From Big Fish to Big Whales
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| CREDIT: ©ROBERT NICHOLLS, PALAEOCREATIONS |
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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 LaIn
3 and varying numbers of layers of the heavy fermion material
CeIn
3. As the number of layers of CeIn
3 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
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| CREDIT: XU ET AL. |
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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
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| CREDIT: SONG ET AL. |
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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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