122 research outputs found

    Free induction signal from biexcitons and bound excitons

    Full text link
    A theory of the free induction signal from biexcitons and bound excitons is presented. The simultaneous existence of the exciton continuum and a bound state is shown to result in a new type of time dependence of the free induction. The optically detected signal increases in time and oscillates with increasing amplitude until damped by radiative or dephasing processes. Radiative decay is anomalously fast and can result in strong picosecond pulses. The expanding area of a coherent exciton polarization (inflating antenna), produced by the exciting pulse, is the underlying physical mechanism. The developed formalism can be applied to different biexciton transients.Comment: RevTeX, 20 p. + 2 ps fig. To appear in Phys. Rev. B1

    Ultrafast Coulomb-induced dynamics of 2D magnetoexcitons

    Full text link
    We study theoretically the ultrafast nonlinear optical response of quantum well excitons in a perpendicular magnetic field. We show that for magnetoexcitons confined to the lowest Landau levels, the third-order four-wave-mixing (FWM) polarization is dominated by the exciton-exciton interaction effects. For repulsive interactions, we identify two regimes in the time-evolution of the optical polarization characterized by exponential and {\em power law} decay of the FWM signal. We describe these regimes by deriving an analytical solution for the memory kernel of the two-exciton wave-function in strong magnetic field. For strong exciton-exciton interactions, the decay of the FWM signal is governed by an antibound resonance with an interaction-dependent decay rate. For weak interactions, the continuum of exciton-exciton scattering states leads to a long tail of the time-integrated FWM signal for negative time delays, which is described by the product of a power law and a logarithmic factor. By combining this analytic solution with numerical calculations, we study the crossover between the exponential and non-exponential regimes as a function of magnetic field. For attractive exciton-exciton interaction, we show that the time-evolution of the FWM signal is dominated by the biexcitonic effects.Comment: 41 pages with 11 fig

    Effects of genome-wide copy number variation on expression in mammalian cells

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>There is only a limited understanding of the relation between copy number and expression for mammalian genes. We fine mapped <it>cis </it>and <it>trans </it>regulatory loci due to copy number change for essentially all genes using a human-hamster radiation hybrid (RH) panel. These loci are called copy number expression quantitative trait loci (ceQTLs).</p> <p>Results</p> <p>Unexpected findings from a previous study of a mouse-hamster RH panel were replicated. These findings included decreased expression as a result of increased copy number for 30% of genes and an attenuated relationship between expression and copy number on the X chromosome suggesting an <it>Xist </it>independent form of dosage compensation. In a separate glioblastoma dataset, we found conservation of genes in which dosage was negatively correlated with gene expression. These genes were enriched in signaling and receptor activities. The observation of attenuated X-linked gene expression in response to increased gene number was also replicated in the glioblastoma dataset. Of 523 gene deserts of size > 600 kb in the human RH panel, 325 contained <it>trans </it>ceQTLs with -log<sub>10 </sub><it>P </it>> 4.1. Recently discovered genes, ultra conserved regions, noncoding RNAs and microRNAs explained only a small fraction of the results, suggesting a substantial portion of gene deserts harbor as yet unidentified functional elements.</p> <p>Conclusion</p> <p>Radiation hybrids are a useful tool for high resolution mapping of <it>cis </it>and <it>trans </it>loci capable of affecting gene expression due to copy number change. Analysis of two independent radiation hybrid panels show agreement in their findings and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome.</p

    Interleukin-4 Alters Early Phagosome Phenotype by Modulating Class I PI3K Dependent Lipid Remodeling and Protein Recruitment

    Get PDF
    Phagocytosis is a complex process that involves membranelipid remodeling and the attraction and retention of key effector proteins. Phagosome phenotype depends on the type of receptor engaged and can be influenced by extracellular signals. Interleukin 4 (IL-4) is a cytokine that induces the alternative activation of macrophages (MΦs) upon prolonged exposure, triggering a different cell phenotype that has an altered phagocytic capacity. In contrast, the direct effects of IL-4 during phagocytosis remain unknown. Here, we investigate the impact of short-term IL-4 exposure (1 hour) during phagocytosis of IgG-opsonized yeast particles by MΦs. By time-lapse confocal microscopy of GFP-tagged lipid-sensing probes, we show that IL-4 increases the negative charge of the phagosomal membrane by prolonging the presence of the negatively charged second messenger PI(3,4,5)P3. Biochemical assays reveal an enhanced PI3K/Akt activity upon phagocytosis in the presence of IL-4. Blocking the specific class I PI3K after the onset of phagocytosis completely abrogates the IL-4-induced changes in lipid remodeling and concomitant membrane charge. Finally, we show that IL-4 direct signaling leads to a significantly prolonged retention profile of the signaling molecules Rac1 and Rab5 to the phagosomal membrane in a PI3K-dependent manner. This protracted early phagosome phenotype suggests an altered maturation, which is supported by the delayed phagosome acidification measured in the presence of IL-4. Our findings reveal that molecular differences in IL-4 levels, in the extracellular microenvironment, influence the coordination of lipid remodeling and protein recruitment, which determine phagosome phenotype and, eventually, fate. Endosomal and phagosomal membranes provide topological constraints to signaling molecules. Therefore, changes in the phagosome phenotype modulated by extracellular factors may represent an additional mechanism that regulates the outcome of phagocytosis and could have significant impact on the net biochemical output of a cell

    Enhancement of Cell Membrane Invaginations, Vesiculation and Uptake of Macromolecules by Protonation of the Cell Surface

    Get PDF
    The different pathways of endocytosis share an initial step involving local inward curvature of the cell’s lipid bilayer. It has been shown that to generate membrane curvature, proteins or lipids enforce transversal asymmetry of the plasma membrane. Thus it emerges as a general phenomenon that transversal membrane asymmetry is the common required element for the formation of membrane curvature. The present study demonstrates that elevating proton concentration at the cell surface stimulates the formation of membrane invaginations and vesiculation accompanied by efficient uptake of macromolecules (Dextran-FITC, 70 kD), relative to the constitutive one. The insensitivity of proton induced uptake to inhibiting treatments and agents of the known endocytic pathways suggests the entry of macromolecules to proceeds via a yet undefined route. This is in line with the fact that neither ATP depletion, nor the lowering of temperature, abolishes the uptake process. In addition, fusion mechanism such as associated with low pH uptake of toxins and viral proteins can be disregarded by employing the polysaccharide dextran as the uptake molecule. The proton induced uptake increases linearly in the extracellular pH range of 6.5 to 4.5, and possesses a steep increase at the range of 4> pH>3, reaching a plateau at pH≤3. The kinetics of the uptake implies that the induced vesicles release their content to the cytosol and undergo rapid recycling to the plasma membrane. We suggest that protonation of the cell’s surface induces local charge asymmetries across the cell membrane bilayer, inducing inward curvature of the cell membrane and consequent vesiculation and uptake

    Update of complications and functional outcome of the ileo-pouch anal anastomosis: overview of evidence and meta-analysis of 96 observational studies

    Get PDF
    Item does not contain fulltextOBJECTIVE: The objective of this study is to provide a comprehensive update of the outcome of the ileo-pouch anal anastomosis (IPAA). DATA SOURCES: An extensive search in PubMed, EMBASE, and The Cochrane Library was conducted. STUDY SELECTION AND DATA EXTRACTION: All studies published after 2000 reporting on complications or functional outcome after a primary open IPAA procedure for UC or FAP were selected. Study characteristics, functional outcome, and complications were extracted. DATA SYNTHESIS: A review with similar methodology conducted 10 years earlier was used to evaluate developments in outcome over time. Pooled estimates were compared using a random-effects logistic meta-analyzing technique. Analyses focusing on the effect of time of study conductance, centralization, and variation in surgical techniques were performed. RESULTS: Fifty-three studies including 14,966 patients were included. Pooled rates of pouch failure and pelvic sepsis were 4.3% (95% CI, 3.5-6.3) and 7.5% (95% CI 6.1-9.1), respectively. Compared to studies published before 2000, a reduction of 2.5% was observed in the pouch failure rate (p = 0.0038). Analysis on the effect of the time of study conductance confirmed a decline in pouch failure. Functional outcome remained stable over time, with a 24-h defecation frequency of 5.9 (95% CI, 5.0-6.9). Technical surgery aspects did not have an important effect on outcome. CONCLUSION: This review provides up to date outcome estimates of the IPAA procedure that can be useful as reference values for practice and research. It is also shows a reduction in pouch failure over time.1 juli 201

    Boron isotopes in foraminifera : systematics, biomineralisation, and CO2 reconstruction

    Get PDF
    Funding: Fellowship from University of St Andrews, $100 (pending) from Richard Zeebe, UK NERC grants NE/N003861/1 and NE/N011716/1.The boron isotope composition of foraminifera provides a powerful tracer for CO2 change over geological time. This proxy is based on the equilibrium of boron and its isotopes in seawater, which is a function of pH. However while the chemical principles underlying this proxy are well understood, its reliability has previously been questioned, due to the difficulty of boron isotope (δ11B) analysis on foraminferal samples and questions regarding calibrations between δ11B and pH. This chapter reviews the current state of the δ11B-pH proxy in foraminfera, including the pioneering studies that established this proxy’s potential, and the recent work that has improved understanding of boron isotope systematics in foraminifera and applied this tracer to the geological record. The theoretical background of the δ11B-pH proxy is introduced, including an accurate formulation of the boron isotope mass balance equations. Sample preparation and analysis procedures are then reviewed, with discussion of sample cleaning, the potential influence of diagenesis, and the strengths and weaknesses of boron purification by column chromatography versus microsublimation, and analysis by NTIMS versus MC-ICPMS. The systematics of boron isotopes in foraminifera are discussed in detail, including results from benthic and planktic taxa, and models of boron incorporation, fractionation, and biomineralisation. Benthic taxa from the deep ocean have δ11B within error of borate ion at seawater pH. This is most easily explained by simple incorporation of borate ion at the pH of seawater. Planktic foraminifera have δ11B close to borate ion, but with minor offsets. These may be driven by physiological influences on the foraminiferal microenvironment; a novel explanation is also suggested for the reduced δ11B-pH sensitivities observed in culture, based on variable calcification rates. Biomineralisation influences on boron isotopes are then explored, addressing the apparently contradictory observations that foraminifera manipulate pH during chamber formation yet their δ11B appears to record the pH of ambient seawater. Potential solutions include the influences of magnesium-removal and carbon concentration, and the possibility that pH elevation is most pronounced during initial chamber formation under favourable environmental conditions. The steps required to reconstruct pH and pCO2 from δ11B are then reviewed, including the influence of seawater chemistry on boron equilibrium, the evolution of seawater δ11B, and the influence of second carbonate system parameters on δ11B-based reconstructions of pCO2. Applications of foraminiferal δ11B to the geological record are highlighted, including studies that trace CO2 storage and release during recent ice ages, and reconstructions of pCO2 over the Cenozoic. Relevant computer codes and data associated with this article are made available online.Publisher PDFPeer reviewe

    A molecular mechanism for bacterial susceptibility to zinc

    Get PDF
    Transition row metal ions are both essential and toxic to microorganisms. Zinc in excess has significant toxicity to bacteria, and host release of Zn(II) at mucosal surfaces is an important innate defence mechanism. However, the molecular mechanisms by which Zn(II) affords protection have not been defined. We show that in Streptococcus pneumonia extracellular Zn(II) inhibits the acquisition of the essential metal Mn(II) by competing for binding to the solute binding protein PsaA. We show that, although Mn(II) is the high-affinity substrate for PsaA, Zn(II) can still bind, albeit with a difference in affinity of nearly two orders of magnitude. Despite the difference in metal ion affinities, high-resolution structures of PsaA in complex with Mn(II) or Zn(II) showed almost no difference. However, Zn(II)-PsaA is significantly more thermally stable than Mn(II)-PsaA, suggesting that Zn(II) binding may be irreversible. In vitro growth analyses show that extracellular Zn(II) is able to inhibit Mn(II) intracellular accumulation with little effect on intracellular Zn(II). The phenotype of S. pneumoniae grown at high Zn(II):Mn(II) ratios, i.e. induced Mn(II) starvation, closely mimicked a DpsaA mutant, which is unable to accumulate Mn(II). S. pneumoniae infection in vivo elicits massive elevation of the Zn(II):Mn(II) ratio and, in vitro, these Zn(II):Mn(II) ratios inhibited growth due to Mn(II) starvation, resulting in heightened sensitivity to oxidative stress and polymorphonuclear leucocyte killing. These results demonstrate that microbial susceptibility to Zn(II) toxicity is mediated by extracellular cation competition and that this can be harnessed by the innate immune response.Christopher A. McDevitt, Abiodun D. Ogunniyi, Eugene Valkov, Michael C. Lawrence, Bostjan Kobe, Alastair G. McEwan and James C. Pato
    • …
    corecore