quinta-feira, 18 de fevereiro de 2010

THIS WEEK IN SCIENCE - February 19 2010

From Big Fish to Big Whales

Whales are the largest animals today, and many feed on the abundant plankton, particularly diatoms, in the oceans. Whales arose and diversified in the Cenozoic, about 30 to 40 million years ago (see the Perspective by Cavin). Marx and Uhen (p. 993) show that their diversity parallels the diversity of diatoms and changes in ocean temperature. Whether there were large predators of plankton before whales has been enigmatic, because the fossil record during the Mesozoic (245 to 65 million years ago) is sparse. Friedman et al. (p. 990) now show that a group of large fish filled this role for nearly 100 million years in the Mesozoic. Although not as large as whales, these globally distributed fish were still several meters long. Their extinction at the Cretaceous-Paleogene boundary 65.5 million years ago may have cleared the seas for the evolution of whales.

To Degrade or Not to Degrade

Regulating the turnover of proteins within the cell is of fundamental importance to almost every physiological process. Hwang et al. (p. 973, published online 28 January; see the Perspective by Mogk and Bukau) now find that acetylated N-terminal methionine (Met) is a degradation signal. This degron is recognized by Saccharomyces cerevisiae Doa10, a transmembrane E3 ubiquitin ligase that resides in the endoplasmic reticulum and inner nuclear membrane. The removal of N-terminal Met by Met-aminopeptidases generates N-terminal residues that are often N-terminally acetylated. Doa10 selectively binds to the resulting N-degrons, which may represent the most prevalent class of cellular protein degradation signals.

2D Quantum Critical Transitions

Quantum critical transitions occur at near-zero temperatures when the properties of quantum matter are tuned by an external parameter such as the magnetic field or pressure. Heavy fermion materials, which have effective charge carrier masses hundreds of times heavier than the bare electron mass, have emerged as a prototypical system for studying these transitions. Now, Shishido et al. (p. 980; see the Perspective by Coleman) use a heavy fermion compound to experimentally realize a new type of quantum phase transition where the tuning parameter is the dimensionality of the system. They engineer a family of superlattices made up of a fixed number of layers of the conventional metal LaIn3 and varying numbers of layers of the heavy fermion material CeIn3. As the number of layers of CeIn3 is decreased, the system gradually changes character from three- to two-dimensional, with corresponding changes in its transport properties.

Detecting Distant Planets

More than 400 planets have been detected outside the solar system, most of which have masses similar to that of the gas giant planet, Jupiter. Borucki et al. (p. 977, published online 7 January) summarize the planetary findings derived from the first six weeks of observations with the Kepler mission whose objective is to search for and determine the frequency of Earth-like planets in the habitable zones of other stars. The results include the detection of five new exoplanets, which confirm the existence of planets with densities substantially lower than those predicted for gas giant planets.

Silicate in the Primordial Soup

Direct evidence for how prebiotic synthesis of complex organic molecules paved the way for the origin of life is extremely scarce. Thus, studies are mainly limited to controlled simulations of likely reactions in early Earth conditions. Similarly, chemical reactions in the laboratory may generate the products necessary for biosynthesis, but may nevertheless be geochemically irrelevant. Lambert et al. (p. 984) show that silicate ions, present in Earth's surface waters at relatively high concentrations, catalyze the formation of four- and six-carbon sugars from simple sugars via the formose reaction. The resulting complexes stabilize the sugar molecules, allowing sugars to accumulate in greater abundance. Silicate stabilization also circumvents the need for the formose reaction to proceed at high temperatures, thus extending the range of possible environments in which life could have originated.

Acid Assistance

Protons are quite versatile catalysts of organic reactions, but because they are achiral, they cannot induce stereoselectivity on their own. One productive way around this problem has been to use chiral conjugate bases and perform reactions in media where the bases remain tightly attracted to protonated substrates. Xu et al. (p. 986; see the Perspective by Schreiner) thoroughly explored the mechanism of an alternative approach, in which an achiral acid was used in conjunction with a second, chiral molecule (a urea derivative) for catalysis. High selectivity was attained with this method in the coupling of aryl imines with olefins. Extensive kinetic and computational studies showed that the acid and its chiral partner acted cooperatively in binding the substrates, optimizing the tradeoff between speed and selectivity.

Metabolic Regulation Through Acetylation

Covalent modification of lysine residues in various proteins in the nucleus is a recognized mechanism for control of transcription. Now two papers suggest that acetylation may represent an important regulatory mechanism controlling the function of metabolic enzymes (see the Perspective by Norvell and McMahon). Zhao et al. (p. 1000) found that a large proportion of enzymes in various metabolic pathways were acetylated in human liver cells. Acetylation regulated various enzymes by distinct mechanisms, directly activating some, inhibiting one, and controlling the stability of another. Control of metabolism by acetylation appears to be evolutionarily conserved: Wang et al. (p. 1004) found that the ability of the bacterium Salmonella entericum to optimize growth on distinct carbon sources required differential acetylation of key metabolic enzymes, thus controlling flux through metabolic pathways.

Cropland Acidification in China

China is experiencing increasing problems with acid rain, groundwater pollution, and nitrous oxide emissions. Rapid development of industry and transportation has accelerated nitrate (N) emissions to the atmosphere. Consequently, soil degradation, water shortage, and pollution, in addition to atmospheric quality decline are becoming major public concerns across China. Since the 1990s, China has become both the largest consumer of chemical N fertilizers and the highest cereal producer in the world, which has consequences for arable soil acidification. Guo et al. (p. 1008, published online 11 February) present a meta-analysis of a regional acidification phenomenon in Chinese arable soils that is largely associated with higher N fertilization and higher crop production. Such large-scale soil acidification is likely to threaten the sustainability of agriculture and affect the biogeochemical cycles of nutrients and also toxic elements in soils.

Predictable Travel Routines

While people rarely perceive their actions to be random, current models of human activity are fundamentally stochastic. Processes that rely on human mobility patterns, like the prediction of new epidemics, traffic engineering, or city planning, could benefit from highly accurate predictive models. To investigate the predictability of human dynamics, Song et al. (p. 1018) used the recorded trajectories of millions of mobile phone users, collected by mobile phone companies and anonymized for research purposes. They hypothesized that given the wide range of travel patterns that different users follow, there would be significant differences between their predictability as well: Users who travel less should be easier to predict than those who are constantly on the road. Surprisingly, there was 93% predictability across the whole user base, and individuals' predictability did not in general fall significantly below 80%.

Killing Pseudomonas

Gram-negative Pseudomonas bacteria are opportunistic pathogens, and drug-resistant strains present a serious health problem. Srinivas et al. (p. 1010) synthesized a family of peptidomimetic antibiotics that is active only against Pseudomonas. These antibiotics do not lyse the cell membrane, but instead target an essential outer membrane protein, LptD, which plays a role in the assembly of lipopolysaccharide in the outer cell membrane. Activity in a mouse infection model suggests that the antibiotics might have therapeutic potential. In addition, LptD is widely distributed in gram-negative bacteria and so its validation as a target has the potential to drive development of antibiotics with a broader spectrum of activity against gram-negative pathogens.

Examining the Backbone

Determination of tertiary protein structures by nuclear magnetic resonance (NMR) currently relies heavily on side-chain NMR data. The assignment of side-chain atoms is challenging. In addition, proteins larger than 15 kilodaltons (kD) must be deuterated to improve resolution and this eliminates the possibility of measuring long-range interproton distance constraints. Now Raman et al. (p. 1014, published online 4 February) use backbone-only NMR data—chemical shifts, residual dipolar coupling, and backbone amide proton distances—available from highly deuterated proteins to guide conformational searching in the Rosetta structure prediction protocol. Using this new protocol, they were able to generate accurate structures for proteins of up to 25 kD.

Histones and Alternative Splicing

Alternative splicing—the inclusion of different combinations of gene exons within a messenger RNA transcript—occurs in the majority of human genes and is regulated by basal and tissue-specific splicing factors, by transcription kinetics, and by chromatin structure. Luco et al. (p. 996, published online 4 February) analyzed the alternative splicing of the human fibroblast growth factor receptor 2 gene in tissue culture cells and found that inclusion of exon IIIb or IIIc was modulated by the levels of histone H3 lysine 36 trimethylation (H3-K36me3) and H3-K4me3. Histone H3-K36me3 enrichment correlated with binding of the chromatin protein, MRG15. The MRG15 protein in turn recruited the polypyrimidine tract–binding protein (PTB) splicing factor, which acts to repress alternative exon inclusion, thus establishing a direct link between histone modifications and the splicing machinery.

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