A Matter of Trust

Borderline personality disorder (BPD) is characterized by the inability to maintain stable interpersonal relationships and control one’s impulses and emotions. In a Research Article in the 8 Aug 2008 Science, King-Casas et al. used an economic trust game and neuroimaging to shed light on the neural mechanisms underlying the breakdown of cooperative in behavior in patients with BPD (listen to the related podcast interview). In the game, money is exchanged between an investor, who decides how much money to commit, and a trustee, who decides how much of the investment (which is tripled during the transfer) to repay the investor. If both cooperate, both benefit from the exchange, much more so than if the investor keeps most of the money. The researchers found that BPD patients were less likely to establish or maintain a cooperative relationship -- as trustees, they paid back less of the profit they earned than did other players, thus causing investors to scale back subsequent investments. Moreover, BPD patients were less able to repair these breaches of trust, for example, by offering generous payouts to encourage bigger investments. Interestingly, measurements of neural activity in the anterior insula -- a brain region that reacts strongly to adverse or uncomfortable social interactions such as unfairness, as well as to the intentions or emotional states of others -- indicated that the BPD patients did not seem to process the offer of trust (a high investment) any differently from an expression of distrust (a low investment). An accompanying Perspective by A. Meyer-Lindenberg noted that the study establishes game theory as a new paradigm for investigating social dysfunction in other mental illnesses.


Scents of Success

Flowers face the dual challenges of needing to attract pollinators while repelling nectar thieves and florivores (flower-eating predators). Enter Nicotiana attenuata, a white-flowered wild tobacco plant that laces its sweet-smelling floral nectar with nicotine -- a known turnoff to its hawkmoth and hummingbird pollinators. In a Report in the 29 Aug 2008 Science, Kessler et al. used a combination of genetics, secondary products chemistry, and field experiments to investigate how opposing floral scents influence the plant’s pollination, predation, rates of outcrossing, and overall reproductive success. By silencing the genes associated with the biosynthesis of nicotine and benzyl acetone (the flower’s most attractive scent component) in varying combinations, the team found that both repellant and attractant are required to maximize floral visitation. While benzyl acetone helps lure hummingbirds and hawkmoths to flowers, nicotine encourages modest nectar drinking behavior from individual flowers, but increases the number of flowers visited. In addition, flowers with nicotine deterred florivery by caterpillars and nectar-robbing by carpenter bees, both of which could directly reduce reproductive fitness. Interestingly, flowers that produced both nicotine and benzyl acetone also sired more seeds than other plants and produced larger seed capsules themselves. As noted in an accompanying Perspective by R. A. Raguso, these results suggest that chemically mediated "pull" and "push" strategies optimize the plant’s reproductive fitness by attracting pollinators, preventing them from loitering, and deterring floral enemies. The study’s corresponding author Ian Baldwin discussed the work in a related podcast interview.


Unwitting Accomplices

Many parasitic diseases are transmitted by the bite of an infected insect, yet the early events that occur as the pathogen is introduced to the host are poorly understood. In a Report in the 15 Aug 2008 Science, Peters et al. used in vivo imaging in a mouse model to visualize the initial events following infection with the sand fly-transmitted parasite Leishmania major. Although Leishmania normally infects macrophages, the researchers found that neutrophils were among the first immune cells to arrive at the site of the insect bites. These cells are armed with toxic oxygen radicals and lytic enzymes that typically destroy the pathogens they ingest. In the case of Leishmania, however, the team observed that parasites remain viable and infective once engulfed. Thus, rather than helping the host deal with the parasite, neutrophils become accomplices in the ongoing process of infection. Another unexpected finding was that instead of engulfing the infected neutrophils, macrophages appeared to acquire parasites that had been released from neutrophils undergoing cell death. An accompanying Perspective by B. John and C. A. Hunter noted that this result raises the interesting question of whether parasites released from dying neutrophils are somehow better adapted to survive in macrophages.


Understanding Pain

The body’s peripheral pain pathways are activated by a range of stimuli including heat, cold, and pressure. Attempts to ascribe these different types of pain to particular pain receptors have been difficult, however, probably because of the existence of multiple damage-sensing molecules in the body. In a Report in the 1 Aug 2008 Science, Abrahamsen et al. offered new insights into the cellular and molecular basis of three types of pain. Using a genetic approach to kill a subset of pain-sensing neurons, followed by behavioral and electrophysiological assays, the team showed that sensory neurons expressing a specific type of sodium channel (Nav1.8) are essential for transmitting cold, mechanical, and inflammatory pain. This sodium channel has previously been shown to be associated with damage-sensing neurons and with feeling pain in the cold. Interestingly, Nav1.8-expressing nerve cells are not involved in pain behavior associated with nerve damage or heat. In a related podcast interview, senior author John Wood discussed how further understanding the molecular underpinnings of pain could aid the development of more effective analgesics.


Channel Gating Insights

The uncontrolled flow of water can have disastrous consequences. Engineers have designed structures like dams, levees, and faucets to deal with the problem. Cells cope by way of membrane channels that allow for the release of cellular contents in response to hypoosmotic shock. When an Escherichia coli cell is suddenly exposed to fresh water, for example, the mechanosensitive channel MscS opens to allow rapid ion efflux, relieving the pressure on the cell membrane that would otherwise destroy the cell. Now, two studies in the 29 Aug 2008 Science provide new insight into the molecular basis of MscS channel gating. Wang et al. presented the crystal structure of the MscS channel in an open conformation, while Vásquez et al. used patch-clamp techniques, electron paramagnetic resonance spectroscopy, and computational analyses to determine the structural rearrangements associated with MscS activation in membranes. Their studies reveal that circularly arrayed transmembrane helices expand like the iris of a camera to open the channel and allow the outflow of ions -- and that tilting of the helices helps facilitate this process. An accompanying Perspective by C. S. Gandhi and D. C. Rees discussed how this mechanism compares with structural changes in the permeation pathways of other gated ion channels.


Alternative Antibiotic Development Strategy

A continuing challenge for medicine is to develop new drugs against pathogens that are resistant to current antimicrobial agents. One promising strategy is to identify drugs that inhibit microbial virulence rather than microbial growth, because these agents should present less selective pressure for the generation of resistance. In a Report in the 22 Aug 2008 Science, Rasko et al. described some encouraging results using this approach. Many bacterial pathogens sense that they are in a potential host through detection of the host adrenergic signaling molecules epinephrine and norepinephrine. These microbes appear to use the same sensor kinase protein, QseC, to recognize the host signals and mediate activation of the organism’s virulence genes. In the new study, the researchers identified a non-toxic small molecule that blocks the binding of signals to QseC, thus inhibiting the subsequent activation of virulence gene expression. In animal models, the inhibitor was somewhat effective against gastrointestinal infections of pathogenic Escherichia coli and Salmonella typhimurium. More promisingly, the molecule was quite effective against the Francisella tularensis, the causative agent of rabbit fever: A single oral dose protected 80% of infected mice from death. Because QseC is present in many important animal and plant pathogens, but not in mammals, targeting this sensor protein offers a strategy for the development of broad-spectrum antimicrobial drugs. Senior author Vanessa Sperandio discussed the work in a related podcast interview.


Digitizing Text While Screening Out Spam

CAPTCHAs (Completely Automated Public Turing test to tell Computers and Humans Apart) are widespread security measures used to protect Web sites such as free email providers, ticket sellers, and social networking sites from automated and abusive programs deployed by spammers. They require users to read a distorted word or line of text and retype it in a designated box -- something that few optical scanners or digital-text readers can do. Now, researchers have devised a way to harness the human mental effort spent decoding CAPTCHAs for another useful purpose: helping to digitize old printed material by asking users to decipher scanned words from books that computerized optical character recognition software has failed to recognize. As described in a Report by von Ahn et al. published online in Science Express on 14 Aug 2008, the reCAPTCHA program presents users with one optically unreadable word and one "control" CAPTCHA word for which the solution is known. Getting the control word right identifies the user as a human, and the program records the user’s response to the unreadable word and adds it to its database. To improve the accuracy of the system, reCAPTCHA sends the most difficult words to multiple users and selects the consensus response as correct. As noted in a related ScienceNOW story by P Berardelli, the program can transcribe text with word accuracy over 99%, matching the guarantee of professional human transcribers. reCAPTCHA is currently deployed in over 40,000 Web sites and has so far helped resolve some 440 million words from scanned text documents.


Challenges in Theoretical Chemistry
Introduction to Special Issue

Not long ago, experiments in the synthetic chemistry lab were performed without detailed calculations or predictions. Now, many chemists are turning to computational and theoretical methods for deeper insights into the electronic structure of chemical systems and chemical reactivity at the atomic scale. In a special section of the 8 Aug 2008 issue, Science looked at the complementary roles of theory and experiment in exploring chemical questions. Perspective articles discussed the importance of calculating a potential energy function to describe the energy of a particular system as a function of the position of the atoms, the status of predicting reactions between isolated small molecules in the gas phase, the limitations of density functional theory for describing electron interactions, progress in modeling molecule/surface interactions, and the use of large-scale molecular dynamics simulations to explore self-assembly in complex fluids and biological systems. Theoretical chemistry is also being used to address complex problems in biochemistry and materials science. On this front, a News story described recent successes in simulating protein folding -- a problem long hindered by the computational intractability of the immense number of possible configurations -- and a Perspective described some of the challenges of modeling materials properties without experimental input.


Stretchable Conductors

Conventional electronic devices rely on hard, rigid circuit boards. These circuits are suitable for computers and other stationary devices, but engineers are eager to develop malleable electronics for applications ranging from large, stretchable video displays to artificial skin for robots. Now, in a Report published online in Science Express on 7 Aug 2008, Sekitani et al. describe the creation of a novel rubbery, elastic conducting material -- the first step toward building a flexible circuit. To build the material, the researchers first mixed a batch of millimeter-long carbon nanotubes with an ionic liquid--a liquid containing charged molecules -- to prevent the tubes from clumping. This produced a black, pasty substance that was then combined with a liquid polymer and poured onto a glass plate. Last, the team coated the substance with silicone rubber and punched tiny holes all over the material to increase its elasticity. The resulting material can be stretched by up to 38% of its original length without loss of conductivity. Moreover, when the team used the elastic conductors to connect an array of organic transistors, the matrix showed excellent mechanical and electrical properties under high tensile strain. An accompanying ScienceNOW story by P. Berardelli highlighted the Report.


New Water-Splitting Catalyst

Sunlight has great potential to remedy the world’s energy problems, but has so far been confined to a daytime-only energy source. That’s because current methods for storing extra solar energy for later use are both prohibitively expensive and inefficient. What is needed are catalysts capable of taking electricity and using it to split water to generate hydrogen gas, a clean fuel, and oxygen. This is a two-step process involving the chemical rearrangement of oxygen and water to make O2 and of the protons in water to make H2. The O2 catalyzing step has been particularly difficult to achieve; platinum works but is too rare and expensive to be viable on an industrial scale. Now, in a Report in the 22 Aug 2008 Science (published online 31 Jul), Kanan and Nocera report the design of a new highly efficient water-splitting catalyst made from cobalt and phosphorus -- two cheap and abundant elements (see the related News story by R.F. Service in the 1 Aug issue). To make the catalyst, the team immersed an indium tin oxide electrode in water and mixed in cobalt and potassium phosphate. When a voltage is applied to the electrode, cobalt, potassium, and phosphate accumulate on the electrode, forming a catalyst that can oxidize the water to form oxygen gas and free hydrogen ions (hydrogen ions form hydrogen gas at another electrode). Moreover, the process works at neutral pH and room temperature -- conditions that are highly desirable for industrial-scale production. Dr. Nocera discussed the system, as well planned improvements to it, in a related podcast interview.


Simulating Star Formation

At the end of the cosmic dark ages -- the first billion years after the Big Bang -- the first stars began to form and light up the universe. The formation and eventual explosions of these primordial starts provided the seeds for subsequent stars to come into being. Two Reports in Science this month offered new insights into the birth of stars in the early universe as well as the formation of more recent stars near the massive black hole in our Galaxy.

--Yoshida et al. (1 Aug 2008) presented computer simulations of the first stars to appear in the universe that follow the atomic and molecular processes in a primordial gas cloud undisturbed by turbulence or magnetic fields. Their results show how minute variations in the density of dark matter and gas can grow under the influence of gravity and seed the formation of a tiny protostar with a mass just 1% that of the Sun, and how this protostar could have evolved into a massive star capable of synthesizing heavy elements soon after the Big Bang. An accompanying Perspective by V. Bromm highlighted the study.

--Bonnell and Rice (22 Aug 2008) investigated star formation near supermassive black holes, presenting numerical simulations showing that, an ordinary molecular cloud -- formed at distances large enough to be immune from the black hole’s dangerous tidal forces -- could survive the inward plunge to deposit a fraction of its gas into an eccentric disk that can nucleate stars (see the related Perspective by P. J. Armitage). Under appropriate conditions including heating and compression of gas as it is torn apart by black hole, most of these become massive stars.


Elusive Substorm Source

Geomagnetic substorms -- explosive bursts of solar wind energy in Earth’s magnetosphere -- wreak havoc on satellites, power grids, and communications systems and trigger periodic brightening of the multicolored light displays of the aurora borealis, or Northern Lights. There have been two competing models to explain the onset of these mysterious atmospheric events. One holds that substorms are triggered about 60,000 kilometers above Earth -- about a sixth of the way to the moon -- when electromagnetic turbulence disrupts the flow of space currents. The posits that the source is magnetic reconnection farther out in Earth’s magnetotail, about 120,000 kilometers above Earth, where Earth’s geomagnetic field lines collide with the solar magnetic field lines, flinging charged particles back toward the Earth’s atmosphere. Now, in a Research Article in the 15 Aug 2008 Science (published online 24 Jul), Angelopoulos et al. present some of the first results of a NASA project aimed at elucidating the triggers of substorm onset. The team analyzed satellite measurements of magnetic and electric fields of the plasma above Earth’s atmosphere, as well as images of auroral lights captured by ground-based observatories, of a substorm that occurred in February 2008. The data indicate that magnetic reconnection started the event, triggering an aurora display 1.5 minutes later. An accompanying Perspective by A. A. Petrukovich highlighted the study.


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In Science Signaling

Second Messenger Candidate

Until recently, the intracellular signaling landscape in bacteria looked to be deserted. In particular, small secondary signaling molecules seemed uncommon, restricted to cyclic adenosine 3’,5’-monophosphate (cAMP), used to signal changes in glucose concentration, and guanosine-tetraphosphate (ppGpp), produced in response to nutrient stress. The cyclic dinucleotide signaling molecule cyclic diguanylic acid (c-di-GMP), the synthesis of which is stimulated by a broad range of signals, has since been recognized as a second messenger used by many bacteria associated with biofilm formation. In a Perspective in the 19 Aug 2008 issue, Römling highlighted recent work indicating the presence of another previously unrecognized cyclic dinucleotide signaling molecule in bacteria: 3’-5’-cyclic diadenylic acid or c-di-AMP. The study showed that in the soil bacterium Bacillus subtilis, a domain of DisA (DNA integrity scanning protein) -- a protein that provides a checkpoint for DNA damage during sporulation -- has diadenylate cyclase activity. Interestingly, this activity is abolished when DisA binds to branched DNA, which can result from spontaneous double-strand breaks during DNA replication. c-di-AMP may thus serve as a signal of DNA integrity. The presence of the diadenylate cyclase domain in other bacterial and archaeal proteins suggests that c-di-AMP acts as a second messenger molecule in response to various signals besides branched DNA.

Also in Science Signaling this month:
--J. M. Sanger and J. W. Sanger discussed the dynamic Z bands of striated muscle cells (12 Aug 2008)
--Lamb et al. discussed how proteins that bind NAD(H) or NADP(H) may couple cellular redox state to transcription or other signaling pathways (19 Aug 2008)
--S. Na and N. Wang described a protocol for quantifying mechano-chemical signaling activities in a living cell (26 Aug 2008)