How cell commitment and differentiation are controlled in the early stages of embryogenesis is a problem that has long fascinated developmental biologists. Retinoic acidinduced differentiation of embryonal carcinoma cells in culture provides a model in which these questions can be explored. Recent work has yielded exciting insights into the central series of molecular changes which drives the commitment of these cells to formation of a new phenotype. Interacting with the key molecules in this central pathway is a variety of transcription (...) factors, many of which show changes in availability and/or activity during differentiation. In various combinations, these modulate the activities of genes involved in both cell proliferation and in the production of extracellular matrix and other proteins characteristic of differentiated cells. (shrink)

Invertebrate genetic models with their tractable neuromuscular systems are effective vehicles for the study of human nerve and muscle disorders. This is exemplified by insights made into spinal muscular atrophy (SMA) using the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. For speed and economy, these invertebrates offer convenient, whole‐organism platforms for genetic screening as well as RNA interference (RNAi) and chemical library screens, permitting the rapid testing of hypotheses related to disease mechanisms and the exploration of new (...) therapeutic routes and drug candidates. Here, we discuss recent developments encompassing synaptic physiology, RNA processing, and screening of compound and genome‐scale RNAi libraries, showcasing the importance of invertebrate SMA models.Editor's suggested further reading in BioEssays: SMN and Gemins: ‘We are family’... or are we? Abstract. (shrink)

Tuberculosis (TB) is theTuberculosis (TB) second leading infectious cause of mortality worldwide and arguably the most important neglected topic in bioethics. This chapter: (1) explains the ethical importance of TB, (2) documents its neglect in bioethics discourse, (3) maps the terrain of ethical issues associated with TBTuberculosis (TB), and (4) advocates a moderate pluralistic approach to ethical issues associated with TB.

R. C. Sleigh's Leibniz and Arnauld: A Commentary on Their Correspondence is a very good book: it is detailed, clearly written, well argued and attentive to the historical background. The more I read it, the more I enjoyed it and the more I learned. Not only does it offer a wide variety of interesting points for the reader to agree and disagree with, it has, also, the virtue of pretty well forcing the reader to think about the issues involved (...) and their connection with a variety of other philosophical problems. It breaks a good deal of new ground and, as is the way with new ground-breaking, it sometimes only scratches the surface: it points out both the need for further, more detailed investigations and the way in which such investigations might fruitfully proceed. By and large, however, it does a great deal more than scratch the surface: its depth of discussion is such that only a comparably sized book could hope to discuss in all their ramifications the problems raised by Sleigh. (shrink)

While discussing how the grounded theory mediod has been situated during the five moments of qualitative research history, a detailed analysis is offered of die differences between the classic mode of die mediod and Strauss and Corbin's reformulation of the mediod. Such differences include: philosophical perspectives, paradigm of inquiry, intended product, dieoretical underpinnings, procedural steps and claims of rigour. Reasons for Strauss. and Corbin's elaboration of the mediod are suggested, widiin an historical context.

In 2020, the BSHS hosted two major online events, the first of their kind in our collective experience. The first, a Twitter conference, was planned and accomplished before COVID-19 had quite been established as a serious global issue. The conference was planned, rather, as an innovation in travel-free conferencing, something that has been on the BSHS agenda since the IPCC report of 2018, calling for net-zero-carbon activity in all areas by 2050. As we discussed the Twitter conference, and watched the (...) amazing energy, intellect and resourcefulness of its planners and hosts, we quickly saw that online delivery offered other advantages too – chiefly, wider participation. The pandemic offered the society a chance to take these lessons very boldly into the most important event of our scholarly calendar, which usually takes the form of an in-person annual conference, but this time was executed as an online festival. (shrink)

Recent studies indicate that mammalian chromosomes contain discretecis‐acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non‐coding RNA gene ASAR6 results in late replication, an under‐condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono‐allelic expression and asynchronous replication timing. (...) Additional “chromosome engineering” studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain “inactivation/stability centers” that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types ofcis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)

Health research ethics training is highly variable, with some researchers receiving little to none, which is why ethical frameworks represent critical tools for ethical deliberation and guiding responsible practice. However, these documents' voluntary and abstract nature can leave health researchers seeking more operationalised guidance, such as in the form of checklists, even though this approach does not support reflection on the meaning of principles nor their implications. In search of more reflective and participatory practices in a pandemic context with distance (...) learning, this study explored whether co-design could support engagement and reflection on ethical principles amongst early-stage health researchers. In a pilot test using the Swiss Personalized Health Network's ethical framework for Responsible Usage of Personal Data in Health Research as a case study, we engaged health researchers to design visuals of four ethical principles. In two online workshops, participants (N = 10, N = 8) completed activities such as individual reflection, collaborative ideation, sketching, prototyping, discussion, and feedback. Our analysis shows that the co-design process helped foster in-depth engagement and reflection on the meaning and relevance of the SPHN ethical principles. Participants reported enjoying the experience, and most felt that visuals could motivate engagement with ethical frameworks. This study demonstrates the feasibility of a participatory, design-oriented approach to promote engagement with research ethics among early-career health researchers and highlights key challenges and lessons learned. In doing so, it lays the foundation for future research to investigate the impact of design-oriented, participatory learning to foster reflection and deliberation in ethics education. (shrink)

Vaesen infers unique properties of mind from the appearance of specific cultural innovation – a correlation without causal direction. Shifts in habitat, population density, and group dynamics are the only independently verifiable incentives for changes in cultural practices. The transition from Acheulean to Late Stone Age technologies requires that we consider how population and social dynamics affect cultural innovation and mental function.

In numerous texts Leibniz claimed that while metaphysical necessity is inconsistent with free choice, moral necessity is not. A question naturally arises concerning what Leibniz took moral necessity to be. In a series of recent articles Michael Murray has argued that the concept of moral necessity Leibniz utilized is one developed and deployed by a group of 17th century Spanish Jesuits. This chapter argues that Leibniz's commitment to certain deep metaphysical principles suggests otherwise.

Damaris Cudworth, later Lady Masham, was born in 1659 and died in 1708. She was the daughter of Ralph Cudworth, the wife of Sir Francis Masham, and the close friend, confidante, and, ultimately, caretaker of John Locke. Her philosophical writings — and writings to or about philosophers — consist in the following: (1) an account of Locke's life contained in a letter to Jean le Clerc; (2) various letters — mostly personal — to Locke; (3) letters to various other philosophers, (...) including Van Limborch, Shaftesbury, and Leibniz; (4) two monographs, each published anonymously: A Discourse Concerning the Love of God, which appeared in 1696, and Occasional Thoughts in Reference to a Vertuous or Christian Life, which appeared in 1705. This chapter focuses on correspondence between Masham and Leibniz. The correspondence is printed in volume 3 of Gerhardt's Die Philosophischen Schriften von Leibniz. (shrink)

Orthologic is defined by weakening the axioms and rules of inference of the classical propositional calculus. The resulting Lindenbaum-Tarski quotient algebra is an orthoimplication algebra which generalizes the author's implication algebra. The associated order structure is a semi-orthomodular lattice. The theory of orthomodular lattices is obtained by adjoining a falsity symbol to the underlying orthologic or a least element to the orthoimplication algebra.

Background Despite the bourgeoning of digital tools for bioethics research, education, and engagement, little research has empirically investigated the impact of interactive visualizations as a way to translate ethical frameworks and guidelines. To date, most frameworks take the format of text-only documents that outline and offer ethical guidance on specific contexts. This study’s goal was to determine whether an interactive-visual format supports frameworks in transferring ethical knowledge by improving learning, deliberation, and user experience.Methods An experimental comparative study was conducted with (...) a pre-, mid-, and post-test design using the online survey platform Qualtrics. Participants were university based early-stage health researchers who were randomly assigned to either the control condition (text-only document) or the experimental condition (interactive-visual). The primary outcome variables were learning, (measured using a questionnaire), deliberation (using cases studies) and user experience (measured using the SED/UD Scale). Analysis was conducted using descriptive statistics and mixed-effects linear regression.Results Of the 80 participants, 44 (55%) used the text-only document and 36 (45%) used the interactive-visual. Results of the knowledge-test scores showed a statistically significant difference between participants’ post-test scores, indicating that the interactive-visual format better supported understanding, acquisition, and application of the framework’s knowledge. Findings from the case studies showed both formats supported ethical deliberation. Results further indicated the interactive-visual provided an overall better episodic and remembered user experience compared with the text-only document.Conclusions Our findings show that ethical frameworks formatted with interactive and visual qualities provide a more pleasing user experience and are effective formats for ethics learning and deliberation. These findings have implications for practitioners developing and deploying ethical frameworks and guidelines (e.g., in educational or employee-onboarding settings), in that the knowledge generated can lead to more effective dissemination practices of normative guidelines and health data ethics concepts. (shrink)

I appreciate Benson Mates's generous review of my book, and also the editor's willingness to allow me to comment on it. There is one point where Professor Mates attributes to me a view I did not intend to assert, although what I did say is so compressed that even I have had some difficulty divining my intentions. And it may well be that Professor Mates will find the view that I did intend to assert even less satisfactory than the view (...) that he attributes to me, which I did not intend to assert. (shrink)

There is much scholarly disagreement with regard to the program of the Enlightenment. Something in the vicinity of agreement is achievable provided one remains suitably vague. I intend to take advantage of that. One item that seems to me characteristic of the Enlightenment is the general (and admittedly, vague) idea that human reason is the ultimate arbiter in all matters concerning warranted human belief—matters of religion included. And I have no doubt that Leibniz’s philosophizing properly understood, contributes to that general (...) idea. In what follows, I concentrate on some aspects of Leibniz’s thinking that seem to me especially relevant to this theme. (shrink)