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Spermatogenesis
No full textSpermatogenesis is an extraordinarily complex cellular reorganization producing distinctive elongated haploid gametes. Successful spermatogenesis is critical to reproduction and species survival, and sperm, and the genes expressed in them, evolve rapidly. Across insects, sperm display a huge variety of forms. In this chapter, we explore current knowledge of insect spermatogenesis, with a primary focus on Drosophila melanogaster where genetic tools have provided insight into the molecular underpinning of the many cellular processes involved. We discuss the mechanisms by which germline stem cells and early germ cells (spermatogonia) interact with somatic cells to sustain lifelong spermatogenesis, then how spermatocytes acquire a unique transcriptome and undergo meiosis, eventually undergoing the characteristic morphogenetic events of spermiogenesis to produce mature sperm, and finally, we describe the diversity of sperm forms and mechanisms that produce such variety. New technologies will undoubtedly lead to profound new insights into this most important of cell transformations, with implications on understanding evolution and influencing fertility
The role of European Union (EU) metagovernance in supporting the voluntary and community sector in Northern Ireland
Get PDFThis article argues that European Union (EU) peacebuilding scholarship can benefit from organizational research on the socio‐spatial dynamics of policy implementation. It introduces a strategic‐relational heuristic to address two key gaps: the marginalization of grassroots agency in spatial analyses and the separation of strategy from structure. Drawing on the Strategic‐Relational Approach (SRA), the paper examines EU peacebuilding as a form of metagovernance. Using Northern Ireland as a case study, it shows how voluntary and community groups not only respond to but also shape metagovernance as an opportunity structure. Key dimensions—geographic reach, thematic focus, governance mechanisms, and spatial elements like territory, place, scale, and networks—are central to this process. Yet, persistent shortcomings reveal tensions where policy and politics intertwine. The article concludes that metagoverning peacebuilding is a dynamic, context‐specific process shaped by diverse actor strategies and overlapping territorial influences, requiring an understanding of both strategic tools and opportunity structure
Dental practitioners' thresholds for restorative intervention in carious lesions: a survey based systematic review update
Get PDFIntroduction: Despite evidence supporting the clinical and cost-effectiveness of minimally invasive dentistry (MID), its adoption by the dental profession has been slow. A systematic review in 2016 found the majority of dentists intervene invasively earlier than necessary. The aim was to update this review of the assessment of dental practitioners’ thresholds for providing restorative treatment for carious lesions given changes in evidence, teaching, and guidelines since 2016. The primary outcome was dental practitioners’ restorative thresholds (the extent of the lesion when they would decide to intervene restoratively). Secondary outcomes were changes over time, caries risk, regional differences, and primary/permanent dentition. Methods: This updated review replicated the methodology for the initial review, following the PRISMA 2020 guidelines (PROSPERO; CRD42023431906). Embase, MEDLINE (via PubMed), and Web of Science databases were searched (2016–2023) for observational studies reporting on dental clinicians’ thresholds for restorative interventions in adults and children without language, time, or quality restrictions. Screening, data extraction, and risk of bias assessment (Modified Newcastle-Ottawa Scale) were carried out independently and in duplicate. Meta-analyses were performed using a random-effects model. No funding sought. Results: Overall, 47 publications (30 from original publication and 17 from updated search) met the inclusion criteria and 65 datasets were included in the meta-analyses: 19 for occlusal lesions (16 pre-2016 and 3 post-2016; n = 11,946) and 46 for proximal lesions (38 pre-2016 and 8 post 2016; n = 20,428). The meta-analyses found that for occlusal lesions confined to enamel, there were fewer practitioners intervening invasively: 5% (95% confidence interval [CI]; 1–20%) post-2016, compared with 15% (95% CI; 9–23%) pre-2016. The opposite was found for proximal lesions with increased intervention levels, 27% (95% CI; 18–40%) for lesions confined to enamel post-2016, compared with 19% (95% CI; 12–29%) pre-2016, and for lesions extending up to the enamel-dentine junction 61% (95% CI; 36–81%) post-2016, compared with 39% (95% CI; 29–51%) pre-2016. There was variance between regions but too few studies to draw conclusions on individual regions. Conclusion: There was a suggestion of less invasive treatment of occlusal lesions over time; however, this was not evident for proximal lesions
Experimental Cancer Medicine Centre (ECMC) network proposal for a consensus gene panel for pan-cancer sequencing: a Delphi methodology
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The Experimental Cancer Medicine Centre (ECMC) Network supports UK-wide access to experimental cancer therapies, many of which require specific genomic alterations. This study aimed to develop expert consensus on essential genes for a pan-cancer sequencing panel, involving subject matter experts (SMEs) from the ECMC Network and the pharmaceutical industry.
Methods
A pilot with 8 SMEs graded 526 genes, refining the list to 210. A three-round Delphi process was then used, with SMEs iteratively evaluating each gene. In the final round, SMEs also assessed the inclusion of tumour mutational burden (TMB), microsatellite instability (MSI), and mutation types (structural variations, copy number variations, and/or fusions).
Results
Consensus was reached on a final panel of 99 genes applicable across multiple cancers. High agreement was also achieved for including TMB, MSI, and screening for structural variations, copy number variants, and fusions. The panel is intended for both adult and paediatric tumour types.
Conclusions
This consensus-based gene panel offers a standardised approach to pan-cancer genomic screening. It supports harmonised diagnostics and could improve patient access to personalised therapies and research trials across clinical and NHS settings
New pieces, a high-status early medieval settlement in the Welsh Marches: preliminary results from the 1996-2000 excavations
No full textClaiming land, claiming water: Borders and the people who crossed them in the Early Modern Atlantic
No full textClaiming Land, Claiming Water shares what historians and geographers wish readers knew about maps and borders before, during, and after the founding of the United States. The essays collected in this volume model how people can learn to interpret maps as arguments, rather than as historical facts, and to read maps for evidence of people and places that were elided, renamed, or destroyed.
Contributors travel through the sixteenth, seventeenth, eighteenth, and nineteenth centuries in the place known by many names: the Atlantic World; the North American continent; borderlands; and homelands. Onto this place where people exercised power over space by forging relationships, colonizers came and imagined borders onto maps. Featuring reproductions of twenty historical maps, the book takes readers through this era of immense disruption to teach them strategies for reading and interpreting these maps critically. Essays attend carefully to water alongside land and land alongside water in search of new interpretive avenues that reframe what we know about space, control, and sovereignty.
By using historical examples of people--farmers, fishers, hunters, religious leaders, colonial projectors, traders, sailors, soldiers, diplomats, and cartographers, it becomes possible to resist the temptation to impose modern geographical constructs backwards onto the histories we read, teach, and write. Claiming Land, Claiming Water investigates why some of these people imagined and made claims to bounded space, and how and why other people confounded and challenged those claims.
Contributors: Sarah Chute, Edward G. Gray, Kim M. Gruenwald, Rachel B. Herrmann, Christian J. Koot, Chad McCutchen, Jennifer Monroe McCutchen, John Morton, Paul Musselwhite, Charles Prior, Karen Rann, Jessica Choppin Roney, Samuel Truett, Harvey Amani Whitfield, Alex Zukas
From Gen Z to Boomers: Motivational drivers shaping industry 5.0 and the future of work
Get PDFThe rise of Industry 5.0 (I5.0)—with human-centricity as its defining pillar, complemented by sustainability and resilience—coincides with an unprecedented moment in workforce history: the simultaneous presence of four generations, including the emerging Generation Z. Human-centricity in this paradigm emphasizes well-being, purpose, and meaningful work as critical elements in reconfiguring organizations. Despite its centrality, there is still limited scholarly understanding of how generational motivations align or diverge in shaping this human-centered future of work. This study addresses that gap by exploring work-related motivators across Baby Boomers, Generation X, Y, and Z, aiming to inform foresight-driven organizational strategies. Using an inductive, two-phase approach—a Generation Z-focused workshop followed by a global multigenerational survey—we applied Correspondence Analysis to map value clusters among the generations. Findings reveal that Gen Y and Z converge on priorities like work-life balance, career development, and non-monetary incentives, while Gen X shares Z’s sense of purpose, albeit with more organizational and societal framing. Baby Boomers diverge most, valuing stability, creativity, and structured environments. Theoretically, the study contributes to futures scholarship by conceptualizing generational values as foresight variables—early signals of paradigm shifts in leadership, purpose, and motivation that reinforce and extend the human-centric vision of I5.0. Practically, we offer recommendations for designing inclusive, foresight-informed HR strategies that leverage generational diversity as a foundation for socially just and future-resilient organizations
Developing interferon-β as a safe in vivo experimental-medicine model of human inflammation
Get PDFBackground
Inflammation is increasingly implicated in a wide range of neuropsychiatric and neurodegenerative disorders from depression to dementia. Compelling evidence for an inflammatory role in these disorders includes experimental-medicine studies with IFN-α and endotoxin, alongside therapeutic benefits observed with anti-cytokine agents.
Aim
To develop and characterise a new, safe in-vivo mild inflammatory response that is titratable, elicits robust host sickness manifestations within an experimentally tractable timeframe, and has minimal cardiovascular effects, avoiding the requirement for continuous cardiac monitoring and ensuring applicability across diverse experimental contexts and participant groups, from the young to the elderly.
Methods
Using a randomized, blinded, placebo-controlled, repeated measures cross-over design, physiological, behavioural, cytokine, cellular and transcriptomic immune responses were collected from 30 healthy volunteers (15 young (18–34) and 15 older (60–75) years) on two separate occasions, once after 100 µg subcutaneous IFN-β (EXTAVIA®) and once after subcutaneous saline (placebo) injection.
Results
IFN-β increased ∼15-fold at 4 h and 9-fold at 6½ hours and rapidly induced anticipated increases in negative mood, tiredness, tension and sickness symptoms and reduced vigour (all p < 0.01) without serious side effects. It was associated with a modest increase in temperature (mean: +1.1C) and heart rate (mean: +11 bpm) but no change in blood-pressure or cardiovascular instability. IL-6, TNF-α, neutrophil to lymphocyte ratio and monocyte count all showed significant increases (all p < 0.05). Transcriptomic analyses confirmed activation of classical Interferon signalling pathways as well as Toll-like Receptor (TLR), Inflammasome, Pyroptosis, MyD88 and a variety of other host response pathways that have been implicated in the pathophysiology of neuropsychiatric or neurodegenerative disorders.
Conclusions
IFN-β is a safe, robust new experimental model of mild inflammation that can be safely used to induce transient changes in systemic inflammation in healthy individuals from 18-75 years. Modulation of diverse immunological processes suggests it could be a valuable new experimental medicine tool across neuropsychiatric and neurodegenerative disorders
CXCR3 expression on antigen experienced B-cells is systemically dysregulated in type 1 diabetes
Get PDFAims/hypothesis
The chemokine receptor C-X-C chemokine receptor type 3 (CXCR3) is a key chemoattractant molecule that facilitates the migration of activated T cells to the pancreas, leading to beta cell death. In this study, we investigated CXCR3 responses in B cells during type 1 diabetes progression.
Methods
Peripheral blood samples were obtained from individuals with recent-onset and long-duration type 1 diabetes, who were age- and sex-matched to non-diabetic donors. We isolated peripheral blood mononuclear cells (PBMCs) and examined changes in CXCR3 expression on lymphocytes from donors, performing multiparameter flow cytometry and functional cell culture assays. Human post-mortem pancreatic tissue was obtained from the Exeter Archival Diabetes Biobank. Immunofluorescence staining was used to assess CXCR3 expression in pancreatic tissues.
Results
We observed reduced CXCR3 expression on antigen-experienced B cells in individuals with a long duration of type 1 diabetes, although B cells remained responsive to IFNγ. In individuals who were recently diagnosed, IFNγ treatment resulted in increased CXCR3 expression compared with B cells from non-diabetic donors. B cells in pancreases that were recovered post-mortem from young recent-onset donors lacked CXCR3 expression, but co-staining to detect CD8+ T cells revealed a CXCR3+CD20+CD8+ T cell population, with their circulating counterpart showing increased CXCR3 expression.
Conclusions/interpretation
We conclude that the CXCR3 response in antigen-experienced B cells is dysregulated during the progression of type 1 diabetes. CXCR3 expression is limited in CD20+ B cells in pancreases from recent-onset individuals diagnosed with type 1 diabetes under 7 years of age, but evident on CD8+ T cells that express CD20
Mapping social participation interventions for adults with a neurodegenerative condition: a scoping review of in-person and digital community approaches
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Individuals with neurodegenerative conditions, such as Parkinson’s, Huntington’s, Dementia, and Multiple Sclerosis, often experience significant social isolation due to physical and cognitive limitations that hinder social participation. Social isolation can lead to loneliness and reduced quality of life. This scoping review aimed to map interventions designed to enhance social connectedness and mitigate these effects.
Methods
Following Arksey and O’Malley’s scoping review framework, key databases were searched. Inclusion criteria focused on interventions fostering social participation in adults with neurodegenerative conditions. Themes were identified through a narrative synthesis approach.
Results
A total of 1,038 articles were screened, with 37 meeting the inclusion criteria. Most interventions involved in-person group activities, with digital interventions representing a smaller area. The synthesis revealed three themes: intervention details, theoretical frameworks, and evaluations. These themes highlighted key components and theoretical foundations that informed interventions but also identified implementation challenges with accessibility and inclusivity for individuals with varied needs.
Conclusions
The findings underscore the need for diverse, accessible interventions to foster social connectedness for individuals with neurodegenerative conditions. Future research should focus on refining intervention design to improve inclusivity, addressing barriers to enhance participation in both in-person and digital formats