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https://www.readbyqxmd.com/read/29244835/tumor-suppressor-protein-p53-mediated-repression-of-human-mitotic-centromere-associated-kinesin-gene-expression-is-exerted-via-down-regulation-of-sp1-level
#1
Do Youn Jun, Ji Young Lee, Hae Sun Park, Yun Han Lee, Young Ho Kim
The repressive role of p53 on the human mitotic centromere-associated kinesin (MCAK) core promoter from ‒266 to +54, relative to the transcription start site, has been determined. The MCAK mRNA and protein levels were 2.1- and 3.0-fold higher, respectively, in HCT116 (p53‒/‒) than in HCT116 (p53+/+) cells. Enforced down-regulation of p53 levels either in HCT116 (p53+/+) cells by p53 RNAi treatment or in MCF-7 cells using shRNA for p53 (shp53) resulted in a remarkable increase in the MCAK protein level...
2017: PloS One
https://www.readbyqxmd.com/read/29227814/synthesis-and-evaluation-of-99mtc-re-tricarbonyl-complexes-of-the-triphenylphosphonium-cation-for-mitochondrial-targeting
#2
Georgios Paparidis, Melpomeni Akrivou, Vicky Tsachouridou, Antonio Shegani, Ioannis S Vizirianakis, Ioannis Pirmettis, Minas S Papadopoulos, Dionysia Papagiannopoulou
INTRODUCTION: Lipophilic delocalized cations accumulate in tumor cell mitochondria due to their higher transmembrane potential. In this work, this strategy was adopted for the development of 99mTc tumor-targeted imaging agents. METHODS: Two tridentate ligands containing the triphenylphosphonium cation, L1 (S-cysteinyl) and L2 (N-iminodiacetate) as well as the respective 99mTc/ReL1 and 99mTc/ReL2 tricarbonyl complexes were synthesized. The effect of the ligands and the Re complexes on cell growth in U-87 MG glioblastoma cells was assessed...
November 13, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29215012/rest-regulates-the-cell-cycle-for-cardiac-development-and-regeneration
#3
Donghong Zhang, Yidong Wang, Pengfei Lu, Ping Wang, Xinchun Yuan, Jiangyun Yan, Chenleng Cai, Ching-Pin Chang, Deyou Zheng, Bingruo Wu, Bin Zhou
Despite the importance of cardiomyocyte proliferation in cardiac development and regeneration, the mechanisms that promote cardiomyocyte cell cycle remain incompletely understood. RE1 silencing transcription factor (REST) is a transcriptional repressor of neuronal genes. Here we show that REST also regulates the cardiomyocyte cell cycle. REST binds and represses the cell cycle inhibitor gene p21 and is required for mouse cardiac development and regeneration. Rest deletion de-represses p21 and inhibits the cardiomyocyte cell cycle and proliferation in embryonic or regenerating hearts...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146047/maternal-immune-activation-delays-excitatory-to-inhibitory-gamma-aminobutyric-acid-switch-in-offspring
#4
Irene Corradini, Elisa Focchi, Marco Rasile, Raffaella Morini, Genni Desiato, Romana Tomasoni, Michela Lizier, Elsa Ghirardini, Riccardo Fesce, Diego Morone, Isabella Barajon, Flavia Antonucci, Davide Pozzi, Michela Matteoli
BACKGROUND: The association between maternal infection and neurodevelopmental defects in progeny is well established, although the biological mechanisms and the pathogenic trajectories involved have not been defined. METHODS: Pregnant dams were injected intraperitoneally at gestational day 9 with polyinosinic:polycytidylic acid. Neuronal development was assessed by means of electrophysiological, optical, and biochemical analyses. RESULTS: Prenatal exposure to polyinosinic:polycytidylic acid causes an imbalanced expression of the Na+-K+-2Cl- cotransporter 1 and the K+-Cl- cotransporter 2 (KCC2)...
November 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28842657/rest-a-master-regulator-of-neurogenesis-evolved-under-strong-positive-selection-in-humans-and-in-non-human-primates
#5
Alessandra Mozzi, Franca Rosa Guerini, Diego Forni, Andrea Saul Costa, Raffaello Nemni, Francesca Baglio, Monia Cabinio, Stefania Riva, Chiara Pontremoli, Mario Clerici, Manuela Sironi, Rachele Cagliani
The transcriptional repressor REST regulates many neuronal genes by binding RE1 motifs. About one third of human RE1s are recently evolved and specific to primates. As changes in the activity of a transcription factor reverberate on its downstream targets, we assessed whether REST displays fast evolutionary rates in primates. We show that REST was targeted by very strong positive selection during primate evolution. Positive selection was also evident in the human lineage, with six selected sites located in a region that surrounds a VNTR in exon 4...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801606/linkage-mapping-aided-by-de-novo-genome-and-transcriptome-assembly-in-portunus-trituberculatus-applications-in-growth-related-qtl-and-gene-identification
#6
Jianjian Lv, Baoquan Gao, Ping Liu, Jian Li, Xianliang Meng
A high-resolution genetic linkage map is an essential tool for decoding genetics and genomics in non-model organisms. In this study, a linkage map was constructed for the swimming crab (Portunus trituberculatus) with 10,963 markers; as far as we know, this number of markers has never been achieved in any other crustacean. The linkage map covered 98.85% of the whole genome with a mean marker interval of 0.51 cM. The de novo assembly based on genome and transcriptome sequencing data enabled 2,378 explicit annotated markers to be anchored to the map...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28764392/the-pacemaker-role-of-thalamic-reticular-nucleus-in-controlling-spike-wave-discharges-and-spindles
#7
Denggui Fan, Fucheng Liao, Qingyun Wang
Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles...
July 2017: Chaos
https://www.readbyqxmd.com/read/28717007/epigenetic-suppression-of-human-telomerase-htert-is-mediated-by-the-metastasis-suppressor-nme2-in-a-g-quadruplex-dependent-fashion
#8
COMPARATIVE STUDY
Dhurjhoti Saha, Ankita Singh, Tabish Hussain, Vivek Srivastava, Suman Sengupta, Anirban Kar, Parashar Dhapola, Vishnu Dhople, Ramesh Ummanni, Shantanu Chowdhury
Transcriptional activation of the human telomerase reverse transcriptase (hTERT) gene, which remains repressed in adult somatic cells, is critical during tumorigenesis. Several transcription factors and the epigenetic state of the hTERT promoter are known to be important for tight control of hTERT in normal tissues, but the molecular mechanisms leading to hTERT reactivation in cancer are not well-understood. Surprisingly, here we found occupancy of the metastasis suppressor non-metastatic 2 (NME2) within the hTERT core promoter in HT1080 fibrosarcoma cells and HCT116 colon cancer cells and NME2-mediated transcriptional repression of hTERT in these cells...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28686854/rest-final-exon-truncating-mutations-cause-hereditary-gingival-fibromatosis
#9
Yavuz Bayram, Janson J White, Nursel Elcioglu, Megan T Cho, Neda Zadeh, Asuman Gedikbasi, Sukru Palanduz, Sukru Ozturk, Kivanc Cefle, Ozgur Kasapcopur, Zeynep Coban Akdemir, Davut Pehlivan, Amber Begtrup, Claudia M B Carvalho, Ingrid Sophie Paine, Ali Mentes, Kivanc Bektas-Kayhan, Ender Karaca, Shalini N Jhangiani, Donna M Muzny, Richard A Gibbs, James R Lupski
Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene (SOS1) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern...
July 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28676433/the-neurotoxicant-pcb-95-by-increasing-the-neuronal-transcriptional-repressor-rest-down-regulates-caspase-8-and-increases-ripk1-ripk3-and-mlkl-expression-determining-necroptotic-neuronal-death
#10
Natascia Guida, Giusy Laudati, Angelo Serani, Luigi Mascolo, Pasquale Molinaro, Paolo Montuori, Gianfranco Di Renzo, Lorella M T Canzoniero, Luigi Formisano
Our previous study showed that the environmental neurotoxicant non-dioxin-like polychlorinated biphenyl (PCB)-95 increases RE1-silencing transcription factor (REST) expression, which is related to necrosis, but not apoptosis, of neurons. Meanwhile, necroptosis is a type of a programmed necrosis that is positively regulated by receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like (MLKL) and negatively regulated by caspase-8. Here we evaluated whether necroptosis contributes to PCB-95-induced neuronal death through REST up-regulation...
October 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28624413/srsf3-regulated-mir-132-212-controls-cell-migration-and-invasion-by-targeting-yap1
#11
Hye Ree Kim, Su Jin Hwang, Chang Hoon Shin, Kyung Hee Choi, Takbum Ohn, Hyeon Ho Kim
Although SRSF3 (Serine/arginine-rich splicing factor 3) plays a significant role in various biological processes, many of its functions still remain unclear. More particularly, little is known about SRSF3's involvement in the regulation of miRNA. In this report, we found that invasive and migratory abilities were inhibited in SRSF3-silenced U2OS and HeLa cells. We also found that a knockdown of SRSF3 results in a decreased expression level of REST (RE1-silencing transcription factor). The silencing of REST increased the expression of primary miR-132/212 as well as their mature forms...
September 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28612866/technetium-99m-complexes-of-l-arginine-derivatives-for-targeting-amino-acid-transporters
#12
Maurício Morais, Vera F C Ferreira, Flávio Figueira, Filipa Mendes, Paula Raposinho, Isabel Santos, Bruno L Oliveira, João D G Correia
Although relevant from the clinical point of view, radiotracers targeting cationic amino acid transporters are relatively unexplored and, in particular, no metal-based radiotracers are known. The rare examples of complexes recognized by amino acid transporters, namely by the Na(+)-independent neutral l-type amino acid transporter 1 (LAT1), are (99m)Tc(i)/Re(i) compounds. Herein, we describe conjugates comprising a pyrazolyl-diamine chelating unit and the cationic amino acid l-arginine (l-Arg) linked by a propyl (L1) or hexyl linker (L2), which allowed the preparation of stable complexes of the type fac-[(99m)Tc(CO)3(k(3)-L)](+) (Tc1, L = L1; Tc2, L = L2) and of the respective surrogates Re1 and Re2...
October 31, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28483947/regulation-of-usp37-expression-by-rest-associated-g9a-dependent-histone-methylation
#13
Tara H W Dobson, Rashieda J Hatcher, Jyothishmathi Swaminathan, Chandra M Das, Shavali Shaik, Rong-Hua Tao, Ciro Milite, Sabrina Castellano, Pete H Taylor, Gianluca Sbardella, Vidya Gopalakrishnan
The deubiquitylase (DUB) USP37 is a component of the ubiquitin system and controls cell proliferation by regulating the stability of the cyclin-dependent kinase inhibitor 1B, (CDKN1B/p27Kip1). The expression of USP37 is downregulated in human medulloblastoma tumor specimens. In the current study, we show that USP37 prevents medulloblastoma growth in mouse orthotopic models, suggesting that it has tumor-suppressive properties in this neural cancer. Here, we also report on the mechanism underlying USP37 loss in medulloblastoma...
August 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28416887/a-preliminary-study-of-pcbs-pahs-pesticides-and-trace-metals-contamination-in-cold-pressed-rapeseed-oils-from-conventional-and-ecological-cultivations
#14
Małgorzata Wroniak, Agnieszka Rękas
The purpose of this study was to investigate the levels of polycyclic aromatic hydrocarbons [benzo(a)anthracene, chrysene, benzo(b)fluoranthene, and benzo(a)pyrene], polychlorinated biphenyls (6 marker and 12 dioxin-like), pesticides (74 compounds) and heavy metals (Pb, Cd, As, Hg, Fe, Cu), in the cold-pressed rapeseed oils from conventional (RC) and ecological cultivations (RE). Similar level of PAHs, PCBs and heavy metals was found in the investigated cold-pressed oils; moreover, no effect of rapeseeds cultivation practice on the level of pesticide residues was found...
April 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28411269/novel-regulatory-mechanisms-for-the-soxc-transcriptional-network-required-for-visual-pathway-development
#15
Kun-Che Chang, Jonathan Hertz, Xiong Zhang, Xiao-Lu Jin, Peter Shaw, Brooke A Derosa, Janet Y Li, Praseeda Venugopalan, Daniel A Valenzuela, Roshni D Patel, Kristina R Russano, Shomoukh A Alshamekh, Catalina Sun, Kevin Tenerelli, Chenyi Li, Dmitri Velmeshev, Yuyan Cheng, Timothy M Boyce, Alexandra Dreyfuss, Mohammed S Uddin, Kenneth J Muller, Derek M Dykxhoorn, Jeffrey L Goldberg
What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor in regulating RGC fate, and further describe a newly identified, Sox4-regulated site for post-translational modification with small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11's nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system...
May 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28408934/sdf-1-cxcr4-signaling-maintains-stemness-signature-in-mouse-neural-stem-progenitor-cells
#16
Shih-Yin Ho, Thai-Yen Ling, Hsing-Yu Lin, Jeffrey Tsai-Jui Liou, Fei-Chih Liu, I-Chun Chen, Sue-Wei Lee, Yu Hsu, Dar-Ming Lai, Horng-Huei Liou
SDF-1 and its primary receptor, CXCR4, are highly expressed in the embryonic central nervous system (CNS) and play a crucial role in brain architecture. Loss of SDF-1/CXCR4 signaling causes abnormal development of neural stem/progenitor cells (NSCs/NPCs) in the cerebellum, hippocampus, and cortex. However, the mechanism of SDF-1/CXCR4 axis in NSCs/NPCs regulation remains unknown. In this study, we found that elimination of SDF-1/CXCR4 transduction caused NSCs/NPCs to lose their stemness characteristics and to encounter neurogenic differentiation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28379941/myt1l-safeguards-neuronal-identity-by-actively-repressing-many-non-neuronal-fates
#17
Moritz Mall, Michael S Kareta, Soham Chanda, Henrik Ahlenius, Nicholas Perotti, Bo Zhou, Sarah D Grieder, Xuecai Ge, Sienna Drake, Cheen Euong Ang, Brandon M Walker, Thomas Vierbuchen, Daniel R Fuentes, Philip Brennecke, Kazuhiro R Nitta, Arttu Jolma, Lars M Steinmetz, Jussi Taipale, Thomas C Südhof, Marius Wernig
Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs. In reprogramming, the same factors are often used to reprogram many different donor cell types. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors, it remains unclear how identical combinations of transcription factors can silence so many different donor programs. Distinct lineage repressors would have to be induced in different donor cell types...
April 13, 2017: Nature
https://www.readbyqxmd.com/read/28369444/med12-related-xlid-disorders-are-dose-dependent-of-immediate-early-genes-iegs-expression
#18
Lise-Marie Donnio, Baptiste Bidon, Satoru Hashimoto, Melanie May, Alexey Epanchintsev, Colm Ryan, William Allen, Anna Hackett, Jozef Gecz, Cindy Skinner, Roger E Stevenson, Arjan P M de Brouwer, Charles Coutton, Christine Francannet, Pierre-Simon Jouk, Charles E Schwartz, Jean-Marc Egly
Mediator occupies a key role in protein coding genes expression in mediating the contacts between gene specific factors and the basal transcription machinery but little is known regarding the role of each Mediator subunits. Mutations in MED12 are linked with a broad spectrum of genetic disorders with X-linked intellectual disability that are difficult to range as Lujan, Opitz-Kaveggia or Ohdo syndromes. Here, we investigated several MED12 patients mutations (p.R206Q, p.N898D, p.R961W, p.N1007S, p.R1148H, p...
June 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28345906/malonylginsenosides-with-potential-antidiabetic-activities-from-the-flower-buds-of-panax-ginseng
#19
Shi Qiu, Wen-Zhi Yang, Chang-Liang Yao, Xiao-Jian Shi, Jing-Ya Li, Yang Lou, Ya-Nan Duan, Wan-Ying Wu, De-An Guo
LC-MS-guided phytochemical isolation of malonylginsenosides, featuring neutral elimination of CO2 and C3H2O3 by the negative mode collision-induced dissociation, from the flower buds of Panax ginseng led to the isolation of 19 malonyl-substituted triterpenoid saponins. They include 15 new malonylginsenosides, malonylfloralginsenosides-Re1-Re3 (1-3), -Rb1 and -Rb2 (4, 5), -Rd1-Rd6 (6-11), and -Rc1-Rc4 (12-15), and the known m-Rb1, m-Rc, m-Rb2, and m-Rd (16-19). Compound 11 represents the first dimalonyl saponin isolated from the Panax genus, while 2-4, 9, and 10 are five ginsenosides with single malonylation at the C-20 sugar chain...
April 28, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28218430/stepwise-assembly-of-functional-c-terminal-rest-nrsf-transcriptional-repressor-complexes-as-a-drug-target
#20
Ken Inui, Zongpei Zhao, Juan Yuan, Sakthidasan Jayaprakash, Le T M Le, Srdja Drakulic, Bjoern Sander, Monika M Golas
In human cells, thousands of predominantly neuronal genes are regulated by the repressor element 1 (RE1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF). REST/NRSF represses transcription of these genes in stem cells and non-neuronal cells by tethering corepressor complexes. Aberrant REST/NRSF expression and intracellular localization are associated with cancer and neurodegeneration in humans. To date, detailed molecular analyses of REST/NRSF and its C-terminal repressor complex have been hampered largely by the lack of sufficient amounts of purified REST/NRSF and its complexes...
May 2017: Protein Science: a Publication of the Protein Society
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