BioEssays

Pheomelanin - a pigment that may have evolved as an excretory mechanism. Higher vertebrates synthesize two forms of melanin: eumelanin and pheomelanin. While eumelanin has well known adaptive benefits, the mechanisms by which pheomelanin has evolved remain a mystery because of several physiological costs and no clear benefits. In this issue (pages 565–568), Galván et al. suggest that pheomelanin has evolved because the incorporation of thiol groups to the structure of this pigment helps to remove cysteine, which can be toxic if in excess. Pheomelanogenesis may thus be favored when environmental conditions promote excess cysteine. This may explain why humans with a pheomelanic phenotype are more common at high latitudes, and raises the question whether these humans may have a greater ability to avoid diseases associated with excess cysteine. The photo shows a common kingfisher Alcedo atthis exhibiting orange belly by the presence of pheomelanin in feathers (Toral et al. 2008, Comp Biochem Physiol B).

Blueprint for a postsynaptic density substructure. The postsynaptic density is a massive protein assembly that is attached to the postsynaptic membrane of excitatory synapses. One of its key roles is coordinating different synaptic activation patterns with changes in synaptic strength, a process that is thought to underlie memory formation. Determining its three-dimensional structure is essential to understand how it performs this role at the molecular level as discussed by Matthew Gold on pages 599–608 of this issue. The image shows the architecture of a complex nucleated within the postsynaptic density by the anchoring protein AKAP79. This model was developed by integration of data from multiple structural biology techniques and exemplifi es on a small scale how the complete structural model of the PSD can be assembled.

Backcover by M. Gold

The signal transduction mediator ECSIT (evolutionarily conserved signaling intermediate in Toll pathway) may act as an early pathogenic sensor in Alzheimer's disease, integrating multiple signaling inputs to generate precise cellular responses in a temporal/spatial pattern, which were — individually — already known to be involved in the disease.

By using a combination of quantitative experimentation and mathematical modeling it is possible to identify key mediators of signal processing. These key mediators seem to act early in the signal transduction process, finally governing long-term cell fate decisions.

Leucine-rich repeat-containing 8 (LRRC8) proteins contain four transmembrane helices and 17 leucine-rich repeats. Previously assumed to act as receptors, the hypothesis presented here instead proposes that LRRC8 proteins form hexameric channels. In contrast to earlier models, their leucine-rich repeats are likely on the intracellular side, and function in signalling cascades.

Apoptosis is not only involved in patterning by removal of tissue (destructive apoptotic patterning), but it can also function in signalling the site of de novo tissue generation via morphogenic signals (instructive apoptotic patterning).

Pheomelanogenesis may have evolved as an excretory mechanism to remove excess cysteine, and in humans this might potentially confer a greater ability to avoid disease such as Parkinson's and Alzheimer's disease, in which excess cysteine is a contributory cause.

There is evidence that Tregs are multipotent suppressors that have the ability to suppress all effector T cell lineages through different molecular mechanisms.

Moonlighting proteins have acquired one or more additional functions - with respect to their canonical function - during evolution. This phenomenon seems to be more widespread than previously thought. This review presents the structural basis of moonlighting and discusses numerous examples.

The NAIP-NLRC4 inflammasomes appear to function as receptors for specific bacterial molecules, but it remains unclear how NAIPs (NLR family, apoptosis inhibitory proteins) recognize and distinguish ligands, and what role NLRC4 (NLR family, CARD domain-containing 4) plays in ligand recognition, but it probably serves as an adaptor for caspase-1.

The postsynaptic density (PSD) is a massive multi-protein complex involved in synaptic transmission and plasticity. The use of different techniques such as proteomics, super-resolution imaging and crystallography contributes to a more complete understanding of the PSD structure and may provide insight into the molecular mechanisms underlying neural phenomena at a higher level.

Sperm function declines with male age, yet females of many species still choose to mate with older males. Do hidden advantages of mating with older males off-set costs related to fertility or can females detect declines in fertility and avoid mating with males that reduce offspring fitness?.

This meeting united participants from the fields of experimental epigenetics, mathematics and computational biology, to discuss results and challenges in the endeavour to explore points of synergy between these fields. The design shown here expresses the idea of moving complex biological phenomena (left nucleosome) towards precise mathematical descriptions (right nucleosome).