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https://www.readbyqxmd.com/read/29346777/prrt2-regulates-synaptic-fusion-by-directly-modulating-snare-complex-assembly
#1
Jeff Coleman, Ouardane Jouannot, Sathish K Ramakrishnan, Maria N Zanetti, Jing Wang, Vincenzo Salpietro, Henry Houlden, James E Rothman, Shyam S Krishnakumar
Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the pre-synaptic terminals and is believed to regulate neurotransmitter release. However, the mechanism of action is unclear. Here, we use reconstituted single vesicle and bulk fusion assays, combined with live cell imaging of single exocytotic events in PC12 cells and biophysical analysis, to delineate the physiological role of PRRT2. We report that PRRT2 selectively blocks the trans SNARE complex assembly and thus negatively regulates synaptic vesicle priming...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346734/fluctuation-effects-on-the-brush-structure-of-mixed-brush-nanoparticles-in-solution
#2
Jason P Koski, Amalie L Frischknecht
A potentially attractive way to control nanoparticle assembly is to graft one or more polymers on the nanoparticle, to control the nanoparticle-nanoparticle interactions. When two immiscible polymers are grafted on the nanoparticle, they can microphase separate to form domains at the nanoparticle surface. Here we computationally investigate the phase behavior of such binary mixed brush nanoparticles in solution, across a large and experimentally relevant parameter space. Specifically, we calculate the mean-field phase diagram, assuming uniform grafting of the two polymers, as a function of the nanoparticle size relative to the length of the grafted chains, the grafting density, the enthalpic repulsion between the grafted chains, and the solvent quality...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#3
Janina-Miriam Noy, Hongxu Lu, Philip Hogg, Jia-Lin Yang, Martina H Stenzel
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anti-cancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition fragmentation chin transfer) polymerization with poly(polyethylene glycol methyl ether methacrylate) (PEGMA) as comonomer and poly(methylmethacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt...
January 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29346728/design-and-assembly-of-chiral-coordination-cages-for-asymmetric-sequential-reactions
#4
Jingjing Jiao, Chunxia Tan, Zijian Li, Yan Liu, Xing Han, Yong Cui
Supramolecular nanoreactors featuring multiple catalytically active sites are of great importance, especially for asymmetric catalysis, are yet challenging to construct. Here we report the design and assembly of five chiral single- and mixed-linker tetrahedral coordination cages using six dicarboxylate ligands derived-from enantiopure Mn(salen), Cr(salen) and/or Fe(salen) as linear linkers and four Cp3Zr3 clusters as three-connected vertices. The formation of these cages was confirmed by a variety of techniques including single-crystal and powder X-ray diffraction, inductively coupled plasma optical emission spectrometer, quadrupole-time of flight mass spectrometry and energy dispersive X-ray spectrometry...
January 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29346724/structural-and-biophysical-characterization-of-human-extl3-domain-organisation-glycosylation-and-solution-structure
#5
Wael Awad, Sven Kjellstrom, Gabriel Svensson Birkedal, Katrin Mani, Derek Thomas Logan
Heparan sulfate proteoglycans are proteins substituted with one or more heparan sulfate (HS) polysaccharides, found in abundance at cell surfaces. HS chains influence the activity of many biologically important molecules involved in cellular communication and signaling. The exostosin (EXT) proteins are glycosyltransferases in the Golgi apparatus that assemble HS chains on HSPGs. The EXTL3 enzyme mainly works as an initiator in HS biosynthesis. In this work, human lumenal N-glycosylated EXTL3 (EXTL3ΔN) was cloned, expressed in human embryonic kidney cells and purified...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29346720/nanoscale-control-of-molecular-self-assembly-induced-by-plasmonic-hot-electron-dynamics
#6
Sabrina Simoncelli, Yi Li, Emiliano Cortes, Stefan A Maier
Self-assembly processes allow designing and creating complex nanostructures using molecules as building blocks and surfaces as scaffolds. This autonomous driven construction is possible due to a complex thermodynamic balance of molecule-surface interactions. As such, nanoscale guidance and control over this process is hard to achieve. Here we use the highly localized light-to-chemical-energy conversion of plasmonic materials to spatially cleave Au-S bonds on pre-determined locations within a single nanoparticle, enabling a high degree of control over this archetypal system for molecular self-assembly...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346644/genome-wide-analysis-of-disease-progression-in-age-related-macular-degeneration
#7
Qi Yan, Ying Ding, Yi Liu, Tao Sun, Lars G Fritsche, Traci Clemons, Rinki Ratnapriya, Michael L Klein, Richard J Cook, Yu Liu, Ruzong Fan, Lai Wei, Gonçalo R Abecasis, Anand Swaroop, Emily Y Chew, Daniel E Weeks, Wei Chen
Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related Macular Degeneration (AMD), one of the first batch and most successful examples of genome-wide association study (GWAS). However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization [CNV] or geographic atrophy [GA]). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2,721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29346625/complete-genomic-and-transcriptional-landscape-analysis-using-third-generation-sequencing-a-case-study-of-saccharomyces-cerevisiae-cen-pk113-7d
#8
Piroon Jenjaroenpun, Thidathip Wongsurawat, Rui Pereira, Preecha Patumcharoenpol, David W Ussery, Jens Nielsen, Intawat Nookaew
Completion of eukaryal genomes can be difficult task with the highly repetitive sequences along the chromosomes and short read lengths of second-generation sequencing. Saccharomyces cerevisiae strain CEN.PK113-7D, widely used as a model organism and a cell factory, was selected for this study to demonstrate the superior capability of very long sequence reads for de novo genome assembly. We generated long reads using two common third-generation sequencing technologies (Oxford Nanopore Technology (ONT) and Pacific Biosciences (PacBio)) and used short reads obtained using Illumina sequencing for error correction...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346586/plasflow-predicting-plasmid-sequences-in-metagenomic-data-using-genome-signatures
#9
Pawel S Krawczyk, Leszek Lipinski, Andrzej Dziembowski
Plasmids are mobile genetics elements that play an important role in the environmental adaptation of microorganisms. Although plasmids are usually analyzed in cultured microorganisms, there is a need for methods that allow for the analysis of pools of plasmids (plasmidomes) in environmental samples. To that end, several molecular biology and bioinformatics methods have been developed; however, they are limited to environments with low diversity and cannot recover large plasmids. Here, we present PlasFlow, a novel tool based on genomic signatures that employs a neural network approach for identification of bacterial plasmid sequences in environmental samples...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346504/baum-improving-genome-assembly-by-adaptive-unique-mapping-and-local-overlap-layout-consensus-approach
#10
Anqi Wang, Zhanyu Wang, Zheng Li, Lei M Li
Motivation: It is highly desirable to assemble genomes of high continuity and consistency at low cost. The current bottleneck of draft genome continuity using the Second Generation Sequencing (SGS) reads is primarily caused by uncertainty among repetitive sequences. Even though the Single-Molecule Real-Time sequencing technology is very promising to overcome the uncertainty issue, its relatively high cost and error rate add burden on budget or computation. Many long-read assemblers take the overlap-layout-consensus (OLC) paradigm, which is less sensitive to sequencing errors, heterozygosity and variability of coverage...
January 15, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29346368/mechanical-feedback-coordinates-cell-wall-expansion-and-assembly-in-yeast-mating-morphogenesis
#11
Samhita P Banavar, Carlos Gomez, Michael Trogdon, Linda R Petzold, Tau-Mu Yi, Otger Campàs
The shaping of individual cells requires a tight coordination of cell mechanics and growth. However, it is unclear how information about the mechanical state of the wall is relayed to the molecular processes building it, thereby enabling the coordination of cell wall expansion and assembly during morphogenesis. Combining theoretical and experimental approaches, we show that a mechanical feedback coordinating cell wall assembly and expansion is essential to sustain mating projection growth in budding yeast (Saccharomyces cerevisiae)...
January 18, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29346330/formulation-of-poloxamers-for-drug-delivery
#12
REVIEW
Andrew M Bodratti, Paschalis Alexandridis
Poloxamers, also known as Pluronics®, are block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character and useful association and adsorption properties emanating from this. Poloxamers find use in many applications that require solubilization or stabilization of compounds and also have notable physiological properties, including low toxicity. Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current challenges facing nanomedicine revolve around the transport of typically water-insoluble drugs throughout the body, followed by targeted delivery...
January 18, 2018: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/29346320/c-phycocyanin-and-phycocyanobilin-as-remyelination-therapies-for-enhancing-recovery-in-multiple-sclerosis-and-ischemic-stroke-a-preclinical-perspective
#13
REVIEW
Giselle Pentón-Rol, Javier Marín-Prida, Viviana Falcón-Cama
Myelin loss has a crucial impact on behavior disabilities associated to Multiple Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are approved, none of them promote remyelination in patients, limiting their ability for chronic recovery. With no available therapeutic options, enhanced demyelination in stroke survivors is correlated with a poorer behavioral recovery. Here, we show the experimental findings of our group and others supporting the remyelinating effects of C-Phycocyanin (C-PC), the main biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin (PCB), in models of these illnesses...
January 18, 2018: Behavioral Sciences
https://www.readbyqxmd.com/read/29346292/isoform-sequencing-and-state-of-art-applications-for-unravelling-complexity-of-plant-transcriptomes
#14
REVIEW
Dong An, Hieu X Cao, Changsheng Li, Klaus Humbeck, Wenqin Wang
Single-molecule real-time (SMRT) sequencing developed by PacBio, also called third-generation sequencing (TGS), offers longer reads than the second-generation sequencing (SGS). Given its ability to obtain full-length transcripts without assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is advantageous for genome annotation, identification of novel genes and isoforms, as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq gives access to the direct detection of alternative splicing, alternative polyadenylation (APA), gene fusion, and DNA modifications...
January 18, 2018: Genes
https://www.readbyqxmd.com/read/29346288/application-of-computational-intelligence-to-improve-education-in-smart-cities
#15
Everton Gomede, Fernando Henrique Gaffo, Gabriel Ulian Briganó, Rodolfo Miranda de Barros, Leonardo de Souza Mendes
According to UNESCO, education is a fundamental human right and every nation's citizens should be granted universal access with equal quality to it. Because this goal is yet to be achieved in most countries, in particular in the developing and underdeveloped countries, it is extremely important to find more effective ways to improve education. This paper presents a model based on the application of computational intelligence (data mining and data science) that leads to the development of the student's knowledge profile and that can help educators in their decision making for best orienting their students...
January 18, 2018: Sensors
https://www.readbyqxmd.com/read/29346275/a-review-on-recent-advances-in-stabilizing-peptides-proteins-upon-fabrication-in-hydrogels-from-biodegradable-polymers
#16
REVIEW
Faisal Raza, Hajra Zafar, Ying Zhu, Yuan Ren, Aftab -Ullah, Asif Ullah Khan, Xinyi He, Han Han, Md Aquib, Kofi Oti Boakye-Yiadom, Liang Ge
Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner...
January 18, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29346173/the-subresolution-datscan-phantom-a-cost-effective-flexible-alternative-to-traditional-phantom-technology
#17
Jonathan C Taylor, Nicholas Vennart, Ian Negus, Robin Holmes, Oliver Bandmann, Christine Lo, John Fenner
The Alderson striatal phantom is frequently used to assess I-FP-CIT (Ioflupane) image quality and to test semi-quantification software. However, its design is associated with a number of limitations, in particular: unrealistic image appearances and inflexibility. A new physical phantom approach is proposed on the basis of subresolution phantom technology. The design incorporates thin slabs of attenuating material generated through additive manufacturing, and paper sheets with radioactive ink patterns printed on their surface, created with a conventional inkjet printer...
January 17, 2018: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/29346004/universal-lead-screening-requirement-a-california-case-study
#18
Sara B McMenamin, Sarah P Hiller, Erin Shigekawa, Troy Melander, Riti Shimkhada
OBJECTIVES: To estimate potential impacts of California Assembly Bill (AB) 1316: a requirement for universal screening and insurance coverage for child blood lead testing. METHODS: In April 2017 the California Health Benefits Review Program (Oakland, CA) analyzed AB 1316 for the California legislature, including a systematic review of lead screening effectiveness, commercial insurer surveys regarding screening coverage, and actuarial utilization and cost implication assessments...
January 18, 2018: American Journal of Public Health
https://www.readbyqxmd.com/read/29345989/assembly-of-copi-and-copii-vesicular-coat-proteins-on-membranes
#19
Julien Béthune, Felix T Wieland
In eukaryotes, distinct transport vesicles functionally connect various intracellular compartments. These carriers mediate transport of membranes for the biogenesis and maintenance of organelles, secretion of cargo proteins and peptides, and uptake of cargo into the cell. Transport vesicles have distinct protein coats that assemble on a donor membrane where they can select cargo and curve the membrane to form a bud. A multitude of structural elements of coat proteins have been solved by X-ray crystallography...
January 18, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29345953/micro-to-nanoscale-engineering-of-surface-precipitates-using-reconfigurable-contact-lines
#20
Prasenjit Kabi, Swetaprovo Chaudhuri, Saptarshi Basu
Nanoscale engineering has traditionally adopted the chemical route of synthesis or opto-chemical techniques like lithography requiring large process times, expensive equipment and an inert environment. Directed self-assembly using evaporation of nanocolloidal droplet can be a potential low-cost alternative across various industries ranging from semiconductors to biomedical systems. It is relatively simple to scale and re-orient the evaporation driven internal flow field in an evaporating droplet which can direct dispersed matter into functional agglomerates...
January 18, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
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