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https://www.readbyqxmd.com/read/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#1
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27911853/recurrence-of-cervical-cancer-and-its-resistance-to-progestin-therapy-in-a-mouse-model
#2
Fabiola F Mehta, Seunghan Baik, Sang-Hyuk Chung
Studies using K14E6/K14E7 transgenic mice expressing E6 and E7 oncoprotein of human papillomavirus type 16 (HPV16) have demonstrated that estrogen (E2) is required for the genesis and growth of cervical cancer. Our prior study using the same mouse model has showed that progestin drug medroxyprogesterone acetate (MPA) promotes regression of primary cervical cancer. In the present study, we use the same transgenic mouse model to determine whether the cancer recurs after MPA therapy. Cervical cancer recurred even if MPA treatment was continued...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911412/reproducible-arterial-denudation-injury-by-infrarenal-abdominal-aortic-clamping-in-a-murine-model
#3
Aditya S Shirali, Austin I McDonald, Julia J Mack, M Luisa Iruela-Arispe
Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These complications can be attributed to impairments in re-endothelialization within the wound margins. Yet, the cellular and molecular mechanisms of re-endothelialization remain to be defined. While several animal models to study re-endothelialization after arterial denudation are available, few are performed in the mouse because of surgical limitations. This undermines the opportunity to exploit transgenic mouse lines and investigate the contribution of specific genes to the process of re-endothelialization...
November 24, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911392/optogenetic-random-mutagenesis-using-histone-minisog-in-c-elegans
#4
Kentaro Noma, Yishi Jin
Forward genetic screening in model organisms is the workhorse to discover functionally important genes and pathways in many biological processes. In most mutagenesis-based screens, researchers have relied on the use of toxic chemicals, carcinogens, or irradiation, which requires designated equipment, safety setup, and/or disposal of hazardous materials. We have developed a simple approach to induce heritable mutations in C. elegans using germline-expressed histone-miniSOG, a light-inducible potent generator of reactive oxygen species...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911326/localization-and-processing-of%C3%A2-the%C3%A2-amyloid-%C3%AE-protein-precursor-in%C3%A2-mitochondria-associated-membranes
#5
Dolores Del Prete, Jan M Suski, Bénédicte Oulès, Delphine Debayle, Anne Sophie Gay, Sandra Lacas-Gervais, Renaud Bussiere, Charlotte Bauer, Paolo Pinton, Patrizia Paterlini-Bréchot, Mariusz R Wieckowski, Frédéric Checler, Mounia Chami
Alteration of mitochondria-associated membranes (MAMs) has been proposed to contribute to the pathogenesis of Alzheimer's disease (AD). We studied herein the subcellular distribution, the processing, and the protein interactome of the amyloid-β protein precursor (AβPP) and its proteolytic products in MAMs. We reveal that AβPP and its catabolites are present in MAMs in cellular models overexpressing wild type AβPP or AβPP harboring the double Swedish or London familial AD mutations, and in brains of transgenic mice model of AD...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911309/longitudinal-characterization-of-18f-fdg-and-18f-av45-uptake-in-the-double-transgenic-tastpm-mouse-model
#6
Ann-Marie Waldron, Leonie Wyffels, Jeroen Verhaeghe, Jill C Richardson, Mark Schmidt, Sigrid Stroobants, Xavier Langlois, Steven Staelens
We aimed to monitor the timing of amyloid-β deposition in relation to changes in brain function using in vivo imaging with [18F]-AV45 and [18F]-FDG in a mouse model of Alzheimer's disease. TASTPM transgenic mice and wild-type controls were scanned longitudinally with [18F]-AV45 and [18F]-FDG before (3 months of age) and at multiple time points after the onset of amyloid deposition (6, 9, 12, and 15 months of age). As expected with increasing amyloidosis, TASTPM mice demonstrated progressive age-dependent increases in [18F]-AV45 uptake that were significantly higher than for WT from 9 months onwards and correlated to ex vivo measures of amyloid burden...
November 25, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911305/nitrosylation-of-vesicular-transporters-in-brain-of-amyloid-precursor-protein-presenilin-1-double-transgenic-mice
#7
Ying Wang, Zhu Zhou, Hua Tan, Shenghua Zhu, Yiran Wang, Yingxia Sun, Xin-Min Li, Jun-Feng Wang
Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer's disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911303/amylin-treatment-reduces-neuroinflammation-and-ameliorates-abnormal-patterns-of-gene-expression-in%C3%A2-the-cerebral-cortex-of-an-alzheimer-s-disease-mouse-model
#8
Erming Wang, Haihao Zhu, Xiaofan Wang, Adam Gower, Max Wallack, Jan Krzysztof Blusztajn, Neil Kowall, Wei Qiao Qiu
Our recent study has demonstrated that peripheral amylin treatment reduces the amyloid pathology in the brain of Alzheimer's disease (AD) mouse models, and improves their learning and memory. We hypothesized that the beneficial effects of amylin for AD was beyond reducing the amyloids in the brain, and have now directly tested the actions of amylin on other aspects of AD pathogenesis, especially neuroinflammation. A 10-week course of peripheral amylin treatment significantly reduced levels of cerebral inflammation markers, Cd68 and Iba1, in amyloid precursor protein (APP) transgenic mice...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911148/effects-of-chronic-estrogen-administration-in-the-ventromedial-nucleus-of-the-hypothalamus-vmh-on-fat-and-bone-metabolism-in-ovariectomized-rats
#9
Z Zhang, J Liu, A G Veldhuis-Vlug, Y Su, E Foppen, B C J van der Eerden, M Koedam, N Bravenboer, A Kalsbeek, A Boelen, E Fliers, P H Bisschop
Estrogen deficiency after ovariectomy (OVX) results in increased adiposity and bone loss, which can be prevented by systemic 17-β estradiol (E2) replacement. Studies in transgenic mice suggested that in addition to direct actions of estrogen in peripheral tissues, also estrogen signaling in the hypothalamus regulates fat distribution and bone metabolism. We hypothesized that the protective effect of systemic E2 on fat and bone metabolism in the OVX model is partly mediated through the ventromedial nucleus of the hypothalamus (VMH)...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27910070/mig-6-mouse-model-of-endometrial-cancer
#10
Tae Hoon Kim, Jung-Yoon Yoo, Jae-Wook Jeong
Endometrial cancer is a frequently occurring gynecological disorder. Estrogen-dependent endometrioid carcinoma is the most common type of gynecological cancer. One of the major pathologic phenomena of endometrial cancer is the loss of estrogen (E2) and progesterone (P4) control over uterine epithelial cell proliferation. P4 antagonizes the growth-promoting properties of E2 in the uterus. P4 prevents the development of endometrial cancer associated with unopposed E2 by blocking E2 actions. Mitogen inducible gene 6 (Mig-6, Errfi1, RALT, or gene 33) is an immediate early response gene that can be induced by various mitogens and common chronic stress stimuli...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27910041/efficient-genome-editing-in-induced-pluripotent-stem-cells-with-engineered-nucleases-in-vitro
#11
Vittavat Termglinchan, Timon Seeger, Caressa Chen, Joseph C Wu, Ioannis Karakikes
Precision genome engineering is rapidly advancing the application of the induced pluripotent stem cells (iPSCs) technology for in vitro disease modeling of cardiovascular diseases. Targeted genome editing using engineered nucleases is a powerful tool that allows for reverse genetics, genome engineering, and targeted transgene integration experiments to be performed in a precise and predictable manner. However, nuclease-mediated homologous recombination is an inefficient process. Herein, we describe the development of an optimized method combining site-specific nucleases and the piggyBac transposon system for "seamless" genome editing in pluripotent stem cells with high efficiency and fidelity in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909192/the-more-the-merrier-scoring-statistics-and-animal-welfare-in-experimental-autoimmune-encephalomyelitis
#12
Pushpalatha Palle, Filipa M Ferreira, Axel Methner, Thorsten Buch
Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants...
December 2016: Laboratory Animals
https://www.readbyqxmd.com/read/27909098/reversible-disruption-of-neuronal-mitochondria-by-ischemic-and-traumatic-injury-revealed-by-quantitative-two-photon-imaging-in-the-neocortex-of-anesthetized-mice
#13
Mikhail Kislin, Jeremy Sword, Ioulia V Fomitcheva, Deborah Croom, Evgeny Pryazhnikov, Eero Lihavainen, Dmytro Toptunov, Heikki Rauvala, Andre S Ribeiro, Leonard Khiroug, Sergei A Kirov
: Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under such pathological conditions as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries ranging from severe to mild...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27908891/the-paraoxonase-gene-cluster-protects-against-abdominal-aortic-aneurysm-formation
#14
Yun-Fei Yan, Jian-Fei Pei, Ran Zhang, Fang Wang, Peng Gao, Zhu-Qin Zhang, Ting-Ting Wang, Yang Zhang, Zhi-Gang She, Hou-Zao Chen, De-Pei Liu
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular pathology, the pathogenesis of which is closely related to oxidative stress. However, an effective pharmaceutical treatment is lacking because the exact cause of AAA remains unknown. Here, we aimed at delineating the role of the paraoxonases (PONs) gene cluster (PC), which prevents atherosclerosis through the detoxification of oxidized substrates, in AAA formation. APPROACH AND RESULTS: PC transgenic (Tg) mice were crossed to an Apoe(-/-) background, and an angiotensin II-induced AAA mouse model was used to analyze the effect of the PC on AAA formation...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908425/copper-accumulation-in-rodent-brain-astrocytes-a-species-difference
#15
Brendan Sullivan, Gregory Robison, Yulia Pushkar, John K Young, Kebreten F Manaye
Changes in Cu homeostasis have been implicated in multiple neurodegenerative diseases. Factors controlling and regulating the distribution of Cu in the brain remain largely unknown. We have previously reported that a sub-set of astrocytes in the subventricular zone (SVZ) contain Cu-rich aggregates. Here we expand previous studies with detailed X-ray fluorescent imaging (XRF) analysis of the additional brain areas of hippocampus (HP) and rostral migratory stream (RMS). We also use conventional DAB (3,3'-diaminobenzidine) staining which accesses both peroxidase and pseudo-peroxidase activities...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27908291/muscle-pgc-1%C3%AE-modulates-satellite-cell-number-and-proliferation-by-remodeling-the-stem-cell-niche
#16
Ivana Dinulovic, Regula Furrer, Markus Beer, Arnaud Ferry, Bettina Cardel, Christoph Handschin
BACKGROUND: The myogenic capacity of satellite cells (SCs), adult muscle stem cells, is influenced by aging, exercise, and other factors. In skeletal muscle, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a key regulator of oxidative metabolism and endurance training adaptation. However, a link between PGC-1α and SC behavior remains unexplored. METHODS: We have now studied SC function in a PGC-1α fiber-specific gain-of-function animal model...
December 2, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27907905/association-of-high-microvessel-%C3%AE-v%C3%AE-3-and-low-pten-with-poor-outcome-in-stage-3-neuroblastoma-rationale-for-using-first-in-class-dual-pi3k-brd4-inhibitor-sf1126
#17
Anat Erdreich-Epstein, Alok R Singh, Shweta Joshi, Francisco M Vega, Pinzheng Guo, Jingying Xu, Susan Groshen, Wei Ye, Melissa Millard, Mihaela Campan, Guillermo Morales, Joseph R Garlich, Peter W Laird, Robert C Seeger, Hiroyuki Shimada, Donald L Durden
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but only on 34% (means) in MYCN-non-amplified tumors (p < 0.001; n = 54). PTEN, a tumor suppressor involved in αvβ3 signaling, was expressed in neuroblastomas either diffusely, focally or not at all (immunohistochemistry)...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906672/non-toxic-dose-of-liposomal-honokiol-suppresses-metastasis-of-hepatocellular-carcinoma-through-destabilizing-egfr-and-inhibiting-the-downstream-pathways
#18
Jianhong Yang, Heying Pei, Hong Luo, Afu Fu, Hansuo Yang, Jia Hu, Chengjian Zhao, LuLu Chai, Xiang Chen, Ximing Shao, Chunyu Wang, Wenshuang Wu, Li Wan, Haoyu Ye, Qiang Qiu, Aihua Peng, Yuquan Wei, Li Yang, Lijuan Chen
At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#19
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#20
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
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