| 1. |
- Donaldson, M., et al.
(författare)
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Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy
- 2019
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 91:3, s. 153-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17 beta-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17 beta-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions. (C) 2019 S. Karger AG, Basel
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| 2. |
- Cooper, Ian R., et al.
(författare)
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Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors
- 2016
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 26:17, s. 4179-4183
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.
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| 3. |
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| 4. |
- Gault, B., et al.
(författare)
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Atom probe microscopy characterization of as quenched Zr-0.8 wt% Fe and Zr-0.15 wt% Cr binary alloys
- 2013
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Ingår i: Materials letters (General ed.). - : Elsevier BV. - 0167-577X .- 1873-4979. ; 91, s. 63-66
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Tidskriftsartikel (refereegranskat)abstract
- Two binary Zr-alloys with a β-quenched structure were analysed by atom probe tomography to provide a better understanding of how Fe and Cr perform in industrial Zr alloys. In a Zr-0.8 Fe (wt%) alloy, we observed a dispersion of precipitates with a composition close to Zr3Fe, and Fe segregated to a grain boundary. In a Zr-0.15 Cr (wt%) alloy, Cr was observed in solid solution in the Zr-matrix and segregated to grain boundary where it formed small spherical particles or elongated atmospheres.
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| 5. |
- Andrade, AC, et al.
(författare)
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Hormones and genes of importance in bone physiology and their influence on bone mineralization and growth in Turner syndrome
- 2010
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 73:3, s. 161-165
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Tidskriftsartikel (refereegranskat)abstract
- This mini review summarizes papers presented in a Joint Symposium between the Bone, Growth Plate and Turner Syndrome Working Groups of the European Society for Paediatric Endocrinology (ESPE) that was held on September 9, 2009, in New York.The program had been composed to give an update on hormones and genes of importance in bone physiology and their influence on bone mineralization and growth in Turner syndrome. This paper summarizes the data and highlights the main topics and discussions related to each presentation.
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| 6. |
- Bolla, Jani Reddy, et al.
(författare)
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A Mass-Spectrometry-Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
- 2020
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:9, s. 3523-3528
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Tidskriftsartikel (refereegranskat)abstract
- Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non-specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid-binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent-resistant lipids bound at the dimer interface in the leucine transporter show decreased k(off) rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid-II results in the formation of a 1:1 protein-lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non-annular lipids based on their exchange rates in solution.
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| 7. |
- Costeira-Paulo, Joana, et al.
(författare)
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Lipids Shape the Electron Acceptor-Binding Site of the Peripheral Membrane Protein Dihydroorotate Dehydrogenase
- 2018
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Ingår i: Cell Chemical Biology. - : Elsevier BV. - 2451-9456 .- 2451-9448. ; 25:3, s. 309-317
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Tidskriftsartikel (refereegranskat)abstract
- The interactions between proteins and biological membranes are important for drug development, but remain notoriously refractory to structural investigation. We combine non-denaturing mass spectrometry (MS) with molecular dynamics (MD) simulations to unravel the connections among co-factor, lipid, and inhibitor binding in the peripheral membrane protein dihydroorotate dehydrogenase (DHODH), a key anticancer target. Interrogation of intact DHODH complexes by MS reveals that phospholipids bind via their charged head groups at a limited number of sites, while binding of the inhibitor brequinar involves simultaneous association with detergent molecules. MD simulations show that lipids support flexible segments in the membrane-binding domain and position the inhibitor and electron acceptor-binding site away from the membrane surface, similar to the electron acceptor-binding site in respiratory chain complex I. By complementing MS with MD simulations, we demonstrate how a peripheral membrane protein uses lipids to modulate its structure in a similar manner as integral membrane proteins.
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| 8. |
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| 9. |
- Johansen, Marcus, 1994, et al.
(författare)
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Unravelling lithium distribution in carbon fibre electrodes for structural batteries with atom probe tomography
- 2024
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Ingår i: Carbon. - 0008-6223. ; 225
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Tidskriftsartikel (refereegranskat)abstract
- Carbon fibres in structural batteries are multifunctional by acting both as structural reinforcement and as lithium (Li)-ion battery electrode. The relationship between the microstructure and mechanical capabilities of carbon fibres are well established, but much remains unexplored regarding their electrochemical properties. Specifically needed is a nanoscale understanding of how Li atoms distribute and interact in the carbon fibres. Atom probe tomography (APT) is uniquely positioned to provide subnanometre resolution in three dimensions. However, it has previously been hampered by undesirable Li migration during analysis. Here, we show that APT is successfully used to analyse electrochemically cycled polyacrylonitrile-based carbon fibres, through electrostatic shielding by means of conductive coating. We measure ∼1.5 at% Li in the carbon fibres after full delithiation, and thus identify trapped Li to constitute a substantial part of the initial capacity fade. After lithiation, Li accounts for ∼9 at% and according to frequency distribution analysis tend to agglomerate on the atomic scale. With nearest neighbour analysis, Li agglomeration is shown independent of heteroatom dopants such as nitrogen. Thus, the agglomeration is more likely induced by differing accessibility for Li in the crystalline and amorphous domains in the carbon fibre. The method used in this study can inform APT experiments on other type of Li-containing carbon electrodes. The findings of the study can be used to guide design of novel carbon fibres for structural batteries with enhanced electrochemical properties.
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| 10. |
- Katnagallu, Shyam, et al.
(författare)
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Impact of local electrostatic field rearrangement on field ionization
- 2018
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Ingår i: Journal of Physics D. - : IOP PUBLISHING LTD. - 0022-3727 .- 1361-6463. ; 51:10
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Tidskriftsartikel (refereegranskat)abstract
- Field ion microscopy allows for direct imaging of surfaces with true atomic resolution. The high charge density distribution on the surface generates an intense electric field that can induce ionization of gas atoms. We investigate the dynamic nature of the charge and the consequent electrostatic field redistribution following the departure of atoms initially constituting the surface in the form of an ion, a process known as field evaporation. We report on a new algorithm for image processing and tracking of individual atoms on the specimen surface enabling quantitative assessment of shifts in the imaged atomic positions. By combining experimental investigations with molecular dynamics simulations, which include the full electric charge, we confirm that change is directly associated with the rearrangement of the electrostatic field that modifies the imaging gas ionization zone. We derive important considerations for future developments of data reconstruction in 3D field ion microscopy, in particular for precise quantification of lattice strains and characterization of crystalline defects at the atomic scale.
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