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https://www.readbyqxmd.com/read/29793055/fatty-acid-activation-in-thermogenic-adipose-tissue
#1
REVIEW
Sandra Steensels, Baran A Ersoy
Channeling carbohydrates and fatty acids to thermogenic tissues, including brown and beige adipocytes, have garnered interest as an approach for the management of obesity-related metabolic disorders. Mitochondrial fatty acid oxidation (β-oxidation) is crucial for the maintenance of thermogenesis. Upon cellular fatty acid uptake or following lipolysis from triglycerides (TG), fatty acids are esterified to coenzyme A (CoA) to form active acyl-CoA molecules. This enzymatic reaction is essential for their utilization in β-oxidation and thermogenesis...
May 21, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29792991/codon-adaptation-biases-among-sylvatic-and-urban-genotypes-of-dengue-virus-type-2
#2
Marielton Dos Passos Cunha, Ayda Susana Ortiz-Baez, Caio César de Melo Freire, Paolo Marinho de Andrade Zanotto
Dengue virus (DENV) emerged from the sylvatic environment and colonized urban settings, being sustained in a human-Aedes-human transmission chain, mainly by the bites of females of the anthropophilic species Aedes aegypti. Herein, we sought evidence for fine-tuning in viral codon usage, possibly due to viral adaptation to human transmission. We compared the codon adaptation of DENV serotype 2 (DENV-2) genotypes from urban and sylvatic habitats and tried to correlate the findings with key evolutionary determinants...
May 21, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29792687/co-mobility-of-gabarap-and-phosphatidylinositol-4-kinase-2a-on-cytoplasmic-vesicles
#3
Yan Chen, Hui-Qiao Sun, John P Eichorst, Joseph P Albanesi, Helen Yin, Joachim D Mueller
We previously reported that recruitment of the Type IIA phosphatidylinositol 4-kinase (PI4K2A) to autophagosomes by GABARAP, a member of the Atg8 family of autophagy-related proteins, is important for autophagosome-lysosome fusion. Because both PI4K2A and GABARAP have also been implicated in the intracellular trafficking of plasma membrane receptors in the secretory/endocytic pathway, we characterized their interaction in cells under non-autophagic conditions. Fluorescence fluctuation spectroscopy measurements revealed that GABARAP exists predominantly as a cytosolic monomer in live cells, but is recruited to small cytoplasmic vesicles upon overexpression of PI4K2A...
May 24, 2018: Biochemistry
https://www.readbyqxmd.com/read/29792531/the-expression-of-lysophosphatidic-acid-receptor-5-is-necessary-for-the-regulation-of-intestinal-na-h-exchanger-3-by-lysophosphatidic-acid-in-vivo
#4
Kayte A Jenkin, Peijian He, C Chris Yun
Lysophosphatidic acid (LPA) is a bioactive lipid molecule, which regulates a broad range of pathophysiological processes. Recent studies have demonstrated that LPA modulates electrolyte flux in the intestine and its potential as an anti-diarrheal agent has been suggested. Of six LPA receptors, LPA5 is highly expressed in the intestine. Recent studies by our group have demonstrated activation of Na+ /H+ exchanger 3 (NHE3) by LPA5 . However, much of what has been elucidated was achieved using colonic cell lines that were transfected to express LPA5 ...
May 24, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29791203/short-term-thermoneutral-housing-alters-glucose-metabolism-and-markers-of-adipose-tissue-browning-in-response-to-a-high-fat-diet-in-lean-mice
#5
Zachary Stephen Clayton, Carrie E McCurdy
Systemic insulin resistance and glucose intolerance occur with as little as 3 days of a high-fat diet (HFD) in mice and humans; the mechanisms that initiate acute insulin resistance are unknown. Most laboratories house mice at 22{degree sign}C, which is below their thermoneutral temperature (~30{degree sign}C). Cold stress has been shown to increase white adipose tissue (WAT) browning, alter lipid trafficking and impair immune function, while energy intake and expenditure decrease with increasing ambient temperature; importantly, dysregulation of these parameters have been strongly linked to obesity-induced insulin resistance...
May 23, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29791141/fluorogenic-probing-of-membrane-protein-trafficking
#6
Chenge Li, Aurélien Mourton, Marie-Aude Plamont, Vanessa Rodrigues, Isabelle Aujard, Michel Volovitch, Thomas Le Saux, Franck Perez, Sophie Vriz, Ludovic Jullien, Alain Joliot, Arnaud Gautier
Methods to differentially label cell-surface and intracellular membrane proteins are indispensable for understanding their function and the regulation of their trafficking. We present an efficient strategy for the rapid and selective fluorescent labeling of membrane proteins based on the chemical-genetic fluorescent marker FAST (fluorescence-activating and absorption-shifting tag). Cell-surface FAST-tagged proteins could be selectively and rapidly labeled using fluorogenic membrane-impermeant 4-hydroxybenzylidene rhodanine (HBR) analogs...
May 23, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29790818/endosomal-and-phagosomal-snares
#7
Ilse Dingjan, Peter T A Linders, Danielle R J Verboogen, Natalia H Revelo, Martin Ter Beest, Geert van den Bogaart
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes with other endosomes, lysosomes, the Golgi apparatus, the plasma membrane, and the endoplasmic reticulum. The goal of this review is to provide an overview of the SNAREs involved in endosomal and phagosomal trafficking...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29790281/suppressing-tawny-crazy-ant-nylanderia-fulva-by-rnai-technology
#8
Jia Meng, Jiaxin Lei, Andrew Davitt, Jocelyn R Holt, Jian Huang, Roger Gold, Edward L Vargo, Aaron M Tarone, Keyan Zhu-Salzman
The tawny crazy ant (Nylanderia fulva) is a new invasive pest in the United States. At present, its management mainly relies on the use of synthetic insecticides, which are generally ineffective at producing lasting control of the pest, necessitating alternative environmentally friendly measures. In this study, we evaluated the feasibility of gene silencing to control this ant species. Six housekeeping genes encoding actin (NfActin), coatomer subunit β (NfCOPβ), arginine kinase (NfArgK), and V-type proton ATPase subunits A (NfvATPaseA), B (NfvATPaseB) and E (NfvATPaseE) were cloned...
May 22, 2018: Insect Science
https://www.readbyqxmd.com/read/29788979/marcks-and-marcks-like-proteins-in-development-and-regeneration
#9
REVIEW
Mohamed El Amri, Una Fitzgerald, Gerhard Schlosser
BACKGROUND: The Myristoylated Alanine-Rich C-kinase Substrate (MARCKS) and MARCKS-like protein 1 (MARCKSL1) have a wide range of functions, ranging from roles in embryonic development to adult brain plasticity and the inflammatory response. Recently, both proteins have also been identified as important players in regeneration. Upon phosphorylation by protein kinase C (PKC) or calcium-dependent calmodulin-binding, MARCKS and MARCKSL1 translocate from the membrane into the cytosol, modulating cytoskeletal actin dynamics and vesicular trafficking and activating various signal transduction pathways...
May 22, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29788888/scap-srebps-are-central-players-in-lipid-metabolism-and-novel-metabolic-targets-in-cancer-therapy
#10
Xiang Cheng, Jianying Li, Deliang Guo
Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavage-activating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29788265/gene-expression-profile-in-frontal-cortex-in-sporadic-frontotemporal-lobar-degeneration-tdp
#11
Pol Andrés-Benito, Ellen Gelpi, Mónica Povedano, Gabriel Santpere, Isidro Ferrer
Molecular alterations compromising key metabolic pathways are poorly understood in sporadic frontotemporal lobar degeneration with TDP-43 pathology (sFTLD-TDP). Whole-transcriptome array, RT-qPCR validation, gel electrophoresis, and Western blotting, and mitochondrial electron transport chain (ETC) activity were comparatively examined in frontal cortex (area 8) of 16 sFTLD-TDP cases and 14 controls. Assessment of 111 genes by RT-qPCR showed deregulation of 81 genes linked to neurotransmission and synapses, neuronal architecture, cytoskeleton of axons and dendrites, vesicle trafficking, purines, mitochondria, and energy metabolism in sFTLD-TDP...
May 19, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29788248/respiratory-tract-infections-in-patients-with-inflammatory-bowel-disease-safety-analyses-from-vedolizumab-clinical-trials
#12
Brian G Feagan, Fatima Bhayat, Mona Khalid, Aimee Blake, Simon P L Travis
Background and Aims: Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab. Methods: Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn's disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled...
May 17, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29788201/genetic-variants-in-autism-related-cntnap2-impair-axonal-growth-of-cortical-neurons
#13
Giorgia Canali, Marta Garcia, Bruno Hivert, Delphine Pinatel, Aline Goullancourt, Ksenia Oguievetskaia, Margaux Saint-Martin, Jean-Antoine Girault, Catherine Faivre-Sarrailh, Laurence Goutebroze
The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro...
June 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29787980/autophagy-and-mhc-restricted-antigen-presentation
#14
REVIEW
Jan Valečka, Catarina R Almeida, Bing Su, Philippe Pierre, Evelina Gatti
Major histocompatibility complex (MHC) molecules present peptide antigens to T lymphocytes and initiate immune responses. The peptides loaded onto MHC class I or MHC class II molecules can be derived from cytosolic proteins, both self and foreign. A variety of cellular processes, including endocytosis, vesicle trafficking, and autophagy, play critical roles in presentation of these antigens. We discuss the role of autophagy, a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation...
May 19, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29787767/influence-of-gag-and-rre-sequences-on-hiv-1-rna-packaging-signal-structure-and-function
#15
Siarhei Kharytonchyk, Joshua D Brown, Krista Stilger, Saif Yasin, Aishwarya S Iyer, John Collins, Michael F Summers, Alice Telesnitsky
The packaging signal (Ψ) and Rev. responsive element (RRE), enable unspliced HIV-1 RNAs' export from the nucleus and packaging into virions. For some retroviruses, engrafting Ψ onto a heterologous RNA is sufficient to direct encapsidation. In contrast, HIV-1 RNA packaging requires 5' leader Ψ elements plus poorly defined additional features. We previously defined minimal 5' leader sequences competitive with intact Ψ for HIV-1 packaging, and here examined the potential roles of additional downstream elements...
May 19, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29787242/membrane-topology-of-trafficking-regulator-of-glut4-1-trarg1
#16
Xiaowen Duan, James Krycer, Kristen Cooke, Guang Yang, David E James, Daniel Fazakerley
Trafficking regulator of GLUT4 1 (TRARG1) was recently identified to localise to glucose transporter type 4 (GLUT4) storage vesicles (GSVs) and to positively regulate GLUT4 trafficking. Our knowledge of TRARG1 structure and membrane topology is limited to predictive models, hampering efforts to further our mechanistic understanding of how it carries out its functions. Here, we use a combination of bioinformatics prediction tools and biochemical assays to define the membrane topology of the 173-amino acid mouse TRARG1...
May 22, 2018: Biochemistry
https://www.readbyqxmd.com/read/29786613/biophysics-of-membrane-curvature-remodeling-at-molecular-and-mesoscopic-lengthscales
#17
Natesan Ramakrishnan, Ryan P Bradley, Richard W Tourdot, Ravi Radhakrishnan
At the micron scale, where cell organelles display an amazing complexity in their shape and organization, the physical properties of a biological membrane can be better-understood using continuum models subject to thermal (stochastic) undulations. Yet, the chief orchestrators of these complex and intriguing shapes are a specialized class of membrane associating often peripheral proteins called curvature remodeling proteins (CRPs) that operate at the molecular level through specific protein-lipid interactions...
May 22, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29784874/select-%C3%AE-arrestins-control-cell-surface-abundance-of-the-mammalian-kir2-1-potassium-channel-in-a-yeast-model
#18
Natalie A Hager, Collin J Krasowski, Timothy D Mackie, Alexander R Kolb, Patrick G Needham, Andrew A Augustine, Alison Dempsey, Christopher Szent-Gyorgyi, Marcel P Bruchez, Daniel J Bain, Adam V Kwiatkowski, Allyson F O'Donnell, Jeffrey L Brodsky
Protein composition at the plasma membrane is tightly regulated, with rapid protein internalization and selective targeting to the cell surface occurring in response to environmental changes. For example, ion channels are dynamically relocalized to or from the plasma membrane in response to physiological alterations, allowing cells and organisms to maintain osmotic and salt homeostasis. To identify additional factors that regulate the selective trafficking of a specific ion channel, we used a yeast model for a mammalian potassium channel, the K+ inwardly rectifying channel Kir2...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29784647/regulation-of-rabgaps-involved-in-insulin-action
#19
REVIEW
Samaneh Mafakheri, Alexandra Chadt, Hadi Al-Hasani
Rab (Ras-related proteins in brain) GTPases are key proteins responsible for a multiplicity of cellular trafficking processes. Belonging to the family of monomeric GTPases, they are regulated by cycling between their active GTP-bound and inactive GDP-bound conformations. Despite possessing a slow intrinsic GTP hydrolysis activity, Rab proteins rely on RabGAPs (Rab GTPase-activating proteins) that catalyze GTP hydrolysis and consequently inactivate the respective Rab GTPases. Two related RabGAPs, TBC1D1 and TBC1D4 (=AS160) have been described to be associated with obesity-related traits and type 2 diabetes in both mice and humans...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29784041/lipid-metabolism-reprogramming-and-its-potential-targets-in-cancer
#20
REVIEW
Chunming Cheng, Feng Geng, Xiang Cheng, Deliang Guo
Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. Lipids constitute the basic structure of membranes and also function as signaling molecules and energy sources. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors in the endoplasmic reticulum, play a central role in the regulation of lipid metabolism. Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth...
May 21, 2018: Cancer communications
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