Hierarchy or Heterarchy of Mammalian Circadian Timekeepers?

Mammalian circadian biologists commonly characterize the relation between circadian clocks as hierarchical, with the clock in the suprachiasmatic nucleus at the top of the hierarchy. The lineage of research since the suprachiasmatic nucleus (SCN) was first identified as in mammals has challenged this perspective, revealing clocks in peripheral tissues, showing that they respond to their own zeitgebers, coordinate oscillations among themselves, and in some cases modify the behavior of the SCN. Increasingly circadian timekeepers appear to constitute a heterarchical network, with control distributed and operating along multiple pathways.

Minding the gap: discovering the phenomenon of chemical transmission in the nervous system.

The neuron doctrine, according to which nerves consist of discontinuous neurons, presented investigators with the challenge of determining what activities occurred between them or between them and muscles. One group of researchers, dubbed the sparks, viewed the electrical current in one neuron as inducing a current in the next neuron or in muscles. For them there was no gap between the activities of neurons or neurons and muscles that required filling with a new type of activity.

Using neurons to maintain autonomy: Learning from C. elegans.

Understanding how biological organisms are autonomous-maintain themselves far from equilibrium through their own activities-requires understanding how they regulate those activities. In multicellular animals, such control can be exercised either via endocrine signaling through the vasculature or via neurons. In C.

Discovering autoinhibition as a design principle for the control of biological mechanisms.

Autoinhibition is a design principle realized in many molecular mechanisms in biology. After explicating the notion of a design principle and showing that autoinhibition is such a principle, we focus on how researchers discovered instances of autoinhibition, using research establishing the autoinhibition of the molecular motors kinesin and dynein as our case study. Research on kinesin and dynein began in the fashion described in accounts of mechanistic explanation but, once the mechanisms had been discovered, researchers discovered that they exhibited a second phenomenon, autoinhibition.