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Dr. Emilianne M. Limbrick Audrey E. Yñigez-Gutierrez Callie C. Dulin Dagmara K. Derewacz Dr. Jeffrey M. Spraggins Dr. Kathryn M. McCulloch Prof. T. M. Iverson Prof. Brian O. Bachmann 《Chembiochem : a European journal of chemical biology》2020,21(23):3349-3358
Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A1, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A1- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A1-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates. 相似文献
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An explicit extraction of the retinal vessel is a standout amongst the most significant errands in the field of medical imaging to analyze both the ophthalmological infections, for example, Glaucoma, Diabetic Retinopathy (DR), Retinopathy of Prematurity (ROP), Age-Related Macular Degeneration (AMD) as well as non retinal sickness such as stroke, hypertension and cardiovascular diseases. The state of the retinal vasculature is a significant indicative element in the field of ophthalmology. Retinal vessel extraction in fundus imaging is a difficult task because of varying size vessels, moderately low distinction, and presence of pathologies such as hemorrhages, microaneurysms etc. Manual vessel extraction is a challenging task due to the complicated nature of the retinal vessel structure, which also needs strong skill set and training. In this paper, a supervised technique for blood vessel extraction in retinal images using Modified Adaboost Extreme Learning Machine (MAD-ELM) is proposed. Firstly, the fundus image preprocessing is done for contrast enhancement and in-homogeneity correction. Then, a set of core features is extracted, and the best features are selected using “minimal Redundancy-maximum Relevance (mRmR).” Later, using MAD-ELM method vessels and non vessels are classified. DRIVE and DR-HAGIS datasets are used for the evaluation of the proposed method. The algorithm’s performance is assessed based on accuracy, sensitivity and specificity. The proposed technique attains accuracy of 0.9619 on the DRIVE database and 0.9519 on DR-HAGIS database, which contains pathological images. Our results show that, in addition to healthy retinal images, the proposed method performs well in extracting blood vessels from pathological images and is therefore comparable with state of the art methods. 相似文献
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Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti 《International journal of molecular sciences》2015,16(8):19612-19630
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies. 相似文献