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There is concern among the general public that information technology (IT) innovations may make existing jobs redundant. This may be perceived to pose a greater problem to future generations because new technologies, not limited to IT innovations, will be sophisticated in the future. Our previous work revealed that messages reminding people of familial support as a nudge can moderate risk-averse attitudes toward risks that are perceived to threaten future generations, which could be effective for other kinds of risks. Therefore, we conducted a randomized controlled trial to examine the message effects for information provision on IT innovations. The study was conducted via an online questionnaire survey in January 2020, before the COVID-19 pandemic, and more than 3,200 samples were collected from respondents aged 20 years or older living in Japan. The treatment groups received basic information supplemented with additional text or additional text and an illustration that highlighted IT innovations as support from previous generations. The control group received only the basic textual information. The effects of the intervention were evaluated by comparing changes in average subjective assessment of IT in the treatment groups with those in the control group. The intervention effect was statistically significant, and the sense of familial support after receiving the intervention messages was significantly increased in the treatment group that viewed the illustration compared with the control group. Additionally, we discuss how each component of the HEXACO personality traits influences responses to the intervention messages. Through a series of surveys, we demonstrated the potential of our framework for a wide variety of applications involving information provision perceived to involve future generations.

Nudging is a method for eliciting a desired behavior. One approach to nudging involves information provision. When information presented for this purpose is designed from an evolutionary perspective, it may reveal a deeper level of rationality within human decision-making that might otherwise appear to be irrational. Based on insights from the evolution of altruism, we previously designed a message to remind people of the benefits they have received from the actions of relatives to realize industrialization. We then demonstrated that using this message in Japan was effective at moderating extreme risk-averse attitudes toward air pollution resulting from industrialization. However, the universality of the intervention effect, including whether it could be affected by exogenous factors, was not explored. Therefore, in the present study, we conducted a randomized controlled trial based on an online survey carried out in Japan, Canada, and the US. The intervention was shown to be effective in all the three countries, but the effect size varied according to segment. Although women showed more intervention effects than men in Japan and the US, no significant sex difference was observed in Canada. In terms of personality traits, higher agreeableness significantly contributed to the intervention effects. The influence of the COVID-19 pandemic, which necessitated many lifestyle changes, was found to weaken the intervention effect by increasing the message effect in the control group. We propose that this effect was caused by an increased perception of familial support in everyday life. These results suggest that the nudge message was universally effective, although the effect size might have been affected by cultural factors and social events.

Disposable plastics are drawing considerable attention as a source of environmental risk despite their benefits in daily life. Banning the use of disposable plastics could increase other types of risks, which may damage the public good in the long run. Considering the trade-off of the risks and benefits, one way to improve social welfare is to conduct proper recycling and to continue using plastics but limit them to essential use, avoiding an unnecessary ban. A potential barrier to such a policy might be risk-averse attitudes toward actions that are perceived to threaten future generations, which is a well-known phenomenon. We previously designed a framework for information provision using messages that remind individuals about familial support, which had significant effects in multiple countries on increasing positive attitudes toward air pollution caused by industrialization. We hypothesized that this information provision could also be effective for disposable plastic use. Thus, we conducted a randomized controlled trial via online surveys in Japan, Canada, and the US to identify the effects of our designed messages about recycling on increasing positive attitudes toward disposable plastics. The intervention effects were measured by the difference-in-difference method and panel analysis based on linear regression models using the respondents' attributes and personality traits. The effects were consistently correlated with a sense of familial support, with the effect sizes varying according to country (US > Japan > Canada). Attributes that positively contributed to the message being more effective were higher agreeableness, lower Machiavellianism, lower psychopathy, and being a woman. Although personal fear about COVID-19 moderated the message effects, concern about the threats to relatives and family boosted the effects. Although the effect sizes were influenced by external factors, the results suggested that our proposed framework for information provision has the potential to be applied to a wider variety of risk-related topics.

BackgroundAlzheimer's disease (AD) is assessed by carefully examining a patient's cognitive impairment. However, previous studies reported inadequate diagnostic accuracy for dementia in primary care settings. Many hospitals use the automated quantitative evaluation method known as the Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD), wherein brain MRI data are used to evaluate brain morphological abnormalities associated with AD. Similarly, an automated quantitative evaluation application called the easy Z-score imaging system (eZIS), which uses brain SPECT data to detect regional cerebral blood flow decreases associated with AD, is widely used. These applications have several indicators, each of which is known to correlate with the degree of AD. However, it is not completely known whether these indicators work better when used in combination in real-world clinical practice.MethodsWe included 112 participants with mild cognitive impairment (MCI) and 128 participants with early AD in this study. All participants underwent MRI, SPECT, and the Mini-Mental State Examination (MMSE). Demographic and clinical characteristics were assessed by univariate analysis, and logistic regression analysis with a combination of MMSE, VSRAD and eZIS indicators was performed to verify whether the diagnostic accuracy in discriminating between MCI and early AD was improved.ResultsThe area under the receiver operating characteristic curve (AUC) for the MMSE score alone was 0.835. The AUC was significantly improved to 0.870 by combining the MMSE score with two quantitative indicators from the VSRAD and eZIS that assessed the extent of brain abnormalities.ConclusionCompared with the MMSE score alone, the combination of the MMSE score with the VSRAD and eZIS indicators significantly improves the accuracy of discrimination between patients with MCI and early AD. Implementing VSRAD and eZIS does not require professional clinical experience in the treatment of dementia. Therefore, the accuracy of dementia diagnosis by physicians may easily be improved in real-world primary care settings.

Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker's organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL.

A well-known phenomenon is that humans perceive risks to threaten future generations as more dangerous in many cases. However, this tendency could be changed depending on certain conditions and could potentially be explained by the evolution of altruism. Our multi-agent simulation model, which was constructed to identify attributes contributing to subjective assessment of a risk source based on kin selection theory, showed that support from relatives can affect the agents' subjective risk assessment. We utilize this insight, which has never been explored in the context of nudge, to show that real-world messages reminding respondents that they are supported by their relatives can moderate the perception of a risk source as extremely dangerous. A randomized control trial based on an internet questionnaire survey was conducted to identify the intervention effect of such messages, using air pollution caused by industrialization as the risk source for the case study. Our analysis suggests that messages moderate extreme attitudes. Presentation of additional visual information can boost the sense of familial support and increase the effect of a message compared with a message comprising only textual information. The attributes and personality traits of the respondents who are responsive to the intervention message are also discussed.

Patterned cell culturing is one of the most useful techniques for understanding the interaction between geometric conditions surrounding cells and their behaviors. The authors previously proposed a simple method for cell patterning with an agarose gel microstructure fabricated by microcasting with a degassed polydimethylsiloxane (PDMS) mold. Although the vacuum pressure produced from the degassed PDMS can drive a highly viscous agarose solution, the influence of solution viscosity on the casting process is unknown. This study investigated the influences of micro-channel dimensions or solution viscosity on the flow of the solution in a micro-channel of a PDMS mold by both experiments and numerical simulation. It was found experimentally that the degassed PDMS mold was able to drive a solution with a viscosity under 575 mPa·s. A simulation model was developed which can well estimate the flow rate in various dimensions of micro-channels. Cross-linked albumin has low viscosity (1 mPa·s) in aqueous solution and can undergo a one-way dehydration process from solution to solid that produces cellular repellency after dehydration. A microstructure of cross-linked albumin was fabricated on a cell culture dish by the microcasting method. After cells were seeded and cultivated on the cell culture dish with the microstructure for 7 days, the cellular pattern of mouse skeletal myoblast cell line C2C12 was observed. The microcasting with cross-linked albumin solution enables preparation of patterned cell culture systems more quickly in comparison with the previous agarose gel casting, which requires a gelation process before the dehydration process.

Pine wilt disease (PWD) constitutes a serious threat to pine forests. Since development depends on temperature and drought, there is a concern that future climate change could lead to the spread of PWD infections. We evaluated the risk of PWD in 21 susceptible Pinus species on a global scale. The MB index, which represents the sum of the difference between the mean monthly temperature and 15 when the mean monthly temperatures exceeds 15°C, was used to determine current and future regions vulnerable to PWD (MB ≥ 22). For future climate conditions, we compared the difference in PWD risks among four different representative concentration pathways (RCPs 2.6, 4.5, 6.0, and 8.5) and two time periods (2050s and 2070s). We also evaluated the impact of climate change on habitat suitability for each Pinus species using species distribution models. The findings were then integrated and the potential risk of PWD spread under climate change was discussed. Within the natural Pinus distribution area, southern parts of North America, Europe, and Asia were categorized as vulnerable regions (MB ≥ 22; 16% of the total Pinus distribution area). Representative provinces in which PWD has been reported at least once overlapped with the vulnerable regions. All RCP scenarios showed expansion of vulnerable regions in northern parts of Europe, Asia, and North America under future climate conditions. By the 2070s, under RCP 8.5, an estimated increase in the area of vulnerable regions to approximately 50% of the total Pinus distribution area was revealed. In addition, the habitat conditions of a large portion of the Pinus distribution areas in Europe and Asia were deemed unsuitable by the 2070s under RCP 8.5. Approximately 40% of these regions overlapped with regions deemed vulnerable to PWD, suggesting that Pinus forests in these areas are at risk of serious damage due to habitat shifts and spread of PWD.

The geometrical confinement of small cell colonies gives differential cues to cells sitting at the periphery versus the core. To utilize this effect, for example to create spatially graded differentiation patterns of human mesenchymal stem cells (hMSCs) in vitro or to investigate underpinning mechanisms, the confinement needs to be robust for extended time periods. To create highly repeatable micro-fabricated structures for cellular patterning and high-throughput data mining, we employed here a simple casting method to fabricate more than 800 adhesive patches confined by agarose micro-walls. In addition, a machine learning based image processing software was developed (open code) to detect the differentiation patterns of the population of hMSCs automatically. Utilizing the agarose walls, the circular patterns of hMSCs were successfully maintained throughout 15 days of cell culture. After staining lipid droplets and alkaline phosphatase as the markers of adipogenic and osteogenic differentiation, respectively, the mega-pixels of RGB color images of hMSCs were processed by the software on a laptop PC within several minutes. The image analysis successfully showed that hMSCs sitting on the more central versus peripheral sections of the adhesive circles showed adipogenic versus osteogenic differentiation as reported previously, indicating the compatibility of patterned agarose walls to conventional microcontact printing. In addition, we found a considerable fraction of undifferentiated cells which are preferentially located at the peripheral part of the adhesive circles, even in differentiation-inducing culture media. In this study, we thus successfully demonstrated a simple framework for analyzing the patterned differentiation of hMSCs in confined microenvironments, which has a range of applications in biology, including stem cell biology.

Tax1 encoded by the human T-cell leukemia virus type 1 (HTLV-1) has been believed to dysregulate the expression of cellular genes involved in cell survival and mortality, leading to the development of adult T-cell leukemia (ATL). The function of Tax1 in ATL development however is still controversial, primarily because Tax1 induces cell cycle progression and apoptosis. To systemically understand cell growth phase-dependent induction of cell survival or cell death by Tax1, we established a single experimental system using an interleukin 2 (IL-2)-dependent human T-cell line Kit 225 that can be forced into resting phase by IL-2 deprivation. Introduction of Tax1 and HTLV-2 Tax (Tax2B) decreased mitochondrial activity alongside apoptosis in growing cells but not in resting cells. Cell cycle profile analysis indicated that Tax1 and Tax2B were likely to perturb the S phase in growing cells. Studies with Tax1 mutants and siRNA for NF-κB/RelA revealed that Tax1-mediated cell growth inhibition and apoptosis in growing Kit 225 cells depend on RelA. Interestingly, inactivation of the non-canonical NF-κB and p38 MAPK pathways relieved Tax1-mediated apoptosis, suggesting that the Tax1-NF-κB-p38 MAPK axis may be associated with apoptosis in growing cells. Inflammatory mediators such as CCL3 and CCL4, which are involved in oncogene-induced senescence (OIS), were induced by Tax1 and Tax2B in growing cells. In contrast, RelA silencing in resting cells reduced mitochondrial activity, indicating that NF-κB/RelA is also critical for Tax1-mediated cell survival. These findings suggest that Tax1-mediated cell survival and death depend on the cell growth phase. Both effects of Tax1 may be implicated in the long latency of HTLV-1 infection.

Cancer stem cells contribute to the malignant phenotypes of a variety of cancers, but markers to identify human hypopharyngeal cancer (HPC) stem cells remain poorly understood. Here, we report that the CD271(+) population sorted from xenotransplanted HPCs possesses an enhanced tumor-initiating capability in immunodeficient mice. Tumors generated from the CD271(+) cells contained both CD271(+) and CD271(-) cells, indicating that the population could undergo differentiation. Immunohistological analyses of the tumors revealed that the CD271(+) cells localized to a perivascular niche near CD34(+) vasculature, to invasive fronts, and to the basal layer. In accordance with these characteristics, a stemness marker, Nanog, and matrix metalloproteinases (MMPs), which are implicated in cancer invasion, were significantly up-regulated in the CD271(+) compared to the CD271 (-) cell population. Furthermore, using primary HPC specimens, we demonstrated that high CD271 expression was correlated with a poor prognosis for patients. Taken together, our findings indicate that CD271 is a novel marker for HPC stem-like cells and for HPC prognosis.

The long non-coding RNA HOTAIR has been reported to be a poor prognostic biomarker in a variety of malignant tumors. However, little is known about the association of HOTAIR with gastric cancer. We examined the expression of HOTAIR in 68 gastric cancer samples using quantitative real-time RT-PCR and analyzed its correlation with the clinical parameters. The functional role of HOTAIR was examined by generating human gastric cancer cell lines with increased or suppressed HOTAIR expression. The anchorage -independent growth was assessed by soft agar assay. The increased or suppressed HOTAIR expressing gastric cancer cells were injected into the tail vein or peritoneal cavity of immunodeficient mice to examine the effect of this molecule on metastasis and peritoneal dissemination. The expression of HOTAIR was significantly higher in cancer lesions than in adjacent non-cancerous tissues in human gastric cancers. In the diffuse type of gastric cancer, the High-HOTAIR group (HOTAIR/GAPDH > 1) showed significantly more venous invasion, frequent lymph node metastases and a lower overall survival rate compared to the Low-HOTAIR group (HOTAIR/GAPDH < 1). Colony formation on the soft agar was enhanced in a HOTAIR-dependent manner. HOTAIR-expressing MKN74 formed more liver metastasis compared to control when they were injected into the tail vein of mice. In addition, reduced expression of HOTAIR in KATO III suppressed peritoneal dissemination. These results suggest that HOTAIR plays a pivotal role in the development of gastric cancer.

Many neurodegenerative diseases share a common pathological feature: the deposition of amyloid-like fibrils composed of misfolded proteins. Emerging evidence suggests that these proteins may spread from cell-to-cell and encourage the propagation of neurodegeneration in a prion-like manner. Here, we demonstrated that α-synuclein (αSYN), a principal culprit for Lewy pathology in Parkinson's disease (PD), was present in endosomal compartments and detectably secreted into the extracellular milieu. Unlike prion protein, extracellular αSYN was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. Surprisingly, impaired biogenesis of multivesicular body (MVB), an organelle from which exosomes are derived, by dominant-negative mutant vacuolar protein sorting 4 (VPS4) not only interfered with lysosomal targeting of αSYN but facilitated αSYN secretion. The hypersecretion of αSYN in VPS4-defective cells was efficiently restored by the functional disruption of recycling endosome regulator Rab11a. Furthermore, both brainstem and cortical Lewy bodies in PD were found to be immunoreactive for VPS4. Thus, VPS4, a master regulator of MVB sorting, may serve as a determinant of lysosomal targeting or extracellular secretion of αSYN and thereby contribute to the intercellular propagation of Lewy pathology in PD.