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https://www.readbyqxmd.com/read/29334397/recombinant-phosphatidylserine-binding-nanobodies-for-targeting-of-extracellular-vesicles-to-tumor-cells-a-plug-and-play-approach
#1
Sander A A Kooijmans, Jerney J J M Gitz-Francois, Raymond M Schiffelers, Pieter Vader
Extracellular vesicles (EVs) are increasingly being recognized as candidate drug delivery systems due to their ability to functionally transfer biological cargo between cells. However, manipulation of targeting properties of EVs through engineering of the producer cells can be challenging and time-consuming. As a novel approach to confer tumor targeting properties to isolated EVs, we generated recombinant fusion proteins of nanobodies against the epidermal growth factor receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin (C1C2)...
January 15, 2018: Nanoscale
https://www.readbyqxmd.com/read/29334370/scaffolds-that-mimic-antigen-presenting-cells-enable-ex-vivo-expansion-of-primary-t-cells
#2
Alexander S Cheung, David K Y Zhang, Sandeep T Koshy, David J Mooney
Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads)...
January 15, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29332844/understanding-carbon-nanotube-channel-formation-in-the-lipid-membrane
#3
Moon-Ki Choi, Hyunki Kim, Byung Ho Lee, Teayeop Kim, Junsuk Rho, Moon Ki Kim, Kyunghoon Kim
Carbon nanotube (CNT) has been considered as a prominent nano-channel in cell membranes because of their prominent ion-conductance and ion-selectivity, offering agents for biomimetic channel platform. Using a coarse-grained molecular dynamics simulation, we clarify a construction mechanism of vertical CNT nano-channels in the lipid membrane for a long period, that has been difficult to observe in previous CNT-lipid interaction simulations. The result shows that both lipid coating density and length of CNT affect the suitable fabrication condition for a vertical and stable CNT-channel...
January 15, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29332576/current-understanding-of-physicochemical-mechanisms-for-cell-membrane-penetration-of-arginine-rich-cell-penetrating-peptides-role-of-glycosaminoglycan-interactions
#4
Yuki Takechi-Haraya, Hiroyuki Saito
Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet...
January 11, 2018: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29332565/beyond-the-lock-and-key-paradigm-targeting-lipid-rafts-to-induce-the-selective-apoptosis-of-cancer-cells
#5
Anna Carolina Schneider Alves, Reinaldo Antonio Dias, Luciano Porto Kagami, Gustavo Machado das Neves, Fernando Cidade Torres, Vera Lucia Eifler-Lima, Ivone Carvalho, Carolina de Miranda Silva, Daniel Fabio Kawano
For more than 40 years, the fluid mosaic model of cellular membranes have supported our vision of an inert lipid bilayer containing membrane protein receptors that are randomly hit by extracellular molecules to trigger intracellular signaling events. However, the notion that compartmentalized cholesterol- and sphingomyelin-rich membrane microdomains (known as lipid rafts) spatially arrange receptors and effectors to promote kinetically favorable interactions necessary for the signal transduction sounds much more realistic...
January 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29332291/analysis-of-reactive-carbonyl-species-generated-under-oxidative-stress
#6
Jun'ichi Mano, Md Sanaullah Biswas
Oxidation of membrane lipids by reactive oxygen species primarily generates lipid peroxides, from which various carbonyls, i.e., aldehydes and ketones, are formed. Among them, those with a carbonyl-conjugated C-C double bond have significant biological functions and are designated as reactive carbonyl species (RCS). A dozen kinds of RCS occurring in plant cells have a broad spectrum of reactivity and biological effects, depending on the structure. Several RCS have been recently found to activate caspase-like proteases in plants, thereby initiating PCD...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29332151/1h-13c-and-15n-backbone-and-partial-side-chain-resonance-assignments-of-the-c-terminal-domain-of-hiv-1-pr55gag-encompassed-in-ncp15
#7
Valéry Larue, Marjorie Catala, Anissa Belfetmi, Loussiné Zargarian, Olivier Mauffret, Carine Tisné
During HIV-1 assembly, the Pr55Gag polyprotein precursor (Gag) interacts with the genomic RNA, with lipids of the plasma membrane, with host proteins (ALIX, TSG101) through the ESCRT complex, with the viral protein Vpr and are involved in intermolecular interactions with other Pr55Gag proteins. This network of interactions is responsible for the formation of the viral particle, the selection of genomic RNA and the packaging of Vpr. The C-terminal domain of Gag encompassed in NCp15 is involved in the majority of these interactions, either by its nucleocapsid or its p6 domains...
January 13, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29331881/ameliorative-role-of-genistein-against-age-dependent-chronic-arsenic-toxicity-in-murine-brains-via-the-regulation-of-oxidative-stress-and-inflammatory-signaling-cascades
#8
Sukanya Saha, Pritam Sadhukhan, Sushweta Mahalanobish, Sayanta Dutta, Parames C Sil
Brain is highly prone to oxidative damage due to its huge lipid content and extensive energy requirements. Exogenous insult in brain via oxidative injury can lead to severe pathophysiological conditions. Age-dependent deterioration of normal brain functions is also noteworthy. Genistein, a polyphenolic isoflavonoid, obtained from the soy plant, is well known to protect against several diseased conditions. Here, in this study chronic brain toxicity model was developed using oral administration of arsenic for 90 days in adult and aged murines...
December 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29331649/friend-or-foe-reactive-oxygen-species-production-scavenging-and-signaling-in-plant-response-to-environmental-stresses
#9
Weronika Czarnocka, Stanisław Karpiński
In the natural environment, plants are exposed to a variety of biotic and abiotic stress conditions that trigger rapid changes in the production and scavenging of reactive oxygen species (ROS). The production and scavenging of ROS is compartmentalized, which means that, depending on stimuli type, they can be generated and eliminated in different cellular compartments such as the apoplast, plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic reticulum. Although the accumulation of ROS is generally harmful to cells, ROS play an important role in signaling pathways that regulate acclimatory and defense responses in plants, such as systemic acquired acclimation (SAA) and systemic acquired resistance (SAR)...
January 10, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29330605/membrane-ion-interactions
#10
Ran Friedman
Biomembranes assemble and operate at the interface with electrolyte solutions. Interactions between ions in solutions and the lipid affect the membrane structure, dynamics and electrostatic potential. In this article, I review some of the experimental and computational methods that are used to study membrane-ions interactions. Experimental methods that account for membrane-ion interactions directly and indirectly are presented first. Then, studies in which molecular dynamics simulations were used to gain an understanding of membrane-ion interactions are surveyed...
January 12, 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29330446/effect-of-puerarin-in-promoting-fatty-acid-oxidation-by-increasing-mitochondrial-oxidative-capacity-and-biogenesis-in-skeletal-muscle-in-diabetic-rats
#11
Xiu-Fang Chen, Lei Wang, Yong-Zheng Wu, Shi-Yu Song, Hai-Yan Min, Yan Yang, Xuan He, Qiao Liang, Long Yi, Yong Wang, Qian Gao
BACKGROUND: Type 2 diabetes is characterized by dyslipidemia and the accumulation of lipids in non-adipose tissue, including skeletal muscle. Puerarin, which is a natural isoflavonoid isolated from the root of the plant Pueraria lobata, has been shown to have antidiabetic activity. However, the lipid-reducing effect of puerarin, in particular in skeletal muscle, has not yet been addressed. METHODS: We examined the effect of puerarin on mitochondrial function and the oxidation of fatty acids in the skeletal muscle of high-fat diet/streptozotocin-induced diabetic rats...
January 12, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29330366/each-protomer-of-a-dimeric-yidc-functions-as-a-single-membrane-insertase
#12
Dirk Spann, Eva Pross, Yuanyuan Chen, Ross E Dalbey, Andreas Kuhn
The membrane insertase YidC catalyzes the entrance of newly synthesized proteins into the lipid bilayer. As an integral membrane protein itself, YidC can be found as a monomer, a dimer or also as a member of the holotranslocase SecYEGDF-YajC-YidC. To investigate whether the dimeric YidC is functional and whether two copies cooperate to insert a single substrate, we constructed a fusion protein where two copies of YidC are connected by a short linker peptide. The 120 kDa protein is stable and functional as it supports the membrane insertion of the M13 procoat protein, the C-tailed protein SciP and the fusion protein Pf3-Lep...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330356/metabolic-and-molecular-changes-associated-with-the-increased-skeletal-muscle-insulin-action-24-48%C3%A2-h-after-exercise-in-young-and-old-humans
#13
REVIEW
Francis B Stephens, Kostas Tsintzas
The molecular and metabolic mechanisms underlying the increase in insulin sensitivity (i.e. increased insulin-stimulated skeletal muscle glucose uptake, phosphorylation and storage as glycogen) observed from 12 to 48 h following a single bout of exercise in humans remain unresolved. Moreover, whether these mechanisms differ with age is unclear. It is well established that a single bout of exercise increases the translocation of the glucose transporter, GLUT4, to the plasma membrane. Previous research using unilateral limb muscle contraction models in combination with hyperinsulinaemia has demonstrated that the increase in insulin sensitivity and glycogen synthesis 24 h after exercise is also associated with an increase in hexokinase II (HKII) mRNA and protein content, suggesting an increase in the capacity of the muscle to phosphorylate glucose and divert it towards glycogen synthesis...
January 12, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29330108/membrane-lipid-associated-lncrna-a-new-regulator-in-cancer-signaling
#14
Yanxiu Ma, Junmei Zhang, Lixia Wen, Aifu Lin
Long noncoding RNAs (LncRNAs) are one of the emerging regulators which are involved in diverse biological processes. LncRNAs can participate in the regulation of gene expression via various ways in the cytoplasm and the nucleus. The function of the nuclear lncRNAs has been studied a lot. Recent studies have shown that the regulatory roles of cytoplasmic lncRNA, including membrane lipid associated lncRNA, may open an unexplored mechanistic territory. LncRNA dysregulated expression represents a common event in pathogenesis of a variety of human genetic diseases including cancer...
January 9, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330069/conformation-and-trimer-association-of-the-transmembrane-domain-of-the-parainfluenza-virus-fusion-protein-in-lipid-bilayers-from-solid-state-nmr-insights-into-the-sequence-determinants-of-trimer-structure-and-fusion-activity
#15
Myungwoon Lee, Hongwei Yao, Byungsu Kwon, Alan J Waring, Peter Ruchala, Chandan Singh, Mei Hong
Enveloped viruses enter cells by using their fusion proteins to merge the virus lipid envelope and the cell membrane. While crystal structures of the water-soluble ectodomains of many viral fusion proteins have been determined, the structure and assembly of the C-terminal transmembrane domain (TMD) remains poorly understood. Here we use solid-state NMR to determine the backbone conformation and oligomeric structure of the TMD of the parainfluenza virus 5 (PIV5) fusion protein. 13C chemical shifts indicate that the central leucine-rich segment of the TMD is α-helical in POPC/cholesterol membranes and POPE membranes, while the Ile- and Val-rich termini shift to the β-strand conformation in the POPE membrane...
January 9, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29330047/an-intrinsically-disordered-domain-in-polaribacter-irgensii-kopri-22228-cspb-confers-extraordinary-freeze-tolerance
#16
Youn Hong Jung, Ji-Hyun Uh, Kyunghee Lee, Hana Im
Organisms living in extremely cold environments possess mechanisms to survive low temperatures. Among the known cold-induced genes, cold-shock proteins (Csps) are the most prominent. A csp-homologous gene, cspBPi, has been cloned from the Arctic bacterium Polaribacter irgensii KOPRI 22228, and overexpression of this gene greatly increased the freezing tolerance of its host. This protein consists of a unique N-terminal domain and a well conserved C-terminal cold shock domain. To elucidate the detailed mechanisms involved in the extraordinary freeze-tolerance conferred by CspBPi, we identified the responsible domain by mutational analysis...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330024/nucleophosmin-1-regions-associated-with-acute-myeloid-leukemia-interact-differently-with-lipid-membranes
#17
Augusta De Santis, Sara La Manna, Irene Russo Krauss, Anna Maria Malfitano, Ettore Novellino, Luca Federici, Antonella De Cola, Adele Di Matteo, Gerardino D'Errico, Daniela Marasco
No abstract text is available yet for this article.
January 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29329756/phospholipid-composition-of-the-outer-membrane-of-escherichia-coli-influences-its-susceptibility-against-antimicrobial-peptide-apidaecin-1b
#18
Rico Schmidt, Ding Yonghong, Ralf Hoffmann
Proline-rich antimicrobial peptides (PrAMPs) kill bacteria in a multimodal mechanism by inhibiting the 70S ribosome (i.e., protein translation) as dominant lethal mechanism besides inhibition of several other proteins, such as chaperone DnaK. PrAMPs pass the outer membrane of Gram-negative bacteria, probably by a self-promoted uptake followed by a transporter-mediated uptake from the periplasm. Mutation of transporter protein SbmA is a well-studied resistance mechanism observed in vitro by resistance induction with PrAMPs...
November 21, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29329415/establishment-of-a-three-dimensional-model-to-study-human-uterine-angiogenesis
#19
Camille L Duran, Colette A Abbey, Kayla J Bayless
STUDY QUESTION: Can primary human uterine microvascular endothelial cells (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic responses when stimulated with proangiogenic factors, including sphingosine 1-phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), physiological levels of wall shear stress (WSS), human chorionic gonadotropin (hCG) and various combinations of estrogen and progesterone...
December 21, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29328670/the-surface-oxidation-of-graphene-oxide-determines-membrane-damage-lipid-peroxidation-and-cytotoxicity-in-macrophages-in-a-pulmonary-toxicity-model
#20
Ruibin Li, Linda M Guiney, Chong Hyun Chang, Nikhita D Mansukhani, Zhaoxia Ji, Xiang Wang, Yu-Pei Liao, Wen Jiang, Bingbing Sun, Mark C Hersam, Andre E Nel, Tian Xia
While 2-dimensional graphene oxide (GO) is used increasingly in biomedical applications, there is uncertainty on how specific physicochemical properties relate to biocompatibility in mammalian systems. Although properties such as lateral size and the colloidal properties of the nanosheets are important, the specific material properties that we address here is the oxidation state and reactive surface groups on the planar surface. In this study, we used a GO library, comprised of pristine, reduced (rGO), and hydrated GO (hGO), in which quantitative assessment of the hydroxyl, carboxyl, epoxy and carbon radical contents were used to study the impact on epithelial cells and macrophages, as well as in the murine lung...
January 12, 2018: ACS Nano
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