Measuring selection coefficients below 10(-3): method, questions, and prospects

Measuring fitness with precision is a key issue in evolutionary biology, particularly in studying mutations of small effects. It is usually thought that sampling error and drift prevent precise measurement of very small fitness effects. We circumvented these limits by using a new combined approach to measuring and analyzing fitness. We estimated the mutational fitness effect (MFE) of three independent mini-Tn10 transposon insertion mutations by conducting competition experiments in large populations of Escherichia coli under controlled laboratory conditions. Using flow cytometry to assess genotype frequencies from very large samples alleviated the problem of sampling error, while the effect of drift was controlled by using large populations and massive replication of fitness measures. Furthermore, with a set of four competition experiments between ancestral and mutant genotypes, we were able to decompose fitness measures into four estimated parameters that account for fitness effects of our fluorescent marker (α), the mutation (β), epistasis between the mutation and the marker (γ), and departure from transitivity (τ). Our method allowed us to estimate mean selection coefficients to a precision of 2 × 10(-4). We also found small, but significant, epistatic interactions between the allelic effects of mutations and markers and confirmed that fitness effects were transitive in most cases. Unexpectedly, we also detected variation in measures of s that were significantly bigger than expected due to drift alone, indicating the existence of cryptic variation, even in fully controlled experiments. Overall our results indicate that selection coefficients are best understood as being distributed, representing a limit on the precision with which selection can be measured, even under controlled laboratory conditions.     

Nanoindentation measurements of biomechanical properties in mature and newly formed bone tissue surrounding an implant

The characterization of the biomechanical properties of newly formed bone tissue around implants is important to understand the osseointegration process. The objective of this study is to investigate the evolution of the hardness and indentation modulus of newly formed bone tissue as a function of healing time. To do so, a nanoindentation device is employed following a multimodality approach using histological analysis. Coin-shaped implants were placed in vivo at a distance of 200 μm from the cortical bone surface, leading to an initially empty cavity of 200 μm * 4.4 mm. Three New Zealand White rabbits were sacrificed after 4, 7, and 13 weeks of healing time. The bone samples were embedded and analyzed using histological analyses, allowing to distinguish mature and newly formed bone tissue. The bone mechanical properties were then measured in mature and newly formed bone tissue. The results are within the range of hardness and apparent Young's modulus values reported in previous literature. One-way ANOVA test revealed a significant effect of healing time on the indentation modulus (p < 0.001, F = 111.24) and hardness (p < 0.02, F = 3.47) of bone tissue. A Tukey-Kramer analysis revealed that the biomechanical properties of newly formed bone tissue (4 weeks) were significantly different from those of mature bone tissue. The comparison with the results obtained in Mathieu et al. (2011, "Micro-Brillouin Scattering Measurements in Mature and Newly Formed Bone Tissue Surrounding an Implant," J. Biomech. Eng., 133, 021006). shows that bone mass density increases by approximately 13.5% between newly formed bone (7 weeks) and mature bone tissue.     

Acute running stimulates hippocampal dopaminergic neurotransmission in rats, but has no influence on brain-derived neurotrophic factor

Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours postexercise, the rats were killed, and the hippocampus was dissected. In experiments without microdialysis, hippocampus and serum samples were collected immediately after exercise. Exercise induced a twofold increase in hippocampal dopamine release. Noradrenaline and serotonin release were not affected. Hippocampal BDNF levels were not influenced, whether they were measured immediately or 2 h after the exercise protocol. Serum BDNF levels did not change either, but serum BDNF was negatively correlated to peripheral corticosterone concentrations, indicating a possible inhibitory reaction to the stress of running. Sixty minutes of exercise enhances dopamine release in the hippocampus of the rat in vivo. However, this increase is not associated with changes in BDNF protein levels immediately nor 2 h after the acute exercise bout. An increased corticosterone level might be the contributing factor for the absence of changes in BDNF.     

A MatP-divisome interaction coordinates chromosome segregation with cell division in E. coli

Initiation of chromosome segregation in bacteria is achieved by proteins acting near the origin of replication. Here, we report that the precise choreography of the terminus region of the Escherichia coli chromosome is also tightly controlled. The segregation of the terminus (Ter) macrodomain (MD) involves the structuring factor MatP. We characterized that migration of the Ter MD from the new pole to mid-cell and its subsequent persistent localization at mid-cell relies on several processes. First, the replication of the Ter DNA is concomitant with its recruitment from the new pole to mid-cell in a sequential order correlated with the position on the genetic map. Second, using a strain carrying a linear chromosome with the Ter MD split in two parts, we show that replisomes are repositioned at mid-cell when replication of the Ter occurs. Third, we demonstrate that anchoring the Ter MD at mid-cell depends on the specific interaction of MatP with the division apparatus-associated protein ZapB. Our results reveal how segregation of the Ter MD is integrated in the cell-cycle control.     

MHC-dependent mate choice in humans: why genomic patterns from the HapMap European American dataset support the hypothesis

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC-dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC-dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC-dependent mate choice in some human populations.     

Incrimination of Anopheles (Anopheles) intermedius Peryassú, An. (Nyssorhynchus) nuneztovari Gabaldón, An. (Nys.) oswaldoi Peryassú as natural vectors of Plasmodium falciparum in French Guiana

Anopheles darlingi Root is the major vector of human malaria in the Neotropics and has been considered to be the sole malaria vector in French Guiana. The presence of other potential vectors suggests that malaria may be transmitted by other species under certain conditions. From 2006-2011, all anopheline specimens collected from 11 localities were assayed to determine if the Plasmodium circumsporozoite protein was present. In addition to An. darlingi, we found Anopheles oswaldoi, Anopheles intermedius and Anopheles nuneztovari specimens that were infected with Plasmodium sp. Further investigations on the behaviour and ecology of An. oswaldoi, An. intermedius and An. nuneztovari are necessary to determine their role in malaria transmission in French Guiana.     

A Predictive Computational Model of the Dynamic 3D Interphase Yeast Nucleus

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Highlights? We describe a predictive computational model of dynamic chromosomes in the yeast nucleus ? The model quantitatively recapitulates experimental data on nuclear organization ? The model predicts nuclear reorganization in response to treatment by rapamycin ? Large-scale nuclear organization is dominated by unspecific effects of crowded polymers