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https://www.readbyqxmd.com/read/29740596/neuregulin-1-type-i-overexpression-is-associated-with-reduced-nmda-receptor-mediated-synaptic-signaling-in-hippocampal-interneurons-expressing-pv-or-cck
#1
Dimitrios Kotzadimitriou, Wiebke Nissen, Melinda Paizs, Kathryn Newton, Paul J Harrison, Ole Paulsen, Karri Lamsa
Hypofunction of N -methyl-d-aspartate receptors (NMDARs) in inhibitory GABAergic interneurons is implicated in the pathophysiology of schizophrenia (SZ), a heritable disorder with many susceptibility genes. However, it is still unclear how SZ risk genes interfere with NMDAR-mediated synaptic transmission in diverse inhibitory interneuron populations. One putative risk gene is neuregulin 1 ( NRG1 ), which signals via the receptor tyrosine kinase ErbB4, itself a schizophrenia risk gene. The type I isoform of NRG1 shows increased expression in the brain of SZ patients, and ErbB4 is enriched in GABAergic interneurons expressing parvalbumin (PV) or cholecystokinin (CCK)...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29730188/discovery-of-new-erbb4-inhibitors-repositioning-an-orphan-chemical-library-by-inverse-virtual-screening
#2
Assunta Giordano, Giovanni Forte, Luigia Massimo, Raffaele Riccio, Giuseppe Bifulco, Simone Di Micco
Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range...
April 12, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29729836/prognostic-value-of-egfr-family-expression-in-lymph-node-negative-esophageal-squamous-cell-carcinoma-patients
#3
Weiwei Yu, Xi Yang, Li Chu, Kuaile Zhao, Haiquan Chen, Jiaqing Xiang, Yawei Zhang, Hecheng Li, Weixin Zhao, Menghong Sun, Qiao Wei, Xiaolong Fu, Congying Xie, Zhengfei Zhu
The human epidermal growth factor receptor (EGFR) family has been widely studied in cancer, however, the prognostic role of EGFR family expression in lymph node-negative esophageal squamous cell carcinoma (ESCC) patients have not been invalidated. This study was designed to determine the prognostic value of EGFR family expression in a population of lymph node-negative ESCC patients treated with curative resection. EGFR family protein expression was examined by immunohistochemical analysis of tissue microarrays of 94 patients with lymph node-negative ESCC after radical esophagectomy with three-field lymphadenectomy...
April 30, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29705689/polymorphisms-that-affect-gaba-neurotransmission-predict-processing-of-aversive-prediction-errors-in-humans
#4
Irina Baetu, Julia B Pitcher, Sarah Cohen-Woods, Benjamin Lancer, Nathan Beu, Lauren M Foreman, Paul D Taylor, Nicholas R Burns
Learning is one of our most adaptive abilities, allowing us to adjust our expectations about future events. Aberrant learning processes may underlie disorders such as anxiety, motivating the search for the neural mechanisms that underpin learning. Animal studies have shown that the neurotransmitter GABA is required for the computation of prediction errors, the mismatches between anticipated and experienced outcomes, which drive new learning. Given that evidence from human studies is lacking, we sought to determine whether these findings extend to humans...
April 26, 2018: NeuroImage
https://www.readbyqxmd.com/read/29702367/targeting-natural-compounds-against-her2-kinase-domain-as-potential-anticancer-drugs-applying-pharmacophore-based-molecular-modelling-approaches
#5
Shailima Rampogu, Minky Son, Ayoung Baek, Chanin Park, Rabia Mukthar Rana, Amir Zeb, Saravanan Parameswaran, Keun Woo Lee
Human epidermal growth factor receptors are implicated in several types of cancers characterized by aberrant signal transduction. This family comprises of EGFR (ErbB1), HER2 (ErbB2, HER2/neu), HER3 (ErbB3), and HER4 (ErbB4). Amongst them, HER2 is associated with breast cancer and is one of the most valuable targets in addressing the breast cancer incidences. For the current investigation, we have performed 3D-QSAR based pharmacophore search for the identification of potential inhibitors against the kinase domain of HER2 protein...
April 20, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29674181/high-glucose-forces-a-positive-feedback-loop-connecting-erbb4-expression-and-mtor-s6k-pathway-to-aggravate-the-formation-of-tau-hyperphosphorylation-in-differentiated-sh-sy5y-cells
#6
Sheng-Dan Nie, Xin Li, Can-E Tang, Fang-Yuan Min, Xia-Jie Shi, Liang-Yan Wu, Shan-Lei Zhou, Zi Chen, Jing Wu, Tao Song, Zhi-Jie Dai, Jiao Zheng, Jia-Jia Liu, Shan Wang
High glucose (HG)-induced mammalian target of rapamycin (mTOR) overactivation acts as a signaling hub for the formation of tau hyperphosphorylation, which contributes to the development of diabetes-associated cognitive deficit. How HG induces the sustained activation of mTOR in neurons is not clearly understood. ErbB4, a member of the receptor tyrosine kinase family, plays critical roles in development and function of neural circuitry, relevant to behavioral deficits. Here, we showed HG-induced ErbB4 overexpression in differentiated SH-SY5Y cells and primary hippocampal neurons and hippocampal pyramidal neurons of streptozotocin-induced diabetic rats...
March 23, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29669012/characterization-of-the-acute-heat-stress-response-in-gilts-iii-genome-wide-association-studies-of-thermotolerance-traits-in-pigs
#7
K-S Kim, J T Seibert, Z Edea, K L Graves, E-S Kim, A F Keating, L H Baumgard, J W Ross, M F Rothschild
Heat stress (HS) is one of the limiting factors negatively affecting pig production, health, and fertility. Characterizing genomic regions responsible for variation in HS tolerance would be useful in identifying important genetic factor(s) regulating physiological responses to HS. In the present study, we performed genome-wide association analyses for respiration rate (RR), rectal temperature (TR) and skin temperature (TS) during HS in 214 crossbred gilts genotyped for 68,549 single nucleotide polymorphisms (SNP) using the Porcine SNP 70K BeadChip...
April 16, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29628188/dynamic-erbb4-activity-in-hippocampal-prefrontal-synchrony-and-top-down-attention-in-rodents
#8
Zhibing Tan, Heath L Robinson, Dong-Min Yin, Yu Liu, Fang Liu, Hongsheng Wang, Thiri W Lin, Guanglin Xing, Lin Gan, Wen-Cheng Xiong, Lin Mei
Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity...
April 3, 2018: Neuron
https://www.readbyqxmd.com/read/29620274/erbb4-promotes-the-proliferation-of-gastric-cancer-cells-via-the-pi3k-akt-signaling-pathway
#9
Ji Xu, Lijie Gong, Zhenyuan Qian, Guangyuan Song, Jinming Liu
ERBB4 is one of the members of the epidermal growth factor receptor (EGFR) family. ERBB4 is a large transmembrane glycoprotein and has tyrosine kinase activity. Once combined with epidermal growth factor (EGF), ERBB4 can activate the related genes in the nucleus, thus promoting cell division and proliferation. In the present study, we investigated the effect of ERBB4 in the proliferation of gastric cancer cells. We found that high ERBB4 levels were closely related to the poor prognosis of gastric cancer patients...
March 30, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29568012/modulation-of-the-neuregulin-1-erbb-system-after-skeletal-muscle-denervation-and-reinnervation
#10
Michela Morano, Giulia Ronchi, Valentina Nicolò, Benedetta Elena Fornasari, Alessandro Crosio, Isabelle Perroteau, Stefano Geuna, Giovanna Gambarotta, Stefania Raimondo
Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/reinnervation processes...
March 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29551924/involvement-of-erbb4-and-tumor-marker-genes-in-renal-carcinoma-regulatory-network
#11
Xiaofu Wang, Bin Hao, Changbao Xu, Xinghua Zhao, Changwei Liu, Xiaohan Chu, Yuan Lv, Yongli Zhao, Shengwei Zhang, Pengsen Wang, Youzhi Wang
Background: Renal carcinoma is a common urologic tumor, and there is no ideal tumor marker for clinical diagnosis except for imaging diagnosis. This study aims to screen the serum tumor markers closely related with the benign and malignant of renal carcinoma out and chart out the regulatory network that involves renal carcinoma-related genes. Methods: Based on 96 pathologically diagnosed renal cancer patients, factors strongly linked to renal carcinoma character were selected using Fisher discriminant analysis...
December 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29545886/expression-and-secretion-of-neuregulin-1-in-cardiac-microvascular-endothelial-cells-treated-with-angiogenic-factors
#12
Chengqiang Wu, Chun Gui, Lang Li, Yiheng Pang, Zhongli Tang, Jing Wei
Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29534586/identification-of-biomarkers-and-potential-molecular-mechanisms-of-clear-cell-renal-cell-carcinoma
#13
F Wu, S Wu, X Gou
Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer in adults. The aim of this study is to identify the biomarkers and potential molecular mechanisms of ccRCC. Three gene expression profiles and two miRNA expression profiles were downloaded from GEO database. A total of 330 up-regulated differentially expressed genes (DEGs), 545 down-regulated DEGs, 26 up-regulated differentially expressed miRNAs (DEMs) and 11 down-regulated DEMs were identified by GEO2R. The gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by KOBAS software...
2018: Neoplasma
https://www.readbyqxmd.com/read/29528383/neuregulin-1-attenuates-stress-induced-vascular-senescence
#14
Hadis Shakeri, Andreas B Gevaert, Dorien M Schrijvers, Guido R Y De Meyer, Gilles W De Keulenaer, Pieter-Jan D F Guns, Katrien Lemmens, Vincent F Segers
Aims: Cardiovascular ageing is a key determinant of life expectancy. Cellular senescence, a state of irreversible cell cycle arrest, is an important contributor to ageing due to the accumulation of damaged cells. Targeting cellular senescence could prevent age-related cardiovascular diseases. In this study, we investigated the effects of neuregulin-1 (NRG-1), an epidermal growth factor with cardioprotective and anti-atherosclerotic effects, on cellular senescence. Methods & results: Senescence was induced in cultured rat aortic endothelial cells (ECs) and aortic smooth muscle cells (SMCs) by 2 hours exposure to 30 µM hydrogen peroxide (H2O2)...
March 8, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29483666/uncovering-the-genetic-lesions-underlying-the-most-severe-form-of-hirschsprung-disease-by-whole-genome-sequencing
#15
Clara Sm Tang, Xuehan Zhuang, Wai-Yee Lam, Elly Sau-Wai Ngan, Jacob Shujui Hsu, Y U Michelle, S O Man-Ting, Stacey S Cherny, Ngoc Diem Ngo, Pak C Sham, Paul Kh Tam, Maria-Mercè Garcia-Barcelo
Hirschsprung disease (HSCR) is a complex birth defect characterized by the lack of ganglion cells along a variable length of the distal intestine. A large proportion of HSCR patients remain genetically unexplained. We applied whole-genome sequencing (WGS) on 9 trios where the probands are sporadically affected with the most severe form of the disorder and harbor no coding sequence variants affecting the function of known HSCR genes. We found de novo protein-altering variants in three intolerant to change genes-CCT2, VASH1, and CYP26A1-for which a plausible link with the enteric nervous system (ENS) exists...
February 26, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29480208/a-genetic-study-of-psychosis-in-huntington-s-disease-evidence-for-the-involvement-of-glutamate-signaling-pathways
#16
Debby W Tsuang, Tiffany A Greenwood, Suman Jayadev, Marie Davis, Andrew Shutes-David, Thomas D Bird
BACKGROUND: Psychotic symptoms of delusions and hallucinations occur in about 5% of persons with Huntington's disease (HD). The mechanisms underlying these occurrences are unknown, but the same symptoms also occur in schizophrenia, and thus genetic risk factors for schizophrenia may be relevant to the development of psychosis in HD. OBJECTIVE: To investigate the possible role of genes associated with schizophrenia in the occurrence of psychotic symptoms in HD. METHODS: DNA from subjects with HD and psychosis (HD+P; n = 47), subjects with HD and no psychosis (HD-P; n = 126), and controls (CTLs; n = 207) was genotyped using the Infinium PsychArray-24 v1...
2018: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/29464684/neuregulin-directed-molecular-mechanisms-of-visual-cortical-plasticity
#17
REVIEW
Steven F Grieco, Todd C Holmes, Xiangmin Xu
Experience-dependent critical period (CP) plasticity has been extensively studied in the visual cortex. Monocular deprivation during the CP affects ocular dominance, limits visual performance, and contributes to the pathological etiology of amblyopia. Neuregulin-1 (NRG1) signaling through its tyrosine kinase receptor ErbB4 is essential for the normal development of the nervous system and has been linked to neuropsychiatric disorders such as schizophrenia. We discovered recently that NRG1/ErbB4 signaling in PV neurons is critical for the initiation of CP visual cortical plasticity by controlling excitatory synaptic inputs onto PV neurons and thus PV-cell mediated cortical inhibition that occurs following visual deprivation...
February 21, 2018: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29463705/controlling-of-glutamate-release-by-neuregulin3-via-inhibiting-the-assembly-of-the-snare-complex
#18
Ya-Nan Wang, Dwight Figueiredo, Xiang-Dong Sun, Zhao-Qi Dong, Wen-Bing Chen, Wan-Peng Cui, Fang Liu, Hong-Sheng Wang, Hai-Wen Li, Heath Robinson, Er-Kang Fei, Bing-Xing Pan, Bao-Ming Li, Wen-Cheng Xiong, Lin Mei
Neuregulin3 (NRG3) is a growth factor of the neuregulin (NRG) family and a risk gene of various severe mental illnesses including schizophrenia, bipolar disorders, and major depression. However, the physiological function of NRG3 remains poorly understood. Here we show that loss of Nrg3 in GFAP-Nrg3 f/f mice increased glutamatergic transmission, but had no effect on GABAergic transmission. These phenotypes were observed in Nex-Nrg3 f/f mice, where Nrg3 was specifically knocked out in pyramidal neurons, indicating that Nrg3 regulates glutamatergic transmission by a cell-autonomous mechanism...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29453196/genome-wide-association-study-identifies-erbb4-on-2q34-as-a-novel-locus-associated-with-sperm-motility-in-japanese-men
#19
Youichi Sato, Atsushi Tajima, Takehiro Sato, Shiari Nozawa, Miki Yoshiike, Issei Imoto, Aiko Yamauchi, Teruaki Iwamoto
BACKGROUND: The decrease in sperm motility has a potent influence on fertilisation. Sperm motility, represented as the percentage of motile sperm in ejaculated sperms, is influenced by lifestyle habits or environmental factors and by inherited factors. However, genetic factors contributing to individual differences in sperm motility remain unclear. To identify genetic factors that influence human sperm motility, we performed a genome-wide association study (GWAS) of sperm motility. METHODS: A two-stage GWAS was conducted using 811 Japanese men in a discovery stage, followed by a replication study using an additional 779 Japanese men...
February 16, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29438802/endocannabinoid-signaling-in-embryonic-neuronal-motility-and-cell-cell-contact-role-of-mglur5-and-trpc3-channels
#20
Pauli M Turunen, Lauri M Louhivuori, Verna Louhivuori, Jyrki P Kukkonen, Karl E Åkerman
Cell-cell communication plays a central role in the guidance of migrating neuronal precursor cells during the development of the cerebral cortex. Endocannabinoids (eCBs) have previously been shown to be one of the central factors regulating neuronal migration. In this study the effects of eCBs on different parameters, expected to affect embryonic cortical neuronal motility have been analyzed in neurosphere-derived neuroblasts using time-lapse microscopy. Increased endogenous production of the endocannabinoid 2-arachidonyl glycerol (2-AG) causes bursts of neuroblast motility...
April 1, 2018: Neuroscience
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