The ATXN2 gene is located on chromosome 12q24.1 and encodes the ataxin-2 protein, which is involved in the regulation of RNA metabolism, protein synthesis, and intracellular signaling. The CAG tract encoding glutamine can cause expansion, leading to a range of neurodegenerative diseases. Our theoretical results show that expansion of the CAG tract in the ATXN2 gene induces intrinsic mechanical instability at the DNA level. Even under weak, physiologically relevant torsional stress, the expanded CAG region forms collective conformational states and pronounced bending, acting as a structural hot spot. This phenomenon can be considered a novel mechanistic contributor to the development of ataxia type 2 (SCA2). It is important to note that these effects arise without the formation of open states in DNA, suggesting that instability emerges at an earlier stage than those described by known mechanisms. Thus, this mechanism does not replace established RNA- or protein-mediated models of toxicity but rather complements them by accounting for the mechanical contribution to DNA dynamics, which may predispose the ATXN2 locus to genomic instability and pathological progression.
Despite the remarkable successes of molecular biology over the past three quarters of a century, there is growing recognition that organisms must be understood as integrated systems if we are to fully grasp their most distinctive features. Yet considerable uncertainty remains (and, in some quarters, outright skepticism) about how ‘systems thinking’ can actually deepen our understanding of organisms—beyond simply reminding us of such familiar maxims as ‘the whole is more than the sum of its parts’. In this paper, I draw on the largely forgotten organicist ideas of the experimental and theoretical biologist Paul Weiss (1898–1989) to outline a workable, intuitive, and non-formal systems-oriented conception of the organism, and proceed to illustrate its value and effectiveness across a range of explanatory contexts. Specifically, I argue that a proper understanding of the organism as a system—lucidly anticipated by Weiss more than half a century ago—provides the necessary conceptual resources to diagnose and overcome the problems with four prominent doctrines that remain deeply entrenched in contemporary biology: reductionism, genocentrism, determinism, and mechanicism.
While projects in philosophy of science often focus on similar sorts of topics, there are often massive differences in how philosophers approach them. One approach that has enjoyed significant success-and that is modeled in the work of Wimsatt and others-involves taking a conceptual engineering perspective in analyzing these topics. In this paper, we outline main features of this conceptual engineering approach and use it to advance three emerging claims regarding causal explanation in biology and neuroscience. We suggest that causal explanation in these domains is non-reductive in contrast to always requiring (or improving with) lower-level details, that it is guided by precise explanatory targets in contrast to complete or multidimensional explanatory targets, and that it is pluralist in involving importantly distinct types of causal systems.
This article examines neoteny and regressive evolution in two emblematic amphibian species: Ambystoma mexicanum (axolotl) and Proteus anguinus (olm). Rather than framing larval persistence and trait loss as evolutionary shortcomings, the paper proposes an alternative interpretation in which developmental arrest functions as a viable population-level outcome of selection under specific ecological constraints, rather than as a developmental shortcoming. Drawing on evo-devo literature, endocrine regulation of metamorphosis, and comparative life-history analysis, the study argues that both species exemplify non-teleological evolutionary pathways. By foregrounding strategy over deficiency, the article contributes to broader debates on normativity, progress, and directionality in evolutionary biology.
