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Organisms depend on visual, auditory, and olfactory cues to signal the presence of danger that could impact survival and reproduction. Drosophila melanogaster emits an olfactory alarm signal, termed the Drosophila stress odorant (dSO), in response to mechanical agitation or electric shock. While it has been shown that conspecifics avoid areas previously occupied by stressed individuals, the contextual underpinnings of the emission of, and response to dSO, have received little attention. Using a binary choice assay, we determined that neither age and sex of emitters, nor the time of the day, affected the emission or avoidance of dSO. However, both sex and mating status affected the response to dSO. We also demonstrated that while D. melanogaster, D. simulans, and D. suzukii, have different dSO profiles, its avoidance was not species-specific. Thus, dSO should not be considered a pheromone but a general alarm signal for Drosophila. However, the response levels to both intra- and inter-specific cues differed between Drosophila species and possible reasons for these differences are discussed.

Rationale & Objective Pathogenic variants in type IV collagen have been reported to account for a significant proportion of chronic kidney disease. Accordingly, genetic testing is increasingly used to diagnose kidney diseases, but testing also may reveal rare missense variants that are of uncertain clinical significance. To aid in interpretation, computational prediction (called in silico) programs may be used to predict whether a variant is clinically important. We evaluate the performance of in silico programs for COL4A3/A4/A5 variants. Study Design, Setting, & Participants Rare missense variants in COL4A3/A4/A5 were identified in disease cohorts, including a local focal segmental glomerulosclerosis (FSGS) cohort and publicly available disease databases, in which they are categorized as pathogenic or benign based on clinical criteria. Tests Compared & Outcomes All rare missense variants identified in the 4 disease cohorts were subjected to in silico predictions using 12 different programs. Comparisons between the predictions were compared with: (1) variant classification (pathogenic or benign) in the cohorts and (2) functional characterization in a randomly selected smaller number (17) of pathogenic or uncertain significance variants obtained from the local FSGS cohort. Results In silico predictions correctly classified 75% to 97% of pathogenic and 57% to 100% of benign COL4A3/A4/A5 variants in public disease databases. The congruency of in silico predictions was similar for variants categorized as pathogenic and benign, with the exception of benign COL4A5 variants, in which disease effects were overestimated. By contrast, in silico predictions and functional characterization classified all 9 pathogenic COL4A3/A4/A5 variants correctly that were obtained from a local FSGS cohort. However, these programs also overestimated the effects of genomic variants of uncertain significance when compared with functional characterization. Each of the 12 in silico programs used yielded similar results. Limitations Overestimation of in silico program sensitivity given that they may have been used in the categorization of variants labeled as pathogenic in disease repositories. Conclusions Our results suggest that in silico predictions are sensitive but not specific to assign COL4A3/A4/A5 variant pathogenicity, with misclassification of benign variants and variants of uncertain significance. Thus, we do not recommend in silico programs but instead recommend pursuing more objective levels of evidence suggested by medical genetics guidelines.

Organisms depend on visual, auditory, and olfactory cues to signal the presence of danger that could impact survival and reproduction. Drosophila melanogaster emits an olfactory alarm signal, termed the Drosophila stress odorant (dSO), in response to mechanical agitation or electric shock. While it has been shown that conspecifics avoid areas previously occupied by stressed individuals, the contextual underpinnings of the emission of, and response to dSO, have received little attention. Using a binary choice assay, we determined that neither age and sex of emitters, nor the time of the day, affected the emission or avoidance of dSO. However, both sex and mating status affected the response to dSO. We also demonstrated that while D. melanogaster, D. simulans, and D. suzukii, have different dSO profiles, its avoidance was not species-specific. Thus, dSO should not be considered a pheromone but a general alarm signal for Drosophila. However, the response levels to both intra- and inter-specific cues differed between Drosophila species and possible reasons for these differences are discussed.

Social interactions are crucial for the reproduction and survival of many organisms, including those using visual, auditory and olfactory cues to signal the presence of danger.Drosophila melanogasteremits an olfactory alarm signal, termed theDrosophilastress odorant (dSO) in response to mechanical agitation or electric shock, and conspecifics avoid areas previously occupied by stressed individuals. However, the contextual, genetic and neural underpinnings of the emission of, and response to dSO, have received little attention. Using a binary choice assay, we determined that neither age and sex of emitters, nor the time of the day, affected the emission or avoidance of dSO. However, both sex and mating status affected the response to dSO. We also demonstrated that dSO was not species specific so it should not be considered a pheromone but a general alarm signal for Drosophila. However, the response levels to both intra and inter-specific cues differed between species and possible reasons for these differences are discussed.HIGHLIGHTSEmission of dSO, a highly volatile chemical blend emitted by stressed flies, is not context specificResponse to dSO is context specific, affected by factors such as age and mating status.As flies respond to volatiles for stressed heterospecifics, dSO should not be considered an alarm pheromone, but as an alarm cue.

Dr. Dan Lizotte is an assistant professor cross-appointed in the Department of Computer Science and the Department of Epidemiology & Biostatistics at The University of Western Ontario. His current research focuses on transforming knowledge gleaned from reinforcement learning, machine learning, and statistical techniques into actionable information to be used in the healthcare world. After obtaining his Bachelor of Computer Science at the University of New Brunswick, Dr. Lizotte went to the University of Alberta to complete his Master of Science and Ph.D. in Computing Science. WURJHNS managing editor, Emerald Liang, had the pleasure of interviewing him to learn more about his research, its impact on medicine and advice for Western undergraduate students.

Dr. Jessica Grahn is an Associate Professor in the Brain and Mind Institute and the Department of Psychology at Western University. Her research focuses on how movement and rhythm may be connected in the brain with a practical focus on how music influences the dysfunctional movements of Parkinson patients. She currently supervises music neuroscience MSc and PhD students in the Behavioural and Cognitive Neuroscience program and the Neuroscience program at Western University. Emerald Liang, a member of the academic affairs committee for WURJHNS, had the pleasure of interviewing Dr Jessica Grahn to find out a bit about her unique career choice and to acquire some insightful advice for current undergraduate students.

Dr. Patrick O’Donoghue is an Assistant Professor in the Faculty of Biochemistry at the University of Western Ontario who currently holds the Canada Research Chair in Chemical Biology. His research is focused on non-canonical amino acids, more specifically on the synthesis of abnormal enzymes for industrial and medical applications. WURJHNS First Year Representative, Emerald Liang, had the pleasure of interviewing him to learn more about his research and career.