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https://www.readbyqxmd.com/read/28934389/the-16p11-2-homologs-fam57ba-and-doc2a-generate-certain-brain-and-body-phenotypes
#1
Jasmine M McCammon, Alicia Blaker-Lee, Xiao Chen, Hazel Sive
Deletion of the 16p11.2 CNV affects 25 core genes and is associated with multiple symptoms affecting brain and body, including seizures, hyperactivity, macrocephaly, and obesity. Available data suggest that most symptoms are controlled by haploinsufficiency of two or more 16p11.2 genes. To identify interacting 16p11.2 genes, we used a pairwise partial loss of function antisense screen for embryonic brain morphology, using the accessible zebrafish model. fam57ba, encoding a ceramide synthase, was identified as interacting with the doc2a gene, encoding a calcium-sensitive exocytosis regulator, a genetic interaction not previously described...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28933423/omega-3-pufa-ameliorates-hyperhomocysteinemia-induced-hepatic-steatosis-in-mice-by-inhibiting-hepatic-ceramide-synthesis
#2
Yong-Qiang Dong, Xing-Zhong Zhang, Lu-Lu Sun, Song-Yang Zhang, Bo Liu, Hui-Ying Liu, Xian Wang, Chang-Tao Jiang
Hyperhomocysteinemia (HHcy) is a key risk factor in hepatic steatosis. In this study, we applied a metabolomic approach to investigate the changes in the metabolite profile due to HHcy-induced hepatic steatosis and the effects of omega-3 PUFA (polyunsaturated fatty acid) supplementation in mice. HHcy was induced in mice by giving DL-Hcy (1.8 g/L) in drinking water for 6 weeks, then the mice were sacrificed, and the metabolic profiles of the liver and plasma were analyzed through UPLC-ESI-QTOFMS-based lipidomics...
September 21, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28930754/simvastatin-a-novel-stimulator-of-eryptosis-the-suicidal-erythrocyte-death
#3
Abdulla Al Mamun Bhuyan, Sigrid Nüßle, Hang Cao, Shaqiu Zhang, Florian Lang
BACKGROUND/AIMS: The 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase inhibitor simvastatin has been shown to trigger apoptosis of several cell types. The substance has thus been proposed as an additional treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the extracellular face of the erythrocyte cell membrane...
September 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28928759/identification-of-biomarkers-for-defense-response-to-plasmopara-viticola-in-a-resistant-grape-variety
#4
Giulia Chitarrini, Evelyn Soini, Samantha Riccadonna, Pietro Franceschi, Luca Zulini, Domenico Masuero, Antonella Vecchione, Marco Stefanini, Gabriele Di Gaspero, Fulvio Mattivi, Urska Vrhovsek
Downy mildew (Plasmopara viticola) is one of the most destructive diseases of the cultivated species Vitis vinifera. The use of resistant varieties, originally derived from backcrosses of North American Vitis spp., is a promising solution to reduce disease damage in the vineyards. To shed light on the type and the timing of pathogen-triggered resistance, this work aimed at discovering biomarkers for the defense response in the resistant variety Bianca, using leaf discs after inoculation with a suspension of P...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28925253/novel-trimodal-maldi-imaging-mass-spectrometry-ims3-at-10-%C3%AE-m-reveals-spatial-lipid-and-peptide-correlates-implicated-in-a%C3%AE-plaque-pathology-in-alzheimer-s-disease
#5
Ibrahim Kaya, Dimitri Brinet, Wojciech Michno, Mehmet Baskurt, Henrik Zetterberg, Kaj Blennow, Jörg Hanrieder
Multimodal chemical imaging using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) can provide comprehensive molecular information in situ within the same tissue sections. This is of relevance for studying different brain pathologies such as Alzheimer's Disease (AD), where recent data suggest a critical relevance of co-localizing Aβ peptides and neuronal lipids. We here developed a novel trimodal, high-resolution (10µm) MALDI imaging MS (IMS) paradigm for negative- and positive ion mode lipid analysis and subsequent protein ion imaging on the same tissue section...
September 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28924659/sted-imaging-of-golgi-dynamics-with-cer-sir-a-two-component-photostable-high-density-lipid-probe-for-live-cells
#6
Roman S Erdmann, Derek Toomre, Alanna Schepartz
Long time-lapse super-resolution imaging in live cells requires a labeling strategy that combines a bright, photostable fluorophore with a high-density localization probe. Lipids are ideal high-density localization probes, as they are >100 times more abundant than most membrane-bound proteins and simultaneously demark the boundaries of cellular organelles. Here, we describe Cer-SiR, a two-component, high-density lipid probe that is exceptionally photostable. Cer-SiR is generated in cells via a bioorthogonal reaction of two components: a ceramide lipid tagged with trans-cyclooctene (Cer-TCO) and a reactive, photostable Si-rhodamine dye (SiR-Tz)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28923368/insights-into-the-structural-biology-of-gaucher-disease
#7
REVIEW
Laura Smith, Stephen Mullin, Anthony H V Schapira
Gaucher disease, the most common lysosomal storage disorder, is caused by mutations in the gene encoding the acid-β-glucosidase lysosomal hydrolase enzyme that cleaves glucocerebroside into glucose and ceramide. Reduced enzyme activity and impaired structural stability arise due to >300 known disease-causing mutations. Several of these mutations have also been associated with an increased risk of Parkinson disease (PD). Since the discovery of the acid-β-glucosidase X-ray structure, there have been major advances in our understanding of the structural properties of the protein...
September 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28922657/methods-employed-in-cytofluorometric-assessment-of-eryptosis-the-suicidal-erythrocyte-death
#8
Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, Florian Lang
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28922150/synthesis-radiosynthesis-and-preliminary-in-vitro-and-in-vivo-evaluation-of-the-fluorinated-ceramide-trafficking-inhibitor-hpa-12-for-brain-applications
#9
Simone M Crivelli, Andreas Paulus, Jozef Markus, Matthias Bauwens, Dusan Berkes, Helga E De Vries, Monique T Mulder, Jochen Walter, Felix M Mottaghy, Mario Losen, Pilar Martinez-Martinez
Ceramide levels are increased in blood and brain tissue of Alzheimer's disease (AD) patients. Since the ceramide transporter protein (CERT) is the only known protein able to mediate non-vesicular transfer of ceramide between organelle membranes, the modulation of CERT function may impact on ceramide accumulation. The competitive CERT inhibitor N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12) interferes with ceramide trafficking. To understand the role of ceramide/CERT in AD, HPA-12 can be a useful tool to modulate ceramide trafficking...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28915027/structure-and-dynamics-of-membrane-proteins-and-membrane-associated-proteins-with-native-bicelles-from-eukaryotic-tissues
#10
Sean T Smrt, Adrian W Draney, Indira Singaram, Justin L Lorieau
In vitro studies of protein structure, function and dynamics typically preclude the complex range of molecular interactions found in living tissues. In vivo studies elucidate these complex relationships, yet they are typically incompatible with the extensive and controlled biophysical experiments available in vitro. We present an alternative approach by extracting membranes from eukaryotic tissues to produce native bicelles to capture the rich and complex molecular environment of in vivo studies while retaining the advantages of in vitro experiments...
September 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28914377/the-permeability-enhancing-mechanism-of-menthol-on-skin-lipids-a-molecular-dynamics-simulation-study
#11
Huanjie Wang, Fancui Meng
The stratum corneum (SC), the outermost layer of skin, represents the primary barrier to molecules penetrating the skin. Menthol is widely used in clinical medicine as a penetration enhancer due to its high efficiency and relative safety. In this study, molecular dynamics simulations have been performed to investigate the effect of menthol molecules on the structural and permeability of both single component and ternary mixed bilayers. The lipid matrix is modeled as pure ceramide (CER2) or as a 2:2:1 mixture of CER2, cholesterol (CHOL), and free fatty acid (FFA)...
September 15, 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28911866/molecular-dynamics-simulations-of-stratum-corneum-lipid-mixtures-a-multiscale-perspective
#12
Timothy C Moore, Christopher R Iacovella, Anne Leonhard, Annette L Bunge, Clare McCabe
The lipid matrix of the stratum corneum (SC) layer of skin is essential for human survival; it acts as a barrier to prevent rapid dehydration while keeping potentially hazardous material outside the body. While the composition of the SC lipid matrix is known, the molecular-level details of its organization are difficult to infer experimentally, hindering the discovery of structure-property relationships. To this end, molecular dynamics simulations, which give molecular-level resolution, have begun to play an increasingly important role in understanding these relationships...
September 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28911799/effects-of-glucocorticoids-on-stratum-corneum-lipids-and-function-in-human-skin-a-detailed-lipidomic-analysis
#13
Mads A Røpke, Cristina Alonso, Sora Jung, Hanne Norsgaard, Claudia Richter, Maxim E Darvin, Thomas Litman, Annika Vogt, Jürgen Lademann, Ulrike Blume-Peytavi, Jan Kottner
BACKGROUND: Topical glucocorticoids (GCs) are known to induce atrophy of human skin including thinning of epidermal and dermal compartments by influencing keratinocyte proliferation and synthesis of extracellular matrix proteins. GCs are also known to reduce skin barrier integrity but little is known about the changes in lipid composition in human skin following topical administration of GCs. OBJECTIVE: This study investigated the effects of GCs on stratum corneum (SC) function and lipid profile of human skin in vivo...
August 26, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28906043/diluted-sodium-hypochlorite-bleach-in-dogs-antiseptic-efficacy-local-tolerability-and-in-vitro-effect-on-skin-barrier-function-and-inflammation
#14
Frane Banovic, Thierry Olivry, Wolfgang Bäumer, Judy Paps, Jessica Stahl, Ana Rogers, Megan Jacob
BACKGROUND: Diluted sodium hypochlorite represents an inexpensive and widely available topical antiseptic, but there are no tolerability and efficacy data in veterinary dermatology. OBJECTIVES: To determine the in vivo antibacterial effect and tolerability of topical diluted bleach application and to assess its in vitro effect on skin barrier lipids and anti-inflammatory properties on keratinocytes. METHODS: Topical hypochlorite at 0.05% and tap water were applied to both sides of the thorax of four healthy dogs...
September 14, 2017: Veterinary Dermatology
https://www.readbyqxmd.com/read/28905881/identification-of-asah1-as-a-susceptibility-gene-for-familial-keloids
#15
Regie Lyn P Santos-Cortez, Ying Hu, Fanyue Sun, Fairouz Benahmed-Miniuk, Jian Tao, Jitendra K Kanaujiya, Samuel Ademola, Solomon Fadiora, Victoria Odesina, Deborah A Nickerson, Michael J Bamshad, Peter B Olaitan, Odunayo M Oluwatosin, Suzanne M Leal, Ernst J Reichenberger
Keloids result from abnormal proliferative scar formation with scar tissue expanding beyond the margin of the original wound and are mostly found in individuals of sub-Saharan African descent. The etiology of keloids has not been resolved but previous studies suggest that keloids are a genetically heterogeneous disorder. Although possible candidate genes have been suggested by genome-wide association studies using common variants, by upregulation in keloids or their involvement in syndromes that include keloid formation, rare coding variants that contribute to susceptibility in non-syndromic keloid formation have not been previously identified...
October 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28905096/comparison-of-suction-blistering-and-tape-stripping-for-analysis-of-epidermal-genes-proteins-and-lipids
#16
Marek Svoboda, Marta Hlobilová, Markéta Marešová, Michaela Sochorová, Andrej Kováčik, Kateřina Vávrová, Iva Dolečková
Analysis of epidermal genes, proteins and lipids is important in the research and diagnosis of skin diseases. Although punch biopsy is the first-choice technique for the skin sampling, it is unnecessarily invasive for obtaining a sample just for the epidermal analysis. Here we compare two less invasive methods, suction blistering (SB) and tape stripping (TS), for the analysis of selected epidermal genes (quantitative real-time reverse transcription PCR, qRT-PCR), proteins (western blotting, WB), and lipids in ten healthy volunteers...
September 13, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28894119/evidence-for-biochemical-barrier-restoration-topical-solenopsin-analogs-improve-inflammation-and-acanthosis-in-the-kc-tie2-mouse-model-of-psoriasis
#17
Jack L Arbiser, Ron Nowak, Kellie Michaels, Yuliya Skabytska, Tilo Biedermann, Monica J Lewis, Michael Y Bonner, Shikha Rao, Linda C Gilbert, Nabiha Yusuf, Isabella Karlsson, Yi Fritz, Nicole L Ward
Psoriasis is a chronic inflammatory skin disease affecting 2.5-6 million patients in the United States. The cause of psoriasis remains unknown. Previous human and animal studies suggest that patients with a susceptible genetic background and some stimulus, such as barrier disruption, leads to a coordinated signaling events involving cytokines between keratinocytes, endothelial cells, T cells, macrophages and dendritic cells. Ceramides are endogenous skin lipids essential for maintaining skin barrier function and loss of ceramides may underlie inflammatory and premalignant skin...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890071/serum-lipid-alterations-in-gba-associated-parkinson-s-disease
#18
Leonor Correia Guedes, Robin Barry Chan, Marcos António Gomes, Vasco A Conceição, Raquel Bouça Machado, Tiago Soares, Yimeng Xu, Paulo Gaspar, Joao André Carriço, Roy N Alcalay, Joaquim J Ferreira, Tiago Fleming Outeiro, Gabriel Miltenberger-Miltenyi
INTRODUCTION: Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. METHODS: We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2...
September 1, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28889959/metabolic-profiles-revealed-anti-ischemia-reperfusion-injury-of-yangxinshi-tablet-in-rats
#19
Hai Zhang, Yahong Zhao, Zhengxiang Xia, Hongli Du, Yue Gao, Dan Xue, Zhenyu Zhu, Yifeng Chai
ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial ischemia-reperfusion (I/R) injury is a serious injury that is resulted from the recovery of blood supply after myocardial ischemia. Yangxinshi tablet is a compound Chinese herbal preparation and often used to alleviate the myocardial ischemia in clinical, but its protective mechanism of anti-myocardial ischemia reperfusion injury remains unclear. The objective of this study was to evaluate the anti-I/R injury effect of Yangxinshi tablet on a myocardial I/R rat model and to identify serum biomarker metabolites associated with I/R based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomic method, and explore the metabolic mechanism of anti-I/R injury of Yangxinshi tablet...
September 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28889482/tlr-induced-smpd3-defects-enhance-inflammatory-response-of-b-cell-and-macrophage-in-the-pathogenesis-of-sle
#20
Fei Liu, Xiaojing Li, Huimin Yue, Jianjian Ji, Ming You, Liang Ding, Hongye Fan, Yayi Hou
B lymphocyte and macrophages may contribute to SLE pathogenesis through cytokine production after TLR stimulation. Emerging evidences suggested that defects of sphingolipid metabolism was responsible for SLE pathogenesis. However, it is not clear whether these defects exist in B cells and macrophages under SLE condition and whether TLR signaling pathway was related to the dysfunction of sphingolipid metabolism in SLE. Here we demonstrated that the enzymes involved in the sphingolipid metabolism expressed abnormally in B cells from SLE patients and lupus-prone mice...
September 10, 2017: Scandinavian Journal of Immunology
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