Wolverhampton Intellectual Repository and E-Theses
WIRE is the open access repository for research publications and outputs by researchers based at the University of Wolverhampton.
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Item The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein(Rockefeller University Press, 2023-03-22)Cytoplasmic dynein-driven movement of chromosomes during prophase I of mammalian meiosis is essential for synapsis and genetic exchange. Dynein connects to chromosome telomeres via KASH5 and SUN1 or SUN2, which together span the nuclear envelope. Here, we show that KASH5 promotes dynein motility in vitro, and cytosolic KASH5 inhibits dynein’s interphase functions. KASH5 interacts with a dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminal, and this region is also needed for dynein’s recruitment to other cellular membranes. KASH5’s N-terminal EF-hands are essential as the interaction with dynein is disrupted by mutation of key calcium-binding residues, although it is not regulated by cellular calcium levels. Dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5–dynein complex. Altogether, we show that the transmembrane protein KASH5 is an activating adaptor for dynein and shed light on the hierarchy of assembly of KASH5–dynein–dynactin complexes.Item RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1.(American Society for Clinical Investigation, 2022-01-13)Despite being the first homolog of the bacterial RecQ helicase to be identified in humans, the function of RECQL1 remains poorly characterized. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here, we identify 2 families with a genome instability disorder that we have named RECON (RECql ONe) syndrome, caused by biallelic mutations in the RECQL gene. The affected individuals had short stature, progeroid facial features, a hypoplastic nose, xeroderma, and skin photosensitivity and were homozygous for the same missense mutation in RECQL1 (p.Ala459Ser), located within its zinc binding domain. Biochemical analysis of the mutant RECQL1 protein revealed that the p.A459S missense mutation compromised its ATPase, helicase, and fork restoration activity, while its capacity to promote single-strand DNA annealing was largely unaffected. At the cellular level, this mutation in RECQL1 gave rise to a defect in the ability to repair DNA damage induced by exposure to topoisomerase poisons and a failure of DNA replication to progress efficiently in the presence of abortive topoisomerase lesions. Taken together, RECQL1 is the fourth member of the RecQ family of helicases to be associated with a human genome instability disorder.Item The approaches carrying out research with organisation AX(Palgrave MacMillan, 2025-03-11)This short Pivot explores the the physical, emotional, and psychological impact of the lived experiences of asylum seekers on the staff and volunteers of third sector organisations who assist and support them. The understanding of the issues, challenges and barriers of frontline staff who work with asylum seekers by understanding how Covid-19 affected their support work is often overlooked and not widely reported. Many organisations work diligently and without much media attention and are motivated by their mission to help and support vulnerable individuals from marginalised social groups. This research adopts a Constructivist Grounded Theory (CGT) which is a qualitative research method that involves co-constructing theories with participants. It is based on the theory that we all form views based on our own life experiences. As this work is multi-disciplinary, this approach is justified and used in many examples of social science research. The views of staff are heard within the research to give meaning to the work that they do and understand how their work impacts the lives of asylum seekers and refugees. It also is used as a means of reflection as to their own emotions, and feeling based on their experiences during the pandemic helping others. Similarly, the views and opinions of asylum seekers are necessary as they describe the impact that the pandemic had on them and the way they were still accommodated by staff during the social restrictions which were in place at that time.Item Tourism, place branding, and consumer behaviour(Springer Nature Switzerland, 2025-03-11)Given the symbolic significance of places such as nations, regions, cities, and gated communities, the ideas of brands and branding are being applied to them in recent times. For example, nation branding is becoming common especially as countries compete among themselves for resources and opportunities like investment inflows and skilled professionals. Similarly, consumers make inferences about goods and services offered in the marketplace based on the extent of the attractiveness of the countries where they originated from. This is commonly tagged country-of-origin (COO) effect. As there are several stakeholders associated with places such as tourists, residents, and governments, it becomes imperative for place marketers to consider inclusivity in the formulation of brand strategies. This chapter explores these issues and how they are being influenced by the digital transformation which permeates virtually all elements of the marketing systems. Apart from unpacking these salient issues with references to some pertinent cases, the chapter also features a discussion of the future of place branding consumer behaviour as well as the wide-ranging implications of the ideas.
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