Totalsynthese von 2-Deshexyl-Thuggacin C und Oxazol-Thuggacin B Derivaten & Studien zur Totalsynthese von aza-Thuggacin

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Off-grid: solar powered LED illumination impacts epigeal arthropods

Advances in LED technology combined with solar, storable energy bring light to places remote from electricity grids. Worldwide more than 1.3 billion of people are living off-grid, often in developing regions of high insect biodiversity. In developed countries, dark refuges for wildlife are threatened by ornamental garden lights. Solar powered LEDs (SPLEDs) are cheaply available, dim, and often used to illuminate foot paths, but little is known on their effects on ground living (epigeal) arthropods. We used off-the-shelf garden lamps with a single ‘white’ LED (colour temperature 7250 K) to experimentally investigate effects on attraction and nocturnal activity of ground beetles (Carabidae). We found two disparate and species-specific effects of SPLEDs. (i) Some nocturnal, phototactic species were not reducing activity under illumination and were strongly attracted to lamps (>20-fold increase in captures compared to dark controls). Such species aggregate in lit areas and SPLEDs may become ecological traps, while the species is drawn from nearby, unlit assemblages. (ii) Other nocturnal species were reducing mobility and activity under illumination without being attracted to light, which may cause fitness reduction in lit areas. Both reactions offer mechanistic explanations on how outdoor illumination can change population densities of specific predatory arthropods, which may have cascading effects on epigeal arthropod assemblages. The technology may thus increase the area of artificial light at night (ALAN) impacting insect biodiversity. Measures are needed to mitigate effects, such as adjustment of light colour temperature and automated switch-offs

Inflammatory markers in a 2-year soy intervention among premenopausal women

Epidemiologic evidence supports a role of soy foods in breast cancer etiology. Because chronic inflammation appears to be a critical component in carcinogenesis, we examined the potential anti-inflammatory effects of soy foods.The original 2-year dietary intervention randomized 220 premenopausal women of whom 183 women (90 in the intervention group and 93 in the control group) were included in the current investigation; 40% were of Asian ancestry. The intervention group consumed two daily soy servings containing 50 mg of isoflavones (aglycone equivalents), whereas the controls maintained their regular diet. Five serum samples obtained at month 0, 3, 6, 12, and 24 were analyzed for interleukin (IL)-6, C-reactive protein (CRP), leptin, and adiponectin by ELISA. For statistical analysis, mixed models were applied to incorporate the repeated measurements.Results:The levels of all analytes were lower in Asian than Caucasian women. Overweight women had significantly higher levels of CRP, IL-6, and leptin and lower levels of adiponectin than normal weight women. We did not observe a significant effect of soy foods on the four markers, but leptin increased in the control and not in the intervention group (p = 0.20 for group-time effect); this difference was significant for Asian (p = 0.01) and obese women (p = 0.005).During this 2-year intervention, soy foods did not modify serum levels of CRP, IL-6, leptin, and adiponectin in premenopausal women although leptin levels remained stable among women in the intervention group who were obese or of Asian ancestry. Further studies with diverse markers of inflammation are necessary to clarify the specific effect of soy on immune responses

Growth and differentiation of primary and passaged equine bronchial epithelial cells under conventional and air-liquid-interface culture conditions

<p>Abstract</p> <p>Background</p> <p>Horses develop recurrent airway obstruction (RAO) that resembles human bronchial asthma. Differentiated primary equine bronchial epithelial cells (EBEC) in culture that closely mimic the airway cells <it>in vivo </it>would be useful to investigate the contribution of bronchial epithelium in inflammation of airway diseases. However, because isolation and characterization of EBEC cultures has been limited, we modified and optimized techniques of generating and culturing EBECs from healthy horses to mimic <it>in vivo </it>conditions.</p> <p>Results</p> <p>Large numbers of EBEC were obtained by trypsin digestion and successfully grown for up to 2 passages with or without serum. However, serum or ultroser G proved to be essential for EBEC differentiation on membrane inserts at ALI. A pseudo-stratified muco-ciliary epithelium with basal cells was observed at differentiation. Further, transepithelial resistance (TEER) was more consistent and higher in P₁cultures compared to P₀cultures while ciliation was delayed in P₁cultures.</p> <p>Conclusions</p> <p>This study provides an efficient method for obtaining a high-yield of EBECs and for generating highly differentiated cultures. These EBEC cultures can be used to study the formation of tight junction or to identify epithelial-derived inflammatory factors that contribute to lung diseases such as asthma.</p

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 x 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p &lt; 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p &lt; 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment.O

An epigenome-wide association study identifies multiple DNA methylation markers of exposure to endocrine disruptors

Background: Exposure to environmental endocrine disrupting chemicals (EDCs) may play an important role in the epidemic of metabolic diseases. Epigenetic alterations may functionally link EDCs with gene expression and metabolic traits. Objectives: We aimed to evaluate metabolic-related effects of the exposure to endocrine disruptors including five parabens, three bisphenols, and 13 metabolites of nine phthalates as measured in 24-hour urine on epigenome-wide DNA methylation. Methods: A blood-based epigenome-wide association study was performed in 622 participants from the Lifelines DEEP cohort using Illumina Infinium HumanMethylation450 methylation data and EDC excretions in 24-hour urine. Out of the 21 EDCs, 13 compounds were detected in >75% of the samples and, together with bisphenol F, were included in these analyses. Furthermore, we explored the putative function of identified methylation markers and their correlations with metabolic traits. Results: We found 20 differentially methylated cytosine-phosphate-guanines (CpGs) associated with 10 EDCs at suggestive p-value < 1 × 10−6, of which four, associated with MEHP and MEHHP, were genome-wide significant (Bonferroni-corrected p-value < 1.19 × 10−7). Nine out of 20 CpGs were significantly associated with at least one of the tested metabolic traits, such as fasting glucose, glycated hemoglobin, blood lipids, and/or blood pressure. 18 out of 20 EDC-associated CpGs were annotated to genes functionally related to metabolic syndrome, hypertension, obesity, type 2 diabetes, insulin resistance and glycemic traits. Conclusions: The identified DNA methylation markers for exposure to the most common EDCs provide suggestive mechanism underlying the contributions of EDCs to metabolic health. Follow-up studies are needed to unravel the causality of EDC-induced methylation changes in metabolic alterations

Cell type-specific regulation of CCN2 protein expression by PI3K–AKT–FoxO signaling

The biological activity of connective tissue growth factor (CTGF, CCN2) is regulated at the level of intracellular signaling leading to gene expression, and by its extracellular interaction partners which determine the functional outcome of CCN2 action. In this overview, we summarize the data which provide evidence that one of the major signaling pathways, phosphatidylinositol-3 kinase (PI3K)–AKT signaling, shows a remarkable cell type-dependence in terms of regulation of CCN2 expression. In smooth muscle cells, fibroblasts, and epithelial cells, inhibition of this pathway either reduced CCN2 expression or was not involved in CCN2 gene expression depending on the stimulus used. In microvascular endothelial cells by contrast, activation of PI3K–AKT signaling was inversely related to CCN2 expression. Upregulation of CCN2 upon inhibition of PI3K–AKT was also observed in primary cultures of human endothelial cells (HUVEC) exposed to laminar flow in an in vitro flow-through system. In different types of endothelial cells, FoxO transcription factors, which are negatively regulated by AKT, were identified as potent activators of CCN2 gene expression. In HUVEC, we observed a correlation between enhanced nuclear localization of FoxO1 and increased synthesis of CCN2 protein in areas of non-uniform shear stress. These data indicate that FoxO proteins are key regulators of CCN2 gene expression which determine the effect of PI3K–AKT activation in terms of CCN2 regulation. Short summary Phosphatidylinositol-3 kinase (PI3K)–AKT signaling shows a remarkable cell type-dependence in terms of regulation of CCN2 expression. In endothelial cells activation of PI3K - AKT signaling was inversely related to CCN2 expression. FoxO transcription factors, which are negatively regulated by AKT, were identified as potent activators of CCN2 gene expression

Genetic and epigenetic regulation of gene expression in fetal and adult human livers

Background: The liver plays a central role in the maintenance of homeostasis and health in general. However, there is substantial inter-individual variation in hepatic gene expression, and although numerous genetic factors have been identified, less is known about the epigenetic factors. Results: By analyzing the methylomes and transcriptomes of 14 fetal and 181 adult livers, we identified 657 differentially methylated genes with adult-specific expression, these genes were enriched for transcription factor binding sites of HNF1A and HNF4A. We also identified 1,000 genes specific to fetal liver, which were enriched for GATA1, STAT5A, STAT5B and YY1 binding sites. We saw strong liver-specific effects of single nucleotide polymorphisms on both methylation levels (28,447 unique CpG sites (meQTL)) and gene expression levels (526 unique genes (eQTL)), at a false discovery rate (FDR) <0.05. Of the 526 unique eQTL associated genes, 293 correlated significantly not only with genetic variation but also with methylation levels. The tissue-specificities of these associations were analyzed in muscle, subcutaneous adipose tissue and visceral adipose tissue. We observed that meQTL were more stable between tissues than eQTL and a very strong tissue-specificity for the identified associations between CpG methylation and gene expression. Conclusions: Our analyses generated a comprehensive resource of factors involved in the regulation of hepatic gene expression, and allowed us to estimate the proportion of variation in gene expression that could be attributed to genetic and epigenetic variation, both crucial to understanding differences in drug response and the etiology of liver diseases

Prevalences of cardiometabolic risk and lifestyle factors in young parents: evidence from a German birth cohort study

Background Studies show that parents significantly impact their children’s health through their cardiometabolic risk profile and health behavior. There is only little information about the prevalence of cardiometabolic risk factors and lifestyle factors among new parents yet. The aims of this study are therefore to evaluate the prevalences of cardiometabolic risk factors in parents of infants in Germany and to examine their lifestyle and health behavior. Methods In the KUNO-Kids health study, an ongoing birth cohort, parents (n = 930 mothers and 769 fathers) were asked about cardiometabolic risk factors (obesity/hypertension/type 2 diabetes mellitus) and lifestyle factors (dietary/sports/smoking habits/alcohol consumption) during the first year after the birth of their children via questionnaires. Chi-square as well as fisher exact tests were conducted to analyse associations between lifestyle factors and cardiometabolic risk factors. Results 34.2% of mothers and 58.5% of fathers were overweight or obese. In 11.8% of the families, at least one parent suffered from hypertension, in 2.4% from type 2 diabetes mellitus. One year after delivery, 8.5% of mothers were smoking, 6.9% showed a risky alcohol consumption (> 10 g/d). 16.0% of fathers were smoking 4 weeks after childbirth, 10.7% showed risky alcohol consumption (> 20 g/d). 21.6% of mothers carried out sports activity for more than 2 h a week then. Parental hypertension was linked to a higher prevalence of risky alcohol consumption, obesity to a lower prevalence of daily fruits consumption. Conclusions Cardiometabolic risk factors were widespread among new parents with obesity and overweight having the highest prevalences. A considerable number of parents also practiced an unhealthy lifestyle showing that there is potential for improvement to promote the healthy development of their children

Meta-analyses identify DNA methylation associated with kidney function and damage

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs