1,589 research outputs found

    A rare case of orbital osteogenic sarcoma

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    Osteogenic sarcoma is a malignant bony tumor of mesenchymal cell ori gin. The association of osteogenic sarcoma with Paget's disease of the bone (osteitis deformans) is well-known. However, orbital involvement is rare; only two other cases have been reported in all of the literature. Untreated, the tumor is lethal, with death usually occurring from extension into the cranial fossa

    Stereoselective functionalization at C-2 and C-3 of the gibberellin via an intramolecular free radical cyclization approach

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    Stereoselective functionalization at C-2 and C-3 of the gibberellin skeleton was achieved via an intramolecular free radical cyclization approach using a tethered C-19 halomethyl ester as the radical precursor

    Access Anglesey 2018: Lessons from an inclusive field course

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    Abstract. Traditional methods of fieldwork delivery can present learners with a range of physical, cognitive and social challenges which may subsequently hinder their ability to engage effectively with learning. We developed a residential geoscience field course designed to be physically accessible to, and socially inclusive of, a diverse range of learners including those with limited physical mobility and neurodiverse conditions. This paper presents the logistical and pedagogical challenges involved in delivering such a field course. In terms of pedagogic design scheduling, pace and timing, and the ability to access content in multiple ways were critical to ensuring that all students were included in the learning. The most effective mitigations were the simplest and benefitted the whole group. Practical interventions found to support access and inclusion for the benefit of all participants included using an audio tour-guide system to communicate with students at field locations, using a four-wheel drive vehicle to improve access to specific locations, providing alternative exercises such as prepared photomicrographs and rock specimens, providing electronic tablets with suitable apps, and selecting accommodation with accessible common-room spaces, and a dedicated quiet room. </jats:p

    Programmed Iteration Controls the Assembly of the Nonanoic Acid Side Chain of the Antibiotic Mupirocin

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    \ua9 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. Mupirocin is a clinically important antibiotic produced by Pseudomonas fluorescens NCIMB 10586 that is assembled by a complex trans-AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown. Herein we report the application of NMR spectroscopy, mass spectrometry, chemical probes and in vitro assays to establish the remaining steps of 9HN biosynthesis. These investigations reveal a complex interplay between a novel iterative or “stuttering” KS-AT didomain (MmpF), the multidomain module MmpB and multiple ACPs. This work has important implications for understanding the late-stage biosynthetic steps of mupirocin and will be important for future engineering of related trans-AT biosynthetic pathways (e.g. thiomarinol)

    Cognitive interviewing techniques used in developing questionnaires on functional electrical stimulation in spinal cord injury

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    © 2016 MA Healthcare Ltd. Background/Aims: This paper illustrates the application of a technique, cognitive interviewing, which was used in the development of three questionnaires to determine the views of use of functional electrical stimulation by people with spinal cord injury, health care professionals and researchers working in spinal cord injury. Methods: Three questionnaires for the three populations were developed in order to explore views about the current and future use of functional electrical stimulation. The questionnaires were reviewed and discussed by the team. Cognitive interviews were carried out at participants’ homes, university or workplace and each interview lasted a mean time of 65 minutes. The interviewer used ‘think aloud’ techniques. They were transcribed and analysed using content analysis. Results: Twelve participants (four people with spinal cord injury, four health care professionals and four researchers) from across the United Kingdom took part. The process identified several areas for modification, including clarification of words, format and legibility of questions, changes to sections, and the layout of the questionnaires. Conclusions: Cognitive interviewing ensured that the questionnaires were readable, clear and relevant, unambiguous and related to current clinical practice and research. The technique resulted in good quality questionnaires with enhanced patient-centred language

    Structure and Function of the α-Hydroxylation Bimodule of the Mupirocin Polyketide Synthase

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    \ua9 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.Mupirocin is a clinically important antibiotic produced by a trans-AT Type I polyketide synthase (PKS) in Pseudomonas fluorescens. The major bioactive metabolite, pseudomonic acid A (PA−A), is assembled on a tetrasubstituted tetrahydropyran (THP) core incorporating a 6-hydroxy group proposed to be introduced by α-hydroxylation of the thioester of the acyl carrier protein (ACP) bound polyketide chain. Herein, we describe an in vitro approach combining purified enzyme components, chemical synthesis, isotopic labelling, mass spectrometry and NMR in conjunction with in vivo studies leading to the first characterisation of the α-hydroxylation bimodule of the mupirocin biosynthetic pathway. These studies reveal the precise timing of hydroxylation by MupA, substrate specificity and the ACP dependency of the enzyme components that comprise this α-hydroxylation bimodule. Furthermore, using purified enzyme, it is shown that the MmpA KS0 shows relaxed substrate specificity, suggesting precise spatiotemporal control of in trans MupA recruitment in the context of the PKS. Finally, the detection of multiple intermodular MupA/ACP interactions suggests these bimodules may integrate MupA into their assembly

    Lung Cancer in Pulmonary Fibrosis: Tales of Epithelial Cell Plasticity

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    Lung epithelial cells exhibit a high degree of plasticity. Alterations to lung epithelial cell function are critically involved in several chronic lung diseases such as pulmonary fibrosis. Pulmonary fibrosis is characterized by repetitive injury and subsequent impaired repair of epithelial cells, which leads to aberrant growth factor activation and fibroblast accumulation. Increased proliferation and hyper- and metaplasia of epithelial cells upon injury have also been observed in pulmonary fibrosis; this epithelial cell activation might represent the basis for lung cancer development. Indeed, several studies have provided histopathological evidence of an increased incidence of lung cancer in pulmonary fibrosis. The mechanisms involved in the development of cancer in pulmonary fibrosis, however, remain poorly understood. This review highlights recently uncovered molecular mechanisms shared between lung cancer and fibrosis, which extend the current evidence of a common trait of cancer and fibrosis, as provided by histopathological observations. Copyright (C) 2011 S. Karger AG, Base

    Interrogation of an Enzyme Library Reveals the Catalytic Plasticity of Naturally Evolved [4+2] Cyclases

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    \ua9 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.Stereoselective carbon-carbon bond forming reactions are quintessential transformations in organic synthesis. One example is the Diels-Alder reaction, a [4+2] cycloaddition between a conjugated diene and a dienophile to form cyclohexenes. The development of biocatalysts for this reaction is paramount for unlocking sustainable routes to a plethora of important molecules. To obtain a comprehensive understanding of naturally evolved [4+2] cyclases, and to identify hitherto uncharacterised biocatalysts for this reaction, we constructed a library comprising forty-five enzymes with reported or predicted [4+2] cycloaddition activity. Thirty-one library members were successfully produced in recombinant form. In vitro assays employing a synthetic substrate incorporating a diene and a dienophile revealed broad-ranging cycloaddition activity amongst these polypeptides. The hypothetical protein Cyc15 was found to catalyse an intramolecular cycloaddition to generate a novel spirotetronate. The crystal structure of this enzyme, along with docking studies, establishes the basis for stereoselectivity in Cyc15, as compared to other spirotetronate cyclases

    Fetus in fetu: a case report

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
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