Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.
Nagwa S. M. Aly;Hiroaki Matsumori;Thi Quyen Dinh;Akira Sato;Shin-Ichi Miyoshi;Kyung-Soo Chang;Hak Sun Yu;Fumie Kobayashi;Hye-Sook Kim
Parasites, Hosts and Diseases
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v.61
no.1
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pp.33-41
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2023
The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.
Myung Ji Kim; Su Hee Cho; Yongbo Seo; Sang-Dae Kim; Hae-Chul Park; Bum-Joon Kim
Journal of Korean Neurosurgical Society
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v.67
no.5
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pp.510-520
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2024
Objective : Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of disease-modifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the disease-modifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD.
New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.
Education is one of the priority sectors specified in Tanzania, and it has committed to provide 11 years of compulsory free basic education for all from pre-primary to lower secondary level. Despite the Government's efforts to provide free basic education to all children, there are 2.0 million (23.2 per cent) out of 8.5 million children at the primary school age of 7-13, who are out of school in Tanzania. The ICT class should be offered as a regular class in all secondary schools in Tanzania, recommended by the ministry of education. However, many schools are struggling to implement this mandate. Most of schools offer the ICT class with theory without any real hardware. Some schools were given with computers but they were not maintained for operation. There is a huge task to make ICT education universal. Main issues include: remoteness (off-grid area), lack of ICT teachers, lack of resources such as hardware, infrastructure, and lack of practical lessons or projects to be used at schools. An innovative blended ICT/STEM education program is being conducted not only for Tanzanian public and private/international schools, but also for out-of-school adolescents through institutions, NGO centers, home visits and at the E3 Empower academy center. For effective STEM education to take place and remain sustainable, more practical curriculum, and close-up teacher support need to be accompanied concurrently. Practical, project-based simple coding lessons have been developed and employed that students experience true learning. The effectiveness of the curriculum has been demonstrated in various project centers, and it showed that students are showing new interests in exploring new discovery, even though this was a totally new area for them. It has been designed for an easy replication, thus students who learned can repeat the lessons themselves to other students. The ultimate purpose of this project is to have IT education offered as universally as possible throughout the whole Tanzania. Quality education for all children is a key for better future for all. Previously it was hoped that education with discipline will improve the active learning. But now more than ever, we believe that children have the ability to learn on their own with given proper STEM education tools, guidelines and environment. This gives promising hope to all of us, including those in the developing countries.
Journal of the Korean Institute of Traditional Landscape Architecture
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v.40
no.3
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pp.1-9
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2022
This study compared and reviewed the recognition determinants by applying the OECMs criteria, focusing on old big trees, plant of natural monument that are natural heritage under the national heritage system of the Cultural Heritage Administration, and the results are as follows. First, among the protected areas designated and managed by government agencies according to each protection purpose, it is necessary to actively introduce new conservation measures, OECMs, to fulfill the Biodiversity strategy for 2030 while the land area is already saturated. Second, the OECMs are geographically defined areas(CBD, 2018), not currently recognized as a protected areas, governed and managed in a way that achieves positived sustained and effective contribution to in situ conservation of biodiversity. Since the selection of term, the scope of application criteria, and the context of interpretation are inevitably different, it is necessary to separately legislate and establish related laws of the OECMs suitable for each country's situation. Third, as a result of reviewing the OECMs criteria for plant of natural monument, the final 58 potential resources were recognized. Important elements among the OECMs criteria are that buffer zones should be spaced apart from designated zones to secure a certain area, and that economic activities through commercial production should not occur and meet biodiversity standards. Among the potential candidates, 23 areas were analyzed to be geographically isolated and independent, such as Forest of Oriental Arborvitae in Do-dong, Daegu, and forest types such as Carstor Aralia of Gungchon-ri, Samcheok and Forest of Common Camellias in Maryang-ri, Seocheon. As a result of reviewing the application of OECMs criteria for plant of natural monument, it was confirmed that the functions as a traditional uses were specialized among the values of biodiversity, and ecosystem services and cultural and spiritual values were inherited through Korea's unique culture of old big trees and Dangsan ritual. In terms of biodiversity criteria, it can be used as an important factor in connecting human and natural ecosystem networks without the discovery of new species.
In crime scene investigation, fingerprint identification is regarded to be one of the most important techniques for personal identification. However, objective and unbiased evaluation methods that would compare the fingerprints with diverse available and developing methods are currently lacking. To develop an objective and quantitative method to improve fingerprint evaluation, a preliminary study was performed to extract useful research information from the analysis with densitometric image analysis (CP Atlas 2.0) and the Automated Fingerprint Identification System (AFIS) for the developed fingerprints on porous surfaces. First, inked fingerprints obtained by varying pressure (kg.f) and pressing time (sec.) to find optimal conditions for obtaining fingerprint samples were analyzed, because they could provide fingerprints of a relatively uniform quality. The extracted number of minutiae from the analysis with AFIS was compared with the calculated areas of friction ridge peaks from the image analysis. Inked fingerprints with a pressing pressure of 1.0 kg.f for 5 seconds provided the most visually clear fingerprints, the highest number of minutiae points, and the largest average area of the peaks of the friction ridge. In addition, the images of the developed latent fingerprints on thermal paper with the iodine fuming method were analyzed. Fingerprinting condition of 1.0 kg.f/5 sec was also found to be optimal when generating highest minutiae number and the largest average area of peaks of ridges. Additionally, when the concentration of ninhydrin solution (0.5 % vs. 5 %) was used to compare the developed latent fingerprints on print paper, the best fingerprinting condition was 2.0 kg.f/5 sec and 5 % of ninhydrin concentration. It was confirmed that the larger the average area of the peaks generated by the image analysis, the higher the number of minutiae points was found. With additional tests for fingerprint evaluation using the densitometric image analysis, this method can prove to be a new quantitative and objective assessment method for fingerprint development.
Mothers of Children with Disabilities have many difficulties in parenting because of their children's disabilities. The purpose of this study was to examine the effects of a Group music psychotherapy programs on parenting stress and self efficacy, and to explore the experiences of the mothers who participated in the program. Twenty mothers of children with disabilities participated in this study. These twenty mothers were divided into 10 mothers of each group. The Experimental group participated in the Group music psychotherapy programs, while the control group did not. The Group music psychotherapy program was implemented for 8 weeks. To prove the effects of the program, pretest-posttest control group design was applied. The differences between pre-test and post-test of two groups were analyzed using independent t-test. The quantitative results of the study were as follows: First, a significant differences was found between the experimental group and control group in parenting stress level. Second, a significant differences was found between the experimental group and control group in self-efficacy level. From the qualitative analyses, four themes emerged from the decrement of parenting stress; Positive change of recognition about their children, Getting rid of stress, Keeping their composure, and Sharing of their emotions. And three themes emerged from the increment of self-efficacy; Discovery of oneself, New stimulus, and Mental support. All the result described above shows that group music psychotherapy program gives positive effect to decrease in parenting stress and also to increase in self-efficacy. And new possibility and effectiveness can be proposed in the music therapeutic approach to the parents of children with disabilities.
Owing to the risk of fetal loss associated with prenatal diagnostic procedures (amniocentesis, chorionic villus sampling), noninvasive prenatal diagnosis (NIPD) is ultimate goal of prenatal diagnosis. The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma in 1997 has opened up new probabilities for NIPD by Dr. Lo et al. The last decade has seen great development in NIPD. Fetal sex and fetal RhD status determination by cffDNA analysis is already in clinical use in certain countries. For routine use, this test is limited by the amount of cell-free maternal DNA in blood sample, the lack of universal fetal markers, and appropriate reference materials. To improve the accuracy of detection of fetal specific sequences in maternal plasma, internal positive controls to confirm to presence of fetal DNA should be analyzed. We have developed strategies for noninvasive determination of fetal gender, and fetal RhD genotyping using cffDNA in maternal plasma, using real-time quantitative polymerase chain reaction (RT-PCR) including RASSF1A epigenetic fetal DNA marker (gender-independent) as internal positive controls, which is to be first successful study of this kind in Korea. In our study, accurate detection of fetal gender through gestational age, and fetal RhD genotyping in RhD-negative pregnant women was achieved. In this assay, we show that the assay is sensitive, easy, fast, and reliable. These developments improve the reliability of the applications of circulating fetal DNA when used in clinical practice to manage sex-linked disorders (e.g., hemophilia, Duchenne muscular dystrophy), congenital adrenal hyperplasia (CAH), RhD incompatibility, and the other noninvasive pregnant diagnostic tests on the coming soon. The study was the first successful case in Korea using cffDNA in maternal plasma, which has created a new avenue for clinical applications of NIPD.
This study aimed to provide new interpretations of the ceramics excavated from the archaeological site of the royal palace of Goryeo (918~1392), where only limited access was permitted due to its location in Gaeseong, North Korea. The interpretations were based on the existing understanding of the arrangement of the palace buildings at the site and historical records. The study of the general aspects of the celadons discovered during eight excavations at the Goryeo Palace site in Gaeseong revealed that most of the vessels found at the site were produced during the early and middle phases of the Goryeo dynasty. The study involved classifying the celadons bearing inscribed texts and symbols into 18 different types according to their characteristic features and periods of production. The inscribed celadons have provided detailed information of the site where they were found, thereby making it possible to make strong presumptions about the date of construction, function, and status of the building in the palace connected with the discoveries. The excavations from the Goryeo Palace site and related historical literature suggest that the celadons bearing the inscription "Sojeon (燒錢)" were used during the first half of the 13th century, although the existing view had been that they were used during the second half of the century. This new conclusion is based on the use of the symbols ${\circ}$ and ${\odot}$, the celadons found together with the Sojeon-inscribed celadons, the date of the celadons bearing the inscription "Seong (成)," and the location of their discovery behind the site of Seongyeongjeon (aka Hoegyeongjeon) Hall, which had been one of the main palace buildings. The Taoist rituals performed for the safety of the Goryeo dynasty were largely held at Ganganjeon (aka Daegwanjeon) Hall in the western part of the royal palace during the second half of the 13th century. It was mostly in the first half of the 13th century just before the transfer of the Goryeo government from Gaeseong to Ganghwa (1232~1270) that the Taoist rituals were held at the location near Seongyeongjeon Hall, where archaeologists found the Sojeon-inscribed celadons. Therefore, the large number of celadon cups with holders, including those inscribed with Sojeon, discovered during the eighth excavation of the palace site suggests that they were used for the rituals held at Seongyeongjeon Hall during the first half of the 13th century.
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