Carboplatin-induced alteration of the thiol homeostasis in the isolated perfused rat kidney

Carboplatin elicits minor side effects with respect to its first generation analogue cisplatin. Nevertheless, a dose-dependent nephrotoxicity of the drug has been reported to occur both in patients and in rats and a possible pathogenic role have been attributed to oxidative stress. We have studied the effect of carboplatin administration on the thiol/disulfide balance, on other biomarkers of oxidative stress and on antioxidant enzymes in the isolated perfused rat kidney. A 5-500 μM carboplatin dose range did not alter renal function but significantly decreased levels of cysteine, glutathione and exposed protein sulfhydryl groups. Only a minimal increment in disulfides was observed, whereas malonyldialdehyde and protein carbonyls did not increase significantly. Among the antioxidant enzymes studied, only thioltransferase was inhibited by the treatment. Our data suggest that a minimal oxidative stress is present under our experimental conditions, thus indicating that platinum-based drugs do not produce significant amount of reactive oxygen species.     

CONTRASTING THOUGHTS ABOUT DECEPTIVE ORCHIDS: A RESPONSE TO SOBEL AND RANDLE

Sobel and Randle (2009) challenge several methodological choices in the comparative study of the evolution of reproductive isolation in Mediterranean deceptive orchids of Scopece et al. (2007) including the species concept used and the selection of taxa, together with the perceived comparison of clades of different ages. They further criticize that pollinator information was taken from the literature and that two different methods were used to estimate pollinator specificity in food-deceptive and sexually deceptive orchids, respectively. Here we reply to these challenges.     

Structural and Functional Divergence within the Dim1/KsgA Family of rRNA Methyltransferases

The enzymes of the KsgA/Dim1 family are universally distributed throughout all phylogeny; however, structural and functional differences are known to exist. The well-characterized function of these enzymes is to dimethylate two adjacent adenosines of the small ribosomal subunit in the normal course of ribosome maturation, and the structures of KsgA from Escherichia coli and Dim1 from Homo sapiens and Plasmodium falciparum have been determined. To this point, no examples of archaeal structures have been reported. Here, we report the structure of Dim1 from the thermophilic archaeon Methanocaldococcus jannaschii. While it shares obvious similarities with the bacterial and eukaryotic orthologs, notable structural differences exist among the three members, particularly in the C-terminal domain. Previous work showed that eukaryotic and archaeal Dim1 were able to robustly complement for KsgA in E. coli. Here, we repeated similar experiments to test for complementarity of archaeal Dim1 and bacterial KsgA in Saccharomyces cerevisiae. However, neither the bacterial nor the archaeal ortholog could complement for the eukaryotic Dim1. This might be related to the secondary, non-methyltransferase function that Dim1 is known to play in eukaryotic ribosomal maturation. To further delineate regions of the eukaryotic Dim1 critical to its function, we created and tested KsgA/Dim1 chimeras. Of the chimeras, only one constructed with the N-terminal domain from eukaryotic Dim1 and the C-terminal domain from archaeal Dim1 was able to complement, suggesting that eukaryotic-specific Dim1 function resides in the N-terminal domain also, where few structural differences are observed between members of the KsgA/Dim1 family. Future work is required to identify those determinants directly responsible for Dim1 function in ribosome biogenesis. Finally, we have conclusively established that none of the methyl groups are critically important to growth in yeast under standard conditions at a variety of temperatures.     

Evidence against a role of ketone bodies in the generation of oxidative stress in human erythrocytes by the application of reliable methods for thiol redox form detection

Aim of this study was to reconsider the previously suggested contribution of ketone bodies in causing oxidative damage in human red blood cells (RBCs) in the light of our recent findings demonstrating some methodological pitfalls that can occur during detection of hematic thiols. RBCs were incubated at 37 °C with 20 mM ketone bodies and analyzed with time for their content of glutathione, glutathione disulfide and S-glutathionylated proteins (in both the hemoglobin and membrane skeletal protein fraction). No changes in the concentrations of glutathione and its related forms were evidenced. Differently from previous reports, our results suggest that ketone bodies do not mediate generation of oxidative stress in human RBCs.     

Revisiting excitation pattern design for magnetic resonance imaging through optimisation of the signal contrast efficiency

The design of excitation signals for Magnetic Resonance Imaging (MRI) is cast as an optimal control problem. Here, we demonstrate that signals other than pulse excitations, which are ubiquitous in MRI, can provide adequate excitation, thus challenging the optimality and ubiquity of pulsed signals. A class of on-resonance piecewise continuous amplitude modulated signals is introduced. It is shown that despite the bilinear nature of the Bloch equations, the spins system response is largely analytically tractable for this class of signals, using Galerkin approximation methods. To challenge the optimality of the pulse excitation, an appropriate cost criterion, the Signal Contrast Efficiency (SCE), is developed. It is to be optimised subject to dynamics expressed by the Bloch equations. To solve the problem the Bloch equation is transferred to the excitation dependent rotating frame of reference. The numerical solutions to the problem for different tissue types show that for a short period of time, pulse excitations provide the maximum signal contrast. However, the problem should be solved for longer periods of time which may result in a different answer than a pulse. For this purpose, the approximate analytic solution which is derived based on averaging the Bloch equation in the excitation dependent rotating frame of reference will be used to find the optimal excitation pattern. The solution to the optimisation problem is potentially useful for all forms of MRI including structural and functional imaging. The objective of this paper is to show that while classically transient response of pulses have been monitored so far, the optimal excitation pattern may be the steady state response of a non-pulse excitation.     

The Bacillus anthracis chromosome contains four conserved, excision-proficient, putative prophages

Background  

Bacillus anthracis is considered to be a recently emerged clone within the Bacillus cereus sensu lato group. The B. anthracis genome sequence contains four putative lambdoid prophages. We undertook this study in order to understand whether the four prophages are unique to B. anthracis and whether they produce active phages.     

Fully Plastic Dye Solar Cell Devices by Low‐Temperature UV‐Irradiation of both the Mesoporous TiO2 Photo‐ and Platinized Counter‐Electrodes

The application of UV irradiation processes are successfully proposed for the first time in the fabrication of both of the two plastic electrodes in flexible dye solar cells (DSCs) and modules. For the realization of the photo‐electrode, a customized TiO₂ paste formulation and UV processing method was developed which yields 134% (48%) performance enhancement with respect to the same (binder‐free) paste treated at 120 °C. UV treatment induces both complete removal of organic media and more efficient charge collection. Significantly, highly catalytic platinized flexible counter‐electrodes are also obtained via UV photo‐induced reduction of screen‐printed platinum precursor pastes based on hexachloroplatinic acid. Using both UV‐processed electrodes, a fully plastic DSC is fabricated with a conversion efficiency of 4.3% under 1 Sun (semitransparent) and 5.3% under 0.2 Sun (opaque). Performance is within 10% of the efficiency of a glass‐based DSC prepared with the same materials but with conventional high temperature processes. The material formulations and processes are simple, and easily up‐scaled over large areas, even directly and simultaneously applicable to the preparation of both the photo‐and counter‐electrode on the same substrate which enabled us to demonstrate the first module on plastic realized with a W series interconnection.     

Palifermin for the protection and regeneration of epithelial tissues following injury: new findings in basic research and pre‐clinical models

Keratinocyte growth factor (KGF) is a paracrine‐acting epithelial mitogen produced by cells of mesenchymal origin, that plays an important role in protecting and repairing epithelial tissues. Pre‐clinical data initially demonstrated that a recombinant truncated KGF (palifermin) could reduce gastrointestinal injury and mortality resulting from a variety of toxic exposures. Furthermore, the use of palifermin in patients with hematological malignancies reduced the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. Based upon these findings, as well as the observation that KGF receptors are expressed in many, if not all, epithelial tissues, pre‐clinical studies have been conducted to determine the efficacy of palifermin in protecting different epithelial tissues from toxic injury in an attempt to model various clinical situations in which it might prove to be of benefit in limiting tissue damage. In this article, we review these studies to provide the pre‐clinical background for clinical trials that are described in the accompanying article and the rationale for additional clinical applications of palifermin.