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Adozelesin is a synthetic analog of the antitumor antibiotic CC-1065, which alkylates the N3 of adenine in the minor groove in a sequence-selective manner. Since the cytotoxic potency of a DNA alkylating agent can be modulated by DNA excision repair system, we investigated whether nucleotide excision repair (NER) and base excision repair (BER) enzymes are able to excise the bulky DNA adduct induced by adozelesin. The UvrABC nuclease and 3-methyladenine-DNA glycosylase, that exhibit a broad spectrum of substrate specificity, were selected as typical NER and BER enzymes, respectively. The adozelesin-DNA adduct was first formed in the radiolabeled restriction DNA fragment and its excision by purified repair enzymes was monitored on a DNA sequencing gel. The treatment of the DNA adduct with a purified UvrABC nuclease and sequencing gel analysis of cleaved DNA showed that UvrABC nuclease was able to incise the adozelesin adduct. The incision site corresponded to the general nuclease incision site. Excision of this adduct by 3-methyladenine-DNA glycosylases was determined following the treatment of the DNA adduct with a homogeneous recombinant bacterial, rat and human 3-methyladenine-DNA glycosylases. Abasic sites generated by DNA glycosyalses were cleaved by the associated lyase activity of the E. coli formamidopyrimidine-DNA glycosylase (Fpg). Resolution of cleaved DNA on a sequencing gel showed that the DNA glycosylase from different sources could not release the N3-adenine adducts. A cytotoxicity assay using E. coli repair mutant strains showed that E. coli mutant strains defective in the uvrA gene were more sensitive to cell killing by adozelesin than E. coli mutant strain defective in the alkA gene or the wild type. These results suggest that the NER pathway seems to be the major excision repair system in protecting cells from the cytotoxicity of adozelesin.

Lignin utilization is gaining significance as it is the most prevalent polyphenol in the environment. Lignin includes numerous polyphenolic compounds, exhibiting potent antioxidant activity. Although the high number of phenolic hydroxyl groups (pH-OH) and low molecular weight (Mw) of lignin have promoted its applications as a natural antioxidant, the outcomes must be improved to suit diverse prospects. The present review describes in detail the boosting effects of enzymatic treatments with laccase and cellulase on the functional properties of modified lignin, particularly antioxidant potential under environmentally sound technologies. In addition, the mechanism of ligninenzyme interaction (lignin with laccases and cellulases) is discussed and also described widely used the 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH•) scavenging free radical method to measure the antioxidant activity. Understanding the effects of modified lignin structure on its antioxidant activity is important for developing more beneficial antioxidants and revealing their scavenging mechanisms to realize various applications. [ABSTRACT FROM AUTHOR]

A smart pixel detector is being developed for Time Resolved Crystallography for biological and material science applications. Using the Pixel Detector presented here, the Laue method will enable the study of the evolution of structural changes that occur within the protein as a function of time. The x-ray pixellated detector is assembled to the integrated circuit through a bump bonding process. Within a pixel size of 150x150[[[micro]meter].sup.2], a low noise preamplifier-shaper, a discriminator, a 3 bit counter and the readout logic are integrated. The read out, based on the Column Architecture principle, will accept hit rates above 5x[10.sup.8]/[cm.sup.2]/s with a maximum hit rate per pixel of 1MHz. This detector will allow time resolved Laue crystallography to be performed in a frameless operation mode, without dead time. Target specifications, architecture and preliminary results on the 8x8 front-end prototype and the column readout are presented.

Experimental characterization and finite-element numerical simulations of the electromagnetic interaction between Au nanoparticles positioned atop a Si pn junction photodiode and incident electromagnetic plane waves have been performed as a function of wavelength. The presence of the Au nanoparticles is found to lead to increased electromagnetic field amplitude within the semiconductor, and consequently increased photocurrent response, over a broad range of wavelengths extending upward from the nanoparticle surface plasmon polariton resonance wavelength. At shorter wavelengths, a reduction in electromagnetic field amplitude and a corresponding decrease in photocurrent response in the semiconductor are observed. Numerical simulations reveal that these different behaviors are a consequence of a shift in the phase of the nanoparticle polarizability near the surface plasmon polariton wavelength, leading to interference effects within the semiconductor that vary strongly with wavelength. These observations have substantial implications for the optimization of device structures in which surface plasmon polariton resonances in metallic nanoparticles are exploited to engineer the performance of semiconductor photodetectors and related devices. [ABSTRACT FROM AUTHOR]

The electromagnetic interactions between Au nanoparticles positioned atop a Si pn junction photodiode and incident electromagnetic plane waves are characterized as a function of wavelength. The results have shown that the phase relationship between the field components have led to either constructive or destructive interference within the semiconductor and hence to either an increase or a decrease in photocurrent response at different wavelengths.

Dysregulation of iron homeostasis is implicated in Alzheimer's disease (AD). In this pilot study, common variants of the apolipoprotein E (APOE) and HFE genes resulting in the iron overload disorder of hereditary hemochromatosis (C282Y, H63D and S65C) were evaluated as factors in sporadic AD in an Ontario sample in which folic acid fortification has been mandatory since 1998. Laboratory studies also were done to search for genetic effects on blood markers of iron status, red cell folates and serum B12. Participants included 58 healthy volunteers (25 males, 33 females) and 54 patients with probable AD (20 males, 34 females). Statistical analyses were interpreted at the 95% confidence level. Contingency table and odds ratio analyses supported the hypothesis that in females of the given age range, E4 significantly predisposed to AD in the presence but not absence of H63D. In males, E4 significantly predisposed to AD in the absence of H63D, and H63D in the absence of E4 appeared protective against AD. Among E4+ AD patients, H63D was associated with significant lowering of red cell folate concentration, possibly as the result of excessive oxidative stress. However, folate levels in the lowest population quartile did not affect the risk of AD. A model is presented to explain the experimental findings. [ABSTRACT FROM AUTHOR]