Miles, L. | Search bioRxiv

bioRxiv2020

The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation

Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons, removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO signaling. Sensory neuron-specific knockout of Atr in adult mice, or pharmacological inhibition of Atr-Chek1 in mammalian neurons in vitro and in flies in vivo enhance regeneration. Our findings reveal the Piezo-Atr-Chek1-Cdc25 axis as an evolutionarily conserved inhibitory mechanism for regeneration, and identify potential therapeutic targets for treating nervous system trauma.

neuroscience↗

bioRxiv2020

Areas of global importance for terrestrial biodiversity, carbon, and water

Summary paragraphTo meet the ambitious objectives of biodiversity and climate conventions, countries and the international community require clarity on how these objectives can be operationalized spatially, and multiple targets be pursued concurrently1. To support governments and political conventions, spatial guidance is needed to identify which areas should be managed for conservation to generate the greatest synergies between biodiversity and natures contribution to people (NCP). Here we present results from a joint optimization that maximizes improvements in species conservation status, carbon retention and water provisioning and rank terrestrial conservation priorities globally. We found that, selecting the top-ranked 30% (respectively 50%) of areas would conserve 62.4% (86.8%) of the estimated total carbon stock and 67.8% (90.7%) of all clean water provisioning, in addition to improving the conservation status for 69.7% (83.8%) of all species considered. If priority was given to biodiversity only, managing 30% of optimally located land area for conservation may be sufficient to improve the conservation status of 86.3% of plant and vertebrate species on Earth. Our results provide a global baseline on where land could be managed for conservation. We discuss how such a spatial prioritisation framework can support the implementation of the biodiversity and climate conventions.

ecology↗