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https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#1
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28078618/decreased-tap63-and-%C3%AE-np63-mrna-levels-in-most-human-pituitary-adenomas-are-correlated-with-notch3-jagged1-relative-expression
#2
Lisiane Cervieri Mezzomo, Frederico Giacomoni Pesce, Josenel Maria Barcelos Marçal, Taiana Haag, Nelson Pires Ferreira, Julia Fernanda Semmelmann Pereira Lima, Carolina Garcia Soares Leães, Miriam Costa Oliveira, Maria Beatriz da Fonte Kohek
Despite recent advances in molecular genetics, the pituitary adenoma initiation, development, progress, and the molecular basis of their unique features are still poorly understood. In this sense, it is proposed that stem cell could be involved in pituitary adenoma tumorigenesis. It is suggested that TP63 has important functions in stem cells, and it may have interplay of TP63 and Notch and its ligand Jagged in this process. This study aimed to evaluate the distinct expression of TP63 isoforms (TAp63 and ΔNp63), as well as its correlation with Notch3 receptor and its ligand Jagged1 in human pituitary adenomas at the messenger RNA (mRNA) level...
January 11, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28068897/neotenic-phenomenon-in-gene-expression-in-the-skin-of-foxn1-deficient-nude-mice-a-projection-for-regenerative-skin-wound-healing
#3
Anna Kur-Piotrowska, Marta Kopcewicz, Leslie P Kozak, Pawel Sachadyn, Anna Grabowska, Barbara Gawronska-Kozak
BACKGROUND: Mouse fetuses up to 16 day of embryonic development and nude (Foxn1- deficient) mice are examples of animals that undergo regenerative (scar-free) skin healing. The expression of transcription factor Foxn1 in the epidermis of mouse fetuses begins at embryonic day 16.5 which coincides with the transition point from scar-free to scar-forming skin wound healing. In the present study, we tested the hypothesis that Foxn1 expression in the skin is an essential condition to establish the adult skin phenotype and that Foxn1 inactivity in nude mice keeps skin in the immature stage resembling the phenomena of neoteny...
January 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28068481/micrornas-and-periodontal-homeostasis
#4
X Luan, X Zhou, J Trombetta-eSilva, M Francis, A K Gaharwar, P Atsawasuwan, T G H Diekwisch
MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28064239/recurrent-somatic-mutations-affecting-b-cell-receptor-signaling-pathway-genes-in-follicular-lymphoma
#5
Kilannin Krysiak, Felicia Gomez, Brian S White, Matthew Matlock, Christopher A Miller, Lee Trani, Catrina C Fronick, Robert S Fulton, Friederike Kreisel, Amanda F Cashen, Kenneth R Carson, Melissa M Berrien-Elliott, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger
Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma, yet it remains only partially characterized at the genomic level. In order to improve our understanding of the genetic underpinnings of this incurable and clinically heterogeneous disease, whole exome sequencing was performed on tumor/normal pairs from a discovery cohort of 24 patients with FL. Using these data, and mutations identified in other B-cell malignancies, 1716 genes were sequenced in 113 FL tumor samples, from 105 primarily treatment-naïve individuals...
November 14, 2016: Blood
https://www.readbyqxmd.com/read/28061457/prognostic-roles-of-mrna-expression-of-notch-receptors-in-non-small-cell-lung-cancer
#6
Jianwen Xiong, Xiaoqiang Zhang, Xianglai Chen, Yiping Wei, De-Guo Lu, Yun-Wei Han, Jianjun Xu, Dongliang Yu
Notch signalling is aberrantly activated in human non-small cell lung cancer (NSCLC). Nevertheless, the prognostic roles of mRNA expression of four Notch receptors in NSCLC patients remain elusive. In this report, we reported the prognostic roles of Notch receptors in a total of 1,926 NSCLC patients through "The Kaplan-Meier plotter" (KM plotter) database which is capable to assess the effect of 22,277 genes on survival of NSCLC patients. We found that mRNA high expression level of Notch1 was associated with better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 0...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060761/identification-of-micrornas-associated-with-glioma-diagnosis-and-prognosis
#7
Xinyun Ye, Wenjin Wei, Zhengyu Zhang, Chunming He, Ruijin Yang, Jinshi Zhang, Zhiwu Wu, Qianliang Huang, Qiuhua Jiang
The sensitivity and specificity of microRNAs (miRNAs) for diagnosing glioma are controversial. We therefore performed a meta-analysis to systematically identify glioma-associated miRNAs. We initially screened five miRNA microarray datasets to evaluate the differential expression of miRNAs between glioma and normal tissues. We next compared the expression of the miRNAs in different organs and tissues to assess the sensitivity and specificity of the differentially expressed miRNAs in the diagnosis of glioma. Finally, pathway analysis was performed using GeneGO...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058624/zebrafish-phenotypic-screen-identifies-novel-notch-antagonists
#8
Vithya Velaithan, Kazuhide Shaun Okuda, Mei Fong Ng, Norazwana Samat, Sze Wei Leong, Siti Munirah Mohd Faudzi, Faridah Abas, Khozirah Shaari, Sok Ching Cheong, Pei Jean Tan, Vyomesh Patel
Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors...
January 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28049659/reciprocal-signaling-by-wnt-and-notch-specifies-a-muscle-precursor-in-the-c-elegans-embryo
#9
Scott M Robertson, Jessica Medina, Marieke Oldenbroek, Rueyling Lin
The MS blastomere produces one third of the body-wall muscles (BWMs) in the C. elegans embryo. MS-derived BWMs require two distinct cell-cell interactions, the first inhibitory and the second, two cell cycles later, required to overcome this inhibition. The inductive interaction is not required if the inhibitory signal is absent. Although the Notch receptor GLP-1 was implicated in both interactions, the molecular nature of the two signals was unknown. We now show that zygotically-expressed MOM-2 (Wnt) is responsible for both interactions...
January 3, 2017: Development
https://www.readbyqxmd.com/read/28045376/priming-of-endothelial-colony-forming-cells-in-a-mesenchymal-niche-improves-engraftment-and-vasculogenic-potential-by-initiating-mesenchymal-transition-orchestrated-by-notch-signaling
#10
Abbas Shafiee, Jatin Patel, Ho Yi Wong, Prudence Donovan, Dietmar W Hutmacher, Nicholas M Fisk, Kiarash Khosrotehrani
The prospect of using endothelial progenitors is currently hampered by their low engraftment upon transplantation. We report that mesenchymal stem/stromal cells (MSCs), independent of source and age, improve the engraftment of endothelial colony forming cells (ECFCs). MSC coculture altered ECFC appearance to an elongated mesenchymal morphology with reduced proliferation. ECFC primed via MSC contact had reduced self-renewal potential, but improved capacity to form tube structures in vitro and engraftment in vivo Primed ECFCs displayed major differences in transcriptome compared to ECFCs never exposed to MSCs, affecting genes involved in the cell cycle, up-regulating of genes influencing mesenchymal transition, adhesion, extracellular matrix...
October 24, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28035411/ellagic-acid-inhibits-human-glioblastoma-growth-in%C3%A2-vitro-and-in%C3%A2-vivo
#11
Dongliang Wang, Qianxue Chen, Yinqiu Tan, Baohui Liu, Chao Liu
Ellagic acid (EA) is present in various fruits and plants and has recently been found to possess anticarcinogenic effects. The objective of this study was to investigate the anti‑glioblastoma effect of EA and its mechanisms in vitro and in vivo. We first studied the anticancer activity of EA in U87 and U118 human glioblastoma cell lines. The cell viability and cell proliferation were examined by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine staining respectively. The cell cycle was detected with propidium iodide staining method by flow cytometry and the DNA damage of the cells caused by EA exposure was evaluated by detection of γ-H2AX foci...
December 22, 2016: Oncology Reports
https://www.readbyqxmd.com/read/28030818/asic1-promotes-differentiation-of-neuroblastoma-by-negatively-regulating-notch-signaling-pathway
#12
Mingli Liu, Koichi Inoue, Tiandong Leng, An Zhou, Shanchun Guo, Zhi-Gang Xiong
In neurons, up-regulation of Notch activity either inhibits neurite extension or causes retraction of neurites. Conversely, inhibition of Notch1 facilitates neurite extension. Acid-sensing ion channels (ASICs) are a family of proton-gated cation channels, which play critical roles in synaptic plasticity, learning and memory and spine morphogenesis. Our pilot proteomics data from ASIC1a knock out mice implicated that ASIC1a may play a role in regulating Notch signaling, therefore, we explored whether or not ASIC1a regulates neurite growth during neuronal development through Notch signaling...
24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027303/olfactory-sensory-neurons-control-dendritic-complexity-of-mitral-cells-via-notch-signaling
#13
Yuko Muroyama, Atsushi Baba, Motoo Kitagawa, Tetsuichiro Saito
Mitral cells (MCs) of the mammalian olfactory bulb have a single primary dendrite extending into a single glomerulus, where they receive odor information from olfactory sensory neurons (OSNs). Molecular mechanisms for controlling dendritic arbors of MCs, which dynamically change during development, are largely unknown. Here we found that MCs displayed more complex dendritic morphologies in mouse mutants of Maml1, a crucial gene in Notch signaling. Similar phenotypes were observed by conditionally misexpressing a dominant negative form of MAML1 (dnMAML1) in MCs after their migration...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/28027012/dynamic-chromatin-regulation-at-notch-target-genes
#14
Benedetto Daniele Giaimo, Franz Oswald, Tilman Borggrefe
RBPJ is the central transcription factor that controls the Notch-dependent transcriptional response by coordinating repressing histone H3K27 deacetylation and activating histone H3K4 methylation. Here, we discuss the molecular mechanisms how RBPJ interacts with opposing NCoR/HDAC-corepressing or KMT2D/UTX-coactivating complexes and how this is controlled by phosphorylation of chromatin modifiers.
December 27, 2016: Transcription
https://www.readbyqxmd.com/read/28019674/hairy-and-enhancer-of-split-related-with-yrpw-motif-like-heyl-is-dispensable-for-bone-remodeling-in-mice
#15
Ernesto Canalis, Stefano Zanotti
Notch induces Hairy Enhancer of Split (Hes)1 and Hes-related with YRPW motif (Hey) Hey1, Hey2 and Hey-like (HeyL) expression in osteoblasts, but it is not known whether any of these target genes mediates the effect of Notch in the skeleton. We demonstrated that Notch1 activation in osteoblasts/osteocytes induces Hes1, Hey1, Hey2 and HeyL, but HeyL was induced to a greater extent than other target genes. To characterize HeyL null mice for their skeletal phenotype, microcomputed tomography (µCT) and histomorphometric analysis of HeyL null and sex-matched littermate controls was performed...
December 26, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28018099/understanding-the-role-of-pin1-in-hepatocellular-carcinoma
#16
REVIEW
Chi-Wai Cheng, Ka-Wai Leong, Eric Tse
PIN1 is a peptidyl-prolyl cis/trans isomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (e.g., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28013292/mib2-variants-altering-notch-signalling-result-in-left-ventricle-hypertrabeculation-non-compaction-and-are-associated-with-m%C3%A3-n%C3%A3-trier-like-gastropathy
#17
Pasquale Piccolo, Sergio Attanasio, Ilaria Secco, Riccardo Sangermano, Caterina Strisciuglio, Giuseppe Limongelli, Erasmo Miele, Margherita Mutarelli, Sandro Banfi, Vincenzo Nigro, Tirso Pons, Alfonso Valencia, Lorena Zentilin, Severo Campione, Gerardo Nardone, Ty C Lynnes, Patricia B S Celestino-Soper, Katherine G Spoonamore, Francesco P D'Armiento, Mauro Giacca, Annamaria Staiano, Matteo Vatta, Chiara Collesi, Nicola Brunetti-Pierri
We performed whole exome sequencing in individuals from a family with autosomal dominant gastropathy resembling Ménétrier disease, a premalignant gastric disorder with epithelial hyperplasia and enhanced EGFR signalling. Ménétrier disease is believed to be an acquired disorder, but its aetiology is unknown. In affected members, we found a missense p.V742G variant in MIB2, a gene regulating NOTCH signalling that has not been previously linked to human diseases. The variant segregated with the disease in the pedigree, affected a highly conserved amino acid residue, and was predicted to be deleterious although it was found with a low frequency in control individuals...
December 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28012856/increased-fndc5-irisin-expression-in-human-hepatocellular-carcinoma
#18
Melania Gaggini, Manuela Cabiati, Serena Del Turco, Teresa Navarra, Paolo De Simone, Franco Filipponi, Silvia Del Ry, Amalia Gastaldelli, Giuseppina Basta
The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors...
December 21, 2016: Peptides
https://www.readbyqxmd.com/read/28009288/engineered-murine-hscs-reconstitute-multi-lineage-hematopoiesis-and-adaptive-immunity
#19
Yi-Fen Lu, Patrick Cahan, Samantha Ross, Julie Sahalie, Patricia M Sousa, Brandon K Hadland, Wenqing Cai, Erik Serrao, Alan N Engelman, Irwin D Bernstein, George Q Daley
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27993985/patterning-of-brain-precursors-in-ascidian-embryos
#20
Rosaria Esposito, Hitoyoshi Yasuo, Cathy Sirour, Antonio Palladino, Antonietta Spagnuolo, Clare Hudson
In terms of their embryonic origins, the anterior and posterior parts of the ascidian central nervous system (CNS) are associated with distinct germ layers. The anterior part of the sensory vesicle, or brain, originates from ectoderm lineages following a neuro-epidermal binary fate decision. In contrast, a large part of the remaining posterior CNS is generated following neuro-mesodermal binary fate decisions. Here, we address the mechanisms that pattern the anterior brain precursors along the medial-lateral axis (future dorsal-ventral) at neural plate stages...
December 19, 2016: Development
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