Science Roundup

This month in Science Roundup:

Cellular Reprogramming Hailed
Special Online Collection

Each year, the editors and news staff of Science look back at the big science stories of the past 12 months, and dub one of them the Breakthrough of the Year. In 2008, the top prize went to advances in the tweaking of cells to assume new identities -- a now flourishing field called cellular reprogramming that may one-day enable the treatment of disease with a patient’s own cells. Other notable achievements worthy of runner-up commendation included the first direct observations of planets orbiting distant Sun-like stars, insights into the genetic landscapes of specific human cancers, discovery of a new family of high-temperature superconductors, and calculation of the mass of a proton. A review of last year’s forecast for advances in 2008, the naming of the global financial crisis as the Breakdown of the Year, and predictions of areas to watch in 2009 rounded out the special section. Online, a video presentation highlighted pioneering work in reprogramming cells, and a special Breakthrough edition of the podcast looked back at the year’s top science stories.


A Golden Route to Dyes

Brightly colored aromatic azobenzene compounds are important components of dyes, but their synthesis at industrial scales currently requires environmentally unfriendly transition metals or nitrite salts. In a Report in the 12 Dec 2008 Science, Grirrane et al. showed that gold nanoparticles supported on titanium dioxide act as highly selective catalysts for the direct preparation of aromatic "azo" compounds from organic compounds called anilines and oxygen. Under mild reaction conditions, the team obtained yields above 98%. Moreover, this same catalyst can also facilitate the clean conversion of nitroaromatic compounds, a second class of dye precursors, into azobenzene through a two-step reduction-oxidation procedure, in a single pot. These findings could eventually pave the way to cheaper and safer dyes useful in pigments, food additives, and drugs.


Tolerating Maternal Influences

A baby developing in the womb receives vital nutrients from its mother, but also some of her cells. Researchers have long known about such maternal crossover cells, but have been unable to explain why they are able to escape attack by the baby’s immune system. In a Report in the 5 Dec 2008 Science, Mold et al. provided new insight into the capabilities of the human fetal immune system. The researchers found that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes and that this crossover spurs the baby to produce regulatory T cells -- white blood cells whose job it is to suppress fetal immune responses -- that persist at least until early adulthood. As noted in an accompanying News story by M. Leslie, the work "suggests a new mechanism for how the human immune system learns to spare the body’s own tissues, a tolerance that breaks down in autoimmune diseases." Lead author Jeff Mold discussed the findings in a related podcast interview.


Dutiful Dinosaur Dads

In more than 90% of living bird species, males play a role in the parental care of their offspring. By comparison, males contribute to parental care in fewer than 5% of mammalian species and even more rarely among non-avian reptiles. The origin of this paternal contribution as well as the overall parental care system in ancestral birds remains unresolved. Now, in a Report in the 19 Dec 2008, Varricchio et al. present compelling evidence that in three species of birdlike dinosaurs -- Troodon, Oviraptor, and Citipati -- males were the individuals responsible for caring for eggs and young (see the ScienceNOW story by E. Stokstad). The team first compared clutch volumes to adult body sizes for a sample of living archosaurs -- the group of reptiles that includes crocodiles, birds, and other dinosaurs. They found that Troodon, Oviraptor, and Citipati had larger clutch volumes (as many as 30 eggs each) for their body sizes than most of the 400+ living birds and crocodiles, but that these clutch sizes scale closely with the expected values for birds with exclusively male parental care. Moreover, the team examined fossil Troodon and Citipati bones associated with nests and found no signs of the histological changes found in reproducing females, supporting the idea that the specimens were males. These findings suggest that paternal care has a deep evolutionary history within the vertebrate phylum. A Perspective by R. O. Prum highlighted the study.


Organ Development Insights
Special Online Collection

The development of individual organs requires complex and dynamic processes, including the formation and differentiation of tissue-specific progenitor cells and the orchestration of cell movements. A special section of the 5 Dec 2008 Science highlighted some of the exciting advances in our understanding of how organs develop. Five Review articles examined the complexities of heart, liver, and pancreas development, and the capacity of these organs for regeneration; the origin of tissue-specific stem cells; the diversity of cell movements observed during organ formation and the core mechanical properties that govern cell shape, arrangement, and motility; and the patterning mechanisms of branched organs such as the vertebrate mammary gland and lung. In a companion issue of Science Signaling published 9 Dec 2008, a Review article examined the signaling events that initiate and direct development of root nodules, a Perspective discussed the peptide signals that influence cell fate decisions in the leaves of plants, and a Research Article offered molecular insights into mammalian kidney formation.


Genetic Link to Heart Health

High blood levels of triglycerides, a common form of dietary fat, have been linked to human heart disease. In a Report in the 12 Dec 2008 Science, Pollin et al. described a genome-wide association study aimed at identifying genes that contribute to interindividual differences in how the body handles these dietary fats. The team studied about 800 volunteers from the genetically homogeneous Lancaster Amish population, whose blood triglyceride levels had been measured before and after consumption of a high-fat, 782-calorie milkshake. Those individuals with the lowest starting triglyceride levels and whose blood levels changed relatively little after drinking the milkshake were found to carry a mutation in the APOC3 gene. This gene encodes a protein called apolipoprotein C-III (apoC-III) that decreases the uptake of fatty particles by the liver and impairs the breakdown of triglycerides. Individuals with the mutation produced half the normal amount of normal apoC-III. They also had a favorable cholesterol profile and had little calcification of their coronary arteries, a measure of early atherosclerosis, as compared with noncarriers, suggesting that they are less likely to develop heart disease. A ScienceNOW story by J. Couzin highlighted the findings.


Earthquake Supercycles in Sumatra

Rupture of the western end of the Sunda megathrust fault in Sumatra, in December 2004, caused the most devastating tsunami the world has seen in many generations. Two subsequent earthquakes ruptured progressively eastward sections of the fault, including a September 2007 quake with a moment magnitude of 8.4. This event elevated concerns that the remainder of the fault -- which last ruptured in two great earthquakes in 1797 and 1833 -- may soon rupture again. According to a Report by Sieh et al. in the 12 Dec 2008 Science, the next large fault rupture may indeed occur within the next few decades. The team analyzed cross-sections of exposed corals off the coast of Sumatra’s Mentawai Islands, directly above the eastern part of the Sunda megathrust. The history of local sea-level change recorded in these corals reflects the raising and lowering of the islands caused by past earthquakes. The record indicates that similar sequences of large earthquakes have occurred along the eastern stretch of the fault about every two centuries, for at least the past 700 years. The September 2007 quake may thus represent the first in a series of quakes that will happen in the next several decades. The durations of the past three earthquake "supercycles" have varied from a few decades to a little over a century, making it difficult to more precisely predict when the next event will occur.


Bidirectional Transcription

RNA polymerase II -- the enzyme that transcribes DNA to generate protein-coding messenger RNAs -- is generally thought to operate in one direction along a strand of DNA. In the 19 Dec 2008 Science, four studies first reported online on 4 Dec painted a more complex picture of mammalian transcriptional activity that includes RNAs being transcribed in both the forward, protein-coding "sense" direction and the backward "antisense" direction at a variety of places within the genome (see the Perspective by S. Buratowski). Seila et al. identified short, bidirectionally transcribed RNAs that flank active promoters with sense and antisense RNAs peaking at 50 nucleotides downstream and 250 nucleotides upstream of transcription start sites, respectively. Core et al. mapped the position, abundance, and orientation of transcriptionally engaged RNA polymerases in human fibroblasts, genome-wide. They found that antisense transcription is prevalent and that most promoters have an engaged polymerase upstream and in an orientation opposite to the annotated gene. Preker et al. identified what may represent yet another class of short RNAs, which are highly unstable, bidirectional, and are produced 0.5 to 2.5 kilobases upstream of active transcription start sites. Finally, He et al. developed a technique that can be used to quantify the number of sense and antisense transcripts from expressed genes at a global level. Their analysis of five human cell lines revealed that antisense transcripts are abundant, nonrandomly distributed across the genome, and differ among cell types.


Stress Shapes Development

The shoot apical meristem of plants is a small group of stem cells that is responsible for the upward growth of the plant and also gives rise to lateral branches and to flowing structures. As new cells grow at the shoot apex, rigid cellulose microfibrils are laid down in ordered patterns to form cell walls. A network of microtubules in the cells’ cytoskeleton is thought to guide the movement of cellulose-synthesizing protein complexes. In a Research Article in the 12 Dec 2008 Science, Hamant et al. analyzed the forces that determine the patterning of the microtubule network and showed that mechanical stress influences microtubule patterns, which in turn influences the growth of new cells at the shoot apex. Using fluorescently labeled microtubules, the team established that the patterns of microtubule orientations in the developing shoot correlates both spatially and temporally with the evolving shape of the shoot. By implementing a simple mechanical model, the researchers then showed that microtubule orientation corresponds to the predicted direction of maximal stress on meristem. Interventions involving ablation of individual cells to change the stress pattern confirmed that microtubule networks generally follow the pattern of physical stresses imposed on the cells. An accompanying Perspective by B. Mulder highlighted the study.


Understanding Electron Conductivity

Why do some solids conduct electricity and others act like insulators? Quantum mechanics has provided simple models for electron conductivity, but the underlying physics in real materials is often complicated by interactions between electrons -- which weakly repel each other -- and because real materials are not perfectly ordered. Clouds of ultracold atoms trapped in artificial crystals by lasers (optical lattices) offer the potential of a clean, defect free, highly tunable system in which to explore the complex interactions between particles. In a Research Article in the 5 Dec 2008 Science, Schneider et al. demonstrated this potential using ultracold potassium atoms confined to a three-dimensional optical lattice. By tuning the depth of the trap, the strength of the interactions between atoms, and the physical confinement of the cold atom cloud, the team showed that the system can be converted from a metal to an insulator. An accompanying Perspective by L. Fallani and M. Inguscio highlighted the study and looked toward future investigations, such as the use of cold atoms as quantum simulators of high-temperature superconductors and for investigating quantum magnetism.


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In Science Signaling

Untangling Allergic Response Pathways

The T cell-derived cytokines interleukin-4 (IL-4) and IL-13 are closely related and are involved in allergic inflammatory responses, such as those that occur in asthma. IL-4 is involved in the proliferation of T helper 2 cells and the synthesis of immunoglobulin E, whereas IL-13 plays a critical role in mediating airway hyperresponsiveness and mucus hypersecretion. Elucidating the mechanisms by which these cytokines mediate their distinct physiological functions has proven difficult because they are structurally similar and share a receptor subunit. In a Research Article in the 23 Dec 2008 issue, Heller et al. provided a potential molecular mechanism to explain the different contributions of IL-4 and IL-13 to allergic inflammation that involves the ability of IL-4 -- but not IL-13 -- to effectively activate the insulin receptor substrate-2 (IRS-2) signaling cascade through binding to its type I receptor, which leads to enhanced transcription of a subset of genes associated with alternatively activated macrophages. An accompanying Perspective by M. Wills-Karp and F. D. Finkelman noted how a better understanding of the separate and overlapping functions of IL-4- and IL-13-dependent signaling may help in the development of more effect treatments for allergic disorders.

-- M.B. Yaffe discussed the challenges of interpreting microarray analyses of RNA expression (23 Dec 2008)
-- Tsigelny et al. examined global gene expression during rat kidney formation and identified candidate genes that may help in orchestrating the transitions between stages of kidney development (9 Dec 2008)
-- H E. Xu and Y. Li discussed the ligand-dependent and -independent regulation of PPARgamma -- a nuclear receptor with essential roles in lipid and glucose metabolism, and inflammatory responses (2 Dec 2008)