• Title/Summary/Keyword: Genetic interaction

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Screening of novel alkaloid inhibitors for vascular endothelial growth factor in cancer cells: an integrated computational approach

  • Shahik, Shah Md.;Salauddin, Asma;Hossain, Md. Shakhawat;Noyon, Sajjad Hossain;Moin, Abu Tayab;Mizan, Shagufta;Raza, Md. Thosif
    • Genomics & Informatics
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    • v.19 no.1
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    • pp.6.1-6.10
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    • 2021
  • Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

A systemic study on the vulnerability and fatality of prostate cancer patients towards COVID-19 through analysis of the TMPRSS2, CXCL10 and their co-expressed genes

  • Raza, Md. Thosif;Mizan, Shagufta
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.31.1-31.15
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    • 2022
  • A pandemic of respiratory disease named coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is reported prostate cancer patients are susceptible to COVID-19 infection. To understand the possible causes of prostate cancer patients' increased vulnerability and mortality from COVID-19 infection, we focused on the two most important agents, transmembrane protease serine subtype 2 (TMPRSS2) and the C-X-C motif 10 (CXCL10). When SARS-CoV-2 binds to the host cell via S protein-angiotensin-converting enzyme-2 receptor interaction, TMPRSS2 contributes in the proteolytic cleavage of the S protein, allowing the viral and cellular membranes to fuse. CXCL10 is a cytokine found in elevated level in both COVID-19 and cancer-causing cytokine storm. We discovered that TMPRSS2 and CXCL10 are overexpressed in prostate cancer and COVID-19 using the UALCAN and GEPIA2 datasets. The functional importance of TMPRSS2 and CXCL10 in prostate cancer development was then determined by analyzing the frequency of genetic changes in their amino acid sequences using the cBioPortal online portal. Finally, we used the PANTHER database to examine the pathology of the targeted genes. We observed that TMPRSS2 and CXCL10, together with their often co-expressed genes, are important in the binding activity and immune responses in prostate cancer and COVID-19 infection, respectively. Finally, we found that TMPRSS2 and CXCL10 are two putative biomarkers responsible for the increased vulnerability and fatality of prostate cancer patients to COVID-19.

Trends in Genetic Parameters with Age and Site for Early Implications of Genetic Improvement in Korean White Pine (잣나무의 유전적(遺傳的) 형질(形質) 개량(改良)의 조기검정(早期檢定)을 위한 수령(樹齡) 및 입지별(立地別) 생장(生長)과 유전모수(遺傳母數)의 특성(特性)에 관(關)한 연구(硏究))

  • Kim, Dae Eun;Chon, Sang Keun
    • Journal of Korean Society of Forest Science
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    • v.79 no.1
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    • pp.56-70
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    • 1990
  • Eighteen Korean white pine (P. koraiensis S. et Z.) families were tested in 3 different regions from age 5 to 9. Family and site were significant sources of variation for seedling survival and field growth, whereas the effects of family x site interaction ware relatively small as compared with the former sources of variation. Variance components estimated from the separate and combined sites indicated that the most variabilities were associated with individual trees within plot. Family ${\times}$ site interaction components as a percentage of family variance decreased sharply with age. Heritability estimates varied with testing site and tree age. Combined analyses, however, showed a moderate change in heritability with increasing tree ages, and demonstrated high and stable trends of estimates, particularly in family heritabilities of tree height ($h_F{^2}=0.789-0.798$). The gains estimated from combined analysis have expected maximum or near-maximum efficiencies at age 6 or 7. Given equal intensity of selection, mass selection showed the most efficient gains within and across the sites. However, for the differences between mass and combined selections are small, selection made on the combination of family and within-family would be more effective in improving genetic gains. Indirect selection method indicated that 5-and 6-years height were all good predictors of 9-year-old height with little loss of relative efficiency (less than 10%) as compared with direct family selection at age 9. Phenotypic and genetic correlations computed on the basis of family mean values of height and diameter have shown predominantly high, positive, and statistically significant (1% level) relationships between all tested pairs of traits, which indicates that family growth maintained statistically consistent trends with age. The best families are those that maintained a stable superiority overall sites and ages in growth performance, therefore, it can be suggested that early identification of superior families at age 9 is feasible at age 5 or 6 in Pinus koraiensis S. et Z.

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Effects of the interaction between seaweed consumption and the polygenic risk score on inflammation in Korean adults (한국 성인의 해조류 섭취와 다유전자 위험 점수 간의 상호작용이 염증에 미치는 영향)

  • Gayeon Hong;Dayeon Shin
    • Journal of Nutrition and Health
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    • v.57 no.2
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    • pp.211-227
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    • 2024
  • Introduction: Seaweed is a sustainable and underexplored source of bioactive compounds with potent anti-inflammatory activities. However, studies on the interaction between seaweed and genes on inflammation are limited. Purpose: We aimed to evaluate the relationships between seaweed consumption and the polygenic risk scores (PRS) and their interactions with high-sensitivity C-reactive protein (hs-CRP) levels. Methods: Information on seaweed consumption was collected using a food frequency questionnaire, which included laver, kelp, and sea mustard among the items consumed. A total of 31 hs-CRP-related single nucleotide polymorphisms (SNPs) were selected using genome-wide association studies and clumping analysis, and the individual PRS were calculated by weighting the effect size of each allele in the selected SNPs of 39,369 middle-aged (≥40 years) Koreans using the Korean Genome and Epidemiology Study (KoGES)-Health Examinees (HEXA) cohort data. To investigate the interaction between seaweed intake and the PRS on hs-CRP levels >1 mg/L, hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed using multivariable Cox proportional hazards models. Results: During a mean follow-up period of 4.8 years, we recorded 436 patients with elevated hs-CRP levels. Women in the highest tertile of the PRS with the lowest quartile of seaweed intake had an increased incidence of elevated hs-CRP levels compared with women in the lowest tertile of the PRS with the lowest seaweed intake quartile (HR 2.34, 95% CI 1.23-4.45). No significant association was observed among the men. Conclusion: In conclusion, we identified a new interaction between the PRS, seaweed intake, and inflammation in Korean women, and this study suggests that the interaction between the identification of genetic predisposition and dietary seaweed intake may have an impact on determining the risk of developing hyperinflammation in the future.

Protein-protein Interaction Analysis of Bradykinin Receptor B2 with Bradykinin and Kallidin

  • Nagarajan, Santhosh Kumar;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.10 no.2
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    • pp.74-77
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    • 2017
  • Bradykinin receptor B2 (B2R) is a GPCR protein which binds with the inflammatory mediator hormone bradkynin. Kallidin, a decapeptide, also signals through this receptor. B2R is crucial in the cross-talk between renin-angiotensin system (RAS) and the kinin-kallikrein system (KKS) and in many processes including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Thus the structural study of the receptor becomes important. We have predicted the peptide structures of Bradykinin and Kallidin from their amino acid sequences and the structures were docked with the receptor structure. The results obtained from protein-protein docking could be helpful in studying the B2R structural features and in the pathophysiology in various diseases related to it.

P22-Based Challenge Phage Constructs to Study DNA-Protein Interactions between the $\sigma$54-Dependent Promoter, dctA, and Its Transcriptional Regulators

  • Kim, Euhgbin;Kim, Daeyou;Lee, Joon-Haeng
    • Journal of Microbiology
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    • v.38 no.3
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    • pp.176-179
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    • 2000
  • A challenge phage system was used to study the DNA-protein interaction between C4-dicarboxylic acid transport protein D(DCTD) or $\sigma$54, and a $\sigma$54 -dependent promoter, dctAp. R. meliloti dctA promoter regulatory region replaced the Omnt site on the phage. S. typhimurium strains overproducing either DCTD or $\sigma$54 directed this challenge phage towards lysogency, indicating that DCTD or E$\sigma$54 recognized the dctA promoter on the phage and repressed transcription of the ant gene. These challenge phage constructs will be useful for examining interactions between DCTD(or $\sigma$54) and the dctA promoter region.

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Use of .lambda.gt 11 and antibody probes to isolate genes encoding RNA polymerase subunits from bacillus subtilis

  • Suh, Joo-Won;Price, Chester
    • The Microorganisms and Industry
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    • v.14 no.1
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    • pp.17-20
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    • 1988
  • A genetic analysis of the complex Bacillus subtilis transcriptional apparatus is essential to understand the function, regulation, and interaction of the transcriptase components during growth and sporulation. This approach in Escherichia coli has uncovered fundamental mechanisms regulating gene expression Cole and Nomura, 1986; Lindahl and Zengel, 1986) and an analysis of the B. subtilis transcriptase will allow comoparison of the E.coli system to another bacterium that has evolved under different selective pressures. To this end we used antibody probes to isolate the alpha, beta, and beta' core subunit genes from a .lambda.gtill expression vector library. To address the question of function ans regulation of the minor sigma factors that confer promoter specifity on the polymerase core (Losick et al., 1986), we used the same approach to isolate the gene for the 37,000 dalton sigma factor, sigma-37.

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Update of Therapeutic Clinical Trials for Amyotrophic Lateral Sclerosis (근위축측삭경화증에 대한 치료약물 임상시험 현황)

  • Kim, Nam-Hee;Lee, Min Oh
    • Annals of Clinical Neurophysiology
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    • v.17 no.1
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    • pp.1-16
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    • 2015
  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by progressive death of motor neurons in the cortex, brainstem, and spinal cord. Until now, many treatment strategies have been tested in ALS, but so far only Riluzole has shown efficacy of slightly slowing disease progression. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. Other motor neuron disease such as spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) are also progressive neurodegenerative disease with loss of motor neuron as ALS. This common thread of motor neuron loss has provided a target for the development of therapies for these motor neuron diseases. A better understanding of these pathogenic mechanisms and the potential pathological relationship between the various cellular processes have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.

Biological Therapy for Inflammatory Bowel Disease in Children

  • Na, So-Young;Shim, Jung-Ok
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.15 no.1
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    • pp.13-18
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    • 2012
  • The pathogenesis of inflammatory bowel diseases is not very well understood; it is currently thought to be caused by the interaction between genetic factors, environmental factors, intestinal microbes, and immune factors. Biological agents such as anti-tumor necrosis factor (anti-TNF) are widely being used as therapeutic agents. Infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, has been demonstrated to have an effect in the induction and maintenance of remission in Crohn's disease in children. The effects of biological agents, typified by anti-TNFs, in inflammatory bowel disease in children; the recent concern on the administration of biological agents in combination with immunomodulators; and 'Top-down' therapy are some of the topics covered in this review.