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| Open AccessmiR-26a and miR-384-5p are required for LTP maintenance and spine enlargement
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. Here, the authors demonstrate that miR-26a and miR-384-5p affect the maintenance, but not induction, of LTP as well as spine enlargement by regulating the expression of RSK3.
- Qin-Hua Gu
- , Danni Yu
- & Zheng Li
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Article
| Open AccessNew basal cell carcinoma susceptibility loci
Basal cell carcinoma is a common cancer among people of European ancestry, with associated high economic costs to monitor and treat. Here Stacey et al.conduct a genome-wide association study on Icelandic and other European populations, identifying four novel loci associated with cancer susceptibility.
- Simon N. Stacey
- , Hannes Helgason
- & Kari Stefansson
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Transcriptional refractoriness is dependent on core promoter architecture
Genes are often transcribed in random bursts followed by long periods of inactivity. Here the authors show, by a light-inducible transcription system in Neurospora, that refractory promoters carry a physical memory of their previous transcription history.
- François Cesbron
- , Michael Oehler
- & Michael Brunner
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Metal ion-directed dynamic splicing of DNA through global conformational change by intramolecular complexation
Higher-order structured DNA molecules can be manipulated to carry out specific enzymatic functions. Here the authors demonstrate the metal ion-directed global conformational control of DNA structure, using intramolecular coordination chemistry to manipulate the DNAzyme activity.
- Toshihiro Ihara
- , Hiroyuki Ohura
- & Yusuke Kitamura
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Article
| Open AccessUltrafast myoglobin structural dynamics observed with an X-ray free-electron laser
Localized chemical events such as the breakage of a bond between a protein and a ligand may trigger a global protein conformational change. Here, the authors use an X-ray free-electron laser to track the motion of myoglobin in response to photoinduced ligand release, and observe a picosecond proteinquake.
- Matteo Levantino
- , Giorgio Schirò
- & Marco Cammarata
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Article
| Open AccessGenomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis
The bacterium Streptococcus suiscauses respiratory tract infections in pigs and meningitis in humans. Here, the authors show that human disease isolates are limited to a single virulent population and find no consistent genomic differences between pig and human isolates.
- Lucy A. Weinert
- , Roy R. Chaudhuri
- & Vanessa Terra
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Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia
Myopia is a significant and increasing public health concern. Here Miyake et al. conduct a genome-wide association study and identify WNT7Bas a susceptibility gene across different ethnic groups, suggesting a possible role in the development of myopia.
- Masahiro Miyake
- , Kenji Yamashiro
- & Nagahisa Yoshimura
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Article
| Open AccessLabel-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells
Overexpression of underglycosylated MUC1 (uMUC1) is found in most malignant adenocarcinomas of epithelial origin. Here the authors use chemical exchange saturation transfer (CEST) MRI to detect uMUC1 and to distinguish between malignant and nonmalignant tumours.
- Xiaolei Song
- , Raag D. Airan
- & Jeff W. M. Bulte
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Article
| Open AccessGenome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA
Long non-coding RNAs (lncRNAs) have emerged as important regulators of gene expression through several distinct mechanisms. Here the authors further delineate the role of p53-induced lncRNAs within the p53-responsive pathways through the activation of enhancers.
- Nicolas Léveillé
- , Carlos A. Melo
- & Reuven Agami
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Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis
The protein tyrosine phosphatase Pez controls intestinal stem cell proliferation in Drosophila by inhibiting the Hippo pathway transcription factor Yorkie. Wang et al. reveal that Pez protein stability is regulated by interactions with the E3 ubiquitin ligase Suppressor of Deltex.
- Chao Wang
- , Wenxiang Zhang
- & Lei Zhang
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A megacomplex composed of both photosystem reaction centres in higher plants
Plants have two types of photosystem reaction centres, PSI and PSII, that are traditionally thought to be spatially separate. Here, Yokono et al. show in Arabidopsisthat around half of PSII physically interacts with PSI to efficiently transfer excitation energy between the complexes, and this interaction is regulated by light.
- M. Yokono
- , A. Takabayashi
- & A. Tanaka
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Article
| Open AccessMulti-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies
Animal models are important to study organismal immune responses to infection with influenza viruses. Here, Fukuyama et al.report a new generation of fluorescently labelled influenza viruses that facilitate the study of viral infections in animal models at cellular level.
- Satoshi Fukuyama
- , Hiroaki Katsura
- & Yoshihiro Kawaoka
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Pharyngeal sense organs drive robust sugar consumption in Drosophila
Sweet taste plays a key role in promoting ingestion of nutritionally rich sources of carbohydrates. Here, the authors demonstrate that the pharyngeal sense organs in adult Drosophilaare important for directing the sustained consumption of sweet compounds.
- Emily E. LeDue
- , Yu-Chieh Chen
- & Michael D. Gordon
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Genome-wide identification of microRNA expression quantitative trait loci
As important post-transcriptional regulators of gene expression, microRNAs play a key role in the generation of complex phenotypes. Here, Huan et al.identify miR-eQTLs in whole blood samples to create a roadmap linking regulation of microRNA expression to complex diseases.
- Tianxiao Huan
- , Jian Rong
- & Jane E. Freedman
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Article
| Open AccessOscillation of the velvet worm slime jet by passive hydrodynamic instability
The velvet worm emits a rapidly oscillating jet of proteinaceous slime to capture prey. Here, Concha et al. combine high-speed videography and a physical simulacrum to establish that this passive mechanism is the result of elastohydrodynamic instability during high-speed flow through the oral papillae.
- Andrés Concha
- , Paula Mellado
- & Julián Monge-Nájera
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Structural and evolutionary versatility in protein complexes with uneven stoichiometry
Although many heteromeric protein complexes exhibit 1:1 ratios between their components, a significant number feature uneven stoichiometry. Marsh et al. perform a global analysis of uneven stoichiometry, identifying structural mechanisms by which it is achieved, and explaining its differential conservation.
- Joseph A. Marsh
- , Holly A. Rees
- & Sarah A. Teichmann
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Article
| Open AccessSensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo
Surgical removal of the metastases remains a life-extending approach to ovarian cancer, but the nodules are difficult to detect. Here the authors show that a new cell-permeable probe for β-galactosidase can sensitively and specifically detect peritoneal metastases in mouse models of ovarian cancer.
- Daisuke Asanuma
- , Masayo Sakabe
- & Yasuteru Urano
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Visualization of nanocrystal breathing modes at extreme strains
Nanoscale dimensions can lead to unique functional properties, often achieved via large-amplitude strains. Here, the authors use femtosecond X-rays to visualize light-induced strains in semiconductor nanocrystals, showing that they correspond to anisotropic ‘breathing modes’, which collapse after straining.
- Erzsi Szilagyi
- , Joshua S. Wittenberg
- & Aaron M. Lindenberg
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Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation
Anticancer treatments are tested in mice housed below thermoneutrality which represents chronic cold-stress. Here Eng et al. show that these mice have activated stress responses leading to therapeutic resistance and that inhibiting adrenergic signaling increases efficacy of anticancer therapies.
- Jason W.-L. Eng
- , Chelsey B. Reed
- & Bonnie L. Hylander
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Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells
The CRISPR/Cas9 system can be used for genome editing. Here, Liao et al. show that the system can be adapted to inhibit HIV expression and replication, excise the integrated HIV genome and provide long-term protection against new infections in human cells, including pluripotent stem cells.
- Hsin-Kai Liao
- , Ying Gu
- & Juan Carlos Izpisua Belmonte
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| Open AccessStructure of CPV17 polyhedrin determined by the improved analysis of serial femtosecond crystallographic data
Serial femtosecond crystallography and the use of X-ray free-electron lasers (XFEL) promise to revolutionize structural biology. Here, the authors describe refinements that reduce the redundancy required to obtain quality XFEL data and report a 1.75-Å structure—not obtainable by synchrotron radiation—using less than 6,000 crystals.
- Helen M. Ginn
- , Marc Messerschmidt
- & David I. Stuart
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Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways
ADAR1 is an adenosine deaminase that converts adenosine to inosine (A-to-I) mostly on Alu repeats in human RNA. Here by analysing transcriptome-wide ADAR1–RNA interactions, the authors show that ADAR1 also binds non-Alusequences to regulate alternative 3′ UTR usage and miRNA biogenesis in the nucleus.
- Jae Hoon Bahn
- , Jaegyoon Ahn
- & Xinshu Xiao
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Article
| Open AccessWhole-genome sequence-based analysis of thyroid function
Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.
- Peter N. Taylor
- , Eleonora Porcu
- & Pingbo Zhang
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Visually induced initiation of Drosophila innate courtship-like following pursuit is mediated by central excitatory state
Male Drosophilaexhibit a complex suite of courtship behaviours in response to a variety of sensory stimuli. Here, the authors demonstrate the involvement of specific, genetically defined clusters of central neurons in visually induced initiation and maintenance of courtship behaviours.
- Soh Kohatsu
- & Daisuke Yamamoto
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Article
| Open AccessHighly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour
Alterations of p53 are associated with more than half of all human cancers. Here the authors present a new pH-sensitive nanoparticle that is delivered via systemic circulation and combines gene delivery to restore p53 with expression of Killerred protein to induce photosensitization.
- S.-Ja Tseng
- , Zi-Xian Liao
- & Ivan M. Kempson
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Article
| Open Access3D hotspots of recurrent retroviral insertions reveal long-range interactions with cancer genes
Retroviral insertional mutagenesis is used for identifying genes involved in the development of cancer. Here, the authors overlay cancer-causing insertions with genome-wide Hi-C data and find that retroviral elements tend to cluster in 3D hotspots.
- Sepideh Babaei
- , Waseem Akhtar
- & Jeroen de Ridder
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Article
| Open AccessPredicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity
Efficacy of anticancer treatments vary across patients, imposing a need for personalized approaches. Here the authors show that responsiveness to chemotherapy can be predicted using tumour explant cultures in a patient-matched microenvironment, coupled with a machine-learning algorithm.
- Biswanath Majumder
- , Ulaganathan Baraneedharan
- & Pradip K. Majumder
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Article
| Open AccessAn analytical framework for optimizing variant discovery from personal genomes
The standardization of clinical sequencing data generation and analysis is of critical importance. Here, the authors develop the Genome Comparison and Analytic Testing platform to facilitate the development of performance metrics and comparisons of analysis tools for clinical sequencing studies.
- Gareth Highnam
- , Jason J. Wang
- & David Mittelman
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Engineered pairs of distinct photoswitches for optogenetic control of cellular proteins
Photoreceptor-based photoswitches have proved to be powerful tools for the specific control of protein activity in live cells. Here the authors describe Magnets, a new set of photoswitches based on the Vivid photoreceptor with enhanced hetero-dimerization specificity and variable activation kinetics.
- Fuun Kawano
- , Hideyuki Suzuki
- & Moritoshi Sato
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Article
| Open AccessA highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins
There is no licensed vaccine or therapeutic for dengue virus (DENV) infection. Here, the authors show that a highly potent human monoclonal antibody binds to DENV particles in an unusual and very effective way by interacting with three viral envelope proteins.
- Guntur Fibriansah
- , Joanne L. Tan
- & Shee-Mei Lok
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Article
| Open AccessCapture Hi-C identifies the chromatin interactome of colorectal cancer risk loci
Multiple regulatory elements distant from their targets on the linear genome can influence gene expression through chromatin looping. Here, the authors report an improved chromosome conformation capture approach that can be used to identify long-range chromatin interactions in cancer risk loci.
- Roland Jäger
- , Gabriele Migliorini
- & Richard S. Houlston
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Article
| Open AccessAntagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses
The hypothalamic-pituitary-adrenal axis coordinates behavioral and physiological responses to stress but the mechanisms are poorly understood. Here, the authors show that neurons that produce hypocretin/orexin in the lateral hypothalamic area regulate corticosterone release and a variety of behaviors related to the stress response.
- Patricia Bonnavion
- , Alexander C. Jackson
- & Luis de Lecea
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Biophysical mechanisms that maintain biodiversity through trade-offs
Trade-offs between life history traits are key to understanding biodiversity. Here, the authors use population genetics models and experimental microbial evolution to show that trade-off geometry can be deduced from fundamental biological principles, and used to predict biodiversity stability.
- Justin R. Meyer
- , Ivana Gudelj
- & Robert Beardmore
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Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue
The ciliary margin of the eye functions as a source of multipotent progenitor cells in certain organisms but whether it plays this role in humans has not been easy to study. Here the authors culture human embryonic stem cells that self-organize into retinal tissue, and show that ciliary margin-like growth zones emerge from the developing human retinal tissue and contain stem cell niches.
- Atsushi Kuwahara
- , Chikafumi Ozone
- & Yoshiki Sasai
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Multiplex CRISPR/Cas9-based genome editing for correction of dystrophin mutations that cause Duchenne muscular dystrophy
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene. Here, Ousterout et al. use multiplexed CRISPR/Cas9 genome editing to excise a large portion of the gene that carries over 60% of known dystrophin mutations. They show that this excision restores dystrophin expression in patient-derived cells.
- David G. Ousterout
- , Ami M. Kabadi
- & Charles A. Gersbach
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| Open AccessEpigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs
Tissue-specific functions have been established for some lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, the authors report tissue-specific epigenomic regulation of 3,753 lincRNAs and their strong connection with tissue-specific pathways.
- Viren Amin
- , R. Alan Harris
- & Aleksandar Milosavljevic
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A cnidarian homologue of an insect gustatory receptor functions in developmental body patterning
Insect gustatory and olfactory receptor genes encode transmembrane proteins that detect diverse chemicals, but their evolutionary origins are unclear. This study identifies homologues of these genes in non-Bilateria and reveals an unexpected role for one in sea anemone embryonic development.
- Michael Saina
- , Henriette Busengdal
- & Richard Benton
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Article
| Open AccessExploiting light chains for the scalable generation and platform purification of native human bispecific IgG
Bispecific antibodies allow for novel therapeutic approaches but industrial-scale production and immunogenicity represent significant challenges. Here Fischer et al.describe a unique human bispecific antibody format that exploits differing light chains to overcome these obstacles.
- Nicolas Fischer
- , Greg Elson
- & Marie Kosco-Vilbois
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Article
| Open AccessA rapid bioluminescence assay for measuring myeloperoxidase activity in human plasma
Levels of the enzyme myeloperoxidase in the blood are considered a biomarker for the severity of cardiovascular disease. Here the authors report a rapid and inexpensive method for measuring myeloperoxidase activity in human plasma by luminescence, after adsorption of the enzyme to a polymer surface.
- Reece J. Goiffon
- , Sara C. Martinez
- & David Piwnica-Worms
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Article
| Open AccessUltrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets
Antigenic peptides are loaded into major histocompatibility complex class I (MHC I) molecules after entering the ER via the TAP transporter. Here, Fischbach et al. develop a flow cytometry assay to monitor TAP-dependent peptide translocation that is sensitive enough to use on scarce primary cell subsets.
- Hanna Fischbach
- , Marius Döring
- & Robert Tampé
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The transcriptional regulator BBX24 impairs DELLA activity to promote shade avoidance in Arabidopsis thaliana
Plants respond to shade by elongating their stems to grow toward the light. Here, Crocco et al. show that the BBX24 transcriptional regulator promotes the shade avoidance response by activating gibberellin signalling and the PIF4 transcription factor under low light conditions.
- Carlos D. Crocco
- , Antonella Locascio
- & Javier F. Botto
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Article
| Open AccessGenomic analysis of hybrid rice varieties reveals numerous superior alleles that contribute to heterosis
The principle of heterosis, whereby a hybrid variety outperforms both parents, is commonly exploited in agriculture to maximize crop yield. Here Huang et al.show that the accumulation of multiple superior alleles in hybrid varieties contributes to hybrid vigour and increased yield in rice.
- Xuehui Huang
- , Shihua Yang
- & Bin Han
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Article
| Open AccessDense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis with a significant genetic component. Here, the authors analyse immune-related genetic markers in 1,962 PsA patients and 8,923 controls to identify novel PsA risk loci and highlight distinct genetic differences between psoriasis and PsA.
- John Bowes
- , Ashley Budu-Aggrey
- & Anne Barton
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Synthetic lateral inhibition governs cell-type bifurcation with robust ratios
Cell-type diversity results from a series of binary cell fate decisions. Here, Matsuda et al.find that cells engineered with a Notch/Delta lateral inhibition circuit spontaneously bifurcate into Notch-active and Delta-positive subpopulations that are robust at the individual and population levels.
- Mitsuhiro Matsuda
- , Makito Koga
- & Miki Ebisuya
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Quantitative high throughput screening using a primary human three-dimensional organotypic culture predicts in vivo efficacy
Tumour microenvironment affects the outcome of pharmacological anticancer treatments. Here, Kenny et al. show that organotypic cultures of ovarian cancer cells can recapitulate metastasis. They identify several new compounds that block cancer invasion and metastasis and improve survival in mouse models.
- Hilary A. Kenny
- , Madhu Lal-Nag
- & Ernst Lengyel
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Article
| Open AccessThe jasmonate-responsive GTR1 transporter is required for gibberellin-mediated stamen development in Arabidopsis
GTR1 is known to transport glucosinolates in Arabidopsis. Here, Saito et al. show that GTR1 also transports the plant hormones jasmonate and gibberellin when heterologously expressed in Xenopus oocytes, and that gtr1mutant plants show a gibberellin-related fertility phenotype.
- Hikaru Saito
- , Takaya Oikawa
- & Hiroyuki Ohta
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Article
| Open AccessGenetic blueprint of the zoonotic pathogen Toxocara canis
Toxocara canis is a zoonotic parasite of major worldwide socioeconomic importance. Here, the authors sequence the genome and transcriptome of T. canis, and highlight potential mechanisms involved in development and host–parasite interactions that could support the pursuit of new drug interventions.
- Xing-Quan Zhu
- , Pasi K. Korhonen
- & Robin B. Gasser
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Sorting of small infectious virus particles by flow virometry reveals distinct infectivity profiles
Individual viral particles can display heterogeneity in their composition of lipids, proteins or nucleic acids. Here, the authors apply advanced flow cytometry techniques to sort Junin virus particles and show that particle size and envelope glycoprotein concentration correlate with infectivity.
- Raphaël Gaudin
- & Natasha S Barteneva
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Article
| Open AccessA high-throughput optomechanical retrieval method for sequence-verified clonal DNA from the NGS platform
One of the biggest bottlenecks in large-scale DNA synthesis is the retrieval of target clonal DNA from high-density sequencing platforms. Here, the authors present a method called ‘Sniper Cloning’ that allows for precise mapping of target clone features and rapid retrieval of targets for full utilization of DNA clones.
- Howon Lee
- , Hyoki Kim
- & Sunghoon Kwon
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