Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes

The Logic of Fashion Cycles

Many cultural traits exhibit volatile dynamics, commonly dubbed fashions or fads. Here we show that realistic fashion-like dynamics emerge spontaneously if individuals can copy others' preferences for cultural traits as well as traits themselves. We demonstrate this dynamics in simple mathematical models of the diffusion, and subsequent abandonment, of a single cultural trait which individuals may or may not prefer. We then simulate the coevolution between many cultural traits and the associated preferences, reproducing power-law frequency distributions of cultural traits (most traits are adopted by few individuals for a short time, and very few by many for a long time), as well as correlations between the rate of increase and the rate of decrease of traits (traits that increase rapidly in popularity are also abandoned quickly and vice versa). We also establish that alternative theories, that fashions result from individuals signaling their social status, or from individuals randomly copying each other, do not satisfactorily reproduce these empirical observations

Time-Lapse Analysis and Mathematical Characterization Elucidate Novel Mechanisms Underlying Muscle Morphogenesis

Skeletal muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction (MTJ). In vertebrates, a great deal is known about muscle specification as well as how somitic cells, as a cohort, generate the early myotome. However, the cellular mechanisms that generate long muscle fibers from short cells and the molecular factors that limit elongation are unknown. We show that zebrafish fast muscle fiber morphogenesis consists of three discrete phases: short precursor cells, intercalation/elongation, and boundary capture/myotube formation. In the first phase, cells exhibit randomly directed protrusive activity. The second phase, intercalation/elongation, proceeds via a two-step process: protrusion extension and filling. This repetition of protrusion extension and filling continues until both the anterior and posterior ends of the muscle fiber reach the MTJ. Finally, both ends of the muscle fiber anchor to the MTJ (boundary capture) and undergo further morphogenetic changes as they adopt the stereotypical, cylindrical shape of myotubes. We find that the basement membrane protein laminin is required for efficient elongation, proper fiber orientation, and boundary capture. These early muscle defects in the absence of either lamininβ1 or lamininγ1 contrast with later dystrophic phenotypes in lamininα2 mutant embryos, indicating discrete roles for different laminin chains during early muscle development. Surprisingly, genetic mosaic analysis suggests that boundary capture is a cell-autonomous phenomenon. Taken together, our results define three phases of muscle fiber morphogenesis and show that the critical second phase of elongation proceeds by a repetitive process of protrusion extension and protrusion filling. Furthermore, we show that laminin is a novel and critical molecular cue mediating fiber orientation and limiting muscle cell length

Enzyme sequestration as a tuning point in controlling response dynamics of signalling networks

Signalling networks result from combinatorial interactions among many enzymes and scaffolding proteins. These complex systems generate response dynamics that are often essential for correct decision-making in cells. Uncovering biochemical design principles that underpin such response dynamics is a prerequisite to understand evolved signalling networks and to design synthetic ones. Here, we use in silico evolution to explore the possible biochemical design space for signalling networks displaying ultrasensitive and adaptive response dynamics. By running evolutionary simulations mimicking different biochemical scenarios, we find that enzyme sequestration emerges as a key mechanism for enabling such dynamics. Inspired by these findings, and to test the role of sequestration, we design a generic, minimalist model of a signalling cycle, featuring two enzymes and a single scaffolding protein. We show that this simple system is capable of displaying both ultrasensitive and adaptive response dynamics. Furthermore, we find that tuning the concentration or kinetics of the sequestering protein can shift system dynamics between these two response types. These empirical results suggest that enzyme sequestration through scaffolding proteins is exploited by evolution to generate diverse response dynamics in signalling networks and could provide an engineering point in synthetic biology applications

On the Dynamics of the Spontaneous Activity in Neuronal Networks

Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features. Indeed, in both networks: i) the inter-spike intervals distribution of the spontaneous firing of single neurons is either regular or periodic or bursting, with the fraction of bursting neurons depending on the network activity; ii) bursts of spontaneous spikes have the same broad distributions of size and duration; iii) the degree of correlated activity increases with the bin width, and the power spectrum of the network firing rate has a 1/f behavior at low frequencies, indicating the existence of long-range temporal correlations; iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is necessary for the onset of the long-range correlations and for the presence of large bursts; v) blockage of inhibitory synaptic pathways mediated by GABA(A) receptors causes instead an increase in the correlation among neurons and leads to a burst distribution composed only of very small and very large bursts. These results suggest that the spontaneous electrical activity in neuronal networks with different architectures and functions can have very similar properties and common dynamics

The evolutionary significance of polyploidy

Polyploidy, or the duplication of entire genomes, has been observed in prokaryotic and eukaryotic organisms, and in somatic and germ cells. The consequences of polyploidization are complex and variable, and they differ greatly between systems (clonal or non-clonal) and species, but the process has often been considered to be an evolutionary 'dead end'. Here, we review the accumulating evidence that correlates polyploidization with environmental change or stress, and that has led to an increased recognition of its short-term adaptive potential. In addition, we discuss how, once polyploidy has been established, the unique retention profile of duplicated genes following whole-genome duplication might explain key longer-term evolutionary transitions and a general increase in biological complexity

The role of inflammation in epilepsy.

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis

Multidrug efflux pumps:structure, function and regulation

Infections arising from multidrug-resistant pathogenic bacteria are spreading rapidly throughout the world and threaten to become untreatable. The origins of resistance are numerous and complex, but one underlying factor is the capacity of bacteria to rapidly export drugs through the intrinsic activity of efflux pumps. In this Review, we describe recent advances that have increased our understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria. Clinical and laboratory data indicate that efflux pumps function not only in the drug extrusion process but also in virulence and the adaptive responses that contribute to antimicrobial resistance during infection. The emerging picture of the structure, function and regulation of efflux pumps suggests opportunities for countering their activities