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Michiyo Deushi, Mizuko Osaka, Kaku Nakano, Kyoichi Osada, Kensuke Egashira, Masayuki Yoshida
Oxidized cholesterol (oxysterols) plays an important and multifaceted role in lipid metabolism. Here we examined whether dietary oxysterols accelerate hepatic lipid accumulation and inflammation in nonhuman primates. We also examined the effect of the Niemann-Pick C1-like1 inhibitor, ezetimibe (Ez). Macaca fascicularis (5-year-old males) were fed either regular cholesterol + high-fat diet (control-HFD) or oxysterols + high-fat diet (ox-HFD; with 0.015% of oxysterols cholesterol) for 24 weeks. Compared with control-HFD, ox-HFD did not affect plasma lipid levels, but it did affect hepatic lipid levels [total cholesterol, 40...
October 2016: FEBS Open Bio
Takeshi Funakoshi, Toshihiko Aki, Masateru Tajiri, Kana Unuma, Koichi Uemura
Aberrant cellular accumulation of cholesterol is associated with neuronal lysosomal storage disorders such as Niemann-Pick disease Type C (NPC). We have shown previously that l-norephedrine (l-Nor), a sympathomimetic amine, induces necrotic cell death associated with massive cytoplasmic vacuolation in SH-SY5Y human neuroblastoma cells. To reveal the molecular mechanism underling necrotic neuronal cell death caused by l-Nor, we examined alterations in the gene expression profile of cells during l-Nor exposure...
October 18, 2016: Journal of Biological Chemistry
Glennah Kerubo, Evans Amukoye, Stefan Niemann, Samuel Kariuki
BACKGROUND: Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in slums. Slum environments create a conducive environment for the spread of tuberculosis (TB) due to high population density and lack of basic amenities such as decent housing, access to clean water, lack of drainage and basic sanitation. Furthermore, ineffective health services in crowded and poorer populations, poor patient compliance, a large pool of untreated cases, delayed diagnosis and inappropriate treatment regimens are likely to favour selection and spread of drug resistant Mycobacterium tuberculosis (Mtb) strains in such settings, however, precise data on this problem are only sparsely available...
October 19, 2016: BMC Infectious Diseases
R Rabl, A Horvath, C Breitschaedel, S Flunkert, H Roemer, B Hutter-Paier
BACKGROUND: Evaluation of motor deficits in rodents is mostly restricted to limb motor tests that are often high stressors for the animals. NEW METHOD: To test rodents for orofacial motor impairments in a stress-free environment, we established the pasta gnawing test by measuring the biting noise of mice that eat a piece of spaghetti. Two parameters were evaluated, the biting speed and the biting peaks per biting episode. To evaluate the power of this test compared to commonly used limb motor and muscle strength tests, three mouse models of Parkinson's disease, amyotrophic lateral sclerosis and Niemann pick disease were tested in the pasta gnawing test, RotaRod and wire suspension test...
October 13, 2016: Journal of Neuroscience Methods
Claudia Niemann, Ben Godde, Claudia Voelcker-Rehage
Physical activity is positively related to cognitive functioning and brain volume in older adults. Interestingly, different types of physical activity vary in their effects on cognition and on the brain. For example, dancing has become an interesting topic in aging research, as it is a popular leisure activity among older adults, involving cardiovascular and motor fitness dimensions that can be positively related to cognition. However, studies on brain structure are missing. In this study, we tested the association of long-term senior dance experience with cognitive performance and gray matter brain volume in older women aged 65 to 82 years...
2016: Neural Plasticity
Yuki Kondo, Hiroko Tokumaru, Yoichi Ishitsuka, Tomoko Matsumoto, Makiko Taguchi, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Muneaki Matsuo, Katsumi Higaki, Kousaku Ohno, Tetsumi Irie
No abstract text is available yet for this article.
October 9, 2016: Molecular Genetics and Metabolism
Yan-Feng Zhou, Matthew C Metcalf, Scott C Garman, Tim Edmunds, Huawei Qiu, Ronnie R Wei
Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann-Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site...
October 11, 2016: Nature Communications
Tracey G Simon, Kathleen E Corey, Raymond T Chung, Robert Giugliano
Nonalcoholic fatty liver disease (NAFLD) is widely considered to be the hepatic manifestation of the metabolic syndrome and is closely linked to dyslipidemia, obesity, and insulin resistance. Patients with NAFLD have increased mortality when compared to the general population, primarily related to cardiovascular disease or malignancy. The biologic mechanisms that link NAFLD to cardiovascular disease include expansion of visceral adipose tissue, atherogenic dyslipidemia, impaired insulin signaling, systemic inflammation, and endothelial dysfunction...
October 6, 2016: Digestive Diseases and Sciences
Constantin Brinkmann, Inga Nehlmeier, Kerstin Walendy-Gnirß, Julia Nehls, Mariana González Hernández, Markus Hoffmann, Xiangguo Qiu, Ayato Takada, Michael Schindler, Stefan Pöhlmann
: The glycoprotein of Ebola virus (EBOV-GP), a member of the Filoviridae family, facilitates viral entry into target cells. In addition, EBOV-GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV-release from infected cells. However, it is unclear how EBOV-GP antagonizes tetherin and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV-GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells...
October 5, 2016: Journal of Virology
Qinghua Yuan, Zhenyan Fu, Jian Wei, Pei-Shan Li, Hong-Hua Miao, Yu-Xiu Qu, Jie Xu, Jie Qin, Bo-Liang Li, Bao-Liang Song, Yitong Ma
BACKGROUND: Plasma levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for cardiovascular disease and are influenced by both heredity and dietary habits. The Niemann-Pick C1 like 1 (NPC1L1) protein mediates efficient dietary cholesterol absorption and contributes to variations in human LDL-C levels. METHODS: In the present study, using high throughput sequencing we identified three non-synonymous (NS) variations and 64 synonymous variations in the NPC1L1 gene from subsets of Chinese Han, Uygur and Kazakh populations with high or low LDL-C...
October 28, 2016: Biochemical and Biophysical Research Communications
Immacolata Iovinella, Liping Ban, Limei Song, Paolo Pelosi, Francesca Romana Dani
In arthropods, the large majority of studies on olfaction have been focused on insects, where most of the proteins involved have been identified. In particular, chemosensing in insects relies on two families of membrane receptors, olfactory/gustatory receptors (ORs/GRs) and ionotropic receptors (IRs), and two classes of soluble proteins, odorant-binding proteins (OBPs) and chemosensory proteins (CSPs). In other arthropods, such as ticks and mites, only IRs have been identified, while genes encoding for OBPs and CSPs are absent...
September 29, 2016: Insect Biochemistry and Molecular Biology
Robin M Ireland
No abstract text is available yet for this article.
September 29, 2016: Blood
Yoojin Seo, Hyung-Sik Kim, Insung Kang, Soon Won Choi, Tae-Hoon Shin, Ji-Hee Shin, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Myung Geun Kook, Kyung-Sun Kang
Microglia can aggravate olfactory dysfunction by mediating neuronal death in the olfactory bulb (OB) of a murine model of Niemann-Pick disease type C1 (NPC1), a fatal neurodegenerative disorder accompanied by lipid trafficking defects. In this study, we focused on the crosstalk between neurons and microglia to elucidate the mechanisms underlying extensive microgliosis in the NPC1-affected brain. Microglia in the OB of NPC1 mice strongly expressed CX3C chemokine receptor 1 (Cx3cr1), a specific receptor for the neural chemokine C-X3-C motif ligand 1 (Cx3cl1)...
September 30, 2016: Glia
Friederike Hammersen, Hildegard Niemann, Jens Hoebel
The health implications of environmental noise, especially cardiovascular effects, have been studied intensively. Research on associations between noise and mental health, however, has shown contradictory results. The present study examined associations between individual levels of noise annoyance due to noise from various sources in the living environment and mental health of adults in Germany. It evaluated whether these associations persisted after adjusting for potential covariates. Data were obtained from the cross-sectional "German Health Update" study 2012 (GEDA 2012), a national health interview survey among adults in Germany conducted by the Robert Koch Institute (n = 19,294)...
2016: International Journal of Environmental Research and Public Health
Xi Zoë Zhong, Xue Sun, Qi Cao, Gaofeng Dong, Raphael Schiffmann, Xian-Ping Dong
Efficient lysosomal Ca(2+) release plays an essential role in lysosomal trafficking. We have recently shown that lysosomal big conductance Ca(2+)-activated potassium (BK) channel forms a physical and functional coupling with the lysosomal Ca(2+) release channel Transient Receptor Potential Mucolipin-1 (TRPML1). BK and TRPML1 forms a positive feedback loop to facilitate lysosomal Ca(2+) release and subsequent lysosome membrane trafficking. However, it is unclear whether the positive feedback mechanism is common for other lysosomal storage diseases (LSDs) and whether BK channel agonists rescue abnormal lysosomal storage in LSDs...
September 27, 2016: Scientific Reports
Philip Sergelius, Johannes Gooth, Svenja Bäßler, Robert Zierold, Christoph Wiegand, Anna Niemann, Heiko Reith, Chandra Shekhar, Claudia Felser, Binghai Yan, Kornelius Nielsch
Weyl semimetals are often considered the 3D-analogon of graphene or topological insulators. The evaluation of quantum oscillations in these systems remains challenging because there are often multiple conduction bands. We observe de Haas-van Alphen oscillations with several frequencies in a single crystal of the Weyl semimetal niobium phosphide. For each fundamental crystal axis, we can fit the raw data to a superposition of sinusoidal functions, which enables us to calculate the characteristic parameters of all individual bulk conduction bands using Fourier transform with an analysis of the temperature and magnetic field-dependent oscillation amplitude decay...
September 26, 2016: Scientific Reports
Eva-Maria Kuech, Graham Brogden, Hassan Y Naim
Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes...
September 21, 2016: Biochimie
Mariana Acuña, Víctor Castro-Fernández, Mauricio Latorre, Juan Castro, Edward H Schuchman, Victoria Guixé, Mauricio González, Silvana Zanlungo
Niemann-Pick disease (NPD) type A and B are recessive hereditary disorders caused by deficiency in acid sphingomyelinase (ASM). The p.Ala359Asp mutation has been described in several patients but its functional and structural effects in the protein are unknown. In order to characterize this mutation, we modeled the three-dimensional ASM structure using the recent available crystal of the mammalian ASM as a template. We found that the p.Ala359Asp mutation is localized in the hydrophobic core and far from the sphingomyelin binding site...
October 21, 2016: Biochemical and Biophysical Research Communications
Haitang Wang, Yuen Yi C Tam, Sam Chen, Josh Zaifman, Roy van der Meel, Marco A Ciufolini, Pieter R Cullis
The therapeutic applications of lipid nanoparticle (LNP) formulations of small interfering RNA (siRNA) are hampered by inefficient delivery of encapsulated siRNA to the cytoplasm following endocytosis. Recent work has shown that up to 70% of endocytosed LNP-siRNA particles are recycled to the extracellular medium and thus cannot contribute to gene silencing. Niemann-Pick type C1 (NPC1) is a late endosomal/lysosomal membrane protein required for efficient extracellular recycling of endosomal contents. Here we assess the influence of NP3...
September 16, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Nichole Bosson, Amy H Kaji, Andrea Fang, Joseph L Thomas, William J French, David Shavelle, James T Niemann
BACKGROUND: The purpose of this study was to evaluate sex differences in out-of-hospital cardiac arrest (OHCA) characteristics, interventions, and outcomes. METHODS AND RESULTS: This is a retrospective analysis from a regionalized cardiac arrest system. Data on patients treated for OHCA are reported to a single registry, from which all adult patients were identified from 2011 through 2014. Characteristics, treatment, and outcomes were evaluated with stratification by sex...
September 2016: Journal of the American Heart Association
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