Evaluation of plasma activity of matrix metalloproteinase-2 and -9 in dogs with myxomatous mitral valve disease

To investigate whether plasma activity of matrix metalloproteinase (MMP)-2 and -9 was associated with severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between MMP activity and dog characteristics, echocardiographic variables, systolic arterial blood pressure (SAP), heart rate, cardiac troponin I (cTnI) concentration, and C-reactive protein concentration. ANIMALS: 75 client-owned dogs. PROCEDURES: Severity of MMVD was assessed by use of echocardiography. Plasma activity of latent (pro-MMP) and active MMP-2 and -9 was analyzed via zymography. Plasma concentration of cTnI was analyzed with a high-sensitivity cTnI assay, and C-reactive protein concentration was analyzed with a canine-specific ELISA. RESULTS: Pro-MMP-9, active MMP-9, and pro-MMP-2 were detected, but active MMP-2 was not. No significant differences were found in MMP concentrations among the 4 MMVD severity groups. Activity of pro-MMP-9 decreased with decreases in SAP and was higher in male dogs than in female dogs. Activity of MMP-9 decreased with increases in left ventricular end-systolic dimension and with decreases in SAP and cTnI concentration. Left ventricular end-systolic dimension was the variable most strongly associated with MMP-9 activity. No associations were found between the activity of pro-MMP-2 and investigated variables. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma MMP-9 activity decreased with increases in the end-systolic left ventricular internal dimension and decreases in SAP. Hence, evaluation of MMP-9 activity has the potential to provide unique information about the myocardial remodeling process in dogs with MMVD

The structure of idealization in biological theories: the case of the Wright-Fisher model.

In this paper we present a new framework of idealization in biology. We characterize idealizations as a network of counterfactual and hypothetical conditionals that can exhibit different “degrees of contingency”. We use this idea to say that, in departing more or less from the actual world, idealizations can serve numerous epistemic, methodological or heuristic purposes within scientific research. We defend that, in part, this structure explains why idealizations, despite being deformations of reality, are so successful in scientific practice. For illustrative purposes, we provide an example from population genetics, the Wright-Fisher Mode

Introduction to Special Issue on 'Actual Causation'

An actual cause of some token effect is itself a (distinct) token event (or fact, or state of affairs, …) that helped to bring about that effect. The notion of an actual cause is different from that of a potential cause – for example a pre-empted backup – which had the capacity to bring about the effect, but which wasn't in fact operative on the occasion in question. Sometimes actual causes are also distinguished from mere background conditions: as when we judge that the struck match was a cause of the fire, while the presence of oxygen was merely part of the relevant background against which the struck match operated. Actual causation is also to be distinguished from type causation: actual causation holds between token events in a particular, concrete scenario; type causation, by contrast, holds between event kinds in scenario kinds