Taxonomy, Phylogeny, and Host Expansion of Powdery Mildew Fungi Parasitic to Veronica Species.

Powdery mildew is a prevalent fungal disease that affects various Veronica spp. (Plantaginaceae), caused by species in the genera Podosphaera and Golovinomyces (Erysiphales). There have been recent taxonomic changes in these groups and ongoing disease occurrence on a range of Veronica species previously unrecognized as hosts; however, the pathogen found in Korea remains unidentified. This study aimed to identify the causative agent of powdery mildew on Veronica spp. in Korea through molecular phylogenetic analysis of internal transcribed spacer (ITS) and large subunit (LSU) sequences of rDNA and morphological examination. Our study identified Golovinomyces bolayi as the sole pathogen affecting all nine Veronica species in Korea and confirmed that G. cichoracearum s. str., which was previously identified as the pathogen, was not the causal agent. These results expand the known host range of G. bolayi, including the addition of five Veronica species in Korea: V. hederifolia, V. kiusiana var. glabrifolia, V. longifolia, V. polita, and V. serpyllifolia. Notably, V. kiusiana has been added as a new global host of powdery mildew. These findings substantially enhance our understanding of the taxonomy of powdery mildew pathogens on Veronica species and provide valuable insights into their evolutionary host expansion.

A New Cloud-Native Tool for Pharmacogenetic Analysis.

BACKGROUND: The advancement of next-generation sequencing (NGS) technologies provides opportunities for large-scale Pharmacogenetic (PGx) studies and pre-emptive PGx testing to cover a wide range of genotypes present in diverse populations. However, NGS-based PGx testing is limited by the lack of comprehensive computational tools to support genetic data analysis and clinical decisions. METHODS: Bioinformatics utilities specialized for human genomics and the latest cloud-based technologies were used to develop a bioinformatics pipeline for analyzing the genomic sequence data and reporting PGx genotypes. A database was created and integrated in the pipeline for filtering the actionable PGx variants and clinical interpretations. Strict quality verification procedures were conducted on variant calls with the whole genome sequencing (WGS) dataset of the 1000 Genomes Project (G1K). The accuracy of PGx allele identification was validated using the WGS dataset of the Pharmacogenetics Reference Materials from the Centers for Disease Control and Prevention (CDC). RESULTS: The newly created bioinformatics pipeline, Pgxtools, can analyze genomic sequence data, identify actionable variants in 13 PGx relevant genes, and generate reports annotated with specific interpretations and recommendations based on clinical practice guidelines. Verified with two independent methods, we have found that Pgxtools consistently identifies variants more accurately than the results in the G1K dataset on GRCh37 and GRCh38. CONCLUSIONS: Pgxtools provides an integrated workflow for large-scale genomic data analysis and PGx clinical decision support. Implemented with cloud-native technologies, it is highly portable in a wide variety of environments from a single laptop to High-Performance Computing (HPC) clusters and cloud platforms for different production scales and requirements.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

First Report of Leaf Spot Caused by Arthrinium arundinis on Amaranthus hybridus in Korea.

Amaranthus hybridus (=A. patulus), often called green amaranth, is an annual herbaceous plant of the Amaranthaceae. This plant is considered a harmful weed in the agricultural context of North America and has expanded its distribution to Asia and Europe. In Korea, it has become a problematic invasive issue, leading to economic losses due to reduced crop yields and rising weed management costs (Park et al., 2014), although its seeds and young leaves are edible and frequently consumed. In October 2020, we observed leaf spot symptoms on A. hybridus plants that were growing within perilla farms (Perilla frutescens var. japonica) located in Damyang (35°14'07"N, 126°59'40"E), Korea, with a disease incidence of 20 to 30% of the inspected plants. The initial signs appeared as grey to brown dots on the leaves, which gradually expanded into irregular, brown patches with a diameter of 2-3 cm. A single spore was isolated from the diseased leaf under a dissecting microscope, placed onto a 2% water agar plate, and incubated in darkness at 25°C for three days. Pure cultures were obtained by transferring single hyphal tips onto potato dextrose agar (PDA) plates. Five single-spore isolates were the same in the cultural and morphological examination, and a representative isolate (P309) was preserved at the Korean Agricultural Culture Collection (KACC49813), Korea. Colonies appeared light gray to white with regular margins and reached 4 to 5 cm in diameter after a week. After two weeks, black patches of spores were often visible in the aerial mycelia. Conidiophores were brown to pale brown, often branched, thick-walled, and measured 6.8 × 2.7 µm (n = 30). Conidia were single-celled, dark brown, globose to ellipsoid, and measured 6.8 × 5.0 µm (n = 50), with a ratio of length/width of 1.1 to 1.6 (n = 50). These morphological characteristics matched those of Arthrinium arundinis (Crous et al., 2013). For molecular identification, genomic DNA was extracted from conidia and mycelia on two-week-old PDA culture of the KACC49813. PCR was performed for the internal transcribed spacer (ITS) (primers ITS1/ITS4, White et al. 1990), the large subunit (LSU) rDNA (primers LROR/LR5, Vilgalys et al. 1990), the beta-tubulin gene (TUB) (primers T1/Bt-2b, O'Donnell and Cigelnik 1997), and the translation elongation factor 1-alpha (TEF) (primers EF1-728F/EF-2, Crous et al. 2013). A BLASTn search of the resulting sequences of ITS (560 bp; OL744431), LSU (881 bp; OL744432), TUB (790 bp; PP084934), and TEF (445 bp; PP084935) revealed 100 % similarity (e-value=0.0, coverage=100%) to previously reported sequences of Arthrinium arundinis (e.g. MF627422 for ITS, KF144930 for LSU, KF144973 for TUB, and KY705146 for TEF), confirming the identity of the Korean isolate. Pathogenicity assays were performed twice by spraying 1 ml of a conidial suspension (1.1 × 104 conidia per mL) onto the leaf surface of sixteen healthy A. hybridus plants. Sixteen control plants were sprayed with sterile water. All plants were kept in a growth chamber at 80% relative humidity and 23 °C with a 12-h light/dark cycle. Three weeks after the inoculation, initial symptoms mirroring the aforementioned ones appeared, while the control plants remained symptomless. Fungal isolates were successfully re-isolated from the inoculated leaves, and their identity as A. arundinis was confirmed by DNA sequencing, thus fulfilling Koch's postulates. To our knowledge, this is the first report of leaf spot caused by A. arundinis on Amaranthus hybridus, not only in Korea but globally. Arthrinium arundinis has also been reported as a plant pathogen on some agricultural crops (Ji et al. 2020; Liao et al. 2022; Farr and Rossman 2023), suggesting its polyphagous behavior. Then, this pathogen could represent a potential risk to the cultivation of edible amaranth in Korea and other crops where Amaranthus species are spread as weeds. For this reason, continuous monitoring is necessary to assess the impact of this fungus on Amaranthus and other crops.

First Report of Powdery Mildew Caused by Golovinomyces ambrosiae on Xanthium orientale in Korea.

Xanthium orientale L. (syn. Xanthium canadense Mill., Asteraceae), known as cocklebur, is an annual weed native to North America, which is now a neophyte distributed throughout the world. This plant was accidentally introduced to Korea in the late 1970s ( So et al. 2008) and is considered a problematic exotic weed in orchards, for which many herbicides are ineffective (Kim et al. 2020). In September 2018, powdery mildew was observed on X. orientale in Jeju, Korea. The disease incidence ranged from 40 to 60%. Voucher specimens were deposited in the Korea University Herbarium (Accession No. KUS-F30795) and Kunsan National University Herbarium (KSNUH1988). Symptoms appeared as round to irregular white patches with abundant hyphal growth on the leaf surface. Hyphal appressoria were nipple-shaped, and 3 to 6 µm diam. Conidiophores (n = 30) were 145 to 206 × 9 to 11.6 µm and produced 2 to 5 immature conidia in chains with a sinuate outline. Foot-cells of the conidiophores were straight, cylindrical, and 43 to 100.9 µm long. Conidia (n = 30) were ellipsoid-ovoid, doliiform to somewhat limoniform, 25.2 to 31.8 × 13.6 to 16.8 µm (l/w 1.6 to 2.1), and devoid of distinct fibrosin bodies. The morphological characteristics corresponded to those of Golovinomyces ambrosiae (Schwein.) U. Braun & R.T.A. Cook (Braun and Cook 2012, under Golovinomyces spadiceus (Beck. & M.A. Curtis) U. Braun; Qiu et al. 2020). To confirm the identity of the causal fungus, the internal transcribed spacer (ITS), large subunit (LSU) (Bradshaw and Tobin 2020), the intergenic spacer (IGS) of rDNA, and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene (Bradshaw et al. 2022) were amplified for a herbarium specimen (KUS-F30795). A BLASTn search of these sequences revealed 100% identity with reference sequences of G. ambrosiae on diverse Asteraceae plants (AB077644 for ITS, AB077643 for LSU, ON361171 for IGS, and ON075648 for GAPDH). However, there was a single nucleotide difference on both the IGS and GAPDH sequences when compared to the closely related species Golovinomyces latisporus. The sequences were deposited in GenBank (Accession No. OQ165157 (ITS), OQ165164 (LSU), OR050524 (IGS), and OR086076 (GAPDH)). Phylogenetic analyses of ITS, LSU, IGS, and GAPDH sequences revealed the Korean sample formed a well-supported group with other G. ambrosiae sequences, confirming its identity. A pathogenicity test was performed through inoculation by gently pressing diseased leaves onto the leaves of five healthy plants. Five non-inoculated plants served as controls. All plants were maintained in a greenhouse at 25±2°C. Powdery mildew colonies developed on the inoculated plants after ten days, whereas the control plants remained symptomless. The fungus present on the inoculated leaves was morphologically identical to that observed on the initially diseased leaves, fulfilling Koch's postulates. Powdery mildew on X. orientale has previously been reported as Golovinomyces cichoracearum (≡ Erysiphe cichoracearum) sensu lato in the USA, G. ambrosiae (= G. spadiceus) throughout all continents, and Podosphaera fusca sensu lato (now P. xanthii) in Korea (Braun and Cook 2012; Farr and Rossman 2023). To date, powdery mildew in Korea has been reported only on Xanthium strumarium as G. cichoracearum s. lat. and Podosphaera xanthii (KSPP 2022). To our knowledge, this is the first report of powdery mildew caused by G. ambrosiae on X. orientale in Korea.

Quantitative imaging of vesicle-protein interactions reveals close cooperation among proteins.

Membrane-bound vesicles such as extracellular vesicles (EVs) can function as biochemical effectors on target cells. Docking of the vesicles onto recipient plasma membranes depends on their interaction with cell-surface proteins, but a generalizable technique that can quantitatively observe these vesicle-protein interactions (VPIs) is lacking. Here, we describe a fluorescence microscopy that measures VPIs between single vesicles and cell-surface proteins, either in a surface-tethered or in a membrane-embedded state. By employing cell-derived vesicles (CDVs) and intercellular adhesion molecule-1 (ICAM-1) as a model system, we found that integrin-driven VPIs exhibit distinct modes of affinity depending on vesicle origin. Controlling the surface density of proteins also revealed a strong support from a tetraspanin protein CD9, with a critical dependence on molecular proximity. An adsorption model accounting for multiple protein molecules was developed and captured the features of density-dependent cooperativity. We expect that VPI imaging will be a useful tool to dissect the molecular mechanisms of vesicle adhesion and uptake, and to guide the development of therapeutic vesicles.

Clozapine Use for Bipolar Disorder: An Asian Psychotropic Prescription Patterns Consortium Study.

BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing. METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling. RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months. CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

Efficient Labeling of Vesicles with Lipophilic Fluorescent Dyes via the Salt-Change Method.

Fluorescent labeling allows for imaging and tracking of vesicles down to single-particle level. Among several options to introduce fluorescence, staining of lipid membranes with lipophilic dyes provides a straightforward approach without interfering with vesicle content. However, incorporating lipophilic molecules into vesicle membranes in an aqueous solution is generally not efficient because of their low water solubility. Here, we describe a simple, fast (<30 min), and highly effective procedure for fluorescent labeling of vesicles including natural extracellular vesicles. By adjusting the ionic strength of the staining buffer with NaCl, the aggregation status of DiI, a representative lipophilic tracer, can be controlled reversibly. Using cell-derived vesicles as a model system, we show that dispersion of DiI under low-salt condition improved its incorporation into vesicles by a factor of 290. In addition, increasing NaCl concentration after labeling induced free dye molecules to form aggregates, which can be filtered and thus effectively removed without ultracentrifugation. We consistently observed 6- to 85-fold increases in the labeled vesicle count across different types of dyes and vesicles. The method is expected to reduce the concern about off-target labeling resulting from the use of high concentrations of dyes.

First Report of Powdery Mildew Caused by Golovinomyces ambrosiae on Erigeron annuus in Korea.

Erigeron annuus (L.) Pers., known as annual fleabane or eastern daisy fleabane, is native to North America and was unintentionally introduced to Korea in the 1910s (Park, 1995). It is now widely naturalized throughout Korea and was designated as one of the ten major introduced plants in Korea by the Korea National Arboretum. In September 2012, several dozen annual fleabanes were found to be heavily infected with powdery mildew. Symptoms first appeared as circular to irregular white patches, which subsequently showed abundant hyphal growth on both sides of the leaves. The same symptoms have continuously been found on annual fleabane throughout the country, where the disease incidence was often higher than 80%. Five voucher specimens were deposited in the Korea University Herbarium (KUS-F30208, 31414, 31774, 31784 and 32003). Hyphae were septate, branched, and 4.5 to 6.7 µm wide. Appressoria on the mycelium were lobed. Conidiophores (n = 30), measured 154 to 215 × 9 to 12.5 µm, were simple and produced 2 to 4 immature conidia in chains with a sinuate outline, followed by 2 to 3 cells. Foot-cells of conidiophores were straight, cylindrical, and 40 to 98 µm long. Conidia (n = 30) were hyaline, ellipsoid to barrel-shaped, measured 25.3 to 35.8 × 13 to 17 µm (length/width ratio = 1.62 to 2.31), lacked distinct fibrosin bodies, and showed reticulate wrinkling of the outer walls. Primary conidia were apically rounded and basally truncated and generally smaller than the secondary conidia. Germ tubes were produced on the subterminal position of conidia. No chasmothecia were observed. The structures described above were typical of the Euoidium anamorph of the genus Golovinomyces, and the fungus measurements were compatible with those of G. ambrosiae (Schwein.) U. Braun & R.T.A. Cook (Qiu et al., 2020). To confirm the identity of the causal fungus, the internal transcribed spacer (ITS) and large subunit (LSU) regions of rDNA from the five herbarium specimens were amplified with primers PM10/ITS4 for ITS and PM3/TW14 for LSU (Bradshaw and Tobin, 2020; Mori et al., 2000; White et al., 1990) and sequenced directly. The resulting sequence was deposited in GenBank (Accession No. OP788040-4 for ITS and OP788045-9 for LSU). Comparison with the sequences available in the GenBank database revealed that the isolates showed 100% sequence similarity with those of G. ambrosiae from the family Asteraceae (e.g., MT355557, MF612182, etc.). Pathogenicity was confirmed through inoculation by gently pressing diseased leaves onto the leaves of five healthy potted plants. Five non-inoculated plants served as controls. Plants were maintained in a greenhouse at 22 to 28°C. Inoculated plants developed signs and symptoms after seven days, whereas the control plants remained healthy. The fungus present on the inoculated plants was morphologically identical to that observed initially on diseased plants, fulfilling Koch's postulates. Powdery mildew infections of Erigeron spp. associated with Golovinomyces species have been known in the United States, France, and China (Farr and Rossman, 2022). To our knowledge, this is the first report of powdery mildew disease caused by G. ambrosiae on E. annuus outside of North America as well as in Korea. According to our field observation, powdery mildew infections were found only on annual fleabanes growing in shady areas, not in sunny places.

First Report of Powdery Mildew Caused by Golovinomyces ambrosiae on New York Aster (Symphyotrichum novi-belgii) in Korea.

Symphyotrichum novi-belgii (L.) G.L. Nesom (syn. Aster novi-belgii L.), known as New York aster, is a perennial herb used in gardens and as a potted plant. The plant is native to North America but has been developed into various horticultural varieties. In Korea, it is one of the most common plants used for autumn bloom. In September 2011, New York asters (variety unknown) showing typical signs of powdery mildew were observed in a public garden in Seoul, Korea. Since then, the disease on New York asters has been continuously found in parks and flower markets in different regions of Korea. Voucher specimens (n=3) were deposited in the Korea University Herbarium (KUS-F 30752, 31865, and 32103). On leaves, circular to irregular white patches appeared which subsequently showed abundant hyphal growth on both sides of the leaves and on young stems and inflorescences, reducing the aesthetic value and vigor of the plants affected. Hyphae were septate, branched, and 4 to 8 µm wide. Appressoria on the mycelium were nipple-shaped. Conidiophores measured 110 to 200 × 9 to 11.5 µm, were simple, and produced 2 to 5 immature conidia in chains with a sinuate outline, followed by 2 to 3 cells. Foot-cells of conidiophores were straight, cylindric, and 55 to 125 µm long. Conidia were hyaline, ellipsoid to barrel-shaped, measured 22 to 52 × 15 to 20 µm (length/width ratio = 1.5-2.5), lacked distinct fibrosin bodies, and produced germ tubes on the subterminal position, with reticulate wrinkling of the outer walls. No chasmothecia were observed. The structures described above were typical of the Oidium subgenus Euoidium anamorph of the genus Golovinomyces, and the fungus measurements were consistent with those of G. ambrosiae (Schwein.) U. Braun & R.T.A. Cook (Braun and Cook 2012, Qiu et al. 2020). To confirm the identity of the causal fungus, the internal transcribed spacer (ITS) and large subunit (LSU) regions of rDNA were amplified with primers PM10/ITS4 for ITS and PM3/TW14 for LSU (Mori et al. 2000, Bradshaw and Tobin 2020). The resulting sequences were deposited in GenBank (Accession No. OP028065-7 for ITS and OP028053-5 for LSU). A GenBank BLAST search of these sequences revealed 100% identity with sequences of G. ambrosiae on many asteraceous plants, including S. novi-belgii from China (MK452575-9 for ITS and MK452648-52 for LSU). Pathogenicity was confirmed through inoculation by gently pressing diseased leaves onto leaves of five healthy potted New York aster plants. Five non-inoculated plants served as controls. Plants were maintained in an incubator at 24°C. Inoculated plants developed signs and symptoms after three weeks, whereas the control plants remained symptomless. The fungus present on the inoculated plants was morphologically identical to that observed initially on diseased plants, fulfilling Koch's postulates. The powdery mildew infections of S. novi-belgii associated with G. ambrosiae have been widely known in Europe and North America but only recently in China (Qiu et al. 2020, Farr and Rossman 2022). In Japan, Podosphaera fuliginea was known to be associated with powdery mildew of S. novi-belgii (Farr and Rossman 2022). To our knowledge, this is the first report of powdery mildew caused by G. ambrosiae on S. novi-belgii in Korea. The powdery mildew on this ornamental plant can be considered a severe threat.

First Report of Powdery Mildew Caused by Golovinomyces ambrosiae on Leucanthemum vulgare in Korea.

Leucanthemum vulgare Lam. (Asteraceae), known as ox-eye daisy, is a perennial herb native to Europe and western Asia (Clements et al. 2004, McDougall et al. 2018). In Korea, this plant was introduced for ornamental purposes but has been naturalized as a widespread invasive species. In June 2015, symptoms of a powdery mildew disease were observed on L. vulgare in a public garden in Goseong (38°14'18"N, 128°32'56"E), Korea. Since then, its findings have continued throughout the country, including Mokpo and Seogwipo (in 2018), Hongcheon and Seoul (in 2020), Boeun, Gunsan, and Namwon (in 2022), where the disease incidence was often higher than 80%. Symptoms first appeared as circular to irregular white powdery patches covering leaves and stems. Affected plants became distorted, eventually losing their aesthetic and ornamental value. A total of sixteen samples were deposited in the herbarium of Korea University (KUS-F), Korea. Microscopic observations showed that hyphal appressoria were nipple-shaped. Conidiophores were cylindrical, 98 to 157 × 9 to 12 µm, and produced 2 to 5 immature conidia in chains with a sinuate outline. Foot cells were cylindrical, straight, and 37 to 65 µm long. Conidia were ellipsoid to barrel-shaped, 23 to 39 × 12 to 19 µm, with a length/width ratio of 1.4 to 2.3 and devoid of fibrosin bodies. Germ tubes were produced in the perihilar position of the conidia. Primary conidia were apically rounded and basally subtruncated. No chasmothecia were found until the plants died in winter. The morphological characteristics were typical for anamorph of the genus Golovinomyces. To identify the fungus, genomic DNA was extracted from the four herbarium specimens (KUS-F 28650, 30839, 31728, and 31787). PCR products were amplified using the primer sets PM10/ITS4 for internal transcribed spacer (ITS) and PM3/TW14 for the large subunit (LSU) of the rDNA (Mori et al. 2000, Bradshaw and Tobin 2020). Sequences obtained in the present study were deposited at GenBank (accession numbers ON834488-91 for ITS and ON834494-7 for LSU). A BLASTn search of the Korean specimens showed 100% identity with reference sequences of G. ambrosiae in GenBank (KX98730, MK452580, and MK452588 for ITS and MF612182, MK452653, and MK452661 for LSU). In phylogenetic trees of a concatenated dataset of the ITS and LSU sequences, the Korean specimens formed a well-supported clade with the reference sequences of G. ambrosiae. Pathogenicity tests were carried out by touching and dusting an infected leaf (KUS-F 31787) onto the upper leaf surface of five healthy plants. Five non-inoculated plants served as controls. After two weeks, all inoculated plants formed white patches on the surface of leaves and stems, whereas the control plants remained symptomless. The fungus on the inoculated plants was identical to that observed on the initially diseased plant, fulfilling Koch's postulates. As a result, the causal agent of the powdery mildew on L. vulgare was confirmed as G. ambrosiae (Schwein.) U. Braun & R.T.A. Cook, based on the current taxonomy and nomenclature of this species by Qiu et al. (2020).. Previously powdery mildew collections on L. vulgare have been reported as Golovinomyces cichoracearum (≡ Erysiphe cichoracearum) s. lat. in Estonia, Finland, Germany, and Switzerland, Golovinomyces biocellatus in Spain, and Podosphaera fusca (probably P. xanthii according to the current taxonomy) in the former Soviet Union (now Russia and adjacent countries) (Farr and Rossman 2022). This study is the first report of powdery mildew disease caused by G. ambrosiae on L. vulgare in Korea. Qiu et al. (2020) confirmed the occurrence of G. ambrosiae on L. maximum, another species of the genus Leucanthemum. As powdery mildew causes damage to the cultivation of L. vulgare by loss of ornamental value, appropriate control measures should be developed.

Dosing of Mood Stabilizers for Bipolar Disorder Patients in the Research on Asian Psychotropic Prescription Patterns Consortium Study.

BACKGROUND: Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (BD) patients in Asia are not well documented, we examined prevalence and clinical correlates of treatment of Asian BD patients with relatively high doses of MSs. METHODS: We conducted a pharmacoepidemiological survey across 13 Asian countries and territory in the Research on Asian Psychotropic Prescription Patterns Consortium. Mood stabilizer doses were converted to lithium carbonate equivalents (Li-eq milligrams per day). We compared relatively high (>900 Li-eq mg/day) versus lower MS doses by bivariate comparisons, followed by multivariable linear regression to identify factors associated with higher MS doses. RESULTS: Among 1647 participants, MS dose averaged 584 (confidence interval, 565-603 Li-eq mg/d). Preliminarily, the 13.1% of the subjects given greater than 900 mg/d versus those given lower doses were younger, male, currently hospitalized, not currently depressed, and reported lifetime suicidal ideation; they also received relatively high doses of antipsychotics, received electroconvulsive treatment within the previous 12 months, and had greater ratings of tremors and sedation. By linear regression modeling, the mean proportion given high doses of MS was associated significantly and independently with higher doses of antipsychotics, younger age, male sex, hospitalized, more years of illness, country, higher body mass index, recent electroconvulsive treatment, and being in illness remission. CONCLUSIONS: Relatively high doses of MSs for BD are prevalent, but vary markedly among Asian countries, and are particularly likely among young males, ill for many years, and given high doses of antipsychotics or ECT. These characteristics allow better identification of patient profiles that can guide treatment of BD patients.

Development of an attenuated smallpox vaccine candidate: The KVAC103 strain.

Smallpox, a disease caused by the variola virus, is one of the most dangerous diseases and had killed numerous people before it was eradicated in 1980. However, smallpox has emerged as the most threatening bio-terrorism agent; as the first- and second-generation smallpox vaccines have been controversial and have caused severe adverse reactions, new demands for safe smallpox vaccines have been raised and some attenuated smallpox vaccines have been developed. We have developed a cell culture-based highly attenuated third-generation smallpox vaccine candidate KVAC103 strain by 103 serial passages of the Lancy-Vaxina strain derived from the Lister in Vero cells. Several clones were selected, taking into consideration their shape, size, and growth rate in mammalian cells. The clones were then inoculated intracerebrally in suckling mice to test for neurovirulence by observing survival. Protective immune responses in adult mice were examined by measuring the levels of neutralization antibodies and IFN-γ expression. Among several clones, clone 7 was considered the best alternative candidate because there was no mortality in suckling mice against a lethal challenge. In addition, enhanced neutralizing antibodies and T-cell mediated IFN-γ production were observed in clone 7-immunized mice. Clone 7 was named "KVAC103" and was used for the skin toxicity test and full-genome analysis. KVAC103-inoculated rabbits showed reduced skin lesions compared to those inoculated with the Lister strain, Lancy-Vaxina. A whole genome analysis of KVAC103 revealed two major deleted regions that might contribute to the reduced virulence of KVAC103 compared to the Lister strain. Phylogenetic inference supported the close relationship with the Lister strain. Collectively, our data demonstrate that KVAC103 holds promise for use as a third-generation smallpox vaccine strain due to its enhanced safety and efficacy.

Lipolytic and Lipophagic Effects of Pinellia ternata Pharmacopuncture on Localized Adiposity.

Localized adiposity is not only a common aesthetic issue but also a health risk factor. Pharmacopuncture can be a therapeutic option for the imbalance of regional fat distribution. The tuber of Pinellia ternata has been prescribed as antitussive and expectorant as a traditional Korean medicine. This study investigated the effects of pharmacopuncture with P. ternata water extract (PT) on localized adiposity. Male C57BL/6J mice were fed on a high-fat diet (HFD) for 6 weeks. 100 µL of 10 mg/mL of PT was injected into the left-side inguinal fat pad, while saline was injected into the right-side inguinal fat pad as self-control. Treatments were performed 3 times per week for 4 weeks. The inguinal fat weight was analyzed by dual-energy X-ray absorptiometry. PT pharmacopuncture significantly decreased the weight of the inguinal fat pad. The adipocyte size was reduced with increases of lipolytic enzymes and lipophagy-related factors by PT pharmacopuncture. There was marked inhibition of lipid accumulation content in 3T3-L1 adipocytes by PT treatment. The expressions of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), autophagy-related gene (ATG) 5, ATG7, and LC3 were markedly increased by PT treatments in vivo and in vitro. This study suggests that pharmacopuncture of Pinellia ternata has ameliorative effects on adiposity by lipid catabolic effects via activating both lipolysis and lipophagy in a localized region.

An elegant route to overcome fundamentally-limited light extraction in AlGaN deep-ultraviolet light-emitting diodes: Preferential outcoupling of strong in-plane emission.

While there is an urgent need for semiconductor-based efficient deep ultraviolet (DUV) sources, the efficiency of AlGaN DUV light-emitting diodes (LEDs) remains very low because the extraction of DUV photons is significantly limited by intrinsic material properties of AlGaN. Here, we present an elegant approach based on a DUV LED having multiple mesa stripes whose inclined sidewalls are covered by a MgF2/Al omni-directional mirror to take advantage of the strongly anisotropic transverse-magnetic polarized emission pattern of AlGaN quantum wells. The sidewall-emission-enhanced DUV LED breaks through the fundamental limitations caused by the intrinsic properties of AlGaN, thus shows a remarkable improvement in light extraction as well as operating voltage. Furthermore, an analytic model is developed to understand and precisely estimate the extraction of DUV photons from AlGaN DUV LEDs, and hence to provide promising routes for maximizing the power conversion efficiency.

Distinct U-shape efficiency-versus-current curves in AlGaN-based deep-ultraviolet light-emitting diodes.

The efficiency of an AlGaN deep-ultraviolet light-emitting diode with peak emission wavelength of 285 nm is investigated as a function of current over a wide range of temperatures (110 K to 300 K). We find that the efficiency-versus-current curve exhibits unique and distinct features over the entire temperature range including three points of inflection. At low temperatures, the change in slope in the efficiency-versus-current curve is particularly pronounced producing a minimum in the efficiency after which the efficiency rises again. Furthermore, at high current density, the low-temperature efficiency exceeds the room-temperature efficiency. The feature-rich efficiency-versus-current curve is consistent with an enhancement in p-type conductivity by field-ionization of acceptors that occurs in the high-injection regime and is particularly pronounced at low temperatures. Differential conductivity measurements show a marked rise in the high-injection regime that is well correlated to the minimum point in the efficiency-versus-current curve.

The Effects of Visual Field Conditions on Electromyography of the Lower Extremities during Reaching Tasks in Healthy Adults.

[Purpose] The purpose of this study was to identify the effects of visual field condition on electromyography of the lower extremities during arm reaching in healthy adults, and to compare differences in electromyography of the lower extremities between young and old adults according to visual fields condition. [Subjects and Methods] Twenty-nine young persons in their 20s and 19 elderly persons in their 60s, a total of 48 persons, participated in this study. Prior to participation in the study, each subject signed an informed consent form to comply with ethics guidelines dictated by the ethics committee for research at Silla University, Korea. We collected the muscle activation data for both of tibialis anterior and gastrocnemius muscle during reaching by subjects using electromyography. Data analysis with SPSS for Window Version 20.0 was performed using repeated one-way analysis of variance according to visual fields and age. [Results] There were no significantly differences between subjects in their 20s and 60s to visual field conditions except for left tibialis anterior muscle activation during left-side reaching. Left tibialis anterior muscle activation in subjects in their 60s was higher than in subjects in their 20s during left-side reaching. [Conclusion] We determined that tibialis anterior muscle activation in subjects in their 60s was higher than in subjects in their 20s. We suggest that visual field conditions are the important factor for physical therapy interventions to improve balance and priority of intervention .

Factors associated with suicide method among psychiatric patients in a general hospital in Korea.

This study aims to highlight the factors associated with suicide method among psychiatric patients in a general hospital in Korea. In a sample of 467 suicides by patients who had received mental health care in a general hospital in Korea, the relationship between suicide method and time of death as well as clinical characteristics, including psychiatric adiagnosis, was examined using multinomial logistic regression analysis. Compared with the general population, psychiatric patients, regardless of disorder, committed suicide by jumping from heights more often than by hanging (OR=2.35-8.64). In particular, patients with psychotic disorders and female patients were more likely to use jumping from a height than hanging to kill themselves (OR=2.98 and 1.83, respectively). Patients were more likely to use suicide methods other than hanging (e.g., OR=6.7 for jumping, 5.3 for drowning, and 2.7 for self-poisoning) between midnight and dawn. Possible suicide-prevention strategies suggested by this study include limiting access to or fencing off tall structures in close proximity to psychiatric institutions and residential care homes. At night, limiting access to or instituting heightened supervision of tall structures is specifically indicated.