Biodegradability of the anticancer drug etoposide and identification of the transformation products

Etoposide susceptibility to microbiological breakdown was studied in a batch biotransformation system, in the presence or absence of artificial wastewater containing nutrients, salts and activated sludge at two concentration levels. The primary focus of the present study was to study etoposide transformation products by ultra-high performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry (MS/MS). Data-dependent experiments combining full-scan MS data with product ion spectra were acquired to identify the molecular ions of etoposide transformation products, to propose the molecular formulae and to elucidate their chemical structures. Due to the complexity of the matrix, visual inspection of the chromatograms showed no clear differences between the controls and the treated samples. Therefore, the software package MZmine was used to facilitate the identification of the transformation products and speed up the data analysis. In total, we propose five transformation products; among them, four are described as etoposide transformation products for the first time. Even though the chemical structures of these new compounds cannot be confirmed due to the lack of standards, their molecular formulae can be used to target them in monitoring studies.     

First inter-laboratory comparison exercise for the determination of anticancer drugs in aqueous samples

The results of an inter-laboratory comparison exercise to determine cytostatic anticancer drug residues in surface water, hospital wastewater and wastewater treatment plant effluent are reported. To obtain a critical number of participants, an invitation was sent out to potential laboratories identified to have the necessary knowledge and instrumentation. Nine laboratories worldwide confirmed their participation in the exercise. The compounds selected (based on the extent of use and laboratories capabilities) included cyclophosphamide, ifosfamide, 5-fluorouracil, gemcitabine, etoposide, methotrexate and cisplatinum. Samples of spiked waste (hospital and wastewater treatment plant effluent) and surface water, and additional non-spiked hospital wastewater, were prepared by the organising laboratory (Jo?ef Stefan Institute) and sent out to each participant partner for analysis. All analytical methods included solid phase extraction (SPE) and the use of surrogate/internal standards for quantification. Chemical analysis was performed using either liquid or gas chromatography mass (MS) or tandem mass (MS/MS) spectrometry. Cisplatinum was determined using inductively coupled plasma mass spectrometry (ICP-MS). A required minimum contribution of five laboratories meant that only cyclophosphamide, ifosfamide, methotrexate and etoposide could be included in the statistical evaluation. z-score and Q test revealed 3 and 4 outliers using classical and robust approach, respectively. The smallest absolute differences between the spiked values and the measured values were observed in the surface water matrix. The highest within-laboratory repeatability was observed for methotrexate in all three matrices (CV?≤?12 %). Overall, inter-laboratory reproducibility was poor for all compounds and matrices (CV 27–143 %) with the only exception being methotrexate measured in the spiked hospital wastewater (CV?=?8 %). Random and total errors were identified by means of Youden plots.     

Sympatry and allopatry in the deeply divergent mitochondrial DNA clades of the estuarine pulmonate gastropod genus <Emphasis Type="Italic">Phallomedusa</Emphasis> (Mollusca,Gastropoda)

DNA sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene were collected from estuarine snails in the genus Phallomedusa to examine the effects of estuarine isolation on population structure and gene flow. Three clades were recovered, one corresponding to Phallomedusa austrina and two others with the morphology of Phallomedusa solida. The haplotype diversity in all three clades indicated recent population expansion. Phallomedusa austrina was restricted to the west of a previous land bridge in the Bass Strait between mainland Australia and Tasmania, and P. solida to its east and to northern Tasmania. Phylogeographic analysis of P. austrina and P. solida shows strong geographic separation of species, but no local genetic structure indicative of regional or estuarine isolation. The clades of P. solida exhibit substantial genetic divergence and were sympatric across their entire distribution in eastern Tasmania and mainland Australia. Such a situation, which has not previously been observed in phylogeographic studies of southeast Australia, suggests that P. solida has had a complex refugial history during periods of environmental challenge.     

Corruption in natural resource management: Implications for policy makers

Corruption is the main reason why resource-rich countries perform badly in economic terms. Corruption in resource-rich countries takes two main forms, rent-seeking and patronage. Resource rents induce rent-seeking as individuals compete for a share of the rents rather than use their time and skills more productively. And resource revenues induce patronage as governments pay off supporters to stay in power, resulting in reduced accountability and an inferior allocation of public funds. This paper systematically reviews the literature on natural resources and corruption, and outlines the main policy implications for donors and domestic policy makers. A main conclusion is that priority should be given to policies that address rent-seeking and patronage. In other words, policy in resource-rich countries should be less about macro-economic management and more about institutions to prevent rent-seeking and patronage, and about giving the right incentives to players in the resource sector. Moreover, all policies need to take into account their impact on rent-seeking and patronage, and some current policies may actually be harmful in this respect.     

NABat: A top-down,bottom-up solution to collaborative continental-scale monitoring

Collaborative monitoring over broad scales and levels of ecological organization can inform conservation efforts necessary to address the contemporary biodiversity crisis. An important challenge to collaborative monitoring is motivating local engagement with enough buy-in from stakeholders while providing adequate top-down direction for scientific rigor, quality control, and coordination. Collaborative monitoring must reconcile this inherent tension between top-down control and bottom-up engagement. Highly mobile and cryptic taxa, such as bats, present a particularly acute challenge. Given their scale of movement, complex life histories, and rapidly expanding threats, understanding population trends of bats requires coordinated broad-scale collaborative monitoring. The North American Bat Monitoring Program (NABat) reconciles top-down, bottom-up tension with a hierarchical master sample survey design, integrated data analysis, dynamic data curation, regional monitoring hubs, and knowledge delivery through web-based infrastructure. NABat supports collaborative monitoring across spatial and organizational scales and the full annual lifecycle of bats.     

Cx43 regulates mechanotransduction mechanisms in human preterm amniotic membrane defects

Objective

The effects of mechanical stimulation in preterm amniotic membrane (AM) defects were explored.

Methods

Preterm AM was collected from women undergoing planned preterm caesarean section (CS) due to fetal growth restriction or emergency CS after spontaneous preterm prelabour rupture of the membranes (sPPROM). AM explants near the cervix or placenta were subjected to trauma and/or mechanical stimulation with the Cx43 antisense. Markers for nuclear morphology (DAPI), myofibroblasts (αSMA), migration (Cx43), inflammation (PGE₂) and repair (collagen, elastin and transforming growth factor β [TGFβ₁]) were examined by confocal microscopy, second harmonic generation, qPCR and biochemical assays.

Results

In preterm AM defects, myofibroblast nuclei were highly deformed and contractile and expressed αSMA and Cx43. Mechanical stimulation increased collagen fibre polarisation and the effects on matrix markers were dependent on tissue region, disease state, gestational age and the number of fetuses. PGE₂ levels were broadly similar but reduced after co-treatment with Cx43 antisense in late sPPROM AM defects. TGFβ₁ and Cx43 gene expression were significantly increased after trauma and mechanical stimulation but this response dependent on gestational age.

Conclusion

Mechanical stimulation affects Cx43 signalling and cell/collagen mechanics in preterm AM defects. Establishing how Cx43 regulates mechanosignalling could be an approach to repair tissue integrity after trauma.