Luciferin Amides Enable in Vivo Bioluminescence Detection of Endogenous Fatty Acid Amide Hydrolase Activity

Firefly luciferase is homologous to fatty acyl-CoA synthetases. We hypothesized that the firefly luciferase substrate d-luciferin and its analogs are fatty acid mimics that are ideally suited to probe the chemistry of enzymes that release fatty acid products. Here, we synthesized luciferin amides and found that these molecules are hydrolyzed to substrates for firefly luciferase by the enzyme fatty acid amide hydrolase (FAAH). In the presence of luciferase, these molecules enable highly sensitive and selective bioluminescent detection of FAAH activity in vitro, in live cells, and in vivo. The potency and tissue distribution of FAAH inhibitors can be imaged in live mice, and luciferin amides serve as exemplary reagents for greatly improved bioluminescence imaging in FAAH-expressing tissues such as the brain

Alcohol And Cannabis Use Among Women With Infertility: Associations With Psychological Distress, Attempts To Conceive, And Engagement In Fertility Treatment

Objective: An infertility diagnosis can lead to distress. Although substance use is common and can also lead to distress, little is known about use among those with an infertility diagnosis. This is important since substance use can have implications for fertility. The purpose of this study was to estimate the rate of alcohol and cannabis use among women with infertility and examine whether substance use had associations with psychiatric symptoms, attempts to conceive, and engagement in fertility treatments. Materials and Methods: Patients from one healthcare system were eligible if they received a female infertility diagnosis within the past 2 years. Participants (N=188) completed an online questionnaire on their alcohol use, cannabis use, and psychiatric symptoms. Results: The rates of hazardous alcohol use, any cannabis use, and hazardous cannabis use were 30.3%, 30.9%, and 8.5%, respectively. Hazardous alcohol use was not associated with depression or anxiety (p’s\u3e .05). Those with any cannabis use were more likely to have higher depression scores than those without (p= .02). Those with hazardous cannabis use were also more likely to have higher depression scores (p= .001) and higher anxiety scores (p= .03). Substance use was not associated with actively trying to conceive. However, participants pursuing fertility treatments were less likely to engage in hazardous alcohol use (p= .02). Conclusion: Cannabis use was associated with depression and anxiety scores, suggesting that cannabis may be used for coping. Though many women engage in hazardous alcohol or cannabis use, pursuing fertility treatments may serve as a protective factor

Firefly genomes illuminate parallel origins of bioluminescence in beetles

Fireflies and their luminous courtships have inspired centuries of scientific study. Today firefly luciferase is widely used in biotechnology, but the evolutionary origin of bioluminescence within beetles remains unclear. To shed light on this long-standing question, we sequenced the genomes of two firefly species that diverged over 100 million-years-ago: the North American Photinus pyralis and Japanese Aquatica lateralis. To compare bioluminescent origins, we also sequenced the genome of a related click beetle, the Caribbean Ignelater luminosus, with bioluminescent biochemistry near-identical to fireflies, but anatomically unique light organs, suggesting the intriguing hypothesis of parallel gains of bioluminescence. Our analyses support independent gains of bioluminescence in fireflies and click beetles, and provide new insights into the genes, chemical defenses, and symbionts that evolved alongside their luminous lifestyle