125 research outputs found

    The multiple facets of the Hsp90 machine

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    International audienceThe Ninth International Conference on the Hsp90 Chaperone Machine concluded in October 2018, in Leysin, Switzerland. The program highlighted findings in various areas, including integrated insight into molecular mechanism of Hsp90, cochaperones, and clients’ structure and function.Heat shock protein-90 (Hsp90) is a molecular chaperone critical for the folding, stability, and activity of client proteins 1. Hsp90 and its orthologs, including bacterial HtpG, mitochondrial TRAP1 and endoplasmic reticulum Grp94, exist as dimers, hydrolyze ATP, and cycle between distinct conformational states. Hsp90 preferentially binds proteins in near native states facilitating their remodeling for protein interactions and signaling. At the 9th International Conference on the Hsp90 Chaperone Machine approximately one-third of the attendees shared their data on Hsp90 structure and function through short talks (Figure 1). Here, we distill and summarize their finding

    Cooperative coupling of ultracold atoms and surface plasmons

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    Cooperative coupling between optical emitters and light fields is one of the outstanding goals in quantum technology. It is both fundamentally interesting for the extraordinary radiation properties of the participating emitters and has many potential applications in photonics. While this goal has been achieved using high-finesse optical cavities, cavity-free approaches that are broadband and easy to build have attracted much attention recently. Here we demonstrate cooperative coupling of ultracold atoms with surface plasmons propagating on a plane gold surface. While the atoms are moving towards the surface they are excited by an external laser pulse. Excited surface plasmons are detected via leakage radiation into the substrate of the gold layer. A maximum Purcell factor of ηP=4.9\eta_\mathrm{P}=4.9 is reached at an optimum distance of z=250 nmz=250~\mathrm{nm} from the surface. The coupling leads to the observation of a Fano-like resonance in the spectrum.Comment: 9 pages, 4 figure

    Human metapneumovirus induces more severe disease and stronger innate immune response in BALB/c mice as compared with respiratory syncytial virus

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    BACKGROUND: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are members of the Pneumovirinae subfamily of Paramyxoviridae and can cause severe respiratory disease, especially in infants and young children. Some differences in the clinical course of these infections have been described, but there are few comparative data on pathogenesis in humans and animal models. In this study, HMPV and RSV were compared for replication, pathogenesis and immune induction in BALB/c mice infected with equivalent inocula of either virus. METHODS: Viral titers in the lungs and in the nasal turbinates of mice were determined by plaque assay. Histopathological changes in the lungs as well as weight loss and levels of airway obstruction were monitored in the infected mice to record the severity of illness. Inflammatory cells recruited to the lungs were characterized by flow cytometry and by differential staining. In the case of natural killer cells, cytotoxic activity was also measured. Cytokine levels in the BAL were determined by cytometric bead array. RESULTS: RSV replicated to higher titers than HMPV in the lung and in the upper respiratory tract (URT), and virus elimination from the lungs was more rapid in HMPV-infected mice. Clinical illness as determined by airway obstruction, weight loss, and histopathology was significantly more severe after HMPV infection. A comparison of the cellular immune response revealed similar recruitment of T lymphocytes with a predominance of IFN-γ-producing CD8+ T cells. By contrast, there were obvious differences in the innate immune response. After HMPV infection, more neutrophils could be detected in the airways and there were more activated NK cells than in RSV-infected mice. This correlated with higher levels of IL-6, TNF-α and MCP-1. CONCLUSION: This study shows important differences in HMPV and RSV pathogenesis and suggests that the pronounced innate immune response observed after HMPV infection might be instrumental in the severe pathology

    Dissecting Early Differentially Expressed Genes in a Mixture of Differentiating Embryonic Stem Cells

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    The differentiation of embryonic stem cells is initiated by a gradual loss of pluripotency-associated transcripts and induction of differentiation genes. Accordingly, the detection of differentially expressed genes at the early stages of differentiation could assist the identification of the causal genes that either promote or inhibit differentiation. The previous methods of identifying differentially expressed genes by comparing different cell types would inevitably include a large portion of genes that respond to, rather than regulate, the differentiation process. We demonstrate through the use of biological replicates and a novel statistical approach that the gene expression data obtained without prior separation of cell types are informative for detecting differentially expressed genes at the early stages of differentiation. Applying the proposed method to analyze the differentiation of murine embryonic stem cells, we identified and then experimentally verified Smarcad1 as a novel regulator of pluripotency and self-renewal. We formalized this statistical approach as a statistical test that is generally applicable to analyze other differentiation processes

    Identification of a Novel Chromosomal Passenger Complex and Its Unique Localization during Cytokinesis in Trypanosoma brucei

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    Aurora B kinase is a key component of the chromosomal passenger complex (CPC), which regulates chromosome segregation and cytokinesis. An ortholog of Aurora B was characterized in Trypanosoma brucei (TbAUK1), but other conserved components of the complex have not been found. Here we identified four novel TbAUK1 associated proteins by tandem affinity purification and mass spectrometry. Among these four proteins, TbKIN-A and TbKIN-B are novel kinesin homologs, whereas TbCPC1 and TbCPC2 are hypothetical proteins without any sequence similarity to those known CPC components from yeasts and metazoans. RNAi-mediated silencing of each of the four genes led to loss of spindle assembly, chromosome segregation and cytokinesis. TbKIN-A localizes to the mitotic spindle and TbKIN-B to the spindle midzone during mitosis, whereas TbCPC1, TbCPC2 and TbAUK1 display the dynamic localization pattern of a CPC. After mitosis, the CPC disappears from the central spindle and re-localizes at a dorsal mid-point of the mother cell, where the anterior tip of the daughter cell is tethered, to start cell division toward the posterior end, indicating a most unusual CPC-initiated cytokinesis in a eukaryote

    Progress and Research Needs of Plant Biomass Degradation by Basidiomycete Fungi

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    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]
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