Staying Off the Beating Track
- Paula A. Kiberstis
Atrial fibrillation, the most common heart arrhythmia observed in the clinic, occurs when the heart's normal pacemaker activity is disrupted by an aberrant electrical stimulus that in many cases originates in the pulmonary veins. Although individuals with cardiovascular disease are often affected, atrial fibrillation can also arise in healthy folks, and the cellular mechanisms that launch and maintain it are not fully understood. To date, research and treatment efforts have focused on pulmonary vein myocytes as the source of the electrical activity that triggers atrial arrhythmias.
Levin et al. describe an unusual cell type whose dysfunction can initiate atrial arrhythmia—at least in mice. These cells, referred to as cardiac melanocytes because they express the melanin synthetic enzyme dopachrome tautomerase (DCT), reside in regions associated with atrial arrhythmia (for instance, in the pulmonary veins and atria) and in culture, display action potentials resembling those of atrial myocytes. Mice lacking cardiac melanocytes are more resistant than wild-type mice to treatments that induce atrial arrhythmias. Furthermore, the enzyme DCT functions as more than a cell marker; mice that lack DCT are more susceptible to atrial arrhythmias, suggesting that this enzyme reduces the likelihood of ectopic electrical activity, possibly via buffering of intracellular calcium and reactive oxygen species. Cardiac melanocytes are also present in relevant areas of the human heart and pulmonary veins, but whether they contribute to atrial fibrillation in humans remains to be determined.
J. Clin. Invest. 119, 10.1172/JCI39109 (2009).
Fertilizing Fool's Gold
- Nicholas S. Wigginton
High levels of nitrates released from agricultural fertilizers pose a serious threat to groundwater quality. Ameliorating this problem is not easy, but some help may be available from the natural soil bacterial communities that reduce nitrate into inert N2 gas. The rate of this denitrification step typically depends on the nature and concentration of the compounds that feed electrons into the process, providing the bacteria with energy. Most often bacteria use abundant organic matter, but in certain environments the iron(II) in minerals such as pyrite (FeS2) can also be oxidized. By monitoring the groundwater below a stretch of farmland in the Netherlands, Zhang et al. found that pyrite-coupled denitrification was the dominant nitrate-consuming reaction. Due at least in part to this reaction, nitrate levels in the groundwater were lower than levels measured 10 years ago; however, groundwater below a nearby unfertilized forest actually became enriched in nitrate over this same period. The transport of nitrate away from the farmland suggests that despite abundant pyrite remaining in the aquifer, complete denitrification occurs more slowly than nitrate's residence time. Complicating matters is the fact that levels of trace elements associated with pyrite (e.g., As, Zn, Ni) increased below the forest as well, signifying that these bacteria may be mobilizing heavy metals in the subsurface despite their benevolence in removing some of the nitrates.
Geochim. Cosmochim. Acta 73, 6716 (2009).
Something from Nothing
- Guy Riddihough
Gene duplication is a common means for generating the raw material of new genes, especially because the duplicated coding and regulatory regions provide a ready-made, fully active substrate for evolutionary processes that lead to sub- or neofunctionalization. The de novo origin of genes—which refers to the so-called orphan genes whose ancestry cannot be traced to known genes—is less frequently encountered and thought to occur when transposable elements or genome rearrangements bring together fragments of genetic clay from which a transcribable structure can be built.
Heinen et al. identify an orphan gene that has been born directly from a virgin intergenic region in the mouse genome. This gene is limited to the genus Mus and appeared roughly 3 million years ago. It is under positive selection, having been subject to a selective sweep in the recent past. Although there are two open reading frames in the transcript, it seems to function as a noncoding RNA that is alternatively spliced and hence named Polymorphic derived intron-containing (Poldi). Poldi is expressed in mouse testis, and knockout of the gene results in reduced testis weight and sperm motility. As differential expression of Poldi requires only a simple promoter, and cryptic splicing and polyadenylation signals are already present in intergenic regions, the birth of new genes may be less rare than we thought.
Curr. Biol. 19, 1527 (2009).
A Stack of Amides
- Jake Yeston
Amides are well arranged to form hydrogen bonds with one another, an interaction that plays a major role in the three-dimensional organization of proteins as well as synthetic supramolecular assemblies. James III et al. have discovered that in the case of γ-peptides, a competing and comparably strong organizing force arises from the amide moiety's substantial dipole. Specifically, they probe small test substrates bearing two amide groups using highly sensitive ultraviolet-infrared double resonance spectroscopy in the gas phase. By comparing the data with simulations, they uncover a conformation in which the planar amides at either end of the molecule stack against one another in antiparallel fashion, so their dipoles adopt a mutually attractive orientation. The authors anticipate that the stacking tendency could prove a useful design element in construction of synthetic foldamers.
J. Am. Chem. Soc. 131, 14243 (2009).
- Applied Physics
Quantum Problem Solvers
- Ian S. Osborne
Quantum computers, when they become available, will harness the power of quantum mechanics to perform calculations and searches, outperforming classical computers at certain tasks. The development of quantum computers is two-pronged: Both hardware and software must be devised. The focus in the software realm is on which problems can be solved and how to do so. Solving a set of linear equations is a generic and important problem in many fields of science, engineering, and mathematics. On a classical computer the computational cost of extracting a solution grows linearly with the size of the system. Harrow et al. have developed a quantum algorithm that will solve the problem much more rapidly (scaling as the logarithm of the system size), requiring exponentially less time. Now we wait for the machinery to arrive.
Phys. Rev. Lett. 103, 150502 (2009).
Sensing Non-Self DNA
- Kristen L. Mueller
One way the immune system recognizes infection is by sensing the presence of foreign nucleic acids in the cytoplasm. Although it had been established that microbial double-stranded DNA (dsDNA) triggered the production of the inflammatory cytokine interferon-β, the identity of the dsDNA sensor remained elusive.
Chiu et al. and Ablasser et al. suggest that RNA polymerase III (Pol III) is the culprit. Pol III, which transcribes genes encoding several kinds of RNA (such as transfer and ribosomal), has been shown to be present in the cytoplasm, but what it did there was unclear. These authors show that cytoplasmic Pol III transcribes AT-rich microbial dsDNA into 5′-triphosphate–containing RNA that is then detected by the retinoic acid–induced gene I (RIG-I), which proceeds to switch on the production of interferon-β. In the absence of Pol III, infection with Legionella pneumophila or Epstein-Barr virus does not induce interferon-β, indicating that Pol III is required for proper immunity both to bacterial and to viral infection.
Cell 138, 576 (2009); Nat. Immunol. 10, 1065 (2009).
Leveraging Bank Deposits
- Pamela J. Hines
Stem cells are essential, yet exceedingly scarce, components of regenerating tissues such as skin and blood. The more broadly useful stem cell—the pluripotent stem cell—can be derived from embryo cells. Remarkably, cells with similar potential can be derived from more specialized cells that have been induced to backtrack under the direction of a suite of four transcription factors. Nevertheless, each of these stem cell sources suffers from distinct problems of availability, utility, and ethics.
Two groups introduce another source of pluripotent stem cells: umbilical cord blood. This blood can be collected fairly easily with little risk to the donor, has suffered less exposure than adult cells to environmental insult, and has found favor in recent years as a source of hematopoietic stem cells. Giorgetti et al. show that pluripotency can be induced, even from previously frozen cord blood bank samples, with the use of only two transcription factors. Haase et al. describe the derivation of pluripotent cells from the endothelial cells of cord blood and demonstrate the differentiation of these into cells similar to cardiomyocytes (shown above with a cardiac-specific isoform of the muscle protein troponin T in red).
Cell Stem Cell 5, 353; 434 (2009).