Michael A. Wride

Early career researchers (ECRs) are the most abundant workforce in the fields of science, technology, engineering, mathematics, and medicine (STEMM). ECRs are generally mentored by experienced principal investigators (PIs) who direct the research objectives. The ECR mentee- mentor partnership can be mutually beneficial, but it is a critical relationship for ECRs with implications for publishing and career development. In this study, a mixed methods approach involving a survey, X polls (formally Twitter), and semi-structured interviews were used to determine how the ECR mentor-mentee relationship affects ECRs and their perceptions of career development in STEMM. To address this aim, two main research questions were developed: (1) Who do the STEMM ECR mentees and mentors currently perceive to be ECRs? and (2) What characteristics of the ECR mentee-mentor relationship are perceived to be important for ECR publishing practices and career progression? The main survey findings indicate that respondents largely from the life sciences and health field and they consider Ph.D. researchers and postdoctoral researchers as ECRs, but mentors also to a greater extent than mentees perceive new PIs (< 2 years experiences) as ECRs. Survey respondents also mostly agree on publishing practices regarding journal selection criteria such as journal scope and impact factor, although mentees appear to favor journal prestige and open access publishing more than mentors. This is likely due to the importance of visibility early in one’s career. Mentees take the lead in preparing manuscripts for submission, although a minority have described issues regarding authorship disputes. Finally, setting clear expectations, being collegial, mutually respectful, and having regular communication was identified by survey respondents and interviewees as integral features of a healthy ECR mentee- mentor relationship. In conclusion, the mentee-mentor relationship is critically important for ECR career development, and the findings of this study have wider implications for the development of effective ECR mentee and mentor training programs across the STEMM disciplines.

Purpose: This paper explores the experience of students and facilitators of Enquiry/Problem-Based Learning (E/PBL) as it transitioned online during the COVID-19 pandemic. Method: This two-phased mixed-methods sequential explanatory design study targeted academic staff and students engaged in online E/PBL during COVID-19 restrictions. The experience of enforced transition to online provision of E/PBL was examined in terms of the impact of digital tools on curriculum delivery and student perception of online E/PBL. In Phase 1, academic staff (n=21) and students (n= 67) responded to a survey that explored use of digital tools and experiences of online E/PBL. In Phase 2, academic staff (n=6) and students (n=2) participated in focus groups which were designed to elicit current and retrospective perspectives of the transition to online E/PBL. Results: Findings revealed that a number of digital tools were beneficial in assisting the delivery of online E/PBL. However, challenges were experienced by both facilitators and students with respect to technological competence and variance in IT access. Student responses suggested that communication barriers, inherent to the online environment, impacted on interactivity, which resulted in more active input being required from facilitators to promote student engagement. Most respondents revealed that they became increasingly comfortable in the online environment despite initial reservations, and that some changes in practice can help overcome limitations of digital tools. Conclusion: Engaging in online E/PBL presented diverse views amongst both facilitators and students on how best to support transition to student-centred learning and teaching methodology online. Recommendations from this study highlight the need for digital and technological training to enhance facilitator competence and the importance of building rapport, structure activities, and promote social cohesion amongst learners.

Carrying out research means being innovative, which requires novelty. Novelty is an important source of scientific breakthroughs and has great technological impact. Research institutions stand to benefit from fostering innovation. Here, we outline what academic institutions can do to help their scientists become more innovative.

Purpose: – The purpose of this paper is to highlight the profound learning associated with the Goethean methodology in the Holistic Science MSc at Schumacher College, Devon, UK. This is presented as a case study in profound pedagogy and as an exploration of the implications for workplace learning. Some comparisons are also made with reflective practice.Design/methodology/approach: – Background is provided on Goethe’s “way of science” and Barfield’s “participation”. Students were also interviewed about their learning and reflect on their experiences and challenges in learning the Goethean methodology, particularly regarding perceptions and participation, on their altered modes of thinking and feelings about learning, as well as on an “immediate”, corporeal and potentially co-operative mode of knowing in a “community of practice”, which can be extrapolated to the workplace.Findings: – The profoundness of the student experience and personal transformation presented in the interviews reveals that Goethean methodology has a place alongside the more specific analytical knowledge focus of universities. While the method has challenges in reconciling existing modes of knowing with the new approach, the students are able to see and intuit the wholeness and dynamism of phenomena more easily, and they gain a different perspective and learn to participate more fully in the world.Originality/value: – The paper asks that this template for educational practice be considered more widely relevant to today’s educational landscape in better providing skills and preparing students for the workplace in a world of “super-complexity”.

Survivin (Birc5) is the smallest member of the inhibitor of apoptosis (IAP) protein family, which regulates the cell cycle/apoptosis balance. The purpose of this study was to examine Survivin expression in the embryonic chick lens, in chick lens epithelial cell cultures, and in the postnatal mouse lens. Survivin expression was examined using a combination of quantitative real-time polymerase chain reaction, western blotting, and immunocytochemistry. To correlate Survivin expression with the timing of proliferation, we determined the profile of cell proliferation in the developing lens using the cell cycle marker proliferating cell nuclear antigen (PCNA) in quantitative western blotting and immunocytochemistry studies. We also examined the expression of PCNA and the extent of denucleation using terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick-end labeling (TUNEL) of lentoids (lens fiber-like cells) during chick lens epithelial cell differentiation in vitro. At embryonic day (ED) 4, Survivin immunostaining was present in two pools in lens epithelial cells and fiber cells: cytoplasmic and nuclear. The nuclear staining became more pronounced as the lens epithelial cells differentiated into lens fiber cells. At ED12, Survivin staining was observed in lens fiber cell nuclei containing marginalized chromatin, indicative of early denucleation events. Using western blotting, Survivin expression peaked at ED6, diminishing thereafter. This profile of expression correlated with the events in chick lens epithelial cell cultures: i) increased Survivin expression was associated with an increase in PCNA staining up to day 6 of culture and ii) downregulation of Survivin expression at day 8 of culture was coincident with a dramatic decrease in PCNA staining and an increase in TdT-mediated biotin-dUTP nick-end labeling in lentoids. In early postnatal mouse lenses, Survivin and PCNA were highly expressed and decreased thereafter during postnatal lens maturation. Survivin is expressed during chick and mouse lens development and in chick lens epithelial cell cultures. High levels of Survivin expression correlated with high rates of proliferation of lens epithelial cells at early stages of development. Downregulation of Survivin expression with development and its progressive localization to the nuclei of lens fiber cells was coincident with a decrease in cell proliferation and increased denucleation in differentiating lens fiber cells. These studies suggest an important role for Survivin as a dual regulator of lens epithelial cell proliferation and lens fiber cell differentiation.

Background Hirschsprung’s disease is characterised by the absence of ganglion cells in the distal bowel, a process which is controlled by complex genetic pathways. Homeobox genes have a major role in gut development and this is depicted by the enteric Hox code which describes the different spatial and temporal expression of Hox genes. Hoxa9 and Hoxa13 mutations have been discovered in patients with Hirschsprung’s disease (HD). The aim of this study was to determine the spatio-temporal pattern of Hoxa9 and Hoxa13 in enteric nervous system (ENS) development using the zebrafish model. Methods Purified plasmids that contained the gene of interest were obtained and inoculated into culture medium to exponentially increase the number of bacteria containing the plasmid. Cells were then harvested by centrifugation and plasmid DNA was extracted, which was then linearised and precipitated. RNA digoxigenin-labelled probes were made by in vitro transcription reaction. In situ hybridisation was carried out using these probes on zebrafish embryos which were collected from 24 to 120 h post fertilisation (hpf), by which time the zebrafish intestine is fully developed. Embryos were then mounted in glycerol and imaged using an Olympus B40 microscope and images were taken using an Olympus Super F1.8 digital camera. Results At 24 hpf, Hoxa9 expression is seen in the forebrain and hindbrain and also in the very distal myotome whereas Hoxa13 expression, however, is seen only at the forebrain and hindbrain. At 48 hpf, Hoxa9- and Hoxa13-labelled cells are seen migrating distally from the forebrain into the notochord and spinal cord. At 72 hpf, Hoxa9-labelled cells can be seen throughout the spinal cord whereas Hoxa13 positive cells are seen migrating down from the spinal cord and in the proximal gut. By 96 hpf, Hoxa9- and Hoxa13-labelled cells have migrated down the full length of the spinal cord and along the proximal and mid intestine. By 120 hpf, Hoxa9 and Hoxa13 positive cells can be seen along the entire length of the zebrafish intestine. Conclusions These results show further evidence that Hoxa9 and Hoxa13 are involved in the early and organised patterning of ENS development in the zebrafish model.

Purpose. To investigate the developmental and ocular expression of Opa3 in a mouse model of 3-methylglutaconicaciduria type III and the effect of mutation on protein localization and mitochondrial morphology. Methods. The B6 C3-Opa3^L122P mouse carrying a missense mutation in exon 2 (c.365T>C; p.L122P) of Opa3, which displays features of recessive 3-methylglutaconic aciduria type III was studied. The expression of Opa3 was determined with RT-PCR, quantitative PCR, and Western blot, in embryos (embryonic day [E]8 to postnatal day [P]0) and adult tissues, and by ocular immunohistochemistry. Mitochondria were stained using a mitochondrion-selective probe in mouse embryonic fibroblasts from Opa3^−/− mutants and imaged by electron microscopy of the retinas. Results. The splice variants Opa3a and Opa3b were expressed in the lenses and the retinas in the Opa3^−/− mice, with the expression of the Opa3a isoform predominant. Opa3 was expressed throughout embryonic development, with high levels of expression in the developing brain, retina, optic nerve, and lens. Opa3 localized to the mitochondria, and the L122P mutant protein did not mislocalize. Neither protein localized to the peroxisome. Opa3^−/− mice displayed disrupted mitochondrial morphology in the retina. Wild-type Opa3 protein increased as the lenses aged, despite the reduction in Opa3 mRNA occurring as a part of lens differentiation. However, mutant Opa3 mRNA was upregulated in homozygous mutant lenses, suggesting a compensatory increase in expression, which may further increase Opa3 protein levels. Conclusions. Mutant Opa3 protein retains its mitochondrial localization and induces disrupted mitochondrial morphology. Opa3 accumulates in the lens. The results may reflect a slow turnover of Opa3 protein in vivo and may be important in normal lens physiology.

Millions are rendered blind or exhibit visual impairment due to pathologies of the lens of the eye. Lens research therefore addresses the direct need to gain insights into the cellular and molecular basis of disease, but, moreover, serves as a valuable experimental system to answer fundamental biological questions. This themed issue showcases the scientific knowledge of the processes involved in the development, structure, ultrastructure, physiology and pathology of the lens and how this information has the potential to significantly further knowledge in various fields of research. The issue is divided into three main areas. Firstly, the lens is discussed as a developmental model for embryonic induction, as an elegant system for studying the role of growth factors in development, and for analysis of the molecular control and cellular basis of cellular differentiation. The genetic basis of disorders of lens development, including paediatric cataract (lens opacity), are also discussed in this section. Secondly, adult lens structure and ultrastructure are covered, as well as the lens as a model for homeostasis and solute exchange. Finally, the papers in the latter part of the special issue review lens pathology, including the lens as a model for normal and pathological ageing, vitreoretinal influences on lens function and cataract and the lens as a model for fibrotic disease. Overall, the articles highlight the lens as a continuing, very important and attractive model system for biologists working in many different research areas.

The programmed removal of organelles from differentiating lens fibre cells contributes towards lens transparency through formation of an organelle-free zone (OFZ). Disruptions in OFZ formation are accompanied by the persistence of organelles in lens fibre cells and can contribute towards cataract. A great deal of work has gone into elucidating the nature of the mechanisms and signalling pathways involved. It is apparent that multiple, parallel and redundant pathways are involved in this process and that these pathways form interacting networks. Furthermore, it is possible that the pathways can functionally compensate for each other, for example in mouse knockout studies. This makes sense given the importance of lens clarity in an evolutionary context. Apoptosis signalling and proteolytic pathways have been implicated in both lens fibre cell differentiation and organelle loss, including the Bcl-2 and inhibitor of apoptosis families, tumour necrosis factors, p53 and its regulators (such as Mdm2) and proteolytic enzymes, including caspases, cathepsins, calpains and the ubiquitin–proteasome pathway. Ongoing approaches being used to dissect the molecular pathways involved, such as transgenics, lens-specific gene deletion and zebrafish mutants, are discussed here. Finally, some of the remaining unresolved issues and potential areas for future studies are highlighted.