Abstract:
:Molecular imaging probes have potential for in vivo identification of apoptosis and other intracellular processes. TcapQ, a cell-penetrating, near-infrared fluorescent peptide probe designed to be optically silent through intramolecular fluorescence quenching and activated by effector caspases, has been previously described and validated in vitro. Herein, using NMDA-induced apoptosis of retinal ganglion cells (RGCs), representing an in vivo rat model of glaucoma, we assessed the ability of TcapQ to image single-cell apoptosis through effector caspase activity. Following intravitreal injection, intracellular TcapQ activation occurred specifically in RGCs, identified individual apoptotic cells, showed a clear dose-response relationship with NMDA, and colocalized with TUNEL labeling in the retina. There was a significant diminution of probe activation following pretreatment with a specific inhibitor of caspase-3. Stereospecificity was also exhibited by the lack of intracellular fluorescence upon administration of the noncleavable isomer, dTcapQ. TcapQ has potential utility in detecting and monitoring single-cell apoptosis in glaucoma in vivo.
journal_name
Proc Natl Acad Sci U S Aauthors
Barnett EM,Zhang X,Maxwell D,Chang Q,Piwnica-Worms Ddoi
10.1073/pnas.0812884106subject
Has Abstractpub_date
2009-06-09 00:00:00pages
9391-6issue
23eissn
0027-8424issn
1091-6490pii
0812884106journal_volume
106pub_type
杂志文章abstract::The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a transcriptional coactivator that controls expression of metabolic/energetic genes, programming cellular responses to nutrient and environmental adaptations such as fasting, cold, or exercise. Unlike other coactivators, PGC-1α contai...
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.2000643117
更新日期:2020-09-08 00:00:00
abstract::Gene regulation is a process with many steps allowing for stochastic biochemical reactions, which leads to expression noise-i.e., the cell-to-cell stochastic fluctuation in protein abundance. Such expression noise can give rise to drastically diverse phenotypes, even within isogenic cell populations. Although numerous...
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.0914302107
更新日期:2010-06-08 00:00:00
abstract::DNA methylation is an epigenetic mark that silences transposable elements (TEs) and repeats. Whereas the establishment and maintenance of DNA methylation are relatively well understood, little is known about their dynamics and biological relevance in plant and animal innate immunity. Here, we show that some TEs are de...
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.1211757110
更新日期:2013-02-05 00:00:00
abstract::Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 (V(1393)I, K(1584)E) were predicted to confer susceptibility for DM2. Here, we show using patch...
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.1113811109
更新日期:2012-07-10 00:00:00
abstract::A patterning method termed "RIPPLE" (reactive interface patterning promoted by lithographic electrochemistry) is applied to the fabrication of arrays of dielectric and metallic optical elements. This method uses cyclic voltammetry to impart patterns onto the working electrode of a standard three-electrode electrochemi...
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.1504280112
更新日期:2015-04-28 00:00:00
abstract::Two virus-specific RNA species of 7.5 and 7.0 kilobases have been identified in avian myeloblastosis virus (AMV) by denaturing gel electrophoresis and blot hybridization analysis, and they were found to be in a 10:1 ratio. The individual RNAs direccted the cell-free synthesis of the 76,000-dalton "gag" protein and 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.78.4.2057
更新日期:1981-04-01 00:00:00
abstract::Patchy particles with shape complementarity can serve as building blocks for assembling colloidal superstructures. Alternatively, encoding information on patches using DNA can direct assembly into a variety of crystalline or other preprogrammed structures. Here, we present a tool where DNA is used both to engineer sha...
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.1918504117
更新日期:2020-05-19 00:00:00
abstract::Development of pharyngeal muscle in nematodes and cardiac muscle in vertebrates and insects involves the related homeobox genes ceh-22, nkx2.5, and tinman, respectively. To determine whether the nematode and vertebrate genes perform similar functions, we examined activity of the zebrafish nkx2.5 gene in transgenic Cae...
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.95.9.5072
更新日期:1998-04-28 00:00:00
abstract::Animal development is remarkably robust; cell fates are specified with spatial and temporal precision despite physiological and environmental contingencies. Favorable conditions cause Caenorhabditis elegans to develop rapidly through four larval stages (L1-L4) to the reproductive adult. In unfavorable conditions, L2 l...
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.0908131106
更新日期:2009-11-03 00:00:00
abstract::Aphids maintain mutualistic symbioses involving consortia of coinherited organisms. All possess a primary endosymbiont, Buchnera, which compensates for dietary deficiencies; many also contain secondary symbionts, such as Hamiltonella defensa, which confers defense against natural enemies. Genome sequences of uncultiva...
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.0507029102
更新日期:2005-11-22 00:00:00
abstract::Previous studies have demonstrated that mutation in the forkhead domain of the forkhead box P2 (FOXP2) protein (R553H) causes speech-language disorders. To further analyze FOXP2 function in speech learning, we generated a knockin (KI) mouse for Foxp2 (R552H) [Foxp2 (R552H)-KI], corresponding to the human FOXP2 (R553H)...
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.0712298105
更新日期:2008-02-26 00:00:00
abstract::We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecule...
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.1901734117
更新日期:2020-01-07 00:00:00
abstract::Accurate real-time tracking of influenza outbreaks helps public health officials make timely and meaningful decisions that could save lives. We propose an influenza tracking model, ARGO (AutoRegression with GOogle search data), that uses publicly available online search data. In addition to having a rigorous statistic...
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.1515373112
更新日期:2015-11-24 00:00:00
abstract::The expression of CD5 increases progressively as thymocytes mature. We have shown that CD5 expression is controlled by a tissue-specific regulatory promoter located upstream of the CD5 translation start sites. Deletion of this regulatory promoter, which contains three potential transcription factor binding sites (CCAA...
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.0308764101
更新日期:2004-03-16 00:00:00
abstract::beta 2-Glycoprotein I (beta 2-GPI), a phospholipid-binding plasma protein, is an absolute requirement (cofactor) for the binding of autoimmune-type anti-cardiolipin (aCL) antibodies to cardiolipin (CL). The nature of this cofactor activity and the specific regions of the molecule involved have not yet been determined....
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.90.6.2141
更新日期:1993-03-15 00:00:00
abstract::The triphenylmethane derivative aurintricarboxylic acid (ATA), but not aurin, selectively prevented the binding of OKT4A/Leu-3a monoclonal antibody (mAb) and, to a lesser extent, OKT4 mAb to the CD4 cell receptor for human immunodeficiency virus type 1 (HIV-1). The effect was seen within 1 min at an ATA concentration ...
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.86.9.3322
更新日期:1989-05-01 00:00:00
abstract::The thylakoid compartments of plant chloroplasts are a vital destination for copper. Copper is needed to form holo-plastocyanin, which must shuttle electrons between photosystems to convert light into biologically useful chemical energy. Copper can bind tightly to proteins, so it has been hypothesized that copper part...
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.0600142103
更新日期:2006-05-30 00:00:00
abstract::The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivi...
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.0909603107
更新日期:2010-01-12 00:00:00
abstract::A detailed conformational analysis of the known crystal structures of vitamin A, carotenoid, and xanthenoid derivatives has been made. These studies suggest that the visual chromophore 11-cis retinal and its isomers may each occur in several different conformational states, which would be expected to have different li...
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.69.6.1569
更新日期:1972-06-01 00:00:00
abstract::How can collective action evolve when individuals benefit from cooperation regardless of whether they pay its participation costs? According to one influential perspective, collective action problems are common, especially when groups are large, but may be solved when individuals who have more to gain from the collect...
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.1701582114
更新日期:2017-07-11 00:00:00
abstract::Poliovirus type 1 cDNA sequences coding for viral capsid polypeptide VP1 were inserted into the beta-lactamase sequence of Escherichia coli plasmid pBR322. Resulting recombinant plasmid pSW119 expressed in Escherichia coli a VP1-beta-lactamase fusion protein that reacted with antibodies raised against poliovirus capsi...
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.80.16.5080
更新日期:1983-08-01 00:00:00
abstract::Nuclear RNA of high molecular weight, approximately 15 to 30 x 10(3) nucleotides long, isolated from rat ascites cells, has been shown previously to contain both middle repetitive and single-copy sequences. However, it was not known whether these sequences were located on separate molecules or whether they were inters...
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.71.4.1108
更新日期:1974-04-01 00:00:00
abstract::The attachment of human polymorphonuclear leukocytes (PMN) to bovine endothelial monolayers is increased by pretreatment of the endothelial cells with leukotriene B4 (LTB4). The response is dose dependent with a maximum at 10(-6) M, requires no more than 1 min of preincubation for the maximal effect, and decays linear...
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.81.7.2191
更新日期:1984-04-01 00:00:00
abstract::Genetic variants underlying life-threatening diseases, being unlikely to be transmitted to the next generation, are gradually and selectively eliminated from the population through negative selection. We study the determinants of this evolutionary process in human genes underlying monogenic diseases by comparing vario...
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.2001248118
更新日期:2021-01-19 00:00:00
abstract::The cytosolic concentration of free Ca2+ in bovine neutrophils was monitored by using the intracellular Ca2+ indicator quin2, 2-[[2-bis(acetylamino)-5-methylphenoxy]methyl-6-methoxy-8- bis(acetylamino)]quinoline. Neutrophils at rest have a cytosolic Ca2+ concentration of 85 +/- 5 nM, which in 2-4 min increases to 300-...
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.81.5.1416
更新日期:1984-03-01 00:00:00
abstract::Phonoangiography, the quantitative analysis of sounds produced by blood flow, has been used to investigate local fluid motion in arteries narrowed by atherosclerosis. The sound spectra measured in vivo were found to be identical to those obtained in laboratory investigations of turbulent pipe flow. A theoretical model...
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.67.2.935
更新日期:1970-10-01 00:00:00
abstract::Incubation of a human beta-globin pre-mRNA in a HeLa cell nuclear extract under conditions permissive for efficient splicing resulted in the assembly of the RNA into ribonucleoprotein (RNP) complexes. This RNP formation occurred largely within the characteristic lag period that precedes splicing. Two classes of RNP 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.83.11.3718
更新日期:1986-06-01 00:00:00
abstract::The modern Old World Monkeys (Superfamily Cercopithecoidea, Family Cercopithecidae) can be traced back into the late Miocene, but their origin and subsequent diversification is obscured by the scarcity of terrestrial fossil sites in Africa between 15 and 6 Ma. Here, we document the presence of cercopithecids at 12.5 M...
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.1213691110
更新日期:2013-04-09 00:00:00
abstract::Intact DNA molecules extracted from HSV-1 (herpes simplex virus 1, human herpes virus 1) strain MP virions have a molecular weight of approximately 97 X 10(6), but cleavage with the HinIII restriction enzyme yields fourteen fragments with summed molecular weights of 160 X 10(6). Six "major" fragments occur once in eve...
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.72.11.4243
更新日期:1975-11-01 00:00:00
abstract::Cell-cycle progression is mediated by a co-ordinated interaction between cyclin-dependent kinases and their target proteins including the pRB and E2F/DP-1 complexes. Immunoneutralization and antisense experiments have established that the abundance of cyclin D1, a regulatory subunit of the cyclin-dependent kinases, ma...
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.93.23.12861
更新日期:1996-11-12 00:00:00