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Abstract Chloroplast development adapts to the environment for performing suitable photosynthesis. Brassinosteroids (BRs), plant steroid hormones, have crucial effects on not only plant growth but also chloroplast development. However, the detailed molecular mechanisms of BR signaling in chloroplast development remain unclear. Here, we identify a regulator of chloroplast development, BPG4, involved in light and BR signaling. BPG4 interacts with GOLDEN2-LIKE (GLK) transcription factors that promote the expression of photosynthesis-associated nuclear genes (PhANGs), and suppresses their activities, thereby causing a decrease in the amounts of chlorophylls and the size of light-harvesting complexes. BPG4 expression is induced by BR deficiency and light, and is regulated by the circadian rhythm. BPG4 deficiency causes increased reactive oxygen species (ROS) generation and damage to photosynthetic activity under excessive high-light conditions. Our findings suggest that BPG4 acts as a chloroplast homeostasis factor by fine-tuning the expression of PhANGs, optimizing chloroplast development, and avoiding ROS generation.

Aspergillus flavus produces aflatoxin, a carcinogenic fungal toxin that poses a threat to the agricultural and food industries. There is a concern that the distribution of aflatoxin-producing A. flavus is expanding in Japan due to climate change, and it is necessary to understand what types of strains inhabit. In this study, we sequenced the genomes of four Aspergillus strains isolated from agricultural fields in the Ibaraki prefecture of Japan and identified their genetic variants. Phylogenetic analysis based on single-nucleotide variants revealed that the two aflatoxin-producing strains were closely related to A. flavus NRRL3357, whereas the two non-producing strains were closely related to the RIB40 strain of Aspergillus oryzae, a fungus widely used in the Japanese fermentation industry. A detailed analysis of the variants in the aflatoxin biosynthetic gene cluster showed that the two aflatoxin-producing strains belonged to different morphotype lineages. RT-qPCR results indicated that the expression of aflatoxin biosynthetic genes was consistent with aflatoxin production in the two aflatoxin-producing strains, whereas the two non-producing strains expressed most of the aflatoxin biosynthetic genes, unlike common knowledge in A. oryzae, suggesting that the lack of aflatoxin production was attributed to genes outside of the aflatoxin biosynthetic gene cluster in these strains.

Abstract We revisit classical string motion in a near pp-wave limit of AdS5 × S5. It is known that the Toda lattice models are integrable. But if the exponential potential is truncated at finite order, then the system may become non-integrable. In particular, when the exponential potential in a three-particle periodic Toda chain is truncated at the third order of the dynamical variables, the resulting system becomes a well-known non-integrable system, Henon-Heiles model. The same thing may happen in a near pp-wave limit of AdS5 × S5, on which the classical string motion becomes chaotic.

Abstract In Japan, bathwaters are a potential source of legionellosis; therefore, the bathwater in public facilities must be regularly tested for Legionella spp. Currently, Legionella spp. is detected using the culture method, which is time-consuming and has limited accuracy. Moreover, the reproductive environment of Legionella spp. in bathwater remains unclear. Here, we investigated the environment in which Legionella spp. reproduce by analyzing the bathwater microbiota and its relationship with Legionella spp. We identified the microbiota of 112 bathwater samples collected from bathing facilities by sequencing 16S and 18S rRNA genes. Differences in the microbiota were observed between samples that tested positive and negative for Legionella spp., according to 16S rRNA sequencing and culture methods. Methyloversatilis, Cupriavidus, Phenylobacterium, Vermamoeba, and Aspidisca were highly correlated with Legionella spp. Our results support the development of strategies against legionellosis and elucidate the relationships between Legionella spp. and the coexisting microbiota in various environments.

Abstract This is a case of subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) was diagnosed by skin biopsy in a patient who presented with fever and erythema nodosum in the umbilicum following mRNA‐1273 COVID‐19 vaccination. COVID‐19 vaccines may cause SPTCL and skin biopsy may help in the diagnosis of erythema nodosum.

Objectives: Differences in demographic factors, symptoms, and laboratory data between bacterial and non-bacterial arthritis have not been defined. We aimed to identify predictors of bacterial arthritis, excluding synovial testing. Methods: This retrospective cross-sectional survey was performed at a university hospital. All patients included received arthrocentesis from January 1, 2010, to December 31, 2020. Clinical information was gathered from medical charts from the time of synovial fluid sample collection. Factors potentially predictive of bacterial arthritis were analyzed using the Student’s t -test or chi-squared test, and the chi-squared automatic interaction detector decision tree analysis. The resulting subgroups were divided into three groups according to the risk of bacterial arthritis: low-risk, intermediate-risk, or high-risk groups. Results: A total of 460 patients (male/female = 229/231; mean ± standard deviation age, 70.26 ± 17.66 years) were included, of whom 68 patients (14.8%) had bacterial arthritis. The chi-squared automatic interaction detector decision tree analysis revealed that patients with C-reactive protein > 21.09 mg/dL (incidence of septic arthritis: 48.7%) and C-reactive protein ⩽ 21.09 mg/dL plus 27.70

Abstract Lower gastrointestinal perforation is rare and challenging to diagnose in patients presenting with an acute abdomen. However, no study has examined the frequency and associated factors of diagnostic errors related to lower gastrointestinal perforation. This large-scale multicenter retrospective study investigated the frequency of diagnostic errors and identified the associated factors. Factors at the level of the patient, symptoms, situation, and physician were included in the analysis. Data were collected from nine institutions, between January 1, 2015 and December 31, 2019. Timely diagnosis was defined as diagnosis at the first visit in computed tomography (CT)-capable facilities or referral to an appropriate medical institution immediately following the first visit to a non-CT-capable facility. Cases not meeting this definition were defined as diagnostic errors that resulted in delayed diagnosis. Of the 439 cases of lower gastrointestinal perforation identified, delayed diagnosis occurred in 138 cases (31.4%). Multivariate logistic regression analysis revealed a significant association between examination by a non-generalist and delayed diagnosis. Other factors showing a tendency with delayed diagnosis included presence of fever, absence of abdominal tenderness, and unavailability of urgent radiology reports. Initial misdiagnoses were mainly gastroenteritis, constipation, and small bowel obstruction. In conclusion, diagnostic errors occurred in about one-third of patients with a lower gastrointestinal perforation.

Summary: Aflatoxins are toxic secondary metabolites produced by some aspergilli, including Aspergillus flavus. Recently, ethanol has attracted attention as an agent for the control of aflatoxin contamination. However, as aflatoxin biosynthesis utilizes acetyl coenzyme A, ethanol may be conversely exploited for aflatoxin production. Here, we demonstrated that not only the 13C of labeled ethanol, but also that of labeled 2-propanol, was incorporated into aflatoxin B1 and B2, and that ethanol and 2-propanol upregulated aflatoxin production at low concentrations (

Human body movements are based on the intrinsic trade-off between speed and accuracy. Fitts's law (1954) shows that the time required for movement is represented by a simple logarithmic equation and is applicable to a variety of movements. However, few studies have determined the role of the direction in modulating the performance of upper limb movements and the effects of the interactions between direction and distance and between direction and target size. This study examined the variations in temporal properties of the speed-accuracy trade-off in arm-pointing movements that directly manipulate objects according to the direction, distance, and target size. Participants performed pointing movements to the targets with 3 different sizes presented at 15 locations (5 directions and 3 distances) on a horizontal plane. Movement time (MT) for each trial in each condition was obtained. Subsequently, Mackenzie's model (1992), MT = a + b log2(D/W +1), where D and W represent the distance and width of the target, respectively, was fitted. The slope factor b, a fitted parameter in the equation, was calculated and evaluated according to the changes in the direction, distance, and target size. The results showed that MTs exhibited anisotropy in the hemifield, being the smallest in the right-forward direction. Additionally, the slope factor b, as a function of distance, was smaller in the rightward direction than in the forward and left-forward directions. These results suggest that the degree of difficulty of upper limb movements expands heterogeneously in various directions around the body.

Abstract Recently, Arutyunov, Bassi and Lacroix have shown that 2D non-linear sigma model with a deformed T 1,1 background is classically integrable [arXiv:2010.05573 [hep-th]]. This background includes a Kalb-Ramond two-form with a critical value. Then the sigma model has been conjectured to be non-integrable when the two-form is off critical. We confirm this conjecure by explicitly presenting classical chaos. With a winding string ansatz, the system is reduced to a dynamical system described by a set of ordinary differential equations. Then we find classical chaos, which indicates non-integrability, by numerically computing Poincaré sections and Lyapunov spectra for some initial conditions.

Aspergillus flavus produces aflatoxin, a carcinogenic fungal toxin that poses a threat to the agricultural and food industries. There is a concern that the distribution of aflatoxin-producing A. flavus is expanding in Japan due to climate change, and it is necessary to understand what types of strains inhabit. In this study, we sequenced the genomes of four Aspergillus strains isolated from agricultural fields in the Ibaraki prefecture of Japan and identified their genetic variants. Phylogenetic analysis based on single-nucleotide variants revealed that the two aflatoxin-producing strains were closely related to A. flavus NRRL3357, whereas the two non-producing strains were closely related to the RIB40 strain of Aspergillus oryzae, a fungus widely used in the Japanese fermentation industry. A detailed analysis of the variants in the aflatoxin biosynthetic gene cluster showed that the two aflatoxin-producing strains belonged to different morphotype lineages. RT-qPCR results indicated that the expression of aflatoxin biosynthetic genes was consistent with aflatoxin production in the two aflatoxin-producing strains, whereas the two non-producing strains expressed most of the aflatoxin biosynthetic genes, unlike common knowledge in A. oryzae, suggesting that the lack of aflatoxin production was attributed to genes outside of the aflatoxin biosynthetic gene cluster in these strains. [ABSTRACT FROM AUTHOR]

Probiotic products have been shown to have beneficial effects on human hosts, but what happens in the gastrointestinal tract after its ingestion remains unclear. Our aim was to investigate the changes within the small intestines after a single intake of a fermented milk product containing a probiotic. We have periodically collected the small-intestinal fluids from the terminal ileum of seven healthy subjects for up to 7 h after ingestion by small-intestinal fluid perfusion using an endoscopic retrograde bowel insertion technique. The bacterial composition of the terminal ileum clearly revealed that the ingested probiotics (Lactobacillus casei strain Shirota: LcS and Bifidobacterium breve strain Yakult: BbrY) occupied the ileal microbiota for several hours, temporarily representing over 90% of the ileal microbiota in several subjects. Cultivation of ileal fluids showed that under a dramatic pH changes before reaching the terminal ileum, a certain number of the ingested bacteria survived (8.2 ± 6.4% of LcS, 7.8 ± 11.0% of BbrY). This means that more than 1 billion LcS and BbrY cells reached the terminal ileum with their colony-forming ability intact. These results indicate that there is adequate opportunity for the ingested probiotics to continuously stimulate the host cells in the small intestines. Our data suggest that probiotic fermented milk intake affects intestinal microbes and the host, explaining part of the process from the intake of probiotics to the exertion of their beneficial effects on the host.

A 40-year-old man presented at our hospital with anaemia that had been undiagnosed for 2 years. Blood tests, endoscopy, and contrast-enhanced computed tomography were performed, but a definitive diagnosis could not be made. A subsequent bone marrow biopsy revealed basophilic stippling in transformed red blood cells, which led to a differential diagnosis of lead poisoning. Additional tests revealed elevated levels of lead in the blood. Basophilic stippling is generally found on a peripheral blood smear in lead poisoning patients; however, in this case, basophilic stippling was found only on the bone marrow smear and not in the blood smear. Even if basophilic stippling is not found in the peripheral blood, lead poisoning cannot be excluded.

With the development of measurement technology, data on the movements of actual games in various sports can be obtained and used for planning and evaluating the tactics and strategy. Defense in team sports is generally difficult to be evaluated because of the lack of statistical data. Conventional evaluation methods based on predictions of scores are considered unreliable because they predict rare events throughout the game. Besides, it is difficult to evaluate various plays leading up to a score. In this study, we propose a method to evaluate team defense from a comprehensive perspective related to team performance by predicting ball recovery and being attacked, which occur more frequently than goals, using player actions and positional data of all players and the ball. Using data from 45 soccer matches, we examined the relationship between the proposed index and team performance in actual matches and throughout a season. Results show that the proposed classifiers predicted the true events (mean F1 score > 0.483) better than the existing classifiers which were based on rare events or goals (mean F1 score < 0.201). Also, the proposed index had a moderate correlation with the long-term outcomes of the season (r = 0.397). These results suggest that the proposed index might be a more reliable indicator rather than winning or losing with the inclusion of accidental factors.

ObjectivesAlthough immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.MethodsWe retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.ResultsOf 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4–NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4–NE); p = 0.031].ConclusionThe current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

Aflatoxins (AFs), a class of toxins produced by certain species of the genus Aspergillus, occasionally contaminate food and cause serious damage to human health and the economy. AFs contamination is a global problem, and there is a need to develop effective strategies to control aflatoxigenic fungi. In this study, we focused on isothiocyanates (ITCs) as potential chemical agents for the control of aflatoxigenic fungi. We quantitatively evaluated the effects of four ITCs (allyl ITC (AITC), benzyl ITC (BITC), and methyl and phenylethyl ITCs) in dissolved and gaseous states on the growth and aflatoxin B1 production of Aspergillus flavus. In experiments using dissolved ITCs, BITC was found to be the strongest inhibitor of growth and aflatoxin B1 production by A. flavus. Meanwhile, in the gaseous state, AITC strongly inhibited the A. flavus growth. When the concentration of ITCs in the liquid medium was quantified over time, AITC levels decreased to below the detection limit within 24 h, whereas BITC levels remained stable even after 48 h. These results suggested that when ITCs are utilized to control aflatoxigenic fungi, it is necessary to use them in a dissolved or gaseous state, depending on their volatility.

Nivalenol (NIV) is a trichothecene mycotoxin that is more toxic than deoxynivalenol. It accumulates in grains due to infection with Fusarium species, which are the causative agents of scab or Fusarium head blight. An immunoassay, which is a rapid and easy analytical method, is necessary for monitoring NIV in grains. However, a specific antibody against NIV has not been prepared previously. To establish an immunoassay, we prepared NIV, introduced a linker, and generated antibodies against it. NIV was prepared from a culture of Fusarium kyushuense obtained from pressed barley through chromatographic procedures with synthetic adsorbents and silica gel. NIV was reacted with glutaric anhydride, and the reaction was stopped before mono-hemiglutaryl-NIV was changed to di-hemiglutaryl-NIV. 15-O-Hemiglutaryl-NIV was isolated via preparative HPLC and bound to keyhole limpet hemocyanin (KLH) using the active ester method. Two different monoclonal antibodies were prepared by immunizing mice with the NIV-KLH conjugate. The 50% inhibitory concentration values were 36 and 37 ng/mL. These antibodies also showed high reactivity in a direct competitive enzyme-linked immunosorbent assay and specifically reacted with NIV and 15-acetyl-NIV but not with deoxynivalenol and 4-acetyl-NIV.

Members of the Fusarium graminearum species complex (Fg complex) are the primary pathogens that cause Fusarium head blight in wheat and barley. Fg complex members grow poorly on Fusarium oxysporum-selective media, such as Komada and Fo-G2, that have also been used for the isolation of other Fusarium species. Therefore, Komada medium was modified as FG medium for the isolation of Fg complex members. However, the production of pentachloronitrobenzene that is the most effective component of FG medium is discontinued and new media is required for the selective isolation of Fg complex members. In addition, the rapid diagnosis of isolated fungi is useful for the disease control. Novel tools have been developed for isolating and characterizing Fg complex members. FG21, a semi-selective medium for isolating Fg complex members, was developed using potato dextrose agar. Furthermore, a dipstick DNA chromatography assay was developed both to identify Fusarium graminearum sensu stricto and Fusarium asiaticum in the Fg complex and their trichothecene mycotoxin types. The easier isolation and characterization of Fg complex members in Japan was attained by the combined use of FG21 medium and the dipstick DNA chromatography assay.

Abstract Background The importance of the gut microbiota at the early stage of life and their longitudinal effect on host health have recently been well investigated. In particular, Bifidobacterium longum subsp. longum, a common component of infant gut microbiota, appears in the gut shortly after birth and can be detected there throughout an individual’s lifespan. However, it remains unclear whether this species colonizes in the gut over the long term from early infancy. Here, we investigated the long-term colonization of B. longum subsp. longum by comparing the genotypes of isolates obtained at different time points from individual subjects. Strains were isolated over time from the feces of 12 subjects followed from early infancy (the first six months of life) up to childhood (approximately six years of age). We also considered whether the strains were transmitted from their mothers’ perinatal samples (prenatal feces and postnatal breast milk). Results Intra-species diversity of B. longum subsp. longum was observed in some subjects’ fecal samples collected in early infancy and childhood, as well as in the prenatal fecal samples of their mothers. Among the highlighted strains, several were confirmed to colonize and persist in single individuals from as early as 90 days of age for more than six years; these were classified as long-term colonizers. One of the long-term colonizers was also detected from the corresponding mother’s postnatal breast milk. Quantitative polymerase chain reaction data suggested that these long-term colonizers persisted in the subjects’ gut despite the existence of the other predominant species of Bifidobacterium. Conclusions Our results showed that several strains belonging to B. longum subsp. longum colonized in the human gut from early infancy through more than six years, confirming the existence of long-term colonizers from this period. Moreover, the results suggested that these strains persisted in the subjects’ gut while co-existing with the other predominant bifidobacterial species. Our findings also suggested the importance of microbial-strain colonization in early infancy relative to their succession and showed the possibility that probiotics targeting infants might have longitudinal effects. Trial Registration TRN: ISRCTN25216339. Date of registration: 11/03/2016. Prospectively registered.

Concurrent body movements have been shown to enhance the accuracy of spatial judgment, but it remains unclear whether they also contribute to perceptual estimates of gravitational space not involving body movements. To address this, we evaluated the effects of static or dynamic arm movements during prolonged whole-body tilt on the subsequent perceptual estimates of visual or postural vertical. In Experiment 1, participants were asked to continuously perform static or dynamic arm movements during prolonged tilt, and we assessed their effects on the prolonged tilt-induced shifts of subjective visual vertical (SVV) at a tilted position (during-tilt session) or near upright (post-tilt session). In Experiment 2, we evaluated how static or dynamic arm movements during prolonged tilt subsequently affected the subjective postural vertical (SPV). In Experiment 1, we observed that the SVV was significantly shifted toward the direction of prolonged tilt in both sessions. The SVV shifts decreased when performing dynamic arm movements in the during-tilt session, but not in the post-tilt session. In Experiment 2, as well as SVV, the SPV was shifted toward the direction of prolonged tilt, but it was not significantly attenuated by the performance of static or dynamic arm movements. The results of the during-tilt session suggest that the central nervous system utilizes additional information generated by dynamic body movements for perceptual estimates of visual vertical.