Integrin αvβ5 is a primary receptor for adenovirus in CAR-negative cells

<p>Abstract</p> <p>Background</p> <p>Viruses bind to specific cellular receptors in order to infect their hosts. The specific receptors a virus uses are important factors in determining host range, cellular tropism, and pathogenesis. For adenovirus, the existing model of entry requires two receptor interactions. First, the viral fiber protein binds Coxsackie and Adenovirus Receptor (CAR), its primary cellular receptor, which docks the virus to the cell surface. Next, viral penton base engages cellular integrins, coreceptors thought to be required exclusively for internalization and not contributing to binding. However, a number of studies reporting data which conflicts with this simple model have been published. These observations have led us to question the proposed two-step model for adenovirus infection.</p> <p>Results</p> <p>In this study we report that cells which express little to no CAR can be efficiently transduced by adenovirus. Using competition experiments between whole virus and soluble viral fiber protein or integrin blocking peptides, we show virus binding is not dependent on fiber binding to cells but rather on penton base binding cellular integrins. Further, we find that binding to low CAR expressing cells is inhibited specifically by a blocking antibody to integrin αvβ5, demonstrating that in these cells integrin αvβ5 and not CAR is required for adenovirus attachment. The binding mediated by integrin αvβ5 is extremely high affinity, in the picomolar range.</p> <p>Conclusions</p> <p>Our data further challenges the model of adenovirus infection in which binding to primary receptor CAR is required in order for subsequent interactions between adenovirus and integrins to initiate viral entry. In low CAR cells, binding occurs through integrin αvβ5, a receptor previously thought to be used exclusively in internalization. We show for the first time that integrin αvβ5 can be used as an alternate binding receptor.</p

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem

Complex chloroplast RNA metabolism: just debugging the genetic programme?

<p>Abstract</p> <p>Background</p> <p>The gene expression system of chloroplasts is far more complex than that of their cyanobacterial progenitor. This gain in complexity affects in particular RNA metabolism, specifically the transcription and maturation of RNA. Mature chloroplast RNA is generated by a plethora of nuclear-encoded proteins acquired or recruited during plant evolution, comprising additional RNA polymerases and sigma factors, and sequence-specific RNA maturation factors promoting RNA splicing, editing, end formation and translatability. Despite years of intensive research, we still lack a comprehensive explanation for this complexity.</p> <p>Results</p> <p>We inspected the available literature and genome databases for information on components of RNA metabolism in land plant chloroplasts. In particular, new inventions of chloroplast-specific mechanisms and the expansion of some gene/protein families detected in land plants lead us to suggest that the primary function of the additional nuclear-encoded components found in chloroplasts is the transgenomic suppression of point mutations, fixation of which occurred due to an enhanced genetic drift exhibited by chloroplast genomes. We further speculate that a fast evolution of transgenomic suppressors occurred after the water-to-land transition of plants.</p> <p>Conclusion</p> <p>Our inspections indicate that several chloroplast-specific mechanisms evolved in land plants to remedy point mutations that occurred after the water-to-land transition. Thus, the complexity of chloroplast gene expression evolved to guarantee the functionality of chloroplast genetic information and may not, with some exceptions, be involved in regulatory functions.</p

Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)

In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described

Observation of the J/ψJ/\psi and ψ(3686)\psi(3686) decays into ηΣ+Σˉ−\eta\Sigma^{+}\bar{\Sigma}^{-}

The decays $J/\psi\to\eta\Sigma^{+}\bar{\Sigma}{}^-$ and $\psi(3686)\to\eta\Sigma^{+}\bar{\Sigma}{}^-$ are observed for the first time, using $(10087 \pm 44)\times 10^{6}$ $J/\psi$ and $(448.1 \pm 2.9)\times 10^{6}$ $\psi(3686)$ events collected with the BESIII detector at the BEPCII collider. We determine the branching fractions of these two decays to be ${\cal B}(J/\psi\to\eta\Sigma^{+}\bar{\Sigma}{}^-)=(6.34 \pm 0.21 \pm 0.37)\times 10^{-5}$ and ${\cal B}(\psi(3686)\to\eta\Sigma^{+}\bar{\Sigma}{}^-)=(9.59 \pm 2.37 \pm 0.61)\times 10^{-6}$, where the first uncertainties are statistical and the second are systematic. The ratio of these two branching fractions is determined to be $\frac{{\cal B}(\psi(3686)\to\eta\Sigma^{+}\bar{\Sigma}{}^-)}{{\cal B}(J/\psi\to\eta\Sigma^{+}\bar{\Sigma}{}^-)}=(15.1 \pm 3.8)\%$, which is in agreement with the "12\% rule."Comment: 9 pages and 10 figure

Measurement of the absolute branching fraction of the inclusive decay Ds+→π+π+π−XD_s^+\to \pi^+\pi^+\pi^- X

Using an $e^+ e^-$ collision data sample with a total integrated luminosity of $3.19$ fb$^{-1}$ collected with the BESIII detector at a center-of-mass energy of 4.178 GeV, the branching fraction of the inclusive decay of the $D_s^+$ meson to final states including at least three charged pions is measured for the first time to be ${\cal B}(D_s^+\to\pi^+ \pi^+ \pi^- X) = (32.81 \pm 0.35_{\rm stat} \pm {0.82_{\rm syst}})\%$. In this measurement the charged pions from $K_S^0$ meson decays are excluded. The partial branching fractions of $D_s^+\to\pi^+ \pi^+ \pi^- X$ are also measured as a function of the $\pi^+ \pi^+ \pi^-$ invariant mass.Comment: 13 pages, 4 figure

Search for a scalar partner of the X(3872)X(3872) via ψ(3770)\psi(3770) decays into γηη′\gamma\eta\eta' and γπ+π−J/ψ\gamma\pi^{+}\pi^{-}J/\psi

Using a data sample corresponding to an integrated luminosity of 2.93 fb$^{-1}$ collected at a center-of-mass energy of 3.773~GeV with the BESIII detector at the BEPCII collider, we search for a scalar partner of the $X(3872)$, denoted as $X(3700)$, via $\psi(3770)\to \gamma\eta\eta'$ and $\gamma\pi^{+}\pi^{-}J/\psi$ processes. No significant signals are observed and the upper limits of the product branching fractions ${\cal B}(\psi(3770)\to\gamma X(3700))\cdot {\cal B}(X(3700)\to \eta\eta')$ and ${\cal B}(\psi(3770)\to\gamma X(3700))\cdot {\cal B}(X(3700)\to\pi^{+}\pi^{-}J/\psi)$ are determined at the 90\% confidence level, for the narrow $X(3700)$ with a mass ranging from 3710 to 3740 MeV/$c^2$, which are from 0.8 to 1.8 $(\times 10^{-5})$ and 0.9 to 3.4 $(\times 10^{-5})$, respectively

Measurement of branching fractions of Λc+\Lambda_{c}^{+} decays to Σ+K+K−\Sigma^{+} K^{+} K^{-}, Σ+ϕ\Sigma^{+}\phi and Σ+K+π−(π0)\Sigma^{+} K^{+} \pi^{-}(\pi^{0})

Based on 4.5 fb$^{-1}$ data taken at seven center-of-mass energies ranging from 4.600 to 4.699 GeV with the BESIII detector at the BEPCII collider, we measure the branching fractions of $\Lambda_{c}^{+}\rightarrow\Sigma^{+}+hadrons$ relative to $\Lambda_{c}^{+}\rightarrow \Sigma^+ \pi^+ \pi^-$. Combining with the world average branching fraction of $\Lambda_{c}^{+}\rightarrow \Sigma^+ \pi^+ \pi^-$, their branching fractions are measured to be $(0.377\pm0.042\pm0.018\pm0.021)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+} K^{+} K^{-}$, $(0.200\pm0.023\pm0.010\pm0.011)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+} K^{+} \pi^{-}$, $(0.414\pm0.080\pm0.029\pm0.023)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+}\phi$ and $(0.197\pm0.036\pm0.008\pm0.011)\%$ for $\Lambda_{c}^{+}\rightarrow\Sigma^{+}K^{+} K^{-}$(non-$\phi$). In all the above results, the first uncertainties are statistical, the second are systematic and the third are from external input of the branching fraction of $\Lambda_{c}^{+}\rightarrow \Sigma^+ \pi^+ \pi^-$. Since no signal for $\Lambda_{c}^{+}\rightarrow\Sigma^{+} K^{+} \pi^{-}\pi^{0}$ is observed, the upper limit of its branching fraction is determined to be 0.11\% at the 90$\%$ confidence level