The effect of (prenatal) smoke exposure on lung progenitor cell behavior and Cyp2a5 gene regulation

Lung progenitor cell behavior and Cyp2a5 gene regulationPrenatal smoke exposure (PSE) is associated with an increased risk for chronic obstructive pulmonary disease (COPD) and cigarette smoke addiction in later in life. One of the proposed underlying mechanisms for PSE-induced risk for COPD and aberrant smoking behavior could be epigenetic modifications of particular genes. UMCG researcher Khosbayar Lkhagvadorj investigated the effect of (prenatal) smoke exposure on lung epithelial cell development and regeneration linked with epidermal growth factor receptor (EGFR) signaling. This was addressed in PSE neonatal mouse offspring and patients with COPD. In addition, he investigated the effect of pre- and/or postnatal smoke exposure on Cyp2a5 DNA methylation in relation to the in vitro nicotine conversion in liver and lung. He has provided evidence in mouse and human lung tissue and organoid models that (prenatal) smoke exposure triggers abnormal lung development, tissue regeneration, and nicotine dependence. Firstly, (prenatal) smoke exposure impaired lung epithelial cell differentiation in mouse offspring, which was associated with EGFR signaling. Moreover, lower expression of the EGFR on alveolar type 2 cells could be related to impaired alveolar progenitor cell function in COPD patients, which could explain impaired lung regeneration in these patients. Secondly, PSE increased the nicotine metabolism, which could be linked to a persistent change of PSE-induced Cyp2a5 methylation across the three developmental stages. If our results in the mouse were translated to the human situation, smoking during pregnancy would pose a threat to the unborn child, as it not only affects the development of the fetal lung but may also increase the risk of nicotine addiction when the offspring starts smoking

Moğolistan’daki Hoton Türkleri (Dilleri – Kültürleri - Edebiyatları)

Hotonlar Moğolistan’da yaşayan Türk kökenli topluluklardandır. Günümüzde özellikle Moğolistan’ın Uvs eyaletinde, Tarialan, Naranbulag ve Ulaangom’da yaşayan Hotonlar 19. yüzyıla kadar kendilerine özgü bir Türk lehçesi konuşurken günümüzde Oyrat dilinin Dörbet lehçesini kullanmaktadır. Bu tezde Hoton Türkleri araştırılacak; Hoton’ların tarihi, dili ve kültürleri literatür taraması ve derlemelerle ortaya konmaya çalışılacaktır. Günümüzde konuşuru olmayan, ölü lehçeler arasında sayılabilecek Hoton Türkçesinin dil verilerinin incelenmesi ve bunların kayıt altına alınması, bu tezin temel amacıdır. Böylece Hotonlar ve Hoton Türkçesi ile ilgili literaturdeki boşluğa bir katkı sağlanması da umulmaktadır

Relationship Between Oral Microorganisms and Dental Caries

Objectives: The purpose of this study was to investigate the relationship between the incidences of dental caries and the amount and motility of oral microorganisms in inter proximal dental plaque. Methods: Oral microorganism samples from 240 volunteers in six different age groups were classified according to morphology using phase contrast microscopy. We observed the amount and motility of the microorganisms and examined for relationships to the incidences of dental caries. Results: There was a statistically significant difference among the age groups (p < 0.05) in the motility of cocci and bacilli and in the amount of spirilla. The decayed tooth (DT), filled tooth (FT), and decayed, missing, filled tooth (DMFT) index for all age groups were calculated as 7.5 ± 4.5, 1.9 ± 3.0, and 14.8 ± 8.1. There was weak, positive relationship between the amount of cocci and bacilli and caries incidence, regardless of age (p < 0.01). Conclusion: Determining the amount and motility of oral microorganisms is an effective method of evaluating and controlling the status of oral health

The Determination of Filaggrin Gene Single Nucleotides Polymorphisms in Patients with Atopic Dermatitis

Objectives: The protein, filaggrin, is important in barrier function and epidermal differentiation facilitation. Filaggrin gene (FLG) mutations have been identified as the cause of ichthyosis vulgaris (IV), and certain mutations have been associated with atopic dermatitis (AD). We aimed to investigate genetic polymorphism of FLG in Mongolian AD patients. Methods: FLG mutations were determined using sequence analysis in 46 AD patients and 12 IV patients. Severity of AD was assessed using the Scoring Atopic Dermatitis (SCORAD) index. Allergen specific IgE were determined from serum. Filaggrin expression in skin punch biopsy samples of AD patients was investigated using immunohistochemistry (IHC). Results: Several single nucleotides polymorphisms (SNPs) (1150C>T, 1741A>T, 1791C>T, 2181C>G, 2191A>G, and 2263G>A) were demonstrated in AD patients using sequence analysis. Total IgE levels were significantly associated with age (p=0.03) and duration of disease (p=0.02). Presence of SNPs and mixed allergen specific IgE was significantly correlated (p=0.02); 2 SNPs were significantly associated with food allergen specific IgE levels (p=0.009). 2263G>A SNP was significantly correlated with food allergen specific IgE (p=0.003) and a history of atopic diseases (p=0.03). Conclusion: New mutations or genetic polymorphisms with ethnic characteristics may be detected among Mongolians

Prenatal smoke effect on mouse offspring Igf1 promoter methylation from fetal stage to adulthood is organ- and sex-specific

Prenatal smoke exposure (PSE) is associated with reduced birth weight, impaired fetal development, and increased risk for diseases later in life. Changes in DNA methylation may be involved, as multiple large-scale epigenome-wide association studies showed that PSE is robustly associated with DNA methylation changes in blood among offspring in early life. Insulin-like growth factor-1 (IGF1) is important in growth, differentiation, and repair processes after injury. However, no studies investigated the organ-specific persistence of PSE-induced methylation change of Igf1 into adulthood. Based on our previous studies on the PSE effect on Igf1 promoter methylation in fetal and neonatal mouse offspring, we now have extended our studies to adulthood. Our data show that basal Igf1 promoter methylation generally increased in the lung but decreased in the liver (except for 2 persistent CpG sites in both organs) across three different developmental stages. PSE changed Igf1 promoter methylation in all three developmental stages, which was organ and sex specific. The PSE effect was less pronounced in adult offspring compared with the fetal and neonatal stages. In addition, the PSE effect in the adult stage was more pronounced in the lung compared with the liver. For most CpG sites, an inverse correlation was found for promoter methylation and mRNA expression when the data of all three stages were combined. This was more prominent in the liver. Our findings provide additional evidence for sex- and organ-dependent prenatal programming, which supports the developmental origins of health and disease (DOHaD) hypothesis

Prenatal smoke exposure induces persistent Cyp2a5 methylation and increases nicotine metabolism in the liver of neonatal and adult male offspring

Prenatal smoke exposure (PSE) is a risk factor for nicotine dependence. One susceptibility gene for nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine and nicotine clearance in the liver. Higher activity of the CYP2A6 enzyme is associated with nicotine dependence, but no research has addressed the PSE effects on the CYP2A6 gene or its mouse homologue Cyp2a5. We hypothesized that PSE affects Cyp2a5 promoter methylation, Cyp2a5 mRNA levels, and nicotine metabolism in offspring. We used a smoke-exposed pregnant mouse model. RNA, DNA, and microsomal protein were isolated from liver tissue of foetal, neonatal, and adult offspring. Enzyme activity, Cyp2a5 mRNA levels, and Cyp2a5 methylation status of six CpG sites within the promoter region were analysed via HPLC, RT-PCR, and bisulphite pyrosequencing. Our data show that PSE induced higher cotinine levels in livers of male neonatal and adult offspring compared to controls. PSE-induced cotinine levels in neonates correlated with Cyp2a5 mRNA expression and promoter methylation at CpG-7 and CpG+45. PSE increased methylation in almost all CpG sites in foetal offspring, and this effect persisted at CpG-74 in male neonatal and adult offspring. Our results indicate that male offspring of mothers which were exposed to cigarette smoke during pregnancy have a higher hepatic nicotine metabolism, which could be regulated by DNA methylation. Given the detected persistence into adulthood, extrapolation to the human situation suggests that sons born from smoking mothers could be more susceptible to nicotine dependence later in life

Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life.</p

Vertical axis rotation (or lack thereof) of the eastern Mongolian Altay Mountains: implications for far-field transpressional mountain building

The Altay Mountains of Western Mongolia accommodate 10–20% of the current shortening of the India-Asia collision in a transpressive regime. Kinematic models of the Altay require faults to rotate anticlockwise about a vertical axis in order to accommodate compressional deformation on the major strike slip faults that cross the region. Such rotations should be detectable by palaeomagnetic data. Previous estimates from the one existing palaeomagnetic study from the Altay, on Oligocene and younger sediments from the Chuya Basin in the Siberian Altay, indicate that at least some parts of the Altay have experienced up to 39 ± 8° of anticlockwise rotation. Here, we present new palaeomagnetic results from samples collected in Cretaceous and younger sediments in the Zereg Basin along the Har-Us-Nuur fault in the eastern Altay Mountains, Mongolia. Our new palaeomagnetic results from the Zereg Basin provide reliable declinations, with palaeomagnetic directions from 10 sites that pass a fold test and include magnetic reversals. The declinations are not significantly rotated with respect to the directions expected from Cretaceous and younger virtual geomagnetic poles, suggesting that faults in the eastern Altay have not experienced a large degree of vertical axis rotation and cannot have rotated >7° in the past 5 m.y. The lack of rotation along the Har-Us-Nuur fault combined with a large amount of rotation in the northern Altay fits with a kinematic model for transpressional deformation in which faults in the Altay have rotated to an orientation that favours the development of flower structures and building of mountainous topography, while at the same time the range widens at the edges as strain is transferred to better oriented structures. Thus the Har-Us-Nuur fault is a relatively young fault in the Altay, and has not yet accommodated significant rotation

Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life

The methodology of studying changes in the Gobi region`s lake area

This study based on remote sensing methods of changes in the multi-year and seasonal changes in areas of the Buuntsagaan, Orog, Olgoy Lakes in the depression of lakes. Using Landsat 5 and 8 satellite 2000-2017, We used 14 pictures of water and vegetation index those were taken from the lake. Over the past decades, the Gobi region’s lakes have been decreased significantly. There are number of factors affecting changes in areas of the lakes. Finally, we concluded that the water level in the Baidrag and Tuin rivers are decreasing in Buuntsagaan and Orog Lakes