Phototoxicity of tetracyclines as related to singlet oxygen production and uptake by polymorphonuclear leukocytes

The photo-induced singlet oxygen production of six tetracyclines was measured as tryptophan degradation. Demethylchlortetracycline was the most efficient singlet oxygen producer followed by doxycycline. The least efficient producer was minocycline. Doxycycline, however, was the most potent inducer of photodamage to polymorphonuclear leukocytes (PMNLs) followed by demethylchlortetracycline. Accordingly, the singlet oxygen production during irradiation did not correlate with the induction of photodamage to the PMNLs. However, the uptake of doxycycline by the cells was 3 times higher than that of demethylchlortetracycline, and the tetracycline-induced photodamage to the PMNLs correlated with the product of singlet oxygen production during irradiation and the drug uptake by the cells.     

Unraveling toxicological mechanisms and predicting toxicity classes with gene dysregulation networks

The use of genes for distinguishing classes of toxicity has become well established. In this paper we combine the reconstruction of a gene dysregulation network (GDN) with a classifier to assign unseen compounds to their appropriate class. Gene pairs in the GDN are dysregulated in the sense that they are linked by a common expression pattern in one class and differ in this pattern in another class. The classifier gives a quantitative measure on this difference by its prediction accuracy. As an in‐depth example, gene pairs were selected that were dysregulated between skin cells treated with either sensitizers or irritants. Pairs with known and novel markers were found such as HMOX1 and ZFAND2A, ATF3 and PPP1R15A, OXSR1 and HSPA1B, ZFP36 and MAFF. The resulting GDN proved biologically valid as it was well‐connected and enriched in known interactions, processes and common regulatory motifs for pairs. Classification accuracy was improved when compared with conventional classifiers. As the dysregulated patterns for heat shock responding genes proved to be distinct from those of other stress genes, we were able to formulate the hypothesis that heat shock genes play a specific role in sensitization, apart from other stress genes. In conclusion, our combined approach creates added value for classification‐based toxicogenomics by obtaining novel, well‐distinguishing and biologically interesting measures, suitable for the formulation of hypotheses on functional relationships between genes and their relevance for toxicity class differences. Copyright © 2012 John Wiley & Sons, Ltd.     

Complexities in the process of translating research documents in cross-cultural settings

ABSTRACT

In multilingual societies, where researchers and participants often do not speak the same language, research is a challenge as a mismatch of understanding between researchers, research instruments and participants often occurs. Reporting on the translation process is crucial because of the potential implications for the validity of the data that follow from it. We aimed to report on the complexities of such a translation process and many considerations that came to our attention. Methodologically, we used a detailed case study to demonstrate that the complexity of translation might be underestimated by researchers who may neglect to report on the challenges that they experience to benefit the wider research community. We emphasise that translating documents, particularly between languages that are not cognate, requires time and financial resources that researchers often do not anticipate or plan for. By discussing what happened to texts that were translated, and how we as researchers were challenged by considerations that were primarily linguistic but also straddled cultural and socio-political domains, we hope to encourage a deeper understanding of the translation task. We conclude that consideration of these complexities is necessary if the aim is the development of translated documents which complement the researchers’ goals.     

Making a Visual Impression (or Not): Current Design Practices of Nutritional Websites

Understanding the influence of visual design, as the access point for online health communication, is key as Americans are increasingly sickened by an obesity epidemic. Nutritional websites that deliver critical health information should be considered as a potential strategy to fight against the grave consequences of obesity, as research indicates that consumers are consistently turning to the Internet as a resource for health information. Focusing on nutritional websites, this study analyzes the use of visual design principles that are known to greatly influence first impressions and appeal of the information from the user’s perspective. The results suggest there are opportunities for improvement to the online communication of nutritional information to increase the likelihood of users’ favorable first impressions, the critical first steps for nutritional information delivery goals.     

A SNP in G6PC2 predicts insulin secretion in type 1 diabetes

We investigated whether single nucleotide polymorphisms in genes related to glucose metabolism correlate with insulin secretion in type 1 diabetes patients. A cohort of 49 type 1 diabetes patients underwent serial mixed meal tolerance tests to assess insulin secretion. Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215. Recently diagnosed patients (<100 days) homozygous for the G allele of G6PC2 had higher area under the curve C-peptide on mixed meal tolerance tests compared to non-homozygous patients (344.8 ± 203.2 vs. 167.9 ± 131.5, p = 0.04). Other SNPs did not correlate with insulin secretion in the new onset period. In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time. A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.