A gene network involving Notch and Pros underlies the glial regenerative response to injury in the Drosophila central nervous system.

Neurotrophin receptors corresponding to vertebrate Trk, p75NTR or Sortilin have not been identified in Drosophila, thus it is unknown how neurotrophism may be implemented in insects. Two Drosophila neurotrophins, DNT1 and DNT2, have nervous system functions, but their receptors are unknown. The Toll receptor superfamily has ancient evolutionary origins and a universal function in innate immunity. Here we show that Toll paralogues unrelated to the mammalian neurotrophin receptors function as neurotrophin receptors in fruit-flies. Toll-6 and Toll-7 are expressed in the central nervous system throughout development, and regulate locomotion, motoraxon targeting and neuronal survival. DNT1 and 2 interact genetically with Toll-6 and 7, bind to Toll-7 and 6 promiscuously, and are distributed in vivo in complementary or overlapping domains. We conclude that in fruit-flies, Tolls are not only involved in development and immunity but also in neurotrophism, revealing an unforeseen relationship between the neurotrophin and Toll protein families.

Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects. By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spätzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases.

We present a detailed report of microwave irradiation of ultranarrow superconducting nanowires. In our nanofabricated circuits containing a superconducting NbSi nanowire, a dc blockade of current flow was observed at low temperatures below a critical voltage V c , a strong indicator of the existence of quantum phase-slip (QPS) in the nanowire. We describe the results of applying microwaves to these samples, using a range of frequencies and both continuous-wave and pulsed drive, in order to search for dual Shapiro steps which would constitute an unambiguous demonstration of quantum phase-slip. We observed no steps, and our subsequent thermal analysis suggests that the electron temperature in the series CrO resistors was significantly elevated above the substrate temperature, resulting in sufficient Johnson noise to wash out the steps. To understand the system and inform future work, we have constructed a numerical model of the dynamics of the circuit for dc and ac bias (both continuous-wave and pulsed drive signals) in the presence of Johnson noise. Using this model, we outline important design considerations for device and measurement parameters which should be used in any future experiment to enable the observation of dual Shapiro steps at experimentally accessible temperatures and, thus, lead to the development of a QPS-based quantum current standard.