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Nathalie Laflamme, Paul Préfontaine, Antoine Lampron, Serge Rivest
Bone marrow transplantation is the standard of care for a host of diseases such as leukemia and multiple myeloma, as well as genetically inherited metabolic diseases affecting the central nervous system. In mouse models, bone marrow transplantation has proven a valuable tool for understanding the hematopoietic system and the homing of hematopoietic cells to their target organs. Many techniques have been developed to create chimeric mice, animals with a hematopoietic system derived from a genetic background that differs from the rest of the body...
September 17, 2018: Current Protocols in Immunology
Stefan Passlick, Ek Raj Thapaliya, Zuxin Chen, Matthew T Richers, Graham C R Ellis-Davies
KEY POINTS: We developed a new caged nicotinic acetylcholine receptor (nAChR) agonist, ABT594, which is photolyzed by one- and two-photon excitation. The caged compound is photolyzed with a quantum yield of 0.20 One-photon uncaging of ABT594 elicited large currents and Ca2+ transients at the soma and dendrites of medial habenula (MHb) neurons of mouse brain slices. Unexpectedly, uncaging of ABT594 also revealed highly Ca2+ -permeable nAChRs on axons of MHb neurons. ABSTRACT: Photochemical release of neurotransmitters has been instrumental to the study of the underlying receptors, with acetylcholine being the exception due to its inaccessibility to photochemical protection...
September 17, 2018: Journal of Physiology
Kerriann M Casey, Amanda L Johnson, Melea N Hunrath, Jenelle K Fraser, Nicole C McCowan, Katherine Wasson, Rosalinda A Doty, Stephen M Griffey, Denise M Imai
Beginning in 2015, athymic nude sentinel mice from conventional, medium-, and high-security facilities presented to the Comparative Pathology Laboratory (CPL) with weight loss, diarrhea, and/or rectal prolapse. Regardless of whether clinical signs were present or absent, the gross observation of ceco-colonic thickening corresponded histologically to pleocellular typhlocolitis with mucosal hyperplasia and lamina proprial multinucleated cells. A subset of affected sentinels exhibited granulomatous serositis and hepatosplenic necrosis with multinucleated cells...
September 16, 2018: Veterinary Pathology
Jordon M Inloes, Hui Jing, Benjamin F Cravatt
Deleterious mutations in the serine hydrolase DDHD domain containing 1 (DDHD1) cause the SPG28 subtype of the neurological disease hereditary spastic paraplegia (HSP), which is characterized by axonal neuropathy and gait impairments. DDHD1 has been shown to display PLA1-type phospholipase activity with a preference for phosphatidic acid. However, the endogenous lipid pathways regulated by DDHD1 in vivo remain poorly understood. Here we use a combination of untargeted and targeted metabolomics to compare the lipid content of brain tissue from DDHD1+/+ and DDHD1-/- mice, revealing that DDHD1 inactivation causes a substantial decrease in the level of polyunsaturated lysophosphatidylinositol (LPI) lipids and a corresponding increase in the level of phosphatidylinositol (PI) lipids...
September 17, 2018: Biochemistry
Xinyu Hu, Shanshan Teng, Jiawei He, Xiaoqi Sun, Mingzhao Du, Ling Kou, Xiaofeng Wang
Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an L‑glutamic acid (L‑Glu)‑damaged HT22 cell apoptosis model and an aluminum chloride plus D‑galactose‑induced AD mouse model. In L‑Glu‑damaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase‑3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase‑3 activity assay kit, and propidium iodide and Annexin V staining...
September 13, 2018: Molecular Medicine Reports
Xiaotong Wang, Xiaopeng Cui, Chuanwu Zhu, Ming Li, Juan Zhao, Zhongyi Shen, Xiaohang Shan, Liang Wang, Han Wu, Yanting Shen, You Ni, Dongmei Zhang, Guoxiong Zhou
Endoplasmic reticulum (ER) stress in intestinal epithelial cells (IECs) has an important role in the pathogenesis of Crohn's disease (CD). FK506 binding protein 11 (FKBP11), a member of the peptidyl‑prolyl cis‑trans isomerase family, is involved in the unfolded protein response (UPR) and is closely associated with inflammation. Previous bioinformatics analysis revealed a potential association between FKBP11 and human CD. Thus, the present study aimed to investigate the potential significance of FKBP11 in IEC homeostasis and CD...
September 14, 2018: Molecular Medicine Reports
Jiancheng Xi, Qinggui Li, Xiaobo Luo, Jinlong Li, Lixin Guo, Haibin Xue, Guangsen Wu
Epigallocatechin‑3‑gallate (EGCG) is a polyphenolic compound extracted and isolated from green tea, which has a variety of important biological activities in vitro and in vivo, including anti‑tumor, anti‑oxidation, anti‑inflammation and lowering blood pressure. The aim of the present study was to investigate the protective effect of EGCG against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were used to analyze runt‑related transcription factor 2 and osterix mRNA expression, and the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression...
September 3, 2018: Molecular Medicine Reports
Lin Shen, Li Li, Man Li, Weiling Wang, Wenbin Yin, Wei Liu, Yanyan Hu
The aim of the present study was to investigate the role of the nucleotide‑binding oligomerization domain (NOD) 2 in high glucose (HG)‑induced myocardial apoptosis and fibrosis in mice. Mouse models of diabetes were induced by streptozotocin (STZ). NOD2 expression was knocked down by injection of lentivirus‑mediated short‑hairpin RNA. Alternatively, small interfering RNA‑NOD2 was transfected into cardiomyocytes and cardiac fibroblasts (CFs). A hemodynamic assay was used to assess the cardiac function in the mouse model...
September 14, 2018: International Journal of Molecular Medicine
Ricardo Imbroisi Filho, Daniel T G Gonzaga, Thaina M Demaria, Joao G B Leandro, Dora C S Costa, Vitor F Ferreira, Mauro Sola-Penna, Fernando de C da Silva, Patricia Zancan
BACKGROUND: Cancer is a major cause of death worldwide, despite the many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. RESULTS: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells...
September 16, 2018: Current Topics in Medicinal Chemistry
Price E Dickson, Tyler A Roy, Kathryn A McNaughton, Troy D Wilcox, Padam Kumar, Elissa J Chesler
Sensation seeking is a multifaceted, heritable trait which predicts the development of substance use and abuse in humans; similar phenomena have been observed in rodents. Genetic correlations among sensation seeking and substance use indicate shared biological mechanisms, but the genes and networks underlying these relationships remain elusive. Here, we used a systems genetics approach in the BXD RI mouse panel to identify shared genetic mechanisms underlying substance use and preference for sensory stimuli, an intermediate phenotype of sensation seeking...
September 17, 2018: Genes, Brain, and Behavior
Peng-Yang Hsu, Hui-Ju Yang, Tao-Hsiang Yang, Che-Chun Su
Psoriasis is a chronic autoimmune disease with keratinocyte activation and lymphocyte infiltration in the skin. Our previous study found that 5-hydroxytrytophan (5(OH)Trp), a tryptophan metabolite alleviated collagen-induced arthritis and suppressed cytokine production. In this study, we evaluated the effects of 5(OH)Trp in a mouse model for psoriasiform dermatitis, induced by imiquimod (IMQ). We showed that 5(OH)Trp significantly reduced the cumulative scores, epidermal thickness, and ki-67 expression in the skin...
September 16, 2018: Experimental Dermatology
Michael P Gallagher, James M Conley, Leslie J Berg
Circulating naive T cells exist in a quiescent state. After TCR contact with the cognate peptide presented by APCs in secondary lymphoid structures, T cells undergo a period of rapid transcriptional changes that set the stage for fate-determining effector or memory programming. We describe a novel method to analyze TCR signaling pathway activation in nuclei isolated from primary mouse naive T cells after stimulation with natural peptide Ags. We prelabeled cells with cell tracking dye to easily distinguish CD8+ T cell nuclei from APC nuclei by conventional flow cytometry...
August 2018: ImmunoHorizons
F Li, J L Chen, X L Zeng, H R Bao, X J Liu
Objective: To investigate the effects of Toll-like receptor 4 (TLR4)-phosphatidylinositol 3-kinase (PI3K) -Ras-related C3 botulinum toxin 1 (Rac1) signaling pathway on macrophage cytoskeleton rearrangement and phagocytosis. Methods: Mouse macrophage cell line RAW264.7 was divided into blank group, negative control group and TLR4-RNA interference (RNAi) group. The lentivirus carrying TLR4 short hairpin RNA (shRNA) and nonsense control sequence were respectively transfected into TLR4-RNAi group and negative control group...
September 11, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
J Ding, Q Li, Y M Niu, W M Tong
Objective: To investigate the biological functions of protein phosphatase 2AC(PP2AC) in the brain, and to detect its spatio-temporal expression and its involvement in neurological disorders in the brains of mice and Alzheimer's patients. Methods: Western blot was used to evaluate the expression level of PP2AC in different organs. Immunohistochemical staining was performed to detect the in situ expression levels of PP2AC in the brains of mice and patients, and the pathological changes were confirmed in the brains of patients with Alzheimer's disease...
September 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Iris F Macheleidt, Priya S Dalvi, So-Young Lim, Sonja Meemboor, Lydia Meder, Olivia Käsgen, Marion Müller, Karolin Kleemann, Lingyu Wang, Peter Nürnberg, Vanessa Rüsseler, Stephan C Schäfer, Esther Mahabir, Reinhard Büttner, Margarete Odenthal
Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Despite the development of novel targeted and immune therapies, the five-year survival rate is still only 21%, necessitating more efficient treatment regimens. Lysine-specific demethylase 1 (LSD1) is an epigenetic eraser which modifies histone 3 methylation status, and is highly overexpressed in LUAD. Using representative human cell culture systems and two autochthonous transgenic mouse models, we investigated inhibition of LSD1 as a novel therapeutic option to treat LUAD...
September 16, 2018: Molecular Oncology
Faith I Uwadiae, Chloe J Pyle, Simone A Walker, Clare M Lloyd, James A Harker
BACKGROUND: Allergic asthma is characterized by chronic inflammation and remodelling of the airways, associated with dysregulated type 2 immune responses and allergen-specific IgE. T follicular helper cells (TFH ) are crucial in T-dependent B cell responses and have been implicated in allergic airway disease (AAD). TFH , unlike other CD4+ T cells are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T cell priming, therefore disrupting this signal can impair TFH responses...
September 16, 2018: Allergy
Katarzyna Skowrońska, Marta Obara-Michlewska, Anna Czarnecka, Katarzyna Dąbrowska, Magdalena Zielińska, Jan Albrecht
Astrocytes express N-methyl-D-aspartate (NMDA) receptor (NMDAR) but its functions in these cells are not well defined. This study shows that the sustained exposure (8-72 h) of mouse astrocytes to NMDA decreases the expression of the functional astroglia-specific proteins, glutamine synthetase (GS), and the water channel protein aquaporin-4 (AQP4) and also reduces GS activity. Similar to rat astrocytes (Obara-Michlewska et al. Neurochem Int 88:20-25, 2015), the exposure of mouse astrocytes to NMDA also decreased the expression of the inward rectifying potassium channel Kir4...
September 15, 2018: Neurotoxicity Research
Eunice W M Chin, Wee Meng Lim, Dongliang Ma, Francisco J Rosales, Eyleen L K Goh
Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Choline, a dietary micronutrient found in most foods, has been shown to be important for brain development and function. However, the exact effects and mechanisms are still unknown. We found that 13 mg/day (1.7 × required daily intake) of postnatal choline treatment to Mecp2-conditional knockout mice rescued not only deficits in motor coordination, but also their anxiety-like behaviour and reduced social preference...
September 15, 2018: Molecular Neurobiology
Xiao-Bin Zhang, Jing-Huang Cai, Yu-Yun Yang, Yi-Ming Zeng, Hui-Qing Zeng, Miao Wang, Xiao Cheng, Xiongbiao Luo, Henry Chidozie Ewurum
PURPOSE: Obstructive sleep apnea (OSA) is associated with renal impairs. As a novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH) enhances apoptosis and autophagy. The present study aims to evaluate the effect of telmisartan on CIH-induced kidney apoptosis and autophagy in a mouse model of OSA. MATERIALS AND METHODS: Mice were randomly allocated to normoxia, CIH, and CIH+telmisartan groups (n = 12 in each group). The CIH exposure duration was 12 weeks...
September 15, 2018: Sleep & Breathing, Schlaf & Atmung
Adriana Marcelo, Filipa Brito, Sara Carmo-Silva, Carlos A Matos, João Alves-Cruzeiro, Ana Vasconcelos-Ferreira, Rebekah Koppenol, Liliana Mendonça, Luís Pereira Almeida, Clévio Nóbrega
Machado-Joseph disease (MJD) is a neurodegenerative disorder, caused by an abnormal expansion of CAG trinucleotide repeats in the disease-causing gene. This mutation leads to an abnormal polyglutamine tract in the protein ataxin-3, resulting in formation of mutant ataxin-3 aggregates. Despite several attempts to develop a therapeutic option for MJD, currently there are no available therapies capable of delaying or stopping disease progression. Recently, our group reported that reducing the expression levels of mutant ataxin-3 lead to a mitigation of several MJD-related behavior and neuropathological abnormalities...
September 13, 2018: Human Molecular Genetics
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