• Title/Summary/Keyword: MI complex

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Molecular insights into the role of genetic determinants of congenital hypothyroidism

  • Kollati, Yedukondalu;Akella, Radha Rama Devi;Naushad, Shaik Mohammad;Patel, Rajesh K.;Reddy, G. Bhanuprakash;Dirisala, Vijaya R.
    • Genomics & Informatics
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    • v.19 no.3
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    • pp.29.1-29.10
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    • 2021
  • In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H2O2. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: -15 vs. -13.8 kcal/mol; and dissociation constant, Kd of wild-type vs. mutant: 7.2E-12 vs. 7.0E-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG(0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.

Implication of microRNA as a potential biomarker of myocarditis

  • Oh, Jin-Hee;Kim, Gi Beom;Seok, Heeyoung
    • Clinical and Experimental Pediatrics
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    • v.65 no.5
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    • pp.230-238
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    • 2022
  • Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition to viruses, play a role in its etiology. Coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis has recently been described, drawing attention to vaccine-induced myocarditis in children and adolescents. Its pathology is based on a series of complex immune responses, including initial innate immune responses in response to viral entry, adaptive immune responses leading to the development of antigen-specific antibodies, and autoimmune responses to cellular injury caused by cardiomyocyte rupture that releases antigens. Chronic inflammation and fibrosis in the myocardium eventually result in cardiac failure. Recent advancements in molecular biology have remarkably increased our understanding of myocarditis. In particular, microRNAs (miRNAs) are a hot topic in terms of the role of new biomarkers and the pathophysiology of myocarditis. Myocarditis has been linked with microRNA-221/222 (miR-221/222), miR-155, miR-10a*, and miR-590. Despite the lack of clinical trials of miRNA intervention in myocarditis yet, multiple clinical trials of miRNAs in other cardiac diseases have been aggressively conducted to help pave the way for future research, which is bolstered by the success of recently U.S. Food and Drug Administration-approved small-RNA medications. This review presents basic information and recent research that focuses on myocarditis and related miRNAs as a potential novel biomarker and the therapeutics.

A Study of the Relationships Between Proximity to an Industrial Complex and Blood Lead Levels and Urinary Cadmium Levels (거주지와 산업단지간의 거리와 혈 중 납 농도 및 요 중 카드뮴 농도의 상관관계에 관한 연구)

  • Heo, Jin-A;Kim, Hyo-Mi;Lee, Jong-Tae
    • Journal of Environmental Health Sciences
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    • v.38 no.2
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    • pp.95-104
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    • 2012
  • Objectives: The goal of this study was to investigate the relationships between proximity to an industrial complex and blood lead levels and urinary cadmium levels. Methods: We conducted a questionnaire survey and analyzed blood lead and urinary cadmium levels using Atomic Absorption Spectrometry (AAs). Data was analyzed using logistic regression analysis. All statistical analyses were conducted with SAS software version 9.2. The distance between the residence and an industrial complex was calculated through a Geographical Information System (GIS). Results: A total of 967 residents living near a large petrochemical complex in Ulsan participated. The geometric mean levels of blood lead and urinary cadmium were $1.70{\mu}g/dl$ (male: $1.77{\mu}g/dl$, female: $1.67{\mu}g/dl$), and $0.72{\mu}g/g$ creatinine (male: $0.49{\mu}g/g$ cr. female: $0.89{\mu}g/g$ cr.), respectively. Blood lead and urinary cadmium levels both increased with age and were higher among smokers compared to never smokers. Both significantly showed a decreasing trend with rising income. Results from multiple logistic regression analysis showed that urinary cadmium levels for subjects aged less than 20 years old were negatively associated with distance from the industrial area to the residence. The results, however, indicated that the blood lead levels were positively associated with the distance. Conclusions: The results of this study support that proximity to an industrial complex is related to urinary cadmium values for children. A positive finding with blood lead can be explained by the ambiguity of lead exposure sources in the general environment.

Identification of a Copy Number Variation on Chromosome 20q13.12 Associated with Osteoporotic Fractures in the Korean Population

  • Park, Tae-Joon;Hwang, Mi Yeong;Moon, Sanghoon;Hwang, Joo-Yeon;Go, Min Jin;Kim, Bong-Jo
    • Genomics & Informatics
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    • v.14 no.4
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    • pp.216-221
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    • 2016
  • Osteoporotic fractures (OFs) are critical hard outcomes of osteoporosis and are characterized by decreased bone strength induced by low bone density and microarchitectural deterioration in bone tissue. Most OFs cause acute pain, hospitalization, immobilization, and slow recovery in patients and are associated with increased mortality. A variety of genetic studies have suggested associations of genetic variants with the risk of OF. Genome-wide association studies have reported various single-nucleotide polymorphisms and copy number variations (CNVs) in European and Asian populations. To identify CNV regions associated with OF risk, we conducted a genome-wide CNV study in a Korean population. We performed logistic regression analyses in 1,537 Korean subjects (299 OF cases and 1,238 healthy controls) and identified a total of 8 CNV regions significantly associated with OF (p < 0.05). Then, one CNV region located on chromosome 20q13.12 was selected for experimental validation. The selected CNV region was experimentally validated by quantitative polymerase chain reaction. The CNV region of chromosome 20q13.12 is positioned upstream of a family of long non-coding RNAs, LINC01260. Our findings could provide new information on the genetic factors associated with the risk of OF.

A Design Suggestion for Improving Apartment Complex Environment through Resident-participated Workshop (주민참여형 워크샵을 통한 공동주택의 주거환경개선 디자인 제시 - 서울시 수서영구임대 단지 사례 연구 -)

  • Oh, Jun-Sik;Suh, Kuee-Sook;Jeong, Su-Mi
    • Proceeding of Spring/Autumn Annual Conference of KHA
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    • 2009.11a
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    • pp.207-212
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    • 2009
  • This research is focused on the 'Resident-participated Workshop' which targets the improvement of residential environment of apartment complex from the residents' point of view. The purpose of the workshop is to induce the residents interest and encourage them to participate in design process, thus, residents will be satisfied with the result with affection and achievement. This research aims the effectiveness of 'Resident-participated' design plan as a program which enables them to maintain and self manage in the long run. The object of this research was the public space within the apartment complex of Susojugong Rental Apartment Complex in Gangnam-ku, Seoul and followings are the contents; 1. Method of 'Resident-participated Workshop'. 2. Program of 'Resident-participated Workshop'. 3. Design analysis of improved apartment complex through 'Resident-participated Workshop' and selection. As a result, it was noticeable that 'Resident-participated Workshop' was an important factor in decision making of designs from the very first stage through communication. As a part of workshop program, design game used cubic models which was useful to enhance the understanding of the participants. It also induced the cubic conception so that intercommunication with the design specialists was possible. But, the development of various workshop method to increase the residents' interest and participation is necessary, especially, program development is required to change the residents' attitude towards the design plan. It is anticipated that a continuous related research is neccsary in this regard.

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Electromagnetic Wave Absorption Properties of Fe73Si16B7Nb3Cu1-Based Nanocrystalline Soft Magnetic Powder Composite Mixed with Charcoal Powder (나노결정 Fe73Si16B7Nb3Cu1 연자성분말과 숯분말 혼합 복합성형체의 전자파흡수 특성)

  • Kim, Sun-I;Kim, Mi-Rae;Sohn, Keun-Yong;Park, Won-Wook
    • Journal of Powder Materials
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    • v.16 no.4
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    • pp.291-295
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    • 2009
  • The electromagnetic wave absorption sheets were fabricated by mixing of $Fe_{73}Si_{16}B_7Nb_3Cu_1$ nanocrystalline soft magnetic powder, charcoal powder and polymer based binder. The complex permittivity, complex permeability, and scattering parameter have been measured using a network analyzer in the frequency range of 10 MHz$\sim$10 GHz. The results showed that complex permittivity of sheets was largely dependent on the frequency and the amount of charcoal powder : The permittivity was improved up to 100 MHz, however the value was decreased above 1 GHz. The power loss of electromagnetic wave absorption data showed almost the same tendency as the results of complex permittivity. However, the complex permeability was not largely affected by the frequency, and the values were decreased with the addition of charcoal powder. Based on the results, it can be summarized that the addition of charcoal powder was very effective to improve the EM wave absorption in the frequency range of 10 MHz$\sim$1 GHz.

Binding Mode Studies of Indenoisoquinoline Analogues into Human Topoisomerase I-DNA Complex Using Flexible Docking (Human Topoisomerase I-DNA 절개가능 복합체에 대한 Indenoisoquinoline 유도체들의 결합양상 연구)

  • Park, In-Seon;Kim, Bo-Yeon;Kim, Choon-Mi;Choi, Sun
    • YAKHAK HOEJI
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    • v.53 no.4
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    • pp.228-234
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    • 2009
  • Topoisomerase I (Topo I) participates in the DNA replication, transcription, and repair. Binding of Topo I inhibitor to the Topo I-DNA cleavage complex forms stabilized ternary complex which blocks DNA religation and ultimately causes cell death. Camptothecin (CPT) and its derivatives have been among the most effective anticancer drugs by inhibition of topo I. However, efforts to synthesize non-CPT drugs have been actively going on because the CPT derivatives have several limitations such as poor solubility, short half-life, and side effects. As an indenoisoquinoline, NSC314622 is not as potent as CPT, but its chemical stability and slower reversibility of the cleavage complex made it a good lead compound. Recently, a series of indenoisoquinoline analogues were synthesized with substituted dimethoxy or methylenedioxy on the aromatic ring and alkylamino on the lactam nitrogen. Some of them showed quite good Topo I inhibitory activity. Using the computer docking program, Surflex-Dock, indenoisoquinoline analogues were docked into the human Topo I-DNA cleavable complex. The docking results showed that the compounds with activity better than NSC314622 intercalated between the -1 and +1 base pairs at the cleavage site, but those with little or no activities did not appear to intercalate. These results could be useful to design new Topo I inhibitors improved than CPT.

Interaction of Ruthenium(II)[(1,10-phenanthroline)2benzodipyrido[3,2-a:2',3'-c]-phenazine]2+ with Single Stranded Poly(dA) and Poly(dT): Turning off the Light Switch

  • Lee, Jeong-Mi;Choi, Ji-Yoon;Kim, Jong-Moon;Lee, Sang-Yong;Lee, Hyo-Sun;Kim, Seog-K.;Cho, Tae-Sub
    • Bulletin of the Korean Chemical Society
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    • v.28 no.6
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    • pp.965-969
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    • 2007
  • The spectral properties, namely the circular dichroism, electric absorption and luminescence properties, of Λ- and Δ-[Ru(II)(1,10-phenanthroline)2benzodipyrido[b:3,2-h:2',3'-j]phenazine]2+ ([Ru(phen)2BDPPZ]2+) in the presence and absence of single stranded poly(dA) and poly(dT) were compared in this work. In the presence of single stranded DNAs, hypochromism in the absorption spectrum and significant changes in the circular dichroism spectrum in the ligand absorption band were apparent, indicating the strong interaction of the [Ru(phen)2BDPPZ]2+ complex with the single stranded DNAs. The luminescence intensity of the Ru(II) complex decreased stoichiometrically with increasing concentrations of the single stranded DNAs. All of these spectral changes were independent of the configuration of the Ru(II) complex and the nature of the DNA bases. Therefore, it is conceivable that both enantiomers of the [Ru(phen)2BDPPZ]2+ complex interact electrostatically with the negatively charged phosphate groups of DNA. However, the spectral properties of [Ru(II)(1,10-phenanthroline)3]2+ were not altered even in the presence of single stranded DNAs. Therefore, the size of the ligand involved in the interaction of the metal complex with the phosphate group of DNA may play an important role, even when the nature of the interaction is electrostatic.

Study on corrosion characteristics of treatment plants in Korea (국내 정수장의 부식성 특성 연구)

  • Min, Byung-dae;Chung, Hyen-mi;Lee, Lee-nae;Choi, Inchol;Ahn, Kyunghee;Park, Ju-hyun
    • Journal of Korean Society of Water and Wastewater
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    • v.30 no.6
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    • pp.707-714
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    • 2016
  • In order to prevent secondary pollution of tap water, corrosion characteristics are investigated, and corrosion index are calculated using LI and LR to manage corrosiveness. As targeted water treatment plants from 2014 (July, once) to 2015 (July and October, 2 times), 70 plants are selected by making a division for each area and water system. (treated water samples, n=240, raw water samples, n=72). In result of pH analysis, treated water was lower than raw water to 7.12, and 7.29, respectively. LI were investigated in the order of Seomjin river, Nakdong river, Han river, Geum river, to -2.08, -1.24, -1.11, -1.10 (at raw water), and -2.18, -1.59, -1.51, -1.35 (at treated water), respectively. In case of water quality goal value (LI = -1) in Japan as control of corrosiveness, management object was investigated about 83.3%.

A Study on the Relationships Among the Social Capital, Community Spirit, and Resident Satisfaction in Urban-Rural Complex Areas (도농복합지역 주민의 사회자본, 공동체의식 및 주민만족 간의 관계에 관한 연구)

  • Yu, Mi Yung;Jo, Dong Hyuk;Cho, Hee Jun
    • Journal of Korean Society for Quality Management
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    • v.50 no.3
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    • pp.333-347
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    • 2022
  • Purpose: The purpose of this study was intended to examine the importance and role of social capital in the local community, and empirically identify the relationships among the social capital, community spirit, resident satisfaction, and community participation of the residents of urban-rural complex areas. Methods: This study conducted a survey was conducted with residents of the urban-rural complex areas to collect data, and the data were statistically and empirically analyzed to verify the hypothesis. Results: As a result of the study, first, networks and trust as local social capital were found to have positive effects on local attachment. Second, networks and trust were found to have positive effects on social ties. Third, local attachment and social ties were found to have positive effects on resident satisfaction. Finally, community participation was found to have moderating effects on the relationship between social ties and resident satisfaction. Conclusion: Through this study, the importance and role of local social capital in urban-rural complex areas, where regional problems are highly likely to occur, were reviewed, and basic data necessary to solve the social problems at hand in urban-rural complex areas and promote continuous development were provided can be said to be the significance of this study.