Phagosomes are formed when cells such as macrophages engulf relatively large particles, like bacteria, from the external milieu. The source of membrane involved in the formation of the phagosome and the ability of other organelles to fuse with the phagosome is a topic of recent controversy. Murray et al. (p. 1492, published online 10 November) describe a fundamental and clever adaptation of phagosomal membrane trafficking in macrophages, whereby recycling endosomes fuse with the newly forming phagosome to create the site for release of tumor necrosis factor--a proinflammatory cytokine involved in innate immunity.
CREDIT: SANGERMANI/UNIVERSITY OF QUEENSLAND
--------------------------------------------------------------------------- Dating Deep Circulation ---------------------------------------------------------------------------
During the transition from the Last Glacial Maximum to the Holocene, a series of changes in the deep-ocean circulation pattern occurred in the North Atlantic. Robinson et al. (p. 1469, published online 3 November) made measurements of the carbon-14 content of the deep-sea coral Desmophyllum dianthus in order to characterize better the changes in circulation of intermediate and deep water in the North Atlantic during that transitional interval. The observed radiocarbon changes in the deep North Atlantic Ocean are consistent with the "bipolar seesaw" model of deep ocean circulation. The greater variability in waters at depths of less than 2500 meters correlates with smaller climate events that occurred near the poles.
Some microbes use the redox reactions of intermediate sulfur compounds as an energy source. These compounds originally formed via oxidation reactions, and thus it has been thought that these microbes evolved after about 1 billion years ago, when the oxygen content of Earth's atmosphere increased and caused a distinctive shift in the main sulfur isotopes (34S/32S) that was recorded in sediments. Johnston et al. (p. 1477) show that including data for 33S isotope in the analysis provides a more accurate signal of microbial sulfur disproportionation. The diagnostic signal emerges considerably earlier than has been thought at about 1.3 billion years ago.
--------------------------------------------------------------------------- Long After the Quake ---------------------------------------------------------------------------
The extending western margin of the Great Basin is one of the more seismically active regions of North America, and four large earthquakes occurred in western Nevada from 1915 to 1954. Gourmelen and Amelung (p. 1473; see the Perspective by Hammond) used radar interferometry to map the continued deformation of this region during the past 10 years and show that the region still seems to be responding slowly to these earthquakes. Consideration of a broad response helps reconcile global positioning satellite data and imply that much of the highly extended crust to the east is now behaving rigidly.
The interiors of carbon nanotubes can be filled by liquids through capillary action, but the surface tension of liquid metals such as mercury is too high for the metal to enter the nanotube by this process. Because of this lack of wetting, mercury has been used to form Ohmic contacts to carbon nanotubes. Chen et al. (p. 1480) present evidence for mercury entering open-ended, single-walled carbon nanotubes (SWNTs) by an electrowetting process that is facilitated by the potential drop created when the nanotube is used as a contact. Application of a bias potential changes the force needed to extract the SWNT from a mercury surface, and postmortem transmission electron microscopy indicates that mercury entered the interiors of the SWNTs and also wetted the exterior surfaces.
--------------------------------------------------------------------------- Bird Heads and Toes ---------------------------------------------------------------------------
Archaeopteryx is broadly recognized as the first known bird. It has been represented by nine specimens dating to about 150 million years ago (Late Jurassic). However, these nine specimens are all somewhat incomplete, particularly in important areas of the head and feet. Mayr et al. (p. 1483; see the news story by Stokstad) now describe a 10th specimen that shows new features in these important areas. Its first toe is only partially inverted, and its second can hyperextend. These features, as well as revealed parts of its skull, are notably similar to proposed theropod ancestors to birds.
--------------------------------------------------------------------------- Heading Off Hearing Impairment ---------------------------------------------------------------------------
Congenitally deaf cats and mice show clear abnormalities in the synaptic structure of auditory nerve endings. Are these abnormalities permanent, or could early treatment restore their original function? Ryugo et al. (p. 1490) compared normal hearing, congenitally deaf, and congenitally deaf cats fitted with a cochlear implant system. They investigated anatomical and functional restoration of the auditory nerve synapses; in particular, changes in a structure called the endbulb of Held. The artificial electrical stimulation of the cochlea by the cochlear implant rescued many of the normal features of this synapse.
--------------------------------------------------------------------------- The Matter of Taste ---------------------------------------------------------------------------
The sensation of taste is generated in taste buds, which then send the information through the gustatory nerves to the brain. The neurotransmitter between the taste buds and the nerve had been thought to be serotonin, but mice genetically manipulated to lack functional serotonin receptors sense taste stimuli normally. Finger et al. (p. 1495) have investigated another candidate neurotransmitter that functions at these synapses, adenosine triphosphate (ATP). Mice lacking the two ionotropic receptors for ATP (P2X2 and P2X3) did not show responses to taste stimuli in the gustatory nerves. In addition, these mice could not detect most tastes in behavioral tests in which they had to show preference for one substance over another. These results, considered with the release of ATP from taste buds when they are stimulated, show that ATP is indeed the neurotransmitter at these synapses.--------------------------------------------------------------------------- Chromatin and Stem Cells ---------------------------------------------------------------------------
Two stem cell types are found in the Drosophila ovary, germline stem cells and somatic stem cells. Self-renewal of these cells requires the function of the Hedgehog, bone morphogenic protein (BMP), and Wingless signaling pathways. Xi and Xie (p. 1487) now show that two adenosine triphosphate-dependent chromatin remodeling factors, Imitation SWI (ISWI) and DOMINO (DOM), also regulate self-renewal in the Drosophila ovary. DOM is required for somatic stem cell self-renewal and ISWI is required for germline stem cell self-renewal in response to BMP signaling in the stem cell microenvironment or "niche." Because this type of chromatin remodeling complex is highly conserved, it is likely that chromatin remodeling may play a role in stem cell self-renewal in other organisms.
CREDIT: XI AND XIE
--------------------------------------------------------------------------- Colon Cancer Connections ---------------------------------------------------------------------------
A previously unrecognized connection between two well-known signaling pathways appears to provide a crucial mechanism for control of proliferation of colon cancer cells. Castellone et al. (p. 1504, published online 17 November) show that the EP2 subtype of prostaglandin E2 receptor mounts a two-pronged attack that activates a transcriptional program that favors cell proliferation. When PGE2 binds to EP2, the associated heterotrimeric guanine nucleotide-binding protein (G protein) is activated. The G protein and subunits act through distinct pathways that converge to promote stabilization and nuclear translocation of-catenin, a protein that promotes transcription of specific genes that increase proliferation of cancer cells. This signaling system may explain why nonsteroidal anti-inflammatory drugs, which inhibit signaling through PGE2, can at times inhibit development of colon cancer in mice and human patients.
--------------------------------------------------------------------------- The IgGs Have It ---------------------------------------------------------------------------
Different classes of antibody (the immunoglobulins; IgA, IgD, IgE, IgG, and IgM) perform divergent functions within the immune system. IgG has also evolved further into subclasses that vary considerably in their potency in particular types of immune responses. Each IgG subclass possesses a range of binding affinities for the different inhibitory and activating receptors that engage the constant Fc region of the antibody molecule. Nimmerjahn and Ravetch (p. 1510; see the Perspective by Woof) used this observation to construct antibodies bearing the same antigenic specificity combined with the subclass-specific portions of Fc. The ability of these hybrid antibodies to mediate their immunological effects in vivo could be predicted by the strength with which the Fc portion bound the different activating or inhibitory Fc receptor (FcR). Thus, the specificity and strength of FcR binding is a central means by which IgG subclasses determine their dominance in a particular immune response.
--------------------------------------------------------------------------- Keeping Survivin on Target ---------------------------------------------------------------------------
Many proteins are involved in the orchestration of the events required for the successful completion of mitosis. Vong et al. (p. 1499, see the Perspective by Earnshaw) searched for proteins that interact with survivin, a protein that functions in regulation of mitosis and accumulates on condensing chromosomes at the centromeres and later on the spindle. A deubiquitinating enzyme known as hFAM was identified that appears to control localization of survivin and its association with other proteins. Survivin was coupled to ubiquitin through Lys63 linkages, a modification that influences protein-protein interactions, and this modification was necessary for proper binding of survivin to centromeres. Preventing ubiquitination by mutating Lys63 disrupted chromosome alignments and mitotic progression. Thus, enzymes regulating protein ubiquitination appear to have key regulatory roles in controlling the dynamic protein interactions required for proper execution of mitosis.
--------------------------------------------------------------------------- Not Lost in Translation ---------------------------------------------------------------------------
The mammalian translation factor eIF3 (a complex of about 750 kilodaltons) prevents premature association of the large and small ribosome subunits; it is involved in start codon detection; and it assists in the assembly of active ribosomes. In addition, eIF3 recruits messenger RNA (mRNA) bearing either a methylated guanosine cap at the 5-end or an internal ribosome entry site (IRES) to the small subunit of the ribosome. Using cryoelectron microscopy reconstructions, single-particle analysis, and modeling, Siridechadilok et al. (p. 1513) now elucidate the structure and interactions of eIF3. eIF3 interacts with the hepatitis C virus (HCV) IRES RNA and the 5-cap binding complex eIF4F via the same domain to position the mRNA strand near the exit site of the 40S ribosomal subunit. This work provides structural insight for translational regulation by eIF3, including the prevention of premature ribosome assembly.
--------------------------------------------------------------------------- DNA Twisted into Tetrahedra ---------------------------------------------------------------------------
One strategy for building molecular nanostructures in three dimensions is to exploit the connectivity afforded by nucleic acid structures. In many cases, the steps needed to select particular base pairing to create structures such as cubes lead to long, multistep syntheses. Goodman et al. (p. 1661) have developed a rapid self-assembly process that creates DNA tetrahedra that have 10 to 30 base pairs on each edge. Four single strands that contain the complementary sequences for six edges anneal in seconds in 95% yield, and single diastereomeric products are formed. The authors also present atomic force microscopy studies of the compression of a single DNA tetrahedron.
CREDIT: GOODMAN ET AL.
--------------------------------------------------------------------------- Restoring the Forests ---------------------------------------------------------------------------
Deforestation in the tropics has had seriously adverse consequences for biodiversity, ecosystem services, and the human inhabitants of the tropical forest. In recent years, projects have been set in motion to restore degraded forest lands in some countries. Lamb et al. (p. 1628) review the range of approaches to restoration and assess the extent to which these approaches might be successful in achieving their aims, particularly with respect to human well-being.
Mach-Zehnder interferometry is a powerful technique to probe quantum optical effects. Such interferometers contain two beam splitters. The first sends two beams of photons along separate paths. The acquired path or phase difference the two beams may acquire creates interference fringes after the second beam splitter recombines the two beams. Oliver et al. (p. 1653, published online 10 November) show that a two-level superconducting qubit can also be made to exhibit similar interference fringes. In this case, the anti-crossing between the ground and excited states acts as the beam splitter, and the energy level splitting between them corresponds to the optical path difference. Multiple photon transitions (up to 20) can be induced, thus illustrating a potentially useful route for the manipulation of superconducting qubits in quantum computing schemes.
Whether added deliberately or by accident, impurities or solutes have long been used to strengthen metals. A more recent discovery was that impurities can soften some metals, but the underlying reasons have not been fully understood. Using simulations, Trinkle and Woodward (p. 1665; see the Perspective by Chrzan ) show that for molybdenum, certain transition metal solutes can influence the energy barriers for dislocation motion, and in some cases, these changes lead to a softening of the metal. By reducing the strength, and thus the tendency to fracture abruptly, these modified metals may find expanded use in structural components.
Determining the relative importance of incision by rivers and glaciers in the creation of alpine valleys is often hampered by difficulties in quantifying rates of glacial erosion. Shuster et al. (p. 1668; see the cover) assessed the timing and rate of glacial erosion by 4He/3He thermochronometry. Using an example from the Coast Mountains of British Columbia, Canada, they determined erosion rates both before and during alpine glaciation. The Klinaklini Valley deepened rapidly by 2 kilometers or more around 1.8 million years ago when it became glaciated, at least six times as fast as during its preglacial state.
--------------------------------------------------------------------------- Moon Magma ---------------------------------------------------------------------------
A giant impact into the early Earth is thought to have ejected a huge amount of debris into orbit that coalesced to form the Moon. Heat from the impact also apparently melted much of the Moon and created a huge ocean of magma. One means of dating these processes is by detecting 182W, the daughter product of a short-lived isotope, 182Hf. Differences in the abundances of 182W are produced when magma, rocks, and crystals separate while 182Hf is still present. Kliene et al. (p. 1671; published online 24 November) report accurate measurements of tungsten isotopes by analyzing metals returned in Apollo samples (metals provide the most accurate measure). The data imply that the giant impact occurred about 30 million years after the formation of the solar system and that the magma ocean had solidified by about 50 million years.
--------------------------------------------------------------------------- Protein Interaction in the Gaseous Phase ---------------------------------------------------------------------------
The identification of transient or readily reversible interactions between proteins is a difficult problem that has been addressed with a variety of methods. Ruotolo et al. (p. 1658; published online 17 November) have now applied mass spectrometry to the problem in order to exploit its advantages of sensitivity and speed. They show that the trp RNA-binding attenuator protein (TRAP) maintains its 11-membered ringlike structure in the gas phase and that binding of RNA and tryptophan influences the shape and stability of the ring in a fashion consistent with its known behavior in aqueous solution.
--------------------------------------------------------------------------- The Liver and the Control of Glucose Metabolism ---------------------------------------------------------------------------
The protein kinase and tumor suppressor LKB1 is a potential activator of the adenosine monophosphate. activated protein kinase (AMPK), a kinase that senses cellular energy levels by binding the metabolite AMP. Shaw et al. (p. 1642; published online 24 November) engineered mice so that LKB1 expression could be acutely blocked only in the liver; they found that its expression plays a critical role in the control of metabolism in the liver and in glucose homeostasis. In the absence of LKB1, AMPK was almost completely inactive. Animals lacking LKB1 in the liver showed hyperglycemia and increased expression of genes encoding enzymes of gluconeogenesis and lipogenesis.
--------------------------------------------------------------------------- Predicting Responses on the Death Pathway ---------------------------------------------------------------------------
Multiple signaling pathways can influence whether a cell commits to the cell death program known as apoptosis. For many years, it has been possible to categorize signals as contributing to the "gas" or to the "brakes." However, predicting the biological outcome of multiple signals that apply some gas here, and a stomp on the brakes there, has remained a challenge. Janes et al. (p. 1646) applied a systems-level approach to this problem and created a model to analyze coupling between almost 8000 measurements of signaling parameters in cultured cells with about 1500 measures of the various stages of apoptosis in cells treated with various combinations of cytokines. The model allows the cellular apoptotic response to be correctly predicted under a variety of conditions.
CREDIT: JANES ET AL.
--------------------------------------------------------------------------- Land-Use Effects on Climate ---------------------------------------------------------------------------
Climate models are still only rather crude representations of real climate systems, and one class of important feedbacks not adequately realized in them is that of land processes. Fedemma et al. (p. 1674; see the Perspective by Pielke) investigate the role of biogeophysical land processes, which directly affect the absorption and distribution of energy at the Earth's surface, by integrating them into a global climate model. Increases in atmospheric CO2 concentrations during the next century and associated greenhouse gas-induced warming led to significant regional impacts directly associated with land cover, mostly in mid-latitude and tropical areas. However, global average temperature was not affected much by land cover change because regional variations that led to more or less warming tended to cancel out.
--------------------------------------------------------------------------- Lipids and Neurotoxins ---------------------------------------------------------------------------
The venom of certain snakes includes neurotoxins capable of paralyzing their victims. Upon intoxication, snake presynaptic phospholipase A2 neurotoxins (SPANs) cause motor nerve terminals in the neuromuscular junction to enlarge and induce exocytosis of neurotransmitters from synaptic vesicles. Rigoni et al. (p. 1678; see the Perspective by Zimmerberg and Chernomordik) now find that a mixture of lysophospholipids and fatty acids, which are released by SPANs acting on phospholipids, closely mimics all of the biological effects of SPANs. Thus, at the presynaptic membrane, lysophospholipids and fatty acids help to generate a membrane conformation that promotes vesicle exocytosis and also inhibits synaptic vesicle retrieval.
In a 2002 news briefing, U.S. Secretary of Defense Donald Rumsfeld famously distinguished between known knowns, known unknowns, and unknown unknowns. The last group remains difficult to discuss, but neuroscientists and economists have joined forces to examine the distinctions between the first two. Hsu et al. (p. 1680; see the Perspective by Rustichini) challenged subjects to choose between risky and ambiguous payoffs, where the former type of choice contains outcomes with known probabilities and the latter type features the same outcomes but with unknown probabilities. Even under conditions where the expected payoffs are equal, normal humans prefer risk over ambiguity, and brain-imaging results suggest that the amygdala and orbitofrontal cortex (OFC), which both become more active with ambiguity, modulate a third area of the brain, the striatum. Notably, patients bearing lesions in the OFC did not exhibit an aversion to ambiguity.
--------------------------------------------------------------------------- Checkpoint for Synapsis ---------------------------------------------------------------------------
The complex mechanics of the eukaryotic cell cycle is monitored at a number of points to ensure that everything is going according to plan, before the next step in the process is executed. Known checkpoints include DNA replication, DNA damage, and spindle function. Bhalla and Dernburg (p. 1683) identify a checkpoint that monitors synapsis, or pairing between homologous chromosomes during the meiotic (haploid gamete-producing) cell cycle in Caenorhabditis elegans, which ensures the accurate chromosome segregation during division. The checkpoint requires chromosomal sites known as pairing centers, where synapsis initiates, and is distinct from the DNA damage checkpoint monitoring meiotic recombination. The checkpoint involves the PCH2 gene, which is also involved in the pachytene checkpoint in budding yeast.
--------------------------------------------------------------------------- Getting to Grips with G Protein Structure ---------------------------------------------------------------------------
Heterotrimeric G protein signaling is important in a wide range of physiological processes; however, little is known about how activated heterotrimer subunits (G) are oriented at the membrane during signal transduction. Tesmer et al. (p. 1686) provide a snapshot of activated G proteins in a 3.1 angstrom crystal structure of G protein-coupled receptor kinase 2 (GRK2) bound simultaneously to activated Gq and G. GRK2 is critical to the phosphorylation-dependent desensitization of many G protein-coupled receptors. In the complex, Gq is fully disassociated from G, oriented away from its position in the heterotrimer, and forms an effector-like interaction with GRK2.
Quantum mechanics offers an exact solution to the forces binding an electron to a proton in the hydrogen atom. However, adding just one more proton and electron to the system presents an intractable complication arising from the correlated motion of the electrons. Vanroose et al. (p. 1787) have improved the approximate solution by numerical computation. They analyze the trajectories of both electrons upon double ionization of the hydrogen molecule by a single photon, specifically focusing on the influence of changing the internuclear separation. The result is distinct from the path taken on double ionization of the helium atom, These findings indicate that significant correlation effects stem from a molecular geometry (an electron pair shared between two protons), as opposed to an atomic geometry (an electron pair symmetrically surrounding two protons).
CREDIT: VANROOSE ET AL.
--------------------------------------------------------------------------- Begin with a Backflip ---------------------------------------------------------------------------
The initiation of diffusion of molecules on surfaces is mainly thought of in terms of translational motion. Backus et al. (p. 1790, published online 10 November; see the Perspective by Ueba and Wolf) followed the diffusion of CO molecules on a stepped Pt surface with ultrafast vibrational spectroscopy by using changes in CO stretching frequencies to distinguish different adsorption sites. Photoexcitation of the CO with a laser pulse revealed very fast motion (a time constant of only 500 femtoseconds) that was associated with CO rotation rather than translation. Density functional theory calculations show that the excitation of frustrated rotational motion of the CO molecule is needed for the molecule to hop to an adjoining adsorption site.
--------------------------------------------------------------------------- The Reptile-Dinosaur-Bird Conundrum ---------------------------------------------------------------------------
Examination of the histology of fossil bones has shown that most dinosaurs, like birds and mammals today, attained their adult size at about the same age after a period of rapid growth, independently of environmental factors. In contrast, many reptiles adjust their growth in response to temperature and other factors, and may attain adult size at rather different ages. By examining a large collection of fossils from central Europe, Sander and Klein (p. 1800; see the news story by Gramling) now show that the most common Triassic dinosaur, the large prosauropod Plateosaurus engelhardti grew more like turtles, snakes, and alligators, unlike later dinosaurs, whose growth response resembles that of birds and mammals.
--------------------------------------------------------------------------- Small Reactors ---------------------------------------------------------------------------
Positron emission tomography (PET) achieves local sensitivity in medical imaging of organs by detecting the emissive decay of isotopically unstable molecular probes. This instability also requires the rapid and efficient synthesis of probe compounds. Lee et al. (p. 1793) have built a computer-controlled device, roughly the size of a penny, for optimizing the speed and cost of such preparations. The micrometer-scale valves and channels achieve rapid mixing and solvent exchange, and efficient heat transfer, as demonstrated in the multistep synthesis of 18F-radiolabeled 2-deoxy-2-fluoro-D-glucose, the most widely used PET probe.
CREDIT: LEE ET AL.
--------------------------------------------------------------------------- The Genetics of Skin Pigmentation ---------------------------------------------------------------------------
Little is known about the specific genes that contribute to the variations in human skin color. An exciting clue has now emerged from an unlikely source, a tiny aquarium fish. Working with a mutant line of zebrafish called golden, whose stripes are paler than those in wild-type fish, Lamason et al. (p. 1782; see the cover and the news story by Balter) found that the altered pigmentation was caused by a mutation in the slc24A5 gene, which encodes a protein potentially involved in cation exchange. The gene is highly conserved in vertebrates, and expression of the human gene in the golden zebrafish restored wild-type pigmentation. European populations carry a slightly different version of the slc24A5 gene than do African and East Asian populations. A genetic polymorphism that changes one amino acid in the coding region of the gene correlates with skin pigmentation levels, which suggests that slc24A5 may contribute to skin color in humans.
--------------------------------------------------------------------------- Hiding in the Long Grass ---------------------------------------------------------------------------
Since the seminal work of MacArthur and Wilson on the theory of island biogeography, studies on this topic have focused mainly on the relation of species richness with island parameters such as area, distance, and habitat variability. The population biology of individual species in the island context has received much less attention. Schoener et al. (p. 1807; see the Perspective by Thorpe) report results from an experiment using Anolis lizards and an introduced lizard predator on small islands in the Bahamas archipelago. In the absence of the predator, there was a highly regular (decreasing) correlation of lizard survival to a key habitat variable (vegetation height). In the presence of the predator, the situation was nearly reversed, such that prey survival was highest in the tallest vegetation.
--------------------------------------------------------------------------- Modification of Electrical Synapses ---------------------------------------------------------------------------
The brain has two main types of synapses, chemical and electrical. Electrical synapses represent a major form of communication between interneurons in the mammalian nervous system. They play an important role in synchronization of activity in local cell populations because their speed and reliability allows signals to spread across whole networks at a time scale that is sufficient to preserve precise timing of signals between distant neurons. In spite of these potentially vital functions, electrical synapses have generally been regarded as stereotypic and nonflexible. However, Landisman and Connors (p. 1809) found that transmission across electrical synapses can undergo long-term modifications just like chemical synapses. The modulation depends on activation of metabotropic glutamate receptors, which presumably trigger intracellular signal cascades modulating the connexins that constitute the electrical synapses.
--------------------------------------------------------------------------- Snails on the Rampage ---------------------------------------------------------------------------
There has been unprecedented and massive die-off of southeastern United States salt marshes during the past 5 years, with potentially serious consequences for coastal protection and integrity. Silliman et al. (p. 1803) surveyed more than 1200 kilometers of coastline and found high-density fronts of plant-grazing snails (~1500 individuals per square meter) mowing down marsh plants at 11 of 12 die-off sites. Die-off was initiated by drought-induced stress. Snail fronts developed at the edges of the die-off zones, and then spread across remaining healthy areas. These interactions between climatic and trophic factors may lead to further degradation or even collapse of these ecologically and economically important systems.
Neuronal axons in the mammalian central and peripheral nervous system are generally ensheathed in myelin that is generated by nonneuronal cells. In response to injury in the peripheral nervous system, new axons can sprout from unmyelinated gaps called the Nodes of Ranvier, but this response rarely occurs in the central nervous system (CNS). Huang et al. (p. 1813, published online 17 November) have identified a precursor oligodendrocyte cell type whose processes envelope nodes in the CNS and inhibit axon sprouting. The processes express a glycoprotein previously thought exclusive to compact myelin. Mice lacking the glycoprotein exhibited abnormal node formation and nodal axon sprouting. Overcoming the inhibitory nature of these cells may be clinically important in recovery from injury.
--------------------------------------------------------------------------- MicroRNA Management of the Genome ---------------------------------------------------------------------------
MicroRNAs (miRNAs), small, ~22-nucleotide noncoding RNAs that have been found in most of the plants and animals so far studied, generally regulate gene expression by suppressing the activity of messenger RNAs (mRNA) bearing complementary target sequences. These targets, or "seeds," are apparently only seven to eight nucleotides long, and so, all things being equal, should occur randomly throughout the genome with relatively high frequency. Farh et al. (p. 1817, published online 24 November) now show that all things are not equal: Expression of regulated seed-bearing mRNAs correlates with the presence of the appropriate miRNA. However, nonregulated mRNAs present at high levels in miRNA-expressing tissues have a paucity of complementary seed matches in their sequence. Thus, miRNAs are influencing the expression, the evolution, or both of the majority of mRNAs.
Many bacteria can take up exogenous DNA, an ability known as natural competence. The causative agent of cholera, Vibrio cholerae, is not known to have this property, but somehow it has clearly acquired virulence attributes, including cholera toxin, from some other source. V. cholerae does possess the genes used by other bacteria to assemble the necessary machinery for DNA uptake, for example, type IV pili. Meibom et al. (p. 1824; see the Perspective by Bartlett and Azam) now show that a chitin (which can be found in the exoskeleton of crabs, a natural host for the bacteria) triggers V. cholerae to produce pili, and to release and exchange functional DNA. This competency remained unnoticed in a pathogen that has been studied for 60 years, which suggests that other noncompetent bacteria may become so under the appropriate growth conditions.
--------------------------------------------------------------------------- Looking at Glasses at Length ---------------------------------------------------------------------------
At the glass transition, the viscosity of a liquid increases dramatically, but static snapshots of the extent of ordering in these amorphous systems (their static correlation lengths) reveal little difference. However, numerical simulations and indirect experimental evidence indicates that as a liquid cools, regions of correlated movements of particles become larger, impeding the overall fluid flow, so that the length scales upon which the material is dynamically heterogeneous appear to be increasing. Berthier et al. (p. 1797) derive a lower bound on the four-point, time-dependent susceptibility4(t), a general measure of dynamic correlation lengths, and analyze data from two experimental systems--supercooled glycerol and colloidal hard spheres--as well as simulated glass, a binary Lennard-Jones mixture. All three systems display peaks in their appropriate dynamic susceptibility whose height increases for slower time scales, which indicate the presence of a growing dynamic length scale as the liquids cool.
--------------------------------------------------------------------------- Bridging the Damaged DNA Gap ---------------------------------------------------------------------------
The main replicative DNA polymerase has evolved to recognize DNA with high fidelity, but this capability also makes it very poor at dealing with damaged DNA, where it very often stalls at the point of damage. A series of "damage-specific" DNA polymerases that can handle distorted or abasic templates are recruited to the stalled polymerase partly through the ubiquitinylation of proliferating cell nuclear antigen (PCNA)--but how this occurs has been a mystery. Bienko et al. (p. 1821) now show that all the Y-family damage-specific translesion synthesis (TLS) polymerases contain two previously undetected types of ubiquitin binding domain. Colocalization of two TLS polymerases with PCNA in replication factories depends on these ubiquitin binding domains, as do the ability to interact with ubiquitinylated-PCNA and the ability to facilitate DNA repair.
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