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https://www.readbyqxmd.com/read/28547763/new-approaches-towards-the-understanding-of-integral-membrane-proteins-a-structural-perspective-on-g-protein-coupled-receptors
#1
REVIEW
Reinhard Grisshammer
Three-dimensional structure determination of integral membrane proteins has advanced in unprecedented detail our understanding of mechanistic events of how ion channels, transporters, receptors and enzymes function. This exciting progress required a tremendous amount of methods development, as exemplified here with G protein-coupled receptors (GPCRs): Optimizing the production of GPCRs in recombinant hosts; increasing the probability of crystal formation using high-affinity ligands, nanobodies, and minimal G proteins for co-crystallization, thus stabilizing receptors into one conformation; using the T4 lysozyme technology and other fusion partners to promote crystal contacts; advancing crystallization methods including the development of novel detergents, and miniaturization and automation of the lipidic cubic phase crystallization method; the concept of conformational thermostabilization of GPCRs; and developing microfocus X-ray synchrotron technologies to analyze small GPCR crystals...
May 25, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28545058/a-systematic-genomic-screen-implicates-nucleocytoplasmic-transport-and-membrane-growth-in-nuclear-size-control
#2
Kazunori Kume, Helena Cantwell, Frank R Neumann, Andrew W Jones, Ambrosius P Snijders, Paul Nurse
How cells control the overall size and growth of membrane-bound organelles is an important unanswered question of cell biology. Fission yeast cells maintain a nuclear size proportional to cellular size, resulting in a constant ratio between nuclear and cellular volumes (N/C ratio). We have conducted a genome-wide visual screen of a fission yeast gene deletion collection for viable mutants altered in their N/C ratio, and have found that defects in both nucleocytoplasmic mRNA transport and lipid synthesis alter the N/C ratio...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28544957/zebrafish-as-a-visual-and-dynamic-model-to-study-the-transport-of-nanosized-drug-delivery-systems-across-the-biological-barriers
#3
Ye Li, Xiaoqing Miao, Tongkai Chen, Xiang Yi, Ruibing Wang, Haitao Zhao, Simon Ming-Yuen Lee, Xueqing Wang, Ying Zheng
With the wide application of nanotechnology to drug delivery systems, a simple, dynamic and visual in vivo model for high-throughput screening of novel formulations with fluorescence markers across biological barriers is desperately needed. In vitro cell culture models have been widely used, although they are far from a complimentary in vivo system. Mammalian animal models are common predictive models to study transport, but they are costly and time consuming. Zebrafish (Danio rerio), a small vertebrate model, have the potential to be developed as an "intermediate" model for quick evaluations...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28544881/mammalian-systems-biotechnology-reveals-global-cellular-adaptations-in-a-recombinant-cho-cell-line
#4
Faraaz Noor Khan Yusufi, Meiyappan Lakshmanan, Ying Swan Ho, Bernard Liat Wen Loo, Pramila Ariyaratne, Yuansheng Yang, Say Kong Ng, Tessa Rui Min Tan, Hock Chuan Yeo, Hsueh Lee Lim, Sze Wai Ng, Ai Ping Hiu, Chung Ping Chow, Corrine Wan, Shuwen Chen, Gavin Teo, Gao Song, Ju Xin Chin, Xiaoan Ruan, Ken Wing Kin Sung, Wei-Shou Hu, Miranda Gek Sim Yap, Muriel Bardor, Niranjan Nagarajan, Dong-Yup Lee
Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544394/muscle-metabolic-alterations-induced-by-genetic-ablation-of-4e-bp1-and-4e-bp2-in-response-to-diet-induced-obesity
#5
Olivier Le Bacquer, Kristell Combe, Christophe Montaurier, Jérôme Salles, Christophe Giraudet, Véronique Patrac, Carla Domingues-Faria, Christelle Guillet, Katie Louche, Yves Boirie, Nahum Sonenberg, Cédric Moro, Stéphane Walrand
SCOPE: In recent years, several studies reported the role of eIF4E-binding proteins (4E-BPs) on the development of diet-induced obesity and insulin resistance. Our aim was to investigate the effect of 4E-BP protein deletion on lipid accumulation and metabolism in skeletal muscle in response to a high fat diet-induced obesity in 4E-BP1/2 DKO mice. METHODS AND RESULTS: Diet-induced obesity engendered increased ectopic accumulation of lipotoxic species in skeletal muscle of 4E-BP1 and 4E-BP2 double-knockout mice (4E-BP1/2 DKO), namely diacylglycerols and ceramides...
May 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28544329/dissolving-microneedle-arrays-for-transdermal-delivery-of-amphiphilic-vaccines
#6
Myunggi An, Haipeng Liu
Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28543308/exocytic-trafficking-pathways-in-plants-why-and-how-they-are-redirected
#7
REVIEW
Takehiko Kanazawa, Takashi Ueda
The membrane trafficking system is responsible for precise transportation and localization of proteins, lipids, and polysaccharides among single membrane-bound organelles, the plasma membrane, and the extracellular space. While the exocytic trafficking pathway is considered to be a default transport pathway in many organisms, including land plants, research has shown that evolutionary processes led to an increase in the number of machinery components involved in the plant exocytic pathway. This study provides an overview of the diversification of exocytic trafficking pathways in plants, which mediate the formation and maintenance of cell polarity, interaction with symbiotic and pathogenic microbes, and cytokinesis...
May 25, 2017: New Phytologist
https://www.readbyqxmd.com/read/28543099/evidence-of-altered-mitochondrial-protein-expression-after-chronic-ethanol-consumption-in-the-aged-estrogen-deficient-female-rat-heart
#8
Alexandra M Garvin, J L Miller-Lee, D R Sharda, G M Kanski, J C Hunter, Donna H Korzick
BACKGROUND: Estrogen loss has been implicated to increase the risk of alcoholic cardiomyopathy in post-menopausal women. The purpose of this study was to identify novel mitochondrial protein targets for the treatment of alcoholic cardiomyopathy in aged women using a state-of-the-art proteomics approach. We hypothesized that chronic ethanol (EtOH) ingestion exacerbates maladaptive mitochondrial protein expression in the aged female heart METHODS: Adult (3 mo) and aged (18 mo) F344 ovary-intact or ovariectomized (OVX) rats were randomly assigned an EtOH or control Lieber-DeCarli 'all liquid' diet for 20 wks...
May 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28541045/orally-absorbed-cyclic-peptides
#9
Daniel S Nielsen, Nicholas E Shepherd, Weijun Xu, Andrew J Lucke, Martin J Stoermer, David P Fairlie
Peptides and proteins are not orally bioavailable in mammals, although a few peptides are intestinally absorbed in small amounts. Polypeptides are generally too large and polar to passively diffuse through lipid membranes, while most known active transport mechanisms facilitate cell uptake of only very small peptides. Systematic evaluations of peptides with molecular weights above 500 Da are needed to identify parameters that influence oral bioavailability. Here we describe 125 cyclic peptides containing four to thirty-seven amino acids that are orally absorbed by mammals...
May 25, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28540446/lipid-per-oxidation-in-mitochondria-an-emerging-target-in-the-ageing-process
#10
REVIEW
O S Ademowo, H K I Dias, D G A Burton, H R Griffiths
Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation...
May 24, 2017: Biogerontology
https://www.readbyqxmd.com/read/28539716/prevention-mechanism-of-2-3-5-4-tetrahydroxy-stilbene-2-o-%C3%AE-d-glucoside-on-lipid-accumulation-in-steatosis-hepatic-l-02-cell
#11
Pei Lin, Jian-Mei Lu, Yan-Fang Wang, Wen Gu, Rong-Hua Zhao, Jie Yu
AIM: 2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG), a natural stilbene, shows great activities in hepatic lipid regulation, especially for hepatic triglyceride lowering. However, information about its mechanisms on biosynthesis and degradation of triglyceride is still limited. This research pays close attention to clarify the mechanism of TSG on prevention of hepatic lipid accumulation. MATERIALS AND METHODS: TSG was given to steatosis hepatocyte L-02 cell induced by fat emulsion incubation...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28539586/whole-blood-transcriptome-analysis-reveals-potential-competition-in-metabolic-pathways-between-negative-energy-balance-and-response-to-inflammatory-challenge
#12
Juliette Bouvier-Muller, Charlotte Allain, Guillaume Tabouret, Francis Enjalbert, David Portes, Céline Noirot, Rachel Rupp, Gilles Foucras
Negative Energy Balance (NEB) is considered to increase susceptibility to mastitis. The objective of this study was to improve our understanding of the underlying mechanisms by comparing transcriptomic profiles following NEB and a concomitant mammary inflammation. Accordingly, we performed RNA-seq analysis of blood cells in energy-restricted ewes and control-diet ewes at four different time points before and after intra mammary challenge with phlogogenic ligands. Blood leucocytes responded to NEB by shutting down lipid-generating processes, including cholesterol and fatty acid synthesis, probably under transcriptional control of SREBF 1...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539275/mucosal-transfer-of-wheat-germ-agglutinin-modified-lipid-polymer-hybrid-nanoparticles-for-oral-delivery-of-oridonin
#13
Ying Liu, Jinguang Liu, Jun Liang, Meiying Zhang, Zhe Li, Zhi Wang, Beilei Dang, Nianping Feng
Wheat germ agglutinin-modified lipid-polymer hybrid nanoparticles (WGA-LPNs) promote cellular uptake after oral delivery via receptor-mediated endocytosis and bioadhesion. Understanding the mucosal transport of WGA-LPNs would help to improve bioavailability and ensure therapeutic efficacy. In this study, WGA-LPNs interacted with mucin, forming larger agglomerates with intact core-shell structure. The interaction of WGA-LPNs with mucin improved enterocyte endocytosis in Caco-2 cells. An in situ intestinal diffusion study in mice confirmed that WGA-LPNs reached enterocytes and underwent endocytosis, despite interference from mucin...
May 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28538724/applying-systems-level-spectral-imaging-and-analysis-to-reveal-the-organelle-interactome
#14
Alex M Valm, Sarah Cohen, Wesley R Legant, Justin Melunis, Uri Hershberg, Eric Wait, Andrew R Cohen, Michael W Davidson, Eric Betzig, Jennifer Lippincott-Schwartz
The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538099/iodide-selective-synthetic-ion-channels-based-on-shape-persistent-organic-cages
#15
Bahiru Punja Benke, Pulakesh Aich, Younghoon Kim, Kyung Lock Kim, Md Rumum Rohman, Soonsang Hong, In-Chul Hwang, Eun Hui Lee, Joon Ho Roh, Kimoon Kim
We report here a synthetic ion channel developed from a shape-persistent porphyrin-based covalent organic cage. The cage was synthesized by employing a synthetically economical dynamic covalent chemistry (DCC) approach. The organic cage selectively transports biologically relevant iodide ions over other inorganic anions by a dehydration-driven, channel mechanism as evidenced by vesicle-based fluorescence assays and planar lipid bilayer-based single channel recordings. Furthermore, the organic cage appears to facilitate iodide transport across the membrane of a living cell, suggesting that the cage could be useful as a biological tool that may replace defective iodide channels in living systems...
May 26, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28536535/role-of-intestinal-lxr%C3%AE-in-regulating-post-prandial-lipid-excursion-and-diet-induced-hypercholesterolemia-and-hepatic-lipid-accumulation
#16
Tibiábin Benítez-Santana, Sarah E Hugo, Amnon Schlegel
Post-prandial hyperlipidemia has emerged as a cardiovascular risk factor with limited therapeutic options. The Liver X receptors (Lxrs) are nuclear hormone receptors that regulate cholesterol elimination. Knowledge of their role in regulating the absorption and handling of dietary fats is incomplete. The purpose of this study was to determine the role of intestinal Lxrα in post-prandial intestinal lipid transport. Using Lxrα knockout (nr1h3(-/-)) and intestine-limited Lxrα over-expressing [Tg(fabp2a:EGFP-nr1h3)] zebrafish strains, we measured post-prandial lipid excursion with live imaging in larvae and physiological methods in adults...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#17
Jing Yang, Lixin Sun, Lu Wang, Hozeifa M Hassan, Xuan Wang, Phillip B Hylemon, Tao Wang, Huiping Zhou, Luyong Zhang, Zhenzhou Jiang
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28536248/the-signaling-lipid-phosphatidylinositol-3-5-bisphosphate-targets-plant-clc-a-anion-h-exchange-activity
#18
Armando Carpaneto, Anna Boccaccio, Laura Lagostena, Eleonora Di Zanni, Joachim Scholz-Starke
Phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) is a low-abundance signaling lipid associated with endo-lysosomal and vacuolar membranes in eukaryotic cells. Recent studies on Arabidopsis indicated a critical role of PI(3,5)P2 in vacuolar acidification and morphology during ABA-induced stomatal closure, but the molecular targets in plant cells remained unknown. By using patch-clamp recordings on Arabidopsis vacuoles, we show here that PI(3,5)P2 does not affect the activity of vacuolar H(+)-pyrophosphatase or vacuolar H(+)-ATPase...
May 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28536105/trappc13-modulates-autophagy-and-the-response-to-golgi-stress
#19
Silvia Ramírez-Peinado, Tatiana I Ignashkova, Bram J van Raam, Jan Baumann, Erica L Sennott, Mathieu Gendarme, Ralph K Lindemann, Michael N Starnbach, Jan H Reiling
Tether complexes play important roles in endo- and exocytic trafficking of lipids and proteins. In yeast, the multisubunit transport protein particle (TRAPP) tether regulates ER-Golgi, intra-Golgi transport and is also implicated in autophagy. The TRAPP complex in addition acts as a GEF for Ypt1, which is homologous to human Rab1. Here, we show that human TRAPPC13 and other TRAPP subunits are critically involved in the survival response to several Golgi disrupting agents. Loss of TRAPPC13 partially preserves the secretory pathway and viability in response to brefeldin A, which is dependent on ARF1 and the large GEF GBF1 and concomitant with reduced caspase activation and ER stress marker induction...
May 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28533679/effect-of-epigallocatechin-3-gallate-major-ingredient-of-green-tea-on-the-pharmacokinetics-of-rosuvastatin-in-healthy-volunteers
#20
Tae-Eun Kim, Na Ha, Yunjeong Kim, Hyunsook Kim, Jae Wook Lee, Ji-Young Jeon, Min-Gul Kim
Previous in vitro studies have demonstrated the inhibitory effect of green tea on drug transporters. Because rosuvastatin, a lipid-lowering drug widely used for the prevention of cardiovascular events, is a substrate for many drug transporters, there is a possibility that there is interaction between green tea and rosuvastatin. The aim of this study was to investigate the effect of green tea on the pharmacokinetics of rosuvastatin in healthy volunteers. An open-label, three-treatment, fixed-sequence study was conducted...
2017: Drug Design, Development and Therapy
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