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https://www.readbyqxmd.com/read/28215090/nonviral-genome-editing-based-on-a-polymer-derivatized-crispr-nanocomplex-for-targeting-bacterial-pathogens-and-antibiotic-resistance
#1
Yoo Kyung Kang, Kyu Kwon, Jea Sung Ryu, Ha Neul Lee, Chankyu Park, Hyun Jung Chung
The overuse of antibiotics plays a major role in the emergence and spread of multidrug-resistant bacteria. A molecularly targeted, specific treatment method for bacterial pathogens can prevent this problem by reducing the selective pressure during microbial growth. Herein, we introduce a nonviral treatment strategy delivering genome editing material for targeting antibacterial resistance. We apply the CRISPR-Cas9 system, which has been recognized as an innovative tool for highly specific and efficient genome engineering in different organisms, as the delivery cargo...
February 19, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28214630/ph-and-reduction-dual-responsive-dipeptide-cationic-lipids-with-%C3%AE-tocopherol-hydrophobic-tail-for-efficient-gene-delivery
#2
Qiang Liu, Rong-Chuan Su, Wen-Jing Yi, Li-Ting Zheng, Shan-Shan Lu, Zhi-Gang Zhao
A series of tocopherol-based cationic lipid 3a-3f bearing a pH-sensitive imidazole moiety in the dipeptide headgroup and a reduction-responsive disulfide linkage were designed and synthesized. Acid-base titration of these lipids showed good buffering capacities. The liposomes formed from 3 and co-lipid 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) could efficiently bind and condense DNA into nanoparticles. Gel binding and HPLC assays confirmed the encapsulated DNA could release from lipoplexes 3 upon addition of 10 mM glutathione (GSH)...
February 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28211573/the-cationic-small-molecule-gw4869-is-cytotoxic-to-high-phosphatidylserine-expressing-myeloma-cells
#3
Slavica Vuckovic, Kate Vandyke, David A Rickards, Padraig McCauley Winter, Simon H J Brown, Todd W Mitchell, Jun Liu, Jun Lu, Philip W Askenase, Elizabeth Yuriev, Ben Capuano, Paul A Ramsland, Geoffrey R Hill, Andrew C W Zannettino, Andrew T Hutchinson
We have discovered that a small cationic molecule, GW4869, is cytotoxic to a subset of myeloma cell lines and primary myeloma plasma cells. Biochemical analysis revealed that GW4869 binds to anionic phospholipids such as phosphatidylserine - a lipid normally confined to the intracellular side of the cell membrane. However, interestingly, phosphatidylserine was expressed on the surface of all myeloma cell lines tested (n = 12) and 9/15 primary myeloma samples. Notably, the level of phosphatidylserine expression correlated well with sensitivity to GW4869...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28210816/efficient-solvothermal-wet-in-situ-transesterification-of-nannochloropsis-gaditana-for-biodiesel-production
#4
Bora Kim, Yong Keun Chang, Jae W Lee
In situ transesterification of wet microalgae is a promising, simplified alternative biodiesel production process that replaces multiple operations of cell drying, extraction, and transesterification reaction. This study addresses enhanced biodiesel production from Nannochloropsis gaditana at elevated temperatures. Compared with the previously reported in situ transesterification process of conducting the reaction at a temperature ranging from 95 to 125 °C, the present work employs higher temperatures of at least 150 °C...
February 16, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28208613/structure-antioxidative-and-anti-inflammatory-activity-relationships-of-purpurin-and-related-anthraquinones-in-chemical-and-cell-assays
#5
Woo Nam, Sung Phil Kim, Seok Hyun Nam, Mendel Friedman
Anthraquinone (9,10-anthraquinone) and several hydroxy derivatives, including purpurin (1,2,4-trihydroxyanthraquinone), anthrarufin (1,5-dihydroxyanthraquinone), and chrysazin (1,8-dihydroxyanthraquinone), were evaluated for antioxidative and anti-inflammatory activities in chemical assays and mammalian cells (murine macrophage RAW 264.7 cells). Several tests were used to assess their activities: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical; ABTS radical cation; hydrogen peroxide scavenging; reduction of potassium ferricyanide; chelation of ferrous ions; inhibition of lipid peroxidation; inhibition of nitric oxide generation; scavenging of the intracellular hydroxyl radical; expression of NLRP3 polypeptide for inflammasome assembly; and quantitation of proinflammatory cytokine interleukin 1β (IL-1β) for inflammasome activation...
February 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28206752/columnar-self-assemblies-of-triarylamines-as-scaffolds-for-artificial-biomimetic-channels-for-ion-and-for-water-transport
#6
Susanne Schneider, Erol-Dan Licsandru, Istvan Kocsis, Arnaud Gilles, Florina Dumitru, Emilie Moulin, Junjun Tan, Jean-Marie Lehn, Nicolas Giuseppone, Mihail Barboiu
Triarylamine molecules appended with crown-ethers or carboxylic moieties form self-assembled supramolecular channels within lipid bilayers. Fluorescence assays and voltage clamp studies reveal that the self-assemblies incorporating the crown ethers work as single channels for the selective transport of K+ or Rb+. The X-ray crystallographic structures confirm the mutual columnar self-assembly of triarylamines and crown-ethers. The dimensional fit of K+ cations within the 18-crown-6, leads to a partial dehydration and to the formation of alternating K+ cation-water wires within the channel...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28198582/cation-selective-channel-regulated-by-anions-according-to-their-hofmeister-ranking
#7
Philip A Gurnev, Torri C Roark, Horia I Petrache, Alexander J Sodt, Sergey M Bezrukov
Specificity of small ions, the Hofmeister ranking, is long-known and has many applications including medicine. Yet it evades consistent theoretical description. Here we study the effect of Hofmeister anions on gramicidin A channels in lipid membranes. Counterintuitively, we find that conductance of this perfectly cation-selective channel increases about two-fold in the H2 PO4(-) <Cl(-) ≈Br(-) ≈NO3(-) <ClO4(-) <SCN(-) series. Channel dissociation kinetics show even stronger dependence, with the dwell time increasing about 20-fold...
February 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28197596/amphiphilic-polymers-formed-from-ring-opening-polymerization-a-strategy-for-the-enhancement-of-gene-delivery
#8
Yi-Mei Zhang, Zheng Huang, Ji Zhang, Wan-Xia Wu, Yan-Hong Liu, Xiao-Qi Yu
Cationic liposomes and polymers are both important candidates for use as non-viral gene vectors. However, both of them have special shortcomings and application limits. This work is devoted to the combination of advantages of liposomes and polymers. The ring-opening polymerization strategy was used for the preparation of amphiphilic polymers from cyclen-based cationic small lipids. The non-hydrophobic polymer and the corresponding lipids were also prepared for performing structure-activity relationship studies...
February 15, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28197373/systemic-activation-of-antigen-presenting-cells-via-rna-loaded-nanoparticles
#9
Elias J Sayour, Gabriel De Leon, Christina Pham, Adam Grippin, Hanna Kemeny, Joshua Chua, Jianping Huang, John H Sampson, Luis Sanchez-Perez, Catherine Flores, Duane A Mitchell
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195195/peptoids-successfully-inhibit-the-growth-of-gram-negative-e-coli-causing-substantial-membrane-damage
#10
Biljana Mojsoska, Gustavo Carretero, Sylvester Larsen, Ramona Valentina Mateiu, Håvard Jenssen
Peptoids are an alternative approach to antimicrobial peptides that offer higher stability towards enzymatic degradation. It is essential when developing new types of peptoids, that mimic the function of antimicrobial peptides, to understand their mechanism of action. Few studies on the specific mechanism of action of antimicrobial peptoids have been described in the literature, despite the plethora of studies on the mode of action of antimicrobial peptides. Here, we investigate the mechanism of action of two short cationic peptoids, rich in lysine and tryptophan side chain functionalities...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193899/structure-of-a-lipid-a-phosphoethanolamine-transferase-suggests-how-conformational-changes-govern-substrate-binding
#11
Anandhi Anandan, Genevieve L Evans, Karmen Condic-Jurkic, Megan L O'Mara, Constance M John, Nancy J Phillips, Gary A Jarvis, Siobhan S Wills, Keith A Stubbs, Isabel Moraes, Charlene M Kahler, Alice Vrielink
Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4' headgroup positions by phosphoethanolamine transferases...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28188804/metabolite-profiling-of-infection-associated-metabolic-markers-of-onchocerciasis
#12
Sasisekhar Bennuru, Sara Lustigman, David Abraham, Thomas B Nutman
The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the "end game". Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LC-MS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and -uninfected individuals (n=20)...
February 8, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28187261/sorption-of-cationic-surfactants-to-artificial-cell-membranes-comparing-phospholipid-bilayers-with-monolayer-coatings-and-molecular-simulations
#13
Niels Timmer, Steven T J Droge
This study reports the distribution coefficient between phospholipid bilayer membranes and PBS medium (DMW,PBS) for 19 cationic surfactants. The method used a sorbent dilution series with solid supported lipid membranes (SSLMs). The existing SSLM protocol, applying a 96 well plate set-up, was adapted to use 1.5 mL glass autosampler vials instead, which facilitated sampling and circumvented several confounding loss processes for some of the cationic surfactants. About 1% of the phospholipids were found to be detached from the SSLM beads, resulting in nonlinear sorption isotherms for compounds with logDMW values above 4...
February 10, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28186523/amphiphilic-dna-tiles-for-controlled-insertion-and-2d-assembly-on-fluid-lipid-membranes-the-effect-on-mechanical-properties
#14
Chikara Dohno, Shingo Makishi, Kazuhiko Nakatani, Sonia Contera
Future lipid membrane-associated DNA nanostructures are expected to find applications ranging from synthetic biology to nanomedicine. Here we have designed and synthesized DNA tiles and modified them with amphiphilic covalent moieties. dod-DEG groups, which consist of a hydrophilic diethylene glycol (DEG) and a hydrophobic dodecyl group, are introduced at the phosphate backbone to create amphiphilic DNA strands which are subsequently introduced into one face of the DNA tiles. In this way the tile becomes able to stably bind to lipid membranes by insertion of the hydrophobic groups inside the bilayer core...
February 10, 2017: Nanoscale
https://www.readbyqxmd.com/read/28185961/non-viral-vectors-based-on-magnetoplexes-lipoplexes-and-polyplexes-for-vegf-gene-delivery-into-central-nervous-system-cells
#15
Ilia Villate-Beitia, Gustavo Puras, Cristina Soto-Sánchez, Mireia Agirre, Edilberto Ojeda, Jon Zarate, Eduardo Fernández, José Luis Pedraz
Nanotechnology based non-viral vectors hold great promise to deliver therapeutic genes into the central nervous system (CNS) in a safe and controlled way. Vascular endothelial growth factor (VEGF) is a potential therapeutic gene candidate for CNS disorders due to its specific roles in brain angiogenesis and neuroprotection. In this work, we elaborated three different non-viral vectors based on magnetic, cationic lipid and polymeric nanoparticles complexed to the phVEGF165aIRESGFP plasmid, which codifies the VEGF protein -extracellular- and the green fluorescent protein (GFP) -intracellular-...
February 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28167534/detection-of-lipid-induced-structural-changes-of-the-marburg-virus-matrix-protein-vp40-using-hydrogen-deuterium-exchange-mass-spectrometry
#16
Kaveesha J Wijesinghe, Sarah Urata, Nisha Bhattarai, Edgar E Kooijman, Bernard S Gerstman, Prem P Chapagain, Sheng Li, Robert V Stahelin
Marburg virus (MARV) is a lipid-enveloped virus from the Filoviridae family containing a negative sense RNA genome. One of the seven MARV genes encodes the matrix protein VP40, which forms a matrix layer beneath the plasma membrane inner leaflet to facilitate budding from the host cell. MARV VP40 (mVP40) has been shown to be a dimeric peripheral protein with a broad and flat basic surface that can associate with anionic phospholipids such as phosphatidylserine. While a number of mVP40 cationic residues have been shown to facilitate binding to membranes containing anionic lipids, much less is known on how mVP40 assembles to form the matrix layer following membrane binding...
February 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28167287/poly-sgrna-sirna-ribonucleoprotein-nanoparticles-for-targeted-gene-disruption
#17
Jong Seong Ha, Jae Sung Lee, Jaepil Jeong, Hejin Kim, Juyoung Byun, Sang Ah Kim, Hee Jae Lee, Hak Suk Chung, Jong Bum Lee, Dae-Ro Ahn
Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) can be used for the specific disruption of a target gene to permanently suppress the expression of the protein encoded by the target gene. Efficient delivery of the system to an intracellular target site should be achieved to utilize the tremendous potential of the genome-editing tool in biomedical applications such as the knock-out of disease-related genes and the correction of defect genes. Here, we devise polymeric CRISPR/Cas9 system based on poly-ribonucleoprotein (RNP) nanoparticles consisting of polymeric sgRNA, siRNA, and Cas9 endonuclease in order to improve the delivery efficiency...
February 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28165217/calcium-assists-dopamine-release-by-preventing-aggregation-on-the-inner-leaflet-of-presynaptic-vesicles
#18
Sini Mokkila, Pekka A Postila, Sami Rissanen, Hanna Juhola, Ilpo Vattulainen, Tomasz Rog
Tightly controlled neurotransmitter-membrane interactions can speed up signal transduction by coordinating the movements of the transmitters inside the synapse. In this study, the dopamine-lipid bilayer interactions were probed with three physiologically relevant ion compositions using atomistic molecular dynamics simulations and free energy calculations. The in silico results show that calcium decreases significantly the binding of dopamine to a neutral (zwitterionic) phosphatidylcholine lipid bilayer used to model the inner leaflet of a presynaptic vesicle...
February 6, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28159514/self-assembling-complexes-between-binary-mixtures-of-lipids-with-different-linkers-and-nucleic-acids-promote-universal-mrna-dna-and-sirna-delivery
#19
Thibault Colombani, Pauline Peuziat, Laurence Dallet, Thomas Haudebourg, Mathieu Mével, Mathieu Berchel, Olivier Lambert, Damien Habrant, Bruno Pitard
Protein expression and RNA interference require efficient delivery of DNA or mRNA and small double stranded RNA into cells, respectively. Although cationic lipids are the most commonly used synthetic delivery vectors, a clear need still exists for a better delivery of various types of nucleic acids molecules to improve their biological activity. To optimize the transfection efficiency, a molecular approach consisting in modifying the chemical structure of a given cationic lipid is usually performed, but an alternative strategy could rely on modulating the supramolecular assembly of lipidic lamellar phases sandwiching the nucleic acids molecules...
February 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28154264/modifying-cationic-liposomes-with-cholesteryl-peg-prevents-their-aggregation-in-human-urine-and-enhances-cellular-uptake-by-bladder-cancer-cells
#20
Takashi Nakamura, Yosuke Noma, Yu Sakurai, Hideyoshi Harashima
Intravesical drug delivery by cationic liposomes (Cat-LPs) represents a potent nanotechnology for enhancing therapeutic effects against bladder disorders. However, preventing the aggregation of Cat-LPs in urine poses a significant barrier. We report on an examination of the effect of modifying liposomes with polyethylene glycol (PEG) lipids to prevent Cat-LPs from aggregating in human urine. Although Cat-LPs underwent significant aggregation in human urine, introducing 5 mol% of PEG2k lipid or 2 mol% of PEG5k lipid completely inhibited the aggregation of the Cat-LPs...
2017: Biological & Pharmaceutical Bulletin
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