So, let's see what's new in PLoS Genetics, PLoS Computational Biology, PLoS Pathogens and PLoS ONE this week. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. Here are my own picks for the week - you go and look for your own favourites:
Robust Food Anticipatory Activity in BMAL1-Deficient Mice:
Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Even though nocturnal rodents prefer to forage at night, daytime food anticipatory activity (FAA) is observed prior to short meals presented at a scheduled time of day. Under this restricted feeding regimen, rodents exhibit two distinct bouts of activity, a nocturnal activity rhythm that is entrained to the light-dark cycle and controlled by the master clock in the suprachiasmatic nuclei (SCN) and a daytime bout of activity that is phase-locked to mealtime. FAA also occurs during food deprivation, suggesting that a food-entrainable oscillator (FEO) keeps time in the absence of scheduled feeding. Previous studies have demonstrated that the FEO is anatomically distinct from the SCN and that FAA is observed in mice lacking some circadian genes essential for timekeeping in the SCN. In the current study, we optimized the conditions for examining FAA during restricted feeding and food deprivation in mice lacking functional BMAL1, which is critical for circadian rhythm generation in the SCN. We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D. While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability. Taken together, our findings suggest that optimization of experimental conditions such as photoperiod may be necessary to visualize FAA in genetically modified mice. Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1.
The Generation of Forces and Moments during Visual-Evoked Steering Maneuvers in Flying Drosophila:
Sideslip force, longitudinal force, rolling moment, and pitching moment generated by tethered fruit flies, Drosophila melanogaster, were measured during optomotor reactions within an electronic flight simulator. Forces and torques were acquired by optically measuring the angular deflections of the beam to which the flies were tethered using a laser and a photodiode. Our results indicate that fruit flies actively generate both sideslip and roll in response to a lateral focus of expansion (FOE). The polarity of this behavior was such that the animal's aerodynamic response would carry it away from the expanding pattern, suggesting that it constitutes an avoidance reflex or centering response. Sideslip forces and rolling moments were sinusoidal functions of FOE position, whereas longitudinal force was proportional to the absolute value of the sine of FOE position. Pitching moments remained nearly constant irrespective of stimulus position or strength, with a direction indicating a tonic nose-down pitch under tethered conditions. These experiments expand our understanding of the degrees of freedom that a fruit fly can actually control in flight.
Producer Nutritional Quality Controls Ecosystem Trophic Structure:
Trophic structure, or the distribution of biomass among producers and consumers, determines key ecosystem values, such as the abundance of infectious, harvestable or conservation target species, and the storage and cycling of carbon and nutrients. There has been much debate on what controls ecosystem trophic structure, yet the answer is still elusive. Here we show that the nutritional quality of primary producers controls the trophic structure of ecosystems. By increasing the efficiency of trophic transfer, higher producer nutritional quality results in steeper ecosystem trophic structure, and those changes are more pronounced in terrestrial than in aquatic ecosystems probably due to the more stringent nutritional limitation of terrestrial herbivores. These results explain why ecosystems composed of highly nutritional primary producers feature high consumer productivity, fast energy recycling, and reduced carbon accumulation. Anthropogenic changes in producer nutritional quality, via changes in trophic structure, may alter the values and functions of ecosystems, and those alterations may be more important in terrestrial ecosystems.
Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis:
Genome sequencing has provided us with "parts lists" of genes for many organisms, but many of the biological roles these genes are still unknown. While a great deal of functional genomic data exists, providing information about these genes and their roles, the rate at which these data are leveraged into concrete biological knowledge lags far behind the rate of data generation. Many computational approaches have been developed to generate accurate predictions of gene functions, with the goal of bridging this divide. However, as no large-scale experimental efforts have been based on such approaches, their validity and utility remains unproven. We have performed a study that experimentally evaluates predictions from a combination of three computational function prediction approaches, focusing on mitochondrion-related processes in brewer's yeast as a model system. By using computational predictions to guide our laboratory investigation, we have greatly accelerated the rate at which proteins can be assigned to biological processes. Further, our results demonstrate that in order to achieve the best results, it is important for computational biologists to consider both the underlying data and the algorithmic foundations of the methods used to predict function. Lastly, we demonstrate that iterating through phases of prediction and validation has quickly and extensively expanded our knowledge of mitochondrial biology.
On the Growth of Scientific Knowledge: Yeast Biology as a Case Study:
It is of great interest to understand the patterns and mechanisms of scientific knowledge growth, but such studies have been hampered by the lack of ideal cases in which the structure of the knowledge is known, the knowledge is quantifiable, and the process of knowledge discovery is well understood and documented. The biological knowledge about a species is in part described by its protein interaction network and genetic interaction network. Here, we conduct a temporal meta-analysis of three decades of discoveries of protein interactions and genetic interactions in baker's yeast to reveal the tempo and mode of the growth of yeast biology. We show that the growth is exponential over time and that important subjects tend to be studied earlier. However, expansions of different domains of knowledge are highly heterogeneous and episodic such that the temporal turnover of knowledge hubs is much greater than that expected by chance. Familiar subjects are preferentially studied over new subjects, leading to a reduced pace of innovation. While research is increasingly done in teams, the number of discoveries per researcher is greater in smaller teams. These findings reveal collective human behaviors in scientific research and help design better strategies in future knowledge exploration.
Computational Model of the Insect Pheromone Transduction Cascade:
All sensory neurons transduce their natural stimulus, whether a molecule, a photon, or a mechanical force, in an electrical current flowing through their sensory membrane via similar molecular and ionic mechanisms. Olfactory receptor neurons (ORNs), whose stimuli are volatile molecules, are no exception, including one of the best known: the exquisitely sensitive ORNs of male moths that detect the sexual pheromone released by conspecific females. We provide a detailed computational model of the intracellular molecular mechanisms at work in this ORN type. We describe qualitatively and quantitatively how the initial event, the interaction of pheromone molecules with specialized receptors at the ORN surface, is amplified through a sequence of linked biochemical and electrical events into a whole cell response, the receptor potential. We detail the respective roles of the upward activating reactions involving a cascade of ionic channels permeable to cations, chloride and potassium, their control by feedback inactivating mechanisms, and the central regulatory role of calcium. This computational model contributes to an integrated understanding of this signalling pathway, provides testable hypotheses, and suggests new experimental approaches.
Broadband Criticality of Human Brain Network Synchronization:
Systems in a critical state are poised on the cusp of a transition between ordered and random behavior. At this point, they demonstrate complex patterning of fluctuations at all scales of space and time. Criticality is an attractive model for brain dynamics because it optimizes information transfer, storage capacity, and sensitivity to external stimuli in computational models. However, to date there has been little direct experimental evidence for critical dynamics of human brain networks. Here, we considered two measures of functional coupling or phase synchronization between components of a dynamic system: the phase lock interval or duration of synchronization between a specific pair of time series or processes in the system and the lability of global synchronization among all pairs of processes. We confirmed that both synchronization metrics demonstrated scale invariant behaviors in two computational models of critical dynamics as well as in human brain functional systems oscillating at low frequencies (<0.5 Hz, measured using functional MRI) and at higher frequencies (1-125 Hz, measured using magnetoencephalography). We conclude that human brain functional networks demonstrate critical dynamics in all frequency intervals, a phenomenon we have described as broadband criticality.
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