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https://www.readbyqxmd.com/read/29161318/loss-of-mtorc2-signaling-in-oligodendrocyte-precursor-cells-delays-myelination
#1
Mark D Grier, Kathryn L West, Nathaniel D Kelm, Cary Fu, Mark D Does, Brittany Parker, Eleanor McBrier, Andre H Lagrange, Kevin C Ess, Robert P Carson
Myelin abnormalities are increasingly being recognized as an important component of a number of neurologic developmental disorders. The integration of many signaling pathways and cell types are critical for correct myelinogenesis. The PI3-K and mechanistic target of rapamycin (mTOR) pathways have been found to play key roles. mTOR is found within two distinct complexes, mTORC1 and mTORC2. mTORC1 activity has been shown to play a major role during myelination, while the role of mTORC2 is not yet well understood...
2017: PloS One
https://www.readbyqxmd.com/read/29160844/altered-aconitase-2-activity-in-huntington-s-disease-peripheral-blood-cells-and-mouse-model-striatum
#2
Chiung-Mei Chen, Yih-Ru Wu, Kuo-Hsuan Chang
Huntington's disease (HD) is caused by an unstable cytosine adenine guanine (CAG) trinucleotide repeat expansion encoding a polyglutamine tract in the huntingtin protein. Previously, we identified several up- and down-regulated protein molecules in the striatum of the Hdh((CAG)150) knock-in mice at 16 months of age, a mouse model which is modeling the early human HD stage. Among those molecules, aconitase 2 (Aco2) located in the mitochondrial matrix is involved in the energy generation and susceptible to increased oxidative stress that would lead to inactivation of Aco2 activity...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29159784/g2a-as-a-threshold-regulator-of-inflammatory-hyperalgesia-modulates-chronic-hyperalgesia
#3
Yeu-Shiuan Su, Yu-Fen Huang, Jen Wong, Chia-Wei Lee, Wei-Shan Hsieh, Wei-Hsin Sun
Tissue injury, pathogen infection, and diseases are often accompanied by inflammation to release mediators that sensitize nociceptors and further recruit immune cells, which can lead to chronic hyperalgesia and inflammation. Tissue acidosis, occurring at the inflammatory site, is a major factor contributing to pain and hyperalgesia. The receptor G2 accumulation (G2A), expressed in neurons and immune cells, responds to protons or oxidized free fatty acids such as 9-hydroxyoctadecadienoic acid produced by injured cells or oxidative stresses...
November 21, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29159687/au-1-from-agavaceae-plants-downregulates-the-expression-of-glycolytic-enzyme-phosphoglycerate-mutase
#4
Tomofumi Fujino, Akihito Yokosuka, Harutaka Ichikawa, Toshiyuki Oshima, Yoshihiro Mimaki, Makio Hayakawa
The spirostanol saponin AU-1 from Agavaceae plants stimulates the expression of the glycolytic enzyme phosphoglycerate mutase (PGAM) in ACHN cells. We hypothesized that this may arise from the downregulation of the NAD(+)-dependent deacetylase SIRT1. In this article, we showed that, unlike in renal adenocarcinoma cells, AU-1 does not affect the expression of SIRT1 in the normal renal cell-derived cell line HK-2. Consistent with the lack of a downregulation of SIRT1, AU-1 did not upregulate, but rather decreased PGAM expression...
November 20, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29159607/high-resolution-melting-analysis-hrm-for-mutational-screening-of-dnajc17-gene-in-patients-affected-by-thyroid-dysgenesis
#5
I C Nettore, S Desiderio, E De Nisco, V Cacace, L Albano, N Improda, P Ungaro, M Salerno, A Colao, P E Macchia
BACKGROUND: Congenital hypothyroidism is a frequent disease occurring with an incidence of about 1/1500 newborns/year. In about 75% of the cases, CH is caused by alterations in thyroid morphogenesis, defined "thyroid dysgenesis" (TD). TD is generally a sporadic disease but in about 5% of the cases a genetic origin has been demonstrated. Previous studies indicate that Dnajc17 as a candidate modifier gene for hypothyroidism, since it is expressed in the thyroid bud, interacts with NKX2...
November 20, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29159133/integration-of-novel-approaches-demonstrates-simultaneous-metabolic-inactivation-and-car-mediated-hepatocarcinogenesis-of-a-nitrification-inhibitor
#6
Jessica L LaRocca, Reza J Rasoulpour, B Bhaskar Gollapudi, David L Eisenbrandt, Lynea A Murphy, Matthew J LeBaron
Nitrapyrin, a nitrification inhibitor, produces liver tumors in mice at high doses. Several experiments were performed to investigate molecular, cellular, and apical endpoints to define the key events leading to the tumor formation. These data support a mode-of-action (MoA) characterized by constitutive androstane receptor (CAR) nuclear receptor activation, increased hepatocellular proliferation leading to hepatocellular foci and tumor formation. Specifically, nitrapyrin induced a dose-related increase in the Cyp2b10/CAR-associated transcript and protein...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/29158889/non-canonical-dorsoventral-patterning-in-the-moth-midge-clogmia-albipunctata
#7
Karl R Wotton, Anna Alcaine-Colet, Johannes Jaeger, Eva Jiménez-Guri
Background: Bone morphogenetic proteins (BMPs) are of central importance for dorsal-ventral (DV) axis specification. They are core components of a signalling cascade that includes the BMP ligand decapentaplegic (DPP) and its antagonist short gastrulation (SOG) in Drosophila melanogaster. These components are very ancient, with orthologs involved in DV patterning in both protostomes and deuterostomes. Despite such strong conservation, recent comparative work in insects has revealed interesting differences in the way the patterning function of the DV system is achieved in different species...
2017: EvoDevo
https://www.readbyqxmd.com/read/29158807/the-prognostic-value-of-peripheral-benzodiazepine-receptor-in-patients-with-esophageal-squamous-cell-carcinoma
#8
You-Fang Chen, Jing-Dun Xie, Yu-Chuan Jiang, Dong-Tai Chen, Jia-Hao Pan, Yong-Hua Chen, Yun-Fei Yuan, Zhe-Sheng Wen, Wei-An Zeng
Background: The peripheral benzodiazepine receptor (PBR) has previously been reported as an oncogene in prostate, breast and colorectal cancers, but its prognostic value, biological behavior and function in esophageal squamous cell carcinoma (ESCC) has not been investigated. Methods: qRT-PCR, western blotting and immunohistochemistry (IHC) were used to detect PBR expression in ESCC and matched non-cancerous tissues. Based on all of the significantly independent factors, a nomogram was established to predict the prognosis of ESCC patients...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158805/histone-methyltransferase-setdb1-promotes-the-progression-of-colorectal-cancer-by-inhibiting-the-expression-of-tp53
#9
Keli Chen, Fengjiao Zhang, Jie Ding, Yonghao Liang, Zetao Zhan, Yizhi Zhan, Long-Hua Chen, Yi Ding
SETDB1 is a novel histone methyltransferase associated with the functional tri-methylation of histone H3K9. Although aberrant high expression of SETDB1 was experimentally obversed in a variety of solid tumors, its underlying mechanisms in human carcinogenesis are not well known. In this study, we investigated the expression of SETDB1 in a large cohort of colorectal cancer (CRC) samples and cell lines for the first time. Our findings showed that SETDB1 was highly expressed in majority CRC tissues and cell lines; moreover, up-regulation of SETDB1 was negatively correlated with the survival rate of CRC patients...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158625/comparative-genomic-hybridization-and-transcriptome-sequencing-reveal-that-two-genes-osi_14279-loc_os03g62620-and-osi_10794-loc_os03g14950-regulate-the-mutation-in-the-%C3%AE-rl-rice-mutant
#10
Xulong Wang, Fanhua Wang, Huiqiong Chen, Xiaoyu Liang, Yingmei Huang, Jicai Yi
We previously established the genetic locus of the rolled-leaf mutant, γ-rl, to chromosome 3. In this study, we performed a comparative genomic hybridization (CGH) analysis to identify the genes responsible for the γ-rl mutant phenotype. This was combined with RNA transcriptome sequencing (RNA-seq) to analyze differences in the mRNA expression in seeds 12 h after germination. Using the reference genome of the "indica type" rice from GenBank, we created a chip with 386,000 high density DNA probes designed to target chromosome 3...
October 2017: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/29158599/application-of-genome-editing-technologies-in-rats-for-human-disease-models
#11
REVIEW
Kazuto Yoshimi, Tomoji Mashimo
Laboratory rats and mice are representative experimental animals for models of human disease. The emergence of genome editing technologies has enabled us to produce a variety of genetically modified animals, including rats, as a means of elucidating the in vivo functions of the gene of interest and characterizing the molecular mechanisms of human disease. Several advanced techniques for knock-in methodologies in rats are currently in development, which permit researchers to introduce precise nucleotide modifications at target sites in the rat's genome...
November 20, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/29158494/mrg15-stimulates-ash1-h3k36-methyltransferase-activity-and-facilitates-ash1-trithorax-group-protein-function-in-drosophila
#12
Chang Huang, Fu Yang, Zhuqiang Zhang, Jing Zhang, Gaihong Cai, Lin Li, Yong Zheng, She Chen, Rongwen Xi, Bing Zhu
Ash1 is a Trithorax group protein that possesses H3K36-specific histone methyltransferase activity, which antagonizes Polycomb silencing. Here we report the identification of two Ash1 complex subunits, Mrg15 and Nurf55. In vitro, Mrg15 stimulates the enzymatic activity of Ash1. In vivo, Mrg15 is recruited by Ash1 to their common targets, and Mrg15 reinforces Ash1 chromatin association and facilitates the proper deposition of H3K36me2. To dissect the functional role of Mrg15 in the context of the Ash1 complex, we identify an Ash1 point mutation (Ash1-R1288A) that displays a greatly attenuated interaction with Mrg15...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158412/induced-gnas-r201h-expression-from-the-endogenous-gnas-locus-causes-fibrous-dysplasia-by-up-regulating-wnt-%C3%AE-catenin-signaling
#13
Sanjoy Kumar Khan, Prem Swaroop Yadav, Gene Elliott, Dorothy Zhang Hu, Ruoshi Xu, Yingzi Yang
Fibrous dysplasia (FD; Online Mendelian Inheritance in Man no. 174800) is a crippling skeletal disease caused by activating mutations of the GNAS gene, which encodes the stimulatory G protein Gαs FD can lead to severe adverse conditions such as bone deformity, fracture, and severe pain, leading to functional impairment and wheelchair confinement. So far there is no cure, as the underlying molecular and cellular mechanisms remain largely unknown and the lack of appropriate animal models has severely hampered FD research...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158112/subtle-behavioral-changes-and-increased-prefrontal-hippocampal-network-synchronicity-in-app-nl-g-f-mice-before-prominent-plaque-deposition
#14
Amira Latif Hernandez, Disha Shah, Kathleen Craessaerts, Takaomi Saido, Takashi Saito, Bart De Strooper, Annemie Van der Linden, Rudi D'Hooge
Amyloid-β (Aβ) peptides occur in the brains of patients with Alzheimer's disease (AD), but their role in functional impairment is still debated. High levels of APP and APP fragments in mice that overexpress APP might confound their use in preclinical research. We examined the occurrence of behavioral, cognitive and neuroimaging changes in APP(NL-G-F) knock-in mice that display Aβ42 amyloidosis in the absence of APP overexpression. Female APP(NL-G-F) mice (carrying Swedish, Iberian and Arctic APP mutations) were compared to APP(NL) mice (APP Swedish) at 3, 7 and 10 months...
November 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29158084/distinct-expression-patterns-of-flk1-and-flt1-in-the-coronary-vascular-system-during-development-and-after-myocardial-infarction
#15
Shota Kurotsu, Rina Osakabe, Mari Isomi, Fumiya Tamura, Taketaro Sadahiro, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Hidenori Tani, Kaori Nara, Yoshiaki Kubota, Masatsugu Ema, Keiichi Fukuda, Takeshi Suzuki, Masaki Ieda
The coronary vascular system is critical for myocardial growth and cardiomyocyte survival. However, the molecular mechanism regulating coronary angiogenesis remains elusive. Vascular endothelial growth factor (VEGF) regulates angiogenesis by binding to the specific receptors Flk1 and Flt1, which results in different functions. Despite the importance of Flk1 and Flt1, their expression in the coronary vasculature remains largely unknown due to the lack of appropriate antibodies for immunostaining. Here, we analyzed multiple reporter mice including Flk1-GFP BAC transgenic (Tg), Flk1-LacZ knock-in, Flt1-DsRed BAC Tg, and Flk1-GFP/Flt1-DsRed double Tg animals to determine expression patterns in mouse hearts during cardiac growth and after myocardial infarction (MI)...
November 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29157665/lipopolysaccharide-induced-increase-in-intestinal-epithelial-tight-permeability-is-mediated-by-toll-like-receptor-4-myeloid-differentiation-primary-response-88-myd88-activation-of-myosin-light-chain-kinase-expression
#16
Meghali Nighot, Rana Al-Sadi, Shuhong Guo, Manmeet Rawat, Prashant Nighot, Martin D Watterson, Thomas Y Ma
Lipopolysaccharides (LPSs) are a major component of the Gram-negative bacterial cell wall and play an important role in mediating intestinal inflammatory responses in inflammatory bowel disease. Although recent studies suggested that physiologically relevant concentrations of LPS (0 to 1 ng/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability, the mechanisms that mediate an LPS-induced increase in intestinal TJ permeability remain unclear. Herein, we show that myosin light chain kinase (MLCK) plays a central role in the LPS-induced increase in TJ permeability...
December 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29157209/transcriptome-sequencing-and-analysis-of-zinc-uptake-related-genes-in-trichophyton-mentagrophytes
#17
Xinke Zhang, Pengxiu Dai, Yongping Gao, Xiaowen Gong, Hao Cui, Yipeng Jin, Yihua Zhang
BACKGROUND: Trichophyton mentagrophytes is an important zoonotic dermatophytic (ringworm) pathogen; causing severe skin infection in humans and other animals worldwide. Fortunately, commonly used fungal skin disease prevention and treatment measures are relatively simple. However, T. mentagrophytes is primarily studied at the epidemiology and drug efficacy research levels, yet current study has been unable to meet the needs of clinical medicine. Zinc is a crucial trace element for the growth and reproduction of fungi and other microorganisms...
November 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29157079/zeb1-inhibition-sensitizes-cells-to-the-atr-inhibitor-ve-821-by-abrogating-epithelial-mesenchymal-transition-and-enhancing-dna-damage
#18
Na Song, Wei Jing, Ce Li, Ming Bai, Yu Cheng, Heming Li, Kezuo Hou, Yanrong Li, Kai Wang, Zhi Li, Yunpeng Liu, Xiujuan Qu, Xiaofang Che
The ataxia-telangiectasia-mutated (ATM) and rad3-related (ATR) checkpoint pathway plays an essential role in modulating cellular responses to replication stress and DNA damage to maintain genomic stability. In various tumors, cancer cells have increased dependence on ATR signaling for survival, making ATR a promising target for cancer therapy. ATR inhibitors sensitize multiple tumor cell types to radiation and DNA-damaging agents, but application of an ATR inhibitor alone shows limited efficacy. In the present study, we investigated the role of epithelial-to-mesenchymal transition (EMT) and the EMT transcription factor ZEB1 in regulating cell sensitivity to the ATR inhibitor VE-821...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156757/a-pten-col17a1-fusion-gene-and-its-novel-regulatory-role-in-collagen-xvii-expression-and-gbm-malignance
#19
Xiaoyan Yan, Chuanbao Zhang, Tingyu Liang, Fan Yang, Haoyuan Wang, Fan Wu, Wen Wang, Zheng Wang, Wen Cheng, Jiangnan Xu, Tao Jiang, Jing Chen, Yaozhong Ding
Collagen XVII expression has recently been demonstrated to be correlated with the tumor malignance. While Collagen XVII is known to be widely distributed in neurons of the human brain, its precise role in pathogenesis of glioblastoma multiforme (GBM) is unknown. In this study, we identified and characterized a new PTEN-COL17A1 fusion gene in GMB using transcriptome sequencing. Although fusion gene did not result in measurable fusion protein production, its presence is accompanied with high levels of COL17A1 expression, revealed a novel regulatory mechanism of Collagen XVII expression by PTEN-COL17A1 gene fusion...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156678/epigenetic-silencing-of-tumor-suppressor-candidate-3-confers-adverse-prognosis-in-early-colorectal-cancer
#20
Elke Burgermeister, Patrick Höde, Johannes Betge, Tobias Gutting, Andreas Merkel, Wen Wu, Marc Tänzer, Maximilian Mossner, Daniel Nowak, Julia Magdeburg, Felix Rückert, Carsten Sticht, Katja Breitkopf-Heinlein, Nadine Schulte, Nicolai Härtel, Sebastian Belle, Stefan Post, Timo Gaiser, Barbara Ingold Heppner, Hans-Michael Behrens, Christoph Röcken, Matthias P A Ebert
Colorectal cancer (CRC) is a biologically and clinically heterogeneous disease. Even though many recurrent genomic alterations have been identified that may characterize distinct subgroups, their biological impact and clinical significance as prognostic indicators remain to be defined. The tumor suppressor candidate-3 (TUSC3/N33) locates to a genomic region frequently deleted or silenced in cancers. TUSC3 is a subunit of the oligosaccharyltransferase (OST) complex at the endoplasmic reticulum (ER) which catalyzes bulk N-glycosylation of membrane and secretory proteins...
October 17, 2017: Oncotarget
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