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The Neandertal Genome
Special Feature Index Page

Recent advances in high-throughput DNA sequencing have provided initial glimpses of the nuclear genome of Neandertals as well as other ancient mammals including cave bears and mammoths. In the 7 May 2010 Science, Green et al. presented the draft sequence of the Neandertal genome, composed of over 3 billion nucleotides collected from the bones of three female Neandertals who lived in Croatia more than 38,000 years ago. By comparing this composite Neandertal genome with the complete genomes of five living humans from different parts of the world, the researchers found that Europeans and Asians -- but not Africans -- share 1% to 4% of their nuclear DNA with Neandertals. This suggests that early modern humans interbred with Neandertals after moderns left Africa, but before they spread into Asia and Europe. A companion paper by Burbano et al. described a new method for filling in gaps in the rough draft of the genome. A News Focus, podcast segment, and special online presentation featuring video commentary, a timeline of Neandertal-related discoveries, and a collection of related articles and Web sites, provided additional context for the findings.


Synthetic Biology Breakthrough

Synthetic biology refers to the design and fabrication of biological components and systems, and it provides a complementary perspective from which to analyze and ultimately understand the living world. In a Research Article published online in ScienceExpress on 20 May 2010, Gibson et al. reported the creation of a synthetic genome capable of directing protein synthesis and bacterial replication when transplanted into a recipient cell (listen to the related podcast interview with senior author J. Craig Venter). The team first embarked on the expensive and labor-intensive process of chemically synthesizing the 1-million-base genome of the bacterium Mycoplasma mycoides, using yeast to assemble the DNA in stages. The synthetic sequence includes "watermark" sequences to distinguish it from the natural genome, as well as intentional gene deletions, and mutations acquired during the building process. Next the researchers transplanted the synthesized genome into the related bacterial species M. capricolum and found that newly formed bacterial colonies grew like, and made proteins characteristic of, M. mycoides rather than M capricolum. Science reporter E. Pennisi, who wrote a News story about the achievement, and Mark Bedau -- a philosopher and scientist at Reed College and editor of the scientific journal Artificial Life -- offered answers to reader questions about the scientific and ethical considerations raised by this work.


Landscapes of Infection
Special Issue Introduction

Infectious disease remains one of the biggest killers in developing countries. Two of them account for an enormous toll: Eleven million people live with tuberculosis (TB), and almost 250 million cases of malaria -- and roughly a million deaths among children -- were reported in 2008. In a special section of the 14 May 2010 Science, two pairs of Reviews investigated the variety of cell, molecular, and epidemiological research strategies currently being used to understand and control malaria and TB. News stories focused exclusively on malaria, from the remarkable successes in disease control in Africa in the past few years to the daunting signs of emerging drug resistance (listen to the related podcast segment). A related Editorial by B.R. Bloom discussed the need for the United States to continue its investment in the Global Fund to fight AIDS, TB, and malaria. In the end, it will be careful, well-funded R&D, combined with political will and strong health care systems, that will help to lessen the impact of these diseases.


Southern Ocean Ventilation

It is generally believed that carbon dioxide accumulates in the deep ocean during glacial periods and that it is released rapidly and in large quantities during deglaciation. This ventilation process is thought to occur primarily via the Southern Ocean because this is the region of the global ocean where most deep water makes its first contact with the sea surface and consequently where carbon dioxide that has accumulated in the deep sea can be released to the atmosphere. However, evidence of deep ocean carbon dioxide storage has been elusive -- until now. In a Report in the 28 May 2010 Science, Skinner et al. presented radiocarbon data derived from the shells of surface- and bottom-dwelling organisms (foraminifera) from the Atlantic sector of the Southern Ocean which indicate that during the last glacial period, deep water circulating around Antarctica was more than two times older than today relative to the atmosphere -- a condition considered indicative of carbon dioxide accumulation and storage. An accompanying Perspective by R.F. Anderson and M.-E. Carr described two scenarios that could account for the rise at atmospheric carbon dioxide at the end of the last ice -- one ascribing a lead role to changes in ocean circulation during deglaciation, and another ascribing a greater role to atmospheric processes.


Water Molecules in Motion

The rotational and translational motion of water molecules in solution can control the rates of important chemical and biochemical processes, including chemical reactions on the surface of aqueous aerosol particles in the atmosphere and electron-transfer reactions critical for respiration and photosynthesis. Two Reports in the 21 May 2010 Science revealed new details about how water molecules move in salt solutions, and add to an emerging picture of water dynamics. Ji et al. used two-dimensional infrared spectroscopy to investigate the ultrafast disbanding and reforming of hydrogen bonds in aqueous sodium perchlorate solution. The researchers found that an individual water molecule shifts its donated H-bonds between water and perchlorate acceptors by means of large, very fast angular jumps, rather that than by smooth incremental rotation, in agreement with recent theoretical predictions. Tielrooij et al. compared the relative impacts of cations and anions on the rigidity of the wider water network, using spectroscopic techniques sensitive to the role of each ion. By surveying a range of salts, they found that certain cation/anion combinations, such as magnesium sulfate, appear to act together to restrict water motion beyond the first solvation shell of water molecules directly surrounding the ion. An accompanying Perspective by J.L. Skinner noted that "[t]hese and related studies herald a new era in our understanding of solvation dynamics in aqueous solutions."


Antarctic Micrometeorites

Much of our understanding of early solar system history comes from the laboratory study of extraterrestrial materials, especially meteorites from the asteroid belt. In the 7 May 2010 Science, Duprat et al. reported the analysis of two micrometeorites (less than 50 micrometers in diameter) collected from Antarctic snow. These dust particles appear particularly well preserved both in terms of the heat alteration that is common when objects fall into our atmosphere, and the physical stress that can result when particles are trapped in ice, as opposed to snow (listen to the related podcast interview with lead author Jean Duprat). Analysis of their chemical composition reveals a high carbon content, enrichment in the hydrogen isotope deuterium, and the presence of embedded crystalline minerals. Taken together, these characteristics suggest that the micrometeorites originate from the cold regions of the Sun's ancient protoplanetary disk, perhaps from comets. These findings contradict the idea that all organics with deuterium excesses are of interstellar origin. An accompanying Perspective by L.R. Nittler discussed the insights provided by this study, as well as analysis of samples obtained from the Stardust mission from comet Wild 2.


Gauging Fairness

Considerations about fairness fundamentally affect human behavior, but our understanding of the nature and development of people's fairness preferences is limited, in part because people often disagree on what is fair. For example, most adults believe that differences in individual achievements can justify unequal distributions of income, but they disagree on whether inequalities reflecting luck or efficiency considerations are fair or not. In a Report in the 28 May 2010 Science, Almås et al. used an economic exchange game to study how views of fairness and inequality develop during adolescence. The team tested Norwegian students from 5th grade to 13th grade and found that 5th graders expressed a preference for equal division of rewards, whereas 13th graders tolerated unequal outcomes, as long as they had been provided with evidence of unequal inputs. That is, the younger children were strict egalitarians, but the older ones tended toward meritocracy. The researchers suggest that more exposure to various achievement-based social activities, like sports, could be one of the reasons why older children shift toward a more merit-based stance. A related podcast segment featuring lead author Ingvild Almås discussed the work.


Poor Flyers

Researchers have long debated whether the earliest birds -- including Archaeopteryx, which lived about 145 million years ago, and Confuciusornis, which lived about 120 million years ago -- were capable of the kind of vigorous wing flapping necessary for sustained flight, or whether they merely glided between treetops and the ground. In a Report in the 14 May Science, Nudds and Dyke used an approached called Euler-Bernoulli beam theory to determine the load-bearing capabilities of the primary feathers of both Archaeopteryx and Confuciusornis and to infer their likely flight capabilities. Measurements of the length of these feathers and the diameters of their central support shafts, together with estimates of the birds' body weight, indicate that the feathers would have been too thin and weak to support flight and barely strong enough to allow gliding. The team argues that unless the feather shafts of these ancient birds were solid rather than hollow as in living birds -- a possibility they consider unlikely -- then powered flight probably arose later in the evolution of birds. A ScienceNOW story by M. Balter highlighted the study.


Clues to Cognitive Aging

Memory decline is a common (albeit distressing) part of aging, but the underlying mechanisms are poorly understood. In a Report in the 7 May 2010 Science, Peleg et al. showed that memory disruption in the aging mouse brain is associated with disrupted histone acetylation -- a specific chemical modification of the proteins around which DNA is packaged. The team found that decreased acetylation at a specific site on histone protein H4 in aged mice correlated with the loss of normal memory-associated gene expression in the hippocampus. Moreover, restoration of histone acetylation increased expression of learning-induced genes and improved cognitive function in the aging mouse. An accompanying Perspective by J.D. Sweatt explained that "[t]he study presents a major advance in thinking about the role of histone modifications in synaptic plasticity and memory formation…". A related ScienceNOW story by G. Miller further noted that if the findings translate to humans, they may one day lead to drugs that stave off dementia or even the normal cognitive declines of old age.


Dwindling Lizard Diversity

Lizards are very good at evading thermal stress, tolerating high body temperatures, and resisting water loss, but according to a Report in the 14 May Science, global warming may pose an insurmountable threat. Sinervo et al. compared recent and historical surveys for 48 Mexican lizard species at 200 sites and determined that since 1975, 12% of local population have gone extinct. Moreover, they found that greater extinction probability was correlated with increased daytime temperature, which limits the time lizards can spend foraging. The team then verified physiological models of extinction risk with local climate data and records of 1216 lizard populations spanning North America, South America, Europe, Africa, and Australia. Based on these data, the researchers estimate that by the year 2080, 20% of all lizard species will be extinct if climate change continues unabated ( listen to the related podcast interview with lead author Barry Sinervo). An accompanying Perspective by Huey et al. noted that "[t]hese observations and projections are disturbing, and concordance between predicted and observed extinctions on different continents suggests that they should be taken seriously." A related ScienceNOW story by M. Price highlighted the study and included a slideshow featuring a handful of lizard species at risk.


Earth's Asymmetric Core

Over the past billion years or so, Earth's liquid iron core has cooled and solidified, resulting in the growth of a solid inner core. The behavior of this inner core controls the planet's heat budget and magnetic field, yet its structure remains enigmatic. For example, seismic properties differ between the eastern and western half of the inner core suggesting structural asymmetry, but it is not clear how this lopsidedness developed. Two Reports in the 21 May 2010 Science (both published online 15 Apr) shed new light on the curious nature of Earth's core ( see the related Perspective by B.A. Buffett). Monnereau et al. modeled grain sizes of crystalline iron -- the predicted dominant mineral phase in the core -- and found that a slow translational motion eastward may trigger melting in the Eastern Hemisphere and solidification in the Western Hemisphere, creating a lopsided core. Duess et al. examined the structure of Earth's core using seismic recordings of 90 large earthquakes that occurred between 1976 and 2009. The data reveal not only hemispherical variations, but also more nuanced regional variations. The similarity of this pattern with Earth's magnetic field suggests that directionally dependent crystal alignment in the inner core formed during the solidification of the core or as a consequence of strong forces exerted by magnetism.




In Science Signaling

Podocyte Disruptor

Podocytes are cells with foot-like extensions that envelop capillaries of the glomerulus in the kidney and prevent protein in the bloodstream from entering the urine. In individuals with idiopathic nephrotic syndrome, podocytes lose their characteristic foot processes (a morphological change known as effacement) and protein appears in their urine (a symptom called proteinuria). Zhang et al. found that in some patients with various types of this kidney disorder, the abundance of a protein known as c-mip was increased in podocytes, and overabundance of c-mip in transgenic mice induced proteinuria and effacement of foot processes. Biochemical analysis indicated that c-mip disrupted the interactions between proteins involved in regulating cytoskeletal reorganization in podocytes. In addition, disruption of c-mip by RNA interference (RNAi) prevented proteinuria induced by an bacterial endotoxin in mice. Thus, c-mip may be a potential therapeutic target in the treatment of idiopathic nephrotic syndrome.

Also in Science Signaling this month:
-- Kagan highlighted recent findings about how the oral pathogen P. gingivalis evades the immune response (4 May 2010)
-- Billadeau commented on a recent study of vesicle dynamics in T cell signaling by Purbhoo et al. (11 May 2010)
-- Shi and Kehrl reported that ubiquitination of Beclin-1 induces autophagy in response to inflammation (25 May 2010)



In Science Translational Medicine

-- Ganem et al. summarized recent evidence from veterinary medicine and experimental virology indicating that viral infections can precipitate a disease that mimics features of human achalasia, a disorder involving impaired movement of food and liquids through the esophagus (26 May 2010)
-- Favre et al. reported that the loss of sentinel immune cells known as T helper 17 cells in patients with AIDS is caused by a metabolite of the amino acid tryptophan. A related Perspective by Murray examined various aspects of the regulation of tryptophan oxidation from the perspective of potential therapeutic intervention (19 May 2010)
-- Michelakis et al. showed that dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase, shifts metabolism away from aerobic glycolysis in glioblastoma tumor cells and may have clinical efficacy in patients (also see the related Editorial by Vander Heiden) (12 May 2010)
-- Rong et al. modeled the emergence of drug resistance in hepatitis C virus and proposed that a combination of drugs that can fight three or more mutated viral strains may be needed to combat HCV infection (5 May 2010)


Image credits (in order of appearance): Max Planck Institute-EVA; Science cover, 14 May 2010/Photo: Adam Nadel (www.adamnadel.net) for Malaria Consortium, www.malaria-bloodsweatandtears.com/; Amolf/XKP; Science/AAAS; Ignacio De la Riva