The human DNA glycosylases NEIL1 and NEIL3 excise psoralen-induced DNA-DNA cross-links in a four-stranded DNA structure

Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct. Furthermore, while Nei and NEIL1 also cleave a psoralen-induced four-stranded DNA substrate to generate two unhooked DNA duplexes with a nick, NEIL3 targets both DNA strands in the ICL without generating single-strand breaks. The DNA substrate specificities of these Nei-like enzymes imply the occurrence of long uninterrupted three- and four-stranded crosslinked DNA-DNA structures that may originate in vivo from DNA replication fork bypass of an ICL. In conclusion, the Nei-like DNA glycosylases unhook psoralen-derived ICLs in various DNA structures via a genuine repair mechanism in which complex DNA lesions can be removed without generation of highly toxic double-strand breaks

An assessment of technology-based service encounters & network security on the e-health care systems of medical centers in Taiwan

<p>Abstract</p> <p>Background</p> <p>Enhancing service efficiency and quality has always been one of the most important factors to heighten competitiveness in the health care service industry. Thus, how to utilize information technology to reduce work load for staff and expeditiously improve work efficiency and healthcare service quality is presently the top priority for every healthcare institution. In this fast changing modern society, e-health care systems are currently the best possible way to achieve enhanced service efficiency and quality under the restraint of healthcare cost control. The electronic medical record system and the online appointment system are the core features in employing e-health care systems in the technology-based service encounters.</p> <p>Methods</p> <p>This study implemented the Service Encounters Evaluation Model, the European Customer Satisfaction Index, the Attribute Model and the Overall Affect Model for model inference. A total of 700 copies of questionnaires from two authoritative southern Taiwan medical centers providing the electronic medical record system and the online appointment system service were distributed, among which 590 valid copies were retrieved with a response rate of 84.3%. We then used SPSS 11.0 and the Linear Structural Relationship Model (LISREL 8.54) to analyze and evaluate the data.</p> <p>Results</p> <p>The findings are as follows: (1) Technology-based service encounters have a positive impact on service quality, but not patient satisfaction; (2) After experiencing technology-based service encounters, the cognition of the service quality has a positive effect on patient satisfaction; and (3) Network security contributes a positive moderating effect on service quality and patient satisfaction.</p> <p>Conclusion</p> <p>It revealed that the impact of electronic workflow (online appointment system service) on service quality was greater than electronic facilities (electronic medical record systems) in technology-based service encounters. Convenience and credibility are the most important factors of service quality in technology-based service encounters that patients demand. Due to the openness of networks, patients worry that transaction information could be intercepted; also, the credibility of the hospital involved is even a bigger concern, as patients have a strong sense of distrust. Therefore, in the operation of technology-based service encounters, along with providing network security, it is essential to build an atmosphere of psychological trust.</p

Antifouling activity of bromotyrosine-derived sponge metabolites and synthetic analogues

Eighteen brominated sponge-derived metabolites and synthetic analogues were analyzed for antilarval settlement of Balanus improvisus. Only compounds exhibiting oxime substituents including bastadin-3 (4), -4 (1), -9 (2), and -16 (3), hemibastadin-1 (6), aplysamine-2 (5), and psammaplin A (10) turned out to inhibit larval settling at 1 to 10 microM. Analogues of hemibastadin-1 (6) were synthesized and tested for structure activity studies. Debromohemibastadin-1 (8) inhibited settling of B. improvisus, albeit at lower concentrations than hemibastadin-1 (6). Both 6 and 8 also induced cyprid mortality. 5,5'-dibromohemibastadin-1 (7) proved to be nontoxic, but settlement inhibition was observed at 10 microM. Tyrosinyltyramine (9), lacking the oxime function, was not antifouling active and was non-toxic at 100 microM. Hemibastadin-1 (6) and the synthetic products showed no general toxicity when tested against brine shrimp larvae. In contrast to the lipophilic psammaplin A (10), the hydrophilic sulfated psammaplin A derivative (11) showed no antifouling activity even though it contains an oxime group. We therefore hypothesize that the compound needs to cross membranes (probably by diffusion) and that the target for psammaplin A lies intracellularly