Characterization of the glutathione conjugate of the semisynthetic flavonoid monoHER

Flavonoids protect against oxidative stress by scavenging free radicals. During this protection flavonoids are oxidized. The oxidized flavonoids formed are often reactive. Consequently, protection by flavonoids can result in the formation of toxic products. In this study the oxidation of 7-mono-O-(β-hydroxyethyl)rutoside (monoHER), which is a constituent of the registered drug Venoruton, was studied in the absence and presence of glutathione (GSH). MonoHER was oxidized by horseradish peroxidase/H₂O₂. Spectrophotometric and HPLC analysis showed that in the presence of GSH, a monoHER–GSH conjugate was formed, which was identified as 2′-glutathionyl monohydroxyethylrutoside by mass spectrometric analysis and ¹H NMR. Preferential formation of this glutathione adduct in the B ring at C2′ was confirmed by molecular quantum chemical calculations. This conjugate was also detected in the bile fluid of a healthy volunteer after iv administration of monoHER, demonstrating its formation in vivo. These results indicate that in the process of offering protection against free radicals, monoHER is converted into an oxidation product that is reactive toward thiols. The formation of this thiol-reactive oxidation product is potentially harmful. Thus, the supposed beneficial effect of monoHER as an antioxidant may be accompanied by the formation of products with an electrophilic, toxic potential.     

Biosensor plates detect mitochondrial physiological regulators and mutations in vivo

The measurement of mitochondrial activity in living cells is usually not straightforward, even though it is quite important in physiological and pathophysiological processes. We describe a high-throughput method for measurement of mitochondrial oxygen consumption in living cells, based on the Becton-Dickinson Biosensor plates.     

Investigation of amino acid containing [FeFe] hydrogenase models concerning pendant base effects

The present investigations deal with the modeling of the peptide surrounding of [FeFe] hydrogenase using amine containing disulphides to simulate possible influences of the amino acid lysine (K237) on the electrochemical and electrocatalytic properties of biomimetic compounds based on [Fe2S2] moieties. Fe₃(CO)₁₂ was reacted with Boc-4-amino-1,2-dithiolane, Boc-Adt-OMe (Adt = 4-amino-1,2-dithiolane-4-carboxylic acid, Boc = tert-butoxycarbonyl) and Boc-Adp tert-butyl ester (Adp = (S)-2-amino-3-(1,2-dithiolan-4-yl)propionic acid) to elongate the FeN distance in comparison to the well known [Fe₂{(SCH₂)₂NR}(CO)₆] model complexes. Efforts to deprotect the complexes containing Boc-4-amino-1,2-dithiolane with trifluoroacetic acid result in the formation of [Fe₃(μ³-O)(μ-O₂C₂F₃)₆(OC₄H₈)₂(H₂O)]. The novel [2Fe2S] complexes are characterized using spectroscopic, electrochemical techniques and X-ray diffraction studies.     

The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions

In this work we report that budding yeasts carrying human-type telomeric repeats at their chromosome termini show a chronic activation of the Rad53-dependent DNA damage checkpoint pathway and a G2/M cell cycle delay. Furthermore, in the absence of either TEL1/ATM or MEC1/ATR genes, which encodes phosphatidylinositol 3-kinase-related kinases (PIKKs), we detected telomere fusions, whose appearance correlates with a reduced cell viability and a high rate of genome instability. Based on sequence analysis, telomere fusions occurred primarily between ultrashort telomeres. Microcolony formation assays argue against the possibility that fusion-containing cells are eliminated by PIKK-dependent signalling.These findings reveal that humanized telomeres in yeast cells are sensed as a chronically damaged DNA but do not greatly impair cell viability as long as the cells have a functional DNA damage checkpoint.     

Zoster ... "a lmost" ... sine herpete: diagnostic utility of real time-polymerase chain reaction

Zoster sine herpete is a particular form of varicella zoster virus (VZV) infection characterized by segmental pain and dysesthesia, without any cutaneous lesions ever becoming perceptible. This report describes the case of a female patient, presenting with intercostal pain associated with a single papulo-vesicular lesion localized within the same area. Thanks to such a lesion, real time-polymerase chain reaction (PCR) analysis on vesicle fluid swab was possible, thus revealing a significant number of VZV genome copies. This innovative tool has proven essential to diagnose this abortive form of herpes zoster, which would otherwise have remained unidentified.     

Integration of metabolic databases for the reconstruction of genome-scale metabolic networks

Background  

Genome-scale metabolic reconstructions have been recognised as a valuable tool for a variety of applications ranging from metabolic engineering to evolutionary studies. However, the reconstruction of such networks remains an arduous process requiring a high level of human intervention. This process is further complicated by occurrences of missing or conflicting information and the absence of common annotation standards between different data sources.     

"From freeze with moths": first discovery of a habitat in Andean salars for noctuid moths

Noctuid moths flutter in the high Andes nights at 4,000 m. s. n. m. Their larvae feed on aerial or underground parts of succulent plants. Many of these species are new to science. Strategies and adaptations of the moths for survival in the high Andes mountains are: a circulatory system that includes an abdominal thoracic countercurrent heat exchanger, and they are insulated from the environment by a coat of dense hair like scales. Recently, during January and July 2004, in the northern desert of Chile, called Salar de Punta Negra, under the salt crust we found a large number of pupae and larvae that correspond to three new species of noctuid moth - this pupation site is located in a 10 m wide area surrounding a water body; the mean observed density is 13 to 15 pupae per 100 cm(2). This is a new extreme habitat conquered by noctuid moths.     

Impaired temperature stress response of a Streptococcus thermophilus deoD mutant

An insertional deoD mutant of Streptococcus thermophilus strain SFi39 had a reduced growth rate at 20 degrees C and an enhanced survival capacity to heat shock compared to the wild type, indicating that the deoD product is involved in temperature shock adaptation. We report evidence that ppGpp is implicated in this dual response.