[Impact of migraine on family members: an investigation by Impact of Migraine on Partners and Adolescent Children (IMPAC)].

Using the Japanese version of the Impact of Migraine on Partners and Adolescent Children (IMPAC) and Family Question prepared based on IMPAC, we investigated the impact of migraine on family members from the perspectives of both patients and their family members. Our results showed that migraine had an impact on the family members living with the patients in Japan as well, and the perception of migraine differed partially between patients and their family members. We also found that the Japanese version of the IMPAC showed a correlation with existing instruments to evaluate impact of migraine, indicating its validity. The application of this study's findings in clinical practice could help alleviate the disease burden of migraine on patients and their family members.

Olfactory modulation of colour working memory: How does citrus-like smell influence the memory of orange colour?

Olfactory modulation of vision is not well understood whereas visual modulation of olfaction has been more fully investigated. This study aimed to reveal in a simple manner whether there is olfactory modulation of colour working memory using an odour that induces a citrus-like smell and is associated with orange colours. We assumed that the odour would have modulatory effects on the colour information stored in working memory. To clarify whether these effects are supportive or disruptive, during the colour working memory task we measured an event-related potential component, P3, which is involved in attentional processes of working memory. The results indicated that odour presentation mediated a decline in the rate of correct guesses for orange colours. Furthermore, the odour suppressed P3 during reddish-colour retrieval, including orange. These results suggest that colour working memory in orange can be disrupted via olfactory modulation with citrus-like odours.

Establishment of Time- and Cell-Specific RNAi in Caenorhabditis elegans.

The nematode worm Caenorhabditis elegans, in which loss-of-function mutants and RNA interference (RNAi) models are available, is a model organism useful for analyzing effects of genes on various life phenomena. In particular, RNAi is a powerful tool that enables time- or cell-specific knockdown via heat shock-inducible RNAi or cell-specific RNAi. However, the conventional RNAi methods are insufficient for investigating pleiotropic genes with various sites of action and life stage-dependent functions. To investigate the temporal- and cell-specific profiles of multifunctional genes, we established a new RNAi method that enables simultaneous time- and cell-specific knockdown (T.C.RNAi) in C. elegans. In this method, one RNA strand is expressed by a cell-specific promoter and the other by a heat shock promoter, resulting in only expression of double-stranded RNA in the target cell when heat shock is induced. We confirmed the effect of T.C.RNAi by the knockdown of GFP and the odr-3 gene which encodes Gα and is essential for olfaction. Further, this technique revealed that the control of glutamate receptors GLR-1 localization in RMD motor neurons requires Ras at the adult stage to regulate locomotion behavior.

Voltage-dependent anion channel (VDAC-1) is required for olfactory sensing in Caenorhabditis elegans.

The Ras-MAP kinase signaling pathway plays important roles for the olfactory reception in olfactory neurons in Caenorhabditis elegans. However, given the absence of phosphorylation targets of MAPK in the olfactory neurons, the mechanism by which this pathway regulates olfactory function is unknown. Here, we used proteomic screening to identify the mitochondrial voltage-dependent anion channel VDAC-1 as a candidate target molecule of MAPK in the olfactory system of C. elegans. We found that Amphid Wing "C" (AWC) olfactory neuron-specific knockdown of vdac-1 caused severe defects in chemotaxis toward AWC-sensed odorants. We generated a new vdac-1 mutant using the CRISPR-Cas9 system, with this mutant also showing decreased chemotaxis toward odorants. This defect was rescued by AWC-specific expression of vdac-1, indicating that functions of VDAC-1 in AWC neurons are essential for normal olfactory reception in C. elegans. We observed that AWC-specific RNAi of vdac-1 reduced AWC calcium responses to odorant stimuli and caused a decrease in the quantity of mitochondria in the sensory cilia. Behavioral abnormalities in vdac-1 knockdown animals might therefore be due to reduction of AWC response, which might be caused by loss of mitochondria in the cilia. Here, we showed that the function of VDAC-1 is regulated by phosphorylation and identified Thr175 as the potential phosphorylation site of MAP kinase.

A highly accurate inclusive cancer screening test using Caenorhabditis elegans scent detection.

Early detection and treatment are of vital importance to the successful eradication of various cancers, and development of economical and non-invasive novel cancer screening systems is critical. Previous reports using canine scent detection demonstrated the existence of cancer-specific odours. However, it is difficult to introduce canine scent recognition into clinical practice because of the need to maintain accuracy. In this study, we developed a Nematode Scent Detection Test (NSDT) using Caenorhabditis elegans to provide a novel highly accurate cancer detection system that is economical, painless, rapid and convenient. We demonstrated wild-type C. elegans displayed attractive chemotaxis towards human cancer cell secretions, cancer tissues and urine from cancer patients but avoided control urine; in parallel, the response of the olfactory neurons of C. elegans to the urine from cancer patients was significantly stronger than to control urine. In contrast, G protein α mutants and olfactory neurons-ablated animals were not attracted to cancer patient urine, suggesting that C. elegans senses odours in urine. We tested 242 samples to measure the performance of the NSDT, and found the sensitivity was 95.8%; this is markedly higher than that of other existing tumour markers. Furthermore, the specificity was 95.0%. Importantly, this test was able to diagnose various cancer types tested at the early stage (stage 0 or 1). To conclude, C. elegans scent-based analyses might provide a new strategy to detect and study disease-associated scents.

A role for Ras in inhibiting circular foraging behavior as revealed by a new method for time and cell-specific RNAi.

BACKGROUND: The nematode worm Caenorhabditis elegans, in which loss-of-function mutants and RNA interference (RNAi) models are available, is a model organism useful for analyzing effects of genes on various life phenomena, including behavior. In particular, RNAi is a powerful tool that enables time- or cell-specific knockdown via heat shock-inducible RNAi or cell-specific RNAi. However, conventional RNAi is insufficient for investigating pleiotropic genes with various sites of action and life stage-dependent functions. RESULTS: Here, we investigated the Ras gene for its role in exploratory behavior in C. elegans. We found that, under poor environmental conditions, mutations in the Ras-MAPK signaling pathway lead to circular locomotion instead of normal exploratory foraging. Spontaneous foraging is regulated by a neural circuit composed of three classes of neurons: IL1, OLQ, and RMD, and we found that Ras functions in this neural circuit to modulate the direction of locomotion. We further observed that Ras plays an essential role in the regulation of GLR-1 glutamate receptor localization in RMD neurons. To investigate the temporal- and cell-specific profiles of the functions of Ras, we developed a new RNAi method that enables simultaneous time- and cell-specific knockdown. In this method, one RNA strand is expressed by a cell-specific promoter and the other by a heat shock promoter, resulting in only expression of double-stranded RNA in the target cell when heat shock is induced. This technique revealed that control of GLR-1 localization in RMD neurons requires Ras at the adult stage. Further, we demonstrated the application of this method to other genes. CONCLUSIONS: We have established a new RNAi method that performs simultaneous time- and cell-specific knockdown and have applied this to reveal temporal profiles of the Ras-MAPK pathway in the control of exploratory behavior under poor environmental conditions.