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RISS 인기검색어
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- 저자 : S. SCHOFIELD (검색결과 5 건)
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Investigations on recyclisation and hydrolysis in avibactam mediated serine β-lactamase inhibition
Choi, Hwanho,Paton, Robert S.,Park, Hwangseo,Schofield, Christopher J. Royal Society of Chemistry 2016 Organic & biomolecular chemistry Vol.14 No.17
<▼1><P>In contrast to the β-lactams, which react irreversibly, avibactam reacts reversibly with serine β-lactamases.</P></▼1><▼2><P>β-Lactams inhibit penicillin-binding proteins (PBPs) and serine β-lactamases by acylation of a nucleophilic active site serine. Avibactam is approved for clinical use in combination with ceftazidime, and is a breakthrough non β-lactam β-lactamase inhibitor also reacting <I>via</I> serine acylation. Molecular dynamics (MD) and quantum chemical calculations on avibactam-mediated inhibition of a clinically relevant cephalosporinase reveal that recyclisation of the avibactam derived carbamoyl complex is favoured over hydrolysis. In contrast, we show that analogous recyclisation in β-lactam mediated inhibition is disfavoured. Avibactam recyclisation is promoted by a proton shuttle, a ‘structural’ water protonating the nucleophilic serine, and stabilization of the negative charge developed on aminocarbonyl oxygen. The results imply the potential of calculations for distinguishing between bifurcating pathways during inhibition and in generating hypotheses for predicting resistance. The inability of β-lactams to undergo recyclisation may be an Achilles heel, but one that can be addressed by suitably functionalized reversibly binding inhibitors.</P></▼2>
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Glider observations of the Dotson Ice Shelf outflow
Miles, T.,Lee, S.H.,Wahlin, A.,Ha, H.K.,Kim, T.W.,Assmann, K.M.,Schofield, O. Pergamon Press 2016 Deep-sea research. Part II, Topical studies in oce Vol.123 No.-
The Amundsen Sea is one of the most productive polynyas in the Antarctic per unit area and is undergoing rapid changes including a reduction in sea ice duration, thinning ice sheets, retreat of glaciers and the potential collapse of the Thwaites Glacier in Pine Island Bay. A growing body of research has indicated that these changes are altering the water mass properties and associated biogeochemistry within the polynya. Unfortunately difficulties in accessing the remote location have greatly limited the amount of in situ data that has been collected. In this study data from a Teledyne-Webb Slocum glider was used to supplement ship-based sampling along the Dotson Ice Shelf (DIS). This autonomous underwater vehicle revealed a detailed view of a meltwater laden outflow from below the western flank of the DIS. Circumpolar Deep Water intruding onto the shelf drives glacial melt and the supply of macronutrients that, along with ample light, supports the large phytoplankton blooms in the Amundsen Sea Polynya. Less well understood is the source of micronutrients, such as iron, necessary to support this bloom to the central polynya where chlorophyll concentrations are highest. This outflow region showed decreasing optical backscatter with proximity to the bed indicating that particulate matter was sourced from the overlying glacier rather than resuspended sediment. This result suggests that particulate iron, and potentially phytoplankton primary productivity, is intrinsically linked to the magnitude and duration of sub-glacial melt from Circumpolar Deep Water intrusions onto the shelf.
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Adult Neurogenesis and Gliogenesis: Possible Mechanisms for Neurorestoration
Zoltán Rusznák,YuHong Fu,Willem Henskens,Emma Schofield,Woojin S. Kim 한국뇌신경과학회 2016 Experimental Neurobiology Vol.25 No.3
The subgranular zone (SGZ) and subventricular zone (SVZ) are developmental remnants of the germinal regions of the brain, hence they retain the ability to generate neuronal progenitor cells in adult life. Neurogenesis in adult brain has an adaptive function because newly produced neurons can integrate into and modify existing neuronal circuits. In contrast to the SGZ and SVZ, other brain regions have a lower capacity to produce new neurons, and this usually occurs via parenchymal and periventricular cell genesis. Compared to neurogenesis, gliogenesis occurs more prevalently in the adult mammalian brain. Under certain circumstances, interaction occurs between neurogenesis and gliogenesis, facilitating glial cells to transform into neuronal lineage. Therefore, modulating the balance between neurogenesis and gliogenesis may present a new perspective for neurorestoration, especially in diseases associated with altered neurogenesis and/or gliogenesis, cell loss, or disturbed homeostasis of cellular constitution. The present review discusses important neuroanatomical features of adult neurogenesis and gliogenesis, aiming to explore how these processes could be modulated toward functional repair of the adult brain.
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