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https://www.readbyqxmd.com/read/29126016/go-and-stop-signals-for-glial-regeneration
#1
REVIEW
Alicia Hidalgo, Ann Logan
The regenerative response of ensheating glia to central nervous system (CNS) injury involves proliferation and differentiation, axonal re-enwrapment and some recovery of behaviour. Understanding this limited response could enable the enhancement of it. In Drosophila, the glial progenitor state is maintained by Notch, an activator of cell division and Prospero (Pros), a repressor. Injury provokes the activation of NFκB and up-regulation of Kon-tiki (Kon), driving cell proliferation. Homeostatic switch-off comes about as two negative feedback loops involving Pros terminate the response...
November 7, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29125842/evaluating-the-glucose-raising-effect-of-established-loci-via-a-genetic-risk-score
#2
Eirini Marouli, Stavroula Kanoni, Vasiliki Mamakou, Sophie Hackinger, Lorraine Southam, Bram Prins, Angela Rentari, Maria Dimitriou, Eleni Zengini, Fragiskos Gonidakis, Genovefa Kolovou, Vassilis Kontaxakis, Loukianos Rallidis, Nikolaos Tentolouris, Anastasia Thanopoulou, Klea Lamnissou, George Dedoussis, Eleftheria Zeggini, Panagiotis Deloukas
Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. We tested the hypothesis here whether the cumulative effect of glucose raising SNPs, assessed via a score, is associated with glucose levels. A total of 1,434 participants of Greek descent from the THISEAS study and 1,160 participants form the GOMAP study were included in this analysis. We developed a genetic risk score (GRS), based on the known glucose-raising loci, in order to investigate the cumulative effect of known glucose loci on glucose levels...
2017: PloS One
https://www.readbyqxmd.com/read/29059430/genome-wide-association-study-to-identify-susceptibility-loci-that-modify-radiation-related-risk-for-breast-cancer-after-childhood-cancer
#3
MULTICENTER STUDY
Lindsay M Morton, Joshua N Sampson, Gregory T Armstrong, Ting-Huei Chen, Melissa M Hudson, Eric Karlins, Casey L Dagnall, Shengchao Alfred Li, Carmen L Wilson, Deo Kumar Srivastava, Wei Liu, Guolian Kang, Kevin C Oeffinger, Tara O Henderson, Chaya S Moskowitz, Todd M Gibson, Diana M Merino, Jeannette R Wong, Sue Hammond, Joseph P Neglia, Lucie M Turcotte, Jeremy Miller, Laura Bowen, William A Wheeler, Wendy M Leisenring, John A Whitton, Laurie Burdette, Charles Chung, Belynda D Hicks, Kristine Jones, Mitchell J Machiela, Aurelie Vogt, Zhaoming Wang, Meredith Yeager, Geoffrey Neale, Matthew Lear, Louise C Strong, Yutaka Yasui, Marilyn Stovall, Rita E Weathers, Susan A Smith, Rebecca Howell, Stella M Davies, Gretchen A Radloff, Kenan Onel, Amy Berrington de González, Peter D Inskip, Preetha Rajaraman, Joseph F Fraumeni, Smita Bhatia, Stephen J Chanock, Margaret A Tucker, Leslie L Robison
Background: Childhood cancer survivors treated with chest-directed radiotherapy have substantially elevated risk for developing breast cancer. Although genetic susceptibility to breast cancer in the general population is well studied, large-scale evaluation of breast cancer susceptibility after chest-directed radiotherapy for childhood cancer is lacking. Methods: We conducted a genome-wide association study of breast cancer in female survivors of childhood cancer, pooling two cohorts with detailed treatment data and systematic, long-term follow-up: the Childhood Cancer Survivor Study and St...
November 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29050214/prox1-represses-il-2-gene-expression-by-interacting-with-nfat2
#4
Shujie Zhang, Ning Yu, Linfang Wang, Yanfeng Liu, Yuying Kong, Jing Liu, Youhua Xie
Interleukin-2 (IL-2) is critical for T lymphocyte activation and regulated by many transcriptional factors. Prospero-related homeobox 1 (Prox1) is a multifunctional transcription factor, which can work as either a transcriptional activator or repressor depending on the cellular and developmental environment. We previously reported the Prox1 expression in T cells, raising the possibility of Prox1 involvement in the regulation of T cell function and IL-2 production. Here we demonstrated that the Prox1 expression in CD4+ T cells was downregulated by T cell receptor (TCR) activation...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28920924/impaired-angiopoietin-tie2-signaling-compromises-schlemm-s-canal-integrity-and-induces-glaucoma
#5
Jaeryung Kim, Dae-Young Park, Hosung Bae, Do Young Park, Dongkyu Kim, Choong-Kun Lee, Sukhyun Song, Tae-Young Chung, Dong Hui Lim, Yoshiaki Kubota, Young-Kwon Hong, Yulong He, Hellmut G Augustin, Guillermo Oliver, Gou Young Koh
Primary open-angle glaucoma (POAG) is often caused by elevated intraocular pressure (IOP), which arises due to increased resistance to aqueous humor outflow (AHO). Aqueous humor flows through Schlemm's canal (SC), a lymphatic-like vessel encircling the cornea, and via intercellular spaces of ciliary muscle cells. However, the mechanisms underlying increased AHO resistance are poorly understood. Here, we demonstrate that signaling between angiopoietin (Angpt) and the Angpt receptor Tie2, which is critical for SC formation, is also indispensable for maintaining SC integrity during adulthood...
October 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28919193/association-analysis-of-genetic-variants-with-metabolic-syndrome-components-in-the-moroccan-population
#6
F Lakbakbi El Yaagoubi, H Charoute, I Morjane, H Sefri, H Rouba, A Ainahi, M Kandil, H Benrahma, A Barakat
This study aimed to analyze the association between UBE2E2, G6PC2, PROX1, DUSP9, ADCY5 and APOC3 polymorphisms and the risk of metabolic syndrome (MetS) in Moroccan patients. The study was applied on 316 unrelated individuals from Morocco, 177 MetS patients and 139 controls. The metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) criteria. All subjects were genotyped for the following polymorphisms: rs7612463 (UBE2E2), rs560887 (G6PC2), rs340874 (PROX1), rs5945326 (DUSP9), rs11708067 (ADCY5) and rs5128 (APOC3) using TaqMan allelic discrimination assay and PCR-RFLP...
September 11, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28916805/an-hdac3-prox1-corepressor-module-acts-on-hnf4%C3%AE-to-control-hepatic-triglycerides
#7
Sean M Armour, Jarrett R Remsberg, Manashree Damle, Simone Sidoli, Wesley Y Ho, Zhenghui Li, Benjamin A Garcia, Mitchell A Lazar
The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR-HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by hepatocyte nuclear factor 4α (HNF4α)...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28867048/signaling-and-gene-regulatory-networks-in-mammalian-lens-development
#8
REVIEW
Ales Cvekl, Xin Zhang
Ocular lens development represents an advantageous system in which to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and the underlying gene regulatory networks. Spatiotemporally regulated domains of BMP, FGF, and other signaling molecules in late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation...
October 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28855864/persistent-decreases-in-adult-subventricular-and-hippocampal-neurogenesis-following-adolescent-intermittent-ethanol-exposure
#9
Wen Liu, Fulton T Crews
Neurogenesis in hippocampal dentate gyrus (DG) and subventricular zone (SVZ) matures during adolescence to adult levels. Binge drinking is prevalent in adolescent humans, and could alter brain neurogenesis and maturation in a manner that persists into adulthood. To determine the impact of adolescent binge drinking on adult neurogenesis, Wistar rats received adolescent intermittent ethanol (AIE) exposure (5.0 g/kg/day, i.g., 2 days on/2 days off from postnatal day, P25-P54) and sacrificed on P57 or P95. Neural progenitor cell proliferation, differentiation, survival and maturation using immunohistochemistry was determined in the DG and SVZ...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28854215/high-prox1-expression-in-gastric-cancer-predicts-better-survival
#10
Alli Laitinen, Camilla Böckelman, Jaana Hagström, Arto Kokkola, Pauliina Kallio, Caj Haglund
BACKGROUND: PROX1 is a transcription factor involved in the development of various organs. It has also an important function in colorectal cancer progression. The aim of this study was to investigate the prognostic role of PROX1 expression in gastric cancer. METHODS: We evaluated PROX1 expression in gastric cancer by immunohistochemistry of tumor-tissue microarrays including tumor specimens from 283 patients who underwent surgery at Helsinki University Hospital...
2017: PloS One
https://www.readbyqxmd.com/read/28814666/rapamycin-reversal-of-vegf-c-driven-lymphatic-anomalies-in-the-respiratory-tract
#11
Peter Baluk, Li-Chin Yao, Julio C Flores, Dongwon Choi, Young-Kwon Hong, Donald M McDonald
Lymphatic malformations are serious but poorly understood conditions that present therapeutic challenges. The goal of this study was to compare strategies for inducing regression of abnormal lymphatics and explore underlying mechanisms. CCSP-rtTA/tetO-VEGF-C mice, in which doxycycline regulates VEGF-C expression in the airway epithelium, were used as a model of pulmonary lymphangiectasia. After doxycycline was stopped, VEGF-C expression returned to normal, but lymphangiectasia persisted for at least 9 months...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28795242/prox1-gfp-flt1-dsred-transgenic-mice-an-animal-model-for-simultaneous-live-imaging-of-angiogenesis-and-lymphangiogenesis
#12
Wei Zhong, Xinbo Gao, Shuangyong Wang, Kyuyeon Han, Masatsugu Ema, Susanne Adams, Ralf H Adams, Mark I Rosenblatt, Jin-Hong Chang, Dimitri T Azar
The roles of angiogenesis in development, health, and disease have been studied extensively; however, the studies related to lymphatic system are limited due to the difficulty in observing colorless lymphatic vessels. But recently, with the improved technique, the relative importance of the lymphatic system is just being revealed. We bred transgenic mice in which lymphatic endothelial cells express GFP (Prox1-GFP) with mice in which vascular endothelial cells express DsRed (Flt1-DsRed) to generate Prox1-GFP/Flt1-DsRed (PGFD) mice...
November 2017: Angiogenesis
https://www.readbyqxmd.com/read/28791751/the-gene-network-underlying-the-glial-regenerative-response-to-central-nervous-system-injury
#13
REVIEW
Kentaro Kato, Maria Losada-Perez, Alicia Hidalgo
Although the central nervous system does not regenerate, injury induces repair and regenerative responses in glial cells. In mammals, activated microglia clear up apoptotic cells and debris resulting from the injury, astrocytes form a scar that contains the lesion, and NG2-glia elicit a prominent regenerative response. NG2-glia regenerate themselves and differentiate into oligodendrocytes, which remyelinate axons leading to some recovery of locomotion. The regenerative response of glial cells is evolutionarily conserved across the animals and Drosophila genetics revealed an underlying gene network...
August 9, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28724617/human-venous-valve-disease-caused-by-mutations-in-foxc2-and-gjc2
#14
Oliver Lyons, Prakash Saha, Christopher Seet, Adam Kuchta, Andrew Arnold, Steven Grover, Victoria Rashbrook, Amélie Sabine, Gema Vizcay-Barrena, Ash Patel, Francesca Ludwinski, Soundrie Padayachee, Tsutomu Kume, Brenda R Kwak, Glen Brice, Sahar Mansour, Pia Ostergaard, Peter Mortimer, Steve Jeffery, Nigel Brown, Taija Makinen, Tatiana V Petrova, Bijan Modarai, Alberto Smith
Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1(hi) endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1(hi) endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events...
July 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28717161/development-and-characterization-of-a-novel-prox1-egfp-lymphatic-and-schlemm-s-canal-reporter-rat
#15
Eunson Jung, Daniel Gardner, Dongwon Choi, Eunkyung Park, Young Jin Seong, Sara Yang, Jorge Castorena-Gonzalez, Antoine Louveau, Zhao Zhou, Gene K Lee, David P Perrault, Sunju Lee, Maxwell Johnson, George Daghlian, Maria Lee, Yeo Jin Hong, Yukinari Kato, Jonathan Kipnis, Michael J Davis, Alex K Wong, Young-Kwon Hong
The lymphatic system plays a key role in tissue fluid homeostasis, immune cell trafficking, and fat absorption. We previously reported a bacterial artificial chromosome (BAC)-based lymphatic reporter mouse, where EGFP is expressed under the regulation of the Prox1 promoter. This reporter line has been widely used to conveniently visualize lymphatic vessels and other Prox1-expressing tissues such as Schlemm's canal. However, mice have a number of experimental limitations due to small body size. By comparison, laboratory rats are larger in size and more closely model the metabolic, physiological, and surgical aspects of humans...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705793/dachsous1-fat4-signaling-controls-endothelial-cell-polarization-during-lymphatic-valve-morphogenesis-brief-report
#16
Francoise Pujol, Tina Hodgson, Ines Martinez-Corral, Anne-Catherine Prats, Danelle Devenport, Masatoshi Takeichi, Elisabeth Genot, Taija Mäkinen, Philippa Francis-West, Barbara Garmy-Susini, Florence Tatin
OBJECTIVE: The purpose of this study was to investigate the role of Fat4 and Dachsous1 signaling in the lymphatic vasculature. APPROACH AND RESULTS: Phenotypic analysis of the lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1. The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1(high) [prospero homeobox protein 1] cells) are disoriented and failed to form proper valve leaflets...
September 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28686870/intestinal-enteroendocrine-lineage-cells-possess-homeostatic-and-injury-inducible-stem-cell-activity
#17
Kelley S Yan, Olivier Gevaert, Grace X Y Zheng, Benedict Anchang, Christopher S Probert, Kathryn A Larkin, Paige S Davies, Zhuan-Fen Cheng, John S Kaddis, Arnold Han, Kelly Roelf, Ruben I Calderon, Esther Cynn, Xiaoyi Hu, Komal Mandleywala, Julie Wilhelmy, Sue M Grimes, David C Corney, Stéphane C Boutet, Jessica M Terry, Phillip Belgrader, Solongo B Ziraldo, Tarjei S Mikkelsen, Fengchao Wang, Richard J von Furstenberg, Nicholas R Smith, Parthasarathy Chandrakesan, Randal May, Mary Ann S Chrissy, Rajan Jain, Christine A Cartwright, Joyce C Niland, Young-Kwon Hong, Jill Carrington, David T Breault, Jonathan Epstein, Courtney W Houchen, John P Lynch, Martin G Martin, Sylvia K Plevritis, Christina Curtis, Hanlee P Ji, Linheng Li, Susan J Henning, Melissa H Wong, Calvin J Kuo
Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5(+) ISCs, the most well-defined ISC pool, but Bmi1-GFP(+) cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP(+) cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1(+) cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28669600/bace1-deficiency-causes-abnormal-neuronal-clustering-in-the-dentate-gyrus
#18
Hailong Hou, Qingyuan Fan, Wanxia He, Hoonkyo Suh, Xiangyou Hu, Riqiang Yan
BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ). Such clusters were rarely observed in wild-type SPZ and not reported in other mouse models. To understand their origins and fates, we examined how neuroblasts in BACE1-null SPZ mature and migrate during early postnatal development...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28646551/prospero-related-homeobox-1-drives-angiogenesis-of-hepatocellular-carcinoma-through-selectively-activating-il-8-expression
#19
Yanfeng Liu, Yonglong Zhang, Shenghao Wang, Qiong-Zhu Dong, Zhongliang Shen, Wei Wang, Shuai Tao, Chenjian Gu, Jing Liu, Youhua Xie, Lun-Xiu Qin
Angiogenesis has been proven to play an important role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying HCC angiogenesis is not well understood. In this study, Prospero-related homeobox 1 (PROX1) was identified as a novel pro-angiogenic factor in HCC cell lines and tissues. A strong positive correlation was found between the levels of PROX1 and microvessel density in HCC tissues. Knockdown of PROX1 expression in HCC cells significantly inhibited the in vitro capillary tube formation by human vascular endothelial cells and in vivo angiogenesis of HCC, while overexpression of PROX1 in HCC cells induced the opposite effects...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28608989/seizure-severity-dependent-selective-vulnerability-of-the-granule-cell-layer-and-aberrant-neurogenesis-in-the-rat-hippocampus
#20
Takeshi Uemori, Keiko Toda, Tatsunori Seki
The pilocarpine-induced status epilepticus rodent model has been commonly used to analyze the mechanisms of human temporal lobe epilepsy. Recent studies using this model have demonstrated that epileptic seizures lead to increased adult neurogenesis of the dentate granule cells, and cause abnormal cellular organization in dentate neuronal circuits. In this study, we examined these structural changes in rats with seizures of varying severity. In rats with frequent severe seizures, we found a clear loss of Prox1 and NeuN expression in the dentate granule cell layer (GCL), which was confined mainly to the suprapyramidal blade of the GCL at the septal and middle regions of the septotemporal axis of the hippocampus...
June 13, 2017: Hippocampus
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