Opening Pandora's Box
- Caroline Ash
The first woman on Earth, Pandora, had a “box,” or rather a jar, that Zeus commanded her to safeguard and never open. Of course she opened it, and thus evil spread around the world. Recently, an extraordinarily distinctive group of giant viruses that parasitize amoebas were described and named Pandoravirus, not because they contain all evil but merely because they are jar-shaped. Le gendre et al. have added to this still-tiny pantheon with another jar-shaped viral particle 1.5 µm long, containing a rather diminutive 600-kb AT-rich genome (as compared to the up to 2.8-Mb genome seen in Pandoraviruses) and a cytoplasmic replication machinery resembling that of the original Megaviridae. The authors named the virus Pithovirus because Pandora's jar was called a “pithos” in ancient Greek. This virus was revived from a Siberian permafrost sample and infects amoebas. Although named for the jar and not its contents, given its origins, this discovery hints that viruses more evil than Pithovirus might be revived as the tundra melts.
Proc. Natl. Acad. Sci. U.S.A. 111, 10.1073/pnas.1320670111 (2014).
A Better-Known Electron Mass
- Jelena Stajic
The mass of the electron is one of the fundamental constants of nature. It is known to a high precision, but improvements are desirable in order to facilitate continued precision testing of the Standard Model of particle physics. The tiny mass, however, makes direct measurements very challenging. Sturm et al. use an indirect technique, in which an electron is bound to a carbon nucleus in a hydrogen-like configuration. This positively charged ion follows a circular orbit in an external magnetic field at the cyclotron frequency, which is proportional to the local magnetic field B. At the same time, the spin of the electron precesses at a frequency also proportional to B. By measuring the ratio of these two frequencies, one can determine the electron mass, knowing the mass of the ion and the g factor of the bound electron, which is different from its well-known free-space value; to estimate it, the authors used the theory of quantum electrodynamics and related measurements in a silicon system. The measurements were performed in a Penning-trap setup and yielded a relative precision of 3 × 10−11 in the electron mass, a value 13 times smaller than the uncertainty of the current accepted mass obtained by weighted averaging of literature values. It is expected that the improved result will enable future fundamental physics experiments that were previously impossible.
Nature 10.1038/nature13026 (2014).
Highly Reactive Abasic DNA
- Phil Szuromi
The base on a DNA residue can be removed to leave an abasic site. This reaction can occur spontaneously, can be catalyzed enzymatically during certain repair processes, or can be induced by certain anticancer drugs and mutagens. The sugar of the abasic site can have two different structures that are in equilibrium: a cyclic hemiacetal form and a ring-opened form that bears an aldehyde group. Price et al. report that if the abasic site is opposite an adenine residue on double-stranded DNA, the aldehyde group of the ring-opened structure can react with the exocycle amino group of the adenine (the N6-amino group) and form a stable covalent cross-link. The formation of cross-links, which are among the most deleterious of DNA mutations, occurs in remarkably high yields, from 15 to 70% under physiologically relevant conditions, versus the 2 to 3% yield observed previously for similar reactions with guanine residues. This difference arises because the N6-amino group of adenine is positioned in the major groove for adenine but the corresponding N2-group of guanine is in the minor groove.
J. Am. Chem. Soc. 10.1021/ja410969x (2014).
- Beverly A. Purnell
DNA association with histone proteins to form nucleosomes provides barriers to transcription and replication and in this way provides careful regulation of these processes. As yeast age, histones are less prevalent and their overexpression is linked to increased life span. Given their regulatory nature, one might expect that a global loss of histones would result in increased expression of all genes; however, it has been reported that the expression of some genes goes up, whereas the expression of others goes down with aging. Hu et al. mapped nucleosome localization in aging yeast and revealed that nucleosomes became “fuzzier”—their positions became more variable along the DNA—and they showed a reduced periodicity, the tendency to recur at certain distances along the DNA. In contrast to studies showing increased repression of some genes during aging, a global loss of approximately 50% of nucleosomes correlated with the induction of expression of the entire genome. Furthermore, genes with the greatest induction contained sequences that more strongly assemble with nucleosomes. In addition to nucleosome loss and the induction of gene expression during aging, there was greater DNA damage at sites such as the ribosomal DNA locus and in mitochondrial DNA, as well as increased chromosomal trans locations. Whether similar changes in nucleosomes are associated with aging in higher eukaryotes is yet to be determined.
Genes Dev. 28, 396 (2014).
Metastasis in the Light
- Paula A. Kiberstis
Cutaneous melanoma is less common than other forms of skin cancer but is far more deadly, especially if not detected at an early stage. Ultraviolet (UV) light from the Sun plays a key role in the initiation of melanoma by inducing mutations in the DNA of melanocytes, the pigment-producing cells in skin. A new study suggests that UV light does damage well beyond this early role: It appears to trigger a chain of pathologic events that facilitate metastasis.
Studying a mouse model, Bald et al. found that repetitive exposure of primary melanomas to UV light did not increase tumor incidence or growth but rather increased the number of lung metastases. Closer examination revealed that UV light induced the recruitment of certain immune cells (neutrophils) to the primary tumor. This inflammatory response in turn activated endothelial cells (cells that line blood vessels) and triggered migration of the melanoma cells toward them, resulting in the expansion of tumor cells along blood vessels. This “angiotrophic” growth pattern is thought to increase the likelihood that tumor cells enter the bloodstream and metastasize. Consistent with this, human melanoma samples with high levels of neutrophils were more metastatic.
Nature 10.1038/nature13111 (2014).
- H. Jesse Smith
Most of the anthropogenic warming of climate caused by greenhouse gas emissions is due to radiative forcing by carbon dioxide, the molecule that has garnered the lion's share of public attention. It is not the only emitted gaseous species that affect climate, however. Another class of compounds, long-lived synthetic greenhouse gases (SGHGs; gases with no significant natural sources and lifetimes of at least 1 year), has received far less attention although its constituents are responsible for a significant amount of warming, providing nearly 20% of the direct radiative forcing increase due to carbon dioxide since the preindustrial era. Rigby et al. examine recent trends in 25 of the most abundant SGHGs and construct emissions scenarios in order to estimate their future impacts on global warming. They find that if the relevant recommendations of the Montreal Protocol are implemented, overall SGHG radiative forcing would be reduced by approximately 26% by 2050, as compared to a policy without such controls, a cumulative reduction equivalent to 0.5 to 2.8 years of carbon dioxide emissions at current levels.
Geophys. Res. Lett. 10.1002/2013GL059099 (2014).
Methylation Sees the Light
- L. Bryan Ray
Animals, including humans, are sensitive to the length of cycles of light and darkness to which they are exposed. Disruptions of normal cycles by shift work or by exposure to bright lighting during normal periods of darkness can cause medical problems or disrupt learning and memory. Azzi et al. explored the mechanism by which mice responded to light/dark cycles that were shifted to be 22 hours long rather than 24 hours. This environmental change caused alterations in the expression of hundreds of genes in the superchiasmatic nuclei of the brain where the master circadian clock is located. Changes in DNA methylation in over 1000 regions of DNA that are associated with the change in light cycle were also observed. Affected genes included those encoding the clock components Per2 and Cry1, where the changes in methylation were correlated with changes in transcription. Treatment of animals with an inhibitor of DNA methylation reduced the effects of the altered light cycle on the behavior of the animals. Thus, changes in DNA methylation at promoters or within the body of genes may mediate some of the effects of changes in light cycle on physiological function.
Nat. Neurosci. 10.1038/nn.3651 (2014).