The norepinephrine transporter critically regulates both neurotransmission and homeostasis of norepinephrine in the nervous system. In this study, we report a previously uncharacterized and common A/T polymorphism at ؊3081 upstream of the transcription initiation site of the human norepinephrine transporter gene [solute carrier family 6, member 2 (SLC6A2)]. Using both homologous and heterologous promoter-reporter constructs, we found that the ؊3081(T) allele significantly decreases promoter function compared with the A allele. Interestingly, this T allele creates a new palindromic E2-box motif that interacts with Slug and Scratch, neural-expressed transcriptional repressors binding to the E2-box motif. We also found that both Slug and Scratch repress the SLC6A2 promoter activity only when it contains the T allele. Finally, we observed a significant association between the ؊3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attentiondeficit hyperactivity disorder and other neuropsychiatric diseases.Snail family ͉ E2-box ͉ Slug ͉ Scratch
The newly emerging field of machine ethics (Anderson and Anderson 2006) is concerned with adding an ethical dimension to machines. Unlike computer ethics-which has traditionally focused on ethical issues surrounding humans' use of machines-machine ethics is concerned with ensuring that the behavior of machines toward human users, and perhaps other machines as well, is ethically acceptable. In this article we discuss the importance of machine ethics, the need for machines that represent ethical principles explicitly, and the challenges facing those working on machine ethics. We also give an example of current research in the field that shows that it is possible, at least in a limited domain, for a machine to abstract an ethical principle from examples of correct ethical judgments and use that principle to guide its own behavior. Articles
Solar ultraviolet (UV) radiation can have deleterious effects on coral assemblages in tropical and subtropical marine environments, but little information is available on UV penetration into ocean waters surrounding corals. Here we provide an extensive data set of optical properties in the UV domain (280[en]400 nm) that were obtained during 1998‐2005 at sites located in the Lower and Middle Keys and the Dry Tortugas. Absorption coefficients of the colored component of the dissolved organic carbon (DOC; colored dissolved organic matter [CDOM]) were 6× to 25× larger than particulate absorption coefficients in the UV region, indicating that CDOM controls UV penetration in the inshore coastal waters and reef tract. CDOM absorption coefficients (αCDOM) and DOC were highly correlated to diffuse attenuation coefficients (Kd) in the UV spectral region. Measurements using moored sensors showed that UV penetration at the reef tract in the Lower Keys varies significantly from day to day and diurnally. The diurnal variations were linked to tidal currents that transport CDOM over the reef tract. Summertime stratification of Case 1 bluewaters near the reef tract during periods of low wind resulted in higher temperatures and UV penetration than that observed during well‐mixed conditions. This result suggests that higher UV exposure accompanying ocean warming during low‐wind doldrums conditions significantly contributes to coral bleaching. Modeling results indicate that changes in underwater sunlight attenuation over the coral reefs can affect UV‐induced deoxyribonucleic acid (DNA) damage and inhibition of coral photosynthesis much more strongly than changes in the stratospheric ozone layer.
Exposure to contaminants can affect survivorship, recruitment, reproductive success, mutation rates and migration, and may play a significant role in the partitioning of genetic variation among exposed and nonexposed populations. However, the application of molecular population genetic data to evaluate such influences has been uncommon and often flawed. We tested whether patterns of genetic variation among native fish populations (Sacramento sucker, Catostomus occidentalis) in the Central Valley of California were consistent with long-term pesticide exposure history, or primarily with expectations based on biogeography. Field sampling was designed to rigorously test for both geographical and contamination influences. Fine-scale structure of these interconnected populations was detected with both amplified fragment length polymorphisms (AFLP) and microsatellite markers, and patterns of variation elucidated by the two marker systems were highly concordant. Analyses indicated that biogeographical hypotheses described the data set better than hypotheses relating to common historical pesticide exposure. Downstream populations had higher genetic diversity than upstream populations, regardless of exposure history, and genetic distances showed that populations from the same river system tended to cluster together. Relatedness among populations reflected primarily directions of gene flow, rather than convergence among contaminant-exposed populations. Watershed geography accounted for significant partitioning of genetic variation among populations, whereas contaminant exposure history did not. Genetic patterns indicating contaminant-induced selection, increased mutation rates or recent bottlenecks were weak or absent. We stress the importance of testing contaminant-induced genetic change hypotheses within a biogeographical context. Strategic application of molecular markers for analysis of fine-scale structure, and for evaluating contaminant impacts on gene pools, is discussed.
Participants at the Napa Conference on Genetic and Molecular Ecotoxicology assessed the status of this field in light of heightened concerns about the genetic effects of exposure to hazardous substances and recent advancements in our capabilities to measure those effects. We present here a synthesis of the ideas discussed throughout the conference, including definitions of important concepts in the field and critical research needs and opportunities. While there were many opinions expressed on these topics, there was general agreement that there are substantive new opportunities to improve the impact of genetic and molecular ecotoxicology on prediction of sublethal effects of exposure to hazardous substances. Future studies should emphasize integration of genetic ecotoxicology, ecological genetics, and molecular biology and should be directed toward improving our understanding of the ecological implications of genotoxic responses. Ecological implications may be assessed at either the population or ecosystem level; however, a population-level focus may be most pragmatic. Recent technical advancements in measuring genetic and molecular responses to toxicant exposure will spur rapid progress. These new techniques have considerable promise for increasing our understanding of both mechanisms of toxicity on genes or gene products and the relevance of detrimental effects to individual fitness. -Environ Health Perspect 102 (Suppl 12):3-8 (1994)
Measurements of simultaneously extracted metals (SEM), acid volatile sulfide (AVS), and invertebrate toxicity were combined with X-ray absorption spectroscopy (XAS) to evaluate metal speciation and ecological hazard of contaminated sediments from the Seaplane Lagoon, Naval Air Station Alameda (CA). This site is characterized by moderate to low toxicity in surface sediments and by metal concentrations in sediments and porewaters that increase with depth. Standard 1-h ΣSEM/AVS measurements for surface sediments were compared with time-series (0.25−24 h) measurements of metal and sulfide release from sediments at 30 cm. Results show that AVS is rapidly and completely evolved after 1 h, but metal extraction continues with time and is not complete after 24 h. Sediment−water interface tests of invertebrate toxicity using sand dollar embryos (D. excentricus) and adult amphipods (E. estuarius) exposed to intact cores showed no to low toxicity in surface sediments. In sediments from 30- and 60-cm depth, high toxicity in several replicates was attributed to factors other than metal concentrations, such as high dissolved ammonia or low dissolved oxygen concentrations. Metal speciation and bonding determined from XAS show that cadmium (100%), zinc (≈80%), and manganese (≈50−70%) are associated with monosulfide phases in the sediments. The remaining fraction of zinc and manganese and all of the chromium and lead are ligated by oxygen atoms, indicating association with oxide, carbonate, or silicate minerals. Iron is present in the sediments in two fractions, as Fe(II) in the sulfide phase pyrite and as oxygen-ligated octahedral iron, probably associated with clay minerals. Bulk chemical measurements of porewaters and sediments, and speciation information from XAS, suggest that AVS could be accounted for by volatilization of porewater sulfide. Our results indicate that metals are removed from porewaters by formation of monosulfide phases only for cadmium and partially for zinc and manganese but not for lead or chromium, even though these are reduced, anoxic sediments typical of a restricted marine estuary environment. Comparison of geochemical, spectroscopic, and biological data provides new insight for the interpretation of ΣSEM/AVS measurements and points out the need for synergistic biological/geochemical tests for determining potential ecological hazard.
We argue that ethically significant behavior of autonomous systems should be guided by explicit ethical principles determined through a consensus of ethicists. Such a consensus is likely to emerge in many areas in which intelligent autonomous systems are apt to be deployed and for the actions they are liable to undertake, as we are more likely to agree on how machines ought to treat us than on how human beings ought to treat one another. Given such a consensus, particular cases of ethical dilemmas where ethicists agree on the ethically relevant features and the right course of action can be used to help discover principles needed for ethical guidance of the behavior of autonomous systems. Such principles help ensure the ethical behavior of complex and dynamic systems and further serve as a basis for justification of this behavior. To provide assistance in discovering ethical principles, we have developed GenEth, a general ethical dilemma analyzer that, through a dialog with ethicists, uses inductive logic programming to codify ethical principles in any given domain. GenEth has been used to codify principles in a number of domains pertinent to the behavior of autonomous systems and these principles have been verified using an Ethical Turing Test, a test devised to compare the judgments of codified principles with that of ethicists.
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