TOR and aging: less is more

Metabolism and mitochondrial activity are thought to be important determinants of life span. A new study in this issue of Cell Metabolism (Bonawitz et al., 2007) suggests that the TOR pathway controls mitochondrial respiration in yeast and that the harder mitochondria work, the longer yeast live.     

In epigenetic therapy, less is more

How DNA methylation inhibitors exert their anticancer effects in patients is not well understood. In the latest issue of Cancer Cell, Tsai et?al. (2012) use low-dose drug treatment to induce persistent attenuation of tumorigenicity by targeting tumor-initiating cells.     

Speckle microscopy: when less is more

Fluorescent speckle microscopy is a new and simplified method for generating fiduciary marks on cellular structures. It promises to become the method of choice for studying polymer movement and dynamics in vivo.     

Less is more, except when less is less: Studying joint effects

Most diseases are complex in that they are caused by the joint action of multiple factors, both genetic and environmental. Over the past few decades, the mathematical convenience of logistic regression has served to enshrine the multiplicative model, to the point where many epidemiologists believe that departure from additivity on a log scale implies that two factors interact in causing disease. Other terminology in epidemiology, where students are told that inequality of relative risks across levels of a second factor should be seen as "effect modification," reinforces an uncritical acceptance of multiplicative joint effect as the biologically meaningful no-interaction null. Our first task, when studying joint effects, is to understand the limitations of our definitions for "interaction," and recognize that what statisticians mean and what biologists might want to mean by interaction may not coincide. Joint effects are notoriously hard to identify and characterize, even when asking a simple and unsatisfying question, like whether two effects are log-additive. The rule of thumb for such efforts is that a factor-of-four sample size is needed, compared with that needed to demonstrate main effects of either genes or exposures. So strategies have been devised that focus on the most informative individuals, either through risk-based sampling for a cohort, or case-control sampling, extreme phenotype sampling, pooling, two-stage sampling, exposed-only, or case-only designs. These designs gain efficiency, but at a cost of flexibility in models for joint effects. A relatively new approach avoids population controls by genotyping case-parent triads. Because it requires parents, the method works best for diseases with onset early in life. With this design, the role of autosomal genetic variants is assessed by in effect treating the nontransmitted parental alleles as controls for affected offspring. Despite advantages for looking at genetic effects, the triad design faces limitations when examining joint effects of genetic and environmental factors. Because population-based controls are not included, main effects for exposures cannot be estimated, and consequently one only has access to inference related to a multiplicative null. We have proposed a hybrid approach that offers the best features of both case-parent and case-control designs. Through genotyping of parents of population-based controls and assuming Mendelian transmission, power is markedly enhanced. One can also estimate main effects for exposures and now flexibly assess models for joint effects.     

The approximately ideal, more or less free distribution

We present the minimum set of requirements necessary and sufficient to represent the foraging behaviour of an animal, and its utilisation of food, in order to explore the emergent properties of behaviour that allow animals to reduce their hunger. We present an individual-based model of foraging that provides a simple quantification of the requirements, which is sufficiently simple to yield some analytical results. Complex interactions beyond the scope of analysis have been explored through simulating animals foraging in regenerating patchy environments. In most cases the populations pass into equilibrium distributions which appear to be stable. The equilibria always approximate closely to the ideal free distribution, although typically with a small degree of undermatching. (Undermatching is the term applied to the departure from the ideal free distribution caused by a smaller proportion of the population than expected occupying areas with a higher than average regeneration rate). The model therefore implies that the distribution, hitherto accounted for in terms of ESSs may, in fact, be simply an effect of the animal's utilization of the food it collects to reduce its hunger. The model defines a specific feeling rate, v, the rate at which an animal can feed on a unit of food. This is a function of three parameters, v1, the specific feeding rate when alone, v(infinity), the rate, possibly zero, at which it can feed in the presence of an indefinitely large number of conspecifics, and n1/2, the number of conspecifics that cause v to take the value (v1+v(infinity)/2. Exploitation competition in the absence of interference is represented by setting v1 = v(infinity). Differences in competitive ability in exploitation have been represented by simulating animals with a range of values of v1, those with the larger values, feeding more rapidly, being the more effective competitors, and those with the lower values being the less effective. Interference competition is represented by setting v1 > v(infinity) and social facilitation by v1 < v(infinity). Individual differences in the strength of interaction are represented by different values of n(1/2). In competition, the animals with the larger values of n(1/2) are the more effective competitors: in facilitation, they are the less effective facilitators. The addition of physiological and behavioural detail makes very little alteration to the emergent equilibria, always close to the ideal free distribution, almost always showing undermatching.     

Organelle proteomics: looking at less to see more

The recent finding that the human genome comprises between 21 000 and 39 000 genes, a number much lower than expected, has in no way simplified the complexity associated with the understanding of how cells perform their functions. Elucidation of the molecular mechanisms underlying cell functions will require a global knowledge of the expressed proteins, including splice variant products, their post-translational modifications, their subcellular localizations and their assembly into molecular machines as deduced from protein–protein interactions, at any given time during the life of the cell or under any cellular conditions. Current and expected advances in mass spectrometry and bioinformatics might help the realization of these goals in a shorter time than is currently predicted.     

When more is less: the fitness consequences of predators attacking more unpalatable prey when more are presented

In 1879, Fritz Müller hypothesized that mimetic resemblance in which defended prey display the same warning signal would share the costs of predator education. Although Müller argued that predators would need to ingest a fixed number of prey with a given visual signal when learning to avoid unpalatable prey, this assumption lacks empirical support. We report an experiment which shows that, as the number of unpalatable prey presented to them increased, avian predators attacked higher numbers of those prey. We calculated that, when predators increase attacks, the fitness costs incurred by unpalatable prey can be substantial. This suggests that the survival benefits of mimicry could be lower than Müller proposed. An important finding is, however, that these costs decline in importance as the total number of available prey increases.