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https://www.readbyqxmd.com/read/28922680/pivotal-role-of-tnf-%C3%AE-in-the-development-and-progression-of-nonalcoholic-fatty-liver-disease-in-a-murine-model
#1
Satomi Kakino, Tsuyoshi Ohki, Hitomi Nakayama, Xiahong Yuan, Shuichi Otabe, Toshihiko Hashinaga, Nobuhiko Wada, Yayoi Kurita, Kayo Tanaka, Kento Hara, Eri Soejima, Yuji Tajiri, Kentaro Yamada
Previously, we have shown that the adipocyte-specific nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c) transgenic mice spontaneously developed hepatic lesions that are similar to those of human nonalcoholic steatohepatitis (NASH) with a concomitant elevation of plasma TNF-α. In this study, we analyzed the role of TNF-α in the progression of nonalcoholic fatty liver disease (NAFLD). We established a Tnf knockout nSREBP-1c transgenic mouse line. Glucose tolerance and liver histology were examined at the age of 20 weeks...
September 18, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28922151/dickkopf-3-dkk3-improves-amyloid-%C3%AE-pathology-cognitive-dysfunction-and-cerebral-glucose-metabolism-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#2
Li Zhang, Caixian Sun, Yaxi Jin, Kai Gao, Xudong Shi, Wenying Qiu, Chao Ma, Lianfeng Zhang
Dysfunctional Wnt signaling is associated with Alzheimer's disease (AD), and activation of the Wnt signaling pathway inhibits AD development. Dickkopf 3 (Dkk3) is a modulator of the Wnt signaling pathway and is physiologically expressed in the brain. The role of Dkk3 in the pathogenesis of AD has not been evaluated. In the present study, we determined that Dkk3 expression was significantly decreased in brain tissue from AD patients and the AD transgenic mouse model APPswe/PS1dE9 (AD mice). Transgenic mice with brain tissue-specific Dkk3 expression were generated or crossed with AD mice to study the effects of Dkk3 on AD...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921569/murine-red-blood-cells-from-genetically-distinct-donors-cross-regulate-when-stored-together
#3
Ariel Hay, Heather L Howie, Hayley R Waterman, Karen de Wolski, James C Zimring
BACKGROUND: Donor variability of red blood cell (RBC) storage has been observed in both humans and animal models. We utilized a strain of mice with RBCs known to store well (B6) and a strain known to store poorly (FVB) to test the hypothesis that RBCs affected the storage of other RBCs. STUDY DESIGN AND METHODS: Five strains of mice were used: 1) transgenic B6 mice expressing green fluorescent protein (GFP) in their RBCs (GFP.B6), 2) wild-type B6 mice, 3) wild-type FVB mice, 4) F1 crosses between GFP...
September 16, 2017: Transfusion
https://www.readbyqxmd.com/read/28920936/dopamine-induces-soluble-%C3%AE-synuclein-oligomers-and-nigrostriatal-degeneration
#4
Danielle E Mor, Elpida Tsika, Joseph R Mazzulli, Neal S Gould, Hanna Kim, Malcolm J Daniels, Shachee Doshi, Preetika Gupta, Jennifer L Grossman, Victor X Tan, Robert G Kalb, Kim A Caldwell, Guy A Caldwell, John H Wolfe, Harry Ischiropoulos
Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28920716/transposons-moving-forward-from-preclinical-studies-to-clinical-trials
#5
Jaitip Tipanee, Thierry VandenDriessche, Marinee K Chuah
Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein...
August 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28920078/notch1-activation-depletes-the-pool-of-side-population-stem-cells-in-atl
#6
Xue Tao Bai, Chien-Hung Yeh, Christophe Nicot
BACKGROUND: HTLV-I infection is associated with the development of adult T-cell leukemia (ATL), a malignancy characterized by a high rate of disease relapse and poor survival. Previous studies reported the existence of side population (SP) cells in HTLV-I Tax transgenic mouse models. These studies showed that these ATL-like derived SP cells have both self-renewal and leukemia renewal capacity and represent Cancer Stem Cells (CSC)/Leukemia-Initiating Cells (LIC). Since CSC/LIC are resistant to conventional therapies, a better characterization is needed...
June 2017: Journal of Cancer Sciences
https://www.readbyqxmd.com/read/28919467/distribution-of-spleen-tyrosine-kinase-and-tau-phosphorylated-at-tyrosine-18-in-a-mouse-model-of-tauopathy-and-in-the-human-hippocampus
#7
Christoph Köhler, Vivien Timpa, Maja Dinekov
PURPOSE: Spleen tyrosine kinase (Syk) has been shown to phosphorylate tyrosine 18 of tau in vitro. It has been proposed that increased immunoreactivity for double-phosphorylated Syk in hippocampal neurons of Alzheimer's disease cases indicates a not yet defined neurodegenerative process. To investigate this possibility we have studied Syk and tau phosphorylated at tyrosine 18 (pTyr18) in transgenic mice and human hippocampi. METHODS: We performed immunohistochemistry, immunofluorescence labeling and Western blotting and compared the distribution of Syk double-phosphorylated at tyrosines 525 and 526 and pTyr18 in human tau transgenic pR5 mice and human hippocampi with low and high Braak stages for neurofibrillary tangle pathology...
September 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28919464/corticothalamic-network-dysfunction-and-alzheimer-s-disease
#8
Rohan Jagirdar, Jeannie Chin
Alzheimer's disease (AD) is a devastating neurodegenerative disease that is characterized by progressive cognitive decline and a prominent loss of hippocampal-dependent memory. Therefore, much focus has been placed on understanding the function and dysfunction of the hippocampus in AD. However, AD is also accompanied by a number of other debilitating cognitive and behavioral alterations including deficits in attention, cognitive processing, and sleep maintenance. The underlying mechanisms that give rise to impairments in such diverse behavioral domains are unknown, and identifying them would shed insight into the multifactorial nature of AD as well as reveal potential new therapeutic targets to improve overall function in AD...
September 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28919264/prolactin-alters-the-mammary-epithelial-hierarchy-increasing-progenitors-and-facilitating-ovarian-steroid-action
#9
Kathleen A O'Leary, Michael P Shea, Stephanie Salituro, Courtney E Blohm, Linda A Schuler
Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation...
September 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28918256/transgene-is-specifically-and-functionally-expressed-in-retinal-inhibitory-interneurons-in-the-vgat-chr2-eyfp-mouse
#10
Guo-Zhong Xu, Ling-Jie Cui, Ai-Lin Liu, Wei Zhou, Xue Gong, Yong-Mei Zhong, Xiong-Li Yang, Shi-Jun Weng
Ectopic transgene expression in the retina has been reported in various transgenic mice, indicating the importance of characterizing retinal phenotypes. We examined transgene expression in the VGAT-ChR2-EYFP mouse retina by fluorescent immunohistochemistry and electrophysiology, with special emphasis on EYFP localization in retinal neuronal subtypes identified by specific markers. Strong EYFP signals were detected in both the inner and outer plexiform layers. In addition, the ChR2-EYFP fusion protein was also expressed in somata of the great majority of inhibitory interneurons, including horizontal cells and GABAergic and glycinergic amacrine cells...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28917978/sen1500-a-novel-oral-amyloid-%C3%AE-aggregation-inhibitor-attenuates-brain-pathology-in-a-mouse-model-of-alzheimer-s-disease
#11
D Brunner, S Flunkert, J Neddens, S Duller, D I C Scopes, J M Treherne, B Hutter-Paier
INTRODUCTION: Amyloid-β (Aβ) aggregation is thought to be a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The development of new drugs inhibiting the Aβ aggregation process is, therefore, important. SEN1500, an orally bioavailable and CNS-penetrant Aβ aggregation inhibitor, has previously been shown to reduce spatial learning and memory deficits in an APP transgenic mouse model. To verify that the pharmacological properties of SEN1500 are not unique to this model, we investigated brain Aβ pathology, neuroinflammation, as well as memory in a different mouse model of AD expressing the human amyloid precursor protein with Swedish and London mutations (APPSL)...
September 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28917666/hippocampal-neurophysiology-is-modified-by-a-disease-associated-c-terminal-fragment-of-tau-protein
#12
Francesco Tamagnini, Darren A Walsh, Jon T Brown, Marie K Bondulich, Diane P Hanger, Andrew D Randall
The accumulation of cleaved tau fragments in the brain is associated with several tauopathies. For this reason, we recently developed a transgenic mouse that selectively accumulates a C-Terminal 35 kDa human tau fragment (Tau35). These animals develop progressive motor and spatial memory impairment, paralleled by increased hippocampal glycogen synthase kinase 3β activity. In this neurophysiological study, we focused on the CA1 subfield of the hippocampus, a brain area involved in memory encoding. The accumulation of Tau35 results in a significant increase of short-term facilitation of the synaptic response in the theta frequency range (10 Hz), without affecting basal synaptic transmission and long-term synaptic plasticity...
July 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28917531/hollow-microneedle-mediated-intradermal-delivery-of-model-vaccine-antigen-loaded-plga-nanoparticles-elicits-protective-t-cell-mediated-immunity-to-an-intracellular-bacterium
#13
Anne Marit de Groot, Guangsheng Du, Juha Mönkäre, Anouk C M Platteel, Femke Broere, Joke A Bouwstra, Alice J A M Sijts
The skin is an attractive organ for immunization due to the presence of a large number of epidermal and dermal antigen-presenting cells. Hollow microneedles allow for precise and non-invasive intradermal delivery of vaccines. In this study, ovalbumin (OVA)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles with and without TLR3 agonist poly(I:C) were prepared and administered intradermally by hollow microneedles. The capacity of the PLGA nanoparticles to induce a cytotoxic T cell response, contributing to protection against intracellular pathogens, was examined...
September 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28916638/pharmacological-and-physiological-assessment-of-serotonin-formation-and-degradation-in-isolated-preparations-from-mouse-and-human-heart
#14
Ulrich Gergs, Franziska Jung, Igor B Buchwalow, Britt Hofmann, Andreas Simm, Hendrik Treede, Joachim Neumann
Using transgenic mice (TG) that overexpress the human 5-HT4a-receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor, 5-hydroxy-tryptophan (5-HTP), can exert inotropic and chronotropic effects in cardiac preparations from TG but not from wild type (WT): similar results were found in human atrial preparations, as well as in intact TG animals using echocardiography...
September 15, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28916165/muc1-deficiency-exacerbates-pulmonary-fibrosis-in-a-mouse-model-of-silicosis
#15
Kosuke Kato, Marina A Zemskova, Alec D Hanss, Marianne M Kim, Sandra J Gendler, Ross Summer, Kwang Chul Kim
BACKGROUND: MUC1 (MUC in human and Muc in animals) is a membrane-tethered mucin expressed on the apical surface of lung epithelial cells. However, in the lungs of patients with interstitial lung disease, MUC1 is aberrantly expressed in hyperplastic alveolar type II epithelial (ATII) cells and alveolar macrophages (AM), and elevated levels of extracellular MUC1 are found in bronchoalveolar lavage (BAL) fluid and the serum of these patients. While pro-fibrotic effects of extracellular MUC1 have recently been described in cultured fibroblasts, the contribution of MUC1 to the pathobiology of pulmonary fibrosis is unknown...
September 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28915137/xenoislets-porcine-pancreatic-islets-for-the-treatment-of-type-i-diabetes
#16
Nizar I Mourad, Pierre Rene Gianello
PURPOSE OF REVIEW: Porcine islets are being extensively investigated as alternative sources of insulin-secreting cells for transplantation in insulin-dependent diabetic patients. The present review focuses on recent advances in porcine islet transplantation with particular emphasis on new transgenic pig models, islet encapsulation, and biosafety considerations. RECENT FINDINGS: Genetic modifications aimed to reduce islet cell immunogenicity, to prolong their survival, and to improve their secretory function have been reported...
September 14, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28914974/mucocutaneous-inflammation-in-the-ikaros-family-zinc-finger-1-ikzf1-keratin-5-specifc-transgenic-mice
#17
Mayumi Ueta, Junji Hamuro, Hiromi Nishigaki, Naomi Nakamura, Katsuhiko Shinomiya, Katsura Mizushima, Yuki Hitomi, Risa Tamagawa-Mineoka, Norihiko Yokoi, Yuji Naito, Katsushi Tokunaga, Norito Katoh, Chie Sotozono, Shigeru Kinoshita
BACKGROUND: Our genome-wide association study documented an association between cold medicine related Stevens-Johnson syndrome / toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation. METHODS: Human skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis...
September 15, 2017: Allergy
https://www.readbyqxmd.com/read/28913973/bone-marrow-stem-cells-do-not-contribute-to-endometrial-cell-lineages-in-chimeric-mouse-models
#18
Yih Rue Ong, Fiona L Cousins, Xiaoqing Yang, Ahmed Aedh A Al Mushafi, David T Breault, Caroline E Gargett, James A Deane
Studies from five independent laboratories conclude that bone marrow stem cells transdifferentiate into endometrial stroma, epithelium and endothelium. We investigated the nature of bone marrow-derived cells in the mouse endometrium by reconstituting irradiated wild type recipients with bone marrow containing transgenic mTert-GFP or chicken β-actin-GFP reporters. mTert-GFP is a telomerase marker identifying hematopoietic stem cells and subpopulations of epithelial, endothelial and immune cells in the endometrium...
September 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/28913798/agrobacterium-mediated-transformation-of-wheat-using-immature-embryos
#19
Goetz Hensel, Cornelia Marthe, Jochen Kumlehn
Methods of the Agrobacterium-mediated transformation of bread wheat (Triticum aestivum L.) have been improved in recent years so that genetic engineering can be routinely used for functional genomics as well as for wheat breeding. In the protocol described here, immature embryos of the spring-type model genotype Bobwhite SH 98 26 have been used. Preculture and temperature pretreatment of these explants have led to the reproducible generation of transgenic plants at efficiencies between 5 and 15%. Whereas primary transgenic plants regenerated in vitro commonly show reduced fitness and fertility, no apparent variations with regard to morphology and grain set in their transgenic progeny as compared to wild-type counterparts were observed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28913572/establishment-of-s100a8-transgenic-rats-to-understand-innate-property-of-s100a8-and-its-immunological-role
#20
Kohki Okada, Hiroshi Itoh, Yasuhiko Kamikubo, Souichi Adachi, Masaki Ikemoto
The innate properties of S100A8 as a regulator in acute inflammation have not yet been elucidated in detail. Our aims are to newly establish S100A8 transgenic rats (Tg-S100A8) and to elucidate the immunological functions of S100A8. Following the treatment with 5% dextran sulfate sodium for 1 week, the body weight in Tg-S100A8 weakly decreased after the start; however, that in Japanese Wistar rats (WT) significantly decreased in the end. The serum level of CRP in Tg-S100A8 was significantly lower than that in WT, although the concentration of CRP apparently increased in both Tg-S100A8 and WT...
September 14, 2017: Inflammation
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