Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function

Abuse of alcohol is a major clinical problem with far- reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol- related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast- induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet- induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol- related behavior in other species.Flies fed a high yeast diet consume more nutrients, have decreased levels of internal ethanol when exposed to ethanol vapor and require longer exposure to ethanol to become sedated (ie, increased ST50). Our studies implicate serotonergic neurons as key regulators of nutrient consumption and therefore, the effect of dietary yeast on ethanol sedation in flies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/1/adb12779.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/2/adb12779_am.pd

Developing a Deletion Construct of the \u3ci\u3eHalothiobacillus neapolitanus\u3c/i\u3e csoS1C Gene

The purpose of this research was to develop a deletion construct for the chemoautotrophic bacterium Halothiobacillus neapolitanus, which will be used to generate a mutant lacking a carboxysome shell protein gene. The carboxysome is the location of carbon dioxide fixation. The operon that encodes the carboxysome contains three genes for CsoS1 proteins, the major components of the carboxysome shell. The small CsoS1 proteins self-assemble into hexamers with small central pores. The hexamers arrange into the facets of the icosahedral carboxysome shell. The pores are believed to be involved in selective diffusion of materials necessary for carbon dioxide fixation across the shell. A deletion construct to replace the csoS1C gene with a kanamycin resistance cassette was designed that will allow gene replacement by homologous recombination to determine if the csoS1C paralog is necessary to form functional carboxysomes. This deletion construct will allow the function of this paralog to be studied in the resulting mutant. To develop the construct, primers were designed to amplify the kanamycin resistance gene with short ends that are homologous to regions flanking the csoS1C gene in the H. neapolitanus genome. E. coli DY330 was transformed with the amplified resistance cassette and a plasmid containing the csoS1C region of genomic DNA for homologous recombination that will yield the deletion construct

Pancreatic Pain-Knowledge Gaps and Research Opportunities in Children and Adults:Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop

AbstractA workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered

Correction to: Pain experience in pancreatitis: Strong association of genetic risk loci for anxiety and PTSD in patients With severe, constant, and constant-severe pain

INTRODUCTION: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects. METHODS: The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study. RESULTS: We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP (P \u3c 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations (P \u3c 4.885 × 10-23). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling (HTR2A, DRD3, NPY, and BDNF), hypothalamic-pituitary-adrenal axis (NR3C1 and FKBP5), and cell-cell interaction (CTNND2 and THBS2). DISCUSSION: A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated