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https://www.readbyqxmd.com/read/29334379/highly-parallel-direct-rna-sequencing-on-an-array-of-nanopores
#1
Daniel R Garalde, Elizabeth A Snell, Daniel Jachimowicz, Botond Sipos, Joseph H Lloyd, Mark Bruce, Nadia Pantic, Tigist Admassu, Phillip James, Anthony Warland, Michael Jordan, Jonah Ciccone, Sabrina Serra, Jemma Keenan, Samuel Martin, Luke McNeill, E Jayne Wallace, Lakmal Jayasinghe, Chris Wright, Javier Blasco, Stephen Young, Denise Brocklebank, Sissel Juul, James Clarke, Andrew J Heron, Daniel J Turner
Sequencing the RNA in a biological sample can unlock a wealth of information, including the identity of bacteria and viruses, the nuances of alternative splicing or the transcriptional state of organisms. However, current methods have limitations due to short read lengths and reverse transcription or amplification biases. Here we demonstrate nanopore direct RNA-seq, a highly parallel, real-time, single-molecule method that circumvents reverse transcription or amplification steps. This method yields full-length, strand-specific RNA sequences and enables the direct detection of nucleotide analogs in RNA...
January 15, 2018: Nature Methods
https://www.readbyqxmd.com/read/29334219/mussel-inspired-conductive-polymer-binder-for-si-alloy-anode-in-lithium-ion-batteries
#2
Hui Zhao, Yang Wei, Cheng Wang, Rui-Min Qiao, Wanli Yang, Phillip B Messersmith, Gao Liu
The excessive volume changes during cell cycling of Si-based anode in lithium ion batteries impeded its application. One major reason for the cell failure is particle isolation during volume shrinkage in delithiation process, which makes strong adhesion between polymer binder and anode active material particles a highly desirable property. Here, a biomimetic side-chain conductive polymer incorporating catechol, a key adhesive component of the mussel holdfast protein, was synthesized. Atomic force microscopy (AFM) based single molecule force measurements of mussel-inspired conductive polymer binder contacting a silica surface revealed similar adhesion toward substrate when compared with an effective Si anode binder, homo-polyacrylic acid (PAA), with the added benefit of being electronically conductive...
January 15, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29331760/inotodiol-suppresses-proliferation-of-breast-cancer-in-rat-model-of-type-2-diabetes-mellitus-via-downregulation-of-%C3%AE-catenin-signaling
#3
Xia Zhang, Cuiyu Bao, Jingping Zhang
Breast cancer is amongst the most common cancers causing death of women worldwide. Breast cancer occurrence is more prominent in people with diabetes. A recent trend is management of diabetes and cancer has evolved to be natural remedy including single molecule therapy or combination. In this study, we investigated the effect of inotodiol on breast cancer growth in diabetic conditions. Inotodiol is a lanostane triterpenoid found in natural resources like edible mushroom Inonotus obliquus. We established a rat model of diabetic-breast cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35 mg/kg followed by induction of breast cancer by administration of 7,12-dimethylbenz(a)anthracene (DMBA) at 10 mg/kg...
January 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29331424/ultra-narrow-surface-lattice-resonances-in-plasmonic-metamaterial-arrays-for-biosensing-applications
#4
Artem Danilov, Gleb Tselikov, Fan Wu, Vasyl G Kravets, Igor Ozerov, Frederic Bedu, Alexander N Grigorenko, Andrei V Kabashin
When excited over a periodic metamaterial lattice of gold nanoparticles (~ 100nm), localized plasmon resonances (LPR) can be coupled by a diffraction wave propagating along the array plane, which leads to a drastic narrowing of plasmon resonance lineshapes (down to a few nm full-width-at-half-maximum) and the generation of singularities of phase of reflected light. These phenomena look very promising for the improvement of performance of plasmonic biosensors, but conditions of implementation of such diffractively coupled plasmonic resonances, also referred to as plasmonic surface lattice resonances (PSLR), are not always compatible with biosensing arrangement implying the placement of the nanoparticles between a glass substrate and a sample medium (air, water)...
December 9, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29331122/thermally-induced-charge-current-through-long-molecules
#5
Natalya A Zimbovskaya, Abraham Nitzan
In this work, we theoretically study steady state thermoelectric transport through a single-molecule junction with a long chain-like bridge. Electron transmission through the system is computed using a tight-binding model for the bridge. We analyze dependences of thermocurrent on the bridge length in unbiased and biased systems operating within and beyond the linear response regime. It is shown that the length-dependent thermocurrent is controlled by the lineshape of electron transmission in the interval corresponding to the HOMO/LUMO transport channel...
January 14, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#6
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330363/disulfide-isomerization-reactions-in-titin-immunoglobulin%C3%A2-domains-enable-a-mode-of-protein-elasticity
#7
David Giganti, Kevin Yan, Carmen L Badilla, Julio M Fernandez, Jorge Alegre-Cebollada
The response of titin to mechanical forces is a major determinant of the function of the heart. When placed under a pulling force, the unstructured regions of titin uncoil while its immunoglobulin (Ig) domains unfold and extend. Using single-molecule atomic force microscopy, we show that disulfide isomerization reactions within Ig domains enable a third mechanism of titin elasticity. Oxidation of Ig domains leads to non-canonical disulfide bonds that stiffen titin while enabling force-triggered isomerization reactions to more extended states of the domains...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330337/role-of-germline-aberrations-affecting-ctnna1-map3k6-and-myd88-in-gastric-cancer-susceptibility
#8
Robbert D A Weren, Rachel S van der Post, Ingrid P Vogelaar, J Han van Krieken, Liesbeth Spruijt, Jan Lubinski, Anna Jakubowska, Urszula Teodorczyk, Cora M Aalfs, Liselotte P van Hest, Carla Oliveira, Eveline J Kamping, Hans K Schackert, Guglielmina N Ranzani, Encarna B Gómez García, Frederik J Hes, Elke Holinski-Feder, Maurizio Genuardi, Margreet G E M Ausems, Rolf H Sijmons, Anja Wagner, Lizet E van der Kolk, Annemieke Cats, Inga Bjørnevoll, Nicoline Hoogerbrugge, Marjolijn J L Ligtenberg
BACKGROUND: In approximately 10% of all gastric cancer (GC) cases, a heritable cause is suspected. A subset of these cases have a causative germline CDH1 mutation; however, in most cases the cause remains unknown. Our objective was to assess to what extent these remaining cases may be explained by germline mutations in the novel candidate GC predisposing genes CTNNA1, MAP3K6 or MYD88. METHODS: We sequenced a large cohort of unexplained young and/or familial patients with GC (n=286) without a CDH1germline mutation for germline variants affecting CTNNA1, MAP3K6 and MYD88 using a targeted next-generation sequencing approach based on single-molecule molecular inversion probes...
January 12, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29328918/transmembrane-pickets-connect-cyto-and-pericellular-skeletons-forming-barriers-to-receptor-engagement
#9
Spencer A Freeman, Anthony Vega, Magdalena Riedl, Richard F Collins, Phillip P Ostrowski, Elliot C Woods, Carolyn R Bertozzi, Markku I Tammi, Diane S Lidke, Pauline Johnson, Satyajit Mayor, Khuloud Jaqaman, Sergio Grinstein
Phagocytic receptors must diffuse laterally to become activated upon clustering by multivalent targets. Receptor diffusion, however, can be obstructed by transmembrane proteins ("pickets") that are immobilized by interacting with the cortical cytoskeleton. The molecular identity of these pickets and their role in phagocytosis have not been defined. We used single-molecule tracking to study the interaction between Fcγ receptors and CD44, an abundant transmembrane protein capable of indirect association with F-actin, hence likely to serve as a picket...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328686/three-dimensional-tracking-of-interfacial-hopping-diffusion
#10
Dapeng Wang, Haichao Wu, Daniel K Schwartz
Theoretical predictions have suggested that molecular motion at interfaces-which influences processes including heterogeneous catalysis, (bio)chemical sensing, lubrication and adhesion, and nanomaterial self-assembly-may be dominated by hypothetical "hops" through the adjacent liquid phase, where a diffusing molecule readsorbs after a given hop according to a probabilistic "sticking coefficient." Here, we use three-dimensional (3D) single-molecule tracking to explicitly visualize this process for human serum albumin at solid-liquid interfaces that exert varying electrostatic interactions on the biomacromolecule...
December 29, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29328293/whispering-gallery-mode-resonator-sensor-for-in-situ-measurements-of-hydrogel-gelation
#11
Steven H Huang, Saahil Sheth, Era Jain, Xuefeng Jiang, Silviya P Zustiak, Lan Yang
Whispering gallery mode (WGM) resonators are compact and ultrasensitive devices, which enable label-free sensing at the single-molecule level. Despite their high sensitivity, WGM resonators have not been thoroughly investigated for use in dynamic biochemical processes including molecular diffusion and polymerization. In this work, the first report of using WGM sensors to continuously monitor a chemical reaction (i.e. gelation) in situ in a hydrogel is described. Specifically, we monitor and quantify the gelation dynamics of polyacrylamide hydrogels using WGM resonators and compare the results to an established measurement method based on rheology...
January 8, 2018: Optics Express
https://www.readbyqxmd.com/read/29328231/aberration-accounting-calibration-for-3d-single-molecule-localization-microscopy
#12
Clément Cabriel, Nicolas Bourg, Guillaume Dupuis, Sandrine Lévêque-Fort
We propose a straightforward sample-based technique to calibrate the axial detection in 3D single-molecule localization microscopy. Using microspheres coated with fluorescent molecules, the calibration curves of point spread function-shaping or intensity-based measurements can be obtained over the imaging depth range. This experimental method takes into account the effect of the spherical aberration without requiring computational correction. We demonstrate its efficiency for astigmatic imaging in a 1.2 μm range above the coverslip...
January 15, 2018: Optics Letters
https://www.readbyqxmd.com/read/29327242/self-assembly-of-magnetically-functionalized-star-polymer-nano-colloids
#13
Ronald Blaak, Christos N Likos
We explore the potential of star-polymers that carry super-paramagnetic nano-particles as end-groups with respect to the single-molecule self-assembly process. With the aid of molecular dynamics simulation, the configurations of these macromolecules are analyzed as a function of functionality, magnetic interaction strength, and the length of the polymeric arms. By means of an external magnetic field the nano-particles can be controlled to form static or dynamic dipolar chains, resulting in conformations of isolated stars that can be characterized by the average number of chains and length...
January 12, 2018: European Physical Journal. E, Soft Matter
https://www.readbyqxmd.com/read/29325559/pangenome-analyses-of-the-wheat-pathogen-zymoseptoria-tritici-reveal-the-structural-basis-of-a-highly-plastic-eukaryotic-genome
#14
Clémence Plissonneau, Fanny E Hartmann, Daniel Croll
BACKGROUND: Structural variation contributes substantially to polymorphism within species. Chromosomal rearrangements that impact genes can lead to functional variation among individuals and influence the expression of phenotypic traits. Genomes of fungal pathogens show substantial chromosomal polymorphism that can drive virulence evolution on host plants. Assessing the adaptive significance of structural variation is challenging, because most studies rely on inferences based on a single reference genome sequence...
January 11, 2018: BMC Biology
https://www.readbyqxmd.com/read/29325071/viral-suppressors-of-rnai-employ-a-rapid-screening-mode-to-discriminate-viral-rna-from-cellular-small-rna
#15
Mohamed Fareh, Jasper van Lopik, Iason Katechis, Alfred W Bronkhorst, Anna C Haagsma, Ronald P van Rij, Chirlmin Joo
RNA interference (RNAi) is an indispensable mechanism for antiviral defense in insects, including mosquitoes that transmit human diseases. To escape this antiviral defense system, viruses encode suppressors of RNAi that prevent elimination of viral RNAs, and thus ensure efficient virus accumulation. Although the first animal Viral Suppressor of RNAi (VSR) was identified more than a decade ago, the molecular basis of RNAi suppression by these viral proteins remains unclear. Here, we developed a single-molecule fluorescence assay to investigate how VSRs inhibit the recognition of viral RNAs by Dcr-2, a key endoribonuclease enzyme in the RNAi pathway...
January 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29323897/a-series-of-weakley-type-polyoxomolybdates-synthesis-characterization-and-magnetic-properties-by-a-combined-experimental-and-theoretical-approach
#16
Shan She, Chen Gao, Kun Chen, Aruuhan Bayaguud, Yichao Huang, Bing-Wu Wang, Song Gao, Yongge Wei
Using DCC as the dehydrating agent, a series of Weakley-type polyoxomolybdates [Bu4N]3{Ln[Mo5O13(OMe)4(NO)]2} (Ln = Tb, Dy, Ho, Er) were synthesized in a one-pot reaction and structurally characterized by elemental, IR, UV-vis analysis, PXRD, and single-crystal X-ray diffraction. Furthermore, the static and dynamic measurements were utilized to investigate their magnetic performances. Typically, slow relaxation of magnetization was observed for Dy analogues with an energy barrier for the reversal of the magnetization of 50 K, which is the highest barrier height observed on the polyoxomolybdates-based single-molecule magnets (SMMs)...
January 11, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29323682/two-polymorphic-co-ii-field-induced-single-ion-magnets-with-enormous-angular-distortion-from-the-ideal-octahedron
#17
I Nemec, R Herchel, Z Trávníček
A mononuclear complex [Co(neo)(PhCOO)2,], neo = neocuproine, PhCOO- = the benzoate anion, was prepared in two polymorph forms crystallizing in the C2/c, (1) and P21/c, (2) space groups. The polymorphs differ in the Co-O bond lengths and the level of trigonal distortion of their coordination polyhedra. The static and dynamic magnetic properties of these compounds were thoroughly studied by experimental (magnetometry) and theoretical (ab initio calculations) methods. The analysis of magnetic data was performed using the spin Hamiltonian formalism or the L-S model considering also the orbital angular momentum...
January 11, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29323281/bap-sil1-regulates-the-molecular-chaperone-bip-by-coupling-release-of-nucleotide-and-substrate
#18
Mathias Rosam, Daniela Krader, Christina Nickels, Janine Hochmair, Katrin C Back, Ganesh Agam, Anders Barth, Cathleen Zeymer, Jelle Hendrix, Markus Schneider, Iris Antes, Jochen Reinstein, Don C Lamb, Johannes Buchner
BiP is the endoplasmic member of the Hsp70 family. BiP is regulated by several co-chaperones including the nucleotide-exchange factor (NEF) Bap (Sil1 in yeast). Bap is a two-domain protein. The interaction of the Bap C-terminal domain with the BiP ATPase domain is sufficient for its weak NEF activity. However, stimulation of the BiP ATPase activity requires full-length Bap, suggesting a complex interplay of these two factors. Here, single-molecule FRET experiments with mammalian proteins reveal that Bap affects the conformation of both BiP domains, including the lid subdomain, which is important for substrate binding...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29322780/signal-and-noise-in-fet-nanopore-devices
#19
William M Parkin, Marija Drndic
The combination of a nanopore with a local field-effect transistor (FET-nanopore), like a nanoribbon, nanotube, or nanowire, in order to sense single molecules translocating through the pore is promising for DNA sequencing at megahertz bandwidths. Previously, it was experimentally determined that the detection mechanism was due to local potential fluctuations that arise when an analyte enters a nanopore and constricts ion flow through it, rather than the theoretically proposed mechanism of direct charge coupling between the DNA and nanowire...
January 11, 2018: ACS Sensors
https://www.readbyqxmd.com/read/29322442/single-molecule-fluorescence-in-situ-hybridization-fish-of-circular-rna-cdr1as
#20
Christine Kocks, Anastasiya Boltengagen, Monika Piwecka, Agnieszka Rybak-Wolf, Nikolaus Rajewsky
Individual mRNA molecules can be imaged in fixed cells by hybridization with multiple, singly labeled oligonucleotide probes, followed by computational identification of fluorescent signals. This approach, called single-molecule RNA fluorescence in situ hybridization (smRNA FISH), allows subcellular localization and absolute quantification of RNA molecules in individual cells. Here, we describe a simple smRNA FISH protocol for two-color imaging of a circular RNA, CDR1as, simultaneously with an unrelated messenger RNA...
2018: Methods in Molecular Biology
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