Global impacts of recent Southern Ocean cooling.

Since the beginning of the satellite era, Southern Ocean sea surface temperatures (SSTs) have cooled, despite global warming. While observed Southern Ocean cooling has previously been reported to have minimal impact on the tropical Pacific, the efficiency of this teleconnection has recently shown to be mediated by subtropical cloud feedbacks that are highly model-dependent. Here, we conduct a coupled model intercomparison of paired ensemble simulations under historical radiative forcing: one with freely evolving SSTs and the other with Southern Ocean SST anomalies constrained to follow observations. We reveal a global impact of observed Southern Ocean cooling in the model with stronger (and more realistic) cloud feedbacks, including Antarctic sea-ice expansion, southeastern tropical Pacific cooling, northward-shifted Hadley circulation, Aleutian low weakening, and North Pacific warming. Our results therefore suggest that observed Southern Ocean SST decrease might have contributed to cooler conditions in the eastern tropical Pacific in recent decades.

A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine's behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

First report of soybean root rot caused by Fusarium falciforme in the Republic of Korea.

Phytopathogenic Fusarium species causing root and stem rot diseases in susceptible soybean (Glycine max (L.) Merrill) are a major threat to soybean production worldwide. Several Fusarium species have been reported to infect soybean plants in the Republic of Korea, including F. solani, F. oxysporum, F. fujikuroi, and F. graminearum (Cho et al., 2004; Choi et al., 2019; Kang et al., 2020). During the nationwide survey of soybean diseases in 2015, soybean plants showing symptoms of leaf chlorosis, wilting, and shoot death were found in soybean fields in Seosan, Chungnam. Fusarium isolates were obtained from the margins of sterilized necrotic symptomatic and asymptomatic regions of the stem tissues of diseased samples by culturing on potato dextrose agar (PDA). To examine the morphological characteristics, isolates were cultured on PDA at 25°C in the darkness for 10 days. Colonies produced white aerial mycelia with apricot pigments in the medium. Macroconidia were hyaline, slightly curved in shape with 3 or 4 septa, and their average length and width were 34.6± 0.56 µm (31.4 to 37.8 µm) and 4.7±0.16 µm (4.1 to 5.8 µm), respectively (n = 20). Microconidia were elongated, oval with 0 or 1 septum, and their average length and width were 11.4±0.87 and 5.2±0.32 µm, respectively (n = 20). The colonies and conidia exhibited morphological similarities to those of F. falciforme (Xu et al., 2022). Using the primers described by O'Donnell et al. (2008), identity of a representative strain '15-110' was further confirmed by sequencing portions of two genes, the translation elongation factor 1-alpha (EF-1α) and the second largest subunit of RNA polymerase II (RPB2). The two sequences (GenBank accession No. OQ992718 and OR060664) of 15-110 were 99% similar to those of two F. falciforme strains, 21BeanYC6-14 (GenBank accession nos. ON375419 and ON331931), and 21BeanYC6-16 (GenBank accession nos. ON697187 and ON331933). To test the pathogenicity, a single-spore isolate was cultured on carnation leaf agar (CLA) at 25℃ for 10 days. Pathogenicity test was performed by root-cutting assays using 14-day-old soybean seedlings of 'Daewon' and 'Taekwang'. Ten-day-old mycelia of 15-110 were collected from the CLA plates by scraping with distilled water, and the spore suspension was filtered and diluted to 1 × 106 conidia/mL. The roots of the soybean seedlings were partially cut and inoculated by soaking in the diluted spore suspension for two hours. The seedlings were then transplanted into 12 cm plastic pots (11 cm in height) and grown in a growth chamber at 25°C, 14h light/10h dark for 2 weeks. The infected plants exhibited wilting, observed brown discoloration on the root, and eventually died within 2 weeks, whereas the control plants inoculated with sterile water remained healthy. F. falciforme 15-110 was reisolated from infected plants, but not from the uninoculated controls. The morphology of the re-isolated fungus on PDA and its target gene sequences were identical to those of the original colony. To the best of our knowledge, this is the first report of root rot in soybean caused by F. falciforme in the Republic of Korea. Fusarium spp. induce a range of diseases in soybean plants, including root rot, damping-off, and wilt. Given the variable aggressiveness and susceptibility to fungicides among different Fusarium species, it is imperative to identify the Fusarium species posing a threat to soybean production. This understanding is crucial for developing a targeted and tailored disease management strategy to control Fusarium diseases.

First report of soybean root rot caused by Fusarium proliferatum in the Republic of Korea.

Fusarium species are widespread soilborne pathogens that can cause damping-off, root rot, and wilting in soybean [Glycine max (L.) Merrill], subsequently leading to significant yield suppression. Several Fusarium spp. have already been documented for their pathogenicity on soybean plants in the Republic of Korea. The nationwide monitoring of soybean diseases continues to identify new pathogenic Fusarium spp. In 2016, five plant samples at R3-R4 growth stages, showing symptoms of wilting in the upper parts and root rot, were collected in Suwon, Gyeonggi, Republic of Korea. Fungal colonies were obtained from the diseased root samples, with the surface sterilized in 1% sodium hypochlorite for 2 min, rinsed thrice with sterile distilled water, and placed on water agar at 25°C. Five isolates were collected and purified by single-spore isolation. The fungal mycelium was subsequently cultivated on potato dextrose agar for ten days. The isolates produced abundant, aerial, and white mycelium and became purple in old cultures. Macroconidia were slender, falcate to almost straight, usually 3 to 5 septated, and thin-walled. Microconidia were formed in chains from polyphalides, clavate or oval, usually single-celled with a flattened base. These characteristics of isolates were consistent with the description of F. proliferatum (Leslie and Summerrell 2006), and the representative isolate 16-19 was selected for molecular identification to confirm its identity as F. proliferatum. Two evolutionarily conserved genes, the translation elongation factor 1-alpha (EF-1α) and the second-largest subunit of RNA polymerase II (RPB2) genes, were partially amplified using the primers described by O'Donnell et al. (2008), resulting in nucleotide sequences of 680 and 382 base pairs, respectively. These two sequences (GenBank accession numbers: OQ992720 and OR060666) showed 100 and 99.5% identity to the EF-1α and RPB2 of F. proliferatum A40 (GenBank accession numbers: KP964907 and KP964842). For the Petri-dish pathogenicity assay (Broders et al. 2007), five surface-sterilized seeds were placed on water agar media with either sterile water or actively growing '16-19' culture. After 7 days of incubation in a growth chamber (25°C; 12-hour photoperiod), brown lesions were observed on the roots of the inoculated plants, while no symptoms were observed in the sterile water-treated controls. The experiment was conducted three times. For root-cut pathogenicity assay, conidial suspension (1×106 conidia/ml) of the isolate '16-19' was prepared with harvested mycelia cultured on PDA for 10 days with sterile water. The roots of 10-day-old soybean seedlings were partially cut and soaked in either the suspension or sterile water for 2 hours. The seedlings were transplanted into 12 cm plastic pots (11 cm in height) and grew in a greenhouse (26 ± 3°C, 13-h photoperiod). The experiment followed a completely randomized design with three replicates (i.e. three plants in a pot), and it was repeated twice. The inoculated plants began to wilt 7 days after inoculation, while the sterile water-treated controls remained healthy. Ten days after inoculation, all plants were collected, washed under running tap water, and evaluated for the presence and severity of root rot using a 0-4 scale (Chang et al. 2015). The inoculated plants exhibited reduced vigor and developed dark brown lesions on their roots. F. proliferatum was reisolated from symptomatic root tissues of the infected plants, while not from those of the controls. Its colony and spores were morphologically identical to those of the original isolate. F. proliferatum was previously reported as a causative agent of soybean root rot in the United States (Díaz Arias et al. 2011) and Canada (Chang et al. 2015). This is the first report of soybean root rot caused by F. proliferatum in the Republic of Korea. This finding implies that F. proliferatum may potentially threaten soybean production in the Republic of Korea and suggests that effective disease management strategies should be established for soybean protection against the disease, along with continuous surveillance.

Novel Single Nucleotide Variations Alter Pathogenicity in Korean Isolates of Erwinia amylovora.

Erwinia amylovora, the causal agent of fire blight disease, has become a serious threat to the pome fruit industry in Korea since 2015. In this study, we showed that two new isolates of E. amylovora, Ea17-2187 and Ea19-7, obtained from pear orchards in Anseong, Korea, exhibited unique pathogenicity compared with other isolates thus far. Both were nonpathogenic to immature apple fruits but occasionally caused disease on immature pear fruits at varying reduced rates. Bioinformatic analyses revealed that their genomes are highly similar to those of the type strains TS3128 and ATCC49946 but have different mutations in essential virulence regulatory genes. Ea17-2187 has a single nucleotide substitution in rcsC, which encodes the core components of the Rcs system that activates the exopolysaccharide amylovoran production. In contrast, Ea19-7 contains a single nucleotide insertion in hrpL, which encodes a master regulator of the type III secretion system. In both cases, the mutation can cause premature termination and production of truncated gene products, disrupting virulence regulation. Introduction of the nonmutated rcsC and hrpL genes into Ea17-2187 and Ea19-7, respectively, fully recovered pathogenicity, comparable with that of TS3128; hence, these mutations were responsible for the altered pathogenicity observed. Interestingly, virulence assays on immature pear fruits showed that the hrpL mutant of Ea19-7 was still pathogenic, although its virulence level was markedly reduced. Taken together, these results suggest that the two new isolates might act as opportunistic pathogens or cheaters and that some Korean isolates might have evolved to acquire alternative pathways for activating pathogenicity factors.

Modeling of Fabry disease nephropathy using patient derived human induced pluripotent stem cells and kidney organoid system.

OBJECTIVES: To explore the possibility of kidney organoids generated using patient derived human induced pluripotent stem cells (hiPSC) for modeling of Fabry disease nephropathy (FDN). METHODS: First, we generated hiPSC line using peripheral blood mononuclear cells (PBMCs) from two male FD-patients with different types of GLA mutation: a classic type mutation (CMC-Fb-001) and a non-classic type (CMC-Fb-003) mutation. Second, we generated kidney organoids using wild-type (WT) hiPSC (WTC-11) and mutant hiPSCs (CMC-Fb-001 and CMC-Fb-003). We then compared alpha-galactosidase A (α-GalA) activity, deposition of globotriaosylceremide (Gb-3), and zebra body formation under electromicroscopy (EM). RESULTS: Both FD patients derived hiPSCs had the same mutations as those detected in PBMCs of patients, showing typical pluripotency markers, normal karyotyping, and successful tri-lineage differentiation. Kidney organoids generated using WT-hiPSC and both FD patients derived hiPSCs expressed typical nephron markers without structural deformity. Activity of α-GalA was decreased and deposition of Gb-3 was increased in FD patients derived hiPSCs and kidney organoids in comparison with WT, with such changes being far more significant in CMC-Fb-001 than in CMC-Fb-003. In EM finding, multi-lammelated inclusion body was detected in both CMC-Fb-001 and CMC-Fb-003 kidney organoids, but not in WT. CONCLUSIONS: Kidney organoids generated using hiPSCs from male FD patients might recapitulate the disease phenotype and represent the severity of FD according to the GLA mutation type.

Drug repurposing for viral cancers: A paradigm of machine learning, deep learning, and virtual screening-based approaches.

Cancer management is major concern of health organizations and viral cancers account for approximately 15.4% of all known human cancers. Due to large number of patients, efficient treatments for viral cancers are needed. De novo drug discovery is time consuming and expensive process with high failure rate in clinical stages. To address this problem and provide treatments to patients suffering from viral cancers faster, drug repurposing emerges as an effective alternative which aims to find the other indications of the Food and Drug Administration approved drugs. Applied to viral cancers, drug repurposing studies following the niche have tried to find if already existing drugs could be used to treat viral cancers. Multiple drug repurposing approaches till date have been introduced with successful results in viral cancers and many drugs have been successfully repurposed various viral cancers. Here in this study, a critical review of viral cancer related databases, tools, and different machine learning, deep learning and virtual screening-based drug repurposing studies focusing on viral cancers is provided. Additionally, the mechanism of viral cancers is presented along with drug repurposing case study specific to each viral cancer. Finally, the limitations and challenges of various approaches along with possible solutions are provided.

One-Stop Strategy for Obtaining Controllable Sensitivity and Feasible Self-Patterning in Silver Nanowires/Elastomer Nanocomposite-Based Stretchable Ultrathin Strain Sensors.

In this study, selective photo-oxidation (SPO) is proposed as a simple, fast, and scalable one-stop strategy that enables simultaneous self-patterning and sensitivity adjustment of ultrathin stretchable strain sensors. The SPO of an elastic substrate through irradiation time-controlled ultraviolet treatment in a confined region enables precise tuning of both the surface energy and the elastic modulus. SPO induces the hydrophilization of the substrate, thereby allowing the self-patterning of silver nanowires (AgNWs). In addition, it promotes the formation of nonpermanent microcracks of AgNWs/elastomer nanocomposites under the action of strain by increasing the elastic modulus. This effect improves sensor sensitivity by suppressing the charge transport pathway. Consequently, AgNWs are directly patterned with a width of 100 µm or less on the elastic substrate, and AgNWs/elastomer-based ultrathin and stretchable strain sensors with controlled sensitivity work reliably in various operating frequencies and cyclic stretching. Sensitivity-controlled strain sensors successfully detect both small and large movements of the human hand.

Pectobacterium jejuense sp. nov. Isolated from Cucumber Stem Tissue.

A single Pectobacterium-like strain named 13-115T was isolated from a specimen of diseased cucumber stem tissue collected on Jeju Island, South Korea. The strain presented a rod-like shape and was negative for Gram staining. When grown on R2A medium at 25 °C, strain 13-115T formed round, convex and white colonies. This strain showed growth at temperatures ranging from 10 to 30 °C and tolerated a pH range of 6-9. The strain could also tolerate NaCl concentrations up to 5%. Analysis of the 16S rRNA gene sequence revealed that strain 13-115T exhibited similarity of over 99% with Pectobacterium brasiliense, P. carotovorum, P. polaris, and P. parvum. By conducting multilocus sequence analyses using dnaX, leuS, and recA genes, a separate phylogenetic lineage was discovered between strain 13-115T and other members of the genus Pectobacterium. Moreover, the strain showed relatively low in silico DNA-DNA hybridization (<60.6%) and average nucleotide identity (ANI) (<94.9%) values with recognized Pectobacterium species. The isolate has a genome size of 5,069,478 bp and a genomic G + C content of 52.04 mol%. Major fatty acids identified in the strain included C16:0 (28.99%), summed feature 3 (C16:1 ω7c and/or C16:1 ω6c; 28.85%), and C18:1 ω7c (19.01%). Pathogenicity assay confirmed that the novel strain induced soft rot symptoms in cucumber plants and Koch's postulates were fulfilled. Molecular analysis and phenotypic data indicated that strain 13-115T could be classified as a new species within the Pectobacterium genus, which has been named Pectobacterium jejuense. The type strain is 13-115T (= KCTC 92800T = JCM 35940T).

First report of Stagonosporopsis cucumeris causing internal fruit rot on Oriental melon (Cucumis melo L.) in Korea.

Oriental melon (Cucumis melo L.) is a popular Korean, Japanese, and Chinese fruit (Shin et al. 2017). In April 2022, abnormal fruit (n=20) that were collected in Sangju in Gyeongbuk Province (36°27'54.6"N, 128°10'49.7"E), Korea showed approximately 5% disease incidence with severity of 10-15%. Initial symptoms included shriveling, soaking, softening, dark discoloration, and sunken lesions. Internally, a rot extended to flesh, darkening from brown to black, and producing black mycelial masses. Two fungal strains (OM-rot-01 and OM-rot-02) were isolated and exhibited similar culture characteristics: aerial mycelium that was flat and pale grey to olivaceous on potato dextrose (PDA), malt extract (MEA), and oatmeal agar (OA) after seven days at 25°C and produced abundant buff-colored pycnidial ascomata on OA. Asci were bitunicate, clavate to cylindrical, 48.4 to 69.0 × 6.1 to 6.9 µm (n=10), and ascospores were biseriate, sparse, ellipsoidal, straight to slightly curved, hyaline, smooth, apex obtuse, 1-septate, 11.1 to 14.9 × 3.8 to 5.4 µm (n=20). Conidiomata were pycnidial, mostly solitary, irregular, pale brown to black, semi-immersed, 150 to 220 × 120 to 200 µm. Conidia were oblong or ovoid, smooth, thin-walled, hyaline, aseptate, 4.4 to 6.7 × 2.0 to 2.8 µm (n=35), with 1-3 guttules per conidium. The morphological characteristics corresponded to those of Stagonosporopsis cucumeris (Hou et al. 2020). For molecular identification, genomic DNA was extracted from strains (OM-rot-01 and OM-rot-02), and the ITS regions, partial 28S rDNA (LSU), beta-tubulin (TUB2), and RNA polymerase II second largest subunit (RPB2) genes were amplified and sequenced (White et al. 1990; Woudenberg et al. 2009; Vilgalys & Hester 1990; Liu et al. 1999). The obtained sequences revealed 99-100% homology with S. cucumeris accessions (MH858625, MH870265, MT005554, and MT018021). The sequences were deposited in GenBank with accession nos. for ITS regions (OP788058, OP788059), 28S rDNA (OP788094, OP788095), TUB2 (OP810568, OP810569), and RPB2 (OP810570, OP810571). Phylogenetic analysis combined with ITS, LSU, TUB2, and RPB2 concatenated sequences using neighbor-joining method revealed that the strains were S. cucumeris. To confirm pathogenicity, OM-rot-01 was inoculated onto ripe, asymptomatic Oriental melon fruit (n=6). After they were surface sterilized with 70% alcohol, fruit were wounded using a sterilized needle and corkborer, and 5-mm-diameter mycelial plugs were attached to the wound sites, followed by covering of the fruit with aluminum foil and maintenance in a plastic box (>90% relative humidity) at 25°C. Non-wounded fruit were inoculated and incubated in a similar manner, and fruit that were inoculated with PDA plugs served as controls (n=3). The aluminum foil was removed after three days of inoculation, and other conditions were kept constant. After six days, typical internal fruit rot symptoms were observed in both wounded and non-wounded fruit; brown to black rot extended into flesh, whereas control fruit remained asymptomatic. Fungi reisolated from lesions were morphologically identical to OM-rot-01; identity was confirmed by molecular analysis, fulfilling Koch's postulates, and the pathogenicity test was conducted three times. S. cucumeris was found as a canker on Cucumis sativus in the Netherlands (Hou et al. 2020), but has not been reported elsewhere as a pathogen on Cucumis spp. To our knowledge, this is the first report of S. cucumeris causing internal fruit rot on Oriental melon in Korea. This disease poses a threat to melon production, so accurate identification of the pathogen is a key starting point for development of sustainable management practices.

Development of Real-Time Monitoring System Based on IoT Technology for Curing Compound Application Process during Cement Concrete Pavement Construction.

Among the construction processes of Portland cement concrete pavement (PCCP), the curing compound spraying process is one of the most important processes. If the curing compound spraying amount does not meet the standard or if the curing compound is not applied evenly, distresses occur at the early age of construction, ultimately causing deterioration in concrete pavement performance. The purpose of this study is to develop a real-time monitoring system for a curing compound spraying process based on the Internet of Things (IoT) and sensing technologies to improve the construction quality of concrete pavement. To achieve the goal of this research, we conducted various laboratory and field experiments. The curing compound spraying amount and sprayed status were measured and analyzed using flowmeters, image acquisition sensors, and an image processing program, and the data were provided to workers in real time and simultaneously transmitted to the IoT cloud to form a database. From this study, it is confirmed that the IoT-technology-based curing compound spraying amount and sprayed status monitoring systems can be successfully established to manage construction quality related to the curing of concrete pavement.

Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats.

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders.

CRISPR-Cas9-Mediated Correction of SLC12A3 Gene Mutation Rescues the Gitelman's Disease Phenotype in a Patient-Derived Kidney Organoid System.

The aim of this study is to explore the possibility of modeling Gitelman's disease (GIT) with human-induced pluripotent stem cell (hiPSC)-derived kidney organoids and to test whether gene correction using CRISPR/Cas9 can rescue the disease phenotype of GIT. To model GIT, we used the hiPSC line CMCi002 (CMC-GIT-001), generated using PBMCs from GIT patients with SLC12A3 gene mutation. Using the CRISPR-Cas9 system, we corrected CMC-GIT-001 mutations and hence generated CMC-GIT-001corr. Both hiPSCs were differentiated into kidney organoids, and we analyzed the GIT phenotype. The number of matured kidney organoids from the CMC-GIT-001corr group was significantly higher, 3.3-fold, than that of the CMC-GIT-001 group (12.2 ± 0.7/cm2 vs. 3.7 ± 0.2/cm2, p < 0.05). In qRT-PCR, performed using harvested kidney organoids, relative sodium chloride cotransporter (NCCT) mRNA levels (normalized to each iPSC) were increased in the CMC-GIT-001corr group compared with the CMC-GIT-001 group (4.1 ± 0.8 vs. 2.5 ± 0.2, p < 0.05). Consistently, immunoblot analysis revealed increased levels of NCCT protein, in addition to other tubular proteins markers, such as LTL and ECAD, in the CMC-GIT-001corr group compared to the CMC-GIT-001 group. Furthermore, we found that increased immunoreactivity of NCCT in the CMC-GIT-001corr group was colocalized with ECAD (a distal tubule marker) using confocal microscopy. Kidney organoids from GIT patient-derived iPSC recapitulated the Gitelman's disease phenotype, and correction of SLC12A3 mutation utilizing CRISPR-Cas9 technology provided therapeutic insight.

Inhibition of 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE expression by brassinosteroid reduces carotenoid accumulation in Arabidopsis.

Unlike the indispensable function of the steroid hormone brassinosteroid (BR) in regulating plant growth and development, the metabolism of secondary metabolites regulated by BR is not well known. Here we show that BR reduces carotenoid accumulation in Arabidopsis seedlings. BR-deficient or BR-insensitive mutants accumulated higher content of carotenoids than wild-type plants, whereas BR treatment reduced carotenoid content. We demonstrated that BR transcriptionally suppresses 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE (HPPD) expression involved in carotenogenesis via plastoquinone production. We found that the expression of HPPD displays an oscillation pattern that is expressed more strongly in dark than in light conditions. Moreover, BR appeared to inhibit HPPD expression more strongly in darkness than in light, leading to suppression of a diurnal oscillation of HPPD expression. BR-responsive transcription factor BRASSINAZOLE RESISTANT 1 (BZR1) directly bound to the promoter of HPPD, and HPPD suppression by BR was increased in the bzr1-1D gain-of-function mutation. Interestingly, dark-induced HPPD expression did not cause carotenoid accumulation, due to down-regulation of other carotenoid biosynthetic genes in the dark. Our results suggest that BR regulates different physiological responses in dark and light through inhibition of HPPD expression.

Hematopoietic stem cell-derived functional osteoblasts exhibit therapeutic efficacy in a murine model of osteogenesis imperfecta.

Currently, there is no cure for osteogenesis imperfecta (OI)-a debilitating pediatric skeletal dysplasia. Herein we show that hematopoietic stem cell (HSC) therapy holds promise in treating OI. Using single-cell HSC transplantation in lethally irradiated oim/oim mice, we demonstrate significant improvements in bone morphometric, mechanics, and turnover parameters. Importantly, we highlight that HSCs cause these improvements due to their unique property of differentiating into osteoblasts/osteocytes, depositing normal collagen-an attribute thus far assigned only to mesenchymal stem/stromal cells. To confirm HSC plasticity, lineage tracing was done by transplanting oim/oim with HSCs from two specific transgenic mice-VavR, in which all hematopoietic cells are GFP+ and pOBCol2.3GFP, where GFP is expressed only in osteoblasts/osteocytes. In both models, transplanted oim/oim mice demonstrated GFP+ HSC-derived osteoblasts/osteocytes in bones. These studies unequivocally establish that HSCs differentiate into osteoblasts/osteocytes, and HSC transplantation can provide a new translational approach for OI.

Cocaine-induced locomotor stimulation involves autophagic degradation of the dopamine transporter.

Cocaine exerts its stimulant effect by inhibiting dopamine reuptake leading to increased dopamine signaling. This action is thought to reflect binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share the behavioral actions of cocaine. We previously showed that toxic levels of cocaine induce autophagic neuronal cell death. Here, we show that subnanomolar concentrations of cocaine elicit neural autophagy in vitro and in vivo. Autophagy inhibitors reduce the locomotor stimulant effect of cocaine in mice. Cocaine-induced autophagy degrades transporters for dopamine but not serotonin in the nucleus accumbens. Autophagy inhibition impairs cocaine conditioned place preference in mice. Our findings indicate that autophagic degradation of DAT modulates behavioral actions of cocaine.

Taurine Chloramine Inhibits Leukocyte Migration by Suppressing Actin Polymerization and Extracellular Signal-Regulated Kinase.

Taurine, one of the most abundant amino acids, is ubiquitously distributed in mammalian tissues and is known to react with myeloperoxidase-derived hypochlorous acid (HOCl/OCl-) to produce taurine chloramine (Tau-Cl), which prevents inflammation by both suppressing pro-inflammatory mediators and increasing antioxidant levels. The migration of inflammatory cells, including neutrophils and macrophages, to infection sites is critical to the development of inflammation. In the present study, we investigated whether Tau-Cl suppresses the migration of inflammatory cells. Tau-Cl inhibited thioglycollate-induced leukocyte migration to the peritoneal cavity, as well as both fMLP-induced neutrophil migration and LPS-stimulated macrophage migration in a transwell system. Tau-Cl also inhibited LPS-induced actin polymerization, adhesion, and ERK phosphorylation in macrophages. Together, these findings suggest that Tau-Cl inhibits the infiltration of inflammatory cells into infection sites by inhibiting ERK activation, thereby preventing actin polymerization, and thus, the excessive infiltration of inflammatory cells, which can cause chronic inflammation.

A Highly Sensitive and Flexible Capacitive Pressure Sensor Based on Alignment Airgap Dielectric.

Flexible capacitive pressure sensors with a simple structure and low power consumption are attracting attention, owing to their wide range of applications in wearable electronic devices. However, it is difficult to manufacture pressure sensors with high sensitivity, wide detection range, and low detection limits. We developed a highly sensitive and flexible capacitive pressure sensor based on the porous Ecoflex, which has an aligned airgap structure and can be manufactured by simply using a mold and a micro-needle. The existence of precisely aligned airgap structures significantly improved the sensor sensitivity compared to other dielectric structures without airgaps. The proposed capacitive pressure sensor with an alignment airgap structure supports a wide range of working pressures (20-100 kPa), quick response time (≈100 ms), high operational stability, and low-pressure detection limit (20 Pa). Moreover, we also studied the application of pulse wave monitoring in wearable sensors, exhibiting excellent performance in wearable devices that detect pulse waves before and after exercise. The proposed pressure sensor is applicable in electronic skin and wearable medical assistive devices owing to its excellent functional features.

ERK Inhibition Increases RANKL-Induced Osteoclast Differentiation in RAW 264.7 Cells by Stimulating AMPK Activation and RANK Expression and Inhibiting Anti-Osteoclastogenic Factor Expression.

Bone absorption is necessary for the maintenance of bone homeostasis. An osteoclast (OC) is a monocyte-macrophage lineage cell that absorbs bone tissue. Extracellular signal-regulated kinases (ERKs) are known to play important roles in regulating OC growth and differentiation. In this study, we examined specific downstream signal pathways affected by ERK inhibition during OC differentiation. Our results showed that the ERK inhibitors PD98059 and U0126 increased receptor activator of NF-κB ligand (RANKL)-induced OC differentiation in RAW 264.7 cells, implying a negative role in OC differentiation. This is supported by the effect of ERK2-specific small interfering RNA on increasing OC differentiation. In contrast to our findings regarding the RAW 264.7 cells, the ERK inhibitors attenuated the differentiation of bone marrow-derived cells into OCs. The ERK inhibitors significantly increased the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) but not the activation of p38 MAPK, Lyn, and mTOR. In addition, while the ERK inhibition increased the expression of the RANKL receptor RANK, it decreased the expression of negative mediators of OC differentiation, such as interferon regulatory factor-8, B-cell lymphoma 6, and interferon-γ. These dichotomous effects of ERK inhibition suggest that while ERKs may play positive roles in bone marrow-derived cells, ERKs may also play negative regulatory roles in RAW 264.7 cells. These data provide important information for drug development utilizing ERK inhibitors in OC-related disease treatment.

Pigmentation and Flavonoid Metabolite Diversity in Immature 'Fuji' Apple Fruits in Response to Lights and Methyl Jasmonate.

Artificial pigmentation of apple fruits has been intensely evaluated to generate less pigmented red apples, which are profitable because of the changes in fruit quality. In this study, we analyzed the diversity of flavonoids and the patterns of flavonoid metabolic gene expression under light irradiation with or without methyl jasmonate (MeJA) treatment in immature (S1) and color-turning (S2) staged 'Fuji' apples. Further, we assessed the metabolic regulation at the gene level between anthocyanin and flavonol in light-responsive apple skins. UV-B exposure within 3 days was found to significantly stimulate anthocyanin accumulation in apple skin compared to other light exposure. S1 skin was more sensitive to UV-B and MeJA treatment, in the aspect of indaein accumulation. The enhancement of apple pigmentation following treatment with adequate levels of UV-B and MeJA was maximized at approximately 72 h. Red (range from 4.25 to 17.96 µg·g-1 DW), blue (range from 4.59 to 9.17 µg·g-1 DW) and UV-A (range from 3.98 to 19.12 µg·g-1 DW) lights contributed to the induction of idaein content. Most genes related to the flavonoid pathways increased their expression under UV-B exposure, including the gene expression of the transcription factor, MdMYB10, a well-known upstream factor of flavonoid biosynthesis in apples. The boosted upregulation of MdMYB10, MdCHS, MdF3H MdLDOX, and MdUFGT genes due to MeJA in UV-B was found and may contribute the increase of idaein. UV-A and UV-B caused higher quercetin glycoside content in both S1 and S2 apple skins than longer wavelengths, resulting in significant increases in quercetin-3-O-galactoside and quercetin-3-O-glucoside. These results suggest that the application of adequate UV-B with MeJA in less-pigmented postharvest apples will improve apple color quality within a short period.