Beyond Out of Africa

Analysis of DNA sequence variation has increased our understanding genetic diversity in humans, revealing, for example, that humans migrated out of Africa and dispersed across the globe, displacing other hominids in the process. In order to gain a deeper understanding, Li et al. (p. 1100) studied more than half a million single nucleotide polymorphisms from the Human Genome Diversity Panel, representing 51 populations from around the world. The broad sweep of the analysis uncovers both fine-scale population structure, for example, distinguishing Orcadian, French, and Northern Italian populations from Bergamo and Tuscan groups, and supports the "serial founder model," in which non-African populations form a sequential chain of colonies as they radiated out from Africa.

Tagging + Recruitment = Learning

Stabilizating long-term memories requires the expression of new gene products in the nucleus to generate physical changes or "tags" at a small subset of synapses on the dendrites of neuron. Synthesis of AMPA receptors is increased during learning is suggestive of a possible role in this process. Matsuo et al. (p. 1104) developed transgenic mice to monitor the trafficking and turnover of newly synthesized AMPA receptors in a fear-conditioning paradigm. By coupling expression of fluorescent receptors to neuronal activity, they specifically examined the pool of newly synthesized receptor. New receptors were delivered to spines several hours after behavioral training, which suggests that at the time of learning, changes occur in some spines that allow the capture of newly synthesized AMPA receptors at later time points.

Spike Coding in the Retina

The retina's task is to transduce visual images into neural signals, to process these signals, and to transmit the result through the optic nerve to the brain. The general notion, as in other sensory systems, is that a time-varying visual stimulus will produce time-varying firing rates among retinal ganglion cells, and these rates are what drives the processing in subsequent visual stations. It is unclear, however, whether this type of sensory encoding could support the rapid signal detection and image processing of which the visual system is capable. Gollisch and Meister (p. 1108) show, instead, that a single spike per ganglion cell is sufficient to accurately communicate a new visual image. The meaning of the spike is conveyed by its precise time of occurrence, relative to spikes from other ganglion cells. By several criteria, this message is more powerful and more robust than that conveyed by the firing rate. Most importantly, it transmits image information in the shortest possible time.

Predicting Human Behavior

How well can neuronal networks model human interactive decision-making? Recently, the important role of regret in human decision-making has been demonstrated. Marchiori and Warglien (p. 1111; see the Perspective by Cohen) have now modified neuronal network feedback in 21 interactive games to take the role of regret into account. Introducing regret into the feedback dramatically improved the efficacy of neuronal networks and allowed more precise prediction of human behavior than conventional economic learning theories.

Exploiting Nonlinearity in Molecular Junctions

The use of molecules as switching elements in electronics stems not just from their small size but from the possibility that a molecular junction could exhibit nonlinear responses that enable more compact realizations for logic operations. Galperin et al. (p. 1056)) overview the theory of how electronic transport in molecular junctions moves beyond the tunneling regime. At higher voltages, up to about 0.3 volts, molecular vibrations scatter electrons and provide spectroscopic signatures. At higher biases, strong coupling allows the electron to reside for longer times on the molecule and leads to strong polarization and charging, as well as nonlinear responses such as Coulomb blockades, negative differential resistance, and dynamical switching.

Telomere Tag

Telomeres--the ends of linear mammalian chromosomes--are regulated in length and protected from recognition by DNA damage repair systems by the shelterin complex, which includes the proteins telomeric repeat binding factors 1 and 2 (TRF1 and TRF2). These two proteins recruit other members of the shelterin complex and associated telomere factors, which can negatively regulate telomere length. Chen et al. (p. 1092, published online 17 January) show that TRF1 and TRF2, which are structurally quite similar, interact with such factors in distinct ways. TIN2 binds TRF1 through its N-terminal TRF homology (TRFH) domain and to TRF2 through a C-terminal domain whereas Apollo binds TRF2 via its TRFH domain in the same manner that TRF1 binds TIN2, with two loops in the TRFH domain determining these distinct binding specificities. The binding regions of TIN2 and Apollo share a pentameric sequence that may help identify other telomere accessory proteins.

Regulating the Regulon

In the presence of galactose, the yeast Saccharomyces cerevisiae transports the sugar into its cytoplasm, where the galactose binds the Gal3 protein, which in turn sequesters the Gal80 repressor away from the transcriptional activator Gal4, resulting in the induction of galactose metabolizing enzymes. The induction is so rapid that it has been suggested another unknown factor must somehow be involved in this "galactose regulon." Kumar et al. (p. 1090) have identified this factor as nicotinamide adenine dinucleotide (NAD) and its phosphate (NADP). In the Gal4:Gal80 complex, NAD is sandwiched between the two proteins. NADP, on the other hand, inhibits the interaction between Gal4 and Gal80. Mutations that have the potential to affect the NAD-binding site in Gal80 result in even faster induction, which suggests that Gal80 is sensing the balance between NAD and NADP and thus the metabolic state of the cell.

 CAR  22/2/2008