Recent Submissions

  • Self-assembly of a trigonal bipyramidal architecture with stabilisation of iron in three spin states.

    Taylor, Lauren L K; orcid: 0000-0003-0586-3246; Vitorica-Yrezabal, Iñigo J; Borilović, Ivana; Tuna, Floriana; orcid: 0000-0002-5541-1750; Riddell, Imogen A; orcid: 0000-0002-6801-0198 (2021-10-11)
    Self-assembly and characterisation of a supramolecular trigonal bipyramidal iron cage containing an [Fe (μ -F) (Fe ) ] star motif at its core is reported. The complex can be formed in a one step reaction using an heterotopic ligand that supports site-specific incorporation of iron in three distinct electronic configurations: low-spin Fe , high-spin Fe and high-spin Fe , with iron(II) tetrafluoroborate as the source of the bridging fluorides. Formation of a μ -F bridged mixed-valence Fe -Fe star is unprecedented. The peripheral high-spin Fe centres of the mixed-valence tetranuclear star incorporated in the iron cage are highly anisotropic and engage in F-mediated antiferromagnetic exchange with the central Fe ion.
  • Emerging heterogeneous catalysts for biomass conversion: studies of the reaction mechanism.

    Lin, Longfei; orcid: 0000-0003-2892-6094; Han, Xue; Han, Buxing; orcid: 0000-0003-0440-809X; Yang, Sihai; orcid: 0000-0002-1111-9272 (2021-10-18)
    The development of efficient catalysts to break down and convert woody biomass will be a paradigm shift in delivering the global target of sustainable economy and environment the use of cheap, highly abundant, and renewable carbon resources. However, such development is extremely challenging due to the complexity of lignocellulose, and today most biomass is treated simply as waste. The solution lies in the design of multifunctional catalysts that can place effective control on substrate activation and product selectivity. This is, however, severely hindered by the lack of fundamental understanding of (i) the precise role of active sites, and (ii) the catalyst-substrate chemistry that underpins the catalytic activity. Moreover, active sites alone often cannot deliver the desired selectivity of products, and full understanding of the microenvironment of the active sites is urgently needed. Here, we review key recent advances in the study of reaction mechanisms of biomass conversion over emerging heterogeneous catalysts. These insights will inform the design of future catalytic systems showing improved activity and selectivity.
  • Suicide in probation: Towards the ideation-to-action model

    Brooker, Charlie; orcid: 0000-0003-1005-526X; Tocque, Karen; West, Georgia; Norman-Taylor, Alice; Fowler, James (SAGE Publications, 2021-10-16)
    Suicide in probation services is far higher than the general population. This paper presents secondary analysis of data previously used to evaluate the outcome of delivering psychological treatment to probationers in London. A sample of probation service users who screened positive for clinically significant symptoms of distress and were subsequently assessed and offered treatment ( n = 274) were allocated retrospectively to one of three groups: those with a history of suicidal ideations but no suicide attempts (ideation group), those with a history of a suicidal act (attempt group) or a control group where suicide was not evident (no history group). Results indicate no significant difference between the ideation and the attempt groups, but significant differences between these and the no history group. The findings are discussed within the context of the suicide ideation-to-action models that have been debated in other offender settings. We conclude that a more nuanced understanding of suicidal acts and suicide attempts is required in probation services including a prospective study that tests the ideation-to-action model.
  • Charter to establish clinical exercise physiology as a recognised allied health profession in the UK: a call to action.

    Jones, Helen; orcid: 0000-0001-8282-1459; George, Keith P; Scott, Andrew; Buckley, John P; Watson, Paula M; Oxborough, David L; Thijssen, Dick H; Graves, Lee E F; Whyte, Greg P; McGregor, Gordon; orcid: 0000-0001-8963-9107; et al. (2021-09-21)
    The UK population is growing, ageing and becoming increasingly inactive and unfit. Personalised and targeted exercise interventions are beneficial for ageing and the management of chronic and complex conditions. Increasing the uptake of effective exercise and physical activity (PA) interventions is vital to support a healthier society and decrease healthcare costs. Current strategies for exercise and PA at a population level mostly involve self-directed exercise pathways, delivered largely via the fitness industry. Even for those who opt-in and manage to achieve the current recommendations regarding minimum PA, this generic 'one-size-fits-all' approach often fails to demonstrate meaningful physiological and health benefits. Personalised exercise prescription and appropriate exercise testing, monitoring and progression of interventions for individuals with chronic disease should be provided by appropriately trained and recognised exercise healthcare professionals, educated in the cognate disciplines of exercise science (eg, physiology, biomechanics, motor control, psychology). This workforce has operated for >20 years in the Australian public and private healthcare systems. Accredited exercise physiologists (AEPs) are recognised allied health professionals, with demonstrable health and economic benefits. AEPs have knowledge of the risks and benefits of distinct forms of exercise, skills in the personalised prescription and optimal delivery of exercise, and competencies to support sustained PA behavioural change, based on the established scientific evidence. In this charter, we propose a road map for the training, accreditation and promotion of a clinical exercise physiology profession in the UK. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.]
  • Can we achieve better recruitment by providing better information? Meta-analysis of 'studies within a trial' (SWATs) of optimised participant information sheets.

    Madurasinghe, Vichithranie W; Bower, Peter; orcid: 0000-0001-9558-3349; email:; Eldridge, Sandra; Collier, David; Graffy, Jonathan; Treweek, Shaun; Knapp, Peter; Parker, Adwoa; Rick, Jo; Salisbury, Chris; et al. (2021-09-23)
    <h4>Background</h4>The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded 'studies within a trial' (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment.<h4>Methods</h4>Seven 'host' trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part.<h4>Results</h4>Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I<sup>2</sup> = 0%).<h4>Conclusions</h4>Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies.<h4>Trial registration</h4>Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133).
  • Impedance Spectroscopy Analysis of PbSe Nanostructures Deposited by Aerosol Assisted Chemical Vapor Deposition Approach

    Iram, Sadia; email:; Mahmood, Azhar; orcid: 0000-0003-0881-2612; email:; Ehsan, Muhammad Fahad; email:; Mumtaz, Asad; email:; Sohail, Manzar; email:; Sitara, Effat; orcid: 0000-0002-8774-4242; email:; Mushtaq, Shehla; email:; Malik, Mohammad Azad; email:; Fatima, Syeda Arooj; email:; Shaheen, Rubina; email:; et al. (MDPI, 2021-10-23)
    This research endeavor aimed to synthesize the lead (II) diphenyldiselenophosphinate complex and its use to obtain lead selenide nanostructured depositions and further the impedance spectroscopic analysis of these obtained PbSe nanostructures, to determine their roles in the electronics industry. The aerosol-assisted chemical vapor deposition technique was used to provide lead selenide deposition by decomposition of the complex at different temperatures using the glass substrates. The obtained films were revealed to be a pure cubic phase PbSe, as confirmed by X-ray diffraction analysis. SEM and TEM micrographs demonstrated three-dimensionally grown interlocked or aggregated nanocubes of the obtained PbSe. Characteristic dielectric measurements and the impedance spectroscopy analysis at room temperature were executed to evaluate PbSe properties over the frequency range of 100 Hz–5 MHz. The dielectric constant and dielectric loss gave similar trends, along with altering frequency, which was well explained by the Koops theory and Maxwell–Wagner theory. The effective short-range translational carrier hopping gave rise to an overdue remarkable increase in ac conductivity (σac) on the frequency increase. Fitting of a complex impedance plot was carried out with an equivalent circuit model (Rg Cg) (Rgb Qgb Cgb), which proved that grains, as well as grain boundaries, are responsible for the relaxation processes. The asymmetric depressed semicircle with the center lower to the impedance real axis provided a clear explanation of non-Debye dielectric behavior.
  • Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

    Kodji, Xenia; email:; Kee, Zizheng; email:; McKenna, Robyn; email:; de Sousa Valente, Joao; orcid: 0000-0003-1888-6324; email:; Ravenscroft, Harriet; email:; McMillan, Hayley; email:; Gamble, John; email:; Dombrowski, Yvonne; email:; Moynagh, Paul; email:; Brough, David; email:; et al. (MDPI, 2021-10-23)
    This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) in murine temporomandibular joint (TMJ) inflammatory hyperalgesia and the influence of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Two distinct murine models of TMJ pain and inflammation (zymosan and CFA) were established. Spontaneous pain-like behaviours were observed as unilateral front paw cheek wipes. Ipsilateral cheek blood flow was used as a measure of ongoing inflammation, which, to our knowledge, is a novel approach to assessing real-time inflammation in the TMJ. Joint tissue and trigeminal ganglia were collected for ex vivo investigation. Both zymosan and CFA induced a time-dependent increase in hyperalgesia and inflammation biomarkers. Zymosan induced a significant effect after 4 h, correlating with a significantly increased IL-1β protein expression. CFA (50 µg) induced a more sustained response. The TRPA1 receptor antagonist A967079 significantly inhibited hyper-nociception. The NLRP3 inhibitor MCC950 similarly inhibited hyper-nociception, also attenuating inflammatory markers. In the trigeminal ganglia, CFA-induced CGRP expression showed trends of inhibition by A967079, whilst lba1 immunofluorescence was significantly inhibited by A967079 and MCC950, where the effect of TRPA1 inhibition lasted up to 14 days. Our results show that stimulation of TRPA1 is key to the TMJ pain. However, the inflammasome inhibitor exhibited similar properties in attenuating these pain-like behaviours, in addition to some inflammatory markers. This indicates that in addition to the therapeutic targeting of TRPA1, NLRP3 inhibition may provide a novel therapeutic strategy for TMJ inflammation and pain.
  • Southern actors and the governance of labour standards in global production networks: The case of South African fruit and wine

    Alford, Matthew; orcid: 0000-0002-1614-7862; email:; Visser, Margareet; Barrientos, Stephanie (SAGE Publications, 2021-08-05)
    Recent studies highlight the emergence of standards, including multi-stakeholder initiatives developed and applied within the global South where supplier firms are usually based. This trend has created a complex ethical terrain whereby transnational standards flow through global production networks and intersect with domestic initiatives at places of production. The paper complements global production network analysis with the concepts of ‘space of flows’ and ‘space of places’ and insights from relational economic geography, to examine how some multi-stakeholder initiatives in the global South can shape the broader governance of labour standards in global production networks. The following questions are addressed: How is the governance of labour standards in global production networks shaped by dynamic spatial interactions between actors? What role have diverse Southern multi-stakeholder initiatives played in influencing the governance of South African fruit and wine? We draw on research conducted over seven years into two standards in South Africa, the Wine and Agriculture Ethical Trade Association and Sustainability Initiative of South Africa. Our analysis shows that these two Southern-based multi-stakeholder initiatives contributed to shaping the broader governance of labour standards through dynamic non-linear waves of interaction over time, involving both collaborative and contested exchanges between actors across space of flows and places. We further argue that despite the development of multi-stakeholder initiatives by Southern actors, commercial power asymmetries in global production networks limit their ability to promote significant improvements for producers and workers.
  • The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer

    Orea-Soufi, Alba; email:; Castillo-Lluva, Sonia; orcid: 0000-0001-5357-7178; email:; Salvador-Tormo, Nélida; email:; Martín-Cabrera, Paola; email:; Recuero, Silvia; email:; Gabicagogeascoa, Estíbaliz; email:; Moreno-Valladares, Manuel; email:; Mendiburu-Eliçabe, Marina; orcid: 0000-0003-2573-8709; email:; Blanco-Gómez, Adrián; orcid: 0000-0002-1956-088X; email:; Ramos-Pittol, José Miguel; orcid: 0000-0003-3753-5394; email:; et al. (MDPI, 2021-10-22)
    Background: Tribbles pseudokinase 3 (TRIB3) has been proposed to both promote and restrict cancer generation and progression. However, the precise mechanisms that determine this dual role of TRIB3 in cancer remain to be understood. In this study we aimed to investigate the role of TRIB3 in luminal breast cancer, the most frequent subtype of this malignancy. Methods: We genetically manipulated TRIB3 expression in a panel of luminal breast cancer cell lines and analyzed its impact on cell proliferation, and the phosphorylation, levels, or subcellular localization of TRIB3 and other protein regulators of key signaling pathways in luminal breast cancer. We also analyzed TRIB3 protein expression in samples from luminal breast cancer patients and performed bioinformatic analyses in public datasets. Results: TRIB3 enhanced the proliferation and AKT phosphorylation in luminal A (HER2-) but decreased them in luminal B (HER2+) breast cancer cell lines. TRIB3 negatively regulated the stability of HER2 in luminal B breast cancer cell lines. TRIB3 expression was associated with increased disease-free survival and a better response to therapy in luminal breast cancer patients. Conclusions: Our findings support the exploration of TRIB3 as a potential biomarker and therapeutic target in luminal breast cancer.
  • Discovering the Arrow of Time in Machine Learning

    Kasmire, J.; orcid: 0000-0003-2684-6330; email:; Zhao, Anran; email: (MDPI, 2021-10-22)
    Machine learning (ML) is increasingly useful as data grow in volume and accessibility. ML can perform tasks (e.g., categorisation, decision making, anomaly detection, etc.) through experience and without explicit instruction, even when the data are too vast, complex, highly variable, full of errors to be analysed in other ways. Thus, ML is great for natural language, images, or other complex and messy data available in large and growing volumes. Selecting ML models for tasks depends on many factors as they vary in supervision needed, tolerable error levels, and ability to account for order or temporal context, among many other things. Importantly, ML methods for tasks that use explicitly ordered or time-dependent data struggle with errors or data asymmetry. Most data are (implicitly) ordered or time-dependent, potentially allowing a hidden `arrow of time’ to affect ML performance on non-temporal tasks. This research explores the interaction of ML and implicit order using two ML models to automatically classify (a non-temporal task) tweets (temporal data) under conditions that balance volume and complexity of data. Results show that performance was affected, suggesting that researchers should carefully consider time when matching appropriate ML models to tasks, even when time is only implicitly included.
  • Inter-species interactions alter antibiotic efficacy in bacterial communities.

    Bottery, Michael J; orcid: 0000-0001-5790-1756; email:; Matthews, Jessica L; Wood, A Jamie; orcid: 0000-0002-6119-852X; Johansen, Helle Krogh; Pitchford, Jon W; Friman, Ville-Petri; orcid: 0000-0002-1592-157X (2021-10-09)
    The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members' susceptibility to antibiotics. Here we quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples. We demonstrate that multi-drug resistant Stenotrophomonas maltophilia can provide high levels of antibiotic protection to otherwise sensitive P. aeruginosa. Exposure protection to imipenem was provided by chromosomally encoded metallo-β-lactamase that detoxified the environment; protection was dependent upon S. maltophilia cell density and was provided by S. maltophilia strains isolated from CF sputum, increasing the MIC of P. aeruginosa by up to 16-fold. In contrast, the presence of S. maltophilia provided no protection against meropenem, another routinely used carbapenem. Mathematical ordinary differential equation modelling shows that the level of exposure protection provided against different carbapenems can be explained by differences in antibiotic efficacy and inactivation rate. Together, these findings reveal that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities. [Abstract copyright: © 2021. The Author(s).]
  • Comrades Betrayed: Jewish World War I Veterans Under Hitler

    Grady, Tim; orcid: 0000-0001-5652-9032 (Oxford University Press (OUP), 2021-06-24)
  • New Technique to Improve the Ductility of Steel Beam to Column Bolted Connections: A Numerical Investigation

    Shaheen, Mohamed A.; email:; Galal, Mohamed Ahmed; orcid: 0000-0003-4263-0361; email:; Cunningham, Lee S.; orcid: 0000-0002-7686-7490; email:; Foster, Andrew S. J.; email: (MDPI, 2021-10-22)
    A novel method to improve the robustness of steel end plate connections is presented in this paper. Existing commonly adopted techniques alter the stiffness of the beam or the end plate to improve the connection’s robustness. In this study, the robustness is enhanced by improving the contribution of the bolts to the rotational capacity of connections; the higher the bolts’ elongation, the higher the rotational capacity that can be achieved. However, the brittleness of the bolt material, combined with its small length, results in negligible elongation. Alternatively, the load path between the end plate and the bolts can be interrupted with a ductile element to achieve the required elongation. This can be achieved by inserting a steel sleeve with a designated length, thickness, and wall curvature between the end plate and the washer. The proposed sleeve should be designed so that its ultimate capacity is less than the force in the bolt at failure; accordingly, the sleeve develops a severe bending deformation before the failure of any connection components. Using a validated finite element model, end plate connections with various parameters are numerically investigated to understand the performance of the sleeve device. The proposed system substantially enhances the rotational capacity of the connections, ranging between 1.37 and 2.46 times that of the standard connection. It is also concluded that the sleeved connections exhibit a consistent elastic response with the standard connections, indicating the proposed system is compatible with codified elastic design approaches without modification. Furthermore, for a specific connection, various ductile responses can be achieved without altering the connection capacity nor configuration.
  • Abundance of NO 3 Derived Organo-Nitrates and Their Importance in the Atmosphere

    Foulds, Amy; email:; Khan, M. Anwar H.; orcid: 0000-0001-7836-3344; email:; Bannan, Thomas J.; orcid: 0000-0002-1760-6522; email:; Percival, Carl J.; email:; Lowenberg, Mark H.; orcid: 0000-0002-1373-8237; email:; Shallcross, Dudley E.; email: (MDPI, 2021-10-22)
    The chemistry of the nitrate radical and its contribution to organo-nitrate formation in the troposphere has been investigated using a mesoscale 3-D chemistry and transport model, WRF-Chem-CRI. The model-measurement comparisons of NO2, ozone and night-time N2O5 mixing ratios show good agreement supporting the model’s ability to represent nitrate (NO3) chemistry reasonably. Thirty-nine organo-nitrates in the model are formed exclusively either from the reaction of RO2 with NO or by the reaction of NO3 with alkenes. Temporal analysis highlighted a significant contribution of NO3-derived organo-nitrates, even during daylight hours. Night-time NO3-derived organo-nitrates were found to be 3-fold higher than that in the daytime. The reactivity of daytime NO3 could be more competitive than previously thought, with losses due to reaction with VOCs (and subsequent organo-nitrate formation) likely to be just as important as photolysis. This has highlighted the significance of NO3 in daytime organo-nitrate formation, with potential implications for air quality, climate and human health. Estimated atmospheric lifetimes of organo-nitrates showed that the organo-nitrates act as NOx reservoirs, with particularly short-lived species impacting on air quality as contributors to downwind ozone formation.
  • ChoiceNet: CNN learning through choice of multiple feature map representations

    Rayhan, Farshid; email:; Galata, Aphrodite; Cootes, Tim F. (Springer London, 2021-07-11)
    Abstract: We introduce a new architecture called ChoiceNet where each layer of the network is highly connected with skip connections and channelwise concatenations. This enables the network to alleviate the problem of vanishing gradients, reduces the number of parameters without sacrificing performance and encourages feature reuse. We evaluate our proposed architecture on three independent tasks: classification, segmentation and facial landmark localisation. For this, we use benchmark datasets such as ImageNet, CIFAR-10, CIFAR-100, SVHN CamVid and 300W.
  • A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism

    Thistlethwaite, Sian; email:; Jeffreys, Laura N.; orcid: 0000-0002-0607-6116; email:; Girvan, Hazel M.; orcid: 0000-0003-2299-8644; email:; McLean, Kirsty J.; email:; Munro, Andrew W.; email: (MDPI, 2021-10-21)
    CYP102A1 (BM3) is a catalytically self-sufficient flavocytochrome fusion protein isolated from Bacillus megaterium, which displays similar metabolic capabilities to many drug-metabolizing human P450 isoforms. BM3′s high catalytic efficiency, ease of production and malleable active site makes the enzyme a desirable tool in the production of small molecule metabolites, especially for compounds that exhibit drug-like chemical properties. The engineering of select key residues within the BM3 active site vastly expands the catalytic repertoire, generating variants which can perform a range of modifications. This provides an attractive alternative route to the production of valuable compounds that are often laborious to synthesize via traditional organic means. Extensive studies have been conducted with the aim of engineering BM3 to expand metabolite production towards a comprehensive range of drug-like compounds, with many key examples found both in the literature and in the wider industrial bioproduction setting of desirable oxy-metabolite production by both wild-type BM3 and related variants. This review covers the past and current research on the engineering of BM3 to produce drug metabolites and highlights its crucial role in the future of biosynthetic pharmaceutical production.
  • The role of dark adaptation in understanding early AMD.

    Murray, Ian J; email:; Rodrigo-Diaz, Elena; Kelly, Jeremiah M F; Tahir, Humza J; Carden, David; Patryas, Laura; Parry, Neil Ra (2021-10-06)
    The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD. Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time. Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
  • How do terminal modifications of short designed IIKK peptide amphiphiles affect their antifungal activity and biocompatibility?

    Zhang, Jing; Gong, Haoning; Liao, Mingrui; Li, Zongyi; Schweins, Ralf; Penny, Jeffrey; Lu, Jian R; email: (2021-10-06)
    The widespread and prolonged use of antifungal antibiotics has led to the rapid emergence of multidrug resistant Candida species that compromise current treatments. Natural and synthetic antimicrobial peptides (AMPs) offer potential alternatives but require further development to overcome some of their current drawbacks. AMPs kill pathogenic fungi by permeabilising their membranes but it remains unclear how AMPs can be designed to maximise their antifungal potency whilst minimising their toxicity to host cells. We have designed a group of short (IIKK) AMPs via selective terminal modifications ending up with different amphiphilicities. Their antifungal performance was assessed by minimum inhibition concentration (MICs) and dynamic killing to 4 Candida strains and Cryptococcus neoformans, and the minimum biofilm-eradicating concentrations to kill 95% of the C. albicans biofilms (BEC ). Different antifungal actions were interpreted on the basis of structural disruptions of the AMPs to small unilamellar vesicles from fluorescence leakage, Zeta potential, small angle neutron scattering (SANS) and molecular dynamics simulations (MD). AMPs possess high antifungal activities against the Candida species and Cryptococcus neoformans; some of them displayed faster dynamic killing than antibiotics like amphotericin B. G(IIKK) I-NH and (IIKK) II-NH were particularly potent against not only planktonic microbes but also fungal biofilms with low cytotoxicity to host cells. It was found that their high selectivity and fast action were well correlated to their fast membrane lysis, evident from data measured from Zeta potential measurements, SANS and MD, and also consistent with the previously observed antibacterial and anticancer performance. These studies demonstrate the important role of colloid and interface science in further developing short, potent and biocompatible AMPs towards clinical treatments via structure design and optimization. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]
  • Chemical engines: driving systems away from equilibrium through catalyst reaction cycles.

    Amano, Shuntaro; orcid: 0000-0001-6017-6823; Borsley, Stefan; orcid: 0000-0001-9637-4178; Leigh, David A; orcid: 0000-0002-1202-4507; email:; Sun, Zhanhu; orcid: 0000-0002-1207-781X (2021-10-08)
    Biological systems exhibit a range of complex functions at the micro- and nanoscales under non-equilibrium conditions (for example, transportation and motility, temporal control, information processing and so on). Chemists also employ out-of-equilibrium systems, for example in kinetic selection during catalysis, self-replication, dissipative self-assembly and synthetic molecular machinery, and in the form of chemical oscillators. Key to non-equilibrium behaviour are the mechanisms through which systems are able to extract energy from the chemical reactants ('fuel') that drive such processes. In this Perspective we relate different examples of such powering mechanisms using a common conceptual framework. We discuss how reaction cycles can be coupled to other dynamic processes through positive (acceleration) or negative (inhibition) catalysis to provide the thermodynamic impetus for diverse non-equilibrium behaviour, in effect acting as a 'chemical engine'. We explore the way in which the energy released from reaction cycles is harnessed through kinetic selection in a series of what have sometimes been considered somewhat disparate fields (systems chemistry, molecular machinery, dissipative assembly and chemical oscillators), highlight common mechanistic principles and the potential for the synchronization of chemical reaction cycles, and identify future challenges for the invention and application of non-equilibrium systems. Explicit recognition of the use of fuelling reactions to power structural change in catalysts may stimulate the investigation of known catalytic cycles as potential elements for chemical engines, a currently unexplored area of catalysis research. [Abstract copyright: © 2021. Springer Nature Limited.]
  • Assessment of minimal active space CASSCF-SO methods for calculation of atomic Slater-Condon and spin-orbit coupling parameters in d- and f-block ions.

    Walisinghe, Alvin J; orcid: 0000-0002-7190-1274; Chilton, Nicholas F; orcid: 0000-0002-8604-0171 (2021-10-19)
    Slater-Condon parameters and the spin-orbit (SO) coupling constants for various oxidation states of transition metal ions (3d/4d/5d) and trivalent f-block ions were calculated using minimal active space complete active space self-consistent field (CASSCF)-SO methods in OpenMolcas. The SO coupling constants have a quadratic relationship to atomic number for a fixed d configuration, as do those for the trivalent lanthanides where configuration also changes as a function of . Compared to experimentally-derived values, minimal active space CASSCF-SO approximates SO coupling constants within 200 cm , which is usually <10% error for 4d , 5d and 4f configurations, but up to 30% error for 3d configurations. Slater-Condon parameters are usually overestimated on the order of 10-50%, arising from a lack of dynamic correlation in the method, and thus we do not recommend minimal active space CASSCF-SO methods where accurate term excitation energies are required. However, the error in the Slater-Condon parameters appears to be systematic for divalent 4d and trivalent 4f ions such that scaling may be a useful approach where computational resources are limited, but this is not the case for 3d ions. Hence, caution is advised when using CASSCF-SO methods for comparisons with spectroscopic data, wherein only qualitative results can be expected, and methods accounting for dynamic correlation effects (such as CASPT2 or NEVPT2) should be employed if more quantitative results are required.

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