Bio-Med Roundup

This month in Science Roundup:

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The Macaque Genome
Special Online Collection

From the discovery of the Rh (Rhesus) factor, an important blood type determinant, to modern-day trials of AIDS vaccines, the rhesus macaque monkey (Macaca mulatta) has played a vital role in biomedical research. Its position relative to humans and chimpanzees on the evolutionary tree has also made the macaque an invaluable resource for investigating the last 25 millions years of primate evolution. In a special section of the 13 Apr 2007 issue, Science unveiled the draft genome sequence of this important model organism -- only the third primate genome sequenced to date after human and chimpanzee. A Research Article and four Reports, as well as two News stories, detailed the biomedical and evolutionary insights gained from the macaque genome, including intriguing findings about disease-related alleles and evidence of positive selection across the genome. On the Science Web site, an interactive poster enhanced with images, discussions, and videos explored the significance of the rhesus macaque and its genome sequence to studies of primate biology and evolution. And an accompanying educational resource for high school biology teachers included a lesson plan, teacher background information, and student worksheet.


Genes, Temperature, and Lizard Sex

Sex in reptiles can be determined either by genes on sex chromosomes (as in mammals) or by temperature during embryonic development. These two mechanisms were assumed to be distinct. But in an intriguing study in the 20 Apr 2007 Science, Quinn et al. report the first evidence that both modes of sex determination can operate in the same species. The team focused their study on the Australian central bearded dragon lizard, a species known to develop as male or female on the basis of the chromosomes it inherits: two Z chromosomes produce a male, whereas one Z and one W sex chromosome produce a female. Interestingly, the team found that high incubation temperatures can ovveride the chromosome-determined sex of the lizard such that genotypic males (ZZ) develop as phenotypic females. This suggests that the molecular mechanism directing sex determination in this animal is the dosage of a gene on the Z chromosome rather than the presence of a female-determining gene on the W chromosome. Inactivation of that Z-borne gene at extreme temperatures thus drives the sex reversal. The findings raise the possibility that other reptiles thought to undergo temperature-dependent sex determination also harbor sex chromosomes. The lead author of the study, Dr. Alexander Quinn, discussed the work in a related podcast interview.


Small-Dog Genetics

From the Chihuahua to the Great Dane, the domestic dog shows greater diversity in body size than any other terrestrial vertebrate. In a Report in the 6 Apr 2007 Science, Sutter et al. investigated the genetic origin of this diversity. Through an initial genome-wide scan, the team identified a 15-million-base-pair region of chromosome 15 associated with size variation in the Portuguese water dog (PWD) -- a breed that exhibits notably large variation in skeletal size. Next, researchers sequenced this region in four large and four small PWDs and nine dogs from small (<9 kg) and giant (>30 kg) breeds and discovered 302 single-nucleotide polymorphisms or SNPs -- places where a single DNA base varied from one individual to the next. By measuring the association between these SNPs and skeletal size in a sample of 463 Portuguese water dogs, and then extending the analysis to more than 3,000 dogs from 143 breeds, the team found that a single variant of the gene encoding insulin-like growth factor (IGF1) was common to all small breeds and nearly absent from giant breeds -- suggesting that it is a major contributor to body size in all small dogs. The authors surmise that because the variant appears in distantly related small breeds, that it must have arisen early in the history of dogs -- and that it became widespread through centuries of selective breeding by humans. A related ScienceNOW story by E. Pennisi highlighted the study.


Learning, Memory, and Schemas

Our ability to acquire complex new information often depends on prior knowledge. In general, we tend to learn and remember better when the new material can be related to what we already know by way of an established "mental framework" or schema. In a Research Article in the 6 Apr 2007 Science, Tse et al. showed that animals -- like people -- can bring activated mental schemas to bear during learning. The team trained rats to learn several flavor-place associations, using different flavors of food and sand wells located within a familiar testing environment, over a period of 6 weeks. The task was to learn which flavor was in which location such that when cued with a specific flavor, the animal would be rewarded for going to the correct location by receiving more of that particular food. The researchers found that animals that had been trained with a consistent set of flavor-place pairs were able to quickly learn new flavor-place associations in a single trial. By contrast, animals with an inconsistent training regiment failed at subsequent one-trial learning, presumably because they had not established a stable schema that could guide rapid learning. The acquisition of novel associations was dependent on the hippocampus -- the brain region where new facts and events are initially processed -- but, surprisingly, they became stable memories in the neocortex within 48 hours. Previous studies have shown that this process of memory consolidation usually takes at least a month. An accompanying Perspective by L.R. Squire highlighted the findings.


Knockouts Reveal MicroRNA Meaning

Since their discovery more than a decade ago, small RNA molecules called microRNAs (miRNAs) have captivated biologists and changed our notions about how gene expression is controlled. Now, three studies in the 27 Apr 2007 Science reveal new insights into specific microRNA functions made possible by the creation of the first microRNA "knockout" mice -- animals that harbor deletions of specific microRNA-encoding genes. Rodriguez et al. found that mice deficient in a microRNA molecule called miR-155 developed spontaneous inflammation in the lungs and gut, with accompanying defects in T cell and B cell function and antigen presentation. Thai et al. also investigated the deletion of miR-155 and observed similar T and B cell deficiency as well as impaired response of the germinal center, which is important for T cell–mediated antibody production.

In a separate study, van Rooij et al. (published online 22 March) showed that deletion of a cardiac-specific miRNA called miR-208 impairs the heart’s ability to respond to stress. Specifically, this molecule is important for the control of cardiac growth and gene expression in response to stresses such as pressure overload and hyperthyroidism. As noted in an accompanying News story by J. Couzin the next step in all three studies will be to identify the specific genes targeted by these miRNAs in an effort to elucidate their mechanism(s) of action.


Germ Cell Transitions
Special Online Collection

Constancy in the germline -- the reproductive cells of an organism -- is a must for species continuity, but the life of the germ cell itself is full of change. A special section of the 20 Apr 2007 Science explored the numerous decisions and transitions faced by the germline, highlighting some of the exciting developments in germ cell research. A collection of Review articles focused on the cellular and molecular changes involved in the establishment and maintenance of germ cell fate during development, while two News stories looked at the evolutionary origins of eggs and sperm and technical developments in, and changing attitudes toward, oocyte freezing. Science’s Signal Transduction Knowledge Environment (STKE) took a closer at cell signaling in germs cells with Perspective articles discussing how poppies reject self-pollen and the different mechanisms controlling primordial germ cell movement and survival in mice and flies.


T. rex Protein Analysis

It has long been assumed that the process of fossilization destroys virtually all of the original organic components of an organism. However, the recent discovery of soft tissue in the femur of a 68-million-year-old Tyrannosaurus rex suggested that, under certain conditions, organic remnants may persist across geological time. Now, two Reports in the 13 Apr 2007 Science present detailed analyses of those T. rex soft tissues, as well as samples from a mastodon, which reveal the presence of preserved endogenous proteins. Molecular and chemical analyses by Schweitzer et al. first indicated that collagen I, the main organic component of bone, had been preserved in low concentrations in the T. rex tissue. Asara et al. used mass spectrometry to obtain partial protein sequences from the tissue, as well as from bones of a 160,000- to 600,000-year old extinct mastodon, and confirmed that the material was indeed collagen. Comparison of that sequence data with collagen sequences from extant animals revealed that the majority of the T. rex sequences show similarity to those from chicken, and that the mastodon sequences are more closely related to mammals, including the elephant. The ability to detect and identify endogenous proteins from ancient extinct species can provide insight into the evolutionary links to extant species and more broadly informs theories about the chemical stability of molecules over time.


Eruptive Warming Trigger?

About 55 million years ago, a sudden warming event known as the Paleocene-Eocene Thermal Maximum (PETM) increased global temperatures by 5 to 10 degrees Celsius. The event was marked by the rapid emission of greenhouse gas -- carbon dioxide and/or methane -- but researchers have been unsure about what the trigger was. Now, in a Report in the 27 Apr 2007 Science, Storey et al. present age determinations based on argon-argon dating that link the PETM to a huge eruption of basalt associated with the continental breakup between Greenland and Europe and the opening of the northern Atlantic Ocean. The team dated volcanic rocks in East Greenland that represent breakup-related magmatism, as well as volcanic ash buried in marine sediments in Europe and Greenland that contain a record of the PETM. The dates are identical within error, which implies that the timing of the PETM overlaps that of the massive volcanic sequence. This correlation supports the view that the PETM was triggered by the release of greenhouse gas caused by the immense intrusion of basalt into carbon-rich sediments during the eruptive continental breakup. An accompanying News story by R. A. Kerr highlighted the Report.


Moldable Nanometals

Nanoparticles are receiving growing research interest owing to their unique electrical, chemical, and optical properties. However, efforts to assemble them into useful macroscopic materials have typically resulted in rigid crystals that can’t be reshaped. Now, in a Report in the 13 Apr 2007 Science, Klajn et al. describe a new technique that allows the assembly of tiny metal particles into a plastic substance that can be shaped and thermally hardened, similar to the way that ceramics are formed. The researchers began with metallic nanoparticles (gold, silver, platinum, or palladium) and coated them with a mixture of an organic solvent and soap-like surfactant, and special hydrocarbon linkers that change their conformation when exposed to ultraviolet light. When illuminated with UV, the particles self-assembled into a putty-like material -- consisting of larger "supraspheres" 50 to 300 nanometers in diameter -- that could be molded to form virtually any shape from gears and stars to small figurines. When fired at a modest 50 degrees Celsius, the heat removed the organics from the shapes and welded neighboring nanoparticles together, creating solid and porous metallic structures. In addition to being plastic and moldable, the nanometals are electrically conductive. As noted in an accompanying News story by R. F. Service, the process can create materials composed of either a single metal or alloys of multiple metals, which could be useful for a host of applications including catalysis and optics.


Understanding Saturn’s Spin

Simple observation of the surface of a solid planet can reveal how fast it is spinning. But determining the true inner rotation rate of a giant gaseous planet like Saturn is much more difficult, because the planet is swathed in thick layers of clouds. One measure that has been used is the periodicity of radio emissions that emanate from the plasma suffusing the planet’s ring system. However, researchers have been puzzled by the fact that Saturn’s radio period seems to be slowly changing: a day on Saturn is now about 6 minutes longer than it was in the 1980s. A Report by Gurnett et al. in the 20 Apr 2007 Science (published online 22 March) suggests that apparent changes in Saturn’s spin are caused by processes external to the planet. Observations by instruments on the Cassini spacecraft indicate that most of the radio emission variation occurs at particular longitudes near the orbit of the moon Enceladus -- where geysers emit gases and ice that form a donut-like ring of plasma around the planet. The authors propose that centrifugal instability causes asymmetric plasma flow in this external disk, which weighs down the planet’s magnetic field and causes the plasma disk to slowly slip in phase relative to Saturn’s internal rotation. This slippage causes the radio period, controlled by plasma disk rotation, to be longer than the planet’s actual rotation period. As noted in an accompanying Perspective by P. Bagenal the work "raises new questions about how we are to measure and understand the rotation of the large gas planets."


Ultrasound-Driven Nanogenerator

Although nanoscale devices tend to have very low power requirements, their reliance on external power sources like batteries -- which often require replacement or recharging -- limits their practical application. Now, in a Report in the 6 Apr 2007 Science, Wang et al. describe the development of a nanowire nanogenerator that can generate electrical power from ultrasound-driven vibrations. The work builds on the team’s previous use of zinc oxide nanowires, which create small charges when they are flexed, to convert mechanical energy into electrical energy. The new generator consists of vertically aligned zinc oxide nanowire arrays placed beneath a platinum-coated zigzag electrode that has alternating peaks and trenches. Ultrasonic vibrations cause the electrode to move up and down, which causes the nanowires to bend and/or vibrate. The wires periodically make contact with the peaks of the electrode, transferring their electrical charges. By capturing the tiny amounts of current produced by the hundreds of nanowires moving at different times, the generator can produce a continuous electrical current -- around 0.5 nanoamperes of current for more than an hour. The technique thus provides a new platform for harvesting or recycling energy from the environment to power nanodevices including implantable biological sensors and nanorobots.


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In Science’s STKE

New Avenues for Cancer Treatment

One of the great challenges of cancer research has been to understand precisely how malignant cells differ from their normal counterparts and how these differences can be exploited therapeutically to either eliminate cancer cells or coax them toward more civilized behavior. The 10 Apr 2007 issue of Science’s STKE highlighted recent developments in cancer cell pathophysiology that provide reasons to be hopeful about the development of novel therapies, as well as a collection of relevant articles from the STKE archives. A Review by Carraway et al. described how changes in cellular morphology can contribute to oncogenesis with a focus on epithelial cell shape and how the various specialized membrane regions sequester receptor subunits and may segregate receptors from their ligands, thereby controlling cell behavior. A Perspective by Pan and Mak discussed intriguing new research suggesting that pharmacological manipulation of cellular metabolism to promote oxidative phosphorylation may actually stimulate cancer cell apoptosis and suppress tumor growth. And a Meeting Report by Friedrich et al. offered highlights from the most recent meeting of the Signal Transduction Society, which focused on the translation of basic signaling research into advances in the cancer clinic.

Also in STKE this month:
--Gerden and Eiden discussed the regulation of PC12 cell differentiation by cAMP signaling independent of PKA (17 Apr 2007)
--Yin and Pan described the role of an atypical cadherin in the Hippo signaling pathway, which controls organ size during fruit fly development (3 Apr 2007)
--A Teaching Resource contributed by D. Berry included a description and movie of the molecular events associated with apoptosis induced by the prototypic death receptor Fas (3 Apr 2007)

This month’s Science Roundup is sponsored by:
Barnes & Noble.com’s Deal-A-Day in May!
Up to 50% Off
31 great deals for an entire month of savings. Check back on the site
every day to find out what the exciting Deal of the Day is.
Go to www.bn.com/aaas