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

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

Causality, Teleology, and Thought Experiments in Biology

Thought experiments de facto play many different roles in biology: economical, ethical, technical and so forth. This paper, however, is interested in whether there are any distinctive features of biological TEs as such. The question may be settled in the affirmative because TEs in biology have a function that is intimately connected with the epistemological and methodological status of biology. Peculiar to TEs in biology is the fact that the reflexive, typically human concept of finality may be profitably employed to discover mechanical-experimental causal relations in all living beings\u2014with the obvious caveat that we do not hypostatise and interpret this concept as an ontological quality, since this would land one in an implicitly animistic, pre-Galilean view of nature. From a methodical point of view, the concept of finality is an essential assumption as well as a powerful heuristic tool in the practice of biology, that is, in the investigation of living beings in an intersubjectively testable and reproducible way