Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death.

Apoptosis is a normal component of the development and health of multicellular organisms. However, apoptosis is now considered a prerogative of unicellular organisms, including the trypanosomatids of the genera Trypanosoma spp. and Leishmania spp., causative agents of some of the most important neglected human diseases. Trypanosomatids show typical hallmarks of apoptosis, although they lack some of the key molecules contributing to this process in metazoans, like caspase genes, Bcl-2 family genes and the TNF-related family of receptors. Despite the lack of these molecules, trypanosomatids appear to have the basic machinery to commit suicide. The components of the apoptotic execution machinery of these parasites are slowly coming into light, by targeting essential processes and pathways with different apoptogenic agents and inhibitors. This review will be confined to the events known to drive trypanosomatid parasites to apoptosis.

Intrinsically photosensitive retinal ganglion cells.

The recent discovery of melanopsin-expressing retinal ganglion cells that mediate the pupil light reflex has provided new insights into how the pupil responds to different properties of light. These ganglion cells are unique in their ability to transduce light into electrical energy. There are parallels between the electrophysiologic behavior of these cells in primates and the clinical pupil response to chromatic stimuli. Under photopic conditions, a red light stimulus produces a pupil constriction mediated predominantly by cone input via trans-synaptic activation of melanopsin-expressing retinal ganglion cells, whereas a blue light stimulus at high intensity produces a steady-state pupil constriction mediated primarily by direct intrinsic photoactivation of the melanopsin-expressing ganglion cells. Preliminary data in humans suggest that under photopic conditions, cones primarily drive the transient phase of the pupil light reflex, whereas intrinsic activation of the melanopsin-expressing ganglion cells contributes heavily to sustained pupil constriction. The use of chromatic light stimuli to elicit transient and sustained pupil light reflexes may become a clinical pupil test that allows differentiation between disorders affecting photoreceptors and those affecting retinal ganglion cells.

Alteration in neuromuscular function after a 5 km running time trial

The aim of this study was to characterize the effect of a 5 km running time trial on the neuromuscular properties of the plantar flexors. Eleven well-trained triathletes performed a series of neuromuscular tests before and immediately after the run on a 200 m indoor track. Muscle activation (twitch interpolation) and normalized EMG activity were assessed during maximal voluntary contraction (MVC) of plantar flexors. Maximal soleus H-reflexes and M-waves were evoked at rest (i.e. H (MAX) and M (MAX), respectively) and during MVC (i.e. H (SUP) and M (SUP), respectively). MVC significantly declined (-27%; P < 0.001) after the run, due to decrease in muscle activation (-8%; P < 0.05) and M (MAX)-normalized EMG activity (-13%; P < 0.05). Significant reductions in M-wave amplitudes (M (MAX): -13% and M (SUP): -16%; P < 0.05) as well as H (MAX)/M (MAX) (-37%; P < 0.01) and H (SUP)/M (SUP) (-25%; P < 0.05) ratios occurred with fatigue. Following exercise, the single twitch was characterized by lower peak torque (-16%; P < 0.001) as well as shorter contraction (-19%; P < 0.001) and half-relaxation (-24%; P < 0.001) times. In conclusion, the reduction in plantar flexors strength induced by a 5 km running time trial is caused by peripheral adjustments, which are attributable to a failure of the neuromuscular transmission and excitation-contraction coupling. Fatigue also decreased the magnitude of efferent motor outflow from spinal motor neurons to the plantar flexors and part of this suboptimal neural drive is the result of an inhibition of soleus motoneuron pool reflex excitability.

The ATPase activity of RecA is needed to push the DNA strand exchange through heterologous regions.

The role of ATP hydrolysis during the RecA-mediated recombination reaction is addressed in this paper. Recent studies indicated that the RecA-promoted DNA strand exchange between completely homologous double- and single-stranded DNA can be very efficient in the absence of ATP hydrolysis. In this work we demonstrate that the energy derived from the ATP hydrolysis is strictly needed to drive the DNA strand exchange through the regions where the interacting DNA molecules are not in a homologous register. Therefore, in addition to the role of the ATP hydrolysis in promoting the dissociation of RecA from the products of the recombination reaction, as described earlier, ATP hydrolysis also plays a crucial role in the actual process of strand exchange, provided that the lack of homologous register obstructs the process of branch migration.

Genetic and environmental effects on early life-history traits in salmonids

Les changements environnementaux, tels la température ou les maladies infectieuses, peuvent influencer l'évolution en induisant de la sélection, mais ceci à la seule condition qu'il y ait assez de diversité génétique pour les traits en question ou pour l'expression plastique de ces traits. Au cours cette thèse, nous avons étudié l'effet de potentielles pressions environnementales sur différents phénotypes de trois représentants des sous familles des salmonidés: l'ombre commun (Thymallus thymallus; Thymallinae), la truite de rivière {Salmo trutta; Salmoninae) et le corégone Coregonus palaea (Coregoninae). Les salmonidés se prêtent particulièrement bien à ce type d'expériences car étant hautement sensibles aux conditions environnementales, ils montrent une large variabilité dans leurs traits morphologiques, comportementaux ainsi que d'histoire de vie, tout en bénéficiant d'un large intérêt général. Nous avons testé si le sexe de l'ombre commun pouvait être modifié par la température, ce qui pourrait ainsi expliquer un changement abrupte de sex ratio observé dans l'une des plus grandes populations de Suisse. Nous n'avons trouvé aucun indice permettant de conclure que la température puisse induire ce changement chez l'ombre commun ou chez la truite de rivière. De plus nous avons étudié la plasticité de développement ainsi que d'éclosion, et avons observé des différences entre familles ainsi qu'entre populations. Alors que ces différences comportementales entre populations suggéraient une adaptation aux conditions environnementales locales, cette prédiction n'a pas été confirmée par une expérience de transplantation réciproque d'embryons entre cinq rivières de la même région. Cette étude a montré que les embryons ne survivaient pas mieux dans leur rivière d'origine, indiquant donc une absence d'adaptation locale. Nous avons aussi montré que la mortalité embryonnaire était influencée autant par des "bons gènes" que par des "gènes compatibles", que la qualité des mâles pouvait être signalée par leur coloration, et que le fait d'élever des poissons dans une pisciculture pouvait aboutir a des relations contre-intuitives entre la coloration des mâles et la qualité de leur jeunes. Nos résultats contribuent ainsi à une meilleure compréhension de l'effet de diverses pressions environnementales sur la morphologie, le comportement ou les traits d'histoire de vie chez les salmonidés. - Environmental changes, such as changes in temperatures or infection levels, can induce selection and drive evolution if there is sufficient genetic variation for the traits or the plasticity in trait expression. In this thesis, we investigated the influence of potential environmental stressors on various phenotypes in representatives of the three salmonid subfamilies: the European grayling (Thymallus thymallus; Thymallinae), the brown trout (,Salmo trutta; Salmoninae), and the whitefish Coregonus palaea (Coregoninae). Salmonids are ideal study species, as they seem sensitive to changing environmental conditions, show considerable variability in morphological, behavioral, and life history traits, and are of broad public interest. We investigated whether temperature-induced sex reversal could explain the sex-ratio distortion found in one of Switzerland's largest grayling populations. We found no evidence of temperature-induced sex reversal in either graylings or brown trout. We also examined plasticity in embryo development and the timing of hatching. We found variation at the level of family and population. Although behavioral differences between populations suggested adaptation to local environmental conditions, no indications of local adaptation could be found in reciprocal transplant experiments carried out over five rivers in the same region. We also demonstrate that embryo development and viability is influenced by 'good genes' and 'compatible genes', that the genetic quality of sires can be signaled by their grey coloration, and that raising larvae in a hatchery environment can produce counter-intuitive relationships between male phenotypes and offspring viability. Our results contribute to the understanding of how changing environmental conditions affect the phenotypes and the heritability of early life-history traits in salmonids.

Driving under the influence of cocaine or therapeutic administration of cocaine?

Introduction: In forensic toxicology, cocaine is better known for its powerful stimulating effects of nervous system and its high potential for recreational abuse, than for his therapeutic use. However, cocaine is still use as a topical anesthetic and peripheral vasoconstrictor in surgeries of eye, ear, nose and throat. Last decade, an increase of the presence of cocaine and metabolites in blood samples of drivers suspected to drive under the influence of drugs (DUID) was observed in Switzerland (Augsburger et al., Forensic Sci Int 153 (2005) 11-15; Senna et al., Forensic Sci Int 198 (2010) 11-16). Observed blood concentration ranges of cocaine and benzoylecgonine were 10-925 μg/L and 20-5200 μg/L, respectively. Since 2005, zero-tolerance approach was introduced in the Swiss legislation for different substances, especially cocaine (analytical cutoff: 15 μg/L). Thus, the interpretation often amounts to determine if the concentration is situated above or under the limit. However, it is important for the interpretation to take into account the context and to be critical with the obtained results, at the risk of ending in erroneous conclusions. Methods: Systematical toxicological analyses were performed on blood and urine, if available, for 5 DUID cases, as already published (Augsburger et al., Forensic Sci Int 153 (2005)). Positive results were confirmed and drugs were quantified in biological samples by GCMS, GC-MS/MS or LC-MS/MS. Results: Administration of cocaine after traffic accident was identified in five cases. All people were admitted to the emergency room because of severe trauma. Maxillofacial surgery was done shortly after admission to the emergency room, involving use of nasal application of cocaine (swab). For all cases, use of cocaine swab was not mentioned in the document filled by the police and by medical staff requested for blood and urine sampling. The information was obtained retrospectively after consultation of the medical records, without precise indication of the application time or dose. Case 1. A 83-year old man (pedestrian) was hit by a car. Blood (+11h after the accident): cocaine (16 μg/L), benzoylecgonine (370 μg/L). Urine: cocaine (1700 μg/L), benzoylecgonine (560 μg/L). Case 2. A 84-year old woman (pedestrian) was hit by a car. Blood (+1.5h after the accident): cocaine (230 μg/L), benzoylecgonine (370 μg/L). Urine was not available. Hair (+4 months after the accident): segment 1 (0-2 cm), cocaine not detected; segment 2 (2-4 cm), cocaine: <0.5 ng/mg. Case 3. A 66-year old man was involved in a car/car accident. He died 2 hours and 5 minutes after the crash. Blood (+1.5h after the accident): cocaine and metabolites not detected. Blood (+2h after the accident): cocaine (1750 μg/L), benzoylecgonine (460 μg/L). Blood (post-mortem): cocaine (370 μg/L), benzoylecgonine (200 μg/L). Urine (+1.5h after the accident): cocaine not detected. Case 4. A 57-year old woman on a motor scooter was hit by a car. She died 2 hours and 10 minutes after the crash. Blood (+0.5h after the accident): cocaine and metabolites not detected. Urine (post-mortem): cocaine (<20 μg/L), benzoylecgonine (120 μg/L). Case 5. A 30-year old man was involved in a car accident. Blood (+4h after the accident): cocaine (29 μg/L), benzoylecgonine (< 20 μg/L). Urine (+4h after the accident): cocaine and metabolites not detected. Ethanol (1,32 g/kg) and cannabinoids (THC (2,0 μg/L), THCCOOH (38 μg/L)) were also detected in blood. Conclusion: To our knowledge, this is the first description of DUID cases involving therapeutic use of cocaine after an accident. These results indicate that even if a per se law is effective for prosecution case of DUID, a critical interpretation of the results is always needed, especially if a medical intervention occurs after an accident.

Social Dynamics in Paper Wasps: The case of nest-drifting in Polistes canadensis

Le passage de la vie solitaire à la vie sociale représente une des principales transitions évolutives. La socialité a évolué au sein de plusieurs taxons du règne animal et notamment chez les insectes sociaux qui ont atteint son niveau le plus élevé : l'eusocialité. Les colonies d'insectes sociaux se composent d'une reine, qui monopolise la reproduction, et d'ouvrières, non-reproductrices ou parfois stériles, qui aident à élever la descendance de la reine. Selon la théorie de la sélection de parentèle, les ouvrières augmentent leur fitness (succès reproducteur) non pas à travers leur propre progéniture, mais en aidant des individus apparentés (leur reine) à produire davantage de descendants. Cette théorie prédit ainsi que les ouvrières ont un intérêt à rester fidèles à leur nid natal. Toutefois, chez la guêpe tropicale Polistes canadensis, de nombreuse ouvrières visitent d'autres nids que leur nid natal : un phénomène appelé « dérive des ouvrières ». Le but de ce doctorat est ainsi de mieux comprendre les mécanismes impliqués dans ce comportement particulier des ouvrières ainsi que ces implications pour la théorie de la sélection de parentèle. Nous avons examiné le comportement de dérive des ouvrières à travers une étude des dynamiques sociales chez la guêpe tropicale P. canadensis. Mes résultats montrent que les populations de P. canadensis se composent en différentes agrégations de nids. Malgré de précédentes suggestions, on n'observe qu'une faible viscosité génétique au sein des populations de P. canadensis étudiées. On retrouve toutefois un degré d'apparentement entre nids d'une même agrégation. Ceci suggère que les ouvrières dériveuses sont susceptibles de bénéficier de fitness indirect en aidant les nids proches géographiquement. De plus, ces échanges d'ouvrières ne semblent pas accidentels puisque l'on constate des variations de taux de dérive et puisque les déplacements observés entre nids persistent sur plusieurs périodes de temps. La charge de travail, qui correspond aux différences d'effort de fourragement entre nid visités et natals, est décrite dans notre étude comme potentiel facteur expliquant le comportement de dérive des ouvrières chez P. canadensis. Nos expériences de retrait d'ouvrières et de couvain ont révélées que les dériveuses ne semblent pas répondre aux changements de besoins en aide des nids visités. Les ouvrières dériveuses biaisent leur effort en aidant leur propre nid, par lequel elles bénéficient le plus en termes de fitness indirect, avant de se consacrer à tout autre nid. Dans l'ensemble, ces résultats sur la dérive des ouvrières chez P. canadensis sont cohérents et suggèrent que ce comportement est une importante stratégie de reproduction alternative chez cette espèce qui contribue à la fitness indirecte de ces ouvrières non-reproductrices. De plus, ce doctorat apporte des informations sur la structure génétique des populations de guêpes Polistes et décrit le rôle des ouvrières inactives. Celles-ci semblent servir de réserve en ouvrières apportant du support à la colonie dans l'éventualité d'une perte d'individus. Plus généralement, ce travail met l'accent sur l'organisation complexe et l'adaptabilité des individus dans les sociétés d'insectes. - One major transition in evolution is the shift from solitary to social life. Sociality has evolved in a few taxa of the animal kingdom, most notably in the social insects which have achieved the highest level of sociality: eusociality. Colonies of social insects are formed by a reproductive queen, and many non-reproductive or sterile workers who help raise their mother queen's offspring. Kin selection theory explains worker behaviour in terms of the indirect fitness they gain from raising non-offspring kin. It therefore predicts that workers should stay faithful to their natal nests, to which they are the more related. However, in the tropical paper wasps Polistes canadensis, high levels of nest-drifting, whereby workers spend time on other neighbouring nests, has been reported. This PhD aimed at understanding the mechanisms involved in this peculiar behaviour as well as its implications for kin selection theory. I examined nest-drifting through the study of the social dynamics of the tropical paper wasp P. canadensis. My results showed that populations of this species of paper wasps are composed of different aggregations of nests. The studied populations showed little limited dispersal (viscosity), despite previous suggestion, but nests within these aggregations were more related to each other than nests outside of aggregations. This suggested that drifters may benefit from indirect fitness when helping on neighbouring nests. Drifting was unlikely to be accidental since we found drifting patterns at various rates and consistently over several time periods during monitoring. Workload (differences in colony-level foraging effort) was also a potential factor explaining nest-drifting in P. canadensis. Worker and brood removal experiments revealed that drifters do not respond to any changes in the need for help in the non-natal nests they visit. Drifters thus bias their help in their natal nests, from which they may benefit the most in terms of indirect fitness, before investing in others. Altogether, these results on nest-drifting in P. canadensis are consistent and suggest that nest-drifting is an important alternative reproductive strategy, contributing to the indirect fitness benefits gained by non-reproductive wasps. Additionally, this PhD provides information on the genetic structure of paper wasps' populations and demonstrates the role of inactive or lazy wasps as a "reserve worker force", which provides resilience to the colony in the event of worker mortality. More generally, this work further highlights the complex organization and adaptability of individuals in insect societies.

Cellules souches cancéreuses et futures modalités thérapeutiques du cancer. [Cancer stem cells and future therapeutic implications].

A growing body of evidence indicates that a subpopulation of tumor cells, the so-called cancer stem cells (CSCs), drive tumor growth and metastasis and preclude therapy efficiency. CSCs have been isolated in virtually all type of tumors. These findings may have important consequences for clinical prognostic. Current cancer research aims to unravel the CSCs' unique biological mechanisms. The development of new CSCs-targeted treatments shed therefore new hopes in improving cancer therapy.

Histoires de vie, témoignages, autobiographies de terrain : formes d'énonciation et de textualisation

Dans ce volume collectif, des anthropologues, des historiens et des linguistes s'interrogent, à partir de leur point de vue respectif, sur la relation entre "observateur" et "observé" quand celle-ci est basée sur la collecte, la mise en forme et l'analyse d'un type particulier de documents : les histoires de vie, les biographies de terrain, et plus généralement toutes formes de témoignages, de comptes rendus et de récits se référant aux unes ou aux autres. Il s'agit de faire émerger des points de vue complémentaires sur les formes d'objectivation de l'observation et de représentation du processus de récolte des données, sur les figurations de la voix du narrateur et du sujet-agent, sur le métalangage et son efficacité dans la construction de la connaissance et du type de savoir qui en dérive

Multifunctionality and Diversity in Bacterial Biofilms

Bacteria are highly diverse and drive a bulk of ecosystem processes. Analysis of relationships between diversity and single specific ecosystem processes neglects the possibility that different species perform multiple functions at the same time. The degradation of dissolved organic carbon (DOC) followed by respiration is a key bacterial function that is modulated by the availability of DOC and the capability to produce extracellular enzymes. In freshwater ecosystems, biofilms are metabolic hotspots and major sites of DOC degradation. We manipulated the diversity of biofilm forming communities which were fed with DOC differing in availability. We characterized community composition using molecular fingerprinting (T-RFLP) and measured functioning as oxygen consumption rates, the conversion of DOC in the medium, bacterial abundance and the activities of five specific enzymes. Based on assays of the extracellular enzyme activity, we calculated how the likelihood of sustaining multiple functions was affected by reduced diversity. Carbon source and biofilm age were strong drivers of community functioning, and we demonstrate how the likelihood of sustaining multifunctionality decreases with decreasing diversity

Stick insect genomes reveal natural selection's role in parallel speciation.

Natural selection can drive the repeated evolution of reproductive isolation, but the genomic basis of parallel speciation remains poorly understood. We analyzed whole-genome divergence between replicate pairs of stick insect populations that are adapted to different host plants and undergoing parallel speciation. We found thousands of modest-sized genomic regions of accentuated divergence between populations, most of which are unique to individual population pairs. We also detected parallel genomic divergence across population pairs involving an excess of coding genes with specific molecular functions. Regions of parallel genomic divergence in nature exhibited exceptional allele frequency changes between hosts in a field transplant experiment. The results advance understanding of biological diversification by providing convergent observational and experimental evidence for selection's role in driving repeatable genomic divergence.

Aptitude à la conduite, pathologies psychiatriques et psychotropes chez la personne âgée [Driving ability, mental illness and psychotropic medication in the elderly].

Fitness to drive in elderly drivers is most commonly discussed with a focus on cognitive impairment. Therefore, this article is focussing on mental illness and the use of psychotropic drugs in elderly drivers, which can both interfere with fitness to drive. Based on a detailed literature review and on clinical judgement, we propose signposts and "red flags" to judge the individual risks. Health professionals dealing with elderly patients should in particular be aware of the dangers related to cumulative risks and need to inform the patients appropriately. For medico-legal reasons the information provided to patients must be written down in the medical record. Individual counselling is important as fitness to drive is a complex topic.

CO2 emissions embodied in international trade: A multiregional Inputoutput model for Spain

As a result of globalization and free trade agreements, international trade is enormously growing and inevitably putting more pressure on the environment over the last few decades. This has drawn the attention of both environmentalist and economist in response to the ever growing concerns of climate change and urgent need of international action for its mitigation. In this work we aim at analyzing the implication of international trade in terms of CO2 between Spain and its important partners using a multi-regional input-output (MRIO) model. A fully integrated 13 regions MRIO model is constructed to examine the pollution responsibility of Spain both from production and consumption perspectives. The empirical results show that Spain is a net importer of CO2 emissions which is equivalent to 29% of its emission due to production. Even though the leading partner with regard to import values are countries such as Germany, France, Italy and Great Britain, the CO2 embodied due to trade with China takes the largest share. This is mainly due to the importation of energy intensive products from China coupled with Chinese poor energy mix which is dominated by coal-power plant. The largest portion (67%) of the global imported CO2 emissions is due to intermediate demand requirements by production sectors. Products such as Motor vehicles, chemicals, a variety of machineries and equipments, textile and leather products, construction materials are the key imports that drive the emissions due to their production in the respective exporting countries. Being at its peak in 2005, the Construction sector is the most responsible activity behind both domestic and imported emissions.

Developing methodologies to allow the robust prediction dynamic context dominated by perturbations

El principal objectiu del projecte era desenvolupar millores conceptuals i metodològiques que permetessin una millor predicció dels canvis en la distribució de les espècies (a una escala de paisatge) derivats de canvis ambientals en un context dominat per pertorbacions. En un primer estudi, vàrem comparar l'eficàcia de diferents models dinàmics per a predir la distribució de l'hortolà (Emberiza hortulana). Els nostres resultats indiquen que un model híbrid que combini canvis en la qualitat de l'hàbitat, derivats de canvis en el paisatge, amb un model poblacional espacialment explícit és una aproximació adequada per abordar canvis en la distribució d'espècies en contextos de dinàmica ambiental elevada i una capacitat de dispersió limitada de l'espècie objectiu. En un segon estudi abordarem la calibració mitjançant dades de seguiment de models de distribució dinàmics per a 12 espècies amb preferència per hàbitats oberts. Entre les conclusions extretes destaquem: (1) la necessitat de que les dades de seguiment abarquin aquelles àrees on es produeixen els canvis de qualitat; (2) el biaix que es produeix en la estimació dels paràmetres del model d'ocupació quan la hipòtesi de canvi de paisatge o el model de qualitat d'hàbitat són incorrectes. En el darrer treball estudiarem el possible impacte en 67 espècies d’ocells de diferents règims d’incendis, definits a partir de combinacions de nivells de canvi climàtic (portant a un augment esperat de la mida i freqüència d’incendis forestals), i eficiència d’extinció per part dels bombers. Segons els resultats dels nostres models, la combinació de factors antropogènics del regim d’incendis, tals com l’abandonament rural i l’extinció, poden ser més determinants per als canvis de distribució que els efectes derivats del canvi climàtic. Els productes generats inclouen tres publicacions científiques, una pàgina web amb resultats del projecte i una llibreria per a l'entorn estadístic R.