314 research outputs found

    Tex19.1 Promotes Spo11-Dependent Meiotic Recombination in Mouse Spermatocytes

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    Meiosis relies on the SPO11 endonuclease to generate the recombinogenic DNA double strand breaks (DSBs) required for homologous chromosome synapsis and segregation. The number of meiotic DSBs needs to be sufficient to allow chromosomes to search for and find their homologs, but not excessive to the point of causing genome instability. Here we report that the mammal-specific gene Tex19.1 promotes Spo11-dependent recombination in mouse spermatocytes. We show that the chromosome asynapsis previously reported in Tex19.1-/- spermatocytes is preceded by reduced numbers of recombination foci in leptotene and zygotene. Tex19.1 is required for normal levels of early Spo11-dependent recombination foci during leptotene, but not for upstream events such as MEI4 foci formation or accumulation of H3K4me3 at recombination hotspots. Furthermore, we show that mice carrying mutations in Ubr2, which encodes an E3 ubiquitin ligase that interacts with TEX19.1, phenocopy the Tex19.1-/- recombination defects. These data suggest that Tex19.1 and Ubr2 are required for mouse spermatocytes to accumulate sufficient Spo11-dependent recombination to ensure that the homology search is consistently successful, and reveal a hitherto unknown genetic pathway promoting meiotic recombination in mammals

    Selective Growth of Vertical-aligned ZnO Nanorod Arrays on Si Substrate by Catalyst-free Thermal Evaporation

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    By thermal evaporation of pure ZnO powders, high-density vertical-aligned ZnO nanorod arrays with diameter ranged in 80–250 nm were successfully synthesized on Si substrates covered with ZnO seed layers. It was revealed that the morphology, orientation, crystal, and optical quality of the ZnO nanorod arrays highly depend on the crystal quality of ZnO seed layers, which was confirmed by the characterizations of field-emission scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and photoluminescence measurements. For ZnO seed layer with wurtzite structure, the ZnO nanorods grew exactly normal to the substrate with perfect wurtzite structure, strong near-band-edge emission, and neglectable deep-level emission. The nanorods synthesized on the polycrystalline ZnO seed layer presented random orientation, wide diameter, and weak deep-level emission. This article provides a C-free and Au-free method for large-scale synthesis of vertical-aligned ZnO nanorod arrays by controlling the crystal quality of the seed layer

    Modeling and Reasoning about Preference-Based Context-Aware Agents over Heterogeneous Knowledge Sources

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    © 2017, The Author(s). This paper presents a conceptual framework and multi-agent model for context-aware decision support in dynamic smart environments based on heterogeneous knowledge sources. A ProtĂ©gĂ© plug-in for rules extraction from distributed ontologies has been developed, which allows us to model context-aware agents using the notion of multi-context systems. Extracted rules can be annotated to match the users’ needs and to develop a preference model to support their preferences so as to provide a user with a more personalized services. The use of the proposed framework is illustrated using a simple fact-based preference model developed from ontologies considering two different smart environment domains

    Gut microbiota trajectory in early life may predict development of celiac disease.

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    BACKGROUND: To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease. METHODS: A nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset. RESULTS: The microbiota of infants who remained healthy showed an increase in bacterial diversity over time, characterized by increases in Firmicutes families, but not those who developed CD. Infants who subsequently developed CD showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. An increased relative abundance of Bifidobacterium longum was associated with control children while increased proportions of Bifidobacterium breve and Enterococcus spp. were associated with CD development. CONCLUSION: The findings suggest that alterations in the early trajectory of gut microbiota in infants at CD risk could influence the immune maturation process and predispose to CD, although larger population studies are warranted to confirm this hypothesis

    Conservation of the role of INNER NO OUTER in development of unitegmic ovules of the Solanaceae despite a divergence in protein function

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    The P-SlINO::SlINO-GFP transgene continues to be expressed after fertilization during the onset of fruit development. A-C: Ovules from P-SlINO::SlINO-GFP plants. D, E: Ovules from control plants. Images A (confocal) and B (DIC overlaid with GFP channel) show expression in the outer cell layer in an ovule post-anthesis. C-E are images of the surface cells of the integument of ovules taken from 3–4 mm fruits. C and D are images taken on an epifluorescence microscope (Axioplan) using a Chroma GFP filter set 41017 (Chroma, Bellows Falls, VT). E is a dark-field image of the same ovule in D. These images show expression is present in developing fruit. Scale bar in B represents 20 Όm, scale bar in E represents 20 Όm in C-E. (TIF 4435 kb

    YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of HGF and its receptor, cMET, in human lung cancer cells

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    BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that has a profound effect on cancer cells by stimulating migration and invasion and acting as an angiogenic factor. In lung cancer, the factor also plays a pivotal role and is linked to a poor outcome in patients. In particular, HGF is known to work in combination with EGF on lung cancer cells. In the present study, we investigated the effect of a traditional Chinese medicine reported in cancer therapies, namely YangZheng XiaoJi (YZXJ) on lung cancer and on HGF mediated migration and invasion of lung cancer cells. METHODS: Human lung cancer cells, SKMES1 and A549 were used in the study. An extract from the medicine was used. Cell migration was investigated using the EVOS and by ECIS. Cell–matrix adhesion and in vitro invasion were assessed. In vivo growth of lung cancer was tested using an in vivo xenograft tumour model and activation of the HGF receptor in lung tumours by an immunofluorescence method. RESULTS: Both lung cancer cells increased their migration in response to HGF and responded to YZXJ by reducing their speed of migration. YZXJ markedly reduced the migration and in vitro invasiveness induced by HGF. It worked synergistically with PHA665752 and SU11274, HGF receptor inhibitors on the lung cancer cells both on HGF receptor activation and on cell functions. A combination of HGF and EGF resulted in a greater increase in cell migration, which was similarly inhibited by YZXJ, and in combination with the HGF receptor and EGF receptor inhibitors. In vivo, YZXJ reduced the rate of tumour growth and potentiated the effects of PHA665752 on tumour growth. It was further revealed that YZXJ significantly reduced the degree of phosphorylation of the HGF receptor in lung tumours. CONCLUSION: YZXJ has a significant role in reducing the migration, invasion and in vivo tumour growth of lung cancer and acts to inhibit the migratory and invasive effects induced by HGF and indeed by HGF/EGF. This effect is likely attributed to the inhibition of the HGF receptor activation. These results indicate that YZXJ has a therapeutic role in lung cancer and that combined strategy with methods to block HGF and EGF should be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0639-1) contains supplementary material, which is available to authorized users

    CRISPR-based strategies in infectious disease diagnosis and therapy

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    CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases.info:eu-repo/semantics/publishedVersio
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