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https://www.readbyqxmd.com/read/28147323/the-dna-repair-function-of-cux1-contributes-to-radioresistance
#1
Zubaidah M Ramdzan, Vasudeva Ginjala, Jordan B Pinder, Dudley Chung, Caroline M Donovan, Simran Kaur, Lam Leduy, Graham Dellaire, Shridar Ganesan, Alain Nepveu
Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28112643/layer-specific-chromatin-accessibility-landscapes-reveal-regulatory-networks-in-adult-mouse-visual-cortex
#2
Lucas T Gray, Zizhen Yao, Thuc Nghi Nguyen, Tae Kyung Kim, Hongkui Zeng, Bosiljka Tasic
Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers...
January 23, 2017: ELife
https://www.readbyqxmd.com/read/27986613/oxygen-flux-reduces-cux1-positive-neurons-and-cortical-growth-in-a-gestational-rodent-model-of-growth-restriction
#3
Elaine Fletcher, Jean Wade, Petrina A Georgala, Trudi L Gillespie, David J Price, Elizabeth Pilley, Julie-Clare Becher
BACKGROUND: The mammalian cerebral cortex forms in an inside-out manner, establishing deep cortical layers before superficial layers and is regulated by transcription factors which influence cell differentiation. Preterm birth interrupts the trajectory of normal neurodevelopment and adverse perinatal exposures have been implicated in cortical injury. We hypothesise that growth restriction (GR) and fluctuating hyperoxia (ΔO2) impair cortical laminar development. METHODS: Sprague-Dawley rats received 18% (non-restricted, NR) or 9% (growth restricted, GR) protein diet from E15-P7...
March 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27956696/targeting-the-nuclear-cathepsin-l-ccaat-displacement-protein-cut-homeobox-transcription-factor-epithelial-mesenchymal-transition-pathway-in-prostate-and-breast-cancer-cells-with-the-z-fy-cho-inhibitor
#4
Liza J Burton, Jodi Dougan, Jasmine Jones, Bethany N Smith, Diandra Randle, Veronica Henderson, Valerie A Odero-Marah
The epithelial mesenchymal transition (EMT) promotes tumor migration and invasion by downregulating epithelial markers such as E-cadherin and upregulating mesenchymal markers such as vimentin. Cathepsin L (Cat L) is a cysteine protease that can proteolytically activate CCAAT displacement protein/cut homeobox transcription factor (CUX1). We hypothesized that nuclear Cat L may promote EMT via CUX1 and that this could be antagonized with the Cat L-specific inhibitor Z-FY-CHO. Mesenchymal prostate (ARCaP-M and ARCaP-E overexpressing Snail) and breast (MDA-MB-468, MDA-MB-231, and MCF-7 overexpressing Snail) cancer cells expressed lower E-cadherin activity, higher Snail, vimentin, and Cat L activity, and a p110/p90 active CUX1 form, compared to epithelial prostate (ARCaP-E and ARCaP-Neo) and breast (MCF-7 and MCF-7 Neo) cancer cells...
March 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27835906/whole-exome-and-transcriptome-sequencing-of-refractory-diffuse-large-b-cell-lymphoma
#5
Ha Young Park, Seung-Bok Lee, Hae-Yong Yoo, Seok-Jin Kim, Won-Seog Kim, Jong-Il Kim, Young-Hyeh Ko
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucleotide variants and indels in coding regions were 71 in refractory patients (range 28-120) and 38 (range 19-66) in responsive patients...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27667684/mutations-in-human-accelerated-regions-disrupt-cognition-and-social-behavior
#6
Ryan N Doan, Byoung-Il Bae, Beatriz Cubelos, Cindy Chang, Amer A Hossain, Samira Al-Saad, Nahit M Mukaddes, Ozgur Oner, Muna Al-Saffar, Soher Balkhy, Generoso G Gascon, Marta Nieto, Christopher A Walsh
Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing-showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27590341/special-at-rich-sequence-binding-protein-1-satb1-functions-as-an-accessory-factor-in-base-excision-repair
#7
Simran Kaur, Yan Coulombe, Zubaidah M Ramdzan, Lam Leduy, Jean-Yves Masson, Alain Nepveu
Base excision repair is initiated by DNA glycosylases that recognize specific altered bases. DNA glycosylases for oxidized bases carry both a glycosylase activity that removes the faulty base and an apyrimidinic/apurinic lyase activity that introduces a single-strand DNA incision. In particular, the CUT domains within the CUX1 and CUX2 proteins were recently shown to interact with the 8-oxoguanine (8-oxoG) DNA glycosylase and stimulate its enzymatic activities. SATB1, which contains two CUT domains, was originally characterized as a T cell-specific genome organizer whose aberrant overexpression in breast cancer can promote tumor progression...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27583344/data-on-cux1-isoforms-in-idiopathic-pulmonary-fibrosis-lung-and-systemic-sclerosis-skin-tissue-sections
#8
Tetsurou Ikeda, Maria Fragiadaki, Xu Shi-Wen, Markella Ponticos, Korsa Khan, Christopher Denton, Patricia Garcia, George Bou-Gharios, Akio Yamakawa, Chikao Morimoto, David Abraham
This data article contains complementary figures related to the research article entitled, "Transforming growth factor-β-induced CUX1 isoforms are associated with fibrosis in systemic sclerosis lung fibroblasts" (Ikeda et al. (2016) [2], http://dx.doi.org/10.1016/j.bbrep.2016.06.022), which presents that TGF-β increased CUX1 binding in the proximal promoter and enhancer of the COL1A2 and regulated COL1. Further, in the scleroderma (SSc) lung and diffuse alveolar damage lung sections, CUX1 localized within the α- smooth muscle actin (α-SMA) positive cells (Fragiadaki et al...
September 2016: Data in Brief
https://www.readbyqxmd.com/read/27536221/development-and-maturation-of-embryonic-cortical-neurons-grafted-into-the-damaged-adult-motor-cortex
#9
Nissrine Ballout, Isabelle Frappé, Sophie Péron, Mohamed Jaber, Kazem Zibara, Afsaneh Gaillard
Injury to the human central nervous system can lead to devastating consequences due to its poor ability to self-repair. Neural transplantation aimed at replacing lost neurons and restore functional circuitry has proven to be a promising therapeutical avenue. We previously reported in adult rodent animal models with cortical lesions that grafted fetal cortical neurons could effectively re-establish specific patterns of projections and synapses. The current study was designed to provide a detailed characterization of the spatio-temporal in vivo development of fetal cortical transplanted cells within the lesioned adult motor cortex and their corresponding axonal projections...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27521061/expression-patterns-of-homeobox-genes-in-the-mouse-vomeronasal-organ-at-postnatal-stages
#10
Isabelle Chang, Marta Parrilla
Homeodomain proteins are encoded by homeobox genes and regulate development and differentiation in many neuronal systems. The mouse vomeronasal organ (VNO) generates in situ mature chemosensory neurons from stem cells. The roles of homeodomain proteins in neuronal differentiation in the VNO are poorly understood. Here we have characterized the expression patterns of 28 homeobox genes in the VNO of C57BL/6 mice at postnatal stages using multicolor fluorescent in situ hybridization. We identified 11 homeobox genes (Dlx3, Dlx4, Emx2, Lhx2, Meis1, Pbx3, Pknox2, Pou6f1, Tshz2, Zhx1, Zhx3) that were expressed exclusively in neurons; 4 homeobox genes (Pax6, Six1, Tgif1, Zfhx3) that were expressed in all non-neuronal cell populations, with Pax6, Six1 and Tgif1 also expressed in some neuronal progenitors and precursors; 12 homeobox genes (Adnp, Cux1, Dlx5, Dlx6, Meis2, Pbx2, Pknox1, Pou2f1, Satb1, Tshz1, Tshz3, Zhx2) with expression in both neuronal and non-neuronal cell populations; and one homeobox gene (Hopx) that was exclusively expressed in the non-sensory epithelium...
July 2016: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/27390851/important-role-of-fto-in-the-survival-of-rare-panresistant-triple-negative-inflammatory-breast-cancer-cells-facing-a-severe-metabolic-challenge
#11
Balraj Singh, Hannah E Kinne, Ryan D Milligan, Laura J Washburn, Mark Olsen, Anthony Lucci
We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells...
2016: PloS One
https://www.readbyqxmd.com/read/27245147/fgfr-inhibitors-effects-on-cancer-cells-tumor-microenvironment-and-whole-body-homeostasis-review
#12
Masaru Katoh
Fibroblast growth factor (FGF)2, FGF4, FGF7 and FGF20 are representative paracrine FGFs binding to heparan-sulfate proteoglycan and fibroblast growth factor receptors (FGFRs), whereas FGF19, FGF21 and FGF23 are endocrine FGFs binding to Klotho and FGFRs. FGFR1 is relatively frequently amplified and overexpressed in breast and lung cancer, and FGFR2 in gastric cancer. BCR-FGFR1, CNTRL-FGFR1, CUX1-FGFR1, FGFR1OP-FGFR1, MYO18A-FGFR1 and ZMYM2-FGFR1 fusions in myeloproliferative neoplasms are non-receptor-type FGFR kinases, whereas FGFR1-TACC1, FGFR2-AFF3, FGFR2-BICC1, FGFR2-PPHLN1, FGFR3-BAIAP2L1 and FGFR3-TACC3 fusions in solid tumors are transmembrane-type FGFRs with C-terminal alterations...
July 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27171262/stalled-replication-forks-within-heterochromatin-require-atrx-for-protection
#13
M S Huh, D Ivanochko, L E Hashem, M Curtin, M Delorme, E Goodall, K Yan, D J Picketts
Expansive growth of neural progenitor cells (NPCs) is a prerequisite to the temporal waves of neuronal differentiation that generate the six-layered neocortex, while also placing a heavy burden on proteins that regulate chromatin packaging and genome integrity. This problem is further reflected by the growing number of developmental disorders caused by mutations in chromatin regulators. ATRX gene mutations cause a severe intellectual disability disorder (α-thalassemia mental retardation X-linked (ATRX) syndrome; OMIM no...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27064284/hypomorphism-of-fto-and-rpgrip1l-causes-obesity-in-mice
#14
George Stratigopoulos, Lisa Cole Burnett, Richard Rausch, Richard Gill, David Barth Penn, Alicja A Skowronski, Charles A LeDuc, Anthony J Lanzano, Pumin Zhang, Daniel R Storm, Dieter Egli, Rudolph L Leibel
Noncoding polymorphisms in the fat mass and obesity-associated (FTO) gene represent common alleles that are strongly associated with effects on food intake and adiposity in humans. Previous studies have suggested that the obesity-risk allele rs8050136 in the first intron of FTO alters a regulatory element recognized by the transcription factor CUX1, thereby leading to decreased expression of FTO and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Here, we evaluated the effects of rs8050136 and another potential CUX1 element in rs1421085 on expression of nearby genes in human induced pluripotent stem cell-derived (iPSC-derived) neurons...
May 2, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27016325/microrna-122-regulates-polyploidization-in-the-murine-liver
#15
Shu-Hao Hsu, Evan R Delgado, P Anthony Otero, Kun-Yu Teng, Huban Kutay, Kolin M Meehan, Justin B Moroney, Jappmann K Monga, Nicholas J Hand, Joshua R Friedman, Kalpana Ghoshal, Andrew W Duncan
UNLABELLED: A defining feature of the mammalian liver is polyploidy, a numerical change in the entire complement of chromosomes. The first step of polyploidization involves cell division with failed cytokinesis. Although polyploidy is common, affecting ∼90% of hepatocytes in mice and 50% in humans, the specialized role played by polyploid cells in liver homeostasis and disease remains poorly understood. The goal of this study was to identify novel signals that regulate polyploidization, and we focused on microRNAs (miRNAs)...
August 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26939565/developmental-role-of-the-cell-adhesion-molecule-contactin-6-in-the-cerebral-cortex-and-hippocampus
#16
Amila Zuko, Asami Oguro-Ando, Roland van Dijk, Sara Gregorio-Jordan, Bert van der Zwaag, J Peter H Burbach
The gene encoding the neural cell adhesion molecule Contactin-6 (Cntn6 a.k.a. NB-3) has been implicated as an autism risk gene, suggesting that its mutation is deleterious to brain development. Due to its GPI-anchor at Cntn6 may exert cell adhesion/receptor functions in complex with other membrane proteins, or serve as a ligand. We aimed to uncover novel phenotypes related to Cntn6 functions during development in the cerebral cortex of adult Cntn6(-/-) mice. We first determined Cntn6 protein and mRNA expression in the cortex, thalamic nuclei and the hippocampus at P14, which decreased specifically in the cortex at adult stages...
July 3, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/26858405/adaptive-methylation-regulation-of-p53-pathway-in-sympatric-speciation-of-blind-mole-rats-spalax
#17
Yang Zhao, Jia-Wei Tang, Zhi Yang, Yi-Bin Cao, Ji-Long Ren, Yuval Ben-Abu, Kexin Li, Xue-Qun Chen, Ji-Zeng Du, Eviatar Nevo
Epigenetic modifications play significant roles in adaptive evolution. The tumor suppressor p53, well known for controlling cell fate and maintaining genomic stability, is much less known as a master gene in environmental adaptation involving methylation modifications. The blind subterranean mole rat Spalax eherenbergi superspecies in Israel consists of four species that speciated peripatrically. Remarkably, the northern Galilee species Spalax galili (2n = 52) underwent adaptive ecological sympatric speciation, caused by the sharply divergent chalk and basalt ecologies...
February 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26812355/rna-sequencing-study-of-peripheral-blood-monocytes-in-chronic-periodontitis
#18
COMPARATIVE STUDY
Yao-Zhong Liu, Pooja Maney, Jyoti Puri, Yu Zhou, Melody Baddoo, Michael Strong, Yu-Ping Wang, Erik Flemington, Hong-Wen Deng
BACKGROUND: Monocytes are an important cell type in chronic periodontitis (CP) by interacting with oral bacteria and mediating host immune response. The aim of this study was to reveal new functional genes and pathways for CP at monocyte transcriptomic level. METHODS: We performed an RNA-sequencing (RNA-seq) study of peripheral blood monocytes (PBMs) in 5 non-smoking moderate to severe CP (case) individuals vs. 5 controls. We took advantage of a microarray study of periodontitis to support our findings...
May 1, 2016: Gene
https://www.readbyqxmd.com/read/26804994/cux1-enables-interhemispheric-connections-of-layer-ii-iii-neurons-by-regulating-kv1-dependent-firing
#19
Fernanda M Rodríguez-Tornos, Carlos G Briz, Linnea A Weiss, Alvaro Sebastián-Serrano, Saúl Ares, Marta Navarrete, Laura Frangeul, Maria Galazo, Denis Jabaudon, José A Esteban, Marta Nieto
Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode...
February 3, 2016: Neuron
https://www.readbyqxmd.com/read/26407299/developmental-markers-expressed-in-neocortical-layers-are-differentially-exhibited-in-olfactory-cortex
#20
Peter C Brunjes, Stephen K Osterberg
Neurons in the cerebral cortex stratify on the basis of their time of origin, axonal terminations and the molecular identities assigned during early development. Olfactory cortices share many feature with the neocortex, including clear lamination and similar cell types. The present study demonstrates that the markers differentially expressed in the projection neurons of the cerebral cortex are also found in olfactory areas. Three of the four regions examined (pars principalis of the anterior olfactory nucleus: AONpP, anterior and posterior piriform cortices: APC, PPC, and the olfactory tubercle) expressed transcription factors found in deep or superficial neurons in the developing neocortex, though large differences were found between areas...
2015: PloS One
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