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https://www.readbyqxmd.com/read/28218276/natural-and-laboratory-mutations-in-kuzbanian-are-associated-with-zinc-stress-phenotypes-in-drosophila-melanogaster
#1
Hung Le Manh, Lain Guio, Miriam Merenciano, Quirze Rovira, Maite G Barrón, Josefa González
Organisms must cope with altered environmental conditions such as high concentrations of heavy metals. Stress response to heavy metals is mediated by the metal-responsive transcription factor 1 (MTF-1), which is conserved from Drosophila to humans. MTF-1 binds to metal response elements (MREs) and changes the expression of target genes. kuzbanian (kuz), a metalloendopeptidase that activates the evolutionary conserved Notch signaling pathway, has been identified as an MTF-1 target gene. We have previously identified a putatively adaptive transposable element in the Drosophila melanogaster genome, named FBti0019170, inserted in a kuz intron...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217707/microrna-regulation-of-human-pancreatic-cancer-stem-cells
#2
REVIEW
Yi-Fan Xu, Bethany N Hannafon, Wei-Qun Ding
microRNAs (miRNAs) are a group of small non-coding RNAs that function primarily in the post transcriptional regulation of gene expression in plants and animals. Deregulation of miRNA expression in cancer cells, including pancreatic cancer cells, is well documented, and the involvement of miRNAs in orchestrating tumor genesis and cancer progression has been recognized. This review focuses on recent reports demonstrating that miRNAs are involved in regulation of pancreatic cancer stem cells (CSCs). A number of miRNA species have been identified to be involved in regulating pancreatic CSCs, including miR-21, miR-34, miR-1246, miR-221, the miR-17-92 cluster, the miR-200 and let-7 families...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28216164/conversion-of-glioma-cells-to-glioma-stem-like-cells-by-angiocrine-factors
#3
Jun-Kyum Kim, Hye-Min Jeon, Hee-Young Jeon, Se-Yeong Oh, Eun-Jung Kim, Xiong Jin, Se-Hoon Kim, Sung-Hak Kim, Xun Jin, Hyunggee Kim
Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28216142/astrocytic-calcium-waves-signal-brain-injury-to-neural-stem-and%C3%A2-progenitor%C3%A2-cells
#4
Anna Kraft, Eduardo Rosales Jubal, Ruth von Laer, Claudia Döring, Adriana Rocha, Moyo Grebbin, Martin Zenke, Helmut Kettenmann, Albrecht Stroh, Stefan Momma
Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia...
February 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28215940/elf5-is-a-principal-cell-lineage-specific-transcription-factor-in-the-kidney-that-contributes-to-aqp2-and-avpr2-gene-expression
#5
Justin Grassmeyer, Malini Mukherjee, Jennifer deRiso, Casey Hettinger, Monica Bailey, Satrajit Sinha, Jane E Visvader, Haotian Zhao, Eric Fogarty, Kameswaran Surendran
The mammalian kidney collecting ducts are critical for water, electrolyte and acid-base homeostasis and develop as a branched network of tubular structures composed of principal cells intermingled with intercalated cells. The intermingled nature of the different collecting duct cell types has made it challenging to identify unique and critical factors that mark and/or regulate the development of the different collecting duct cell lineages. Here we report that the canonical Notch signaling pathway components, RBPJ and Presinilin1 and 2, are involved in patterning the mouse collecting duct cell fates by maintaining a balance between principal cell and intercalated cell fates...
February 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28215559/soxc-transcription-factors-promote-contralateral-retinal-ganglion-cell-differentiation-and-axon-guidance-in-the-mouse-visual-system
#6
Takaaki Kuwajima, Célia A Soares, Austen A Sitko, Véronique Lefebvre, Carol Mason
Transcription factors control cell identity by regulating diverse developmental steps such as differentiation and axon guidance. The mammalian binocular visual circuit is comprised of projections of retinal ganglion cells (RGCs) to ipsilateral and contralateral targets in the brain. A transcriptional code for ipsilateral RGC identity has been identified, but less is known about the transcriptional regulation of contralateral RGC development. Here we demonstrate that SoxC genes (Sox4, 11, and 12) act on the progenitor-to-postmitotic transition to implement contralateral, but not ipsilateral, RGC differentiation, by binding to Hes5 and thus repressing Notch signaling...
February 14, 2017: Neuron
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#7
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28207739/overexpression-of-notch-regulated-ankyrin-repeat-protein-is-associated-with-papillary-thyroid-carcinoma-progression
#8
Mingdi Zhang, Yiyu Qin, Bin Zuo, Wei Gong, Shenglai Zhang, Yurong Gong, Zhiwei Quan, Bingfeng Chu
Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28192800/molecular-profiling-of-the-developing-lacrimal-gland-reveals-putative-role-of-notch-signaling-in-branching-morphogenesis
#9
Galina Dvoriantchikova, Wensi Tao, Steve Pappas, Gabriel Gaidosh, David T Tse, Dmitry Ivanov, Daniel Pelaez
Purpose: Although normal function of the lacrimal gland is essential for vision (and thus for human well-being), the lacrimal gland remains rather poorly understood at a molecular level. The purpose of this study was to identify new genes and signaling cascades involved in lacrimal gland development. Methods: To identify these genes, we used microarray analysis to compare the gene expression profiles of developing (embryonic) and adult lacrimal glands. Differential data were validated by quantitative RT-PCR, and several corresponding proteins were confirmed by immunohistochemistry and Western blot analysis...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28179307/selumetinib-inhibits-melanoma-metastasis-to-mouse-liver-via-suppression-of-emt-targeted-genes
#10
Seung-Hee Ryu, Seung-Ho Heo, Eun Young Park, Kyung-Chul Choi, Je-Won Ryu, Seok Ho Lee, Sang-Wook Lee
AIM: We investigated the therapeutic effects of a mitogen-activated protein (MEK) inhibitor, selumetinib, in a hepatic melanoma metastasis model and studied its possible mechanism of action. MATERIALS AND METHODS: Melanoma cell lines were exposed to selumetinib under different experimental conditions. We established a mouse model of liver metastasis and treated mice orally with vehicle or selumetinib and then evaluated metastasis progress. RESULTS: Growth inhibition was observed in melanoma cells as a consequence of G1-phase cell-cycle arrest and the subsequent induction of apoptosis in a dose- and time-dependent manner...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28178391/amino-terminal-enhancer-of-split-gene-aes-encodes-a-tumor-and-metastasis-suppressor-of-prostate-cancer
#11
Yoshiyuki Okada, Masahiro Sonoshita, Fumihiko Kakizaki, Naoki Aoyama, Yoshiro Itatani, Masayuki Uegaki, Hiromasa Sakamoto, Takashi Kobayashi, Takahiro Inoue, Tomomi Kamba, Akira Suzuki, Osamu Ogawa, M Mark Taketo
Major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples...
February 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28176469/epcam-liver-cancer-stem-like-cells-exhibiting-autocrine-wnt-signaling-potentially-originate-in-cirrhotic-patients
#12
Ritu Khosla, Archana Rastogi, Gayatri Ramakrishna, Viniyendra Pamecha, Ashok Mukhopadhyay, Madavan Vasudevan, Shiv Kumar Sarin, Nirupma Trehanpati
Hepatocellular carcinoma (HCC) is believed to originate from cancer stem cells (CSCs). While epithelial cell adhesion molecule (EpCAM) is a marker of normal hepatic stem cells (HSCs), EpCAM+ cells from HCC behave like CSCs. Since HCC mostly develops on a cirrhotic background, we sought to determine whether CSC-like EpCAM+ cells exist in patients with advanced cirrhosis. Both flow cytometry and immunohistochemistry showed that frequency of EpCAM+ cells in advanced cirrhosis was increased as compared to control...
February 8, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28174757/transcriptional-regulation-by-atoh1-and-its-target-spdef-in%C3%A2-the%C3%A2-intestine
#13
Yuan-Hung Lo, Eunah Chung, Zhaohui Li, Ying-Wooi Wan, Maxime M Mahe, Min-Shan Chen, Taeko K Noah, Kristin N Bell, Hari Krishna Yalamanchili, Tiemo J Klisch, Zhandong Liu, Joo-Seop Park, Noah F Shroyer
BACKGROUND & AIMS: The transcription factor atonal homolog 1 (ATOH1) controls the fate of intestinal progenitors downstream of the Notch signaling pathway. Intestinal progenitors that escape Notch activation express high levels of ATOH1 and commit to a secretory lineage fate, implicating ATOH1 as a gatekeeper for differentiation of intestinal epithelial cells. Although some transcription factors downstream of ATOH1, such as SPDEF, have been identified to specify differentiation and maturation of specific cell types, the bona fide transcriptional targets of ATOH1 still largely are unknown...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#14
Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Elisabeth Paietta, Martin S Tallman, Jacob M Rowe, Kim De Keersmaecker, Andrea Califano, Adolfo A Ferrando
The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28174252/trbp-maintains-mammalian-embryonic-neural-stem-cell-properties-by-enhancing-the-notch-signaling-pathway-as-a-novel-transcriptional-coactivator
#15
Sung-Hyun Byun, Juwan Kim, Dasol Han, Mookwang Kwon, Jae Youl Cho, Hui Xuan Ng, Samuel J Pleasure, Keejung Yoon
Transactivation response element RNA-binding protein (TRBP) is known to play important roles in human immunodeficiency virus (HIV) replication and microRNA biogenesis. However, recent studies implicate TRBP in a variety of biological processes as a mediator for cross-talk between signal transduction pathways. Here, we provide the first evidence that TRBP is required for efficient neurosphere formation, and expression of neural stem cell markers and Notch target genes in primary neural progenitor cells in vitro Consistent with this, introduction of TRBP into the mouse embryonic brain in utero increased the fraction of cells expressing Sox2 in the ventricular zone (VZ)...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28166731/metabolomic-analysis-of-pathways-related-to-rice-grain-chalkiness-by-a-notched-belly-mutant-with-high-occurrence-of-white-belly-grains
#16
Zhaomiao Lin, Xincheng Zhang, Zunxin Wang, Yutong Jiang, Zhenghui Liu, Danny Alexander, Ganghua Li, Shaohua Wang, Yanfeng Ding
BACKGROUND: Grain chalkiness is a highly undesirable trait deleterious to rice appearance and milling quality. The physiological and molecular foundation of chalkiness formation is still partially understood, because of the complex interactions between multiple genes and growing environments. RESULTS: We report the untargeted metabolomic analysis of grains from a notched-belly mutant (DY1102) with high percentage of white-belly, which predominantly occurs in the bottom part proximal to the embryo...
February 7, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28165469/notch3-signaling-mediated-melanoma-endothelial-crosstalk-regulates-melanoma-stem-like-cell-homeostasis-and-niche-morphogenesis
#17
Mei-Yu Hsu, Moon Hee Yang, Caroline I Schnegg, Soonyean Hwang, Byungwoo Ryu, Rhoda M Alani
Melanoma is among the most virulent cancers, owing to its propensity to metastasize and its resistance to current therapies. The treatment failure is largely attributed to tumor heterogeneity, particularly subpopulations possessing stem cell-like properties, ie, melanoma stem-like cells (MSLCs). Evidence indicates that the MSLC phenotype is malleable and may be acquired by non-MSLCs through phenotypic switching upon appropriate stimuli, the so-called 'dynamic stemness'. Since the phenotypic characteristics and functional integrity of MSLCs depend on their vascular niche, using a two-dimensional (2D) melanoma-endothelium co-culture model, where the MSLC niche is recapitulated in vitro, we identified Notch3 signaling pathway as a micro-environmental cue governing MSLC phenotypic plasticity via pathway-specific gene expression arrays...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28163178/over-expression-of-jagged1-ameliorates-aged-rat-derived-endothelial-progenitor-cell-functions-and-improves-its-transfusion-efficiency-for-rat-balloon-induced-arterial-injury
#18
Guangxu Zhu, Jinxiang Wang, Mingbao Song, Fang Zhou, Dagan Fu, Guangping Ruan, Yingying Bai, Zhengping Yu, Leilei Zhang, Xiangqing Zhu, Lan Huang, Rongqing Pang, Xinghua Pan
BACKGROUND: Endothelial progenitor cell (EPC) has significant age-dependent alterations in properties, but the role of Jagged1 in ageing-induced decline of EPC functions remains unclear. METHODS: 2 and 20 months old healthy male Sprague-Dawley rats were used in present study. Jagged1 gene transfection was performed in EPC isolated from aged (AEPC) and young rats (YEPC) respectively. Experiments were divided into four groups: a) pIRES2-EGFP (PE) group, b) PE combined N-[N-(3, 5-difluoro-phenacetyl)-1- alany1]-S-phenyglycine t-butyl ester (DAPT) (PE + D) group, c) pIRES2 EGFP- Jagged1 (PEJ) group and d) PEJ combined DAPT (PEJ+D) group...
February 2, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28161537/mir-598-inhibits-metastasis-in-colorectal-cancer-by-suppressing-jag1-notch2-pathway-stimulating-emt
#19
Jia Chen, Haichen Zhang, Ying Chen, Guanglei Qiao, Weihua Jiang, Peihua Ni, Xiangfan Liu, Lijun Ma
MicroRNAs (miRNAs) are a class of endogenous, evolutionarily conserved small non-coding RNA molecules that mediate the posttranscriptional process of target gene, leading to translational repression or degradation of target mRNAs. A series of studies have indicated that miRNAs play an important role in tumor initiation, development and progression. In this study, we found that down regulation of miR-598 was a frequent event in CRC tissues compared to the paracarcinoma tissues. And the study demonstrated that miR-598 was implicated in CRC metastasis...
February 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28158974/a-compendium-of-developmental-gene-expression-in-lake-malawi-cichlid-fishes
#20
R F Bloomquist, T E Fowler, J B Sylvester, R J Miro, J T Streelman
BACKGROUND: Lake Malawi cichlids represent one of a growing number of vertebrate models used to uncover the genetic and developmental basis of trait diversity. Rapid evolutionary radiation has resulted in species that share similar genomes but differ markedly in phenotypes including brains and behavior, nuptial coloration and the craniofacial skeleton. Research has begun to identify the genes, as well as the molecular and developmental pathways that underlie trait divergence. RESULTS: We assemble a compendium of gene expression for Lake Malawi cichlids, across pharyngula (the phylotypic stage) and larval stages of development, encompassing hundreds of gene transcripts...
February 3, 2017: BMC Developmental Biology
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