Nature: Chemistry in Sickness and in Health - Journal of Chemical

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Nature: Chemistry in Sickness and in Health by Sabine Heinhorst and Gordon C. Cannon

Finding articles in Nature related to the topic of human health and wellness was easy: the difficult task was selecting from the many interesting research reports and news features the few for which there is room in this column. We finally settled on this somewhat eclectic collection that runs the gamut from environmental phenomena that affect our wellbeing to genomics and proteomics approaches for disease diagnosis and therapy. Arsenic in Groundwater As scientists with a keen interest in “odd” microbes, the article by Islam and colleagues (2004, 430, July 1, 68–71) from the University of Manchester, the Daresbury Laboratory of Great Britain’s Council for the Central Laboratory of the Research Councils, and the University of Kalyani in India caught our attention not just because it involves interesting microbes but mainly because it demonstrates the power of an interdisciplinary approach to solving a complex biogeochemical problem. The researchers investigated the mechanism by which toxic arsenic salts are released into shallow aquifers in the Bengal province of India and in Bangladesh, reaching levels that are well above those deemed safe by the World Health Organization. The arsenic salts have devastating consequences for the health of an estimated 30–70 million people in the area (http://news.nationalgeographic.com/ news/2003/06/0605_030605_arsenicwater.html; accessed Jul 2004). Arsenic contamination of groundwater, however, is a problem that is by no means limited to the Indian subcontinent. Rather it constitutes a global phenomenon (http:// arsenic.tamu.edu; accessed Jul 2004) that even affects drinking water quality in the U.S. and the well-being of its citizens (http://webserver.cr.usgs.gov/trace/arsenic/; accessed Jul 2004). To study the contribution of biotic processes to the observed release of arsenic into groundwater, Islam and coworkers mixed sediments from a test site in the Ganges delta with artificial groundwater. By exposing these microcosms to a variety of experimental conditions, the researchers found that a consortium of sediment microorganisms that mainly consists of Pseudomonas, Clostridium, and Geobacter species (http://www.geobacter.org/; accessed Jul 2004) is responsible for the reduction of Fe(III), subsequent release of As(V), and its further reduction to mobile As(III). Significant arsenic release requires anaerobic conditions and is greatly stimulated by the addition of acetate, an organic electron donor. These results suggest that microorganisms could be important biotic factors that contribute to arsenic contamination of groundwater in the Ganges delta. Human activities such as irrigation might exacerbate the condition by supplying organic material that can be oxidized by the microorganisms in the sediment, thereby accelerating arsenic mobilization. 1404

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Antibiotic Sunscreen How about a “self-tanning” antibiotic sunscreen? The sweat-like mucus secreted by the hippopotamus might hold the key to this vision for the future (2004, 429, May 27, 363). Saikawa et al. from Keio University in Japan have isolated and characterized the compounds in the hippo “sweat” that cause it to initially appear colorless and that are responsible for its quick color change to red and eventually brown. They found two highly acidic, water-soluble pigments that they named hipposudoric (red) and norhipposudoric acid (orange), respectively. The compounds’ strong absorbance of light in the ultraviolet range suggests that they probably function as the hippo’s natural sunscreen. Hipposudoric acid, in addition, is thought to protect the animal from bacterial infection, since it shows antimicrobial properties against several pathogenic bacteria. The two labile pigments are apparently stabilized to some extent by interaction with the highly alkaline hippo “sweat” but with time turn into a brown polymeric material. CO2H

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Figure 1. Hipposudoric (left) and norhipposudoric acid (right), the main compounds responsible for the observed color change of initially colorless hippopotamus “sweat” to red and finally brown.

RNA Interference In a previous column ( J. Chem. Educ. 1998, 75, 20) we reported the remarkable versatility of ribonucleic acid (RNA) species that can catalyze a variety of biologically important chemical reactions in addition to fulfilling their well-known roles as information-carrying messengers (mRNA) and adaptors (tRNA) between the nucleic acid code and the amino acid sequence of proteins. Most recently, some very small RNA species have been implicated in yet another role, as gene silencers that inhibit transcription and translation. Novina and Sharp (2004, 430, July 8, 161–164) review discovery, mechanisms, and presumed biological functions of this widespread phenomenon, which is collectively known as RNA interference (RNAi). Of particular interest are the short (21 or 22 nucleotides-long), double-stranded RNA species (short interfering or siRNAs) that arise from the degradation of larger double-stranded RNAs—either purposely introduced into an organism or acquired “by accident” such as viral infection. A multi-protein complex binds the strand of the siRNA that is complementary to the endogenous mRNA species. The message is thereby destined for degradation, rather than being

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Figure 2. Overview of the RNA interference pathway that is initiated by double stranded RNA and specifically prevents translation of complementary mRNA into protein.

translated into protein. A detailed, animated explanation of gene silencing by RNAi can be viewed at http://www.nature. com/focus/rnai/animations/animation/animation.htm; accessed Jul 2004. The RNAi approach is widely exploited by researchers in the life sciences to selectively knock out the expression of individual genes and study the biological consequences of such a loss of function. RNAi also provides a means of largescale gene silencing in cultured human cells to study the thousands of human genes whose functions are still unknown. Most exciting, perhaps, is the prospect of developing an RNAi technology-based treatment for recalcitrant diseases such as cancer, by silencing the genes that are specific for the diseased cells. This should be possible if ways can be found to selectively direct the artificial siRNAs to the target cells or tissues. Materials Design, Proteomics, and Drug Discovery Interesting in this context is the review by R. Langer from Massachusetts Institute of Technology and D. A. Tirrell

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from California Institute of Technology (2004, 428, April 1, 487–492) that summarizes proven as well as novel design strategies to develop materials for biological and medical applications. Many materials have already yielded promising products of superior physical properties, biocompatibility, and lifetime in vivo. These are either based on modified versions of naturally occurring polymers, are composites of natural and synthetic polymers, or are composed entirely of synthetic compounds. Medicinal use ranges from vehicles for targeted delivery of therapeutic agents (such as siRNAs) to sensors, tissue implants, and stimuli-responsive devices and diagnostic tools. An entire section of the article is devoted to high throughput approaches for the fabrication of nucleic acid and protein microarrays, which are steadily gaining importance in biomedical research because they permit the interrogation of cell- or tissue-wide changes in gene expression and protein composition, respectively, that characterize disease states. Microarray probing of an organism’s entire gene or mRNA complement (genomics) is rapidly becoming a routine laboratory procedure because commercially produced standard and custom nucleic acid arrays are readily available. The use of protein microchips for analogous proteomics studies has been slower in coming, but a technology feature article by science writer Lisa Melton from the Novartis Foundation in London (2004, 429, May 6, 101–107) gives a synopsis of exciting developments in protein chip fabrication and analysis for large-scale enzyme activity, protein interaction, and ligand binding studies that, when combined with genomics approaches, can greatly accelerate drug discovery and testing procedures (see also the drug discovery and drug target identification technology features in 2004, 430, July 1, 109–115, and 2004, 428, March 11, 225–231). We would like to also mention the excellent series of articles in 2004, 429, May 27, that show how whole-genome sequence information can be brought to bear on diagnosis and treatment of disease. Sabine Heinhorst and Gordon C. Cannon are in the Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406-5043; email: sabine. [email protected] and [email protected].

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