What can polysemy tell us about theories of explanation?

Philosophical accounts of scientific explanation are broadly divided into ontic and epistemic views. This paper explores the idea that the lexical ambiguity of the verb to explain and its nominalisation supports an ontic conception of explanation. I analyse one argument which challenges this strategy by criticising the claim that explanatory talk is lexically ambiguous, 375–394, 2012). I propose that the linguistic mechanism of transfer of meaning, 109–132, 1995) provides a better account of the lexical alternations that figure in the systematic polysemy of explanatory talk, and evaluate the implications of this proposal for the debate between ontic and epistemic conceptions of scientific explanation

Agency, qualia and life: connecting mind and body biologically

Many believe that a suitably programmed computer could act for its own goals and experience feelings. I challenge this view and argue that agency, mental causation and qualia are all founded in the unique, homeostatic nature of living matter. The theory was formulated for coherence with the concept of an agent, neuroscientific data and laws of physics. By this method, I infer that a successful action is homeostatic for its agent and can be caused by a feeling - which does not motivate as a force, but as a control signal. From brain research and the locality principle of physics, I surmise that qualia are a fundamental, biological form of energy generated in specialized neurons. Subjectivity is explained as thermodynamically necessary on the supposition that, by converting action potentials to feelings, the neural cells avert damage from the electrochemical pulses. In exchange for this entropic benefit, phenomenal energy is spent as and where it is produced - which precludes the objective observation of qualia

Potentiality in Biology

We take the potentialities that are studied in the biological sciences (e.g., totipotency) to be an important subtype of biological dispositions. The goal of this paper is twofold: first, we want to provide a detailed understanding of what biological dispositions are. We claim that two features are essential for dispositions in biology: the importance of the manifestation process and the diversity of conditions that need to be satisfied for the disposition to be manifest. Second, we demonstrate that the concept of a disposition (or potentiality) is a very useful tool for the analysis of the explanatory practice in the biological sciences. On the one hand it allows an in-depth analysis of the nature and diversity of the conditions under which biological systems display specific behaviors. On the other hand the concept of a disposition may serve a unificatory role in the philosophy of the natural sciences since it captures not only the explanatory practice of biology, but of all natural sciences. Towards the end we will briefly come back to the notion of a potentiality in biology

Neuromuscular recovery from botulism involves multiple forms of compensatory plasticity

IntroductionBotulinum neurotoxin (BoNT) causes neuroparalytic disease and death by blocking neuromuscular transmission. There are no specific therapies for clinical botulism and the only treatment option is supportive care until neuromuscular function spontaneously recovers, which can take weeks or months after exposure. The highly specialized neuromuscular junction (NMJ) between phrenic motor neurons and diaphragm muscle fibers is the main clinical target of BoNT. Due to the difficulty in eliciting respiratory paralysis without a high mortality rate, few studies have characterized the neurophysiological mechanisms involved in diaphragm recovery from intoxication. Here, we develop a mouse model of botulism that involves partial paralysis of respiratory muscles with low mortality rates, allowing for longitudinal analysis of recovery.Methods and resultsMice challenged by systemic administration of 0.7 LD50 BoNT/A developed physiological signs of botulism, such as respiratory depression and reduced voluntary running activity, that persisted for an average of 8–12 d. Studies in isolated hemidiaphragm preparations from intoxicated mice revealed profound reductions in nerve-elicited, tetanic and twitch muscle contraction strengths that recovered to baseline 21 d after intoxication. Despite apparent functional recovery, neurophysiological parameters remained depressed for 28 d, including end plate potential (EPP) amplitude, EPP success rate, quantal content (QC), and miniature EPP (mEPP) frequency. However, QC recovered more quickly than mEPP frequency, which could explain the discrepancy between muscle function studies and neurophysiological recordings. Hypothesizing that differential modulation of voltage-gated calcium channels (VGCC) contributed to the uncoupling of QC from mEPP frequency, pharmacological inhibition studies were used to study the contributions of different VGCCs to neurophysiological function. We found that N-type VGCC and P/Q-type VGCC partially restored QC but not mEPP frequency during recovery from paralysis, potentially explaining the accelerated recovery of evoked release versus spontaneous release. We identified additional changes that presumably compensate for reduced acetylcholine release during recovery, including increased depolarization of muscle fiber resting membrane potential and increased quantal size.DiscussionIn addition to identifying multiple forms of compensatory plasticity that occur in response to reduced NMJ function, it is expected that insights into the molecular mechanisms involved in recovery from neuromuscular paralysis will support new host-targeted treatments for multiple neuromuscular diseases

Long-Term Potentiation: One Kind or Many?

Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation (LTP). I argue that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds

MICRO-Foundations in Strategic Management: Squaring Coleman's Diagram

Abell, Felin and Foss argue that "macro-explanations" in strategic management, explanations in which organizational routines figure prominently and in which both the explanandum and explanans are at the macro-level, are necessarily incomplete. They take a diagram (which has the form of a trapezoid) from Coleman, Foundations of Social Theory, The Belknap Press of Harvard University Press, Cambridge (Mass.)/London, (1990) to task to show that causal chains connecting two macro-phenomena always involve "macro-to-micro" and "micro-to-macro" links, links that macro-explanations allegedly fail to recognize. Their plea for micro-foundations in strategic management is meant to shed light on these "missing links". The paper argues that while there are good reasons for providing micro-foundations, Abell, Felin and Foss's causal incompleteness argument is not one of them. Their argument does not sufficiently distinguish between causal and constitutive relations. Once these relations are carefully distinguished, it follows that Coleman's diagram has to be squared. This in turn allows us to see that macro-explanations need not be incomplete

A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein

The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection

Knowledge, science and death: the theory of brain-sign

In today’s paradigmatic climate, the possibility of knowledge, and therefore science, still depends upon our being conscious. However, no scientifically accepted account of consciousness exists. In recent years I have developed the theory of brain-sign which replaces consciousness as a wholly physical neural condition. The first tenet is that the brain is a causal organ, not a knowledge organ. The second is that brain-sign, used in inter-neural communication for uncertain or imprecise collective action, derives at each moment from the causal orientation of the brain. Signs are ubiquitous bio-physical entities. Thus there is no problematic dualism, consciousness and world. We now have two accounts of the brain phenomenon. The first (consciousness) is an inexplicable physical anomaly. The second (brain-sign) belongs in the physical universe, and fulfils a crucial neurobiological function. With brain-sign theory we even ‘discover’ that we do not know we are alive or will die