629 research outputs found

    Dynamical SPQEIR model assesses the effectiveness of non-pharmaceutical interventions against COVID-19 epidemic outbreaks.

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    Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to mitigate it. However, it is generally difficult to estimate the joint impact of different control strategies. In this paper, we tackle this question with an extended epidemic SEIR model, informed by a socio-political classification of different interventions. First, we inquire the conceptual effect of mitigation parameters on the infection curve. Then, we illustrate the potential of our model to reproduce and explain empirical data from a number of countries, to perform cross-country comparisons. This gives information on the best synergies of interventions to control epidemic outbreaks while minimising impact on socio-economic needs. For instance, our results suggest that, while rapid and strong lockdown is an effective pandemic mitigation measure, a combination of social distancing and early contact tracing can achieve similar mitigation synergistically, while keeping lower isolation rates. This quantitative understanding can support the establishment of mid- and long-term interventions, to prepare containment strategies against further outbreaks. This paper also provides an online tool that allows researchers and decision makers to interactively simulate diverse scenarios with our model

    Extracellular Signal–Regulated Kinase (Erk) Activation by the Pre-T Cell Receptor in Developing Thymocytes in Vivo

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    The first checkpoint in T cell development occurs between the CD4−CD8− and CD4+CD8+ stages and is associated with formation of the pre-T cell receptor (TCR). The signaling mechanisms that drive this progression remain largely unknown. Here, we show that extracellular signal–regulated kinases (ERKs)-1/2 are activated upon engagement of the pre-TCR. Using a novel experimental system, we demonstrate that expression of the pre-TCR by developing thymocytes induces ERK-1/2 activation within the thymus. In addition, the activation of this pre-TCR signaling cascade is mediated through Lck. These findings directly link pre-TCR complex formation with specific downstream signaling components in vivo

    Integrated olfactory receptor and microarray gene expression databases

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    <p>Abstract</p> <p>Background</p> <p>Gene expression patterns of olfactory receptors (ORs) are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD) to house OR gene expression data. ORMD is integrated with the Olfactory Receptor Database (ORDB), which is a key repository of OR gene information. Both databases aim to aid experimental research related to olfaction.</p> <p>Description</p> <p>ORMD is a Web-accessible database that provides a secure data repository for OR microarray experiments. It contains both publicly available and private data; accessing the latter requires authenticated login. The ORMD is designed to allow users to not only deposit gene expression data but also manage their projects/experiments. For example, contributors can choose whether to make their datasets public. For each experiment, users can download the raw data files and view and export the gene expression data. For each OR gene being probed in a microarray experiment, a hyperlink to that gene in ORDB provides access to genomic and proteomic information related to the corresponding olfactory receptor. Individual ORs archived in ORDB are also linked to ORMD, allowing users access to the related microarray gene expression data.</p> <p>Conclusion</p> <p>ORMD serves as a data repository and project management system. It facilitates the study of microarray experiments of gene expression in the olfactory system. In conjunction with ORDB, ORMD integrates gene expression data with the genomic and functional data of ORs, and is thus a useful resource for both olfactory researchers and the public.</p

    Transgenic Expression of P1A Induced Thymic Tumor: A Role for Onco-Fetal Antigens in Tumorigenesis

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    P1A is the first known tumor rejection antigen. It is expressed in embryonic stem cells and multiple tumors but is silent in adult tissues except for the testis and placenta. Therefore, P1A represents a prototype for onco-fetal antigens. To test the potential function of P1A in tumorigenesis, we used a transgenic mouse expressing P1A in lymphoid cells. We observed that immunodeficient host P1A transgenic mice developed thymic tumors after 7 months of age and had shorter survival rates compared to control groups. Most of the 7 examined tumors displayed B cell lineage markers. The P1A transgenic bone marrow cells had higher proliferation ability and more potential progenitors compared to control bone marrow cells. To our knowledge, our data provided the first example that onco-fetal antigen can promote tumorigenesis

    Key role of T cell defects in age-related vulnerability to West Nile virus

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    West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40–50× more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level of cytokine and lytic granule production, each of which are essential for resistance against WNV, and in the ability to generate multifunctional anti-WNV effector T cells, which are believed to be critical for robust antiviral immunity. In contrast, at the peak of the response, old and adult T cells exhibited superimposable peptide sensitivity. Most importantly, although the adult CD4 or CD8 T cells readily protected immunodeficient mice upon adoptive transfer, old T cells of either subset were unable to provide WNV-specific protection. Consistent with a profound qualitative and quantitative defect in T cell immunity, old brains contained at least 12× fewer total effector CD8 T cells compared with adult mice at the peak of brain infection. These findings identify potential targets for immunomodulation and treatment to combat lethal WNV infection in the elderly

    Identification of the Transgenic Integration Site in Immunodeficient tgε26 Human CD3ε Transgenic Mice

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    A strain of human CD3ε transgenic mice, tgε26, exhibits severe immunodeficiency associated with early arrest of T cell development. Complete loss of T cells is observed in homozygous tgε26 mice, but not in heterozygotes, suggesting that genomic disruption due to transgenic integration may contribute to the arrest of T cell development. Here we report the identification of the transgenic integration site in tgε26 mice. We found that multiple copies of the human CD3ε transgene are inserted between the Sstr5 and Metrn loci on chromosome 17, and that this is accompanied by duplication of the neighboring genomic region spanning 323 kb. However, none of the genes in this region were abrogated. These results suggest that the severe immunodeficiency seen in tgε26 mice is not due to gene disruption resulting from transgenic integration

    Spontaneous focal activation of invariant natural killer T (iNKT) cells in mouse liver and kidney

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    <p>Abstract</p> <p>Background</p> <p>Invariant natural killer T (iNKT) cells differ from other T cells by their hyperactive effector T-cell status, in addition to the expression of NK lineage receptors and semi-invariant T-cell receptors. It is generally agreed that the immune phenotype of iNKT cells is maintained by repeated activation in peripheral tissues although no explicit evidence for such iNKT cell activity <it>in vivo </it>has so far been reported.</p> <p>Results</p> <p>We used an interferon (IFN)-γ-inducible cytoplasmic protein, Irga6, as a histological marker for local IFN-γ production. Irga6 was intensely expressed in small foci of liver parenchymal cells and kidney tubular epithelium. Focal Irga6 expression was unaffected by germ-free status or loss of TLR signalling and was totally dependent on IFN-γ secreted by T cells in the centres of expression foci. These were shown to be iNKT cells by diagnostic T cell receptor usage and their activity was lost in both CD1 d and Jα-deficient mice.</p> <p>Conclusions</p> <p>This is the first report that supplies direct evidence for explicit activation events of NKT cells <it>in vivo </it>and raises issues about the triggering mechanism and consequences for immune functions in liver and kidney.</p
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