Nature view

Research highlights from the NPG family of journals.

Cocaine, heroin and chemical weapons

Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyses the hydrolysis of heroin and cocaine and the detoxification of many chemical weapons, such as sarin, soman and tabun. In a paper in May's Nature Structural Biology, Sompop Bencharit et al. reveal the crystal structures of the hCE1 glycoprotein in complex with both a cocaine and a heroin analogue, providing explicit details about narcotic metabolism in humans. The hCE1 active site contains specific and promiscuous compartments enabling the enzyme to act on structurally distinct chemicals. These new data on the bioscavenger properties of hCE1 will prove essential in the treatment of both narcotic overdose and chemical-weapon exposure.

article
Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme
S. BENCHARIT et al.
Nature Structural Biology 10, 349; May 2003
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Integrating biological databases

Recently, there has been an explosion in the amount of available biological data. Protein and gene-interaction data are accumulating, and more and more genomes are being sequenced and annotated. Biological databases, such as Ensembl and PubMed, have been invaluable in managing these data, as well as aiding accessibility. In a review available free online in this month's Nature Reviews Genetics, Lincoln Stein argues for the integration of such databases. But although they are architecturally similar, this task is not trivial and has so far proved problematic.

review
Integrating biological databases
L. D. STEIN
Nature Reviews Genetics 4, 337; May 2003
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Transplanting cancer

Donor-to-recipient transmission of cancer is a
rare complication of transplantation — so rare that it has not attracted serious attention as a carcinogenic mechanism. That viewpoint may now have to change, as in the current issue of Nature Medicine, Patrizia Barozzi and colleagues show that tumour cells from the organ donor can contribute to one of the most frequent transplant-related malignancies — post-transplant Kaposi sarcoma. The study highlights the need for organ pre-screening. Patrick Moore comments in an accompanying News and Views article.

article
Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors
P. BAROZZI et al.
Nature Medicine 9, 554; May 2003
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news and views
Transplanting cancer: donor-cell transmission of Kaposi sarcoma
P. S. MOORE
Nature Medicine 9, 506; May 2003
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Engineering what comes naturally

Taking their cues from nature, tissue engineers have often looked to natural materials — such as collagens — for the building blocks of new tissues. But as nature's warehouse is limited, scientists are seeking to create synthetic bioactive devices that allow various biological qualities to be predictably 'dialled in' using precise chemistry. The new scaffold described by Matthias Lutolf et al. in this month's Nature Biotechnology draws on the best properties of both biological and manmade materials. Their bone-regenerating device is a precisely engineered construct that directs the host cells to adhere to and degrade the matrix, to release bioactive factor and to regenerate new bone at the repair site. John Wozney and Rebecca Li review in a News and Views article.

article
Repair of bone defects using synthetic mimetics of collagenous extracellular matrices
M. P. LUTOLF et al.
Nature Biotechnology 21, 513; May 2003
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news and views
Engineering what comes naturally
J. M. WOZNEY AND R. H. LI
Nature Biotechnology 21, 506; May 2003
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Are prions flexing their muscles

Until recently, the pathological prion protein PrP^Sc had been found in the central nervous system and some peripheral tissues of infected animals. In the May issue of EMBO reports, Beekes and colleagues from the Robert Koch Institute in Berlin, Germany, expand on observations made by Prusiner's laboratory that the agent can appear in muscles of mice whose brains are injected with prion. The researchers were able to show that hamsters fed prion-infected food express PrP^Sc in a variety of muscles in terminally ill animals. Although this does not necessarily imply that muscles of cows and sheep infected with BSE or scrapie also contain PrP^Sc, it indicates that more research is needed in the interest of public health and food safety.

scientific report
Widespread PrP^sc-accumulation in muscles of hamster orally infected with scrapie
A. THOMZIG, C. KRATZEL, G. LENZ, D. KRÜGER & M. BEEKES
EMBO reports 4, 5, 530; May 2003
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