Retinoic acid, the active metabolite of Vitamin A, is important for the appropriate development of the nervous system (e.g., neurite outgrowth) as well as for cognition (e.g., memory formation) in the adult brain. We have shown that many of the effects of retinoids are conserved in the CNS of the mollusc, Lymnaea stagnalis. RXRs are predominantly nuclear receptors, but the Lymnaea RXR (LymRXR) exhibits a non-nuclear distribution in the adult CNS, where it is also implicated in non-genomic retinoid functions. As such, we developed a CNS Drosophila organ culture-based system to examine the transcriptional activity and ligand-binding properties of LymRXR, in the context of a live invertebrate nervous system. The novel ligand sensor system was capable of reporting both the expression and transcriptional activity of the sensor. Our results indicate that the LymRXR ligand sensor mediated transcription following activation by both 9-cis RA (the high affinity ligand for vertebrate RXRs) as well as the vertebrate RXR synthetic agonist, SR11237. The LymRXR ligand sensor was also activated by all-trans RA, and to a much lesser extent by the vertebrate RAR synthetic agonist, EC23. This sensor also detected endogenous retinoid-like activity in the CNS of developing Drosophila larvae, primarily during the 3rd instar larval stage. These data indicate that the LymRXR sensor can be utilized not only for characterization of ligand activation for studies related to the Lymnaea CNS, but also for future studies of retinoids and their functions in Drosophila development.

The Notch receptor is a titratable, context-specific counter of intercellular interactions that translates productive interactions with ligands on neighbouring cells into corresponding changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using an Optogenetic Notch1 construct in combination with a live imaging transcriptional reporter and super-resolution imaging, we show that the N1ICD activates gene expression through spontaneous self-assembly into transcriptional condensates whose phase separation is driven by C-terminal Intrinsically Disordered Regions (IDR) of the N1ICD. N1ICD condensates recruit and encapsulate a broad set of core transcriptional proteins, thereby facilitating gene expression and promoting super enhancer-looping. We produced a model of Notch1 activity, whereby discrete changes in nuclear NICD abundance is translated into precise changes in target gene expression through the assembly of phase separated N1ICD molecular crucibles that catalyze gene expression in a concentration-dependent manner by enriching essential transcriptional machineries at target genomic loci.

[RETRACTED]Might it be said that they are protected? Would I be able to truly eat the entirety of the cheddar and meat I need ? Will I bite the dust assuming I go into ketosis?

Might it be said that they are protected? Would I be able to truly eat the entirety of the cheddar and meat I need ? Will I bite the dust assuming I go into ketosis?