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In vivo gene silencing

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https://www.readbyqxmd.com/read/28740463/terminal-differentiation-of-adult-hippocampal-progenitor-cells-is-a-step-functionally-dissociable-from-proliferation-and-is-controlled-by-tis21-id3-and-neurod2
#1
Laura Micheli, Manuela Ceccarelli, Roberta Gioia, Giorgio D'Andrea, Stefano Farioli-Vecchioli, Marco Costanzi, Daniele Saraulli, Vincenzo Cestari, Felice Tirone
Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28739643/histone-methyltransferase-dot1l-is-a-coactivator-for-thyroid-hormone-receptor-during-xenopus-development
#2
Luan Wen, Liezhen Fu, Yun-Bo Shi
Histone modifications are associated with transcriptional regulation by diverse transcription factors. Genome-wide correlation studies have revealed that histone activation marks and repression marks are associated with activated and repressed gene expression, respectively. Among the histone activation marks is histone H3 K79 methylation, which is carried out by only a single methyltransferase, disruptor of telomeric silencing-1-like (DOT1L). We have been studying thyroid hormone (T3)-dependent amphibian metamorphosis in two highly related species, the pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, as a model for postembryonic development, a period around birth in mammals that is difficult to study...
July 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28736767/activation-of-mosquito-complement-antiplasmodial-response-requires-cellular-immunity
#3
Julio César Castillo, Ana Beatriz Barletta Ferreira, Nathanie Trisnadi, Carolina Barillas-Mury
The mosquito complement-like system is a major defense mechanism that limits Plasmodium infection. Ookinete midgut invasion results in irreversible damage to invaded cells and triggers epithelial nitration and complement activation. Several lines of evidence suggest that hemocytes participate in early antiplasmodial responses that target ookinetes, but their role remains unclear. The fate of hemocytes in response to Plasmodium infection was investigated by labeling this cell population in vivo. We found that midgut nitration triggers the local release of hemocyte-derived microvesicles (HdMv) into the basal labyrinth of the midgut...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28729426/glycerol-3-phosphate-acyltransferase-2-is-essential-for-normal-spermatogenesis
#4
Maria Belen Garcia-Fabiani, Mauro A Montanaro, Pablo Stringa, Ezequiel Lacunza, Elizabeth R Cattaneo, Marianela Santana, Magali Pellon-Maison, Maria R Gonzalez-Baro
Glycerol-3-phosphate acyltransferases (GPAT) catalyze the first and rate-limiting step in the de novo glycerolipid synthesis. The GPAT2 isoform differs from the other isoforms because its expression is restricted to male germ cells and cancer cells. It has been recently reported that GPAT2 expression in mouse testis fluctuates during sexual maturation and that it is regulated by epigenetic mechanisms in combination with vitamin A derivatives. Despite progress made in this field, information about GPAT2 role in the developing male germ cells remains unclear...
July 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28727810/cucumber-mosaic-virus-coat-protein-modulates-the-accumulation-of-2b-protein-and-antiviral-silencing-that-causes-symptom-recovery-in-planta
#5
Xiao-Peng Zhang, De-Shui Liu, Teng Yan, Xiao-Dong Fang, Kai Dong, Jin Xu, Ying Wang, Jia-Lin Yu, Xian-Bing Wang
Shoot apical meristems (SAM) are resistant to most plant viruses due to RNA silencing, which is restrained by viral suppressors of RNA silencing (VSRs) to facilitate transient viral invasion of the SAM. In many cases chronic symptoms and long-term virus recovery occur, but the underlying mechanisms are poorly understood. Here, we found that wild-type Cucumber mosaic virus (CMVWT) invaded the SAM transiently, but was subsequently eliminated from the meristems. Unexpectedly, a CMV mutant, designated CMVRA that harbors an alanine substitution in the N-terminal arginine-rich region of the coat protein (CP) persistently invaded the SAM and resulted in visible reductions in apical dominance...
July 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28724761/isg15-modulates-type-i-interferon-signaling-and-antiviral-response-during-hepatitis-e-virus-replication
#6
Harini Sooryanarain, Adam J Rogers, Dianjun Cao, Mary Etna R Haac, Yogesh A Karpe, Xiang-Jin Meng
Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes a self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals especially in solid organ transplant recipients. Innate immunity, via type-I interferon (IFN) response, plays an important role during initial stages of a viral infection. ISG15, an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role, as well as can impart a direct antiviral effect against a wide spectrum of virus families...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724212/the-effects-of-microrna-98-inhibits-cell-proliferation-and-invasion-by-targeting-stat3-in-nasopharyngeal-carcinoma
#7
Juying Liu, Wei Chen, Zhenzhang Chen, Jing Wen, Hongliang Yu, Feijiang Wang, Lirong Wu, Xia He
MicroRNA-98 (miR-98) is downregulated in many tumors, and is closely related to tumor progression. In addition, it shows anticarcinogenic functions in various tumor. However, few study show that the biological function and regulatory mechanisms of miR-98 in nasopharyngeal carcinoma (NPC) progression. The identification and its target genes which regulate by dysregulated miRNAs may strengthen our understanding of the molecular mechanisms of NPC. In this study, we observe that miR-98 is not only significantly reduced in NPC tissues, but also decreased markedly in NPC cell lines...
July 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28721629/epha3-targeting-reduces-in-vitro-adhesion-and-invasion-and-in-vivo-growth-and-angiogenesis-of-multiple-myeloma-cells
#8
Francesco La Rocca, Irma Airoldi, Emma Di Carlo, Pina Marotta, Geppino Falco, Vittorio Simeon, Ilaria Laurenzana, Stefania Trino, Luciana De Luca, Katia Todoerti, Oreste Villani, Martin Lackmann, Fiorella D'Auria, Francesco Frassoni, Antonino Neri, Luigi Del Vecchio, Pellegrino Musto, Daniela Cilloni, Antonella Caivano
PURPOSE: Multiple myeloma (MM) is a hematologic malignancy characterized by a clonal expansion of plasma cells (PCs) in the bone marrow (BM). Since MM has so far remained incurable, further insights into its pathogenesis and the concomitant identification of new therapeutic targets are urgently needed. The tyrosine kinase receptor EphA3 is known to be involved in various cellular processes including cell viability, cell movement and cell-cell interactions. Recently, EphA3 has emerged as a potential therapeutic target in several hematologic and solid tumors...
July 18, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28720543/involvement-of-the-bh3-only-pro-apoptotic-bik-nbk-in-braf-mek-inhibitor-induced-apoptosis-in-melanoma-cell-lines
#9
Andreas Borst, Sebastian Haferkamp, Johannes Grimm, Manuel Rösch, Guannan Zhu, Sen Guo, Chunying Li, Tianwen Gao, Svenja Meierjohann, David Schrama, Roland Houben
In patients with BRAF-mutated melanoma specific inhibitors of BRAF(V600E) and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse. As demonstrated previously, BRAF(V600E)-inhibition induces apoptosis only in a fraction of treated cells, while the remaining arrest and survive providing a source or a niche for relapse. To identify factors contributing to the differential initial response towards BRAF/MEK inhibition, we established M14 melanoma cell line-derived single cell clones responding to treatment with BRAF inhibitor vemurafenib and MEK inhibitor trametinib predominantly with either cell cycle arrest (CCA-cells) or apoptosis (A-cells)...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28713871/immune-dysfunctionality-of-replicative-senescent-mesenchymal-stromal-cells-is-corrected-by-ifn%C3%AE-priming
#10
Raghavan Chinnadurai, Devi Rajan, Spencer Ng, Kenneth McCullough, Dalia Arafat, Edmund K Waller, Larry J Anderson, Greg Gibson, Jacques Galipeau
Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro. IFNγ does not upregulate HLA-DR on senescent MSCs, whereas its silencing did not reverse fit MSCs' immunosuppressive properties...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/28712920/amelioration-of-cirrhotic-portal-hypertension-by-targeted-cyclooxygenase-1-sirna-delivery-to-liver-sinusoidal-endothelium-with-polyethylenimine-grafted-hyaluronic-acid
#11
Liteng Lin, Mingyue Cai, Shaohui Deng, Wensou Huang, Jingjun Huang, Xinghua Huang, Mingsheng Huang, Yong Wang, Xintao Shuai, Kangshun Zhu
Portal hypertension (PH), a leading cause of mortality in cirrhosis, lacks effective clinical therapeutic strategies. The increased thromboxane A2 (TXA2), derived primarily from the upregulation of cyclooxygenase-1 (COX-1) in cirrhotic liver sinusoidal endothelial cells (LSECs), is responsible for hepatic endothelial dysfunction and PH. Thus, blocking the COX-1 pathway in cirrhotic LSECs may benefit the treatment of PH. In this study, hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for the targeted delivery of COX-1 siRNA to LSECs...
July 13, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28709980/downregulation-of-usp18-inhibits-growth-and-induces-apoptosis-in-hepatitis-b-virus-related-hepatocellular-carcinoma-cells-by-suppressing-bcl2l1
#12
Jing Cai, Tiande Liu, Xiaoliu Jiang, Changkuo Guo, Anwen Liu, Xinlan Xiao
Ubiquitin-specific peptidase 18 (USP18) is closely related with hepatitis B virus (HBV), which has been involved in tumourigenesis. However, there has been little research into the role of USP18 on the progression of hepatocellular carcinoma (HCC), especially in HBV-related HCC. In present study, we found that USP18 expression was aberrantly elevated in HCC tissues than adjacent non-tumour tissues. Importantly, USP18 expression was higher in HBV-related HCC cell lines (HepG2.2.15 and Hep3B) than HBV-unrelated HCC cell lines...
July 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28706445/histone-demethylase-kdm2b-upregulates-histone-methyltransferase-ezh2-expression-and-contributes-to-the-progression-of-ovarian-cancer-in-vitro-and-in-vivo
#13
Yan Kuang, Fangfang Lu, Jianfeng Guo, Hong Xu, Qi Wang, Chaohuan Xu, Longjia Zeng, Suyi Yi
Aberrant histone methylation contributes to the progression and development of many tumors. Histone methylation is a dynamic process regulated by both histone demethylase and histone methyltransferase, which ultimately alters the levels of gene transcription. However, the relationship between histone demethylase and histone methyltransferase, as well as their regulatory mechanisms in ovarian cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays a role in tumorigenesis via epigenetic mechanisms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28706295/dgk%C3%AE-triggers-endoplasmic-reticulum-release-of-ift88-containing-vesicles-destined-for-the-assembly-of-primary-cilia
#14
Jie Ding, Lei Shao, Yixing Yao, Xin Tong, Huaize Liu, Shen Yue, Lu Xie, Steven Y Cheng
The morphogenic factor Sonic hedgehog (Shh) signals through the primary cilium, which relies on intraflagellar transport to maintain its structural integrity and function. However, the process by which protein and lipid cargos are delivered to the primary cilium from their sites of synthesis still remains poorly characterized. Here, we report that diacylglycerol kinase δ (DGKδ), a residential lipid kinase in the endoplasmic reticulum, triggers the release of IFT88-containing vesicles from the ER exit sites (ERES), thereby setting forth their movement to the primary cilium...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705721/characterization-of-nlrp3-like-gene-from-apostichopus-japonicus-provides-new-evidence-on-inflammation-response-in-invertebrates
#15
Zhimeng Lv, Zhixin Wei, Zhen Zhang, Chenghua Li, Yina Shao, Weiwei Zhang, Xuelin Zhao, Ye Li, Xuemei Duan, Jinbo Xiong
Inflammatory/defensive response after pathogen invasion is considered a local defense reaction in vertebrates. Inflammation response in Apostichopus japonicus was hardly determined due to scarce information available for nucleotide binding domain-like receptor family, pyrin domain-containing (NLRP) family. In the present study, invertebrate NLRP homologue was identified from A. japonicus (designated as AjNLRP3-like) by rapid amplification of cDNA ends. Full-length cDNA of AjNLRP3-like measured 2970 bp with 2265 bp open reading frame encoding a 754-amino acid (aa) residue protein...
July 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28703810/microrna-148a-deficiency-promotes-hepatic-lipid-metabolism-and-hepatocarcinogenesis-in-mice
#16
Li Cheng, Yahui Zhu, Han Han, Qiang Zhang, Kaisa Cui, Hongxing Shen, Jinxiang Zhang, Jun Yan, Edward Prochownik, Youjun Li
miRNAs are involved in many physiologic and disease processes by virtue of degrading specific mRNAs or inhibiting their translation. miR-148a has been implicated in the control of tumor growth and cholesterol and triglyceride homeostasis using in vitro or in vivo gene expression- and silencing-based approaches. Here miR-148a knockout (KO) mice were used to investigate the intrinsic role of miR-148a in liver physiology and hepatocarcinogenesis in mice. miR-148a downregulation was found to be correlated with poor clinical outcomes in hepatocellular carcinoma (HCC) patients...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28702322/mitochondrial-transcription-factor-b2-is-essential-for-mitochondrial-and-cellular-function-in-pancreatic-%C3%AE-cells
#17
Lisa M Nicholas, Bérengère Valtat, Anya Medina, Lotta Andersson, Mia Abels, Inês G Mollet, Deepak Jain, Lena Eliasson, Nils Wierup, Malin Fex, Hindrik Mulder
OBJECTIVE: Insulin release from pancreatic β-cells is controlled by plasma glucose levels via mitochondrial fuel metabolism. Therefore, insulin secretion is critically dependent on mitochondrial DNA (mtDNA) and the genes it encodes. Mitochondrial transcription factor B2 (TFB2M) controls transcription of mitochondrial-encoded genes. However, its precise role in mitochondrial metabolism in pancreatic β-cells and, consequently, in insulin secretion remains unknown. METHODS: To elucidate the role of TFB2M in mitochondrial function and insulin secretion in vitro and in vivo, mice with a β-cell specific homozygous or heterozygous knockout of Tfb2m and rat clonal insulin-producing cells in which the gene was silenced were examined with an array of metabolic and functional assays...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28698491/microrna-signature-of-human-microvascular-endothelium-infected-with-rickettsia-rickettsii
#18
Abha Sahni, Hema P Narra, Jignesh Patel, Sanjeev K Sahni
MicroRNAs (miRNAs) mediate gene silencing by destabilization and/or translational repression of target mRNA. Infection of human microvascular endothelial cells as primary targets of Rickettsiarickettsii, the etiologic agent of Rocky Mountain spotted fever, triggers host responses appertaining to alterations in cellular gene expression. Microarray-based profiling of endothelial cells infected with R.rickettsii for 3 or 24 h revealed differential expression of 33 miRNAs, of which miRNAs129-5p, 200a-3p, 297, 200b-3p, and 595 were identified as the top five up-regulated miRNAs (5 to 20-fold, p ≤ 0...
July 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28698141/epigenetic-silencing-of-the-wnt-antagonist-apcdd1-by-promoter-dna-hyper-methylation-contributes-to-osteosarcoma-cell-invasion-and-metastasis
#19
Weifeng Han, Junpeng Liu
Osteosarcoma (OS) is the most common type of bone tumor in children and adults. However, the molecular mechanism underlying OS tumorigenesis remains unclear. Here, we report that the expression of APCDD1, a Wnt antagonist, was reduced in OS tissues and cells compared to adjacent normal tissue and osteoblast cells, respectively. Mechanistically, this was due to increased levels of methylation in the promoter region of the APCDD1 gene. Consistently, the DNA methyltransferase inhibitor 5-AZA-dC, reduced DNA methylation in the APCDD1 promoter, and restored APCDD1 expression in OS tissue and cells...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28694771/nupr1-modulates-methamphetamine-induced-dopaminergic-neuronal-apoptosis-and-autophagy-through-chop-trib3-mediated-endoplasmic-reticulum-stress-signaling-pathway
#20
Xiang Xu, Enping Huang, Yunchun Tai, Xu Zhao, Xuebing Chen, Chuanxiang Chen, Rui Chen, Chao Liu, Zhoumeng Lin, Huijun Wang, Wei-Bing Xie
Methamphetamine (METH) is an illegal and widely abused psychoactive stimulant. METH exposure causes detrimental effects on multiple organ systems, primarily the nervous system, especially dopaminergic pathways, in both laboratory animals and humans. In this study, we hypothesized that Nuclear protein 1 (Nupr1/com1/p8) is involved in METH-induced neuronal apoptosis and autophagy through endoplasmic reticulum (ER) stress signaling pathway. To test this hypothesis, we measured the expression levels of Nupr1, ER stress protein markers CHOP and Trib3, apoptosis-related protein markers cleaved-caspase3 and PARP, as well as autophagy-related protein markers LC3 and Beclin-1 in brain tissues of adult male Sprague-Dawley (SD) rats, rat primary cultured neurons and the rat adrenal pheochromocytoma cells (PC12 cells) after METH exposure...
2017: Frontiers in Molecular Neuroscience
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