334 research outputs found
Experimental delayed-choice entanglement swapping
Motivated by the question, which kind of physical interactions and processes
are needed for the production of quantum entanglement, Peres has put forward
the radical idea of delayed-choice entanglement swapping. There, entanglement
can be "produced a posteriori, after the entangled particles have been measured
and may no longer exist". In this work we report the first realization of
Peres' gedanken experiment. Using four photons, we can actively delay the
choice of measurement-implemented via a high-speed tunable bipartite state
analyzer and a quantum random number generator-on two of the photons into the
time-like future of the registration of the other two photons. This effectively
projects the two already registered photons onto one definite of two mutually
exclusive quantum states in which either the photons are entangled (quantum
correlations) or separable (classical correlations). This can also be viewed as
"quantum steering into the past"
Runx Expression Is Mitogenic and Mutually Linked to Wnt Activity in Blastula-Stage Sea Urchin Embryos
The Runt homology domain (Runx) defines a metazoan family of sequence-specific transcriptional regulatory proteins that are critical for animal development and causally associated with a variety of mammalian cancers. The sea urchin Runx gene SpRunt-1 is expressed throughout the blastula stage embryo, and is required globally during embryogenesis for cell survival and differentiation.Depletion of SpRunt-1 by morpholino antisense-mediated knockdown causes a blastula stage deficit in cell proliferation, as shown by bromodeoxyuridine (BrdU) incorporation and direct cell counts. Reverse transcription coupled polymerase chain reaction (RT-PCR) studies show that the cell proliferation deficit is presaged by a deficit in the expression of several zygotic wnt genes, including wnt8, a key regulator of endomesoderm development. In addition, SpRunt-1-depleted blastulae underexpress cyclinD, an effector of mitogenic Wnt signaling. Blastula stage cell proliferation is also impeded by knockdown of either wnt8 or cyclinD. Chromatin immunoprecipitation (ChIP) indicates that Runx target sites within 5âČ sequences flanking cyclinD, wnt6 and wnt8 are directly bound by SpRunt-1 protein at late blastula stage. Furthermore, experiments using a green fluorescent protein (GFP) reporter transgene show that the blastula-stage operation of a cis-regulatory module previously shown to be required for wnt8 expression (Minokawa et al., Dev. Biol. 288: 545â558, 2005) is dependent on its direct sequence-specific interaction with SpRunt-1. Finally, inhibitor studies and immunoblot analysis show that SpRunt-1 protein levels are negatively regulated by glycogen synthase kinase (GSK)-3.These results suggest that Runx expression and Wnt signaling are mutually linked in a feedback circuit that controls cell proliferation during development
An Evolutionarily Conserved Arginine Is Essential for Tre1 G Protein-Coupled Receptor Function During Germ Cell Migration in Drosophila melanogaster
BACKGROUND: G protein-coupled receptors (GPCRs) play central roles in mediating cellular responses to environmental signals leading to changes in cell physiology and behaviors, including cell migration. Numerous clinical pathologies including metastasis, an invasive form of cell migration, have been linked to abnormal GPCR signaling. While the structures of some GPCRs have been defined, the in vivo roles of conserved amino acid residues and their relationships to receptor function are not fully understood. Trapped in endoderm 1 (Tre1) is an orphan receptor of the rhodopsin class that is necessary for primordial germ cell migration in Drosophila melanogaster embryos. In this study, we employ molecular genetic approaches to identify residues in Tre1 that are critical to its functions in germ cell migration. METHODOLOGY/PRINCIPAL FINDINGS: First, we show that the previously reported scattershot mutation is an allele of tre1. The scattershot allele results in an in-frame deletion of 8 amino acids at the junction of the third transmembrane domain and the second intracellular loop of Tre1 that dramatically impairs the function of this GPCR in germ cell migration. To further refine the molecular basis for this phenotype, we assayed the effects of single amino acid substitutions in transgenic animals and determined that the arginine within the evolutionarily conserved E/N/DRY motif is critical for receptor function in mediating germ cell migration within an intact developing embryo. CONCLUSIONS/SIGNIFICANCE: These structure-function studies of GPCR signaling in native contexts will inform future studies into the basic biology of this large and clinically important family of receptors
Worries about being judged versus being harmed: Disentangling the association of social anxiety and paranoia with schizotypy
Paranoia is a dimension of clinical and subclinical experiences in which others are believed to have harmful intentions. Mild paranoid concerns are relatively common in the general population, and more clinically severe paranoia shares features with social anxiety and is a key characteristic of schizotypy. Given that subclinical manifestations of schizotypy and paranoia may predict the occurrence of more severe symptoms, disentangling the associations of these related constructs may advance our understanding of their etiology; however no known studies to date have comprehensively evaluated how paranoia relates to social anxiety and schizotypy. The current research sought to examine the association of paranoia, assessed across a broad continuum of severity, with 1) the positive and negative schizotypy dimensions and 2) social anxiety. Specifically, the study tested a series of six competing, a priori models using confirmatory factor analysis in a sample of 862 young adults. As hypothesized, the data supported a four-factor model including positive schizotypy, negative schizotypy, social anxiety, and paranoia factors, suggesting that these are distinct constructs with differing patterns of interrelationships. Paranoia had a strong association with positive schizotypy, a moderate association with social anxiety, and a minimal association with negative schizotypy. The results are consistent with paranoia being part of a multidimensional model of schizotypy and schizophrenia. Prior studies treating schizotypy and schizophrenia as homogenous constructs often produce equivocal or non-replicable results because these dimensions are associated with distinct etiologies, presentations, and treatment responses; thus, the present conceptualization of paranoia within a multidimensional schizotypy framework should advance our understanding of these constructs. © 2014 Horton et al
Adult Body Weight Is Programmed by a Redox-Regulated and Energy-Dependent Process during the Pronuclear Stage in Mouse
In mammals fertilization triggers a series of Ca2+ oscillations that not only are essential for events of egg activation but also stimulate oxidative phosphorylation. Little is known, however, about the relationship between quantitative changes in egg metabolism and specific long-term effects in offspring. This study assessed whether post-natal growth is modulated by early transient changes in NAD(P)H and FAD2+ in zygotes. We report that experimentally manipulating the redox potential of fertilized eggs during the pronuclear (PN) stage affects post-natal body weight. Exogenous pyruvate induces NAD(P)H oxidation and stimulates mitochondrial activity with resulting offspring that are persistently and significantly smaller than controls. Exogenous lactate stimulates NAD+ reduction and impairs mitochondrial activity, and produces offspring that are smaller than controls at weaning but catch up after weaning. Cytosolic alkalization increases NAD(P)+ reduction and offspring of normal birth-weight become significantly and persistently larger than controls. These results constitute the first report that post-natal growth rate is ultimately linked to modulation of NAD(P)H and FAD2+ concentration as early as the PN stage
Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum
Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to âbiological processâ (n = 68), âcellular componentâ (n = 50), or âmolecular functionâ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, proteinâprotein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism
Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches
Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, AndrĂ©s. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; ArgentinaFil: Garavaglia, MatĂas Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de Ing.genĂ©tica y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Goya, MarĂa Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de Ing.genĂ©tica y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
Assertion, Uniqueness and Epistemic Hypocrisy
Pascal Engel (2008) has insisted that a number of notable strategies for rejecting the knowledge norm of assertion are put forward on the basis of the wrong kinds of reasons. A central aim of this paper will be to establish the contrast point: I argue that one very familiar strategy for defending the knowledge norm of assertionâviz., that it is claimed to do better in various respects than its competitors (e.g. the justification and the truth norms)â relies on a presupposition that is shown to be ultimately under motivated. That presupposition is the uniqueness thesisâthat there is a unique epistemic rule for assertion, and that such a rule
will govern assertions uniformly. In particular, the strategy I shall take here will be to challenge the sufficiency leg of the knowledge norm in a way that at the same time counts against Williamsonâs (2000) own rationale for the uniqueness thesis. However, rather than to challenge the sufficiency leg of the knowledge norm via the familiar style of âexpert opinionâ and, more generally, âsecond-hand knowledgeâ cases (e.g. Lackey (2008)), a strategy that has recently been called into question by Benton (2014), Iâll instead advance a very different line of argument against the sufficiency thesis, one which turns on a phenomenon I call epistemic hypocrisy
Asymptotic Expansions for the Sojourn Time Distribution in the -PS Queue
We consider the queue with a processor sharing server. We study the
conditional sojourn time distribution, conditioned on the customer's service
requirement, as well as the unconditional distribution, in various asymptotic
limits. These include large time and/or large service request, and heavy
traffic, where the arrival rate is only slightly less than the service rate.
Our results demonstrate the possible tail behaviors of the unconditional
distribution, which was previously known in the cases and (where it
is purely exponential). We assume that the service density decays at least
exponentially fast. We use various methods for the asymptotic expansion of
integrals, such as the Laplace and saddle point methods.Comment: 45 page
ZFNGenome: A comprehensive resource for locating zinc finger nuclease target sites in model organisms
<p>Abstract</p> <p>Background</p> <p>Zinc Finger Nucleases (ZFNs) have tremendous potential as tools to facilitate genomic modifications, such as precise gene knockouts or gene replacements by homologous recombination. ZFNs can be used to advance both basic research and clinical applications, including gene therapy. Recently, the ability to engineer ZFNs that target any desired genomic DNA sequence with high fidelity has improved significantly with the introduction of rapid, robust, and publicly available techniques for ZFN design such as the Oligomerized Pool ENgineering (OPEN) method. The motivation for this study is to make resources for genome modifications using OPEN-generated ZFNs more accessible to researchers by creating a user-friendly interface that identifies and provides quality scores for all potential ZFN target sites in the complete genomes of several model organisms.</p> <p>Description</p> <p>ZFNGenome is a GBrowse-based tool for identifying and visualizing potential target sites for OPEN-generated ZFNs. ZFNGenome currently includes a total of more than 11.6 million potential ZFN target sites, mapped within the fully sequenced genomes of seven model organisms; <it>S. cerevisiae, C. reinhardtii, A. thaliana</it>, <it>D. melanogaster, D. rerio, C. elegans</it>, and <it>H. sapiens </it>and can be visualized within the flexible GBrowse environment. Additional model organisms will be included in future updates. ZFNGenome provides information about each potential ZFN target site, including its chromosomal location and position relative to transcription initiation site(s). Users can query ZFNGenome using several different criteria (e.g., gene ID, transcript ID, target site sequence). Tracks in ZFNGenome also provide "uniqueness" and ZiFOpT (Zinc Finger OPEN Targeter) "confidence" scores that estimate the likelihood that a chosen ZFN target site will function <it>in vivo</it>. ZFNGenome is dynamically linked to ZiFDB, allowing users access to all available information about zinc finger reagents, such as the effectiveness of a given ZFN in creating double-stranded breaks.</p> <p>Conclusions</p> <p>ZFNGenome provides a user-friendly interface that allows researchers to access resources and information regarding genomic target sites for engineered ZFNs in seven model organisms. This genome-wide database of potential ZFN target sites should greatly facilitate the utilization of ZFNs in both basic and clinical research.</p> <p>ZFNGenome is freely available at: <url>http://bindr.gdcb.iastate.edu/ZFNGenome</url> or at the Zinc Finger Consortium website: <url>http://www.zincfingers.org/</url>.</p
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