Cellular response to efficient dUTPase RNAi silencing in stable HeLa cell lines perturbs expression levels of genes involved in thymidylate metabolism.

dUTPase is involved in preserving DNA integrity in cells. We report an efficient dUTPase silencing by RNAi-based system in stable human cell line. Repression of dUTPase induced specific expression level increments for thymidylate kinase and thymidine kinase, and also an increased sensitization to 5-fluoro-2'-deoxyuridine and 5-fluoro-uracil. The catalytic mechanism of dUTPase was investigated for 5-fluoro-dUTP. The 5F-substitution on the uracil ring of the substrate did not change the kinetic mechanism of dUTP hydrolysis by dUTPase. Results indicate that RNAi silencing of dUTPase induces a complex cellular response wherein sensitivity towards fluoropyrimidines and gene expression levels of related enzymes are both modulated

Formaldehyde Exposure and Asthma in Children: A Systematic Review

Obj e c t i v e: Despite multiple published studies regarding the association between formaldehyde exposure and childhood asthma, a consistent association has not been identified. Here we report the results of a systematic review of published literature in order to provide a more comprehensive picture of this relationship. Data s o u r c e s: After a comprehensive literature search, we identified seven peer-reviewed studies providing quantitative results regarding the association between formaldehyde exposure and asthma in children. Studies were heterogeneous with respect to the definition of asthma (e.g., self-report, physician diagnosis). Most of the studies were cross-sectional

Insect chemical ecology: chemically mediated interactions and novel applications in agriculture

Forum PaperInsect chemical ecology (ICE) evolved as a discipline concerned with plant–insect interactions, and also with a strong focus on intraspecific pheromone-mediated communication. Progress in this field has rendered a more complete picture of how insects exploit chemical information in their surroundings in order to survive and navigate their world successfully. Simultaneously, this progress has prompted new research questions about the evolution of insect chemosensation and related ecological adaptations, molecular mechanisms that mediate commonly observed behaviors, and the consequences of chemically mediated interactions in different ecosystems. Themed meetings, workshops, and summer schools are ideal platforms for discussing scientific advancements as well as identifying gaps and challenges within the discipline. From the 11th to the 22nd of June 2018, the 11th annual PhD course in ICE was held at the Swedish University of Agricultural Sciences (SLU) Alnarp, Sweden. The course was made up of 35 student participants from 22 nationalities (Fig. 1a) as well as 32 lecturers. Lectures and laboratory demonstrations were supported by literature seminars, and four broad research areas were covered: (1) multitrophic interactions and plant defenses, (2) chemical communication focusing on odor sensing, processing, and behavior, (3) disease vectors, and (4) applied aspects of basic ICE research in agriculture. This particular article contains a summary and brief synthesis of these main emergent themes and discussions from the ICE 2018 course. In addition, we also provide suggestions on teaching the next generation of ICE scientists, especially during unprecedented global situationsinfo:eu-repo/semantics/publishedVersio

Substantial variation across geographic regions in the obesity prevalence among 6–8 years old Hungarian children (COSI Hungary 2016)

Abstract Background There have been previous representative nutritional status surveys conducted in Hungary, but this is the first one that examines overweight and obesity prevalence according to the level of urbanization and in different geographic regions among 6–8-year-old children. We also assessed whether these variations were different by sex. Methods This survey was part of the fourth data collection round of World Health Organization (WHO) Childhood Obesity Surveillance Initiative which took place during the academic year 2016/2017. The representative sample was determined by two-stage cluster sampling. A total of 5332 children (48.4% boys; age 7.54 ± 0.64 years) were measured from all seven geographic regions including urban (at least 500 inhabitants per square kilometer; n = 1598), semi-urban (100 to 500 inhabitants per square kilometer; n = 1932) and rural (less than 100 inhabitants per square kilometer; n = 1802) areas. Results Using the WHO reference, prevalence of overweight and obesity within the whole sample were 14.2, and 12.7%, respectively. According to the International Obesity Task Force (IOTF) reference, rates were 12.6 and 8.6%. Northern Hungary and Southern Transdanubia were the regions with the highest obesity prevalence of 11.0 and 12.0%, while Central Hungary was the one with the lowest obesity rate (6.1%). The prevalence of overweight and obesity tended to be higher in rural areas (13.0 and 9.8%) than in urban areas (11.9 and 7.0%). Concerning differences in sex, girls had higher obesity risk in rural areas (OR = 2.0) but boys did not. Odds ratios were 2.0–3.4 in different regions for obesity compared to Central Hungary, but only among boys. Conclusions Overweight and obesity are emerging problems in Hungary. Remarkable differences were observed in the prevalence of obesity by geographic regions. These variations can only be partly explained by geographic characteristics. Trial registration Study protocol was approved by the Scientific and Research Ethics Committee of the Medical Research Council (61158–2/2016/EKU)

High sugar content of European commercial baby foods and proposed updates to existing recommendations

The aim was to determine whether commercial baby foods marketed within Europe (up to 36 months of age) have inappropriate formulation and high sugar content and to provide suggestions to update European regulations and recommendations as part of a nutrient profile model developed for this age group. The latter was produced following recommended World Health Organization (WHO) steps, including undertaking a rapid literature review. Packaging information from countries across the WHO European region was used to determine mean energy from total sugar by food category. The percentage of products containing added sugar and the percentage of savoury meal‐type products containing pureed fruit were also calculated. A total of 2,634 baby foods from 10 countries were summarised: 768 sold in the United Kingdom, over 200 each from Denmark (319), Spain (241), Italy (430) and Malta (243) and between 99–200 from Hungary, Norway, Portugal, Estonia and Slovenia. On average, approximately a third of energy in baby foods in these European countries came from total sugar, and for most food categories, energy from sugar was higher than 10%. Use of added sugars was widespread across product categories, with concentrated fruit juice most commonly used. Savoury meal‐type purees did not contain added sugars except in United Kingdom and Malta; however, fruit as an ingredient was found in 7% of savoury meals, most frequently seen in UK products. Clear proposals for reducing the high sugar content seen in commercial baby foods were produced. These suggestions, relating to both content and labelling, should be used to update regulations and promote product reformulation

Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background.

BackgroundPrevious studies have compared sperm phenotypes between men with partial [1] deletions within the AZFc region of the Y chromosome with non-carriers, with variable results. Here, we have investigated a separate question, the basis of the variation in sperm phenotype within gr/gr deletion carriers, which ranges from normozoospermia to azoospermia. Differences in the genes removed by independent gr/gr deletions, the occurrence of subsequent duplications or the presence of linked modifying variants elsewhere on the chromosome have been suggested as possible causal factors. We set out to test these possibilities in a large sample of gr/gr deletion carriers with known phenotypes spanning the complete range.ResultsWe assembled a collection of 169 men diagnosed with gr/gr deletions from six centres in Europe and one in Australia, and characterized the DAZ and CDY1 copies retained, the presence or absence of duplications and the Y-chromosomal haplogroup. Although our study had good power to detect factors that accounted for 655.5% of the variation in sperm concentration, no such factor was detected. A negative effect of gr/gr deletions followed by b2/b4 duplication was observed within the normospermic group, which remains to be further explored in a larger study population. Finally, we observed significant geographical differences in the frequency of different subtypes of gr/gr deletions which may have relevance for the interpretation of case control studies dealing with admixed populations.ConclusionsWe conclude that the phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background

Adhesion kinetics of human primary monocytes, dendritic cells, and macrophages: Dynamic cell adhesion measurements with a label-free optical biosensor and their comparison with end-point assays

Monocytes, dendritic cells (DCs), and macrophages (MFs) are closely related immune cells that differ in their main functions. These specific functions are, to a considerable degree, determined by the differences in the adhesion behavior of the cells. To study the inherently and essentially dynamic aspects of the adhesion of monocytes, DCs, and MFs, dynamic cell adhesion assays were performed with a high-throughput label-free optical biosensor [Epic BenchTop (BT)] on surfaces coated with either fibrinogen (Fgn) or the biomimetic copolymer PLL-g-PEG-RGD. Cell adhesion profiles typically reached their maximum at ∼60 min after cell seeding, which was followed by a monotonic signal decrease, indicating gradually weakening cell adhesion. According to the biosensor response, cell types could be ordered by increasing adherence as monocytes, MFs, and DCs. Notably, all three cell types induced a larger biosensor signal on Fgn than on PLL-g-PEG-RGD. To interpret this result, the molecular layers were characterized by further exploiting the potentials of the biosensor: by measuring the adsorption signal induced during the surface coating procedure, the authors could estimate the surface density of adsorbed molecules and, thus, the number of binding sites potentially presented for the adhesion receptors. Surfaces coated with PLL-g-PEG-RGD presented less RGD sites, but was less efficient in promoting cell spreading than those coated with Fgn; hence, other binding sites in Fgn played a more decisive role in determining cell adherence. To support the cell adhesion data obtained with the biosensor, cell adherence on Fgn-coated surfaces 30–60 min after cell seeding was measured with three complementary techniques, i.e., with (1) a fluorescence-based classical adherence assay, (2) a shear flow chamber applying hydrodynamic shear stress to wash cells away, and (3) an automated micropipette using vacuum-generated fluid flow to lift cells up. These techniques confirmed the results obtained with the high-temporal-resolution Epic BT, but could only provide end-point data. In contrast, complex, nonmonotonic cell adhesion kinetics measured by the high-throughput optical biosensor is expected to open a window on the hidden background of the immune cell–extracellular matrix interactions