Now showing items 1-20 of 6423

    • 'Relieved to be seen'-patient and carer experiences of psychosocial assessment in the emergency department following self-harm: qualitative analysis of 102 free-text survey responses.

      Quinlivan, Leah M; orcid: 0000-0002-3944-3613; email: leah.quinlivan@manchester.ac.uk; Gorman, Louise; Littlewood, Donna L; Monaghan, Elizabeth; Barlow, Steven J; Campbell, Stephen M; Webb, Roger T; Kapur, Navneet (2021-05-23)
      <h4>Objectives</h4>We sought to explore patient and carer experiences of psychosocial assessments following presentations to hospital after self-harm.<h4>Design</h4>Thematic analysis of free-text responses to an open-ended online survey.<h4>Setting</h4>Between March and November 2019, we recruited 88 patients (82% women) and 14 carers aged ≥18 years from 16 English mental health trusts, community organisations, and via social media.<h4>Results</h4>Psychosocial assessments were experienced as helpful on some occasions but harmful on others. Participants felt better, less suicidal and less likely to repeat self-harm after good-quality compassionate and supportive assessments. However, negative experiences during the assessment pathway were common and, in some cases, contributed to greater distress, less engagement and further self-harm. Participants reported receiving negative and stigmatising comments about their injuries. Others reported that they were refused medical care or an anaesthetic. Stigmatising attitudes among some mental health staff centred on preconceived ideas over self-harm as a 'behavioural issue', inappropriate use of services and psychiatric diagnosis.<h4>Conclusion</h4>Our findings highlight important patient experiences that can inform service provision and they demonstrate the value of involving patients/carers throughout the research process. Psychosocial assessments can be beneficial when empathetic and collaborative but less helpful when overly standardised, lacking in compassion and waiting times are unduly long. Patient views are essential to inform practice, particularly given the rapidly changing service context during and after the COVID-19 emergency.
    • Evidence-based practice and evidence-informed practice competencies in undergraduate pre-registration nursing curricula: A document analysis at a university in England

      Kumah, Dr Elizabeth Adjoa; orcid: 0000-0002-3787-5615; Bettany-Saltikov, Dr Josette; van Schaik, Dr Paul; orcid: 0000-0001-5322-6554; McSherry, Dr Robert (Elsevier, 2021-06-22)
      Background In response to the heightened emphasis on incorporating the best available evidence into healthcare decision-making, healthcare training institutions have been actively incorporating Evidence-Based Practice (EBP), and/or Evidence-Informed Practice (EIP) competencies into undergraduate healthcare curricula. However, there is a gap in the scientific knowledge about the actual contents, as well as the extent of integration of EBP and EIP in undergraduate pre-registration nursing programmes. Method A document analysis utilising Rohwer et al.’s (2014) framework was conducted to review and analyse the content of EBP and EIP competencies in the 2018/2019 curriculum of the undergraduate pre-registration nursing programme of a University located in England, United Kingdom. Results Competencies relevant to EBP were included in four nursing modules. However, EIP competencies were not included in the curriculum. Conclusion There is an urgent need for a more structured and holistic way of teaching and assessing EBP competencies through the integration of the principles of EIP, in order to enhance the effective application of evidence into clinical nursing practice.
    • Investigation of the Performance of Donor–Acceptor Conjugated Polymers in Electrolyte‐Gated Organic Field‐Effect Transistors

      Doumbia, Amadou; orcid: 0000-0002-4136-9029; email: doumbia_amadou@outlook.com; Tong, Jincheng; orcid: 0000-0001-7762-1460; Wilson, Richard J.; Turner, Michael Lewis; orcid: 0000-0003-2853-5632; email: michael.turner@manchester.ac.uk (2021-06-24)
      Abstract: Electrolyte‐gated organic field‐effect transistors (EGOFETs) are gaining interest for application in bioelectronic devices. However, robust performance in terms of charge‐carrier mobility, on‐to‐off drain current ratio (Ion/Ioff), and turn‐on speed are required for real application. Here, donor‐acceptor (D‐A) conjugated polymers, namely poly[2,5‐(2‐octyldodecyl)‐3,6‐diketopyrrolopyrrole‐alt‐5,5‐(2,5‐di(thien‐2‐yl)thieno[3,2‐b]thiophene)] (PDPPDTT) and indacenodithiophene‐co‐benzothiadiazole (PIDTBT), are evaluated in EGOFETs. The operational performance of these materials is compared to that of the well‐established conjugated polymer, poly[2,5‐bis(3‐hexadecylthiophen‐2‐yl)thieno[3,2‐b]thiophene] (PBTTT). The effective mobility extracted for the PDPPDTT (0.18 cm2 V−1 s−1), and PIDTBT (0.16 cm2 V−1 s−1) devices is almost double that of the PBTTT (0.10 cm2 V−1 s−1) based device and the Ion/Ioff is one ((PDPPDTT): 3 × 103) or two ((PIDTBT): 2 × 104) orders of magnitude higher than that of PBTTT (2 × 102) devices. The extracted values compare favorably to those of the highest performing EGOFETs and EGOFETs based on the D‐A polymers turn from off to on state two to ten times faster than the analogous PBTTT device with an improved subthreshold swing. These results show that D‐A polymers with a planar conjugated backbone enable the development of robust EGOFETs that are well appropriate for applications in bioelectronic devices.
    • Friend or fiend? An interpretative phenomenological analysis of moral and relational orientation in authentic leadership

      guest-editor: Iszatt-White, Marian; guest-editor: Carroll, Brigid; guest-editor: Gardiner, Rita A; guest-editor: Kempster, Steve; Bradley-Cole, Kim; orcid: 0000-0003-0853-6080; email: kim.bradley-cole@winchester.ac.uk (SAGE Publications, 2021-05-14)
      Authentic leadership has been developed with insufficient empirical challenge to its definitional components, and alternative conceptualizations have largely been ignored. The theory remains heavily criticized and its distinctiveness from other higher-purpose leadership theories remains in doubt, leading to a circular debate as to its usefulness in practice. In response to the call to return to the definitional drawing table, this article presents the findings of an interpretative phenomenological study that reimagines authentic leadership as a two-component moral and relational model that is closer to Heidegger’s notions of ‘being true’ and ‘care’. The study inductively explores how leaders themselves make sense of authenticity in practice, when it is enacted by their own leaders within the social exchange relationship. It richly describes how managers perceive and attribute authenticity to their leaders within the lived experience of contemporary work. The study also identifies that working for a leader who is perceived as authentic feels like a friendship and is beneficial to followers’ own psychological experience of work, facilitates their own authentic expression and is worthy of retention as a distinct leadership theory that explains how performance is enabled within proximal leader relationships.
    • Impacts of COVID-19 and social isolation on academic staff and students at universities: a cross-sectional study

      Leal Filho, Walter; orcid: 0000-0002-3993-8974; email: walter.leal2@haw-hamburg.de; Wall, Tony; Rayman-Bacchus, Lez; Mifsud, Mark; Pritchard, Diana J.; Lovren, Violeta Orlovic; orcid: 0000-0002-2678-3256; email: violeta.orlovic@f.bg.ac.rs; Farinha, Carla; Petrovic, Danijela S.; Balogun, Abdul-Lateef (BioMed Central, 2021-06-24)
      Abstract: Background: “The impacts of the Coronavirus Disease 2019 (COVID-19) pandemic and the shutdown it triggered at universities across the world, led to a great degree of social isolation among university staff and students. The aim of this study was to identify the perceived consequences of this on staff and their work and on students and their studies at universities. Method: The study used a variety of methods, which involved an on-line survey on the influences of social isolation using a non-probability sampling. More specifically, two techniques were used, namely a convenience sampling (i.e. involving members of the academic community, which are easy to reach by the study team), supported by a snow ball sampling (recruiting respondents among acquaintances of the participants). A total of 711 questionnaires from 41 countries were received. Descriptive statistics were deployed to analyse trends and to identify socio-demographic differences. Inferential statistics were used to assess significant differences among the geographical regions, work areas and other socio-demographic factors related to impacts of social isolation of university staff and students. Results: The study reveals that 90% of the respondents have been affected by the shutdown and unable to perform normal work or studies at their institution for between 1 week to 2 months. While 70% of the respondents perceive negative impacts of COVID 19 on their work or studies, more than 60% of them value the additional time that they have had indoors with families and others. . Conclusions: While the majority of the respondents agree that they suffered from the lack of social interaction and communication during the social distancing/isolation, there were significant differences in the reactions to the lockdowns between academic staff and students. There are also differences in the degree of influence of some of the problems, when compared across geographical regions. In addition to policy actions that may be deployed, further research on innovative methods of teaching and communication with students is needed in order to allow staff and students to better cope with social isolation in cases of new or recurring pandemics.
    • The challenges in data integration – heterogeneity and complexity in clinical trials and patient registries of Systemic Lupus Erythematosus

      Le Sueur, Helen; Bruce, Ian N.; Geifman, Nophar; orcid: 0000-0003-2956-6676; email: nophar.geifman@manchester.ac.uk (BioMed Central, 2020-06-24)
      Abstract: Background: Individual clinical trials and cohort studies are a useful source of data, often under-utilised once a study has ended. Pooling data from multiple sources could increase sample sizes and allow for further investigation of treatment effects; even if the original trial did not meet its primary goals. Through the MASTERPLANS (MAximizing Sle ThERapeutic PotentiaL by Application of Novel and Stratified approaches) national consortium, focused on Systemic Lupus Erythematosus (SLE), we have gained valuable real-world experiences in aligning, harmonising and combining data from multiple studies and trials, specifically where standards for data capture, representation and documentation, were not used or were unavailable. This was not without challenges arising both from the inherent complexity of the disease and from differences in the way data were captured and represented across different studies. Main body: Data were, unavoidably, aligned by hand, matching up equivalent or similar patient variables across the different studies. Heterogeneity-related issues were tackled and data were cleaned, organised and combined, resulting in a single large dataset ready for analysis. Overcoming these hurdles, often seen in large-scale data harmonization and integration endeavours of legacy datasets, was made possible within a realistic timescale and limited resource by focusing on specific research questions driven by the aims of MASTERPLANS. Here we describe our experiences tackling the complexities in the integration of large, diverse datasets, and the lessons learned. Conclusions: Harmonising data across studies can be complex, and time and resource consuming. The work carried out here highlights the importance of using standards for data capture, recording, and representation, to facilitate both the integration of large datasets and comparison between studies. Where standards are not implemented at the source harmonisation is still possible by taking a flexible approach, with systematic preparation, and a focus on specific research questions.
    • Building Information Modelling Diffusion Research in Developing Countries: A User Meta-Model Approach

      Adekunle, Samuel Adeniyi; orcid: 0000-0002-9230-2924; email: sasamuel@uj.ac.za; Ejohwomu, Obuks; orcid: 0000-0001-7098-8999; email: obuks.ejohwomu@manchester.ac.uk; Aigbavboa, Clinton Ohis; email: caigbavboa@uj.ac.za (MDPI, 2021-06-22)
      Building information modelling (BIM) has become a common denominator for information management, efficiency, collaboration, and productivity in the construction industry. The adoption of building information modelling has been assessed to be unequal in the construction industry the world over. It has been observed that developing countries are struggling with BIM adoption and are at a beginner stage in the process. Meanwhile, there have been different research efforts focused on advancing BIM diffusion in developing countries. This study focused on reviewing the research trend and knowledge domains of BIM research in developing countries. The study analysed scholarly publications from selected developing countries sourced from the Scopus database from 2005 to 2019; the study covered BIM research efforts since their commencement in developing countries. The study identified the different research trends and the current focus through visualisations using VOS viewer software. The most influential and productive researchers were also identified. This research contributes to the extant body of knowledge by synthesizing the state of the art of BIM research in developing countries. Furthermore, it provides the pre-COVID-19 BIM diffusion status in developing countries.
    • Generation of anisotropic strain dysregulates wild-type cell division at the interface between host and oncogenic tissue.

      Moruzzi, Megan; Nestor-Bergmann, Alexander; Goddard, Georgina K; Tarannum, Nawseen; Brennan, Keith; Woolner, Sarah; email: sarah.woolner@manchester.ac.uk (2021-06-03)
      Epithelial tissues are highly sensitive to anisotropies in mechanical force, with cells altering fundamental behaviors, such as cell adhesion, migration, and cell division. It is well known that, in the later stages of carcinoma (epithelial cancer), the presence of tumors alters the mechanical properties of a host tissue and that these changes contribute to disease progression. However, in the earliest stages of carcinoma, when a clonal cluster of oncogene-expressing cells first establishes in the epithelium, the extent to which mechanical changes alter cell behavior in the tissue as a whole remains unclear. This is despite knowledge that many common oncogenes, such as oncogenic Ras, alter cell stiffness and contractility. Here, we investigate how mechanical changes at the cellular level of an oncogenic cluster can translate into the generation of anisotropic strain across an epithelium, altering cell behavior in neighboring host tissue. We generated clusters of oncogene-expressing cells within otherwise normal in vivo epithelium, using Xenopus laevis embryos. We find that cells in kRas , but not cMYC, clusters have increased contractility, which introduces radial stress in the tissue and deforms surrounding host cells. The strain imposed by kRas clusters leads to increased cell division and altered division orientation in neighboring host tissue, effects that can be rescued by reducing actomyosin contractility specifically in the kRas cells. Our findings indicate that some oncogenes can alter the mechanical and proliferative properties of host tissue from the earliest stages of cancer development, changes that have the potential to contribute to tumorigenesis. [Abstract copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.]
    • Extensive cone-dependent spectral opponency within a discrete zone of the lateral geniculate nucleus supporting mouse color vision.

      Mouland, Josh W; Pienaar, Abigail; Williams, Christopher; Watson, Alex J; Lucas, Robert J; Brown, Timothy M; email: timothy.brown@manchester.ac.uk (2021-06-02)
      Color vision, originating with opponent processing of spectrally distinct photoreceptor signals, plays important roles in animal behavior. Surprisingly, however, comparatively little is understood about color processing in the brain, including in widely used laboratory mammals such as mice. The retinal gradient in S- and M-cone opsin (co-)expression has traditionally been considered an impediment to mouse color vision. However, recent data indicate that mice exhibit robust chromatic discrimination within the central-upper visual field. Retinal color opponency has been reported to emerge from superimposing inhibitory surround receptive fields on the cone opsin expression gradient, and by introducing opponent rod signals in retinal regions with sparse M-cone opsin expression. The relative importance of these proposed mechanisms in determining the properties of neurons at higher visual processing stages remains unknown. We address these questions using multielectrode recordings from the lateral geniculate nucleus (LGN) in mice with altered M-cone spectral sensitivity (Opn1mw ) and multispectral stimuli that allow selective modulation of signaling by individual opsin classes. Remarkably, we find many (∼25%) LGN cells are color opponent, that such cells are localized to a distinct medial LGN zone and that their properties cannot simply be explained by the proposed retinal opponent mechanisms. Opponent responses in LGN can be driven solely by cones, independent of cone-opsin expression gradients and rod input, with many cells exhibiting spatially congruent antagonistic receptive fields. Our data therefore suggest previously unidentified mechanisms may support extensive and sophisticated color processing in the mouse LGN. [Abstract copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.]
    • Violence, Control and Restraint: The Harms to Young Adults Particularly Upon Transition

      Price, Jayne; orcid: 0000-0003-3719-1851 (Wiley, 2021-06-15)
    • Exploring the STEP-uP to practice: A survey of UK Lead Midwives for Education views of the STudent midwife Extended Practice Placement during the first wave of the COVID-19 pandemic.

      Cooke, Alison; email: alison.cooke@manchester.ac.uk; Hancock, Angela; email: angela.hancock@manchester.ac.uk; White, Helen; email: helen.white@manchester.ac.uk; Clark, Nicky; email: n.j.clark@hull.ac.uk; Gibb, Fiona; email: f.gibb@rgu.ac.uk; McNeill, Jenny; email: j.mcneill@qub.ac.uk; Thomas, Grace; email: thomassg4@cardiff.ac.uk; Lloyd, Carmel; email: carmel.lloyd@rcm.org.uk; Furber, Christine; email: christine.furber@manchester.ac.uk (2021-05-28)
      to assess the effect of implementation of the extended placement option available to midwifery students during the first wave of the COVID-19 pandemic. Online survey open from 2nd June 2020 to 15th July 2020. United Kingdom. Lead Midwives for Education (LMEs). A total of 38 of 55 LMEs responded (response rate 69%). The majority of Approved Education Institutions (AEIs) offered an extended placement to students, but with some variation in the choices offered, unrelated to geographical location or size of student cohort. AEIs appeared to provide the majority of decisional support for students. Many practice learning environments became unavailable, particularly community, gynaecology/medical wards and neonatal units. LMEs experienced both internal and external pressures to instigate rapid change. The impact of COVID-19 on midwifery education is significant and will need continual scrutiny to minimise future detriment. The pressures of providing midwifery education throughout the early phase of COVID-19 were substantial, but it is important that we learn from the immediate changes made, value and pursue the changes that have been beneficial, and learn from those that were not. Student learning experiences have undergone significant change during the pandemic. It is essential to assess what effect the extended placement has had on student readiness for practice, their confidence, resilience, mental health, and attrition and retention. Educators transitioned to remote working, and rapidly assimilated new skills for online education; exploration of the impact of this is recommended. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
    • Corticosteroid Resistance in Smokers—A Substudy Analysis of the CORTICO-COP Randomised Controlled Trial

      Sivapalan, Pradeesh; email: Pradeesh.sivapalan.02@regionh.dk; Bikov, Andras; orcid: 0000-0002-8983-740X; email: andras.bikov@gmail.com; Suppli Ulrik, Charlotte; email: csulrik@dadlnet.dk; Lapperre, Therese Sophie; orcid: 0000-0002-5176-0101; email: therese.lapperre@uza.be; Mathioudakis, Alexander G.; orcid: 0000-0002-4675-9616; email: alexander.mathioudakis@manchester.ac.uk; Højberg Lassen, Mats Christian; email: mats.christian.hoejbjerg.lassen@regionh.dk; Grundtvig Skaarup, Kristoffer; email: kristoffer.grundtvig.skaarup@regionh.dk; Biering-Sørensen, Tor; email: Tor.Biering-Soerensen@regionh.dk; Vestbo, Jørgen; email: jorgen.vestbo@manchester.ac.uk; Jensen, Jens-Ulrik S.; orcid: 0000-0003-4036-0521; email: jens.ulrik.jensen@regionh.dk (MDPI, 2021-06-21)
      The CORTICO-COP trial showed that eosinophil-guided corticosteroid-sparing treatment for acute exacerbation of chronic obstructive pulmonary disease was non-inferior to standard of care and decreased the accumulated dose of systemic corticosteroids that patients were exposed to by approximately 60%. Smoking status has been shown to affect corticosteroid responsiveness. This post hoc analysis investigated whether eosinophil-guided treatment is non-inferior to conventional treatment in current smokers. The main analysis of current smokers showed no significant difference in the primary endpoint, days alive, and out of hospital within 14 days between the control group (mean, 9.8 days; 95% confidence interval (CI), 8.7–10.8) and the eosinophil-guided group (mean, 8.7 days; 95% CI, 7.5–9.9; p = 0.34). Secondary analyses of the number of exacerbations or deaths, the number of intensive care unit admissions or deaths, lung function improvement, and change in health-related quality of life also showed no significant differences between the two groups. The results of a sensitivity analysis of ex-smokers are consistent with the main analysis. Our results suggest that eosinophil-guided treatment is non-inferior to standard of care in current smokers and ex-smokers. Because data on the impact of smoking status on eosinophil-guided treatments are sparse, more randomised trials are needed to confirm our results.
    • Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-03-25)
      Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown.
    • Physiological Characteristics of Female Soccer Players and Health and Performance Considerations: A Narrative Review

      Randell, Rebecca K.; orcid: 0000-0003-1141-9766; email: rebecca.randell@pepsico.com; Clifford, Thomas; Drust, Barry; Moss, Samantha L.; Unnithan, Viswanath B.; De Ste Croix, Mark B. A.; Datson, Naomi; Martin, Daniel; Mayho, Hannah; Carter, James M.; et al. (Springer International Publishing, 2021-04-12)
      Abstract: Female soccer has seen a substantial rise in participation, as well as increased financial support from governing bodies over the last decade. Thus, there is an onus on researchers and medical departments to develop a better understanding of the physical characteristics and demands, and the health and performance needs of female soccer players. In this review, we discuss the current research, as well as the knowledge gaps, of six major topics: physical demands, talent identification, body composition, injury risk and prevention, health and nutrition. Data on female talent identification are scarce, and future studies need to elucidate the influence of relative age and maturation selection across age groups. Regarding the physical demands, more research is needed on the pattern of high-intensity sprinting during matches and the contribution of soccer-specific movements. Injuries are not uncommon in female soccer players, but targeting intrinsically modifiable factors with injury prevention programmes can reduce injury rates. The anthropometric and physical characteristics of female players are heterogeneous and setting specific targets should be discouraged in youth and sub-elite players. Menstrual cycle phase may influence performance and injury risk; however, there are few studies in soccer players. Nutrition plays a critical role in health and performance and ensuring adequate energy intake remains a priority. Despite recent progress, there is considerably less research in female than male soccer players. Many gaps in our understanding of how best to develop and manage the health and performance of female soccer players remain.
    • Universal credit, lone mothers and poverty: some ethical challenges for social work with children and families

      Carey, Malcolm; University of Chester (Taylor and Francis, 2021-06-22)
      This article critically evaluates and contests the flagship benefit delivery system Universal Credit for lone mothers by focusing on some of the ethical challenges it poses, as well as some key implications it holds for social work with lone mothers and their children. Universal Credit was first introduced in the United Kingdom (UK) in 2008, and echoes conditionality-based welfare policies adopted by neoliberal governments internationally on the assumption that paid employment offers a route out of poverty for citizens. However, research evidence suggests that the risks of conditionality polices for lone parents can often include increased poverty, a deterioration in mental health or even destitution posed by paternalistic sanctions or precarious low-paid employment, which can undermine parenting capacities and children’s well-being. The article also critically appraises and questions challenges posed by an increased reliance upon contractual ethics by governments, alongside the wider behaviour modifying policies of the workfare-orientated state. This includes that working-class lone mothers can erroneously be stigmatised as representing a morally challenged dependent burden through activation policies and risk-averse social work practices.
    • Assessment of energy availability and associated risk factors in professional female soccer players

      Moss, Samantha L.; Randell, Rebecca K.; Burgess, Darren; Ridley, Stephanie; ÓCairealláin, Cairbre; Allison, Richard; Rollo, Ian (Informa UK Limited, 2020-08-06)
    • The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences.

      Clark, Sam; orcid: 0000-0002-6865-4452; Jowitt, Thomas A; Harris, Lynda K; Knight, Christopher G; orcid: 0000-0001-9815-4267; Dobson, Curtis B; orcid: 0000-0002-6483-4608; email: curtis.dobson@manchester.ac.uk (2021-05-21)
      Our understanding of the activity of cationic antimicrobial peptides (AMPs) has focused on well-characterized natural sequences, or limited sets of synthetic peptides designed de novo. We have undertaken a comprehensive investigation of the underlying primary structural features that give rise to the development of activity in AMPs. We consider a complete set of all possible peptides, up to 7 residues long, composed of positively charged arginine (R) and / or hydrophobic tryptophan (W), two features most commonly associated with activity. We found the shortest active peptides were 4 or 5 residues in length, and the overall landscapes of activity against gram-positive and gram-negative bacteria and a yeast were positively correlated. For all three organisms we found a single activity peak corresponding to sequences with around 40% R; the presence of adjacent W duplets and triplets also conferred greater activity. The mechanistic basis of these activities comprises a combination of lipid binding, particularly to negatively charged membranes, and additionally peptide aggregation, a mode of action previously uninvestigated for such peptides. The maximum specific antimicrobial activity appeared to occur in peptides of around 10 residues, suggesting 'diminishing returns' for developing larger peptides, when activity is considered per residue of peptide.
    • MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function.

      Roberts, Luke B; orcid: 0000-0003-1143-304X; Jowett, Geraldine M; orcid: 0000-0002-8436-6637; Read, Emily; orcid: 0000-0002-0376-2989; Zabinski, Tomas; Berkachy, Rita; orcid: 0000-0002-2053-5913; Selkirk, Murray E; orcid: 0000-0002-6274-6014; Jackson, Ian; Niazi, Umar; orcid: 0000-0001-7176-8883; Anandagoda, Nelomi; Araki, Masatake; et al. (2021-05-21)
      Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following <i>Nippostrongylus brasiliensis</i> infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, <i>Socs1</i> and <i>Gfi1</i> expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions.
    • A promiscuous glycosyltransferase generates poly-β-1,4-glucan derivatives that facilitate mass spectrometry-based detection of cellulolytic enzymes.

      Bulmer, Gregory S; orcid: 0000-0003-4794-2858; Mattey, Ashley P; orcid: 0000-0002-6564-7150; Parmeggiani, Fabio; Williams, Ryan; Ledru, Helene; Marchesi, Andrea; orcid: 0000-0002-1560-5921; Seibt, Lisa S; orcid: 0000-0002-8230-5371; Both, Peter; Huang, Kun; Galan, M Carmen; orcid: 0000-0001-7307-2871; et al. (2021-06-08)
      Promiscuous activity of a glycosyltransferase was exploited to polymerise glucose from UDP-glucose via the generation of β-1,4-glycosidic linkages. The biocatalyst was incorporated into biocatalytic cascades and chemo-enzymatic strategies to synthesise cello-oligosaccharides with tailored functionalities on a scale suitable for employment in mass spectrometry-based assays. The resulting glycan structures enabled reporting of the activity and selectivity of celluloltic enzymes.
    • Publisher Correction: The blue hue of einsteinium.

      Natrajan, Louise S; orcid: 0000-0002-9451-3557; email: louise.natrajan@manchester.ac.uk; Faulkner, Stephen; email: stephen.faulkner@keble.ox.ac.uk (2021-06-08)