The regulation of ribosome function is a conserved mechanism of growth control. While studies in single cell systems have defined how ribosomes contribute to cell growth, the mechanisms that link ribosome function to organismal growth are less clear. Here we explore this issue using Drosophila Minutes, a class of heterozygous mutants for ribosomal proteins. These animals exhibit a delay in larval development caused by decreased production of the steroid hormone ecdysone, the main regulator of larval maturation. We found that this developmental delay is not caused by decreases in either global ribosome numbers or translation rates. Instead, we show that they are due in part to loss of Rp function specifically in a subset of serotonin (5-HT) neurons that innervate the prothoracic gland to control ecdysone production. We find that these effects do not occur due to altered protein synthesis or proteostasis, but that Minute animals have reduced expression of synaptotagmin, a synaptic vesicle protein, and that the Minute developmental delay can be partially reversed by overexpression of synaptic vesicle proteins in 5-HTergic cells. These results identify a 5-HT cell-specific role for ribosomal function in the neuroendocrine control of animal growth and development.

No abstract

The regulation of ribosome function is a conserved mechanism of growth control. While studies in single cell systems have defined how ribosomes contribute to cell growth, the mechanisms that link ribosome function to organismal growth are less clear. Here we explore this issue using Drosophila Minutes, a class of heterozygous mutants for ribosomal proteins (Rps). These animals exhibit a delay in larval development caused by decreased production of the steroid hormone ecdysone, the main regulator of larval maturation. We found that this developmental delay is not caused by decreases in either global ribosome numbers or translation rates. Instead, we show that they are due in part to loss of Rp function specifically in a subset of serotonin (5-HT) neurons that innervate the prothoracic gland to control ecdysone production. We found that these 5-HT neurons have defective secretion in Minute animals, and that overexpression of synaptic vesicle proteins in 5-HTergic cells can partially reverse the Minute developmental delay. These results identify a cell-specific role for ribosomal function in the neuroendocrine control of animal growth and development.

A clinical case is presented for a patient in sustained remission from opioid use disorder following 12 months of evidence-based treatment who faces deportation due to criminal behavior conducted whilst in active and untreated addiction. A review of the criminal justice and addiction literature suggests that the chance of relapse and recidivism to criminal behavior is low when engaged in evidence-based addiction treatment for over 12 months. Deportation has been shown to disrupt recovery activity and increase recidivism and relapse risk. As addiction is widely now understood to be a disease based in neurobiology, and treatable, we believe that the evidence supports our assertion of deportation as a cruel and unjust treatment of a chronic disease.