Fibronectin in tissue regeneration: timely disassembly of the scaffold is necessary to complete the build

Tissue injury initiates extracellular matrix molecule expression, including fibronectin production by local cells and fibronectin leakage from plasma. To benefit tissue regeneration, fibronectin promotes opsonization of tissue debris, migration, proliferation, and contraction of cells involved in the healing process, as well as angiogenesis. When regeneration proceeds, the fibronectin matrix is fully degraded. However, in a diseased environment, fibronectin clearance is often disturbed, allowing structural variants to persist and contribute to disease progression and failure of regeneration. Here, we discuss first how fibronectin helps tissue regeneration, with a focus on normal cutaneous wound healing as an example of complete tissue recovery. Then, we continue to argue that, although the fibronectin matrix generated following cartilage and central nervous system white matter (myelin) injury initially benefits regeneration, fibronectin clearance is incomplete in chronic wounds (skin), osteoarthritis (cartilage), and multiple sclerosis (myelin). Fibronectin fragments or aggregates persist, which impair tissue regeneration. The similarities in fibronectin-mediated mechanisms of frustrated regeneration indicate that complete fibronectin clearance is a prerequisite for recovery in any tissue. Also, they provide common targets for developing therapeutic strategies in regenerative medicine.     

How to infer explanations from computer simulations

Computer simulations are involved in numerous branches of modern science, and science would not be the same without them. Yet the question of how they can explain real-world processes remains an issue of considerable debate. In this context, a range of authors have highlighted the inferences back to the world that computer simulations allow us to draw. I will first characterize the precise relation between computer and target of a simulation that allows us to draw such inferences. I then argue that in a range of scientifically interesting cases they are particular abductions and defend this claim by appeal to two case studies.     

How to think about analogical inferences: A reply to Norton

In this paper, I raise some worries with John D. Norton's application of his material theory of induction to the study of analogical inferences. Skeptical that these worries can be properly addressed, I propose a principle to guide the philosophical research on analogical inferences and argue for its usefulness.     

A micro-electrode amplifier with an infinite resistance current source for intracellular measurements of membrane potential and resistance changes under current clamp

Summary A microelectrode amplifier for intracellular electrophysiological research is described. It is equipped with an electronic infinite resistance constant current source for the injection of current into biological cells. With this amplifier the potential changes, the resistance changes and the dependence on extrinsic current of single cells can be measured independently and simultaneously.Acknowledgments. I am grateful to Dr D.G. Stavenga who inspired me to start the design. I thank P. Cuperus for stimulating discussions and A.J.Th. Liebrand for the construction of the amplifier. This work was supported financially by the Netherlands Organisation for the Advancement of Pure Research (Z.W.O.).     

A micro-electrode amplifier with an infinite resistance current source for intracellular measurements of membrane potential and resistance changes under current clamp.

A microelectrode amplifier for intracellular electrophysiological research is described. It is equipped with an electronic infinite resistance constant current source for the injection of current into biological cells. With this amplifier the potential changes, the resistance changes and the dependence on extrinsic current of single cells can be measured independently and simultaneously.     

How to (properly) strengthen Bell's theorem using counterfactuals

Bell's theorem in its standard version demonstrates that the joint assumptions of the hidden-variable hypothesis and the principle of local causation lead to a conflict with quantum-mechanical predictions. In his latest counterfactual strengthening of Bell's theorem, Stapp attempts to prove that the locality assumption itself contradicts the quantum-mechanical predictions in the Hardy case. His method relies on constructing a complex, non-truth functional formula which consists of statements about measurements and outcomes in some region R, and whose truth value depends on the selection of a measurement setting in a space-like separated location L. Stapp argues that this fact shows that the information about the measurement selection made in L has to be present in R. I give detailed reasons why this conclusion can and should be resisted. Next I correct and formalize an informal argument by Shimony and Stein showing that the locality condition coupled with Einstein's criterion of reality is inconsistent with quantum-mechanical predictions. I discuss the possibility of avoiding the inconsistency by rejecting Einstein's criterion rather than the locality assumption.     

How to avoid maternal cannibalism after neonatal surgery in rats

Summary Following surgery newborn rats are often eaten by their mothers. This can be avoided if the wound is closed carefully, the blood removed from the skin, and the wound area covered by a plastic film.     

How to make value-driven climate science for policy more ethical

In previous works, I examine inferential methods employed in Probabilistic Weather Event Attribution studies (PEAs), and explored various ways they can be used to aid in climate policy decisions and decision-making about climate justice issues. This paper evaluates limitations of PEAs and considers how PEA researchers’ attributions of “liability” to specific countries for specific extreme weather events could be made more ethical. In sum, I show that it is routinely presupposed that PEA methods are not prone to inductive risks and presuppose that PEA researchers thus have no epistemic consequences or responsibilities for their attributions of liability. I argue that although PEAs are nevertheless crucially useful for practical decision-making, the attributions of liability made by PEA researchers are in fact prone to indicative risks and are influenced by non-epistemic values that PEA researchers should make transparent to make such studies more ethical. Finally, I outline possible normative approaches for making sciences, including PEAs, more ethical; and discuss implications of my arguments for the ongoing debate about how PEAs should guide climate policy and relevant legal decisions.     

How to halve ploidy: lessons from budding yeast meiosis

Maintenance of ploidy in sexually reproducing organisms requires a specialized form of cell division called meiosis that generates genetically diverse haploid gametes from diploid germ cells. Meiotic cells halve their ploidy by undergoing two rounds of nuclear division (meiosis I and II) after a single round of DNA replication. Research in Saccharomyces cerevisiae (budding yeast) has shown that four major deviations from the mitotic cell cycle during meiosis are essential for halving ploidy. The deviations are (1) formation of a link between homologous chromosomes by crossover, (2) monopolar attachment of sister kinetochores during meiosis I, (3) protection of centromeric cohesion during meiosis I, and (4) suppression of DNA replication following exit from meiosis I. In this review we present the current understanding of the above four processes in budding yeast and examine the possible conservation of molecular mechanisms from yeast to humans.     

How to view stereoscopic pictures of crystal structures and molecular models

Summary Methods are presented for practicing the viewing of stereoscopic pictures of crystal structures and molecular models without optical aids.     

How to view stereoscopic pictures of crystal structures and molecular models

Methods are presented for practicing the viewing of stereoscopic pictures of crystal structures and molecular models without optical aids.     

How not to integrate the history and philosophy of science: a reply to Chalmers

Alan Chalmers uses Robert Boyle’s mechanical philosophy as an example of the irrelevance of ‘philosophy’ to ‘science’ and criticizes my 2006 book Atoms and alchemy for overemphasizing Boyle’s successes. The present paper responds as follows: first, it argues that Chalmers employs an overly simplistic methodology insensitive to the distinction between historical and philosophical claims; second, it shows that the central theses of Atoms and alchemy are untouched by Chalmers’s criticisms; and third, it uses Boyle’s analysis of subordinate causes and his debate with Henry More in the 1670s to demonstrate the inadequacy of Chalmers’s construal of the mechanical philosophy.