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https://www.readbyqxmd.com/read/29332044/does-the-genetic-feature-of-the-chinese-tree-shrew-tupaia-belangeri-chinensis-support-its-potential-as-a-viable-model-for-alzheimer-s-disease-research
#1
Yu Fan, Rongcan Luo, Ling-Yan Su, Qun Xiang, Dandan Yu, Ling Xu, Jia-Qi Chen, Rui Bi, Dong-Dong Wu, Ping Zheng, Yong-Gang Yao
Alzheimer's disease (AD) is a neurodegenerative disease with increasing incidence across the world and no cure at the present time. An ideal animal model would facilitate the understanding of the pathogenesis of AD and discovery of potential therapeutic targets. The Chinese tree shrew (Tupaia belangeri chinensis) has a closer genetic affinity to primates relative to rodents, and can attain ages of 8 years or older, which represents another advantage for the study of neurodegenerative diseases such as AD compared to primates...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331866/development-of-a-novel-equine-influenza-virus-live-attenuated-vaccine
#2
Laura Rodriguez, Stephanie Reedy, Aitor Nogales, Pablo R Murcia, Thomas M Chambers, Luis Martinez-Sobrido
H3N8 equine influenza virus (EIV) is an important and significant respiratory pathogen of horses. EIV is enzootic in Europe and North America, mainly due to the suboptimal efficacy of current vaccines. We describe, for the first time, the generation of a temperature sensitive (ts) H3N8 EIV live-attenuated influenza vaccine (LAIV) using reverse-genetics approaches. Our EIV LAIV was attenuated (att) in vivo and able to induce, upon a single intranasal administration, protection against H3N8 EIV wild-type (WT) challenge in both a mouse model and the natural host, the horse...
January 11, 2018: Virology
https://www.readbyqxmd.com/read/29331419/the-therapeutic-potential-of-human-adipose-derived-mesenchymal-stem-cells-producing-cxcl10-in-a-mouse-melanoma-lung-metastasis-model
#3
Hamed Mirzaei, Hossein Salehi, Reza Kazemi Oskuee, Ali Mohammadpour, Hamid Reza Mirzaei, Mohammad Reza Sharifi, Reza Salarinia, Hossein Yousofi Darani, Mojgan Mokhtari, Aria Masoudifar, Amirhossein Sahebkar, Rasoul Salehi, Mahmoud Reza Jaafari
Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330804/in-vivo-manipulation-of-hif-1%C3%AE-expression-during-glioma-genesis
#4
Patricia D B Tiburcio, Séan B Lyne, L Eric Huang
Hypoxia has long been recognized as a driving force of tumor progression and therapeutic resistance, and the transcription factor HIF-1α is believed to play a crucial role in these processes. Here we describe an efficient RCAS/Nes-TVA system that allows for in vivo manipulation of HIF-1α expression in the mouse neural progenitor cells. Simple production of the recombinant avian virus RCAS enables quick delivery of gene of interest through injection into the neural progenitors of transgenic mice expressing the viral cognate receptor TVA under the nestin promoter...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330472/amyloid-deposition-in-a-mouse-model-humanized-at-the-transthyretin-and-retinol-binding-protein-4-loci
#5
Xiangshun Li, Yanyi Lyu, Jingling Shen, Yanshuang Mu, Lixia Qiang, Li Liu, Kimi Araki, Bruno P Imbimbo, Ken-Ichi Yamamura, Shoude Jin, Zhenghua Li
Familial amyloidotic polyneuropathy is an autosomal dominant disorder caused by a point mutation in the transthyretin (TTR) gene. The process of TTR amyloidogenesis begins with rate-limiting dissociation of the TTR tetramer. Thus, the TTR stabilizers, such as Tafamidis and Diflunisal, are now in clinical trials. Mouse models will be useful to testing the efficacy of these drugs. Although several mouse models have been generated, they all express mouse Rbp4. Thus, human TTR associates with mouse RBP4, resulting in different kinetic and thermodynamic stability profiles of TTR tetramers...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29330205/clinical-utility-of-a-stat3-regulated-microrna-200-family-signature-with-prognostic-potential-in-early-gastric-cancer
#6
Liang Yu, Di Wu, Hugh Gao, Jesse Balic, Anna Tsykin, Tae-Su Han, You Dong Liu, Catherine Lydia Kennedy, Ji-Kun Li, Jie-Qi Mao, Patrick Tan, Masanobu Oshima, Gregory J Goodall, Brendan J Jenkins
PURPOSE: The majority of gastric cancer (GC) patients are diagnosed with late stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early stage GC (EGC) because the molecular events promoting GC initiation remain ill-defined. EXPERIMENTAL DESIGN: miRNA microarrays were performed on gastric tissue from the gp130F/F preclinical EGC mouse model, prior to tumor initiation...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#7
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29329488/genetic-and-molecular-insights-into-genotype-phenotype-relationships-in-osteopathia-striata-with-cranial-sclerosis-oscs-through-the-analysis-of-novel-mouse-wtx-mutant-alleles
#8
Glenda Comai, Agnès Boutet, Kristina Tanneberger, Filippo Massa, Ana-Sofia Rocha, Aurelie Charlet, Clara Panzolini, Fariba Jian Motamedi, Robert Brommage, Wolfgang Hans, Thomas Funck-Brentano, Martin Hrabe de Angelis, Christine Hartmann, Martine Cohen-Solal, Jürgen Behrens, Andreas Schedl
The X-linked WTX/AMER1 protein forms an important component of the β-catenin destruction complex that can both enhance and suppress canonical β-catenin signalling. Somatic mutations in WTX/AMER1 have been found in a proportion of the pediatric kidney cancer Wilms' tumour. By contrast, germline mutations cause the severe sclerosing bone dysplasia osteopathia striata congenita with cranial sclerosis (OSCS), a condition usually associated with fetal or perinatal lethality in male patients. Here we addressed the developmental and molecular function of WTX by generating two novel mouse alleles...
January 12, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29329433/rage-mediates-a%C3%AE-accumulation-in-a-mouse-model-of-alzheimer-s-disease-via-modulation-of-%C3%AE-and-%C3%AE-secretase-activity
#9
Fang Fang, Qing Yu, Ottavio Arancio, Doris Chen, Smruti S Gore, Shi Fang Yan, Shirley ShiDu Yan
Receptor for Advanced Glycation End products (RAGE) has been implicated in amyloid β-peptide (Aβ)-induced perturbation relevant to the pathogenesis of Alzheimer's disease (AD). However, whether and how RAGE regulates Aβ metabolism remains largely unknown. Aβ formation arises from aberrant cleavage of amyloid precursor protein (APP) by β- and γ-secretase. To investigate whether RAGE modulates β- and γ-secretase activity potentiating Aβ formation, we generated mAPP mice with genetic deletion of RAGE (mAPP/RO)...
January 10, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29329089/neural-circuit-dysfunction-in-mouse-models-of-neurodevelopmental-disorders
#10
REVIEW
Isabel Del Pino, Beatriz Rico, Oscar Marín
Neuropsychiatric disorders arise from the alteration of normal brain developmental trajectories disrupting the function of specific neuronal circuits. Recent advances in human genetics have greatly accelerated the identification of genes whose variation increases the susceptibility for neurodevelopmental disorders, most notably for autism spectrum disorder (ASD) and schizophrenia. In parallel, experimental studies in animal models-most typically in mice-are beginning to shed light on the role of these genes in the development and function of specific brain circuits...
January 9, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29327342/reduced-lysosomal-clearance-of-autophagosomes-promotes-survival-and-colonization-of-helicobacter-pylori
#11
Lin Zhang, Wei Hu, Chi H Cho, Francis K L Chan, Jun Yu, J Ross Fitzgerald, Cynthia K Y Cheung, Zhan G Xiao, Jing Shen, Long F Li, Ming X Li, Justin C Y Wu, Thomas K W Ling, Jason Y K Chan, Ko Ho, Gary Tse, Siew C Ng, Sidney Yu, Maggie H T Wang, Tony Gin, Hassan Ashktorab, Duane T Smoot, Sunny H Wong, Matthew T V Chan, William K K Wu
Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori-infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacologic ablation of autophagy in mouse and cell line models of H...
January 12, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#12
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29322421/immuno-detection-of-immature-and-bioactive-forms-of-the-inflammatory-cytokine-il-18
#13
Brendan J Jenkins, Virginie Deswaerte
Gastric cancer (GC) is the third most lethal cancer worldwide, and like many other types of cancers, it is associated with precursory chronic inflammatory responses. In the context of many inflammation-associated cancers such as GC, activation of the innate immune response by infectious microbes and/or host-derived molecules is often characterized by production of the cytokines interleukin (IL)-1β and IL-18, which can often have divergent and opposing (i.e., pro or anti) roles in inflammation and oncogenesis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29322407/modelling-intestinal-carcinogenesis-using-in-vitro-organoid-cultures
#14
Thierry Jardé, Genevieve Kerr, Reyhan Akhtar, Helen E Abud
Mouse models of intestinal carcinogenesis are very powerful for studying the impact of specific mutations on tumour initiation and progression. Mutations can be studied both singularly and in combination using conditional alleles that can be induced in a temporal manner. The steps in intestinal carcinogenesis are complex and can be challenging to image in live animals at a cellular level. The ability to culture intestinal epithelial tissue in three-dimensional organoids in vitro provides an accessible system that can be genetically manipulated and easily visualised to assess specific biological impacts in living tissue...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321651/auditory-neural-activity-in-congenitally-deaf-mice-induced-by-infrared-neural-stimulation
#15
Xiaodong Tan, Israt Jahan, Yingyue Xu, Stuart Stock, Changyow Claire Kwan, Carmen Soriano, Xianghui Xiao, Jaime García-Añoveros, Bernd Fritzsch, Claus-Peter Richter
To determine whether responses during infrared neural stimulation (INS) result from the direct interaction with spiral ganglion neurons (SGNs), we tested three genetically modified deaf mouse models: Atoh1-cre; Atoh1 f/f (Atoh1 conditional knockout, CKO), Atoh1-cre; Atoh1 f/kiNeurog1 (Neurog1 knockin, KI), and the Vglut3 knockout (Vglut3 -/-) mice. All animals were exposed to tone bursts and clicks up to 107 dB (re 20 µPa) and to INS, delivered with a 200 µm optical fiber. The wavelength (λ) was 1860 nm, the radiant energy (Q) 0-800 µJ/pulse, and the pulse width (PW) 100-500 µs...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321615/functional-isolation-of-tumor-initiating-cells-using-microfluidic-based-migration-identifies-phosphatidylserine-decarboxylase-as-a-key-regulator
#16
Yu-Chih Chen, Brock Humphries, Riley Brien, Anne E Gibbons, Yu-Ting Chen, Tonela Qyli, Henry R Haley, Matthew E Pirone, Benjamin Chiang, Annie Xiao, Yu-Heng Cheng, Yi Luan, Zhixiong Zhang, Jason Cong, Kathryn E Luker, Gary D Luker, Euisik Yoon
Isolation of tumor-initiating cells currently relies on markers that do not reflect essential biologic functions of these cells. We proposed to overcome this limitation by isolating tumor-initiating cells based on enhanced migration, a function tightly linked to tumor-initiating potential through epithelial-to-mesenchymal transition (EMT). We developed a high-throughput microfluidic migration platform with automated cell tracking software and facile recovery of cells for downstream functional and genetic analyses...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321372/chronic-skin-inflammation-accelerates-macrophage-cholesterol-crystal-formation-and-atherosclerosis
#17
Yvonne Baumer, Qimin Ng, Gregory E Sanda, Amit K Dey, Heather L Teague, Alexander V Sorokin, Pradeep K Dagur, Joanna I Silverman, Charlotte L Harrington, Justin A Rodante, Shawn M Rose, Nevin J Varghese, Agastya D Belur, Aditya Goyal, Joel M Gelfand, Danielle A Springer, Christopher Ke Bleck, Crystal L Thomas, Zu-Xi Yu, Mårten Cg Winge, Howard S Kruth, M Peter Marinkovich, Aditya A Joshi, Martin P Playford, Nehal N Mehta
Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29321164/kras-oncoprotein-expression-is-regulated-by-a-self-governing-eif5a-peak1-feed-forward-regulatory-loop
#18
Ken Fujimura, Huawei Wang, Felicia Watson, Richard L Klemke
There remains intense interest in tractable approaches to target or silence the KRAS oncoprotein as a rational therapeutic strategy to attack pancreatic adenocarcinoma (PDAC) and other cancers which overexpress it. Here we provide evidence that accumulation of the KRAS oncoprotein is controlled by a self-regulating feed-forward regulatory loop that utilizes a unique hypusinated isoform of the translation elongation factor eIF5A and the tyrosine kinase PEAK1. Oncogenic activation of KRAS increased eIF5A-PEAK1 translational signaling, which in turn facilitated increased KRAS protein synthesis...
January 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29321129/novel-reversible-model-of-atherosclerosis-and-regression-using-oligonucleotide-regulation-of-the-ldl-receptor
#19
Debapriya Basu, Yunying Hu, Lesley-Ann Huggins, Adam E Mullick, Mark J Graham, Tomasz A Wietecha, Shelley L Barnhart, Allison Mogul, Katharina Pfeiffer, Andreas Zirlik, Edward A Fisher, Karin E Bornfeldt, Florian Willecke, Ira J Goldberg
Rationale: Animal models have been used to explore factors that regulate atherosclerosis. More recently, they have been used to study the factors that promote loss of macrophages and reduction in lesion size after lowering of plasma cholesterol levels. However, current animal models of atherosclerosis regression require challenging surgeries, time-consuming breeding strategies, and/or methods that block liver lipoprotein secretion. Objective: We sought to develop a more direct and time-effective method to create and then reverse hypercholesterolemia as well as atherosclerosis via transient knockdown of the hepatic LDL receptor (LDLR) followed by its rapid restoration...
January 10, 2018: Circulation Research
https://www.readbyqxmd.com/read/29320870/transgenic-organisms-meet-redox-bioimaging-one-step-closer-to-physiology
#20
Lija Swain, Maithily Nanadikar, Sergej Borowik, Anke Zieseniss, Dörthe Magdalena Katschinski
SIGNIFICANCE: Redox signaling is a common mechanism in the cellular response towards a variety of stimuli. For analyzing redox-dependent specific alterations in a cell, genetically encoded biosensors were highly instrumental in the past. To advance the knowledge about the importance of this signaling mechanism in vivo, models, which are as close as possible to physiology are needed. Recent advances: The development of transgenic redox biosensor animal models has enhanced the knowledge of redox signaling under patho(physio)logical conditions...
January 10, 2018: Antioxidants & Redox Signaling
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