Tissue-specific alternative splicing is an important mechanism for providing spatiotemporal protein diversity. Here we show that an in-frame splice mutation in BBS8, one of the genes involved in ...pleiotropic Bardet-Biedl syndrome (BBS), is sufficient to cause nonsyndromic retinitis pigmentosa (RP). A genome-wide scan of a consanguineous RP pedigree mapped the trait to a 5.6 Mb region; subsequent systematic sequencing of candidate transcripts identified a homozygous splice-site mutation in a previously unknown BBS8 exon. The allele segregated with the disorder, was absent from controls, was completely invariant across evolution, and was predicted to lead to the elimination of a 10 amino acid sequence from the protein. Subsequent studies showed the exon to be expressed exclusively in the retina and enriched significantly in the photoreceptor layer. Importantly, we found this exon to represent the major BBS8 mRNA species in the mammalian photoreceptor, suggesting that the encoded 10 amino acids play a pivotal role in the function of BBS8 in this organ. Understanding the role of this additional sequence might therefore inform the mechanism of retinal degeneration in patients with syndromic BBS or other related ciliopathies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Transient transfection promoter reporter assays are commonly used in the study of transcriptional regulation, and can be used to define and characterize both cis-acting regulatory sequences and ...trans-acting factors. In the process of using a variety of reporter assays designed to study regulation of the rhodopsin (rho) promoter, we discovered that rhodopsin promoter-driven reporter expression could be activated by certain species of shRNA in a gene-target-independent but shRNA sequence-specific manner, suggesting involvement of a specific shRNA associated pathway. Interestingly, the shRNA-mediated increase of rhodopsin promoter activity was synergistically enhanced by the rhodopsin transcriptional regulators CRX and NRL. Additionally, the effect was cell line-dependent, suggesting that this pathway requires the expression of cell-type specific factors. Since microRNA (miRNA) and interferon response-mediated processes have been implicated in RNAi off-target phenomena, we performed miRNA and gene expression profiling on cells transfected with shRNAs that do target a specific gene but have varied effects on rho reporter expression in order to identify transcripts whose expression levels are associated with shRNA induced rhodopsin promoter reporter activity. We identified a total of 50 miRNA species, and by microarray analysis, 320 protein-coding genes, some of which were predicted targets of the identified differentially expressed miRNAs, whose expression was altered in the presence of shRNAs that stimulated rhodopsin-promoter activity in a non-gene-targeting manner. Consistent with earlier studies on shRNA off-target effects, a number of interferon response genes were among those identified to be upregulated. Taken together, our results confirm the importance of considering off-target effects when interpreting data from RNAi experiments and extend prior results by focusing on the importance of including multiple and carefully designed controls in the design and analysis of the effects of shRNA on transient transfection-based transcriptional assays.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cell culturing is a basic experimental technique in cell biology and medical science. However, culturing high-quality cells with a high degree of reproducibility relies heavily on expert skills and ...tacit knowledge, and it is not straightforward to scale the production process due to the education bottleneck. Although many automated culture systems have been developed and a few have succeeded in mass production environments, very few robots are permissive of frequent protocol changes, which are often required in basic research environments. LabDroid is a general-purpose humanoid robot with two arms that performs experiments using the same tools as humans. Combining our newly developed AI software with LabDroid, we developed a variable scheduling system that continuously produces subcultures of cell lines without human intervention. The system periodically observes the cells on plates with a microscope, predicts the cell growth curve by processing cell images, and decides the best times for passage. We have succeeded in developing a system that maintains the cultures of two HEK293A cell plates with no human intervention for 192 h.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•We examined risk judgment on radiation contamination of food.•Thinking trait (intuitive or deliberate) and professions produced individual difference in risk judgments.•Individual difference was ...especially observed in psychological factor representing risk aversion.
Through a large-scale web-based experiment (n=538), we examined variation in risk judgments on radiation contamination of food from the following two perspectives and discussed psychological factors that would be related to such variation. First, we examined how thinking trait (i.e., intuitive or deliberate) would affect risk judgments. Second, we examined whether risk judgments varied by participant profession. Large variation in risk judgments were observed in the latent psychological factor representing risk aversion about radiation contamination, and this variation was explained by the thinking traits and professions of participants. However significant variation was not observed in the factor representing risk tolerance for radiation contamination. These results show that thinking trait and profession play important roles in risk judgments on food contamination by radioactive materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The effects of endothelium-derived hyperpolarizing factors have been attributed to cytochrome P450-derived epoxyeicosatrienoic acids (EETs), but the regulation and role of EETs in endothelial ...dysfunction remain largely unexplored. Hypertension is a primary risk factor for renal dysfunction, which is frequently accompanied by various systemic diseases induced by endothelial dysfunction in the microcirculation. We previously reported that the endothelial growth factor midkine (MK) enhances hypertension in a model of CKD. Here, we investigated the hypothesis that MK regulates EET activity and thereby BP. MK gene-deleted mice were resistant to hypertension and developed less glomerulosclerosis and proteinuria after administration of a nitric oxide synthase (NOS) inhibitor in the setting of uninephrectomy. The hypertension observed in uninephrectomized wild-type mice after NOS inhibition was ameliorated by anti-MK antibody. MK-deficient mice produced higher amounts of EETs, and EETs dominantly regulated BP in these mice. Furthermore, MK administration to MK-deficient mice recapitulated the BP control observed in wild-type mice. EETs also dominantly regulated renal blood flow, which may influence renal function, in MK-deficient mice. Taken together, these results suggest that the MK/EET pathway is physiologically engaged in BP control and could be a target for the treatment of hypertension complicated by endothelial dysfunction.
► The kappa effect is an illusion where the perceived temporal interval of apparent motion increases with distance. ► The magnitude of the kappa effect is influenced by motion direction. ► We examine ...whether different contexts with similar directional changes. ► The directional effect on the kappa effect is not observed consistently. ► The kappa effect is based on perceived events including contexts.
We investigated whether the directional effect on the kappa effect can be attributed to the directional anisotropy of retinotopical space or to the representation of forces provided by environmental contexts (e.g., gravity) in an observed event. We examined whether different contexts with similar directional changes (straight vs. reversed motion) influence the kappa effect in four experiments. The object’s motion appeared to depict only forces under the natural laws of physics on a slope (Experiment 1) or on a horizontal plane (Experiment 2) in virtual 3D space. In Experiments 3 and 4, the motion appeared to be subjected to external or self-driving forces additionally influenced by internal forces on a slope (Experiment 3) or a horizontal plane (Experiment 4).
The results demonstrated that the directional effect on the kappa effect was observed only in Experiment 1, and not in Experiments 2 and 3, while the kappa effect was preserved. Furthermore, not even the kappa effect was observed in the reversed motion of Experiment 4. The results of the present study suggest that the determining factor of direction in the kappa effect is not a simple anisotropy, but rather the context of observed events.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Recent reports have described the efficacy of rituximab in treating steroid-dependent nephrotic syndrome (SDNS) in pediatric patients. However, few reports describe data regarding ...adult-onset SDNS. We investigated the efficacy of rituximab for the management of adult-onset SDNS.
Methods
We performed a retrospective cohort study investigating eight patients with adult-onset SDNS who were treated with rituximab. Clinical data were obtained at the initiation of rituximab therapy. The primary outcomes evaluated were successful suppression of relapses and CD19+ cells after rituximab treatment. The corticosteroid- and immunosuppressant-sparing effect and adverse events were additionally evaluated.
Results
All eight patients were diagnosed with minimal change nephrotic syndrome and received immunosuppressants in addition to corticosteroid. Total number of relapses was 10.5 times as a median value. Rituximab administration was repeated in two patients, whereas six received single-dose rituximab. Three of eight (37.5%) patients showed relapse after rituximab therapy. A rituximab-induced depletion in CD19+ cells noted initially was followed by their reappearance in all patients. There were cases with no relapse after the reappearance of CD19+ cells. The median relapse time pre- and post-rituximab therapy showed a decrease from 1 time/year (interquartile range IQR 1–3 times/year) to 0 time/year (IQR 0–1 time/year). Rituximab treatment induced a significant reduction in the required doses of corticosteroid and cyclosporine (
P
< 0.01). No serious adverse events were observed.
Conclusion
Rituximab treatment was effective not only in childhood-onset but also in adult-onset SDNS. Further studies are needed to establish optimal treatment regimens.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
When people are asked to adjust the color of familiar objects such as fruits until they appear achromatic, the subjective gray points of the objects are shifted away from the physical gray points in ...a direction opposite to the memory color (memory color effect). It is still unclear whether the discrepancy between memorized and actual colors of objects is dependent on the familiarity of the objects. Here, we conducted two experiments in order to examine the relationship between the degree of a subject's familiarity with objects and the degree of the memory color effect by using logographs of food and beverage companies.
In Experiment 1, we measured the memory color effects of logos which varied in terms of their familiarity (high, middle, or low). Results demonstrate that the memory color effect occurs only in the high-familiarity condition, but not in the middle- and low-familiarity conditions. Furthermore, there is a positive correlation between the memory color effect and the actual number of domestic stores of the brand. In Experiment 2, we assessed the semantic association between logos and food/beverage names by using a semantic priming task to elucidate whether the memory color effect of logos relates to consumer brand cognition, and found that the semantic associations between logos and food/beverage names in the high-familiarity brands were stronger than those in the low-familiarity brands only when the logos were colored correctly, but not when they were appropriately or inappropriately colored, or achromatic.
The current results provide behavioral evidence of the relationship between the familiarity of objects and the memory color effect and suggest that the memory color effect increases with the familiarity of objects, albeit not constantly.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► Effect of reputational concern on purchase intention for fair-trade food was explored. ► Relative importance of fair-trade was assessed by using conjoint analysis. ► Consumers valuated fair-trade ...higher when their decision was observable by others.
This study explores whether reputational concerns have an effect on purchase intention for fair-trade food products among Japanese young adults. To manipulate reputation cues, we assessed consumers’ intentions to purchase fair-trade food products under two different experimental situations: the ‘observable’ condition, in which participants’ purchase behaviors were observable by others (N=84); and the ‘anonymous’ condition, in which participants’ purchase behavior could not be observed by others (N=106). The effect of six sensory and extrinsic attributes including fair trade, price, country of manufacture, taste characteristics, polyphenol content and caloric content on consumer intentions to purchase chocolate was evaluated using conjoint analysis. Results demonstrated that participants under the observable condition valuated fair trade higher than those under the anonymous condition, whereas the opposite tendency was observed for the valuation of price and caloric content for their overall purchase intention. These phenomena suggest that ethical consumption, such as purchasing fair-trade foods, is influenced not only by individual’s intrinsic motives for ethical issues but also by extrinsic social factors such as reputation-enhancing opportunities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Previous studies have shown different developmental trajectories for object recognition of solid and non-solid objects. However, there is no evidence as to whether infants have expectations regarding ...certain attributes of objects, such as surface hardness, in the absence of tactile information. In the present study, we examined infants' perception of the hardness of object surfaces from visually presented penetration events using the familiarization-novelty preference procedure. Experiment 1 showed that by 11 months old infants distinguished a relatively soft surface from a crusty surface based on changes in the velocity of a moving object as the moving object penetrated the surface of the target object. Experiment 2 ruled out the possibility that infants were merely sensitive to differences in the velocity changes in the stimuli.
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