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https://www.readbyqxmd.com/read/28329685/critical-role-for-gab2-in-neuroblastoma-pathogenesis-through-the-promotion-of-shp2-mycn-cooperation
#1
Xiaoling Zhang, Zhiwei Dong, Cheng Zhang, Choong Yong Ung, Shuning He, Ting Tao, Andre M Oliveira, Alexander Meves, Baoan Ji, A Thomas Look, Hu Li, Benjamin G Neel, Shizhen Zhu
Growing evidence suggests a major role for Src-homology-2-domain-containing phosphatase 2 (SHP2/PTPN11) in MYCN-driven high-risk neuroblastoma, although biologic confirmation and a plausible mechanism for this contribution are lacking. Using a zebrafish model of MYCN-overexpressing neuroblastoma, we demonstrate that mutant ptpn11 expression in the adrenal gland analog of MYCN transgenic fish promotes the proliferation of hyperplastic neuroblasts, accelerates neuroblastomagenesis, and increases tumor penetrance...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327181/soluble-oligomeric-amyloid-%C3%AE-induces-calcium-dyshomeostasis-that-precedes-synapse-loss-in-the-living-mouse-brain
#2
Michal Arbel-Ornath, Eloise Hudry, Josiah R Boivin, Tadafumi Hashimoto, Shuko Takeda, Kishore V Kuchibhotla, Steven Hou, Carli R Lattarulo, Arianna M Belcher, Naomi Shakerdge, Pariss B Trujillo, Alona Muzikansky, Rebecca A Betensky, Bradley T Hyman, Brian J Bacskai
BACKGROUND: Amyloid-β oligomers (oAβ) are thought to mediate neurotoxicity in Alzheimer's disease (AD), and previous studies in AD transgenic mice suggest that calcium dysregulation may contribute to these pathological effects. Even though AD mouse models remain a valuable resource to investigate amyloid neurotoxicity, the concomitant presence of soluble Aβ species, fibrillar Aβ, and fragments of amyloid precursor protein (APP) complicate the interpretation of the phenotypes. METHOD: To explore the specific contribution of soluble oligomeric Aβ (oAβ) to calcium dyshomeostasis and synaptic morphological changes, we acutely exposed the healthy mouse brain, at 3 to 6 months of age, to naturally occurring soluble oligomers and investigated their effect on calcium levels using in vivo multiphoton imaging...
March 21, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28327131/transcriptome-analysis-of-pancreatic-cells-across-distant-species-highlights-novel-important-regulator-genes
#3
Estefania Tarifeño-Saldivia, Arnaud Lavergne, Alice Bernard, Keerthana Padamata, David Bergemann, Marianne L Voz, Isabelle Manfroid, Bernard Peers
BACKGROUND: Defining the transcriptome and the genetic pathways of pancreatic cells is of great interest for elucidating the molecular attributes of pancreas disorders such as diabetes and cancer. As the function of the different pancreatic cell types has been maintained during vertebrate evolution, the comparison of their transcriptomes across distant vertebrate species is a means to pinpoint genes under strong evolutionary constraints due to their crucial function, which have therefore preserved their selective expression in these pancreatic cell types...
March 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/28326089/dynamic-regulation-of-auxin-response-during-rice-development-revealed-by-newly-established-hormone-biosensor-markers
#4
Jing Yang, Zheng Yuan, Qingcai Meng, Guoqiang Huang, Christophe Périn, Charlotte Bureau, Anne-Cécile Meunier, Mathieu Ingouff, Malcolm J Bennett, Wanqi Liang, Dabing Zhang
The hormone auxin is critical for many plant developmental processes. Unlike the model eudicot plant Arabidopsis (Arabidopsis thaliana), auxin distribution and signaling in rice tissues has not been systematically investigated due to the absence of suitable auxin response reporters. In this study we observed the conservation of auxin signaling components between Arabidopsis and model monocot crop rice (Oryza sativa), and generated complementary types of auxin biosensor constructs, one derived from the Aux/IAA-based biosensor DII-VENUS but constitutively driven by maize ubiquitin-1 promoter, and the other termed DR5-VENUS in which a synthetic auxin-responsive promoter (DR5rev ) was used to drive expression of the yellow fluorescent protein (YFP)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28325782/aibp-limits-angiogenesis-thorough-%C3%AE-secretase-mediated-upregulation-of-notch-signaling
#5
Renfang Mao, Shu Meng, Qilin Gu, Raquel Araujo-Gutierrez, Sandeep Kumar, Qing Yan, Felicidad Almazan, Keith A Youker, Yingbin Fu, Henry J Pownall, John P Cooke, Yury I Miller, Longhou Fang
Rationale: Angiogenesis improves perfusion to the ischemic tissue following acute vascular obstruction. Angiogenesis in pathophysiological settings reactivates signaling pathways involved in developmental angiogenesis. We showed previously that apoA-I binding protein (AIBP)-regulated cholesterol efflux in endothelial cells (ECs) controls zebrafish embryonic angiogenesis. Objective: This study is to determine whether loss of AIBP affects angiogenesis in mice during development and under pathological conditions, and to explore the underlying molecular mechanism...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28324007/aberrant-tgf-%C3%AE-signaling-drives-castration-resistant-prostate-cancer-in-a-male-mouse-model-of-prostate-tumorigenesis
#6
Hong Pu, Diane Begemann, Natasha Kyprianou
The androgen receptor (AR) plays a critical role as a driver of castration-resistant-prostate cancer (CRPC). Our previous studies demonstrated that disruption of transforming growth factor-β (TGF-β) signaling via introduction of dominant-negative TGF-β type II receptor (DNTGF-RβII) in the prostate epithelium of transgenic adenocarcinoma of the prostate (TRAMP) mice accelerated tumor. This study investigated the consequences of disrupted TGF-β signaling on prostate tumor growth under conditions of castration-induced androgen deprivation (ADT) in the pre-clinical model DNTGFβRII...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323022/astrocyte-heme-oxygenase-1-reduces-mortality-and-improves-outcome-after-collagenase-induced-intracerebral-hemorrhage
#7
Jing Chen-Roetling, Pramod Kamalapathy, Yang Cao, Wei Song, Hyman M Schipper, Raymond F Regan
Pharmacotherapies that increase CNS expression of heme oxygenase-1 (HO-1) and other antioxidant proteins have improved outcome in experimental models of spontaneous intracerebral hemorrhage (ICH). In order to more specifically investigate the relationship between HO-1 and ICH outcome, mice expressing human HO-1 driven by the glial fibrillary acidic protein (GFAP) promoter (GFAP·HMOX1 mice) were tested in a model of in situ parenchymal hemorrhage. Injection of collagenase into the striata of wild-type (WT) mice resulted in a 26...
March 17, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28320965/deficiency-of-a-sulfotransferase-for-sialic-acid-modified-glycans-mitigates-alzheimer-s-pathology
#8
Zui Zhang, Yoshiko Takeda-Uchimura, Tahmina Foyez, Shiori Ohtake-Niimi, Narentuya, Hiroyasu Akatsu, Kazuchika Nishitsuji, Makoto Michikawa, Tony Wyss-Coray, Kenji Kadomatsu, Kenji Uchimura
We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer's disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125-220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320590/multitep-platform-based-dna-epitope-vaccine-targeting-n-terminus-of-tau-induces-strong-immune-responses-and-reduces-tau-pathology-in-thy-tau22-mice
#9
Hayk Davtyan, Wesley W Chen, Karen Zagorski, Joy Davis, Irina Petrushina, Konstantin Kazarian, David H Cribbs, Michael G Agadjanyan, Mathew Blurton-Jones, Anahit Ghochikyan
BACKGROUND: By the time clinical symptoms of Alzheimer's disease (AD) manifest in patients there is already substantial tau pathology in the brain. Recent evidence also suggests that tau pathology can become self-propagating, further accelerating disease progression. Over the last decade several groups have tested the efficacy of protein-based anti-tau immunotherapeutics in various animal models of tauopathy. Here we report on the immunological and therapeutic potency of the first anti-tau DNA vaccine based on the MultiTEP platform, AV-1980D, in THY-Tau22 transgenic mice...
March 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28320412/high-resolution-hemodynamic-profiling-of-murine-arteriovenous-fistula-using-magnetic-resonance-imaging-and-computational-fluid-dynamics
#10
Daniel Pike, Yan-Ting Shiu, Maheshika Somarathna, Lingling Guo, Tatyana Isayeva, John Totenhagen, Timmy Lee
BACKGROUND: Arteriovenous fistula (AVF) maturation failure remains a major cause of morbidity and mortality in hemodialysis patients. The two major etiologies of AVF maturation failure are early neointimal hyperplasia development and persistent inadequate outward remodeling. Although hemodynamic changes following AVF creation may impact AVF remodeling and contribute to neointimal hyperplasia development and impaired outward remodeling, detailed AVF hemodynamics are not yet fully known...
March 20, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28320098/inhibition-of-tissue-transglutaminase-attenuates-lipopolysaccharide-induced-inflammation-in-glial-cells-through-akt-mtor-signal-pathway
#11
Yirong Ding, Ji Zhang, Rui Wang
AIM: In view of the facts that tTG protein expression level and its enzyme activity increase in AD brains of both individuals and transgenic animals and compelling evidence of the involvement of inflammation in AD pathogenesis, tTG could be involved in the inflammation responses in the brain. In the present study, we examined the effects of the irreversible and the competitive inhibitor of tTG on the condition of lipopolysaccharide-induced mimic inflammation models in glial cells. METHODS: Western blot and tTG enzyme activity assay were applied to detect tTG and isopeptide protein levels and tTG enzyme activity...
March 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28318232/histology-compatible-maldi-mass-spectrometry-based-imaging-of-neuronal-lipids-for-subsequent-immunofluorescent-staining
#12
Ibrahim Kaya, Wojciech Michno, Dimitri Brinet, Yasmine Iacone, Giulia Zanni, Kaj Blennow, Henrik Zetterberg, Jörg Hanrieder
Matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results...
March 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28317868/hsp70-1-is-required-for-interleukin-5-induced-angiogenic-responses-through-enos-pathway
#13
Sung Lyea Park, Tae-Wook Chung, Sangtae Kim, Byungdoo Hwang, Jung Min Kim, Hwan Myung Lee, Hee-Jae Cha, Yoonhee Seo, Soo Young Choe, Ki-Tae Ha, Gonhyung Kim, Seok-Joong Yun, Sung-Soo Park, Yung Hyun Choi, Bo Kyung Kim, Won-Tae Kim, Eun-Jong Cha, Cam Patterson, Wun-Jae Kim, Sung-Kwon Moon
We report a pivotal role for IL-5 as an angiogenic activator. IL-5 increased proliferation, migration and colony tube formation in HUVECs associated with the phosphorylation of ERK and AKT/eNOS, and promoted microvessel sprouting from an angiogenesis animal model. The angiogenic effects were confirmed in IL-5-deficient mice and addition of IL-5 antibody. HSP70-1 was identified via expression profiling following IL-5 stimulation. A siRNA knockdown of HSP70-1 suppressed angiogenic responses and eNOS phosphorylation induced by IL-5...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317486/abnormal-clock-gene-expression-and-locomotor-activity-rhythms-in-two-month-old-female-appswe-ps1de9-mice
#14
Olaide Oyegbami, Hilary M Collins, Marie C Pardon, Fran Jp Ebling, David M Heery, Paula M Moran
In addition to cognitive decline, Alzheimer's disease (AD) is also characterized by agitation and disruptions in activity and sleep. These symptoms typically occur in the evening or at night and have been referred to as 'sundowning'. These symptoms are especially difficult for carers and there are no specific drug treatments. There is increasing evidence that these symptoms reflect an underlying pathology of circadian rhythm generation and transmission. We investigated whether a transgenic mouse model relevant to AD (APPswe/PS1dE9) exhibits circadian alterations in locomotor activity and expression of clock genes involved in the regulation of the circadian cycle...
March 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28316877/progression-of-pro23his-retinopathy-in-a-miniature-swine-model-of-retinitis-pigmentosa
#15
Patrick A Scott, Juan P Fernandez de Castro, Paul J DeMarco, Jason W Ross, Josephat Njoka, Eric Walters, Randall S Prather, Maureen A McCall, Henry J Kaplan
PURPOSE: We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy. METHODS: The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age...
March 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28316134/feruloylation-and-structure-of-arabinoxylan-in-wheat-endosperm-cell-walls-from-rnai-lines-with-suppression-of-genes-responsible-for-backbone-synthesis-and-decoration
#16
Jackie Freeman, Jane L Ward, Ondrej Kosik, Alison Lovegrove, Mark D Wilkinson, Peter R Shewry, Rowan A C Mitchell
Arabinoxylan (AX) is the major component of the cell walls of wheat grain (70% in starchy endosperm) and is an important determinant of end-use qualities affecting food processing, use for animal feed and distilling and is a major source of dietary fibre in the human diet. AX is a heterogeneous polysaccharide composed of fractions which can be sequentially extracted by water (WE-AX), then xylanase action (XE-AX) leaving an unextractable (XU-AX) fraction. We determined arabinosylation and feruloylation of AX in these fractions in both wild-type wheat and RNAi lines with decreased AX content (TaGT43_2 RNAi, TaGT47_2 RNAi) or decreased arabinose 3-linked to mono-substituted xylose (TaXAT1 RNAi)...
March 17, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28316108/cry1a-b-16-toxin-from-bacillus-thuringiensis-theoretical-refinement-of-three-dimensional-structure-and-prediction-of-peptides-as-molecular-markers-for-detection-of-genetically-modified-organisms
#17
Alexandra Plácido, Andreia Coelho, Lucas Abreu do Nascimento, Andreanne Gomes Vasconcelos, Maria Fátima Barroso, Joilson Ramos-Jesus, Vladimir Costa, Francisco das Chagas Alves Lima, Cristina Delerue-Matos, Ricardo Martins Ramos, Mariela M Marani, José Roberto de Souza de Almeida Leite
Transgenic maize produced by the insertion of the Cry transgene into its genome became the second most cultivated crop worldwide. Cry gene from Bacillus thuringiensis kurstaki expresses protein derivatives of crystalline endotoxins which confer insect resistance onto the maize crop. Mandatory labeling of processed food containing or made by genetically modified organisms is in force in many countries, so, it is very urgent to develop fast and practical methods for GMO identification, e.g., biosensors. In the absence of an available empirical structure of Cry1A(b)16 protein, a theoretical model was effectively generated, in this work, by homology modeling and molecular dynamics simulations based on two available homologous protein structures...
March 18, 2017: Proteins
https://www.readbyqxmd.com/read/28315782/human-comt-over-expression-confers-a-heightened-susceptibility-to-dyskinesia-in-mice
#18
Oscar Solís, Jose-Rubén García-Montes, Patricia Garcia-Sanz, Antonio S Herranz, Maria-José Asensio, Gina Kang, Noboru Hiroi, Rosario Moratalla
Catechol-O-methyltransferase (COMT) degrades dopamine and its precursor l-DOPA and plays a critical role in regulating synaptic dopamine actions. We investigated the effects of heightened levels of COMT on dopamine-regulated motor behaviors and molecular alterations in a mouse model of dyskinesia. Transgenic mice overexpressing human COMT (TG) and their wildtype (WT) littermates received unilateral 6-OHDA lesions in the dorsal striatum and were treated chronically with l-DOPA for two weeks. l-DOPA-induced dyskinesia was exacerbated in TG mice without altering l-DOPA motor efficacy as determined by contralateral rotations or motor coordination...
March 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28315274/role-of-%C3%AF-1-receptors-in-learning-and-memory-and-alzheimer-s-disease-type-dementia
#19
Tangui Maurice, Nino Goguadze
The present chapter will review the role of σ1 receptor in learning and memory and neuroprotection , against Alzheimer's type dementia. σ1 Receptor agonists have been tested in a variety of pharmacological and pathological models of learning impairments in rodents these last past 20 years. Their anti-amnesic effects have been explained by the wide-range modulatory role of σ1 receptors on Ca(2+) mobilizations, neurotransmitter responses, and particularly glutamate and acetylcholine systems, and neurotrophic factors...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315264/the-evolution-of-the-sigma-2-%C3%AF-2-receptor-from-obscure-binding-site-to-bona-fide-therapeutic-target
#20
Chenbo Zeng, Robert H Mach
The sigma-2 (σ2) receptor represents one of the most poorly understood proteins in cell biology. Although this receptor was identified through in vitro binding studies over 25 years ago, the molecular identity of this protein is currently not unambiguously known, and the results from recent attempts to identify the σ2 receptor through protein purification and mass spectral analysis have been the subject of debate in the literature. However, there is overwhelming data demonstrating that the σ2 receptor is an important biomarker of tumor cell proliferation ...
2017: Advances in Experimental Medicine and Biology
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