Dickinsonholman0234

This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Promoters play a key role in driving insect-resistant genes during breeding of transgenic plants. In current transgenic procedures for breeding rice resistance to striped stem borer (Chilo suppressalis Walker, SSB), the constitutive promoter is used to drive the insect-resistant gene. To reduce the burden of constitutive promoters on plant growth, isolation and identification of insect-inducible promoters are particularly important. However, few promoters are induced specifically by insect feeding. RESULTS We found rice hydroperoxide lyase gene (OsHPL2) (LOC_Os02g12680) was upregulated after feeding by SSB. We subsequently cloned the promoter of OsHPL2 and analysed its expression pattern using the β-glucuronidase (GUS) reporter gene. Histochemical assays and quantitative analyses of GUS activity confirmed that P HPL2 GUS was activated by SSB, but did not respond to brown planthopper (Nilaparvata lugens Stål, BPH) infestation, mechanical wounding or phytohormone treatments. A series of 5' truncated assays were conducted and three positive regulatory regions (-1452 to -1213, -903 to -624, and -376 to -176) induced by SSB infestation were identified. P2R123-min 35S and P2TR2-min 35S promoters linked with cry1C of transgenic plants showed the highest levels of Cry1C protein expression and SSB larval mortality. CONCLUSION We identified an SSB-inducible promoter and three positive internal regions. Transgenic rice plants with the OsHPL2 promoter and its positive regions driving cry1C exhibited the expected larvicidal effect on SSB. Our study is the first report of an SSB-inducible promoter that could be used as a potential resource for breeding insect-resistant transgenic crops. © 2020 Society of Chemical Industry.The study of the human response to injury has been hampered by the inherent heterogeneity in the models and methods used. By studying a standard injury longitudinally, using individual patient-level analysis, we endeavoured to better describe its dynamics. We analysed clinical variables, clinical laboratory and plasma cytokines from 20 patients at five time points. Clustering analysis showed two prototype patterns of cytokine behaviour a concordant type, where cytokines behave the same way for all patients (notably IL-0 and TNFα), and a variable type, where different patterns of expression are seen for different patients (notably IL-8, IL-6 and IL-1RA). Analysis of the cytokines at the individual patient-level showed a strong four-way correlation between IL-1RA, GCSF, MIP-1β and MCP-1. As it holds for most patients and not just on average, this suggests that they form a network which may play a central role in the response to gastro-intestinal injuries in humans. In conclusion, the longitudinal analysis of cytokines in a standard model allowed the identification of their underlying patterns of expression. We propose that the two prototype patterns shown may reflect the mechanism that separates the common and individual aspects of the injury response. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) systems produce double strand breaks (DSBs) in targeted sites and generally cause insertion/deletions of one or several bases by non-homologous end joining (NHEJ)-mediated DNA repair. However, many edited cell lines with small insertions/deletions produce abnormal transcripts or proteins causing unexpected effects that complicate functional analysis (Tuladhar et al., 2019). This article is protected by copyright. All rights reserved.The mutation of K-RAS represents one of the most frequent genetic alterations in cancer. Targeting of downstream effectors of RAS, including of MEK and ERK, has limited clinical success in cancer patients with K-RAS-mutations. The reduced sensitivity of K-RAS-mutated cells to certain MEK inhibitors is associated with the feedback phosphorylation of MEK by CRAF and with the reactivation of mitogen-activated protein kinase (MAPK) signaling. Here, we report that the RAF dimer inhibitors, lifirafenib (BGB-283) and Compound C, show a strong synergistic effect with MEK inhibitors (MEKi), including mirdametinib (PD-0325901) and selumetinib, in suppressing the proliferation of K-RAS-mutated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cell lines. This synergistic effect was not observed with the B-RAFV600E selective inhibitor, vemurafenib. NSC-664704 Our mechanistic analysis revealed that RAF dimer inhibition suppresses RAF-dependent MEK reactivation and leads to the sustained inhibition of MAPK signaling in K-RAS-mutated cells. This synergistic effect was also observed in several K-RAS mutant mouse xenograft models. A pharmacodynamic analysis supported a role for the synergistic phospho-ERK blockade in enhancing the antitumor activity observed in the K-RAS mutant models. These findings support a vertical inhibition strategy in which RAF dimer and MEK inhibitors are combined to target K-RAS-mutated cancers, and has led to a Phase 1b/2 combination therapy study of lifirafenib and mirdametinib in solid tumor patients with K-RAS mutations and other MAPK pathway aberrations. This article is protected by copyright. All rights reserved.In this video, we propose a modified Natural Orifice Specimen Extraction Surgery (NOSES) technology called Three-trocar tubeless NOSES to radically resect rectosigmoid cancer, which can avoid a large abdominal incision for the extraction of specimen. Besides, only three trocar incisions are used to complete the whole procedure, and no tube (for example, nasogastric tube, drainage tube, or catheter) is left insitu after surgery, which can minimize patients' complications and pain. This article is protected by copyright. All rights reserved.Low lying small intestine can limit the ability to deliver safely external beam radiation therapy for pelvic malignancy,because of the risk of iatrogenic enteritis. Pelvic mesh placement, to sling the bowel out from the field, can eliminate this concern and short-life biodegradable (e.g. vicryl) meshes along with a laparoscopic approach minimize any intermediate or long-term morbidity that may result from the additional surgical intervention. This article is protected by copyright. All rights reserved.