Aromatic hydroxylation is a major metabolic pathway of the mycotoxin zearalenone in vitro

Zearalenone (ZEN) is a common mycotoxin, for which only reductive metabolites have been identified so far. We now report that ZEN is extensively monohydroxylated by microsomes from human liver in vitro. Two of the major oxidative metabolites arise through aromatic hydroxylation and are catechols. Their chemical structures have been unambiguously determined by using deuterium‐labeled ZEN and by comparison with authentic reference compounds. Moreover, both catechol metabolites of ZEN were substrates of the enzyme catechol‐O‐methyl transferase. One of the monomethyl ethers represented the major metabolite when ZEN was incubated with rat liver slices, thus demonstrating that catechol formation also takes place under in vivo‐like conditions. Out of ten major human cytochrome P450 (hCYP) isoforms only hCYP1A2 was able to hydroxylate ZEN to its catechols with high activity. Catechol formation represents a novel pathway in the metabolism of ZEN and may be of toxicological relevance.     

Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione

Deficiency of the antioxidant glutathione in brain appears to be connected with several diseases characterized by neuronal loss. To study neuronal glutathione metabolism and metabolic interactions between neurons and astrocytes in this respect, neuron-rich primary cultures and transient cocultures of neurons and astroglial cells were used. Coincubation of neurons with astroglial cells resulted within 24 hr of incubation in a neuronal glutathione content twice that of neurons incubated in the absence of astroglial cells. In cultured neurons, the availability of cysteine limited the cellular level of glutathione. During a 4 hr incubation in a minimal medium lacking all amino acids except cysteine, the amount of neuronal glutathione was doubled. Besides cysteine, also the dipeptides CysGly and gammaGluCys were able to serve as glutathione precursors and caused a concentration-dependent increase in glutathione content. Concentrations giving half-maximal effects were 5, 5, and 200 microM for cysteine, CysGly, and gammaGluCys, respectively. In the transient cocultures, the astroglia-mediated increase in neuronal glutathione was suppressed by acivicin, an inhibitor of the astroglial ectoenzyme gamma-glutamyl transpeptidase, which generates CysGly from glutathione. These data suggest the following metabolic interaction in glutathione metabolism of brain cells: the ectoenzyme gamma-glutamyl transpeptidase uses as substrate the glutathione released by astrocytes to generate the dipeptide CysGly that is subsequently used by neurons as precursor for glutathione synthesis.     

SiGe bipolar transceiver circuits operating at 60 GHz

A low-noise amplifier, direct-conversion quadrature mixer, power amplifier, and voltage-controlled oscillators have been implemented in a 0.12-/spl mu/m, 200-GHz f/sub T/290-GHz f/sub MAX/ SiGe bipolar technology for operation at 60 GHz. At 61.5 GHz, the two-stage LNA achieves 4.5-dB NF, 15-dB gain, consuming 6 mA from 1.8 V. This is the first known demonstration of a silicon LNA at V-band. The downconverter consists of a preamplifier, I/Q double-balanced mixers, a frequency tripler, and a quadrature generator, and is again the first known demonstration of silicon active mixers at V-band. At 60 GHz, the downconverter gain is 18.6 dB and the NF is 13.3 dB, and the circuit consumes 55 mA from 2.7 V, while the output buffers consume an additional 52 mA. The balanced class-AB PA provides 10.8-dB gain, +11.2-dBm 1-dB compression point, 4.3% maximum PAE, and 16-dBm saturated output power. Finally, fully differential Colpitts VCOs have been implemented at 22 and 67 GHz. The 67-GHz VCO has a phase noise better than -98 dBc/Hz at 1-MHz offset, and provides a 3.1% tuning range for 8-mA current consumption from a 3-V supply.     

HPLC quantification of major active components from 11 different saffron (Crocus sativus L.) sources

Eleven certified saffron samples (Crocus sativus L.), one each from Azerbaijan, China, Greece, France, India, Iran, Italy, New Zealand, Spain, Turkey and the Sigma Chemical Company, were analyzed by using an HPLC photodiode array detection method. This analysis quantified the 10 major saffron compounds in each sample and their concentration was analyzed at three different wavelengths. Results indicated that the Greek, Indian, New Zealand, and Spanish saffron extracts possessed the highest concentrations of water-soluble glycosidic carotenoids (?8.0%) suggesting that they could be a good source of this type of metabolites for further biological evaluation.     

两条腿的行走机器

 几百年以来,能行走的机器人一直令人神往。全球很多研究机构从20世纪70年代开始致力于开发能行走的机器人。随着动作装置、传感装置和计算能力的迅猛发展,人们今天已能够开发出复杂的可行走机器人。     

Is sustainability achievable? Exploring the limits of sustainability with model systems

Successful implementation of sustainability ideas in ecosystem management requires a basic understanding of the often nonlinear and nonintuitive relationships among different dimensions of sustainability, particularly the system-wide implications of human actions. This basic understanding further includes a sense of the time scale of possible future events and the limits of what is and is not likely to be possible. With this understanding, systematic approaches can then be used to develop policy guidelines for the system. This article presents an illustration of these ideas by analyzing an integrated ecological-economic-social model, which comprises various ecological (natural) and domesticated compartments representing species along with a macroeconomic price setting model. The stable and qualitatively realistic model is used to analyze different relevant scenarios. Apart from highlighting complex relationships within the system, it identifies potentially unsustainable future developments such as increased human per capita consumption rates. Dynamic optimization is then used to develop time-dependent policy guidelines for the unsustainable scenarios using objective functions that aim to minimize fluctuations in the system's Fisher information. The results can help to identify effective policy parameters and highlight the tradeoff between natural and domesticated compartments while managing such integrated systems. The results should also qualitatively guide further investigations in the area of system level studies and policy development.     

Metabolism of curcumin and induction of mitotic catastrophe in human cancer cells

In cultured cells, curcumin (CUR) causes cell death by interfering with mitosis and leading to fragmented nuclei and disrupted microtubules, a process named mitotic catastrophe. In order to clarify the role of the known CUR metabolites hexahydro-CUR (HHC) and CUR-glucuronide (CUR-gluc) in mitotic catastrophe, the effects of CUR were studied in three human cancer cell lines with different metabolism of CUR. In Ishikawa and HepG2 cells, CUR was metabolized to HHC and small amounts of octahydro-CUR (OHC), whereas the only metabolism in HT29 cells was the formation of CUR-gluc. Despite their different metabolism, all three cell systems responded to CUR with arrest in G2/M phase and mitotic catastrophe. Fractionation of the cells showed that concentrations of CUR were higher in the ER and cytosol than in the incubation medium by a factor of up to about 150 and 8, respectively. In contrast to CUR, the metabolite HHC and the products of spontaneous degradation did not elicit any effects in Ishikawa cells. These results imply that the causative agent of mitotic catastrophe is the parent CUR molecule, whereas reductive metabolism and chemical degradation render CUR inactive.     

Simulation of Unilateral Constrained Systems with Many Bodies

Nowadays the theory of multi-body systems including unilateral constraints is quite well established. However, the tendency towards more and more detailed and complex models may not be compensated with increasing computer power. In fact the growing computational effort demands for improved numerical methods in order to solve large systems. In this paper a time-stepping method is proposed for the computation of multi-body systems with many unilateral constraints. Stability and accuracy are discussed with respect to the given discretisation. In order to handle many contacts an iterative algorithm is applied based on a Gauss-Seidel relaxation scheme. A numerical example shows the efficiency of the relaxation scheme in comparison with Lemke's method and an Augmented Lagrangian approach.     

Functional heterodimeric amino acid transporters lacking cysteine residues involved in disulfide bond

Sera of 125 patients with sexually transmitted diseases (syphilis, gonorrhoea, chlamydiosis, HPV and HIV infections) were investigated for presence of 3 markers of HBV infection; they were found in 41 (33%) patients. Anti-HBc was present in sera of 35 (28%) patients, in 3 of them antigen HBs was found and in 28 anti-HBs was found as well. Antigen HBs alone was present in sera of 6 other patients but they were not reactive in test for anti-HBc. Moreover in this group of 125 patients anti-HCV were discovered in 4 (3%); in 3 of them occurrence of markers of HBV infection was found.