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Contrasting Evolutionary Trajectories Under Paternal Genome Elimination in Male and Female Citrus Mealybugs
No full textMost studies of sex‐biased genes explore their evolution in familiar chromosomal sex determination systems, leaving the evolution of sex differences under alternative reproductive systems unknown. Here we explore the system of paternal genome elimination employed by mealybugs (Hemiptera: Pseudococcidae) which have no sex chromosomes. Instead, all chromosomes are autosomal and inherited in two copies, but sex is determined by the ploidy of expression. Females express both parental alleles, but males reliably silence their paternally inherited chromosomes, creating genome‐wide haploid expression in males and diploid expression in females. Additionally, sons do not express alleles directly inherited from their fathers, potentially disrupting the evolution of male‐benefiting traits. To understand how these dynamics impact molecular evolution, we generated sex‐specific RNAseq, a new gene annotation, and whole‐genome population sequencing of the citrus mealybug, Planococcus citri. We found that genes expressed primarily in females hold more variation and evolve more quickly than those expressed in males or both sexes. Conversely, we found more apparent adaptation in genes expressed mainly in males than in those expressed in females. Put together, in this paternal genome elimination system there is slower change on the male side but, by increasing selective scrutiny, an increase in the degree of adaptation in these genes. These results expand our understanding of evolution in a non‐Mendelian genetic system and the data we generated should prove useful for future research on this pest insect.</p
Modulation of Cell Fate Decisions To Define Novel Cancer Therapies
No full textRegulation of cell fate is important in health and disease, as when these pathways are disrupted in disease, the mechanisms that govern cell fate are often dysfunctional. p53 is an important transcription factor in determining cell fates and is activated in response to damage. Once a damage threshold is reached the transcriptional activity of p53 determines which cell fate occurs, either senescence or apoptosis. p53 interacts with multiple proteins resulting in reciprocal regulation, notably p53 binds to the Tec family kinase BMX causing reciprocal inhibition, but interaction with the multiple domain pro-apoptotic protein BAK results in BAK activation. Furthermore, BMX negatively regulates BAK via Y108 phosphorylation thus the formation of complexes between BMX, BAK and p53 could regulate cell fate. This thesis aims to understand the interplay between these three proteins and determine the resulting cell fate. I aimed to determine the cellular context behind the formation of the complexes between BMX, BAK and p53, and characterise the binding event between the SH3 domain of BMX and the proline rich domain (PRD) of p53. Furthermore, I determined that BMX did not play a role in the induction of senescence, however, treatment of senescent cells with BMX inhibitor BMX-IN-1 and etoposide in combination selectively reduced cell viability in senescent cells. This suggests that whilst BMX is dispensable for inducing senescence, BMX is important in maintaining the viability of senescent cells. Using cell biology techniques, I showed that p53 and BMX form a complex in untreated and senescent cells that upon apoptosis induction dissociates within an hour. This suggests that the complex formed between BMX and p53 is essential in preventing apoptosis through inhibition of p53’s pro-apoptotic functions. Furthermore, the SH3 domain of BMX binds to both BAK and p53 raising the possibility that BAK and p53 competitively bind to BMX.</p
Silence of the Muscles: Wearable Electromyography, Sitting, and Type 2 Diabetes
No full textInterrupting prolonged sitting in type 2 diabetes is associated with metabolic and cardiovascular benefits. Wearable electromyography enables precise quantification of the related muscle-excitation patterns. Integrating metabolic and electromyographic evidence from experimental and free-living conditions should not only inform the personalization of physical activity for type 2 diabetes management, but also open windows of opportunity for future mechanistic insight.</p
A multifactorial intervention to improve cardiovascular outcomes in adults with type 2 diabetes and current or previous diabetic foot ulcer disease: Protocol for a multi‐centre randomised control trial (MiFoot study)
No full textAbstractBackgroundIn the United Kingdom, the prevalence of diabetes‐related foot ulcer disease (DFUD) is 6.3%, and cardiovascular disease (CVD) is the leading cause of mortality in people with DFUD. This study aims to evaluate the effectiveness of a multifactorial intervention to reduce CVD events and mortality in adults with type 2 diabetes (T2D) and DFUD.MethodsThe MiFoot study is a multi‐centre, pragmatic randomised controlled trial to test intervention effectiveness and cost‐effectiveness compared to usual care that will include an internal feasibility study and a process evaluation. English‐speaking adults (≥18 years; n = 392) with T2D and current/previous (within 5 years) DFUD will be recruited from multiple sites across the United Kingdom and randomised 1:1 to intervention (MiFoot multifactorial intervention plus usual care) or control (usual care), with data collected at baseline, 12‐ and 24‐month follow‐up. The MiFoot intervention comprises an individualised assessment with a healthcare practitioner to optimise treatment and assess the suitability of physical activity participation; group‐based disease self management education and physical activity sessions; and a digital‐based programme, consisting of cohort‐relevant topics, physical activity guidance and peer support functionality. The primary outcome will be extended major adverse cardiovascular events (MACE, i.e. myocardial infarction, stroke, cardiovascular death, peripheral arterial bypass, coronary artery bypass, coronary angioplasty or peripheral artery angioplasty) at 24 months.DISCUSSIONThis study will provide evidence on the feasibility and clinical effectiveness, and cost‐effectiveness of a multifactorial intervention to prevent or slow the progression of CVD‐related complications in the extremely high‐risk population with T2D and DFUD.</p
Effectiveness of a theory-informed intervention to increase care home staff influenza vaccination rates: a cluster randomised controlled trial
No full textAbstract
Background
Care home staff’s (CHS’s) influenza vaccination rate in England is 30%–40%, below the 75% WHO recommendation. We describe the effectiveness of a theory-informed and feasibility-tested intervention (in-home clinics; posters/videos to address vaccination hesitancy and care home financial incentives for uptake) to improve CHS vaccination rates.
Method
Recruited care homes in England with CHS vaccination rates <40% were randomised at the home level for intervention or control. Assuming a change in CHS vaccinated from 55% to 75%, 20% attrition, and 90% power, we required 39 homes per arm. Monthly data were collected throughout flu season. The difference in vaccination rates between the arms was compared using the intention-to-treat principle and a random effect logistic regression model.
Findings
The mean % vaccination rate was 28.6% in control (n = 35) and 32.7% in intervention (n = 35) [odds ratio (OR) = 1.29, 95% confidence interval (CI): 0.68–0.4, P = .435]. In a sub-analysis, including only homes receiving at least one clinic, control was 28.6% (n = 35) and intervention was 41.7% (n = 23) (OR = 2.08, 95% CI: 0.67–2.70, P = .045).
Interpretation
No effect on vaccination status was demonstrated. Within homes receiving clinics, a significant increase was observed. Process evaluation evidence suggests that starting 3 months into the influenza season partially explains this. Further evaluation initiating FluCare earlier is warranted.</p
Assessment of an oral corticosteroid withdrawal pathway for severe asthma patients receiving biologic therapies
No full textBackgroundThe optimal approach for weaning maintenance oral corticosteroids (mOCS) in severe asthma patients receiving biologics remains unclear. Previous studies assessed hypothalamic-pituitary-adrenal function at 5 mg daily prednisolone, a supraphysiological dose for many, necessitating further mOCS reduction for adrenal recovery.ObjectiveWe evaluated a protocol-driven nurse-led mOCS withdrawal pathway with clinical oversight for severe asthma patients receiving biologics.MethodsSevere asthma patients receiving biologics who had reduced mOCS to 5 mg prednisolone daily and maintained good asthma control, entered the withdrawal pathway. Prednisolone was decreased to 4 mg daily for 6 weeks then 3 mg daily for 6 weeks, followed by 09.00 serum cortisol measurement. Patients with cortisol >25 nmol/L followed a 20-week weaning protocol. Serum cortisol was re-checked 12 weeks after stopping mOCS.ResultsOf 102 patients, 92 had cortisol >25 nmol/L on 3 mg prednisolone and continued weaning. Seventy-three (72%) successfully discontinued mOCS with median [IQR] cortisol increasing from 192 [88-299] nmol/L on 3 mg prednisolone to 314 [248-437] nmol/L 12 weeks after discontinuation (pConclusionMost clinically stable asthma patients receiving biologics successfully withdrew mOCS without requiring dynamic adrenal function testing.</p
Capabilities and Collaborative Marketing Practices Among Rival Cluster-Based Wine Producers
No full textThis study investigates how owner-managers of wine producers that participate in coopetition relationships (cooperation with competitors) can effectively implement collaborative marketing practices with their cluster-based rivals to facilitate regional sales as a specific place-related strategy. Data collection featured interviews with owner-managers of smaller-sized, independent, family-owned, wine producers in New Zealand, alongside secondary data. Contributions are offered first, by profiling firms via a 2 × 2matrix, regarding decision-makers’ capabilities associated with gaining either a high/low recognition of types of customers’ knowledge and purchase intentions, also, by exhibiting a high/low competitor orientation. Second, unique insights emerge concerning the capability to be strategically flexible in response to environmental conditions. Third, new evidence indicates that capabilities vary, but some are of a lower-order ‘threshold’ rather than higher-order ‘dynamic’ nature.</p
An Impotent Prince, a Powerful Begum, and a Servant Queen: Lives of Women Servants in the Awadh Court (1814-37)
No full textThis article explores the history and social world of women servants at the court of Awadh in North India between 1814 and 1837. It does so by examining the court inquiry of a contentious birth of a son from the union of an allegedly ‘impotent’ prince and a maid servant. This and other similar little-known episodes show that female servants, instead of being low social status, neglected figures, were central to the functioning of the court and held important positions. The article describes female servants’ lives as extending beyond their occupational roles, encompassing intimacy, loyalty, trust and political power. It contributes to the historiography of servitude, labour and gender in early modern South Asia. It shifts scholarly focus away from Awadh’s royal women (begums) and courtesans (tawā’ifs) to women servants who worked in domestic/non-domestic spaces but have remained on the margins of scholarship.</p
Developing a Critical Understanding of Local and Global EFLMaterials: a case study of a Saudi University
No full textThis study provides a more nuanced understanding of the role of global and locally-developed, EFL learning materials in a Saudi university. It focuses on the nature of the materials and the differences between them. The study aims to: (1) analyse the content of locally developed and global materials. (2) investigate the development of local materials in this context, (3) consider end-user perspectives on both types of materials, and (4) explore the impact of the locally developed and global materials on teachers’ professional development. This study adopts a mixed-methods case study approach. It is interpretivist and constructivist in nature. Employing both qualitative and quantitative data collection methods, the research analyses and evaluates the content of the materials. In addition, semi-structured interviews with members of the curriculum committee, focus group interviews with 60 teachers, and follow up individual, semi-structured interviews with 15 teachers, plus an online questionnaire, completed by 102 learners, provide invaluable insights to address the research questions.Analysis of the local materials reveals their hybridised nature which the binary labels of ‘local’ vs ‘global’ fail to capture. The findings also reveal that developing local materials may offer certain advantages, such as greater flexibility for teachers to develop and tailor their materials to learner needs, cultural relevance, and alignment with institutional requirements. Yet, the process can be challenging in terms of time, effort and expertise, and this may affect the quality of the materials. Global coursebooks, in contrast, often provide a variety of resources, a standardised structure, and multicultural topics and benefit from professional editing.Participants in this study expressed their preference for global coursebooks to be used alongside local materials, as both types of materials complement each other and bring certain benefits for the Saudi context. Teachers reported that both types of materials broadened their pedagogical content knowledge (PCK) and enhanced their reflective practice. They also emphasised that developing local materials had enhanced their confidence in materials writing, improved their writing and evaluation skills, and increased collaboration with their colleagues, compared to using the more readily available global coursebooks.This study offers several implications for material developers, policymakers, and educators. It highlights the importance of adopting a flexible curriculum design that integrates both local and global materials to maximise learner language learning development. It also advocates a more dynamic and iterative approach to material selection, where end-users are involved in making decisions. A key recommendation in this study is to enhance teacher training programs to equip teachers with the skills to adapt both local and global materials effectively, which is often a neglected area in teacher professional development.</p
An investigation of Chinese university students’ motivation and psychological needs in learning languages other than English
No full textWhilst motivation to learn English is relatively well-understood, globalisation and national policies to enhance internationalisation from China have indicated a need for learning a language other than English (LOTE). This thesis draws on self-determination theory (SDT), which is well-established in Western contexts, and the L2 Motivational Self-system (L2MSS) to investigate motivation and need satisfaction amongst learners of LOTE in university students in China. A psychometric approach was adopted to develop a new survey instrument, aiming to explore the factor structure of motivation in LOTE learners. An extensive pilot study (N=76) demonstrated the suitability of the tool.The questionnaire was then administered to university learners in China (N=455), with the aim of: 1) confirming the factor structure as explored in the pilot study, 2) comparing the key features of motivation across LOTE, English, and non-language subject learners, and 3) evaluating whether SDT or LSMSS were suitable in accounting for the motivation of LOTE learners in China. Data were collected online via Qualtrics, with respondents from various Chinese universities.1: Exploratory factor analysis produced a robust eight factor models, comprising autonomous motivation, learning experience, the ideal L2 self; anxiety, instrumentality-promotion, learning attitude, controlled motivation and amotivation.2: ANOVA results indicated that LOTE learners exhibited lower motivation, less enjoyable learning experiences, and less clear future self-guides compared to both English and non-language subject learners.3: The basic psychological needs for autonomy, competence and relatedness each play a different role in predicting motivational factors, with competence and relatedness positively predicting autonomous motivation, learning experiences, the ideal L2 self, and LOTE learning attitudes.This thesis presents a case that combining SDT and the L2MSS offers a more comprehensive framework for evaluating the motivation of Chinese university students in LOTE learning. Furthermore, LOTE subject learners require additional attention, as they face motivational challenges compared to English and non-language subject learners.</p