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https://www.readbyqxmd.com/read/29149817/high-density-lipoprotein-hdl-dysfunction-and-future-of-hdl
#1
Sibel Ertek
Although high density lipoprotein cholesterol (HDL-C) levels are inversely proportional to cardiovascular risk in many studies, recent pharmacological interventional studies with HDL-C raising strategies did not show a benefit in terms of vascular events. The HDL particle is heterogenous with anti-atherogenic functions and non-vascular effects. Many factors affect HDL components and may either cause compositional changes, post-translational modifications of proteins, or alter lipids and other cargo molecules; generally these factors cause more than one of these changes, resulting in functional differences...
November 16, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29149599/autophagosomal-content-profiling-reveals-an-lc3c-dependent-piecemeal-mitophagy-pathway
#2
François Le Guerroué, Franziska Eck, Jennifer Jung, Tatjana Starzetz, Michel Mittelbronn, Manuel Kaulich, Christian Behrends
Autophagy allows the degradation of cytosolic endogenous and exogenous material in the lysosome. Substrates are engulfed by double-membrane vesicles, coined autophagosomes, which subsequently fuse with lysosomes. Depending on the involvement of specific receptor proteins, autophagy occurs in a selective or nonselective manner. While this process is well understood at the level of bulky cargo such as mitochondria and bacteria, we know very little about individual proteins and protein complexes that are engulfed and degraded by autophagy...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29148969/the-structure-of-the-copi-coat-determined-within-the-cell
#3
Yury S Bykov, Miroslava Schaffer, Svetlana O Dodonova, Sahradha Albert, Jürgen M Plitzko, Wolfgang Baumeister, Benjamin D Engel, John Ag Briggs
COPI-coated vesicles mediate trafficking within the Golgi apparatus and from the Golgi to the endoplasmic reticulum. The structures of membrane protein coats, including COPI, have been extensively studied with in vitro reconstitution systems using purified components. In a previous paper (Dodonova et al., 2017), we determined a complete structural model of the in vitro reconstituted COPI coat. Here, we applied cryo-focused ion beam milling, cryo-electron tomography and subtomogram averaging to determine the native structure of the COPI coat within vitrified Chlamydomonas reinhardtii cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29147941/artificial-bio-nanomachines-based-on-protein-needles-derived-from-bacteriophage-t4
#4
REVIEW
Hiroshi Inaba, Takafumi Ueno
Bacteriophage T4 is a natural bio-nanomachine which achieves efficient infection of host cells via cooperative motion of specific three-dimensional protein architectures. The relationships between the protein structures and their dynamic functions have recently been clarified. In this review we summarize the design principles for fabrication of nanomachines using the component proteins of bacteriophage T4 based on these recent advances. We focus on the protein needle known as gp5, which is located at the center of the baseplate at the end of the contractile tail of bacteriophage T4...
November 16, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/29147499/nano-microvehicles-for-efficient-delivery-and-bio-sensing-at-the-cellular-level
#5
S Campuzano, B Esteban-Fernández de Ávila, P Yáñez-Sedeño, J M Pingarrón, J Wang
A perspective review of recent strategies involving the use of nano/microvehicles to address the key challenges associated with delivery and (bio)sensing at the cellular level is presented. The main types and characteristics of the different nano/microvehicles used for these cellular applications are discussed, including fabrication pathways, propulsion (catalytic, magnetic, acoustic or biological) and navigation strategies, and relevant parameters affecting their propulsion performance and sensing and delivery capabilities...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147088/evaluation-and-characterization-of-milk-derived-microvescicle-isolated-from-bovine-colostrum
#6
Brighton E Maburutse, Mi-Ri Park, Sangnam Oh, Younghoon Kim
Extracellular microvesicles are membranous nano-sized cellular organelles secreted by a variety of cells under normal and pathological conditions and heterogeneous in size ranging from 30 nm to 1 μm. They carry functional microRNAs that can influence immunity and development. For a particular application of microvesicles, choice of isolation method is particularly important; however, their isolation methods from colostrum in particular have not been described clearly. In this work, differential ultracentrifugation as a conventional method, ultracentrifugation with some modification such as additional precipitations, ultrafiltration, sucrose gradient separation and ExoQuick™ as a commercial reagent were compared...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/29145394/unc-16-jip3-regulates-early-events-in-synaptic-vesicle-protein-trafficking-via-lrk-1-lrrk2-and-ap-complexes
#7
Bikash Choudhary, Madhushree Kamak, Neena Ratnakaran, Jitendra Kumar, Anjali Awasthi, Chun Li, Ken Nguyen, Kunihiro Matsumoto, Naoki Hisamoto, Sandhya P Koushika
JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex...
November 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29144234/lrp1-integrates-murine-macrophage-cholesterol-homeostasis-and-inflammatory-responses-in-atherosclerosis
#8
Xunde Xian, Yinyuan Ding, Marco Dieckmann, Li Zhou, Florian Plattner, Mingxia Liu, John S Parks, Robert E Hammer, Philippe Boucher, Shirling Tsai, Joachim Herz
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGFβ and PDGFRβ in reverse cholesterol transport and the maintenance of vascular wall integrity...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29142313/effects-of-exosome-on-the-activation-of-cd4-t-cells-in-rhesus-macaques-a-potential-application-for-hiv-latency-reactivation
#9
Xiaowu Hong, Blake Schouest, Huanbin Xu
Exosomes are small extracellular vesicles (EVs), released by a wide variety of cell types, carry donor origin-proteins, cytokines, and nucleic acids, transport these cargos to adjacent or distant specific recipient cells, and thereby regulate gene expression and activation of target cells. In this study, we isolated and identified exosomes in rhesus macaques, and investigated their effects on cell tropism and activation, especially their potential to reactivate HIV latency. The results indicated that plasma-derived exosomes preferentially fuse to TCR-activated T cells and autologous parent cells...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29139296/differential-content-of-proteins-mrnas-and-mirnas-suggests-that-mdsc-and-their-exosomes-may-mediate-distinct-immune-suppressive-functions
#10
Lucia Geis-Asteggiante, Ashton T Belew, Virginia K Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Nagib M El-Sayed, Catherine Fenselau
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC...
November 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29138808/the-biology-and-function-of-extracellular-vesicles-in-nasopharyngeal-carcinoma-review
#11
Bo You, Ying Shan, Lili Bao, Jing Chen, Liu Yang, Qicheng Zhang, Wei Zhang, Zhenxin Zhang, Jie Zhang, Si Shi, Yiwen You
Extracellular vesicles are a heterogeneous group of membrane-enclosed vesicles, which play an important role in intercellular communication. Increasing number of studies have shown that tumor-derived extracellular vesicles might be involved in the transfer of oncogenic cargo (proteins, lipids, messenger RNA, microRNA, non-coding RNAs and DNA) through which cancer cells could shape the tumor microenvironment and influence tumor progression. Nasopharyngeal carcinoma-derived extracellular vesicles have also reported to facilitate tumor proliferation, metastasis and immune escape...
November 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29138315/dual-function-for-tango1-in-secretion-of-bulky-cargo-and-in-er-golgi-morphology
#12
L D Ríos-Barrera, S Sigurbjörnsdóttir, M Baer, M Leptin
Tango1 enables ER-to-Golgi trafficking of large proteins. We show here that loss of Tango1, in addition to disrupting protein secretion and ER/Golgi morphology, causes ER stress and defects in cell shape. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect. If large cargos like Dumpy, which we identify as a Tango1 cargo, are removed from the cell, nonbulky proteins reenter the secretory pathway. Removal of blocking cargo also restores cell morphology and attenuates the ER-stress response...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29137858/human-papillomavirus-e6-and-e7-oncoproteins-affect-the-cell-microenvironment-by-classical-secretion-and-extracellular-vesicles-delivery-of-inflammatory-mediators
#13
Marco Iuliano, Giorgio Mangino, Maria Vincenza Chiantore, Maria Simona Zangrillo, Rosita Accardi, Massimo Tommasino, Gianna Fiorucci, Giovanna Romeo
The connection between chronic inflammation and risk of cancer has been supported by several studies. The development of cancer might be a process driven by the presence of a specific combination of inflammatory mediators, including cytokines, chemokines and enzymes, in the tumor microenvironment. Virus-induced tumors, like HPV-induced Squamous Cell Carcinomas, represent a paradigmatic example of the interplay between inflammation, as integral part of the innate antiviral response, and malignant transformation...
November 11, 2017: Cytokine
https://www.readbyqxmd.com/read/29133526/involvement-of-g%C3%AE-%C3%AE-subunits-of-gi-protein-coupled-with-s1p-receptor-on-multivesicular-endosomes-in-f-actin-formation-and-cargo-sorting-into-exosomes
#14
Taketoshi Kajimoto, Nesma Nabil Ibrahim Mohamed, Shaymaa Mohamed Mohamed Badawy, Shubi Ambwene Matovelo, Mitsuhiro Hirase, Shunsuke Nakamura, Daisuke Yoshida, Taro Okada, Takeshi Ijuin, Shun-Ichi Nakamura
Exosomes play a critical role in cell-to-cell communication by delivering cargo molecules to recipient cells. However, the mechanism underlying the generation of the exosomal multivesicular endosome (MVE) is one of the mysteries in the field of endosome research. Although sphingolipid metabolites such as ceramide and sphingosine 1-phosphate (S1P) are known to play important roles in MVE formation and maturation, the detailed molecular mechanisms are still unclear. Here, we show that Rho family GTPases, including Cdc42 and Rac1, are constitutively activated on exosomal MVEs and are regulated by S1P signaling as measured by fluorescence resonance energy transfer (FRET)-based conformational changes...
November 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29133371/turnip-mosaic-virus-counteracts-selective-autophagy-of-the-viral-silencing-suppressor-hcpro
#15
Anders Hafrén, Suayib Üstün, Anton Hochmuth, Steingrim Svenning, Terje Johansen, Daniel Hofius
Autophagy is a conserved intracellular degradation pathway and has emerged as a key mechanism of antiviral immunity in metazoans, including the selective elimination of viral components. In turn, some animal viruses are able to escape and modulate autophagy for enhanced pathogenicity. Whether host autophagic responses and viral countermeasures play similar roles in plant-virus interactions is not well understood. Here, we have identified selective autophagy as antiviral pathway during plant infection with turnip mosaic virus (TuMV), a positive-stranded RNA potyvirus...
November 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29133235/can-the-cellular-internalization-of-cargo-proteins-be-enhanced-by-fusing-a-tat-peptide-in-the-center-of-proteins-a-fluorescence-study
#16
Xiaochao Chen, Jing Chen, Rong Fu, Pingfan Rao, Richard Weller, Jeremy Brasdshaw, Shutao Liu
Aim to investigate whether the cellular uptake of cargo proteins can be enhanced by fusing a Tat peptide in the center of proteins, GST-Tat-GFP and GST-GFP-Tat proteins were firstly constructed and expressed. The cellular internalization of both proteins was then evaluated and compared in HeLa cells by using fluorescent microscopy and flow cytometry, as well as the transdermal delivery in human skin by using confocal microscopy. Results from in-vitro cell experiments showed that GST-Tat-GFP protein efficiently internalized into HeLa cells when a Tat peptide was fused in the center of proteins, whereas its efficiency is lower than that of GST-GFP-Tat protein with a Tat peptide terminal fused...
November 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29131580/modular-self-assembly-of-protein-cage-lattices-for-multistep-catalysis
#17
Masaki Uchida, Kimberly McCoy, Masafumi Fukuto, Lin Yang, Hideyuki Yoshimura, Heini M Miettinen, Ben LaFrance, Dustin P Patterson, Benjamin Schwarz, Jonathan A Karty, Peter E Prevelige, Byeongdu Lee, Trevor Douglas
The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy; the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays...
November 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/29131484/the-major-cellulases-cbh-1-and-cbh-2-of-neurospora-crassa-rely-on-distinct-er-cargo-adaptors-for-efficient-er-exit
#18
Trevor Starr, A Pedro Gonçalves, Neeka Meshgin, N Louise Glass
Filamentous fungi are native secretors of lignocellulolytic enzymes and are used as protein-producing factories in the industrial biotechnology sector. Despite the importance of these organisms in industry, relatively little is known about the filamentous fungal secretory pathway or how it might be manipulated for improved protein production. Here we use Neurospora crassa as a model filamentous fungus to interrogate the requirements for trafficking of cellulase enzymes from the endoplasmic reticulum to the Golgi...
November 13, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29130692/uptake-of-long-protein-polyelectrolyte-nanotubes-by-dendritic-cells
#19
Diana G Ramírez-Wong, Saghi Saghazadeh, Simon Van Herck, Bruno G De Geest, Alain M Jonas, Sophie Demoustier-Champagne
Anisotropic nanostructures, such as nanotubes, incorporating bioactive molecules present interesting features for application as drug delivery carriers. Here, we present the synthesis of layer-by-layer (LbL) nanotubes including protein (ovalbumin) layers and go from simple to more complex synergetic combinations of synthetic and natural polyelectrolytes, leading to structures with tunable properties. The rigidity in organic and aqueous media, the stability in buffer solution and the uptake of different LbL tubes by dendritic cells (DCs) are analyzed to contrast size and chemistry...
November 13, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29129923/ist1-regulates-escrt-iii-assembly-and-function-during-multivesicular-endosome-biogenesis-in-caenorhabditis-elegans-embryos
#20
E B Frankel, Raakhee Shankar, James J Moresco, John R Yates, Niels Volkmann, Anjon Audhya
Degradation of most integral membrane proteins is directed by the endosomal sorting complex required for transport (ESCRT) machinery, which selectively targets ubiquitin-modified cargoes into intralumenal vesicles (ILVs) within multivesicular endosomes (MVEs). To better understand the mechanisms underlying ESCRT-mediated formation of ILVs, we exploited the rapid, de novo biogenesis of MVEs during the oocyte-to-embryo transition in C. elegans. In contrast to previous models suggesting that ILVs form individually, we demonstrate that they remain tethered to one another subsequent to internalization, arguing that they bud continuously from stable subdomains...
November 13, 2017: Nature Communications
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