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We measured diurnal variations in oxidative stress conditions of cyanobacteria utilizing field observations and laboratory experiments in order to evaluate photoinhibition effects. On clear summer days, transparent bottles filled with surface water were set up at several depths and were collected every three hours together with the measurement of the photosynthetically active radiation (PAR). In the laboratory experiment, two cyanobacterial species were exposed to gradually increasing and then decreasing light intensities. The samples were analyzed with the PAR-induced (H 2 O 2 ), along with the total hydrogen peroxide concentrations (total H 2 O 2 ), the catalase activities (CAT), OD 730 , protein (Protein), and chlorophyll a (Chl a) contents, and so on. Protein was significantly proportionate with OD 730 and Chl a, and was used as an indicator of cell biomass. Increasing PAR, H 2 O 2 concentration increased proportionately with the PAR intensity. Then, an oxidative stress indicator in a cell, H 2 O 2 /Protein is given by the PAR divided by cell volume, evaluated by Protein. CAT activity in a cell, far largest among antioxidant activities, solely followed total H 2 O 2 /Protein. The prediction model for H 2 O 2 /Protein was developed with the sufficient agreement with the experimental and field observation results. The model elucidated that the maximum H 2 O 2 /Protein in a day was larger with lower cell density even at the water surface, indicating that the higher photoinhibition was imposed at low density, in addition to the lower attenuation of PAR. These results indicate that H 2 O 2 /Protein is an effective biomarker to indicate the stress level of cyanobacteria; the observed levels of H 2 O 2 to freshwater may prove useful in designing the criteria for cyanobacteria management., Competing Interests: Competing interests: The authors declare no competing interests. Ethical permission: This study has been approved by the Saitama City Government (Besshonuma park Suishitsu Kaizen Taisaku Jisshi Keikaku Ritsuan Gyomu)., (© 2024. The Author(s).)

Earthquakes that cause extensive damage occur frequently in Japan, the most recent being the Noto Peninsula earthquake on January 1, 2024. To facilitate such a recovery, we introduce a community-based participatory research program implemented through cooperation between universities and local communities after the 2011 Great East Japan Earthquake. In this project, the university and the town of Shichigahama, one of the affected areas, collaborated to hold annual workshops in the target area, which evolved into a climate monitoring survey. Even in Japan, where disaster prevention planning is widespread, various problems arise in the process of emergency response, recovery and reconstruction, and building back better when disasters occur. As is difficult for residents and local governments to solve these problems alone, it is helpful when experts participate in the response process. In this study, we interviewed town hall and university officials as representatives of local residents regarding this project and discussed their mutual concerns. The community-based participatory research framework developed in the Shichigahama project could be used in the recovery from the Noto Peninsula Earthquake as well as in future reconstruction and disaster management projects., (© 2024. The Author(s).)

An earthquake with a moment magnitude of 7.5 (Mw) struck the northern Noto Peninsula, Ishikawa Prefecture, Japan, at 16:10 local time on January 1, 2024. This earthquake triggered a tsunami that propagated along the coastline of Ishikawa, Toyama, and Niigata Prefectures facing the Sea of Japan and significantly damaged coastal communities and infrastructure. Approximately 70 researchers from 23 universities or other institutes throughout Japan formed a joint research group to conduct a post-tsunami survey along a 340 km stretch of the coast. Based on the watermarks and traces of the tsunami, the inundation and run-up heights were surveyed using total stations, automatic optical levels, laser range finders, and a real-time kinematic (RTK) Global Navigation Satellite System (GNSS). The tidal correction was adjusted using astronomical tidal tables. In total, 303 survey records have been compiled, generating the NP2024TS (Noto Peninsula 2024 Tsunami Survey) dataset. This dataset provides comprehensive information on the inundation and run-up heights of the tsunami, which is useful for understanding tsunami characteristics and validating numerical tsunami models., (© 2024. The Author(s).)

The scientific evidence based on experiences with past disasters points to the possibility of the occurrence of future mental health issues among those who were affected by the recent Turkey-Syria earthquake. However, post-disaster care information on factors that could give rise to mental health issues among those affected have yet to be provided. In March 2011, Tohoku University compiled and published a booklet with post-disaster healthcare information based on the experiences with the Great East Japan Earthquake. This study aimed to promote the introduction and use of this booklet for post-disaster care in Turkey and Syria by presenting the results of a satisfaction survey conducted with relevant Japanese organizations about the booklet. A total of 505 Japanese organizations participated in the satisfaction survey of, and evaluated, the booklet. The results indicated the need to consider the ease of understanding for the general public when providing information on post-disaster care through booklets. We hope that this study leads to the appropriate provision of easy-to-understand, post-disaster healthcare information to the victims of the Turkey-Syria earthquake and future disasters., (© 2024. The Author(s).)

The massive eruption of the Hunga Tonga-Hunga Ha'apai (HTHH) volcano in Tonga on 15 January 2022 at 04:15 UTC had a global impact and triggered an atmospheric wave and a tsunami. We first analyzed observation data from meteorological stations and tide gauges at 12 locations. Low-frequency trends in the observation data were removed by using a high-pass filter. Fourier and wavelet spectral analyses were applied to determine the frequency characteristics of the filtered data. Modal analysis was developed and used to investigate natural oscillation periods based on bathymetry. The results showed that the Lamb wave generated by the atmospheric pressure wave arrived ~ 7 and ~ 44 h after the eruption. The tsunami arrived ~ 11 and ~ 45 h after the eruption, which corresponded to the arrival time of the Lamb wave. The dominant periods of the Lamb waves were ~ 7.7 and ~ 7.5 min, and for the tsunamis they were ~ 9.9 and ~ 28.7 min. The periods derived from the spectral analysis matched the natural oscillation of the eigenperiod derived from the modal analysis, in eight out of the twelve stations. This study provides valuable insight and information regarding the nonseismic and far-field effects of tsunamis generated by volcanic eruptions., (© 2023. The Author(s).)

Evacuation is a critical life-saving action, especially in devastating natural hazards such as near-field tsunamis. However, the development of effective evacuation measures remains challenging to the extent that a successful example has been referred to as a 'miracle'. Here we show that urban structures have the potential to reinforce attitudes towards evacuation and significantly influence the success of tsunami evacuation. Agent-based evacuation simulations revealed that a distinctive root-like urban structure formed in ria coasts reinforces positive evacuation attitudes by effectively gathering evacuation flows and leads to higher evacuation rates compared to typical grid-like urban structures, which can explain the regional differences in the number of casualties in the 2011 Tohoku tsunami. Although a grid-like structure reinforces negative attitudes under low evacuation tendencies, with leading evacuees, its dense feature helps to propagate positive attitudes and drastically improve evacuation tendencies. These findings pave the way for making successful evacuation inevitable through harmonised urban and evacuation plannings., (© 2023. The Author(s).)

On 15 January 2022 at 04:15 UTC, the Hunga Tonga-Hunga Ha'apai (HTHH) volcano in Tonga produced a massive eruption that triggered a transoceanic tsunami generated by the coupled ocean and atmospheric shock wave produced during the explosion. The tsunami first reached the coast of Tonga and eventually reached many coasts around the world. This volcano previously underwent a massive eruption in 1100 AD, and an eruption occurs approximately every 1000 years. The 2022 HTHH event provides an opportunity to study a major volcanically generated tsunami that caused substantial damage. In this study, we present a numerical simulation of a tsunami with a state-of-the-art numerical model based on a submarine explosion scenario. We constrain the geometry and magnitude of the explosion energy source based on analyses of pre- and post-event satellite images, which demonstrate that the explosion magnitude varied from 1 to 90 megatons of trinitrotoluene (Mt). Estimated submarine explosion geometries result in a suitable explosion magnitude of approximately 25 Mt, as determined with the waveform from the tide gauge in the time and frequency domains. The tsunami wave first reached the northwestern part of Tonga's Tongatapu within 10 min, with a maximum runup height of approximately 15 m, and covered the whole of Tongatapu within 30 min. Finally, the numerical simulation provides deep insights into the physical volcanic explosion processes and improves our understanding and forecasting capabilities of frequent and catastrophic tsunamis caused by submarine volcanic explosions., (© 2022. The Author(s).)

Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) is a complementary and alternative test to tissue-based NGS. We performed NGS analysis of ctDNA samples collected from patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received osimertinib; the samples were collected after second-line treatment, before osimertinib treatment, one week and one month after osimertinib treatment, and at the time of resistance formation. We examinedthe correlation with osimertinib efficacy. From January to December 2018, 34 patients with EGFR-mutated NSCLC harboring EGFR T790M mutations were enrolled, and a total of 132 peripheral blood samples were collected. The fragment sizes of EGFR-mutated ctDNAs were significantly shorter than that of their corresponding normal fragments. Osimertinib treatment of patients with shorter EGFR-mutated ctDNA fragments resulted in shorter progression-free survival (PFS). The disappearance time of EGFR-mutated fragment fractions and clonal evolution patterns (new driver mutation group, additional mutation group vs. attenuation group) were each associated with the PFS achieved with osimertinib treatment; however,multivariate analysis revealed that only shorter EGFR-mutated ctDNA fragments were associated with the PFS resulting from osimertinib treatment. EGFR-mutated ctDNA fragment size, time of disappearance of these fragments, and clonal evolution pattern were related to the effects of osimertinib. In particular, short EGFR-mutated ctDNA fragmentation may be closely related to osimertinib efficacy prediction., (© 2022. The Author(s).)

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome., (© 2022. The Author(s).)

The most frequent mechanism of resistance after 1st/2nd-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is secondary point mutation Thr790Met (T790M) in EGFR. Afatinib followed by osimertinib (Afa group) may provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-G EGFR-TKI followed by osimertinib (1st-G group). We studied 111 consecutive NSCLC patients with T790M mutation treated with osimertinib after progression following 1st/2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed the ratio of T790M to EGFR-activating mutation (T790M ratio) in post EGFR-TKI resistance re-biopsy tissue using droplet digital polymerase chain reaction. And investigated whether afatinib purified the T790M mutation more than 1st-G EGFR-TKI. Among 60 patients with preserved re-biopsy tissue, we analyzed 38 having adequate DNA content. The response rate in Afa group was 81.8% (n = 11) and 1st-G group was 85.2% (n = 27). The mean T790M ratio in total population was 0.3643. The ratio in those with response to osimertinib was significantly higher than in the non-responders (0.395, 0.202; p = 0.0231) and was similar in Afa and 1st-G group (0.371, 0.362; p = 0.9693). T790M ratio significantly correlated with osimertinib response and was similar between the 1st/2nd-G EGFR-TKIs in 1st/2nd-G EGFR-TKI-refractory tumors.

Several recent studies have found signs of recent selection on the carnitine palmitoyl-transferase 1A (CPT1A) gene in the ancestors of Arctic populations likely as a result of their traditional diet. CPT1A is involved in fatty acid transportation and is known to affect circulating fatty acid profiles in Inuit as does the unique traditional diet rich in marine animals. We aimed to assess which fatty acids may have driven the selection of rs80356779, a c.1436C>T (p.(Pro479Leu)) variant in CPT1A, by analyzing a potential interaction between the variant and traditional Inuit diet. We included 3005 genome-wide genotyped individuals living in Greenland, who had blood cell membrane fatty acid levels measured. Consumption of 25 traditional food items was expressed as percentage of total energy intake. We tested for CPT1A × traditional diet interaction while taking relatedness and admixture into account. Increasing intakes of traditional diet was estimated to attenuate the effect of 479L on 20:3 omega-6 levels (p = 0.000399), but increase the effect of the variant on 22:5 omega-3 levels (p = 0.000963). The 479L effect on 22:5 omega-3 more than doubled in individuals with a high intake of traditional diet (90% percentile) compared with individuals with a low intake (10% percentile). Similar results were found when assessing interactions with marine foods. Our results suggest that the association between traditional diet and blood cell fatty acid composition is affected by the CPT1A genotype, or other variants in linkage disequilibrium, and support the hypothesis that omega-3 fatty acids may have been important for adaptation to the Arctic diet.

Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. These include fetal alcohol spectrum disorders (FASDs) with a wide range of cognitive deficiencies, including impaired motor skill development. Although these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells altered gene expression in their descendant neurons. Among the altered genes, an increase of the calcium-activated potassium channel Kcnn2 in the motor cortex correlated with motor learning deficits in a mouse model of FASD. Pharmacologic blockade of Kcnn2 improves these learning deficits, suggesting Kcnn2 blockers as a new intervention for learning disabilities in FASD.

The olfactory mucosa (OM) is exposed to environmental agents and therefore vulnerable to inflammation. To examine the effects of environmental toxin-initiated OM inflammation on the olfactory bulb (OB), we induced persistent rhinitis in mice and analyzed the spatial and temporal patterns of histopathological changes in the OM and OB. Mice received unilateral intranasal administration of lipopolysaccharide (LPS) or saline three times per week, and were immunohistologically analyzed at 1, 3, 7, 14 and 21 days after the first administration. LPS administration induced an inflammatory response in the OM, including the infiltration of Ly-6G-, CD11b-, Iba-1- and CD3-positive cells, the production of interleukin-1β by CD11b- and Iba-1-positive cells, and loss of olfactory sensory neurons (OSNs). In the OB, we observed activation of microglia and astrocytes and decreased expression of tyrosine hydroxylase in periglomerular cells, vesicular glutamate transporter 1, a presynaptic protein, in mitral and tufted projection neurons, and 5T4 in granule cells. Thus, the OM inflammation exerted a detrimental effect, not only on OSNs, but also on OB neurons, which might lead to neurodegeneration.

The biologic activity of individual cancer cells is highly heterogeneous. Hypoxia, one of the prominent features of a tumor microenvironment, is thought to be causal in generating this cellular heterogeneity. In this study, we revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. We found that heterodimer formation of the ERBB family receptor tyrosine kinases (RTKs), and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained. Dormant lung cancer cells were found to be resistant to EGFR tyrosine kinase inhibitor (TKI) treatment. In terms of mechanism, we found that a negative regulator of ERBB signaling, MIG6/ERRFI1/RALT/Gene33, was induced by hypoxia both in vitro and in vivo. MIG6 expression prevented heterodimer formation of ERBB family RTKs, and suppressed their downstream signaling. Knockdown of MIG6 enhanced tumor cell growth under hypoxic conditions, and promoted the phosphorylation of ERK and AKT via increased EGFR-HER3 binding. Critically, sensitivity to an EGFR-TKI, as well as to irradiation under hypoxic conditions, was increased in MIG6 knockdown cells. The expression of MIG6 was partly correlated with a pS6 negative zone in patient tumors. Analyses of tumor sections from 68 patients with activating EGFR mutations showed that patients with high MIG6 expression showed significantly shorter survival after EGFR-TKI treatment than other groups. Collectively, our data suggest that dormant cancer cells with a high MIG6 expression level might be one of the causes of EGFR-TKI resistance in EGFR mutant lung cancer cells.

The limitation of circulating tumor DNA (ctDNA) is its inability to detect cancer cell subpopulations with few or no dying cells. Lung cancer patients subjected to the EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment were prospectively collected, and ctDNA levels represented by the activating and T790M mutations were measured. The first data set (21 patients) consisting of samples collected in the period from before initiation of EGFR-TKI to at least 2 weeks after initiation: the ctDNA dynamics generally exhibited a rapid decrease and/or a transient increase. In 4 patients, we detected a transient increase of ctDNA bearing activating mutations not identified in biopsy samples. ctDNA with the same genotypical pattern was identified in 7 out of the 39 patients of the second data set intended to include samples until the onset of disease progression. In 6 of the 7 patients, this unique ctDNA appeared in the early period after treatment initiation, and did not reappear even after disease progression or chemotherapy. In another patient, similar ctDNA appeared upon radiation therapy. The identification of ctDNA with a unique genotype indicates the presence of cancer cell subpopulations that normally contain few or no dying cells, but generate dead cells because of the treatment.

We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 × 10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation.

Monitoring of disease/therapeutic conditions is an important application of circulating tumor DNA (ctDNA). We devised numerical indices, based on ctDNA dynamics, for therapeutic response and disease progression. 52 lung cancer patients subjected to the EGFR-TKI treatment were prospectively collected, and ctDNA levels represented by the activating and T790M mutations were measured using deep sequencing. Typically, ctDNA levels decreased sharply upon initiation of EGFR-TKI, however this did not occur in progressive disease (PD) cases. All 3 PD cases at initiation of EGFR-TKI were separated from other 27 cases in a two-dimensional space generated by the ratio of the ctDNA levels before and after therapy initiation (mutation allele ratio in therapy, MART) and the average ctDNA level. For responses to various agents after disease progression, PD/stable disease cases were separated from partial response cases using MART (accuracy, 94.7%; 95% CI, 73.5-100). For disease progression, the initiation of ctDNA elevation (initial positive point) was compared with the onset of objective disease progression. In 11 out of 28 eligible patients, both occurred within ±100 day range, suggesting a detection of the same change in disease condition. Our numerical indices have potential applicability in clinical practice, pending confirmation with designed prospective studies.

An odorant receptor map in mammals that is constructed by the glomerular coalescence of sensory neuron axons in the olfactory bulb is essential for proper odor information processing. How this map is linked with olfactory cortex is unknown. Using a battery of methods, including various markers of cell division in combination with tracers of neuronal connections and time-lapse live imaging, we found that early- and late-generated mouse mitral cells became differentially distributed in the dorsal and ventral subdivisions of the odorant receptor map. In addition, the late-generated mitral cells extended substantially stronger projections to the olfactory tubercle than did the early-generated cells. Together, these data indicate that the odorant receptor map is developmentally linked to the olfactory cortices in part by the birthdate of mitral cells. Thus, different olfactory cortical regions become involved in processing information from distinct regions of the odorant receptor map.

Misexpression of the dorsal mesodermal patterning factor goosecoid on the ventral side of amphibian embryos results in inhibition of blood formation in early embryogenesis. To investigate the mechanism of this inhibition, we ectopically expressed goosecoid in erythroleukemia cells. While erythroid differentiation of these cells can be induced by activin, goosecoid expressing cells were unresponsive to activin. We demonstrate an in vitro interaction between the oncogene PU.1, an ets family transcription factor thought to play a role in erythropoiesis, and the goosecoid protein (GSC). Interaction with PU.1 was specific as GSC did not bind to the ets family members, Fli-1 or Ets-2. The ability of goosecoid expressing erythroleukemia cells to differentiate in response to activin was rescued by coexpression of the GSC-binding N-terminal portion of PU.1. The N-terminal portion of PU.1 was co-immunoprecipitated with anti-GSC antibodies as well. The N-terminal domain of PU.1 is the region recognized by the retinoblastoma protein (Rb), a tumor suppressor gene presumably involved in erythroid differentiation. We show that GSC competitively inhibits binding of Rb to PU.1. Our data suggest that the suppression of blood formation by GSC could, at least in part, be mediated by binding to PU.1.