daf-42 is an evolutionarily young gene essential for dauer development in Caenorhabditis elegans.

Under adverse environmental conditions, nematodes arrest into dauer, an alternative developmental stage for diapause. Dauer endures unfavorable environments and interacts with host animals to access favorable environments, thus playing a critical role in survival. Here, we report that in Caenorhabditis elegans, daf-42 is essential for development into the dauer stage, as the null mutant of daf-42 exhibited a "no viable dauer" phenotype in which no viable dauers were obtained in any dauer-inducing conditions. Long-term time lapse microscopy of synchronized larvae revealed that daf-42 is involved in developmental changes from the pre-dauer L2d stage to the dauer stage. daf-42 encodes large, disordered proteins of various sizes that are expressed in and secreted from the seam cells within a narrow time window shortly before the molt into dauer stage. Transcriptome analysis showed that the transcription of genes involved in larval physiology and dauer metabolism is highly affected by the daf-42 mutation. Contrary to the notion that essential genes that control the life and death of an organism may be well conserved across diverse species, daf-42 is an evolutionarily young gene conserved only in the Caenorhabditis genus. Our study shows that dauer formation is a vital process that is controlled not only by conserved genes but also by newly emerged genes, providing important insights into evolutionary mechanisms.

A genetic screen for aldicarb resistance of Caenorhabditiselegans dauer larvae uncovers 2 alleles of dach-1, a cytochrome P450 gene.

Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function at different developmental stages. Here, we investigated the genetic determinants of how animal's sensitivity to drugs that alter synaptic activity is regulated at a specific developmental stage using the free-living nematode Caenorhabditis elegans. C. elegans enters the stress-resistant dauer larval stage under harsh conditions. Although dauer is known to have reduced permeability and increased resistance to most known exogenous chemicals, we discovered that dauer is hypersensitive to a cholinesterase inhibitor, aldicarb. To investigate genes regulating dauer-specific acetylcholine transduction, we first screened for aldicarb-resistant mutations in dauer and then performed a secondary screen to rule out aldicarb-resistant mutations that also affect adults. We isolated 2 different mutations of a single gene called cyp-34A4 or dach-1 encoding a cytochrome P450. In the nondauer stages, dach-1 is mainly expressed in the intestine, but its expression is robustly increased in the epidermis of dauers. By tissue-specific rescue experiments, we found that dach-1 modulates aldicarb sensitivity in a cell nonautonomous manner. In addition, dach-1 plays pleiotropic functions in dauers by regulating quiescence and surviving heat shock and hyperosmolar stress. Our study reveals novel functions of the cytochrome P450 in synaptic and physiological changes during the developmental plasticity.

Occupational therapy, cancer, and occupation-centred practice: impact of training in the model of human occupation.

INTRODUCTION: This study examined the influence of training in an occupation-centred model on the practice of occupational therapists working in a cancer hospital. There is an increased need for occupation-based rehabilitation services for individuals with and surviving cancer. Incorporating an occupation-centred model into practice has unique challenges for occupational therapists working in oncology settings. Utilizing an occupation-centred model of practice may influence the therapeutic reasoning of occupational therapists. METHODS: A generic qualitative inquiry (Patton, 2015) was used to examine therapeutic reasoning as related to post-professional training in a specific occupation-centred model, the Model of Human Occupation (MOHO). Initially, ten occupational therapists with various levels of experience, working across populations in a large cancer centre completed a training session about the MOHO. This was followed by participation in monthly focus groups with an emphasis on the use of MOHO in daily practice (Taylor, 2017). Focus group sessions were video recorded and transcribed. The transcripts were then analysed using open coding and theme generation (Patton, 2015). RESULTS: Three major themes were extracted from the data during the thematic analysis: understanding and using MOHO language; challenges in incorporating a conceptual model of occupation-centred practice in an oncology setting; and therapeutic reasoning implications. Patterns in the themes indicated a progression from learning the model, to applying the model, to reflection on practice. CONCLUSION: Post-professional training in an occupation-based model influenced the therapeutic reasoning and practice of occupational therapists in an oncology setting.

Regulation of a hitchhiking behavior by neuronal insulin and TGF-ß signaling in the nematode Caenorhabditis elegans.

Free-living nematode Caenorhabditis elegans exhibits various behaviors to adapt to the fluctuating environment. When early larvae of C. elegans experience the harsh environmental condition, they develop to an alternative developmental stage called dauer, which shows nictation, a stage-specific waving behavior. Nictation enables dauers to attach to more mobile animals, which helps them disperse to other habitats beyond physical barriers. However, underlying molecular mechanisms that regulate nictation behavior are largely unknown. In this study, we show that insulin signaling and transforming growth beta (TGF-ß) signaling, the two major parallel signaling pathways that mediate dauer development, are involved in the regulation of dauer-specific nictation behavior. Genetic analysis revealed that downregulation of insulin signaling enhanced nictation behavior. Heat-shock induced rescue experiments showed that the action period of the insulin signaling is before dauer formation. Surprisingly, lowering of TGF-ß signaling inhibited the normal performance of nictation, suggesting that TGF-ß signaling acts in an opposite way from that for dauer formation. Cell-specific rescue experiments revealed that two signaling pathways act in the nervous system and an epistasis experiment showed that TGF-ß signaling is epistatic to insulin signaling. Taken together, we propose that the neuroendocrinal insulin signaling and TGF-ß signaling regulate nictation behavior during development in response to environmental conditions.

Telomere maintenance through recruitment of internal genomic regions.

Cells surviving crisis are often tumorigenic and their telomeres are commonly maintained through the reactivation of telomerase. However, surviving cells occasionally activate a recombination-based mechanism called alternative lengthening of telomeres (ALT). Here we establish stably maintained survivors in telomerase-deleted Caenorhabditis elegans that escape from sterility by activating ALT. ALT survivors trans-duplicate an internal genomic region, which is already cis-duplicated to chromosome ends, across the telomeres of all chromosomes. These 'Template for ALT' (TALT) regions consist of a block of genomic DNA flanked by telomere-like sequences, and are different between two genetic background. We establish a model that an ancestral duplication of a donor TALT region to a proximal telomere region forms a genomic reservoir ready to be incorporated into telomeres on ALT activation.