. We sought to identify potential mechanisms responsible for the impaired recovery associated with subacute MMP inhibition in a transient middle cerebral artery occlusion model of focal ischemia in CD rats. Gelatinase inhibition was achieved by intracerebral injection of the Fn-439 MMP inhibitor 7 days after stroke...
April 2016: Journal of Neuropathology and Experimental Neurology
Patricia Fernández-Nogueira, Paloma Bragado, Vanessa Almendro, Elisabet Ametller, Jose Rios, Sibgat Choudhury, Mario Mancino, Pedro Gascón
The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes...
February 2, 2016: Oncotarget
Jia Li, Weian Chen, Yu'an Li, Ying Chen, Zhangna Ding, Dehao Yang, Xu Zhang
OBJECTIVE: This study was to investigate the efficacy of olfactory ensheathing cell (OEC) transplantation on experimental autoimmune encephalomyelitis (EAE). METHODS: EAE models were established by guinea pig spinal cord homogenate (GPSCH) immunization in Lewis rats. OECs were purified and cultured from the olfactory nerve layer of SD rats, and then transplanted to the EAE models through the vena caudalis (Group A) or into the lateral cerebral ventricle (Group B)...
2015: International Journal of Clinical and Experimental Pathology
Tinara Leila de Sousa Aarão, Jorge Rodrigues de Sousa, Beatriz Santos Botelho, Hellen Thais Fuzii, Juarez Antonio Simões Quaresma
Leprosy is a serious public health problem in peripheral and developing countries. Leprosy is a chronic infectious-contagious disease caused by the intracellular, bacillus Mycobacterium leprae, which causes tissue damage and demyelination of peripheral nerves. Recent studies have demonstrated the participation of new subtype's cytokines profile in the inflammatory response of leprosy. Since nerve functions are affected by inflammatory response during the course of leprosy, changes in the production of NGF and its receptor (NGF R) may be directly associated with disability and sensory loss...
January 2016: Microbial Pathogenesis
H F Duncan, A J Smith, G J P Fleming, C Reid, G Smith, P R Cooper
AIM: To characterise dentine matrix component (DMC) release and smear layer removal by histone deacetylase inhibitors (HDACis). METHODOLOGY: DMCs were extracted from powdered human dentine over 14d using three HDACis, valproic acid (VPA), trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) and compared with a control extractant, 10% (w/v) EDTA. Protein compositions of the resultant extracts were analysed by 1D-polyacrylamide gel electrophoresis (1D-PAGE), TGF-β-1 and MMP-9 ELISAs and a high-throughput growth factor antibody array...
November 26, 2015: International Endodontic Journal
Yangzi Jiang, Changchang Hu, Shuting Yu, Junwei Yan, Hsuan Peng, Hong Wei Ouyang, Rocky S Tuan
INTRODUCTION: Interleukin-1β (IL-1β) and nerve growth factor (NGF) are key regulators in the pathogenesis of inflammatory arthritis; specifically, IL-1β is involved in tissue degeneration and NGF is involved in joint pain. However, the cellular and molecular interactions between IL-1β and NGF in articular cartilage are not known. Cartilage stem/progenitor cells (CSPCs) have recently been identified in osteoarthritic (OA) cartilage on the basis of their migratory properties. Here we hypothesize that IL-1β/NGF signaling is involved in OA cartilage degeneration by targeting CSPCs...
November 17, 2015: Arthritis Research & Therapy
Lilai Yuan, Jiasu Li, Jinmiao Zha, Zijian Wang
Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF...
January 2016: Environmental Pollution
Sung Yoon Catherine Kang, Nagarajan Kannan, Lewei Zhang, Victor Martinez, Miriam P Rosin, Connie J Eaves
Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44(+)NGFR(+) and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44(+)NGFR(+) cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells...
December 8, 2015: Stem Cell Reports
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