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https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#1
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28225779/combined-small-rna-and-degradome-sequencing-reveals-complex-microrna-regulation-of-catechin-biosynthesis-in-tea-camellia-sinensis
#2
Ping Sun, Chunzhen Cheng, Yuling Lin, Qiufang Zhu, Jinke Lin, Zhongxiong Lai
MicroRNAs are endogenous non-coding small RNAs playing crucial regulatory roles in plants. Tea, a globally popular non-alcoholic drink, is rich in health-enhancing catechins. In this study, 69 conserved and 47 novel miRNAs targeting 644 genes were identified by high-throughout sequencing. Predicted target genes of miRNAs were mainly involved in plant growth, signal transduction, morphogenesis and defense. To further identify targets of tea miRNAs, degradome sequencing and RNA ligase-mediated rapid amplification of 5'cDNA ends (RLM-RACE) were applied...
2017: PloS One
https://www.readbyqxmd.com/read/28195275/bond-strengths-of-orthodontic-metal-brackets-to-tribochemically-silica-coated-zirconia-surfaces-using-different-10-methacryloyloxydecyl-dihydrogen-phosphate-containing-primers
#3
Na-Hyun Kim, Yoon-Ji Kim, Dong-Yul Lee
PURPOSE: To evaluate the effects of tribochemical silica coating and different 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primers on the shear bond strength (SBS) of orthodontic metal brackets to yttrium-stabilized tetragonal zirconia polycrystal (Y-TZP) surfaces. MATERIALS AND METHODS: One hundred ninety polished Y-TZP specimens were randomly assigned to 19 groups (n = 10): 30 specimens were used for surface analyses after polishing with 600-grit silicon carbide paper, airborneparticle abrasion with 50-μm alumina (A), or tribochemical silica coating (CoJet [C]); 160 specimens were used in SBS testing of orthodontic metal brackets to Y-TZP after alumina airborne-particle abrasion or tribochemical silica coating and application of either ESPE-Sil (S) (ASn, ASa, CSn, CSa), Alloy Primer (AP) (AAPn, AAPa, CAPn, CAPa), Clearfil Ceramic Primer (CP) (ACPn, ACPa, CCPn, CCPa), or Scotchbond Universal (U) (AUn, AUa, CUn, CUa) and either stored in water for 24 h (non-aged, n) or thermocycled 5000 times (aged, a)...
February 10, 2017: Journal of Adhesive Dentistry
https://www.readbyqxmd.com/read/28120733/prediction-of-post-stroke-dementia-using-ninds-csn-5-minute-neuropsychology-protocol-in-acute-stroke
#4
Jae-Sung Lim, Mi Sun Oh, Ju-Hun Lee, San Jung, Chulho Kim, Min Uk Jang, Sang-Hwa Lee, Yeo Jin Kim, Yerim Kim, Jaeseol Park, Yeonwook Kang, Kyung-Ho Yu, Byung-Chul Lee
BACKGROUND: The National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute neuropsychology protocol consists of only verbal tasks, and is proposed as a brief screening method for vascular cognitive impairment. We evaluated its feasibility within two weeks after stroke and ability to predict the development of post-stroke dementia (PSD) at 3 months after stroke. METHOD: We prospectively enrolled subjects with ischemic stroke within seven days of symptom onset who were consecutively admitted to 12 university hospitals...
January 25, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28096463/deneddylase1-counters-automodification-of-neddylating-enzymes-to-maintain-nedd8-homeostasis-in-arabidopsis
#5
Julia Mergner, Bernhard Kuster, Claus Schwechheimer
In eukaryotes, the conjugation of the ubiquitin-like protein NEDD8 onto protein targets is an important post-translational modification. The best understood neddylation targets are the cullins, scaffold subunits of E3 ubiquitin ligases, where neddylation as well as deneddylation, facilitated by the protease activity of the CSN (COP9 signalosome), are required to control ubiquitin ligase assembly, function and ultimately substrate degradation. Little is known about the role of other deneddylating enzymes besides CSN and the role of neddylation and deneddylation of their substrates...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28062449/context-sensitive-network-based-disease-genetics-prediction-and-its-implications-in-drug-discovery
#6
Yang Chen, Rong Xu
MOTIVATION: Disease phenotype networks play an important role in computational approaches to identifying new disease-gene associations. Current disease phenotype networks often model disease relationships based on pairwise similarities, therefore ignore the specific context on how two diseases are connected. In this study, we propose a new strategy to model disease associations using context-sensitive networks (CSNs). We developed a CSN-based phenome-driven approach for disease genetics prediction, and investigated the translational potential of the predicted genes in drug discovery...
January 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28052110/automated-image-sampling-and-classification-can-be-used-to-explore-perceived-naturalness-of-urban-spaces
#7
Roger Hyam
The psychological restorative effects of exposure to nature are well established and extend to just viewing of images of nature. A previous study has shown that Perceived Naturalness (PN) of images correlates with their restorative value. This study tests whether it is possible to detect degree of PN of images using an image classifier. It takes images that have been scored by humans for PN (including a subset that have been assessed for restorative value) and passes them through the Google Vision API image classification service...
2017: PloS One
https://www.readbyqxmd.com/read/28040740/the-role-of-the-unc-82-protein-kinase-in-organizing-myosin-filaments-in-striated-muscle-of-caenorhabditis-elegans
#8
NaTasha R Schiller, Christopher D Duchesneau, Latrisha S Lane, April R Reedy, Emily R Manzon, Pamela E Hoppe
We study the mechanisms that guide the formation and maintenance of the highly-ordered actin-myosin cytoskeleton in striated muscle. The UNC-82 kinase of Caenorhabditis elegans is orthologous to mammalian kinases ARK5/NUAK1 and SNARK/NUAK2. UNC-82 localizes to the M-line and is required for proper organization of thick filaments, but its substrate and mechanism of action are unknown. Antibody staining of three mutants with missense mutations in the UNC-82 catalytic domain revealed muscle structure that is less disorganized than in the null unc-82(0), but which contained distinctive ectopic accumulations not found in unc-82(0) These accumulations contain paramyosin and myosin B, but lack myosin A and myosin A-associated proteins as well as proteins of the integrin-associated complex...
December 30, 2016: Genetics
https://www.readbyqxmd.com/read/27981705/azaindoles-as-zinc-binding-small-molecule-inhibitors-of-the-jamm-protease-csn5
#9
Eva Altmann, Paul Erbel, Martin Renatus, Michael Schaefer, Anita Schlierf, Adelaide Druet, Laurence Kieffer, Mickael Sorge, Keith Pfister, Ulrich Hassiepen, Matthew Jones, Simon Ruedisser, Daniela Ostermeier, Bruno Martoglio, Anne B Jefferson, Jean Quancard
CSN5 is the zinc metalloprotease subunit of the COP9 signalosome (CSN), which is an important regulator of cullin-RING E3 ubiquitin ligases (CRLs). CSN5 is responsible for the cleavage of NEDD8 from CRLs, and blocking deconjugation of NEDD8 traps the CRLs in a hyperactive state, thereby leading to auto-ubiquitination and ultimately degradation of the substrate recognition subunits. Herein, we describe the discovery of azaindoles as a new class of CSN5 inhibitors, which interact with the active-site zinc ion of CSN5 through an unprecedented binding mode...
December 16, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27915049/csn1201-a-subunit-of-the-cop9-signalosome-regulates-the-virulence-in-cryptococcus-neoformans-infection
#10
Yibin Fan, Xiaohua Tao, Weili Pan, Wei Fang, Youming Huang, Mingyan Jia
The COP9 signalosome (CSN) is a multisubunit protein complex, and it now has been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. Cryptococcus neoformans (C. neoformans) is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immune compromised population. Here, we generated CSN deletion mutants to investigate the role in Cryptococcus infection. Compared to other CSN mutants, we identified a CSN1201 mutant exhibited severely attenuated virulence...
November 30, 2016: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/27871853/nur77-downregulation-triggers-pulmonary-artery-smooth-muscle-cell-proliferation-and-migration-in-mice-with-hypoxic-pulmonary-hypertension-via-the-axin2-%C3%AE-catenin-signaling-pathway
#11
Xiaowei Nie, Jianxin Tan, Youai Dai, Wenjun Mao, Yuan Chen, Guowei Qin, Guirong Li, Chenyou Shen, Jingjing Zhao, Jingyu Chen
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases...
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27869306/roles-of-multifunctional-cop9-signalosome-complex-in-cell-fate-and-implications-for-drug-discovery
#12
REVIEW
Ping Li, Longxiang Xie, Yinzhong Gu, Jiang Li, Jianping Xie
The eight subunits containing COP9 signalosome (CSN) complex, is highly conserved among eukaryotes. CSN, identified as a negative regulator of photomorphogenesis, has also been demonstrated to be important in proteolysis, cellular signal transduction and cell cycle regulation in various eukaryotic organisms. This review mainly summarizes the roles of CSN in cell cycle regulation, signal transduction and apoptosis, and its potential as diagnostic biomarkers, drug targets for cancer and infectious diseases. J...
June 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27861949/absolute-quantification-of-micrornas-in-green-tea-camellia-sinensis-by-stem-loop-quantitative-real-time-pcr
#13
Ying-Hui Hou, Anburaj Jeyaraj, Xiao Zhang, Chao-Ling Wei
BACKGROUND: There are some studies to show that food-derived plant microRNAs (miRNAs) may be detected in mammals. The research evidence has provoked a considerable debate whether plant-derived miRNAs exert the same regulatory functions as endogenous animal miRNAs. To test the hypothesis, methods of highly sensitive absolute quantification miRNAs have been developed. However, absolute miRNA quantification of green tea has not yet been reported. This study is the first to build an absolute quantification method to detect miRNAs level in green tea using stem-loop quantitative real-time PCR (qRT-PCR)...
November 12, 2016: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/27836030/validation-of-a-new-technique-to-detect-cryptosporidium-spp-oocysts-in-bovine-feces
#14
Sandra Valéria Inácio, Jancarlo Ferreira Gomes, Bruno César Miranda Oliveira, Alexandre Xavier Falcão, Celso Tetsuo Nagase Suzuki, Bianca Martins Dos Santos, Monally Conceição Costa de Aquino, Rafaela Silva de Paula Ribeiro, Danilla Mendes de Assunção, Pamella Almeida Freire Casemiro, Marcelo Vasconcelos Meireles, Katia Denise Saraiva Bresciani
Due to its important zoonotic potential, cryptosporidiosis arouses strong interest in the scientific community, because, it was initially considered a rare and opportunistic disease. The parasitological diagnosis of the causative agent of this disease, the protozoan Cryptosporidium spp., requires the use of specific techniques of concentration and permanent staining, which are laborious and costly, and are difficult to use in routine laboratory tests. In view of the above, we conducted the feasibility, development, evaluation and intralaboratory validation of a new parasitological technique for analysis in optical microscopy of Cryptosporidium spp...
November 1, 2016: Preventive Veterinary Medicine
https://www.readbyqxmd.com/read/27833851/overexpression-of-cop9-signalosome-subunits-csn7a-and-csn7b-exerts-different-effects-on-adipogenic-differentiation
#15
Xiaohua Huang, Jürgen Ordemann, Johann Pratschke, Wolfgang Dubiel
The COP9 signalosome (CSN) is an essential regulator of cullin-RING-ubiquitin (Ub) ligases (CRLs), which ubiquitinate important cellular regulators and target them for degradation by the Ub proteasome system (UPS). The CSN exhibits deneddylating activity localized on subunit CSN5, which removes the ubiquitin-like protein Nedd8 from the cullins of CRLs. CSN-mediated deneddylation is an important step in the process of CRL remodeling, in which new substrate recognition units are incorporated into Ub ligases to meet changed requirements for proteolysis in cells...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27774986/targeted-inhibition-of-the-cop9-signalosome-for-treatment-of-cancer
#16
Anita Schlierf, Eva Altmann, Jean Quancard, Anne B Jefferson, René Assenberg, Martin Renatus, Matthew Jones, Ulrich Hassiepen, Michael Schaefer, Michael Kiffe, Andreas Weiss, Christian Wiesmann, Richard Sedrani, Jörg Eder, Bruno Martoglio
The COP9 signalosome (CSN) is a central component of the activation and remodelling cycle of cullin-RING E3 ubiquitin ligases (CRLs), the largest enzyme family of the ubiquitin-proteasome system in humans. CRLs are implicated in the regulation of numerous cellular processes, including cell cycle progression and apoptosis, and aberrant CRL activity is frequently associated with cancer. Remodelling of CRLs is initiated by CSN-catalysed cleavage of the ubiquitin-like activator NEDD8 from CRLs. Here we describe CSN5i-3, a potent, selective and orally available inhibitor of CSN5, the proteolytic subunit of CSN...
October 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27748879/quercetin-induced-apoptosis-of-ht-29%C3%A2-colon-cancer-cells-via-inhibition-of-the-akt-csn6-myc-signaling-axis
#17
Lin Yang, Yanqing Liu, Mei Wang, Yayun Qian, Xiaoyun Dong, Hao Gu, Haibo Wang, Shiyu Guo, Tadashi Hisamitsu
Constitutive photomorphogenesis 9 signalosome (CSN) consists of a total of eight subunits (CSN1-CSN8) in mammalian cells. CSN6 may promote carcinogenesis by positively regulating v‑myc avian myelocytomatosis viral oncogene homolog (Myc) and MDM2 proto‑oncogene stability, and is regarded as a potential target for cancer therapy. Quercetin has a substantial anticancer effect on various human cancer cells. The present study investigated the effects of quercetin on HT-29 human colorectal cancer cell viability, apoptosis and cell cycle arrest using an MTT assay, flow cytometry, transmission electron microscopy and western blotting...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27744526/functional-abolition-of-carotid-body-activity-restores-insulin-action-and-glucose-homeostasis-in-rats-key-roles-for-visceral-adipose-tissue-and-the-liver
#18
Joana F Sacramento, Maria J Ribeiro, Tiago Rodrigues, Elena Olea, Bernardete F Melo, Maria P Guarino, Rui Fonseca-Pinto, Cristiana R Ferreira, Joana Coelho, Ana Obeso, Raquel Seiça, Paulo Matafome, Sílvia V Conde
AIMS/HYPOTHESIS: We recently described that carotid body (CB) over-activation is involved in the aetiology of insulin resistance and arterial hypertension in animal models of the metabolic syndrome. Additionally, we have demonstrated that CB activity is increased in animal models of insulin resistance, and that carotid sinus nerve (CSN) resection prevents the development of insulin resistance and arterial hypertension induced by high-energy diets. Here, we tested whether the functional abolition of CB by CSN transection would reverse pre-established insulin resistance, dyslipidaemia, obesity, autonomic dysfunction and hypertension in animal models of the metabolic syndrome...
January 2017: Diabetologia
https://www.readbyqxmd.com/read/27729873/neonatal-maternal-separation-augments-carotid-body-response-to-hypoxia-in-adult-males-but-not-female-rats
#19
Jorge Soliz, Rose Tam, Richard Kinkead
Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27679973/nur77-exacerbates-pc12-cellular-injury-in-vitro-by-aggravating-mitochondrial-impairment-and-endoplasmic-reticulum-stress
#20
Huimin Gao, Zhaoyu Chen, Yongmei Fu, Xiaoyan Yang, Ruihui Weng, Rui Wang, Jianjun Lu, Mengqiu Pan, Kunlin Jin, Chris McElroy, Beisha Tang, Ying Xia, Qing Wang
The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77...
September 29, 2016: Scientific Reports
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