Abstract:
:Circulating exosomal microRNA (miR) represents a new class of blood-based biomarkers for cancer liquid biopsy. The detection of miR at a very low concentration and with single-base discrimination without the need for sophisticated equipment, large volumes, or elaborate sample processing is a challenge. To address this, we present an approach that is highly specific for a target miR sequence and has the ability to provide "digital" resolution of individual target molecules with high signal-to-noise ratio. Gold nanoparticle tags are prepared with thermodynamically optimized nucleic acid toehold probes that, when binding to a target miR sequence, displace a probe-protecting oligonucleotide and reveal a capture sequence that is used to selectively pull down the target-probe-nanoparticle complex to a photonic crystal (PC) biosensor surface. By matching the surface plasmon-resonant wavelength of the nanoparticle tag to the resonant wavelength of the PC nanostructure, the reflected light intensity from the PC is dramatically and locally quenched by the presence of each individual nanoparticle, enabling a form of biosensor microscopy that we call Photonic Resonator Absorption Microscopy (PRAM). Dynamic PRAM imaging of nanoparticle tag capture enables direct 100-aM limit of detection and single-base mismatch selectivity in a 2-h kinetic discrimination assay. The PRAM assay demonstrates that ultrasensitivity (<1 pM) and high selectivity can be achieved on a direct readout diagnostic.
journal_name
Proc Natl Acad Sci U S Aauthors
Canady TD,Li N,Smith LD,Lu Y,Kohli M,Smith AM,Cunningham BTdoi
10.1073/pnas.1904770116subject
Has Abstractpub_date
2019-09-24 00:00:00pages
19362-19367issue
39eissn
0027-8424issn
1091-6490pii
1904770116journal_volume
116pub_type
杂志文章abstract::Previous studies have established that incubation of low density lipoprotein (LDL) with cultured endothelial cells (EC) converts it to a new form (EC-modified LDL) that is now recognized by a specific receptor on macrophages (the acetyl LDL receptor) and is taken up and degraded 3-10 times more rapidly than native LDL...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.9.3000
更新日期:1985-05-01 00:00:00
abstract::Two factors that contribute to the progression of Parkinson disease are a brain defect in mitochondrial respiration and the generation of hydrogen peroxide (H2O2) by monoamine oxidase (MAO). Here we show that the two are linked. Metabolism of the neurotransmitter dopamine, or other monoamines (benzylamine, tyramine), ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.10.4890
更新日期:1997-05-13 00:00:00
abstract::Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1410776112
更新日期:2015-02-17 00:00:00
abstract::Apoptotic cells contain nuclear autoantigens that may initiate a systemic autoimmune response. To explore the mechanism of antibody binding to apoptotic cells, 3H9, a murine autoantibody with dual specificity for phospholipids and DNA, was used. H chain mutants of 3H9 were constructed, expressed as single-chain Fv (sc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.241510698
更新日期:2001-11-20 00:00:00
abstract::The neu gene is distantly related to the erbB gene and encodes a cell surface protein that appears to function as a growth factor receptor. To study the mechanisms that caused the conversion of the normal neu gene to an oncogenic allele, we have isolated molecular clones of the neu oncogene as well as a clone of the c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.2.261
更新日期:1986-01-01 00:00:00
abstract::An established line of mouse fibroblasts, C3H/10T1/2 cells, was used for the assessment in vitro of oncogenic transformations caused by single and split doses of x-rays. The shape of the dose-response relationship was determined over the range from 0.1 to 10 Gy. It was found that splitting the x-ray dose into two equa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.11.5755
更新日期:1979-11-01 00:00:00
abstract::Phages of the Caudovirales order possess a tail that recognizes the host and ensures genome delivery upon infection. The X-ray structure of the approximately 1.8 MDa host adsorption device (baseplate) from the lactococcal phage TP901-1 shows that the receptor-binding proteins are pointing in the direction of the host,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1200966109
更新日期:2012-06-05 00:00:00
abstract::Single-copy transgenes in Caenorhabditis elegans can be subjected to a potent, irreversible silencing process termed small RNA-induced epigenetic silencing (RNAe). RNAe is promoted by the Piwi Argonaute protein PRG-1 and associated Piwi-interacting RNAs (piRNAs), as well as by proteins that promote and respond to seco...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1501979112
更新日期:2015-05-19 00:00:00
abstract::One of the technical bottlenecks in producing nonhuman primate models is that current assisted reproductive techniques, such as in vitro culture and frozen conservation of multicell-stage embryos, often result in poor embryo quality and subsequently lead to low birth rates. We investigated whether pronuclear embryo tr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0805639105
更新日期:2008-09-02 00:00:00
abstract::A model for protein synthesis is proposed in which the donor for the peptide elongation reaction is peptidyl-5S RNA. Space-filling models show that peptide bond formation between peptidyl-5S RNA and aminoacyl-tRNA is eminently feasible from a stereochemical point of view. The peptide is transferred to 5S RNA, while at...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.10.2357
更新日期:1971-10-01 00:00:00
abstract::Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.6.1790
更新日期:1985-03-01 00:00:00
abstract::We have constructed an opal suppressor system in Escherichia coli to complement an existing amber suppressor system to study the structural basis of tRNA acceptor identity, particularly the role of middle anticodon nucleotide at position 35. The opal suppressor tRNA contains a UCA anticodon and the mRNA of the suppres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.23.9260
更新日期:1990-12-01 00:00:00
abstract::The failure of the population of microjunctions forming the frictional interface between two solids is central to fields ranging from biomechanics to seismology. This failure is mediated by the propagation along the interface of various types of rupture fronts, covering a wide range of velocities. Among them are the s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1321752111
更新日期:2014-06-17 00:00:00
abstract::DNA mismatch repair is central to the maintenance of genomic stability. It is initiated by the recognition of base-base mismatches and insertion/deletion loops by the family of MutS proteins. Subsequently, ATP induces a unique conformational change in the MutS-mismatch complex but not in the MutS-homoduplex complex th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2433654100
更新日期:2003-12-09 00:00:00
abstract::Neuronal signal integration as well as synaptic transmission and plasticity highly depend on the morphology of dendrites and their spines. Nogo-A is a membrane protein enriched in the adult central nervous system (CNS) myelin, where it restricts the capacity of axons to grow and regenerate after injury. Nogo-A is also...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1214255110
更新日期:2013-01-15 00:00:00
abstract::A plasmid containing the rat preproinsulin I gene was entrapped in large liposomes and intravenously administered to rats. Four hours after inoculation, the livers were processed for the isolation of hepatocytes. Kupffer cells, and endothelial cells, DNA was purified, and the exogenous DNA was detected in the differen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.23.7128
更新日期:1983-12-01 00:00:00
abstract::Siderophores are essential factors for iron (Fe) acquisition in bacteria during colonization and infection of eukaryotic hosts, which restrain iron access through iron-binding protein, such as lactoferrin and transferrin. The synthesis of siderophores by Escherichia coli is considered to be fully regulated at the tran...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1007805107
更新日期:2010-08-24 00:00:00
abstract::Proofreading mechanisms increase specificity in biochemical reactions by allowing for the dissociation of intermediate complexes. These mechanisms disrupt and reset the reaction to undo errors at the cost of increased time of reaction and free energy expenditure. Here, we draw an analogy between proofreading and micro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1119911109
更新日期:2012-07-24 00:00:00
abstract::MicroRNAs (miRNAs) are 18- to 24-nt RNA molecules that regulate messenger RNAs (mRNAs). Posttranscriptional mechanisms regulate miRNA abundance during development as well as in cancer cells where miRNAs frequently exhibit dysregulated expression. The molecular mechanisms that govern the global efficiency of miRNA biog...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0811523106
更新日期:2009-04-28 00:00:00
abstract::Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated gene inversion is used to change the specificity of the BCR on mature IgM+ IgD+ B cells in vivo to address the fate of lymp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.22.13171
更新日期:1998-10-27 00:00:00
abstract::The electrical currents at the surface of the proximal portion of an isolated and transected lamprey spinal cord were measured with an extracellular vibrating probe. Soon after transection, currents of about 0.5 mA/cm2 enter the cut surface of the spinal cord. These currents fall to about a quarter of their initial va...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.2.1209
更新日期:1980-02-01 00:00:00
abstract::The type of cytokines produced during T cell responses determines susceptibility or resistance to many pathogens and influences the development of autoimmunity and allergy. To define the role of individual accessory molecules in cytokine production during primary immune responses, Drosophila cell lines expressing muri...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.6.3023
更新日期:1999-03-16 00:00:00
abstract::Understanding the relationship between genetic variation and phenotypic variation for quantitative traits is necessary for predicting responses to natural and artificial selection and disease risk in human populations, but is challenging because of large sample sizes required to detect and validate loci with small eff...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1220168110
更新日期:2013-01-15 00:00:00
abstract::It is becoming clear that steroids can be synthesized de novo by the brain and other nervous systems. Such steroids are called neurosteroids, and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. In this study, we show that the newt brain actively produces 7alpha-hydroxypregne...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407176101
更新日期:2004-12-07 00:00:00
abstract::We have used the polymerase chain reaction (PCR) to amplify up to 22 kb of the beta-globin gene cluster from human genomic DNA and up to 42 kb from phaga lambda DNA. We have also amplified 91 human genomic inserts of 9-23 kb directly from recombinant lambda plaques. To do this, we increased pH, added glycerol and dime...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.12.5695
更新日期:1994-06-07 00:00:00
abstract::Inteins are intervening protein sequences that undergo self-excision from a precursor protein with concomitant joining of the flanking sequences. Here, we demonstrate intein trans-splicing in Nicotiana tabacum chloroplasts by using the naturally split Ssp DnaE intein. Trans-splicing occurred whether both intein fragme...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0736538100
更新日期:2003-04-15 00:00:00
abstract::Particular major histocompatibility complex (MHC) class II alleles clearly contribute to T cell-mediated autoimmune type 1 diabetes (T1D) in both humans and nonobese diabetic (NOD) mice. However, studies in NOD mice indicate MHC class I-restricted T cell responses are also essential to T1D development. In humans, epid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.212221199
更新日期:2002-10-15 00:00:00
abstract::The mammalian anx7 gene codes for a Ca(2+)-activated GTPase, which supports Ca(2+)/GTP-dependent secretion events and Ca(2+) channel activities in vitro and in vivo. To test whether anx7 might be involved in Ca(2+) signaling in secreting pancreatic beta cells, we knocked out the anx7 gene in the mouse and tested the i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.24.13783
更新日期:1999-11-23 00:00:00
abstract::When an algorithm in dimension one is extended to dimension d, in nearly every case its computational cost is taken to the power d. This fundamental difficulty is the single greatest impediment to solving many important problems and has been dubbed the curse of dimensionality. For numerical analysis in dimension d, we...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.112329799
更新日期:2002-08-06 00:00:00
abstract::The ecological niche is a key concept for elucidating patterns of species distributions and developing strategies for conserving biodiversity. However, recent times are seeing a widespread debate whether species niches are conserved across space and time (niche conservatism hypothesis). Biological invasions represent ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2004289117
更新日期:2020-09-22 00:00:00