Inhibition of the shade avoidance response by formation of non-DNA binding bHLH heterodimers.

In shade-intolerant plants such as Arabidopsis, a reduction in the red/far-red (R/FR) ratio, indicative of competition from other plants, triggers a suite of responses known as the shade avoidance syndrome (SAS). The phytochrome photoreceptors measure the R/FR ratio and control the SAS. The phytochrome-interacting factors 4 and 5 (PIF4 and PIF5) are stabilized in the shade and are required for a full SAS, whereas the related bHLH factor HFR1 (long hypocotyl in FR light) is transcriptionally induced by shade and inhibits this response. Here we show that HFR1 interacts with PIF4 and PIF5 and limits their capacity to induce the expression of shade marker genes and to promote elongation growth. HFR1 directly inhibits these PIFs by forming non-DNA-binding heterodimers with PIF4 and PIF5. Our data indicate that PIF4 and PIF5 promote SAS by directly binding to G-boxes present in the promoter of shade marker genes, but their action is limited later in the shade when HFR1 accumulates and forms non-DNA-binding heterodimers. This negative feedback loop is important to limit the response of plants to shade.

Need for informed consent in substance use studies--harm of bias?

OBJECTIVE: The aim of this study was to examine the differences between those who gave informed consent to a study on substance use and those who did not, and to analyze whether differences changed with varying nonconsent rates. METHOD: Cross-sectional questionnaire data on demographics, alcohol, smoking, and cannabis use were obtained for 6,099 French- and 5,720 German-speaking 20-year-old Swiss men. Enrollment took place over 11 months for the Cohort Study on Substance Use Risk Factors (C-SURF). Consenters and nonconsenters were asked to complete a short questionnaire. Data for nearly the entire population were available because 94% responded. Weekly differences in consent rates were analyzed. Regressions examined the associations of substance use with consent giving and consent rates and the interaction between the two. RESULTS: Nonconsenters had higher substance use patterns, although they were more often alcohol abstainers; differences were small and not always significant and did not decrease as consent rates increased. CONCLUSIONS: Substance use currently is a minor sensitive topic among young men, resulting in small differences between nonconsenters and consenters. As consent rates increase, additional individuals are similar to those observed at lower consent rates. Estimates of analytical studies looking at associations of substance use with other variables will not differ at reasonable consent rates of 50%-80%. Descriptive prevalence studies may be biased, but only at very low rates of consent.

Unifying Time to Contact Estimation and Collision Avoidance across Species

The -function and the -function are phenomenological models that are widely used in the context of timing interceptive actions and collision avoidance, respectively. Both models were previously considered to be unrelated to each other: is a decreasing function that provides an estimation of time-to-contact (ttc) in the early phase of an object approach; in contrast, has a maximum before ttc. Furthermore, it is not clear how both functions could be implemented at the neuronal level in a biophysically plausible fashion. Here we propose a new framework the corrected modified Tau function capable of predicting both -type ("") and -type ("") responses. The outstanding property of our new framework is its resilience to noise. We show that can be derived from a firing rate equation, and, as , serves to describe the response curves of collision sensitive neurons. Furthermore, we show that predicts the psychophysical performance of subjects determining ttc. Our new framework is thus validated successfully against published and novel experimental data. Within the framework, links between -type and -type neurons are established. Therefore, it could possibly serve as a model for explaining the co-occurrence of such neurons in the brain.

Altruism, spite and choosy females

Natural selection favours the genes which are able to introduce replicates of themselves in the next generation with higher certainty than do rival genes (Hamilton 1963). The fitness of an individual, it?s ability to produce future parents, depends on it?s own behaviour as well as on the behaviour of other individuals in the population. For instance, the intensity of competition an individual experience depends on the exploitation of resources by neighbours. The fitness is thus frequency dependent on what neighbours do. Behaviours can be classified according to the costs and benefits they have on the fitness of the behaver and it?s neighbours (Hamilton 1964, Hamilton 1975). According to this classification there exist four distinct social behaviours. (1) A gene confering the ability to use a new ressource is called selfish because it has a positive e_ect on the bearer of the gene but a negative e_ect on neighbours by the concomitant increase in competition. (2) An altruistic behaviour is defined as an action where an individual increases the fitness of a neighbour at the expense of it?s own. The e_ect is deleterious for the actor but positive for the receptor. (3) More surprinsingly, an individual might sacrifice a fraction of it?s ressources to harm another at no direct benefits. This spitefull behaviour incurs a cost for the actor but is also deleterious for the receptor. (4) Finally a cooperative behaviour breeds benefits for both actors and neighbours. In this thesis I will continue on the path traced by numerous evolutionnary biologist which attempt to fine tune our understanding of the evolution of social behaviours since Hamilton?s foundation (1963, 1964). A critical development over the last 40 years has been the realisation that competition between kin can partly or completely cancel out the role of relatedness as an agent favouring altruism (Wilson et al., 1992; Taylor, 1992a,b). Of importance is thus to determine the scale at which competition and altruism occur. One mechanism avoiding the complete dilution of relatedness by competition is the conditionnal expression of the social behaviors. Focus will be given in this thesis at the role played by di_erent recognition mechanism in paving the way to altruism (Komdeur and Hatchwell, 1999) when the population has a spatial structure. Further, the evolution of spite will also be considered in these settings. The thesis is fractionated into two parts. First, di_erent models promoting altruism cooperation and spite will be compared under the same theoretical umbrella. This is a rather informal and more personnal part of my thesis. It also serve as a justification and basis to "Altruism among kin and non-kin individuals" which is an article attempting to clas- sify the mechanisms leading to altruism and cooperation. Second, in the annexe, there are three research papers about kin selection, altruism and dispersal: "Is sociality driven by the costs of dispersal or the benefits of philopatry?: A role for kin-discrimination mechanism", "Altruism, dispersal and phenotype kin recognition" and "Inbreeding avoidance through kin recognition: choosy female boost male dispersal" this last paper incorporates kin recognition as an agent favoring sex-biased dispersal.

Genome-wide transcriptional responses to shade: Linking shade avoidance and auxin

Plants have the ability to use the composition of incident light as a cue to adapt development and growth to their environment. Arabidopsis thaliana as well as many crops are best adapted to sunny habitats. When subjected to shade, these plants exhibit a variety of physiological responses collectively called shade avoidance syndrome (SAS). It includes increased growth of hypocotyl and petioles, decreased growth rate of cotyledons and reduced branching and crop yield. These responses are mainly mediated by phytochrome photoreceptors, which exist either in an active, far-red light (FR) absorbing or an inactive, red light (R) absorbing isoform. In direct sunlight, the R to FR light (R/FR) ratio is high and converts the phytochromes into their physiologically active state. The phytochromes interact with downstream transcription factors such as PHYTOCHROME INTERACTING FACTOR (PIF), which are subsequently degraded. Light filtered through a canopy is strongly depleted in R, which result in a low R/FR ratio and renders the phytochromes inactive. Protein levels of downstream transcription factors are stabilized, which initiates the expression of shade-induced genes such as HFR1, PIL1 or ATHB-2. In my thesis, I investigated transcriptional responses mediated by the SAS in whole Arabidopsis seedlings. Using microarray and chromatin immunoprecipitation data, we identified genome-wide PIF4 and PIF5 dependent shade regulated gene as well as putative direct target genes of PIF5. This revealed evidence for a direct regulatory link between phytochrome signaling and the growth promoting phytohormone auxin (IAA) at the level of biosynthesis, transport and signaling. Subsequently, it was shown, that free-IAA levels are upregulated in response to shade. It is assumed that shade-induced auxin production takes predominantly place in cotyledons of seedlings. This implies, that IAA is subsequently transported basipetally to the hypocotyl and enhances elongation growth. The importance of auxin transport for growth responses has been established by chemical and genetic approaches. To gain a better understanding of spatio-temporal transcriptional regulation of shade-induce auxin, I generated in a second project, an organ specific high throughput data focusing on cotyledon and hypocotyl of young Arabidopsis seedlings. Interestingly, both organs show an opposite growth regulation by shade. I first investigated the spatio-transcriptional regulation of auxin re- sponsive gene, in order to determine how broad gene expression pattern can be explained by the hypothesized movement of auxin from cotyledons to hypocotyls in shade. The analysis suggests, that several genes are indeed regulated according to our prediction and others are regulated in a more complex manner. In addition, analysis of gene families of auxin biosynthetic and transport components, lead to the identification of essential family members for shade-induced growth re- sponses, which were subsequently experimentally confirmed. Finally, the analysis of expression pattern identified several candidate genes, which possibly explain aspects of the opposite growth response of the different organs.

Climate Change, Neutrality and the Harm Principle

This paper aims at evaluating the compatibility of coercive climate policies with liberal neutrality. More precisely, it focuses on the doctrine of state neutrality as associated with the "harm principle". It argues that given the difficulty of attributing causal responsibilities for climate harms to individuals, the harm principle doesn't work in this case, at least if one endorses a liberal atomistic ontology. Furthermore, the definition of what constitutes climate harms implies making moral assumptions, which makes it impossible to justify climate policies in a neutral way. Finally, the paper shows another consequence of applying neutrality to the case of climate change, that is the risk of a shift from political forms of decision-making to technocracy. Focusing too much on liberty of choice may (paradoxically) be to the detriment of political freedom. The paper concludes that climate change is an intrinsically moral issue and that it should be the occasion of a political debate about our current values and lifestyles. It should not be reduced to a mere question of carbon metric.

Posttraumatic stress avoidance symptoms as mediators in the development of alcohol use disorders after exposure to childhood sexual abuse in a Swiss community sample.

This study examined the role of posttraumatic stress disorder (PTSD) symptoms of re-experience, avoidance, and hyperarousal in the relationship between different types of trauma and alcohol use disorders (AUD). We used data from 731 trauma-exposed individuals who participated in the first wave of the PsyCoLaus-study. Trauma characteristics were assessed relatively to the occurrence of lifetime PTSD symptoms and AUD. The results suggest that lifetime and childhood sexual abuse as well as overall childhood trauma were directly linked to AUD and PTSD symptoms, in particular to avoidance symptoms. From single symptom clusters PTSD avoidance was found to specifically mediate the trauma-AUD pathway. Both childhood and sexual trauma strongly contribute to the comorbidity of PTSD and AUD and avoidance-type symptoms appear to play a central role in maintaining this association. Hence, the alleviation of avoidance symptoms might be an important target for therapeutic intervention among victims of sexual abuse before specific addiction treatment is initiated.

Posttraumatic stress avoidance symptoms as mediators in the development of alcohol use disorders after exposure to childhood sexual abuse in a Swiss community sample.

This study examined the role of posttraumatic stress disorder (PTSD) symptoms of re-experience, avoidance, and hyperarousal in the relationship between different types of trauma and alcohol use disorders (AUD). We used data from 731 trauma-exposed individuals who participated in the first wave of the PsyCoLaus-study. Trauma characteristics were assessed relatively to the occurrence of lifetime PTSD symptoms and AUD. The results suggest that lifetime and childhood sexual abuse as well as overall childhood trauma were directly linked to AUD and PTSD symptoms, in particular to avoidance symptoms. From single symptom clusters PTSD avoidance was found to specifically mediate the trauma-AUD pathway. Both childhood and sexual trauma strongly contribute to the comorbidity of PTSD and AUD and avoidance-type symptoms appear to play a central role in maintaining this association. Hence, the alleviation of avoidance symptoms might be an important target for therapeutic intervention among victims of sexual abuse before specific addiction treatment is initiated.

Incendiaires et pyromanes [Arson and pyromania, update 2015].

While the fire constitutes a threat and provokes avoidance by the entire animal world, its control as lighting and maintenance is inseparable from the history of humankind. For 1% of the population that use is turned to harm, repeatedly and without objective reason, responding to the historical definition of pyromania. The profile of arsonists does not appear to be different from that of the general criminal population: alcohol abuse, nicotine, marijuana and antisocial personality do not make fire setters a special case. However positive fire experience lived in childhood, emotional avoidance and expertise in fire settings' control seems to be specific, as recidivism risk below that of the general criminal population.

Unifying Time to Contact Estimation and Collision Avoidance across Species

The -function and the -function are phenomenological models that are widely used in the context of timing interceptive actions and collision avoidance, respectively. Both models were previously considered to be unrelated to each other: is a decreasing function that provides an estimation of time-to-contact (ttc) in the early phase of an object approach; in contrast, has a maximum before ttc. Furthermore, it is not clear how both functions could be implemented at the neuronal level in a biophysically plausible fashion. Here we propose a new framework- the corrected modified Tau function- capable of predicting both -type ("") and -type ("") responses. The outstanding property of our new framework is its resilience to noise. We show that can be derived from a firing rate equation, and, as , serves to describe the response curves of collision sensitive neurons. Furthermore, we show that predicts the psychophysical performance of subjects determining ttc. Our new framework is thus validated successfully against published and novel experimental data. Within the framework, links between -type and -type neurons are established. Therefore, it could possibly serve as a model for explaining the co-occurrence of such neurons in the brain.

Drinking locations and alcohol-related harm: Cross-sectional and longitudinal associations in a sample of young Swiss men.

BACKGROUND: Alcohol consumption--in particular drinking volume (DV) and risky single occasion drinking (RSOD)--has been related to a wide range of negative consequences and health problems. Previous studies also suggested that drinking in certain locations may be more strongly associated with the occurrence of alcohol-related harm than drinking in others. However, they were conducted in countries culturally and legally different from European countries and were limited to cross-sectional designs. This study investigates the cross-sectional and longitudinal associations of alcohol-related harm with DVs in different locations in a sample of young Swiss men. METHODS: A representative sample of 4536 young Swiss male drinkers completed baseline and 15-month follow-up questionnaires. These assessed DVs in 11 locations, alcohol-related harm (i.e. number of alcohol-related consequences and alcohol use disorder criteria) and frequency of RSOD. Cross-sectional and longitudinal associations of alcohol-related harm with DVs in each location were tested using regression models, with and without adjustment for frequency of RSOD. RESULTS: Both cross-sectional and longitudinal analyses showed significant positive associations between alcohol-related harm and DVs at friends' homes, in discos/nightclubs and in outdoor public places, when controlling for frequency of RSOD. In contrast, the contribution of DVs at one's own home and in restaurants was consistently not significant when adjusted for frequency of RSOD. When controlling for RSOD, associations between alcohol-related harm and DVs in bars/pubs, when playing sports, during other leisure activities, at cinemas/theatres, during sporting events, and during special events were not consistent between cross-sectional and longitudinal analyses. CONCLUSION: Results suggest that prevention interventions should not only target reducing the overall volume of alcohol consumed and the frequency of RSOD in general, but they should additionally focus on limiting alcohol consumption in outdoor public places, discos/nightclubs, and in friends' homes in particular, or at least on preventing harm occurring in these occasions.

The harm principle and the greatest happiness principle: the missing link

In this article I present a possible solution for the classic problem of the apparent incompatibility between Mill's Greatest Happiness Principle and his Principle of Liberty arguing that in the other-regarding sphere the judgments of experience and knowledge accumulated through history have moral and legal force, whilst in the self-regarding sphere the judgments of the experienced people only have prudential value and the reason for this is the idea according to which each of us is a better judge than anyone else to decide what causes us pain and which kind of pleasure we prefer (the so-called epistemological argument). Considering that the Greatest Happiness Principle is nothing but the aggregate of each person's happiness, given the epistemological claim we conclude that, by leaving people free even to cause harm to themselves, we still would be maximizing happiness, so both principles (the Greatest Happiness Principle and the Principle of Liberty) could be compatible.

Long-lasting mnemotropic effect of substance P and its N-terminal fragment (SP1-7) on avoidance learning

We investigated the long-lasting effect of peripheral injection of the neuropeptide substance P (SP) and of some N- or C-terminal SP fragments (SPN and SPC, respectively) on retention test performance of avoidance learning. Male Wistar rats (220 to 280 g) were trained in an inhibitory step-down avoidance task and tested 24 h or 21 days later. Immediately after the training trial rats received an intraperitoneal injection of SP (50 µg/kg), SPN 1-7 (167 µg/kg) or SPC 7-11 (134 µg/kg). Control groups were injected with vehicle or SP 5 h after the training trial. The immediate post-training administration of SP and SPN, but not SPC, facilitated avoidance behavior in rats tested 24 h or 21 days later, i.e., the retention test latencies of the SP and SPN groups were significantly longer (P<0.05, Mann-Whitney U-test) during both training-test intervals. These observations suggest that the memory-enhancing effect of SP is long-lasting and that the amino acid sequence responsible for this effect is encoded by its N-terminal part

Involvement of hippocampal AMPA glutamate receptor changes and the cAMP/protein kinase A/CREB-P signalling pathway in memory consolidation of an avoidance task in rats

Training in step-down inhibitory avoidance (0.3-mA footshock) is followed by biochemical changes in rat hippocampus that strongly suggest an involvement of quantitative changes in glutamate AMPA receptors, followed by changes in the dopamine D1 receptor/cAMP/protein kinase A (PKA)/CREB-P signalling pathway in memory consolidation. AMPA binding to its receptor and levels of the AMPA receptor-specific subunit GluR1 increase in the hippocampus within the first 3 h after training (20-70%). Binding of the specific D1 receptor ligand, SCH23390, and cAMP levels increase within 3 or 6 h after training (30-100%). PKA activity and CREB-P levels show two peaks: a 35-40% increase 0 h after training, and a second increase 3-6 h later (35-60%). The results correlate with pharmacological findings showing an early post-training involvement of AMPA receptors, and a late involvement of the D1/cAMP/PKA/CREB-P pathway in memory consolidation of this task