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https://www.readbyqxmd.com/read/28547531/neonatal-hyperoxia-perturbs-neuronal-development-in-the-cerebellum
#1
Till Scheuer, Yuliya Sharkovska, Victor Tarabykin, Katharina Marggraf, Vivien Brockmöller, Christoph Bührer, Stefanie Endesfelder, Thomas Schmitz
Impaired postnatal brain development of preterm infants often results in neurological deficits. Besides pathologies of the forebrain, maldeveolopment of the cerebellum is increasingly recognized to contribute to psychomotor impairments of many former preterm infants. However, causes are poorly defined. We used a hyperoxia model to define neonatal damage in cerebellar granule cell precursors (GCPs) and in Purkinje cells (PCs) known to be essential for interaction with GCPs during development. We exposed newborn rats to 24 h 80% O2 from age P6 to P7 to identify postnatal and long-term damage in cerebellar GCPs at age P7 after hyperoxia and also after recovery in room air thereafter until P11 and P30...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28529477/prox1-is-a-marker-for-aii-amacrine-cells-in-the-mouse-retina
#2
Luis Pérez de Sevilla Müller, Shaghauyegh S Azar, Janira de Los Santos, Nicholas C Brecha
The transcription factor Prox1 is expressed in multiple cells in the retina during eye development. This study has focused on neuronal Prox1 expression in the inner nuclear layer (INL) of the adult mouse retina. Prox1 immunostaining was evaluated in vertical retinal sections and whole mount preparations using a specific antibody directed to the C-terminus of Prox1. Strong immunostaining was observed in numerous amacrine cell bodies and in all horizontal cell bodies in the proximal and distal INL, respectively...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28488574/prox1-represses-il-2-gene-expression-by-interacting-with-nfat2
#3
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...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28486010/lymphatic-endothelial-cells-under-mechanical-stress-altered-expression-of-inflammatory-cytokines-and-fibrosis
#4
Sheri Wang, Daibang Nie, J Peter Rubin, Lauren Kokai
BACKGROUND: Secondary lymphedema, resulting from damage to lymphatic vessels, is a common sequela following surgical removal of lymph nodes for cancer. Current therapeutics for treating lymphedema are limited and further research on underlying causes is warranted. Published studies on molecular mechanisms of lymphedema primarily focus on lymphatic endothelial cells (LECs), which comprise the innermost lining of lymphatic capillaries and collecting vessels. However, traditional static culture of LECs may not adequately recapitulate the lymphedemous cell phenotype as transcriptomal comparison of human dermal LECs has shown significant differences in ex vivo and in vitro LEC gene expression...
May 9, 2017: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/28453575/genome-wide-association-study-of-red-blood-cell-traits-in-hispanics-latinos-the-hispanic-community-health-study-study-of-latinos
#5
Chani J Hodonsky, Deepti Jain, Ursula M Schick, Jean V Morrison, Lisa Brown, Caitlin P McHugh, Claudia Schurmann, Diane D Chen, Yong Mei Liu, Paul L Auer, Cecilia A Laurie, Kent D Taylor, Brian L Browning, Yun Li, George Papanicolaou, Jerome I Rotter, Ryo Kurita, Yukio Nakamura, Sharon R Browning, Ruth J F Loos, Kari E North, Cathy C Laurie, Timothy A Thornton, Nathan Pankratz, Daniel E Bauer, Tamar Sofer, Alex P Reiner
Prior GWAS have identified loci associated with red blood cell (RBC) traits in populations of European, African, and Asian ancestry. These studies have not included individuals with an Amerindian ancestral background, such as Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. Using a custom genotyping array enriched for Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in 12,502 participants of Hispanic Community Health Study and Study of Latinos (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW), and RBC indices...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28427858/mice-with-conditional-neurod1-knockout-display-reduced-aberrant-hippocampal-neurogenesis-but-no-change-in-epileptic-seizures
#6
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
#7
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. This 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 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24-36 days...
April 20, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28352669/lymphatic-deletion-of-calcitonin-receptor-like-receptor-exacerbates-intestinal-inflammation
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
February 2, 2017: 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
#20
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
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