• 제목/요약/키워드: gene environment interactions

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Ambient air pollution and allergic diseases in children

  • Kim, Byoung-Ju;Hong, Soo-Jong
    • Clinical and Experimental Pediatrics
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    • 제55권6호
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    • pp.185-192
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    • 2012
  • The prevalence of allergic diseases has increased worldwide, a phenomenon that can be largely attributed to environmental effects. Among environmental factors, air pollution due to traffic is thought to be a major threat to childhood health. Residing near busy roadways is associated with increased asthma hospitalization, decreased lung function, and increased prevalence and severity of wheezing and allergic rhinitis. Recently, prospective cohort studies using more accurate measurements of individual exposure to air pollution have been conducted and have provided definitive evidence of the impact of air pollution on allergic diseases. Particulate matter and ground-level ozone are the most frequent air pollutants that cause harmful effects, and the mechanisms underlying these effects may be related to oxidative stress. The reactive oxidative species produced in response to air pollutants can overwhelm the redox system and damage the cell wall, lipids, proteins, and DNA, leading to airway inflammation and hyper-reactivity. Pollutants may also cause harmful effects via epigenetic mechanisms, which control the expression of genes without changing the DNA sequence itself. These mechanisms are likely to be a target for the prevention of allergies. Further studies are necessary to identify children at risk and understand how these mechanisms regulate gene-environment interactions. This review provides an update of the current understanding on the impact of air pollution on allergic diseases in children and facilitates the integration of issues regarding air pollution and allergies into pediatric practices, with the goal of improving pediatric health.

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

  • Maret, Wolfgang
    • Preventive Nutrition and Food Science
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    • 제22권1호
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    • pp.1-8
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    • 2017
  • About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic ${\beta}$- and ${\alpha}$-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the pathobiochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of ${\beta}$-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions.

환경 중의 엔도톡신 노출 및 건강에 미치는 영향 (Exposure to Environmental Endotoxin and Health Effects)

  • 박주형
    • 한국환경보건학회지
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    • 제40권4호
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    • pp.265-278
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    • 2014
  • Microbes such as bacteria, fungi, archaea, protists, and viruses are ubiquitous and people are exposed to them continuously. Endotoxin is a component of the outer membrane of Gram-negative bacteria and a potent proinflammaotry substance. When a person is exposed to environmental endotoxin, an innate immune response is initiated upon the initial recognition and this response produces various inflammatory mediators and recruits inflammatory cells to the exposed tissues. A purified chemical form of endotoxin is called lipopolysaccharide (LPS), and the lipid A portion of the molecule is a biologically active moiety. Exposure to endotoxin may result in various complex health effects depending on time, route, and dose of exposure, as well as host susceptibility. Gene-environment interactions play important roles in health effects of endotoxin exposure, e.g. development or aggravation of asthma. To accurately assess exposure to endotoxin in environmental or epidemiologic studies, methods of sampling, extraction, and analysis must be carefully selected since the selected methods may substantially affect analytical results and there is no internationally-agreed standard method to date. The lack of a standardized method hampers the establishment of exposure-response relationships. While an internationally-agreed health-based exposure limit does not exist, the Dutch Expert Committee on Occupational Safety recently recommended $90EU/m^3$ as a health-based occupational exposure limit. The current article reviews various scientific issues on how we measure environmental endotoxin and the health effects of endotoxin exposure.

The Health Examinees (HEXA) Study: Rationale, Study Design and Baseline Characteristics

  • Health Examinees (HEXA) Study Group
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권4호
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    • pp.1591-1597
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    • 2015
  • Background: Korea has experienced rapid economic development in a very short period of time. A mixture of traditional and modern risk factors coexists and the rapid change in non-genetic factors interacts with genetic constituents. With consideration of these unique aspects of Korean society, a large-scale genomic cohort study-the Health Examinees (HEXA) Study-has been conducted to investigate epidemiologic characteristics, genomic features, and gene-environment interactions of major chronic diseases including cancer in the Korean population. Materials and Methods: Following a standardized study protocol, the subjects were prospectively recruited from 38 health examination centers and training hospitals throughout the country. An interview-based questionnaire survey was conducted to collect information on socio-demographic characteristics, medical history, medication usage, family history, lifestyle factors, diet, physical activity, and reproductive factors for women. Various biological specimens (i.e., plasma, serum, buffy coat, blood cells, genomic DNA, and urine) were collected for biorepository according to the standardized protocol. Skilled medical staff also performed physical examinations. Results: Between 2004 and 2013, a total of 167,169 subjects aged 40-69 years were recruited for the HEXA study. Participants are being followed up utilizing active and passive methods. The first wave of active follow-up began in 2012 and it will be continued until 2015. The principal purpose of passive follow-up is based on data linkages with the National Death Certificate, the National Cancer Registry, and the National Health Insurance Claim data. Conclusions: The HEXA study will render an opportunity to investigate biomarkers of early health index and the chronological changes associated with chronic diseases.

Environmental Change Uncovers Differences in Polygenic Effect of Chromosomes from a Natural Population of Drosophila melanogaster

  • Jeung, Min-Gull;Thompson, James-N.Jr;Lee, Chung-Choo
    • Animal cells and systems
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    • 제1권4호
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    • pp.609-617
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    • 1997
  • Polygenic variation of sternopleural bristle number was investigated at the whole chromosome level in a natural population of Drosophila melanogasfer. Fifty pairs of second and third chromosomes were analyzed at $25^\circ{C}$. Since environmental factors such as temperature influence polygenic expression of quantitative traits, whole chromosomal effects of 28 pairs from the larger original sample were measured under cycling temperature, a $10-30\circ{C}$ cycle in 24 hours, to reveal any polygenic alleles whose effects might be masked under the constant temperature. While third chromosomes typically showed a larger contribution to polygenic variation in both environments, second chromosomes showed greater sensitivity to environmental changes. Cluster analyses of second and third chromosomes produced a limited number of clusters. Such a small number of cluster's implies that there may be a small number of genes, or quantitative trait loci (QTLs), having large effects on phenotypic variation. The genetic structure assessed under constant temperature, however, did not show any correlation with the structure under cycling temperature. The discrepancy could be caused by independent response of each polygenic allele to temperature changes. Thus, polygenic structure in natural populations should be thought of as a temporally changing profile of interactions between gene and ever-changing environment.

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Issues in the Design of Molecular and Genetic Epidemiologic Studies

  • Fowke, Jay H.
    • Journal of Preventive Medicine and Public Health
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    • 제42권6호
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    • pp.343-348
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    • 2009
  • The final decision of study design in molecular and genetic epidemiology is usually a compromise between the research study aims and a number of logistical and ethical barriers that may limit the feasibility of the study or the interpretation of results. Although biomarker measurements may improve exposure or disease assessments, it is necessary to address the possibility that biomarker measurement inserts additional sources of misclassification and confounding that may lead to inconsistencies across the research literature. Studies targeting multi-causal diseases and investigating gene-environment interactions must not only meet the needs of a traditional epidemiologic study but also the needs of the biomarker investigation. This paper is intended to highlight the major issues that need to be considered when developing an epidemiologic study utilizing biomarkers. These issues covers from molecular and genetic epidemiology (MGE) study designs including cross-sectional, cohort, case-control, clinical trials, nested case-control, and case-only studies to matching the study design to the MGE research goals. This review summarizes logistical barriers and the most common epidemiological study designs most relevant to MGE and describes the strengths and limitations of each approach in the context of common MGE research aims to meet specific MEG objectives.

Transcriptional Interplay between Malassezia restricta and Staphylococcus Species Co-Existing in the Skin Environment

  • Hyun Oh Yang;Yong-Joon Cho;Jae Min Lee;Kyoung-Dong Kim
    • Journal of Microbiology and Biotechnology
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    • 제33권3호
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    • pp.319-328
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    • 2023
  • Malassezia and Staphylococcus are the most dominant genera in human skin microbiome. To explore the inter-kingdom interactions between the two genera, we examined the transcriptional changes in Malassezia and Staphylococcus species induced upon co-culturing. RNA-seq analyses revealed that genes encoding ribosomal proteins were upregulated, while those encoding aspartyl proteases were downregulated in M. restricta after co-culturing with Staphylococcus species. We identified MRET_3770 as a major secretory aspartyl protease coding gene in M. restricta through pepstatin-A affinity chromatography followed by mass spectrometry and found that the expression of MRET_3770 was significantly repressed upon co-culturing with Staphylococcus species or by incubation in media with reduced pH. Moreover, biofilm formation by Staphylococcus aureus was inhibited in the spent medium of M. restricta, suggesting that biomolecules secreted by M. restricta such as secretory aspartyl proteases may degrade the biofilm structure. We also examined the transcriptional changes in S. aureus co-cultured with M. restricta and found co-cultured S. aureus showed increased expression of genes encoding ribosomal proteins and downregulation of those involved in riboflavin metabolism. These transcriptome data of co-cultured fungal and bacterial species demonstrate a dynamic interplay between the two co-existing genera.

Expression of Placenta-Related Genes (Cdx2 and GATA6) in Cloned Porcine Development

  • Cha, Byung-Hyun;Hwang, Seong-Soo;Lee, Hwi-Cheul;Park, Mi-Rung;Im, Gi-Sun;Woo, Jae-Seok;Park, Soo-Bong;Cho, Jae-Hyeon;Ko, Yeoung-Gyu
    • Reproductive and Developmental Biology
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    • 제33권4호
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    • pp.195-202
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    • 2009
  • Abnormal development and fetal loss during the post-implantation period are key concerns in the production of cloned animals by somatic cell nuclear transfer (SCNT). We hypothesized that the problems in cloned porcine offspring derived from SCNT are related to interactions between the conceptus and the endometrial environment. In the present study, we investigated expression patterns in the formation of placenta-related genes (Cdx2 and GATA6) in whole in vivo normal porcine embryos (from single cell to blastocyst) and each tissue of a normal fetus at Days 25, 35 and 55 by quantitative mRNA expression analysis using real-time PCR. The expression of Cdx2 and GATA6 mRNA increased to around the blastocyst stage. These genes were gradually decreased from the peri-implantation to post-implantation stage. Moreover, we examined the expression patterns of Cdx2 and GATA6 in Day 35 normal and SCNT cloned fetuses by the same methods. And, the level of Cdx2 and GATA6 gene expression in the extraembryonic tissue of SCNT was significantly higher than that of control tissues. From the present results, it can be postulated that the aberrant expression of Cdx2 and GATA6 genes in the endometrial and extraembryonic tissues at pre- and peri-implantation stages may be closely related to the lower efficiency of animal cloning.

Evaluation of Durum Wheat Genotypes for Resistance against Root Rot Disease Caused by Moroccan Fusarium culmorum Isolates

  • Bouarda, Jamila;Bassi, Filippo M.;Wallwork, Hugh;Benchacho, Mohammed;Labhilili, Mustapha;Maafa, Ilyass;El Aissami, Aicha;Bentata, Fatiha
    • The Plant Pathology Journal
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    • 제38권1호
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    • pp.1-11
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    • 2022
  • Fusarium culmorum is one of the most important causal agents of root rot of wheat. In this study, 10 F. culmorum isolates were collected from farms located in five agro-ecological regions of Morocco. These were used to challenge 20 durum wheat genotypes via artificial inoculation of plant roots under controlled conditions. The isolate virulence was determined by three traits (roots browning index, stem browning index, and severity of root rot). An alpha-lattice design with three replicates was used, and the resulting ANOVA revealed a significant (P < 0.01) effect of isolate (I), genotype (G), and G × I interaction. A total of four response types were observed (R, MR, MS, and S) revealing that different genes in both the pathogen and the host were activated in 53% of interactions. Most genotypes were susceptible to eight or more isolates, while the Moroccan cultivar Marouan was reported resistant to three isolates and moderately resistant to three others. Similarly, the Australian breeding line SSD1479-117 was reported resistant to two isolates and moderately resistant to four others. The ICARDA elites Icaverve, Berghisyr, Berghisyr2, Amina, and Icaverve2 were identified as moderately resistant. Principal component analysis based on the genotypes responses defined two major clusters and two sub-clusters for the 10 F. culmorum isolates. Isolate Fc9 collected in Khemis Zemamra was the most virulent while isolate Fc3 collected in Haj-Kaddour was the least virulent. This work provides initial results for the discovery of differential reactions between the durum lines and isolates and the identification of novel sources of resistance.

Surface Polarity Dependent Solid-state Molecular Biological Manipulation with Immobilized DNA on a Gold Surface

  • Lee, Jiyoung;Kim, Jeong Hee
    • International Journal of Oral Biology
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    • 제37권4호
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    • pp.181-188
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    • 2012
  • As the demand for large-scale analysis of gene expression using DNA arrays increases, the importance of the surface characterization of DNA arrays has emerged. We compared the efficiency of molecular biological applications on solid-phases with different surface polarities to identify the most optimal conditions. We employed thiol-gold reactions for DNA immobilization on solid surfaces. The surface polarity was controlled by creating a self-assembled monolayer (SAM) of mercaptohexanol or hepthanethiol, which create hydrophilic or hydrophobic surface properties, respectively. A hydrophilic environment was found to be much more favorable to solid-phase molecular biological manipulations. A SAM of mercaptoethanol had the highest affinity to DNA molecules in our experimetns and it showed greater efficiency in terms of DNA hybridization and polymerization. The optimal DNA concentration for immobilization was found to be 0.5 ${\mu}M$. The optimal reaction time for both thiolated DNA and matrix molecules was 10 min and for the polymerase reaction time was 150 min. Under these optimized conditions, molecular biology techniques including DNA hybridization, ligation, polymerization, PCR and multiplex PCR were shown to be feasible in solid-state conditions. We demonstrated from our present analysis the importance of surface polarity in solid-phase molecular biological applications. A hydrophilic SAM generated a far more favorable environment than hydrophobic SAM for solid-state molecular techniques. Our findings suggest that the conditions and methods identified here could be used for DNA-DNA hybridization applications such as DNA chips and for the further development of solid-phase genetic engineering applications that involve DNA-enzyme interactions.