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Learning mentoring is an activity to provide assistance by a companion to individuals or groups who need help. The children on Semukit Island are the focus of this activity, children are lagging behind in reading, writing, and arithmetic. This is evidenced by the presence of children who cannot distinguish letters, cannot write, and have difficulty working on addition problems that should be done in a short time. When carrying out calistung learning mentoring, the community service team uses a mentoring strategy with an individual approach, namely one teacher accompanies a minimum of 1 child and a maximum of 3 children. This activity aims to help children catch up on lessons due to the pandemic period, where children miss lessons that are held online. Thus, children will be able to improve learning achievement. This writing uses participatory action research, where this research is to examine the educational process carried out in the community, namely Semukit Island located in Galang, Riau Islands. As a result of this assistance, children are able to recognize letters, read, write, do math, read and memorize English vocabulary.Keywords: children; study; calistung; accompaniment; semukit island AbstrakPendampingan belajar merupakan kegiatan memberikan pertolongan oleh seorang pendamping kepada individu ataupun kelompok yang membutuhkan pertolongan. Anak-anak di Pulau Semukit menjadi fokus kegiatan ini, anak-anak mengalami ketertinggalan dalam membaca, menulis, dan berhitung. Hal tersebut dibuktikan dengan adanya anak-anak yang belum bisa membedakan huruf, tidak bisa menulis, dan kesulitan untuk mengerjakan soal penjumlahan yang seharusnya bisa dikerjakan dalam waktu singkat. Saat melaksanakan pendampingan belajar calistung, tim PkM menggunakan strategi pendampingan dengan pendekatan individual, yakni satu pengajar mendampingi minimal 1 anak dan maksimal 3 anak. Kegiatan ini bertujuan untuk menolong anak-anak dalam mengejar ketertinggalan pelajaran akibat masa pandemi, di mana anak-anak ketinggalan pelajaran yang dilaksanakan secara online. Dengan demikian, anak-anak akan mampu meningkatkan prestasi belajar. Penulisan ini menggunakan penelitian participatory action reseach, di mana penelitian ini adalah untuk meneliti proses pendidikan yang dilaksanakan di tengah masyarakat, yakni Pulau Semukit yang terdapat di Galang Kepualauan Riau. Hasil dari pendampingan ini, anak-anak sudah bisa mengenal huruf, membaca, menulis, mengerjakan matematika, membaca dan menghafal kosakata Bahasa Inggris.Kata kunci: anak; belajar; calistung; pendampingan; pulau semukit

PURPOSE This study was conducted to investigate changes in stress before and after elite shooting athletes participate in a match, and to find out the effect on the match score.METHODS Thirty-wight elite shooting athletes were sampled, questionnaires were distributed to measure psychological stress before and after the match, and saliva was collected before and after the match to measure cortisol. In addition, psychological stress and changes in cortisol before and after the game were investigated, and how psychological stress before and after the game and cortisol affect the score of the game were investigated. Accordingly, a statistical analysis based on data analysis was conducted, and the following research results were obtained.RESULTS The pre-match analysis of psychological stress and cortisol revealed statistically significant changes; both post-match stress and cortisol decreased compared to before the match. Increased psychological stress and cortisol both before and after the match had a negative effect on the match score.CONCLUSIONS These findings confirmed that shooters experience very strong psycho-physiological stress before the match, and the stronger the psychological stress, the lower the game score.

This study was to investigate the effects of Biyeom-go (BYG, an herbal formula) on immune biomarkers present in the nasal mucosa of patients with allergic rhinitis under exposure to particulate matter 2.5 (PM2.5), and on changes in goblet cells and immune biomarkers in mice under exposure to Korea diesel particulate matter (KDP20). Thirty patients showing characteristic allergic rhinitis symptoms were enrolled in Jeonju-si, Korea, and treated with BYG thrice a day for four weeks. Changes in the expression of immune biomarkers (interleukin 4 (IL-4), IL-5, IL-8, IL-13, IL-33, and thymic stromal lymphopoietin (TSLP) mRNA), total nasal symptom scores (TNSS), mini-rhinitis-specific quality of life questionnaire (RQLQ) results, and visual analog scale scores were evaluated after 4 weeks of treatment. Additionally, the difference in PM2.5 concentrations in the air in Jeonju-si, Korea (November, 2019 ∼ March, 2020), was analyzed to determine the change in TNSS. KDP20 (100 μg/mL) was exposed to C57BL/6 mice for 10 days; 0.05% Nasonex (a positive control, mometasone furoate), or BYG was administrated for 5 days twice a day. The expression of inflammatory factors was detected via qRT-PCR using nasopharynx tissue samples of mice. BYG treatment was found to be associated with significant improvement in total nasal symptoms, especially itching and sneezing ( p < 0.0001 ), and mini-RQLQ after 4 weeks. IL-8 ( p < 0.01 ), IL-33 ( p < 0.01 ), and TSLP ( p < 0.001 ) expression levels decreased after BYG treatment. In mice, administration of BYG reduced the number of goblet cells increased through KDP20 treatment. KDP20-induced immune biomarkers (IL-33, TSLP, tumor necrosis factor alpha, and IL-8) were also significantly downregulated in the nasopharynx tissue after BYG treatment. Therefore, BYG may show therapeutic effects against allergic rhinitis in humans, and it was confirmed that the expression of PM-induced inflammatory factors in mice was decreased via BYG treatment.

In this study, Korean time-use survey data for coupled households is analyzed to show that unpaid work time is endogenous in its relationship with paid work time because the views of traditional gender roles affect gender disparity in unpaid work time. The data not only includes time allocation between husbands and wives but also their views of traditional gender roles within their households, and this information can represent gendered social norms that can potentially explain the distribution of unpaid work between husbands and wives. The control function model is estimated to identify the tradeoff between unpaid work time and paid work time by solving the endogeneity problem. The results of this study show that wives' unpaid work is likely to be affected by gendered social norms and that the effect can be larger for those having children. In addition, only in the case of wives, unpaid work time is found to be negatively associated with whether to work full-time, showing that wives' burden of unpaid work could prevent them from working full time. The results indicate that it is crucial to recognize the need to change gendered social norms to address an asymmetric division of unpaid work between husbands and wives.

During a search for natural inflammatory inhibitors, 1-O-acetylbritannilactone (ABL), a sesquiterpene lactone, was isolated from the flowers of Inula britannica. ABL significantly inhibited human neutrophil elastase (HNE) with a half-maximal inhibitory concentration (IC50) of 3.2 ± 0.3 µM, thus did so more effectively than the positive control material (epigallocatechin gallate) (IC50 7.2 ± 0.5 µM). An enzyme kinetic study was performed. ABL noncompetitively inhibited HNE with an inhibition constant Ki of 2.4 µM. ABL inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by RAW 264.7 cells in a dose-dependent manner, as well as the protein-level expression of inducible nitric oxide synthase and cyclooxygenase-2. The anti-inflammatory effect of ABL was confirmed using a transgenic Tg(mpx:EGFP) zebrafish larval model. The exposure of the larvae to ABL inhibited neutrophil recruitment to the site of injury after tail fin amputation.

High-throughput reporter assays such as self-transcribing active regulatory region sequencing (STARR-seq) have made it possible to measure regulatory element activity across the entire human genome at once. The resulting data, however, present substantial analytical challenges. Here, we identify technical biases that explain most of the variance in STARR-seq data. We then develop a statistical model to correct those biases and to improve detection of regulatory elements. This approach substantially improves precision and recall over current methods, improves detection of both activating and repressive regulatory elements, and controls for false discoveries despite strong local correlations in signal.

OBJECTIVE Discovery of a novel antibody would enable diagnosis and early treatment of autoimmune encephalitis. The aim was to discover a novel antibody targeting a synaptic receptor and characterize the pathogenic mechanism. METHOD We screened for unknown antibodies in serum and cerebrospinal fluid samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further processing for antibody discovery, using immunoprecipitation to primary neuronal cells, mass-spectrometry analysis, an antigen-binding assay on an antigen-overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons. RESULTS Two patients had a novel antibody against CaV α2δ (voltage-gated calcium channel alpha-2/delta subunit). The patient samples stained neuropils of the hippocampus, basal ganglia, and cortex in rat brain sections and bound to a CaV α2δ-overexpressing cell line. Knockdown of CaV α2δ expression in cultured neurons turned off the immunoreactivity of the antibody from the patients to the neurons. The patients were associated with preceding meningitis or neuroendocrine carcinoma and responded to immunotherapy. In cultured neurons, the antibody reduced neurotransmitter release from presynaptic nerve terminals by interfering with tight coupling of calcium channels and exocytosis. INTERPRETATION Here, we discovered a novel autoimmune encephalitis associated with anti-CaV α2δ antibody. Further analysis of the antibody in autoimmune encephalitis might promote early diagnosis and treatment. ANN NEUROL 2021;89:740-752.

Weeds are notorious plant species exhibiting a harmful impact on crops. Biological weed control is an efficient and environmentally friendly technique, usually constitutes naturally derived compounds, including bioherbicidal metabolites produced by Streptomyces sp. The isolation and structural identification of phytotoxic compounds from Streptomyces have recently been proposed as an effective way to the discovery of novel bioherbicides. In the screening of bioherbicidal agents, isolated Streptomyces strain KRA17-580 demonstrated significant phytotoxic activity against Digitaria ciliaris. Phylogenetic analysis of the 16S rRNA sequence indicated that isolated KRA17-580 is similar to Streptomyces olivochromogenes. The bacterial culture conditions were optimized for temperature, agitation, and initial pH. Streptomyces strain KRA17-580 showed intense phytotoxic activity and high cell mass at an initial pH of 5.5-7.0, more than 150 rpm, and 25-30 °C. The herbicidal compounds isolated from the culture filtrate of strain KRA17-580 were purified by solvent partition, C18, Sephadex LH20 column chromatography, and high-performance liquid chromatography. By 1D-NMR, 2D-NMR, and electrospray ionization mass spectrometry analysis, the 580-H1 and 580-H2 compounds were identified as a cinnoline-4-carboxamide (MW, 173.0490; C9H7N3O2) and cinnoline-4-carboxylic acid (MW, 174.0503; C9H6N2O2), respectively. Only these two herbicidal compounds showed strong phytotoxic activity against D. ciliaris in foliar applications. However, compound 580-H2 was more phytotoxic than 580-H1 and the toxicity was dose-dependent. The herbicidal metabolite KRA17-580 produced by Streptomyces sp. is a new bioherbicidal candidate that may provide a new lead molecule for more efficient phytotoxic compounds.

Antiseizure medication is the mainstay of treatment for seizures, and adjunctive therapy is widely used to achieve adequate seizure control in patients with epilepsy who fail to respond to the first monotherapy. The newly developed antiepileptic drug cenobamate (YKP3089) as an adjunctive therapy improved seizure control in patients with uncontrolled focal seizures. Cenobamate is thought to reduce neuronal excitability through action on multiple targets, including GABA A receptors (GABAsubA/subRs) and voltage-gated sodium channels. However, its effects on brain function and synaptic plasticity are unclear. Here, we explored the behavioral, synaptic, and cellular actions of cenobamate. Cenobamate influenced novel object recognition, object location memory, and Morris water maze performance in mice. Cenobamate enhanced inhibitory postsynaptic potentials by prolonging inhibitory postsynaptic current (IPSC) decay without affecting presynaptic GABA release or the peak amplitude of IPSCs. In addition, cenobamate suppressed hippocampal excitatory synaptic transmission by reducing the excitability of Schaffer collaterals and interfered with the induction of long-term potentiation. A reduction in neuronal excitability induced by cenobamate was associated with an elevation of action potential (AP) threshold, and which progressively increased in later APs during repetitive firing, indicating the activity-dependent modulation of neuronal sodium currents. Cenobamate suppressed neuronal excitability under the condition that GABAergic neurotransmission is excitatory, and administration of cenobamate rapidly enhanced the phosphorylation of eukaryotic elongation factor 2 in the hippocampus of adult and neonatal mice. Collectively, these results suggest that the combined action of cenobamate on sodium currents and GABAsubA/subR-mediated synapse responses results in reduced excitability in neurons.

The KRA18-249 strain, isolated from a natural recreational forest near Jeongseon, Gangwon-do, when applied to plants induced signs of wilting within 24 h, leading to plant death. The isolated actinomycete was identified as Streptomyces gardneri based on 16S rRNA gene homogeneity analysis. The culture filtrate was solvent fractionated to obtain the active substance, and the active compound 249-Y1 was isolated from the purified fractions via a herbicide activity test using Digitaria ciliaris. NMR and ESI-MS analyses revealed that the molecular formula of 249-Y1 is C

Pest control by biological means is an effective, eco-friendly, and promising method that typically involves compounds naturally derived from actinomycetes. Thus, the present study aimed to screen, characterize, and identify the structure of insecticidal compounds from Streptomyces sp. KR0006 and increase the activity through mutagenesis. In the examination of the insecticidal activity level of the isolates, Streptomyces sp. KR0006 metabolite showed significant activity against larvae and moths of Plutella xylostella. Taxonomic analyses of the 16S rRNA gene sequences revealed that the isolated KR0006 strain tended to be 99% consistent with Streptomyces cinereoruber strain NBRC 12756. Three active compounds isolated from the culture filtrate of KR0006 were purified by solvent partition, mid-pressure liquid chromatography (MPLC), Sephadex LH20 column chromatography, and high-performance liquid chromatography (HPLC). By performing 1H-NMR, 13C-NMR, and 2D-NMR experiments, and high-resolution electrospray ionization mass spectrometry analysis, the 316-HP2, 316-HP3, and 316-HP5 compounds were inferred as antimycin A3a (MW, 519.; C26H36N2O9), antimycin A8a (MW, 534; C27H38N2O9), and antimycin A1a (MW, 548; C28H40N2O9) respectively. Mutant U67 obtained from exposure to ultraviolet (UV) irradiation (254 nm, height 17 cm) for 70 seconds resulted in a 70% more larval mortality than that of the initial wild culture. The second mutation of the culture broth enhanced insecticidal activity by 80 and 100% compared with the first mutation and initial medium, respectively. Our study found that Streptomyces sp. KR0006 strain produces insecticidal active compounds and could be used for practical pest management.

Inborn errors of metabolism (IEMs) are common causes of neurodevelopmental disorders, including microcephaly, hyperactivity, and intellectual disability. However, the synaptic mechanisms of and pharmacological interventions for the neurological complications of most IEMs are unclear. Here, we report that metabolic dysfunction perturbs neuronal NMDA receptor (NMDAR) homeostasis and that the restoration of NMDAR signaling ameliorates neurodevelopmental and cognitive deficits in IEM model mice that lack aminopeptidase P1. Aminopeptidase P1-deficient (Xpnpep1–/–) mice, with a disruption of the proline-specific metalloprotease gene Xpnpep1, exhibit hippocampal neurodegeneration, behavioral hyperactivity, and impaired hippocampus-dependent learning. In this study, we found that GluN1 and GluN2A expression, NMDAR activity, and the NMDAR-dependent long-term potentiation (LTP) of excitatory synaptic transmission were markedly enhanced in the hippocampi of Xpnpep1–/– mice. The exaggerated NMDAR activity and NMDAR-dependent LTP were reversed by the NMDAR antagonist memantine. A single administration of memantine reversed hyperactivity in adult Xpnpep1–/– mice without improving learning and memory. Furthermore, chronic administration of memantine ameliorated hippocampal neurodegeneration, hyperactivity, and impaired learning and memory in Xpnpep1–/– mice. In addition, abnormally enhanced NMDAR-dependent LTP and NMDAR downstream signaling in the hippocampi of Xpnpep1–/– mice were reversed by chronic memantine treatment. These results suggest that the metabolic dysfunction caused by aminopeptidase P1 deficiency leads to synaptic dysfunction with excessive NMDAR activity, and the restoration of synaptic function may be a potential therapeutic strategy for the treatment of neurological complications related to IEMs.

Motivation High-throughput reporter assays dramatically improve our ability to assign function to noncoding genetic variants, by measuring allelic effects on gene expression in the controlled setting of a reporter gene. Unlike genetic association tests, such assays are not confounded by linkage disequilibrium when loci are independently assayed. These methods can thus improve the identification of causal disease mutations. While work continues on improving experimental aspects of these assays, less effort has gone into developing methods for assessing the statistical significance of assay results, particularly in the case of rare variants captured from patient DNA. Results We describe a Bayesian hierarchical model, called Bayesian Inference of Regulatory Differences, which integrates prior information and explicitly accounts for variability between experimental replicates. The model produces substantially more accurate predictions than existing methods when allele frequencies are low, which is of clear advantage in the search for disease-causing variants in DNA captured from patient cohorts. Using the model, we demonstrate a clear tradeoff between variant sequencing coverage and numbers of biological replicates, and we show that the use of additional biological replicates decreases variance in estimates of effect size, due to the properties of the Poisson-binomial distribution. We also provide a power and sample size calculator, which facilitates decision making in experimental design parameters. Availability and implementation The software is freely available from www.geneprediction.org/bird. The experimental design web tool can be accessed at http://67.159.92.22:8080 Supplementary information Supplementary data are available at Bioinformatics online.

Discovery of a novel antibody would enable diagnosis and early treatment of autoimmune encephalitis. The aim was to discover a novel antibody targeting a synaptic receptor and characterize the pathogenic mechanism.We screened for unknown antibodies in serum and cerebrospinal fluid samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further processing for antibody discovery, using immunoprecipitation to primary neuronal cells, mass-spectrometry analysis, an antigen-binding assay on an antigen-overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons.Two patients had a novel antibody against CaHere, we discovered a novel autoimmune encephalitis associated with anti-Ca

Weeds are notorious plant species exhibiting a harmful impact on crops. Biological weed control is an efficient and environmentally friendly technique, usually constitutes naturally derived compounds, including bioherbicidal metabolites produced by

Oxidative stress is a major contributor to muscle aging and loss of muscle tissue. Jakyakgamcho-tang (JGT) has been used in traditional Eastern medicine to treat muscle pain. Here, we compared the total phenolic and flavonoid contents in 30% ethanol and water extracts of JGT and tested the preventive effects against oxidative stress (hydrogen peroxide)-induced cell death in murine C2C12 skeletal muscle cells. The total phenolic content and total flavonoid content in 30% ethanol extracts of JGT were higher than those of water extracts of JGT. Ethanol extracts of JGT (JGT-E) had stronger antioxidant activities of 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2′-diphenyl-1-picrylhydrazyl-scavenging activity (DPPH) than water extracts of JGT (JGT-W). JGT-E contained 19–53% (1.8 to 4.9-fold) more active compounds (i.e., albiflorin, liquiritin, pentagalloylglucose, isoliquiritin apioside, isoliquiritin, liquiritigenin, and glycyrrhizin) than JGT-W. The ethanol extracts of JGT inhibited hydrogen peroxide-induced cell death and intracellular reactive oxygen species generation more effectively than the water extract of JGT in a dose-dependent manner. For the first time, these results suggest that ethanol extract of JGT is relatively more efficacious at protecting against oxidative stress-induced muscle cell death.

Currently, injuries to customers due to health functional foods are annually increasing. To evaluate the antigenicity of Korean red ginseng mixture (KRGM), we tested for systemic anaphylactic shock and passive cutaneous anaphylaxis in guinea pigs. Based on a comparison of measured body weights, there were no changes in body weight for the KRGM treatment group compared with the control group. In the ovalbumin treated group, however, there was a statistically significant decrease in body weight. For the active systemic anaphylaxis test, after the induction, there were no symptoms that suggested anaphylactic shock in the control and KRGM treatment group. In the ovalbumin treated group, there were symptoms that suggested severe anaphylaxis, and those symptoms included restlessness, piloerection, tremor, rubbing or licking the nose, sneezing, coughing, hyperpnea, dyspnea, staggering gait, jumping, gasping and writhing, convulsion, side position and Cheyne-stokes respiration. All animals died within thirty minutes in the ovalbumin treated group. For the passive cutaneous anaphylaxis test in guinea pigs sensitized to KRGM, each anti-serum was diluted in a stepwise manner. This was followed by an intravenous injection of a mixture of KRGM and Evans blue. The results of the test showed that all the responses were negative in the control and the low-dose and high-dose administration groups. However, in the ovalbumin treated group, all the responses were positive. Based on the above results, there were no anaphylactic responses for up to 12 times the amount of human intake of KRGM in Hartley Guinea-pigs. The results suggest that KRGM is safe as measured by the systemic and local antigenicity in guinea pigs.

We consider the use of difference in differences (DD) to evaluate the effect of an activity assistance program on the health of severely disabled Koreans. There are, however, 2 problems in the data: the number of response categories for self-assessed health changed over the waves of the repeated cross-section survey and the "parallel untreated response path" assumption for DD is suspect. We show how to overcome these problems by renormalizing parameters and applying "generalized difference in differences (GDD)." We find a significantly positive effect of the program with DD, but not with GDD. Our solutions should prove useful in applications in which one or other of these problems arise.

The regulator of G protein signaling (RGS) domain proteins generally attenuate heterotrimeric G protein signaling, thereby fine-tune the duration and strength of signal transduction. In this study, we characterize the functions of RgsD, one of the six RGS domain proteins present in the human pathogenic fungus Aspergillus fumigatus. The deletion (Δ) of rgsD results in enhanced asexual sporulation coupled with increased mRNA levels of key developmental activators. Moreover, ΔrgsD leads to increased spore tolerance to UV and oxidative stress, which might be associated with the enhanced expression of melanin biosynthetic genes and increased amount of melanin. Yeast two-hybrid assays reveal that RgsD can interact with the three Gα proteins GpaB, GanA, and GpaA, showing the highest interaction potential with GpaB. Importantly, the ΔrgsD mutant shows elevated expression of genes in the cAMP-dependent protein kinase A (PKA) pathway and PKA catalytic activity. The ΔrgsD mutant also display increased gliotoxin production and elevated virulence toward Galleria mellonella wax moth larvae. Transcriptomic analyses using RNA-seq reveal the expression changes associated with the diverse phenotypic outcomes caused by ΔrgsD. Collectively, we conclude that RgsD attenuates cAMP-PKA signaling pathway and negatively regulates asexual development, toxigenesis, melanin production, and virulence in A. fumigatus.