1,722,395 research outputs found

    Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes.

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    The mechanism of mitochondrial DNA replication is a subject of intense debate. One model proposes a strand-asynchronous replication in which both strands of the circular genome are replicated semi-independently while the other model proposes both a bidirectional coupled leading- and lagging-strand synthesis mode and a unidirectional mode in which the lagging-strand is initially laid-down as RNA by an unknown mechanism (RITOLS mode). Both the strand-asynchronous and RITOLS model have in common a delayed synthesis of the DNA-lagging strand. Mitochondrial DNA is replicated by a limited set of proteins including DNA polymerase gamma (POLG) and the helicase Twinkle. Here, we report the effects of expression of various catalytically deficient mutants of POLG1 and Twinkle in human cell culture. Both groups of mutants reduced mitochondrial DNA copy number by severe replication stalling. However, the analysis showed that while induction of POLG1 mutants still displayed delayed lagging-strand synthesis, Twinkle-induced stalling resulted in maturated, essentially fully double-stranded DNA intermediates. In the latter case, limited inhibition of POLG with dideoxycytidine restored the delay between leading- and lagging-strand synthesis. The observed cause-effect relationship suggests that Twinkle-induced stalling increases lagging-strand initiation events and/or maturation mimicking conventional strand-coupled replication

    Twinkle-Catalyzed Toehold-Mediated DNA Strand Displacement Reaction

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    Strand exchange between homologous nucleic acid sequences is the basis for cellular DNA repair, recombination, and genome editing technologies. Specialized enzymes catalyze cellular strand exchange; however, the reaction occurs spontaneously when a single-stranded DNA toehold can dock the invader strand on the target DNA to initiate strand exchange through branch migration. Due to its precise response, the spontaneous toehold-mediated strand displacement (TMSD) reaction is widely employed in DNA nanotechnology. However, enzyme-free TMSD suffers from slow rates, resulting in slow response times. Here, we show that human mitochondrial DNA helicase Twinkle can accelerate TMSD up to 6000-fold. Mechanistic studies indicate that Twinkle accelerates TMSD by catalyzing the docking step, which typically limits spontaneous reactions. The catalysis occurs without ATP, and Twinkle-catalyzed TMSD rates remain sensitive to base-pair mismatches. The simple catalysis, tunability, and speed improvement of the catalyzed TMSD can be leveraged in nanotechnology, requiring sensitive detection and faster response times

    abocchieri/exploring-synergies-ariel-twinkle-plots: v1.0.0

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    <p>First released version of figures</p> <p><strong>Full Changelog</strong>: https://github.com/abocchieri/exploring-synergies-ariel-twinkle-plots/commits/v1.0.0</p&gt

    An integrated marketing communications campaign for Twinkle Twinkle

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    The integrated marketing communication campaign is intended for Twinkle Twinkle Jewelry by Twinkle Twinkle Trading Company. It is a local costume/fashion jewelry brand established in 2018, offering affordable yet stylish jewelry pieces designed for various occasions. Twinkle Twinkle offers different types of jewelry such as earrings, necklaces, bracelets, brooches, rings, and hair accessories. The brand is currently exclusively available through e-commerce platforms, Lazada and Shopee. With the recurring pandemic, Twinkle Twinkle\u27s sales declined. In addition to the pandemic, the entry of new and unbranded costume jewelry brands on Lazada and Shopee also hinders the brand\u27s current progress. These new entrants sell their products at lower prices compared with Twinkle Twinkle. While other brands have adapted to the impact of the pandemic in this new normal, Twinkle Twinkle needs to maximize various opportunities and resolve the challenges. A big idea was crafted for the proposed integrated marketing communication campaign of Twinkle Twinkle by analyzing the brand\u27s consumer promise and insights gathered from the qualitative parts of the survey. Your Daily Sparkle. , the proposed big idea heavily anchors to the brand identity, which focuses on the affordability and flexibility to daily use or varying occasions even under new normal. The campaign aims to target female social media active users in the Philippines, 25 to 40 years old, and are fond of keeping up with the fashion trends without breaking the bank. Considered as working adults, this demographic is currently heavily immersed with online meetings, streamings, and content creation for entertainment. The proposed campaign is set to launch in Q4 of 2021. The general objectives are to generate incremental sales of Php 2.8 million from these external platforms such as Facebook, Instagram, and Google search engine. This is on top of the historical average sales performance of Php 4.7 million in Q1 and Q4. To increase online store traffic by 142% and conversion by 21% for Twinkle Twinkle Lazada and Shopee through outside media over the campaign period

    Twinkle-twinkle Panda Star

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    Terinspirasi dari deck tarot, The Star merupakan lambang harapan, kekuatan, dan cahaya di tengah gelap. Di sisi lain, Panda merepresentasikan kebahagiaan atas hal-hal sederhana. “Twinkle Twinkle Panda Star” menceritakan tentang seniman yang percaya bahwa selama hati terus bersenandung dan tangan terus berkarya, maka semesta akan selalu membuka jalan. Oh, rupanya sang seniman menitip pesan! “Keyakinan kecilmu itu bisa menuntunmu melewati kabut ketidakpastian paling tebal sekalipun. Toh, bintang tetap ada meski langit tak selalu cerah,” katanya

    Twinkle, twinkle, little star (fiddle tune)

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    fiddlesCollected by Mary Celestia Parler; Transcribed by Neil Byer Fred Smith Bentonville, Ark. October 16, 1955 Reel 231, Item 4 Twinkle, Twinkle, Little Star (fiddle tune)Funding for digitization provided by the Arkansas Humanities Council and the Happy Hollow Foundation

    Nursery school children singing "Twinkle, Twinkle Little Star." [1]

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    Photo of nursery school children in a classroom, identified as singing "Twinkle, Twinkle Little Star," at the Tule Lake Relocation Center in California during World War I

    Nursery school children singing "Twinkle, Twinkle Little Star." [3]

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    Photo of nursery school children, identified as singing "Twinkle, Twinkle Little Star," at the Tule Lake Relocation Center in California during World War I

    Nursery school children singing "Twinkle, Twinkle Little Star." [2]

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    Photo of nursery school children, identified as singing "Twinkle, Twinkle Little Star," at the Tule Lake Relocation Center in California during World War I

    Twinkle: a small satellite spectroscopy mission for the next phase of exoplanet science

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    With a focus on off-the-shelf components, Twinkle is the first in a series of cost competitive small satellites managed and financed by Blue Skies Space Ltd. The satellite is based on a high-heritage Airbus platform that will carry a 0.45 m telescope and a spectrometer which will provide simultaneous wavelength coverage from 0.5-4.5 μm\rm{\mu m}. The spacecraft prime is Airbus Stevenage while the telescope is being developed by Airbus Toulouse and the spectrometer by ABB Canada. Scheduled to begin scientific operations in 2025, Twinkle will sit in a thermally-stable, sun-synchronous, low-Earth orbit. The mission has a designed operation lifetime of at least seven years and, during the first three years of operation, will conduct two large-scale survey programmes: one focused on Solar System objects and the other dedicated to extrasolar targets. Here we present an overview of the architecture of the mission, refinements in the design approach, and some of the key science themes of the extrasolar survey
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