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https://www.readbyqxmd.com/read/28448983/intrauterine-growth-restriction-alters-the-postnatal-development-of-the-rat-cerebellum
#1
Annie R A McDougall, Vanny Wiradjaja, Aminath Azhan, Anqi Li, Nadia Hale, Mary E Wlodek, Stuart B Hooper, Megan J Wallace, Mary Tolcos
Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0...
April 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28448908/biological-impacts-of-glyphosate-on-morphology-embryo-biomechanics-and-larval-behavior-in-zebrafish-danio-rerio
#2
Shuhui Zhang, Jia Xu, Xiangyu Kuang, Shibao Li, Xiang Li, Dongyan Chen, Xin Zhao, Xizeng Feng
All of these days, residues of herbicides such as glyphosate are widely distributed in the environment. The ubiquitous use of glyphosate has drawn extensive attention to its toxicity as an organic pollutant. In this study, we employed larval zebrafish as an animal model to evaluate the effect of different concentrations of glyphosate on early development via morphological, biomechanics, behavioral and physiological analyses. Morphological results showed that an obvious delay occurred in the epiboly process and body length, eye and head area were reduced at concentrations higher than 10 mg/L...
April 21, 2017: Chemosphere
https://www.readbyqxmd.com/read/28448009/using-primary-neurosphere-cultures-to-study-primary-cilia
#3
Issei S Shimada, Hemant Badgandi, Bandarigoda N Somatilaka, Saikat Mukhopadhyay
The primary cilium is fundamentally important for the proliferation of neural stem/progenitor cells and for neuronal differentiation during embryonic, postnatal, and adult life. In addition, most differentiated neurons possess primary cilia that house signaling receptors, such as G-protein-coupled receptors, and signaling molecules, such as adenylyl cyclases. The primary cilium determines the activity of multiple developmental pathways, including the sonic hedgehog pathway during embryonic neuronal development, and also functions in promoting compartmentalized subcellular signaling during adult neuronal function...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28446817/shh-mediated-centrosomal-recruitment-of-pka-promotes-symmetric-proliferative-neuroepithelial-cell%C3%A2-division
#4
Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto, Elisa Martí
Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions...
April 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28446712/aspirin-inhibits-the-shh-gli1-signaling-pathway-and-sensitizes-malignant-glioma-cells-to-temozolomide-therapy
#5
Jianguang Ming, Bo Sun, Ziwei Li, Lin Lin, Xiangqi Meng, Bo Han, Ruijia Wang, Pengfei Wu, Jianlong Li, Jinquan Cai, Chuanlu Jiang
Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28446294/-effect-of-hedgehog-signaling-pathway-abnormality-on-chemothe-rapeutic-resistance-of-multiple-myeloma
#6
Jia-Sheng Hu, Xiao Huang, Ying-Dan Huang, Yan-Yan Lu, Quan-Yi Lu
OBJECTIVE: To study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma. METHODS: The resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445929/the-kinesin-motor-protein-kif7-is-required-for-t-cell-development-and-normal-mhc-expression-on-thymic-epithelial-cells-tec-in-the-thymus
#7
Ching-In Lau, Alessandro Barbarulo, Anisha Solanki, José Ignacio Saldaña, Tessa Crompton
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#8
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28444310/arl3-and-rp2-regulate-the-trafficking-of-ciliary-tip-kinesins
#9
Nele Schwarz, Amelia Lane, Katarina Jovanovich, David A Parfitt, Monica Aguila, Clare L Thompson, Lyndon da Cruz, Peter J Coffey, J Paul Chapple, Alison J Hardcastle, Michael E Cheetham
Ciliary trafficking defects are the underlying cause of many ciliopathies, including Retinitis Pigmentosa (RP). Anterograde intraflagellar transport (IFT) is mediated by kinesin motor proteins; however, the function of the homodimeric Kif17 motor in cilia is poorly understood, whereas Kif7 is known to play an important role in stabilising cilia tips. Here we identified the ciliary tip kinesins Kif7 and Kif17 as novel interaction partners of the small GTPase Arl3 and its regulatory GTPase activating protein (GAP) Retinitis Pigmentosa 2 (RP2)...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28441416/ethanol-itself-is-a-holoprosencephaly-inducing-teratogen
#10
Mingi Hong, Robert S Krauss
Ethanol is a teratogen, inducing a variety of structural defects in developing humans and animals that are exposed in utero. Mechanisms of ethanol teratogenicity in specific defects are not well understood. Oxidative metabolism of ethanol by alcohol dehydrogenase or cytochrome P450 2E1 has been implicated in some of ethanol's teratogenic effects, either via production of acetaldehyde or competitive inhibition of retinoic acid synthesis. Generalized oxidative stress in response to ethanol may also play a role in its teratogenicity...
2017: PloS One
https://www.readbyqxmd.com/read/28441382/hedgehog-signalling-pathway-orchestrates-angiogenesis-in-triple-negative-breast-cancers
#11
Concetta Di Mauro, Roberta Rosa, Valentina D'Amato, Paola Ciciola, Alberto Servetto, Roberta Marciano, Roberta Clara Orsini, Luigi Formisano, Sandro De Falco, Valeria Cicatiello, Maurizio Di Bonito, Monica Cantile, Francesca Collina, Angela Chambery, Bianca Maria Veneziani, Sabino De Placido, Roberto Bianco
BACKGROUND: Several evidences suggest a marked angiogenic dependency in triple-negative breast cancer (TNBC) tumorigenesis and a potential sensitivity to anti-angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway in regulating TNBC-dependent angiogenesis was investigated. METHODS: Expression and regulation of the Hh pathway transcription factor glioma-associated oncogene homolog1 protein (GLI1) were studied on the endothelial compartment and on TNBC-initiated angiogenesis...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28438991/differentiation-of-v2a-interneurons-from-human-pluripotent-stem-cells
#12
Jessica C Butts, Dylan A McCreedy, Jorge Alexis Martinez-Vargas, Frederico N Mendoza-Camacho, Tracy A Hookway, Casey A Gifford, Praveen Taneja, Linda Noble-Haeusslein, Todd C McDevitt
The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10(+) V2a interneurons from human pluripotent stem cells (hPSCs)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28436966/microbial-metabolites-regulate-host-lipid-metabolism-through-nr5a-hedgehog-signalling
#13
Chih-Chun Janet Lin, Meng C Wang
Microorganisms and their hosts share the same environment, and microbial metabolic molecules (metabolites) exert crucial effects on host physiology. Environmental factors not only shape the composition of the host's resident microorganisms, but also modulate their metabolism. However, the exact molecular relationship among the environment, microbial metabolites and host metabolism remains largely unknown. Here, we discovered that environmental methionine tunes bacterial methyl metabolism to regulate host mitochondrial dynamics and lipid metabolism in Caenorhabditis elegans through an endocrine crosstalk involving NR5A nuclear receptor and Hedgehog signalling...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28432834/molecular-control-of-gut-formation-in-the-spider-parasteatoda-tepidariorum
#14
Natália Martins Feitosa, Matthias Pechmann, Evelyn E Schwager, Vitória Tobias-Santos, Alistair P McGregor, Wim G M Damen, Rodrigo Nunes da Fonseca
The development of a digestive system is an essential feature of bilaterians. Studies of the molecular control of gut formation in arthropods have been studied in detail in the fruit fly Drosophila melanogaster. However, little is known in other arthropods, especially in noninsect arthropods. To better understand the evolution of arthropod alimentary system, we investigate the molecular control of gut development in the spider Parasteatoda tepidariorum (Pt), the primary chelicerate model species for developmental studies...
April 22, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28432216/embryonic-cholecystitis-and-defective-gallbladder-contraction-in-the-sox17-haploinsufficient-model-of-biliary-atresia
#15
Hiroki Higashiyama, Aisa Ozawa, Hiroyuki Sumitomo, Mami Uemura, Ko Fujino, Hitomi Igarashi, Kenya Imaimatsu, Naoki Tsunekawa, Yoshikazu Hirate, Masamichi Kurohmaru, Yukio Saijoh, Masami Kanai-Azuma, Yoshiakira Kanai
The gallbladder excretes cytotoxic bile acids to the duodenum through the cystic duct and common bile duct system. Sox17 haploinsufficiency causes the biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos. However, the molecular and cellular mechanisms in the Sox17-haploinsufficient gallbladder and liver in the etiology of biliary atresia remain unclear. In this study, transcriptomic analyses revealed the early onset of cholecystitis in the Sox17(+/-) embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28427488/nr2e1-downregulation-is-involved-in-excess-retinoic-acid-induced-developmental-abnormality-in-the-mouse-brain
#16
Juan Yu, Qian Guo, Jian Bing Mu, Ting Zhang, Ren Ke Li, Jun Xie
OBJECTIVE: This study aimed to investigate the expression pattern and function of Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)-induced brain abnormality. METHODS: The mouse model of brain abnormality was established by administering 28 mg/kg RA, and neural stem cells (NSCs) were isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was detected by whole mount in situ hybridization, RT-PCR, and Western blotting. Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells...
March 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28427431/from-inflammation-to-gastric-cancer-the-importance-of-hedgehog-gli-signaling-in-helicobacter-pylori-induced-chronic-inflammatory-and-neoplastic-diseases
#17
REVIEW
Silja Wessler, Linda M Krisch, Dominik P Elmer, Fritz Aberger
Infections with the human pathogen Helicobacter pylori (H. pylori) are closely associated with the development of inflammatory disorders and neoplastic transformation of the gastric epithelium. Drastic changes in the micromilieu involve a complex network of H. pylori-regulated signal transduction pathways leading to the release of proinflammatory cytokines, gut hormones and a wide range of signaling molecules. Besides controlling embryonic development, the Hedgehog/GLI signaling pathway also plays important roles in epithelial proliferation, differentiation, and regeneration of the gastric physiology, but also in the induction and progression of inflammation and neoplastic transformation in H...
April 20, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28427343/loss-of-pericyte-smoothened-activity-in-mice-with-genetic-deficiency-of-leptin
#18
Guanhua Xie, Marzena Swiderska-Syn, Mark L Jewell, Mariana Verdelho Machado, Gregory A Michelotti, Richard T Premont, Anna Mae Diehl
BACKGROUND: Obesity is associated with multiple diseases, but it is unclear how obesity promotes progressive tissue damage. Recovery from injury requires repair, an energy-expensive process that is coupled to energy availability at the cellular level. The satiety factor, leptin, is a key component of the sensor that matches cellular energy utilization to available energy supplies. Leptin deficiency signals energy depletion, whereas activating the Hedgehog pathway drives energy-consuming activities...
April 20, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28426816/ex-vivo-cultures-combined-with-vivo-morpholino-induced-gene-knockdown-provide-a-system-to-assess-the-role-of-wt1-and-gata4-during-gonad-differentiation
#19
Lucas J Rudigier, Christof Dame, Holger Scholz, Karin M Kirschner
Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper gonadal development. Here we address the contributions of GATA4 and WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo technique for cultivating gonads in hanging droplets of media that were supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in combination at the same developmental stage...
2017: PloS One
https://www.readbyqxmd.com/read/28418873/combined-inhibition-of-gli-and-flt3-signaling-leads-to-effective-anti-leukemic-effects-in-human-acute-myeloid-leukemia
#20
Emily-Marie Latuske, Hauke Stamm, Marianne Klokow, Gabi Vohwinkel, Jana Muschhammer, Carsten Bokemeyer, Manfred Jücker, Maxim Kebenko, Walter Fiedler, Jasmin Wellbrock
Activation of the Hedgehog pathway has been implicated in the pathogenesis of several tumor types including myeloid leukemia. Previously we demonstrated that overexpression of Hedgehog downstream mediators GLI1/2 confers an adverse prognosis to patients with acute myeloid leukemia (AML) and is correlated with a FLT3 mutated status. To analyze a possible non-canonical activation of the Hedgehog pathway via FLT3 and PI3K, we performed blocking experiments utilizing inhibitors for FLT3 (sunitinib), PI3K (PF-04691502) and GLI1/2 (GANT61) in FLT3-mutated and FLT3 wildtype AML cell lines and primary blasts...
March 16, 2017: Oncotarget
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