Repeated evolution of self-compatibility for reproductive assurance

Sexual reproduction in eukaryotes requires the fusion of two compatible gametes of opposite sexes or mating types. To meet the challenge of finding a mating partner with compatible gametes evolutionary mechanisms such as hermaphroditism and self-fertilisation have repeatedly evolved. Combining insight from comparative genomics, computer simulations and experimental evolution in fission yeast, we shed light on the conditions promoting separate mating types or self-compatibility by mating-type switching. Analogous to multiple independent transitions between switchers and non-switchers in natural populations mediated by structural genomic changes, novel switching genotypes were readily evolving under selection in experimental populations. Detailed fitness measurements accompanied by computer simulations show the benefits and costs of switching during sexual and asexual reproduction governing the occurrence of both strategies in nature. Our findings illuminate the trade-off between the benefits of reproductive assurance and its fitness costs under benign conditions governing the evolution of self-compatibility

Long-term culture of genome-stable bipotent stem cells from adult human liver.

Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.This work was supported by grants to MH (EU/236954) and to HC (The United European Gastroenterology Federation (UEGF) Research Prize 2010, EU/232814-StemCellMark and NWO/116002008). MH is supported by The Wellcome Trust Sir Henry Dale fellowship. The Rspo cell line was kindly provided by Dr. Calvin Kuo.This is the final published version. It first appeared at http://www.cell.com/abstract/S0092-8674%2814%2901566-9

The sense of agency as tracking control

Does sense of agency (SoA) arise merely from action-outcome associations, or does an additional real-time process track each step along the chain? Tracking control predicts that deviant intermediate steps between action and outcome should reduce SoA. In two experiments, participants learned mappings between two finger actions and two tones. In later test blocks, actions triggered a robot hand moving either the same or a different finger, and also triggered tones, which were congruent or incongruent with the mapping. The perceived delay between actions and tones gave a proxy measure for SoA. Action-tone binding was stronger for congruent than incongruent tones, but only when the robot movement was also congruent. Congruent tones also had reduced N amplitudes, but again only when the robot movement was congruent.We suggest that SoA partly depends on a real time tracking control mechanism, since deviant intermediate action of the robot reduced SoA over the tone

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Incidence of cancer in the area around Amsterdam Airport Schiphol in 1988–2003: a population-based ecological study

BACKGROUND: Amsterdam Airport Schiphol is a major source of complaints about aircraft noise, safety risks and concerns about long term adverse health effects, including cancer. We investigated whether residents of the area around Schiphol are at higher risk of developing cancer than the general Dutch population. METHODS: In a population-based study using the regional cancer registry, we estimated the cancer incidence during 1988–2003 in residents of the area surrounding Schiphol. We defined a study area based on aircraft noise contours and 4-digit postal code areas, since historical data on ambient air pollution were not available and recent emission data did not differ from the background urban air quality. RESULTS: In residents of the study area 13 207 cancer cases were diagnosed, which was close to the expected number, using national incidence rates as a reference (standardized incidence ratio [SIR] 1.02). We found a statistically significantly increased incidence of hematological malignancies (SIR 1.12, 95% confidence interval [CI]: 1.05, 1.19), mainly due to high rates for non-Hodgkin lymphoma (SIR 1.22, 95% CI: 1.12, 1.33) and acute lymphoblastic leukemia (SIR 1.34, 95% CI: 0.95, 1.83). The incidence of cancer of the respiratory system was statistically significantly decreased (SIR 0.94, 95% CI: 0.90, 0.99), due to the low rate in males (SIR 0.89). In the core zone of the study area, cancer incidence was slightly higher than in the remaining ring zone (rate ratio of the core zone compared to the ring zone 1.05, 95% CI 1.01, 1.10). This was caused by the higher incidence of cancer of the respiratory system, prostate and the female genital organs in the core zone in comparison to the ring zone. CONCLUSION: The overall cancer incidence in the Schiphol area was similar to the national incidence. The moderately increased risk of hematological malignancies could not be explained by higher levels of ambient air pollution in the Schiphol area. This observation warrants further research, for example in a study with focus on substances in urban ambient air pollution, as similar findings were observed in Greater Amsterdam

Alcohol Facilitates CD1d Loading, Subsequent Activation of NKT Cells, and Reduces the Incidence of Diabetes in NOD Mice

Background: Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. Methods: The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. Results: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. Conclusion: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases

The relationship between gambling event frequency, motor response inhibition, arousal, and dissociative experience

Speed of play has been identified as a key structural characteristic in gambling behaviour, where games involving higher playing speeds enhance the experience of gambling. Of interest in the present study is the consistent finding that games with higher event frequencies are preferred by problem gamblers and are associated with more negative gambling outcomes, such as difficulty quitting the game and increased monetary loss. The present study investigated the impact of gambling speed of play on executive control functioning, focusing on how increased speeds of play impact motor response inhibition, and the potential mediating role arousal and dissociative experience play in this relationship. Fifty regular non-problem gamblers took part in a repeated-measures experiment where they gambled with real money on a simulated slot machine across five speed of play conditions. Response inhibition was measured using an embedded Go/No-Go task, where participants had to withhold motor responses, rather than operating the spin button on the slot machine when a specific colour cue was present. Results indicated that response inhibition performance was significantly worse during faster speeds of play, and that the role of arousal in this relationship was independent of any motor priming affect. The implications of these findings for gambling legislation and gambling harm-minimisation approaches are discussed