Metabolic profiling of HepG2 cells incubated with S(−) and R(+) enantiomers of anti-coagulating drug warfarin

Warfarin is a commonly prescribed oral anticoagulant with narrow therapeutic index. It achieves anti-coagulating effects by interfering with the vitamin K cycle. Warfarin has two enantiomers, S(−) and R(+) and undergoes stereoselective metabolism, with the S(−) enantiomer being more effective. We reported the intracellular metabolic profile in HepG2 cells incubated with S(−) and R(+) warfarin by GCMS. Chemometric method PCA was applied to analyze the individual samples. A total of 80 metabolites which belong to different categories were identified. Two batches of experiments (with and without the presence of vitamin K) were designed. In samples incubated with S(−) and R(+) warfarin, glucuronic acid showed significantly decreased in cells incubated with R(+) warfarin but not in those incubated with S(−) warfarin. It may partially explain the lower bio-activity of R(+) warfarin. And arachidonic acid showed increased in cells incubated with S(−) warfarin but not in those incubated with R(+) warfarin. In addition, a number of small molecules involved in γ-glutamyl cycle displayed ratio variations. Intracellular glutathione detection further validated the results. Taken together, our findings provided molecular evidence on a comprehensive metabolic profile on warfarin-cell interaction which may shed new lights on future improvement of warfarin therapy

The Correlation Between DsRed mRNA Levels and Transient DsRed Protein Expression in Plants Depends on Leaf Age and the 5′ Untranslated Region

The yield of recombinant proteins in plants determines their economic competitiveness as a production platform compared to microbes and mammalian cells. The promoter, untranslated regions (UTRs) and codon usage can all contribute to the yield, but potential interactions among these components have not been examined in detail. Here the effect of two promoters (35SS and nos) and four 5′UTRs on the spatiotemporal expression of DsRed mRNA and the accumulation of DsRed protein during transient expression in tobacco (Nicotiana tabacum) mediated by Agrobacterium tumefaciens is investigated. The authors found that the mRNA levels peaked 2–3 days post‐infiltration (dpi), and rapidly declined thereafter, whereas DsRed protein was first detected after ≈3 days and concentrations continued to increase until at least 5 dpi. This temporal decoupling of mRNA and protein expression was strongest in the older leaves, which also produced the lowest DsRed yields. The accumulation of DsRed linearly correlated with mRNA levels in all but the youngest leaves, where more DsRed was synthesized per mRNA molecule. This was the case for both promoters, although the nos promoter had a higher protein/mRNA ratio than the 35SS promoter. Furthermore, the type of 5′UTR affected DsRed protein accumulation by 50% starting from similar levels of mRNA. The authors concluded that DsRed mRNA levels are not the limiting factor for DsRed protein expression in plants, but that translation‐associated processes such as initiation, elongation, and release are bottlenecks that should be addressed in future studies

За кадры. 1979. № 69 (2219)

"По-другому не умею" / В. ФинниковаЕсли подойти творчески / Ю. ДементьевПо вопросам успеваемости / В. ВороновВоспитание начинается с лекций / И. Чащин, Ю. КарбаиновКонференция прошла успешно / Р. ГорскаяСтарший товарищ студента / Г. ЭнтинаНе бывает лишних знаний / Л. РусинаМоральное старение не грозит. Циклотрону 20 лет / А. А. БатуринО делах и дисциплине / Т. ХаринаИнтересная встреча / Н. ЧижикМетодсовет рекомендует / Г. А. Сипайлов, Н. СвендровскаяЛирика / А. Р. Руба

Tropical infections as occupational diseases – labor inspectorate physicians’ aspects of a complex problem

Background: Occupational physicians work directly with individual employees regarding diseases that has been caused or exacerbated by workplace factors. However, employees are increasingly required to travel for their work, including to tropical countries where they risk exposure to diseases they would not normally encounter at home (i.e., malaria). Such disease/s may also take days to months to incubate before becoming symptomatic, even after their return home, thus delaying and complicating the diagnosis. Proving this was an occupational disease with respective sick leave entitlement or compensation can be challenging. There is a lack of data concerning occupational diseases caused by tropical infections.Material and methods: Employee case records for the period 2003-2008 from the State Institute for Occupational Health and Safety of North-Rhine Westphalia in Germany were analysed and assessed within Germany’s regulatory framework. These records included Germany’s largest industrial zone.Results: From 2003-2008the suspected cases of “tropical diseases and typhus”, categorized as occupational disease “Bk 3104” in Germany, have decreased significantly. A high percentage of the suspected cases was accepted as occupational disease, but persistent or permanent sequelae which conferred an entitlement to compensation were rare.Conclusion: There is scope to improve diagnosis and acceptance of tropical diseases as occupational diseases. The most important diseases reported were malaria, amoebiasis, and dengue fever. Comprehensive pre-travel advice and post-travel follow-ups by physicians trained in travel and occupational health medicine should be mandatory. Data indicate that there is a lack of knowledge on how to prevent infectious disease abroad

Magnetocrystalline anisotropy in x-ray magnetic linear dichroism at the 3pp edges of crystalline Fe thin films

X-ray magnetic linear dichroism spectra measured in reflection (XMLD-R) on crystalline bcc Fe thin films across the 3p absorption edges are reported. A series of measurements with varying orientation of the electric field vector of the linear polarized synchrotron radiation with respect to the crystal axes reveals a strong magnetocrystalline anisotropy in the XMLD-R spectra. The spectra agree well with theoretical spectra calculated within the framework of the density-functional theory accounting for the spin-orbital and exchange splitting of the 3p semicore states on an equal footing