Epigenetics, Responsiveness and Embodiment

This short paper comments on the connections between epigenetics, responsiveness and embodiment. Epigenetics has solidified a new conception of DNA as “responsive,” and rightfully so. Yet, the discussion too easily falls back to metaphors of agency and can show a tendency to see responsiveness and embodiment as based on epigenetics, which is shown to be wrong

A Metalloproteinase Secreted by Streptococcus pneumoniae Removes Membrane Mucin MUC16 from the Epithelial Glycocalyx Barrier

The majority of bacterial infections occur across wet-surfaced mucosal epithelia, including those that cover the eye, respiratory tract, gastrointestinal tract and genitourinary tract. The apical surface of all these mucosal epithelia is covered by a heavily glycosylated glycocalyx, a major component of which are membrane-associated mucins (MAMs). MAMs form a barrier that serves as one of the first lines of defense against invading bacteria. While opportunistic bacteria rely on pre-existing defects or wounds to gain entry to epithelia, non opportunistic bacteria, especially the epidemic disease-causing ones, gain access to epithelial cells without evidence of predisposing injury. The molecular mechanisms employed by these non opportunistic pathogens to breach the MAM barrier remain unknown. To test the hypothesis that disease-causing non opportunistic bacteria gain access to the epithelium by removal of MAMs, corneal, conjunctival, and tracheobronchial epithelial cells, cultured to differentiate to express the MAMs, MUCs 1, 4, and 16, were exposed to a non encapsulated, non typeable strain of Streptococcus pneumoniae (SP168), which causes epidemic conjunctivitis. The ability of strain SP168 to induce MAM ectodomain release from epithelia was compared to that of other strains of S. pneumoniae, as well as the opportunistic pathogen Staphylococcus aureus. The experiments reported herein demonstrate that the epidemic disease-causing S. pneumoniae species secretes a metalloproteinase, ZmpC, which selectively induces ectodomain shedding of the MAM MUC16. Furthermore, ZmpC-induced removal of MUC16 from the epithelium leads to loss of the glycocalyx barrier function and enhanced internalization of the bacterium. These data suggest that removal of MAMs by bacterial enzymes may be an important virulence mechanism employed by disease-causing non opportunistic bacteria to gain access to epithelial cells to cause infection

In defence of activities

In this paper, we examine what is to be said in defence of Machamer, Darden and Craver’s (MDC) controversial dualism about activities and entities (Machamer, Darden and Craver’s in Philos Sci 67:1–25, 2000). We explain why we believe the notion of an activity to be a novel, valuable one, and set about clearing away some initial objections that can lead to its being brushed aside unexamined. We argue that substantive debate about ontology can only be effective when desiderata for an ontology are explicitly articulated. We distinguish three such desiderata. The first is a more permissive descriptive ontology of science, the second a more reductive ontology prioritising understanding, and the third a more reductive ontology prioritising minimalism. We compare MDC’s entities-activities ontology to its closest rival, the entities-capacities ontology, and argue that the entities-activities ontology does better on all three desiderata

Beyond quantitative and qualitative traits: three telling cases in the life sciences

This paper challenges the common assumption that some phenotypic traits are quantitative while others are qualitative. The distinction between these two kinds of traits is widely influential in biological and biomedical research as well as in scientific education and communication. This is probably due to both historical and epistemological reasons. However, the quantitative/qualitative distinction involves a variety of simplifications on the genetic causes of phenotypic variability and on the development of complex traits. Here, I examine three cases from the life sciences that show inconsistencies in the distinction: Mendelian traits (dwarfism and pigmentation in plant and animal models), Mendelian diseases (phenylketonuria), and polygenic mental disorders (schizophrenia). I show that these traits can be framed both quantitatively and qualitatively depending, for instance, on the methods through which they are investigated and on specific epistemic purposes (e.g., clinical diagnosis versus causal explanation). This suggests that the received view of quantitative and qualitative traits has a limited heuristic power—limited to some local contexts or to the specific methodologies adopted. Throughout the paper, I provide directions for framing phenotypes beyond the quantitative/qualitative distinction. I conclude by pointing at the necessity of developing a principled characterisation of what phenotypic traits, in general, are

DSM-5 and Psychiatry's Second Revolution: Descriptive vs. Theoretical Approaches to Psychiatric Classification

A large part of the controversy surrounding the publication of DSM-5 stems from the possibility of replacing the purely descriptive approach to classification favored by the DSM since 1980. This paper examines the question of how mental disorders should be classified, focusing on the issue of whether the DSM should adopt a purely descriptive or theoretical approach. I argue that the DSM should replace its purely descriptive approach with a theoretical approach that integrates causal information into the DSM’s descriptive diagnostic categories. The paper proceeds in three sections. In the first section, I examine the goals (viz., guiding treatment, facilitating research, and improving communication) associated with the DSM’s purely descriptive approach. In the second section, I suggest that the DSM’s purely descriptive approach is best suited for improving communication among mental health professionals; however, theoretical approaches would be superior for purposes of treatment and research. In the third section, I outline steps required to move the DSM towards a hybrid system of classification that can accommodate the benefits of descriptive and theoretical approaches, and I discuss how the DSM’s descriptive categories could be revised to incorporate theoretical information regarding the causes of disorders. I argue that the DSM should reconceive of its goals more narrowly such that it functions primarily as an epistemic hub that mediates among various contexts of use in which definitions of mental disorders appear. My analysis emphasizes the importance of pluralism as a methodological means for avoiding theoretical dogmatism and ensuring that the DSM is a reflexive and self-correcting manual

The Case for Regularity in Mechanistic Causal Explanation

How regular do mechanisms need to be, in order to count as mechanisms? This paper addresses two arguments for dropping the requirement of regularity from the definition of a mechanism, one motivated by examples from the sciences and the other motivated by metaphysical considerations regarding causation. I defend a broad- ened regularity requirement on mechanisms that takes the form of a taxonomy of kinds of regularity that mechanisms may exhibit. This taxonomy allows precise explication of the degree and location of regular operation within a mechanism, and highlights the role that various kinds of regularity play in scientific explanation. I defend this reg- ularity requirement in terms of regularity’s role in individuating mechanisms against a background of other causal processes, and by prioritizing mechanisms’ ability to serve as a model of scientific explanation, rather than as a metaphysical account of causation. It is because mechanisms are regular, in the expanded sense described here, that they are capable of supporting the kinds of generalizations that figure prominently in scientific explanations