Moral enhancement,at the peak of pharmacology and at the limit of ethics

The debate over the improvement of moral capacity or moral enhancement through pharmacology has gained momentum in the last decade as a result of advances in neuroscience. These advances have led to the discovery and allowed the alteration of patterns of human behavior, and have permitted direct interventions on the neuronal structure of behavior. In recent years, this analysis has deepened regarding the anthropological foundations of morality and the reasons that would justify the acceptance or rejection of such technology. We present a review of proposals for pharmacological interventions directed directly towards moral enhancement. In addition, we identify the ethical dilemmas that such interventions may generate, as well as the moral assessment of the authors of these studies. There is a moderate consensus on the risks of any intervention on the intimate structure of the human condition, its autonomy and identity, but there are large differences in explaining the reasons for this concern and especially in justifying such interventions. These findings show that it is necessary to investigate the moral assessment of authors and the ethical dimension within the field of pharmacology in order to identify future trends.     

Evolution of Mycosphaerella graminicola at the wheat leaf level and at the field level

Evolution of M. graminicola wheat field populations from a given French county (Morbihan, 56) between years 2005 and 2006 was investigated for thirty seven strains using molecular fingerprinting by microsatellite markers (ST1A4, ST1E3, ST1E7, and ST1D7), and SSCP analysis study of partial actin and beta-tubulin encoding sequences. In addition, twenty nine strains collected from 3 distinct lesions on a same wheat leaf in 2006 in another French county (Nord, 59) were also investigated for genetic diversity. At the field level, we observed similar gene diversity in the 2005 and in the 2006 populations, with no common clones between the two years. This indicates frequent sexual recombination undergone by the fungus. When considering each marker independently and comparing genetic variability of the two populations, we noticed a decrease in genetic variability of the 2006 strains for three of them (ST1A4, ST1D7 and the partial sequence of actin) and an increase for ST1E3, ST1E7 and the partial sequence of beta-tubulin, revealing the importance of the chosen markers. At the lesion level, 69% of the studied strains were haplotypes with 31% of the clonal population found in 2 lesions out of 3. This suggests that at least parts of the lesions were formed after asexual reproduction and dissemination of pycnidiospores by splashing. We also confirmed the exploitative competition that exists between the strains at the lesion level.     

Switching and signaling at the telomere

This review describes the structure of telomeres, the protective DNA-protein complexes at eukaryotic chromosomal ends, and several molecular mechanisms involved in telomere functions. Also discussed are cellular responses to compromising the functions of telomeres and of telomerase, which synthesizes telomeric DNA.     

Cooperation and Defection at the Crossroads

We study a simple traffic model with a non-signalized road intersection. In this model the car arriving from the right has precedence. The vehicle dynamics far from the crossing are governed by the rules introduced by Nagel and Paczuski, which define how drivers behave when braking or accelerating. We measure the average velocity of the ensemble of cars and its flow as a function of the density of cars on the roadway. An additional set of rules is defined to describe the dynamics at the intersection assuming a fraction of drivers that do not obey the rule of precedence. This problem is treated within a game-theory framework, where the drivers that obey the rule are cooperators and those who ignore it are defectors. We study the consequences of these behaviors as a function of the fraction of cooperators and defectors. The results show that cooperation is the best strategy because it maximizes the flow of vehicles and minimizes the number of accidents. A rather paradoxical effect is observed: for any percentage of defectors the number of accidents is larger when the density of cars is low because of the higher average velocity.     

Being at the right place at the right time

I am tremendously honored to receive the 2012 Women in Cell Biology Junior Award. In this essay, I recount my career path over the past 15 years. Although many details are specific to my own experiences, I hope that some generalizations can be made to encourage more women to pursue independent scientific careers. Mine is a story of choosing a captivating question, making the most of your opportunities, and finding a balance with life outside the lab.It is a great honor to have been awarded the 2012 Women in Cell Biology Junior Award from the ASCB. Looking back at the 15 years I have spent doing research in cell biology, my overwhelming feeling is that it has been and still is a lot of fun. I am extremely fortunate to have a job that I truly enjoy and that gives me complete intellectual freedom. My lab choices over the years were motivated by scientific curiosity and enthusiasm for new environments and topics, rather than by career building. It is thus truly amazing to be rewarded for (rather a lot of) work enjoyed.     

Relationship between the behaviour of sows at 6 months old and the behaviour and performance at farrowing

Piglet crushing remains a major problem in pig production. Reduced crushing might be obtained through genetic selection on sow behavioural traits. The aim of the study was to assess the relationship between behavioural responses at 6 months of age, around farrowing, and sows' reproductive performance including crushing levels. At 6 months of age, behavioural responses of 75 nulliparous sows were observed both during behavioural tests to human presence and to the presence of a novel object in their home pen, and their responses when placed in a weighing device. At first farrowing, nervousness of the sows was observed when placed in the farrowing crate 1 week before and the day of farrowing, as well as their fear responses when approached by a human from behind or at the front of the farrowing crate. At 6 months of age, escape from a human tended to be correlated with the reactivity in the weighing device (rs = 0.21, P = 0.09). Around first farrowing, the withdrawal reaction when a human approached at the front was correlated with the fear response when approached from behind and the nervousness of the sow in the crate (rs = 0.29, P < 0.05; rs = 0.37, P < 0.01). The fear response when approached from behind was correlated with nervousness in the crate and around farrowing (rs = 0.70, P < 0.001; rs = 0.25, P < 0.05), and nervousness in the crate was significantly correlated with the nervousness around farrowing (rs = 0.34, P < 0.01). The escape from a human at 6 months was correlated with withdrawal when approached from the front before farrowing (rs = 0.38, P < 0.01) and with nervousness of the sow in the crate (rs = 0.24, P < 0.05). The number of piglets crushed at first farrowing was correlated with the latency to approach a novel object at 6 months and nervousness around farrowing (rs = -0.27, P < 0.05; rs = 0.28, P < 0.05), and tended to be correlated with the escape behaviour from human at 6 months and withdrawal away from human presence before farrowing (rs = 0.21, P = 0.09; rs = 0.22, P = 0.08). These results suggest that behavioural responses to humans and during management practices of nulliparous sows at 6 months of age are, to some extent, related with their behaviour around farrowing and crushing levels of piglets at farrowing.     

To be at the right place at the right time

Diagnosing Alzheimer's disease through MRI neuroimaging biomarkers has been used as a complementary marker for traditional clinical markers to improve diagnostic accuracy and also help in developing new pharmacotherapeutic trials. It has been revealed that longitudinal analysis of the whole brain atrophy has the power of discriminating Alzheimer's disease and elderly normal controls. In this work, effect of involving intermediate atrophy rates and impact of using uncorrelated principal components of these features instead of original ones on discriminating normal controls and Alzheimer's disease subjects, is inspected. In fact, linear discriminative analysis of atrophy rates is used to classify subjects into Alzheimer's disease and controls. Leave-one-out cross-validation has been adopted to evaluate the generalization rate of the classifier along with its memorization. Results show that incorporating uncorrelated version of intermediate features leads to the same memorization performance as the original ones but higher generalization rate. As a conclusion, it is revealed that in a longitudinal study, using intermediate MRI scans and transferring them to an uncorrelated feature space can improve diagnostic accuracy.     

Flies at the Farm: Drosophila at Janelia

On August 1, 2006 the Howard Hughes Medical Institute’s first stand-alone research campus opened at Janelia Farm, near Washington DC. Our mission at Janelia is to do exceptional fundamental research. Our two scientific foci are to understand the function of neural circuits and to develop synergistic imaging technologies. To achieve this we have changed many of the conventions of academic and/or industrial science. The founding director at Janelia is the well-known Drosophilist Gerry Rubin, who has been a central figure in fly molecular, developmental and genomic biology in recent decades. Not coincidentally, we at Janelia fully appreciate the potential of flies to contribute to an understanding of neuronal circuits. Our objectives are ambitious, and in the first ten months of operations at Janelia we have made some good beginnings which I will describe below.     

Flies at the farm: Drosophila at Janelia

On August 1, 2006 the Howard Hughes Medical Institute's first stand-alone research campus opened at Janelia Farm, near Washington DC. Our mission at Janelia is to do exceptional fundamental research. Our two scientific foci are to understand the function of neural circuits and to develop synergistic imaging technologies. To achieve this we have changed many of the conventions of academic and/or industrial science. The founding director at Janelia is the well-known Drosophilist Gerry Rubin, who has been a central figure in fly molecular, developmental and genomic biology in recent decades. Not coincidentally, we at Janelia fully appreciate the potential of flies to contribute to an understanding of neuronal circuits. Our objectives are ambitious, and in the first ten months of operations at Janelia we have made some good beginnings.     

Gene Conversion and Intragenic Recombination at at the SUP6 Locus and the Surrounding Region in SACCHAROMYCES CEREVISIAE

Spontaneous secondary mutations of the ochre suppressor SUP6 were selected in a haploid strain of Saccharomyces cerevisiae . Unselected tetrads were dissected from crosses heterozygous for one of three alleles of SUP6 and for three other loci in this region which span a length of 14 map units (his2, cdc14 and met10). The study showed that all of these markers were characterized by high frequency of meiotic gene conversion and long conversion lengths which frequently extended into adjacent marked loci. Despite the high conversion frequency of SUP6 , recombination between alleles of this locus reached a maximum frequency of only 2 x 10^-3 prototrophs/spore. Although the allelic recombination frequencies were not distance dependent and consequently could not be used to order the alleles, the inequality between the two recombinant outside marker combinations among selected intragenic recombinants produced an internally consistent map of the suppressor locus. Recombination at SUP6 (whether detected as conversion in tetrads or the production of recombinants among random spores) was accompanied by significantly less than 50% outside marker recombination.