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https://www.readbyqxmd.com/read/28427858/mice-with-conditional-neurod1-knockout-display-reduced-aberrant-hippocampal-neurogenesis-but-no-change-in-epileptic-seizures
#1
Rebecca Brulet, Jingfei Zhu, Mahafuza Aktar, Jenny Hsieh, Kyung-Ok Cho
Adult neurogenesis is significantly increased in the hippocampus of rodent models of temporal lobe epilepsy (TLE). These adult-generated neurons have recently been shown to play a contributing role in the development of spontaneous recurrent seizures (SRS). In order to eventually target pro-epileptic adult neurogenesis in the clinical setting, it will be important to identify molecular players involved in the control of aberrant neurogenesis after seizures. Here, we focused on NeuroD1 (ND1), a member of the bHLH family of transcription factors previously shown to play an essential role in the differentiation and maturation of adult-generated neurons in the hippocampus...
April 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28425097/seizure-frequency-correlates-with-loss-of-dentate-gyrus-gabaergic-neurons-in-a-mouse-model-of-temporal-lobe-epilepsy
#2
Paul S Buckmaster, Emily Abrams, Xiling Wen
Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. The present study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31 - 61 d earlier were video-monitored for spontaneous, convulsive seizures 9 h/d every day for 24 - 36 d...
April 20, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28352669/lymphatic-deletion-of-calcitonin-receptor-like-receptor-exacerbates-intestinal-inflammation
#3
Reema B Davis, Daniel O Kechele, Elizabeth S Blakeney, John B Pawlak, Kathleen M Caron
Lymphatics play a critical role in maintaining gastrointestinal homeostasis and in the absorption of dietary lipids, yet their roles in intestinal inflammation remain elusive. Given the increasing prevalence of inflammatory bowel disease, we investigated whether lymphatic vessels contribute to, or may be causative of, disease progression. We generated a mouse model with temporal and spatial deletion of the key lymphangiogenic receptor for the adrenomedullin peptide, calcitonin receptor-like receptor (Calcrl), and found that the loss of lymphatic Calcrl was sufficient to induce intestinal lymphangiectasia, characterized by dilated lacteals and protein-losing enteropathy...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28351298/aberrant-gene-specific-dna-methylation-signature-analysis-in-cervical-cancer
#4
Samatha Bhat, Shama Prasada Kabekkodu, Vinay Koshy Varghese, Sanjiban Chakrabarty, Sandeep P Mallya, Harish Rotti, Deeksha Pandey, Pralhad Kushtagi, Kapaettu Satyamoorthy
Multicomponent molecular modifications such as DNA methylation may offer sensitive and specific cervical intraepithelial neoplasia and cervical cancer biomarkers. In this study, we tested cervical tissues at various stages of tumor progression for 5-methylcytosine and 5-hydroxymethylcytosine levels and also DNA promoter methylation profile of a panel of genes for its diagnostic potential. In total, 5-methylcytosine, 5-hydroxymethylcytosine, and promoter methylation of 33 genes were evaluated by reversed-phase high-performance liquid chromatography, enzyme-linked immunosorbent assay based technique, and bisulfate-based next generation sequencing...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28314928/hilar-granule-cells-of-the-mouse-dentate-gyrus-effects-of-age-septotemporal-location-strain-and-selective-deletion-of-the-proapoptotic-gene-bax
#5
Keria Bermudez-Hernandez, Yi-Ling Lu, Jillian Moretto, Swati Jain, John J LaFrancois, Aine M Duffy, Helen E Scharfman
The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus...
March 17, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28263185/laminar-flow-downregulates-notch-activity-to-promote-lymphatic-sprouting
#6
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Jaehyuk Yoo, Esak Lee, Mingu Hong, Sunju Lee, Hiroaki Ishida, James Burford, Janos Peti-Peterdi, Ralf H Adams, Sonal Srikanth, Yousang Gwack, Christopher S Chen, Hans J Vogel, Chester J Koh, Alex K Wong, Young-Kwon Hong
The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28158247/neuroprotective-effects-of-dexmedetomidine-against-hyperoxia-induced-injury-in-the-developing-rat-brain
#7
Stefanie Endesfelder, Hanan Makki, Clarissa von Haefen, Claudia D Spies, Christoph Bührer, Marco Sifringer
Dexmedetomidine (DEX) is a highly selective agonist of α2-receptors with sedative, anxiolytic, and analgesic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on hippocampal neurogenesis, specifically the proliferation capacity and maturation of neurons and neuronal plasticity following the induction of hyperoxia in neonatal rats. Six-day old sex-matched Wistar rats were exposed to 80% oxygen or room air for 24 h and treated with 1, 5 or 10 μg/kg of dexmedetomidine or normal saline...
2017: PloS One
https://www.readbyqxmd.com/read/28125839/generation-of-functional-lentoid-bodies-from-human-induced-pluripotent-stem-cells-derived-from-urinary-cells
#8
Qiuli Fu, Zhenwei Qin, Xiuming Jin, Lifang Zhang, Zhijian Chen, Jiliang He, Junfeng Ji, Ke Yao
Purpose: The pathological mechanisms underlying cataract formation remain largely unknown on account of the lack of appropriate in vitro cellular models. The aim of this study is to develop a stable in vitro system for human lens regeneration using pluripotent stem cells. Methods: Isolated human urinary cells were infected with four Yamanaka factors to generate urinary human induced pluripotent stem cells (UiPSCs), which were induced to differentiate into lens progenitor cells and lentoid bodies (LBs)...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28118374/dynamic-expression-of-sox2-gata3-and-prox1-during-primary-auditory-neuron-development-in-the-mammalian-cochlea
#9
Koji Nishimura, Teppei Noda, Alain Dabdoub
Primary auditory neurons (PANs) connect cochlear sensory hair cells in the mammalian inner ear to cochlear nucleus neurons in the brainstem. PANs develop from neuroblasts delaminated from the proneurosensory domain of the otocyst and keep maturing until the onset of hearing after birth. There are two types of PANs: type I, which innervate the inner hair cells (IHCs), and type II, which innervate the outer hair cells (OHCs). Glial cells surrounding these neurons originate from neural crest cells and migrate to the spiral ganglion...
2017: PloS One
https://www.readbyqxmd.com/read/28060188/prox1-gene-cc-genotype-as-a-major-determinant-of-early-onset-of-type-2-diabetes-in-slavic-study-participants-from-action-in-diabetes-and-vascular-disease-preterax-and-diamicron-mr-controlled-evaluation-study
#10
Pavel Hamet, Mounsif Haloui, François Harvey, François-Christophe Marois-Blanchet, Marie-Pierre Sylvestre, Muhammad-Ramzan Tahir, Paul H G Simon, Beatriz Sonja Kanzki, John Raelson, Carole Long, John Chalmers, Mark Woodward, Michel Marre, Stephen Harrap, Johanne Tremblay
BACKGROUND: The prevalence of diabetic nephropathy varies according to ethnicity. Environmental as well as genetic factors contribute to the heterogeneity in the presentation of diabetic nephropathy. Our objective was to evaluate this heterogeneity within the Caucasian population. METHODS: The geo-ethnic origin of the 3409 genotyped Caucasian type 2 diabetes (T2D) patients of Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation was determined using principal component analysis...
May 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28055225/overexpression-of-prox1-induces-the-differentiation-of-human-adipose-derived-stem-cells-into-lymphatic-endothelial-like-cells-in-vitro
#11
Jingcheng Deng, Tingting Dai, Yiyu Sun, Qi Zhang, Zhaohua Jiang, Shengli Li, Weigang Cao
Constant levels of homeobox transcription factor Prox1 expression are required throughout the life of lymphatic endothelial cells (LECs) to maintain their differentiated identity. Recent studies have demonstrated that using human LECs for cell transplantation therapy may improve secondary lymphedema in a nude rat model. However, the application is currently limited by the low yield of LECs. In this study, Prox1 was overexpressed in human adipose tissue-derived stem cells (hADSCs) by using the transfection of lentiviral vectors to induce the differentiation of hADSCs to LECs...
February 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28035380/prox1-promotes-human-glioblastoma-cell-proliferation-and-invasion-via-activation-of-the-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway
#12
Xuchang Xu, Xuefeng Wan, Xinting Wei
Prospero homeobox protein 1 (PROX1) is highly expressed in high-grade malignant astrocytic gliomas. However, the role of PROX1 in the pathogenesis of glioblastoma multiforme (GBM) remains unclear. The present study overexpressed PROX1 in human GBM cell lines and examined its effects on cell growth, tumorigenesis, and invasiveness. In addition, the involvement of the nuclear factor‑κB (NF‑κB) signaling pathway in the action of PROX1 was examined. It was identified that overexpression of PROX1 significantly increased the proliferation and colony formation of glioblastoma cells, compared with empty vector‑transfected controls...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28026853/lyve1-and-prox1-in-the-reconstruction-of-hepatic-sinusoids-after-partial-hepatectomy-in-mice
#13
Fanwei Meng
Revascularization is crucial to liver regeneration after liver injury, but the process remains unclear. This study investigated changes in the levels and distribution of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) and prospero homeobox protein 1 (PROX1) in liver tissue sections after partial hepatectomy in mice. Mice were subjected to partial hepatectomy. Control animals were sham-operated. From days 1 through 8, the remaining liver tissues were collected from 8 animals each day. Histology showed that after partial hepatectomy, the remaining liver tissue samples underwent initial degeneration and then hepatocyte proliferation and regeneration...
December 27, 2016: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/28024299/the-role-of-fatty-acid-%C3%AE-oxidation-in-lymphangiogenesis
#14
Brian W Wong, Xingwu Wang, Annalisa Zecchin, Bernard Thienpont, Ivo Cornelissen, Joanna Kalucka, Melissa García-Caballero, Rindert Missiaen, Hongling Huang, Ulrike Brüning, Silvia Blacher, Stefan Vinckier, Jermaine Goveia, Marlen Knobloch, Hui Zhao, Cathrin Dierkes, Chenyan Shi, René Hägerling, Veronica Moral-Dardé, Sabine Wyns, Martin Lippens, Sebastian Jessberger, Sarah-Maria Fendt, Aernout Luttun, Agnès Noel, Friedemann Kiefer, Bart Ghesquière, Lieve Moons, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Diether Lambrechts, Peter Carmeliet
Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, impairs lymphatic development. LECs use fatty acid β-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid β-oxidation...
December 26, 2016: Nature
https://www.readbyqxmd.com/read/28013212/editor-s-highlight-organ-specific-epigenetic-changes-induced-by-the-nongenotoxic-liver-carcinogen-methapyrilene-in-fischer-344-rats
#15
Svitlana Shpyleva, Kostiantyn Dreval, Aline de Conti, Iryna Kindrat, Stepan Melnyk, Jian Yan, Tao Chen, Frederick A Beland, Igor P Pogribny
Continuous lifetime exposure to certain natural and man-made chemicals is a major cause of cancers in humans; therefore, evaluating the carcinogenic risks of chemicals remains important. Currently, substantial progress has been made in identification of genotoxic carcinogens; in contrast, predicting the carcinogenic potential of nongenotoxic compounds is a challenge due to many different modes of action that may lead to tumorigenesis. In the present study, we investigated the effects of the nongenotoxic liver carcinogen methapyrilene and the nongenotoxic noncarcinogen usnic acid, at doses that do not exhibit organ cytotoxicity, on epigenomic alterations in the livers and kidneys of Fischer 344 (F344) rats...
March 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28012947/the-gsk-3-inhibitor-vp2-51-produces-antidepressant-effects-associated-with-adult-hippocampal-neurogenesis
#16
Paloma Pérez-Domper, Valle Palomo, Simona Gradari, Carmen Gil, María L de Ceballos, Ana Martínez, Jose Luis Trejo
Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that has been implicated in the mechanism of action of mood stabilizers. According to the neurogenic hypothesis of depression, newborn neurons in the adult dentate gyrus are required for the antidepressant effects of certain agents. We demonstrate that administration of the GSK-3 inhibitor VP2.51 (2.5 mg/kg ip, for 3.5 weeks) increases cell proliferation (pH3(+) cells), as well as the short- and long-term survival of newborn neurons (assessed by the 24 h survival of BrdU(+) and DCX(+) neurons), while significantly increasing the commitment of cells to the granule neuron lineage (Prox1 immunoreactivity)...
December 22, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27928788/-basic-and-translational-research-progress-of-gastrointestinal-neuroendocrine-neoplasmas
#17
Yuli Song, Xiaoyi Li, Tiantian Song, Guole Lin, Yuanjia Chen
Gastrointestinal neuroendocrine tumors are a group of highly heterogeneous tumors. Their incidences have increased in the Western countries as well as in Asia for years. In recent years, predominant progression has been made in the basic and translational studies on gastrointestinal neuroendocrine tumors. Gastric neuroendocrine neoplasmas are classified as four types: type I( occurs on the basis of autoimmune atrophic gastritis, type II( clinically manifests as multiple endocrine tumor type I( and Zollinger-Ellison syndrome, type III( is sporadic neuroendocrine neoplasmas, and type IIII( is neuroendocrine carcinoma...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27916465/hypoxia-inhibits-lymphatic-thoracic-duct-formation-in-zebrafish
#18
Isabelle Ernens, Andrew I Lumley, Lu Zhang, Yvan Devaux, Daniel R Wagner
Hypoxia promotes blood vessel growth through up-regulation of pro-angiogenic pathways but its role on the lymphatic system remains unclear. The homeobox transcription factor Prox1 is a master control gene for generating lymphatic endothelial cells (LECs) and is up-regulated by hypoxia-inducible factors in mammals. While vascular endothelial growth factor A (VEGFA) is critical for angiogenesis, VEGFC and its receptor VEGF receptor-3 (VEGFR-3) are essential for the initial sprouting and directed migration as well as for the subsequent survival of LECs...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27873085/quantitative-analysis-of-supporting-cell-subtype-labeling-among-creer-lines-in-the-neonatal-mouse-cochlea
#19
Melissa M McGovern, Joseph Brancheck, Auston C Grant, Kaley A Graves, Brandon C Cox
Four CreER lines that are commonly used in the auditory field to label cochlear supporting cells (SCs) are expressed in multiple SC subtypes, with some lines also showing reporter expression in hair cells (HCs). We hypothesized that altering the tamoxifen dose would modify CreER expression and target subsets of SCs. We also used two different reporter lines, ROSA26 (tdTomato) and CAG-eGFP, to achieve the same goal. Our results confirm previous reports that Sox2 (CreERT2) and Fgfr3-iCreER (T2) are not only expressed in neonatal SCs but also in HCs...
April 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/27845051/intrinsic-lens-potential-of-neural-retina-inhibited-by-notch-signaling-as-the-cause-of-lens-transdifferentiation
#20
Hideaki Iida, Yasuo Ishii, Hisato Kondoh
Embryonic neural retinas of avians produce lenses under spreading culture conditions. This phenomenon has been regarded as a paradigm of transdifferentiation due to the overt change in cell type. Here we elucidated the underlying mechanisms. Retina-to-lens transdifferentiation occurs in spreading cultures, suggesting that it is triggered by altered cell-cell interactions. Thus, we tested the involvement of Notch signaling based on its role in retinal neurogenesis. Starting from E8 retina, a small number of crystallin-expressing lens cells began to develop after 20 days in control spreading cultures...
January 15, 2017: Developmental Biology
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