Insights into the biogeographical history of the Lower Guinea Forest Domain: evidence for the role of refugia in the intraspecific differentiation of Aucoumea klaineana.

Determining the biogeographical histories of rainforests is central to our understanding of the present distribution of tropical biodiversity. Ice age fragmentation of central African rainforests strongly influenced species distributions. Elevated areas characterized by higher species richness and endemism have been postulated to be Pleistocene forest refugia. However, it is often difficult to separate the effects of history and of present-day ecological conditions on diversity patterns at the interspecific level. Intraspecific genetic variation could yield new insights into history, because refugia hypotheses predict patterns not expected on the basis of contemporary environmental dynamics. Here, we test geographically explicit hypotheses of vicariance associated with the presence of putative refugia and provide clues about their location. We intensively sampled populations of Aucoumea klaineana, a forest tree sensitive to forest fragmentation, throughout its geographical range. Characterizing variation at 10 nuclear microsatellite loci, we were able to obtain phylogeographic data of unprecedented detail for this region. Using Bayesian clustering approaches, we demonstrated the presence of four differentiated genetic units. Their distribution matched that of forest refugia postulated from patterns of species richness and endemism. Our data also show differences in diversity dynamics at leading and trailing edges of the species' shifting distribution. Our results confirm predictions based on refugia hypotheses and cannot be explained on the basis of present-day ecological conditions.

The French adaptation of the Health of the Nation Outcome Scale for Children and Adolescents Self-Rated Form (F-HoNOSCA-SR): Validation and clinical routine use.

The current study aimed to explore the validity of an adaptation into French of the self-rated form of the Health of the Nation Outcome Scales for Children and Adolescents (F-HoNOSCA-SR) and to test its usefulness in a clinical routine use. One hundred and twenty nine patients, admitted into two inpatient units, were asked to participate in the study. One hundred and seven patients filled out the F-HoNOSCA-SR (for a subsample (N=17): at two occasions, one week apart) and the strengths and difficulties questionnaire (SDQ). In addition, the clinician rated the clinician-rated form of the HoNOSCA (HoNOSCA-CR, N=82). The reliability (assessed with split-half coefficient, item response theory (IRT) models and intraclass correlations (ICC) between the two occasions) revealed that the F-HoNSOCA-SR provides reliable measures. The concurrent validity assessed by correlating the F-HoNOSCA-SR and the SDQ revealed a good convergent validity of the instrument. The relationship analyses between the F-HoNOSCA-SR and the HoNOSCA-CR revealed weak but significant correlations. The comparison between the F-HoNOSCA-SR and the HoNOSCA-CR with paired sample t-tests revealed a higher score for the self-rated version. The F-HoNSOCA-SR was reported to provide reliable measures. In addition, it allows us to measure complementary information when used together with the HoNOSCA-CR.

Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

A case of acute retinal pigment epithelitis: spectral domain optical coherence tomography time course and physiopathologic hypothesis.

PURPOSE: To report the time course of retinal morphologic changes in a patient with acute retinal pigment epithelitis (ARPE) using spectral domain optical coherence tomography (SD-OCT). METHODS: A 30-year old man was referred for blurred vision of his right eye after five days that appeared suddenly 15 days after recovery from a flu-like syndrome. SD-OCT was performed immediately, followed by fluorescein and infracyanine angiography at eight days and then at three weeks. RESULTS: At presentation, a bubble of sub-macular deposit was observed on the right macula with central golden micronodules in a honeycomb pattern. SD-OCT showed an "anterior dislocation" of all the retinal layers up to the inner/outer segment (IS/OS) line and irregular deposits at the OS level together with thickening of the retinal pigment epithelial (RPE) layer. As visual acuity increased, eight days later, the OCT showed reduction of the sub-retinal deposits and an abnormal hyperflectivity of the sub-retinal and RPE layers was observed. The patient showed a positive serology for picornavirus. DISCUSSION: The acute SD-OCT sections of this patient with ARPE were compared with histological sections of a 35 day old Royal College of Surgeons rat. Similar findings could be observed, with preservation of the IS/OS line and accumulation of debris at the OS level, suggesting that ARPE symptoms could result from a transient phagocytic dysfunction of the RPE at the fovea, inducing reversible accumulation of undigested OS. Picornaviruses comprising enterovirus and coxsachievirus described as being associated with acute chorioretinitis. In this case, it was responsible for ARPE. CONCLUSION: We hypothesize that ARPE syndrome results from a transient dysfunction of RPE, which can occur as a post viral reaction.

Guideline adaptation: an approach to enhance efficiency in guideline development and improve utilisation.

BACKGROUND: Developing and updating high-quality guidelines requires substantial time and resources. To reduce duplication of effort and enhance efficiency, we developed a process for guideline adaptation and assessed initial perceptions of its feasibility and usefulness. METHODS: Based on preliminary developments and empirical studies, a series of meetings with guideline experts were organised to define a process for guideline adaptation (ADAPTE) and to develop a manual and a toolkit made available on a website (http://www.adapte.org). Potential users, guideline developers and implementers, were invited to register and to complete a questionnaire evaluating their perception about the proposed process. RESULTS: The ADAPTE process consists of three phases (set-up, adaptation, finalisation), 9 modules and 24 steps. The adaptation phase involves identifying specific clinical questions, searching for, retrieving and assessing available guidelines, and preparing the draft adapted guideline. Among 330 registered individuals (46 countries), 144 completed the questionnaire. A majority found the ADAPTE process clear (78%), comprehensive (69%) and feasible (60%), and the manual useful (79%). However, 21% found the ADAPTE process complex. 44% feared that they will not find appropriate and high-quality source guidelines. DISCUSSION: A comprehensive framework for guideline adaptation has been developed to meet the challenges of timely guideline development and implementation. The ADAPTE process generated important interest among guideline developers and implementers. The majority perceived the ADAPTE process to be feasible, useful and leading to improved methodological rigour and guideline quality. However, some de novo development might be needed if no high quality guideline exists for a given topic.

Role of mutations in the phosphoprotein on RNA polymerase activity of canine distemper virus following cell culture adaptation

Abstract: The canine distemper virus A75/17 wild-type strain, which is unable to replicate in cell lines, was adapted to growth in Vero cells. Sequence comparison between the A75/17 and the Vero cell-adapted A75/17-V virus revealed 7 amino acid differences between the 2 viruses. Three of these were located in the matrix protein, three in the phosphoprotein also changing the V protein but not the C protein and one in the large protein. The phosphoprotein and the large protein constituted the viral RNA polymerase whose activity was studied by transfection experiments using a reverse genetic system with a plasmid encoding a minireplicon and expression plasmids encoding the nucleocapsid protein and the viral RNA polymerase subunits. Surprinsingly, the enzyme of A75/17 CDV was significantly more active in cell lines compared to the polymerase of A75/17-V CDV. The decrease in overall enzyme activity was found to be due to both decreased replication and transcription activity. This polymerase attenuation was confirmed in CHO cells infection stably expressing the dog SLAM receptor mainly found in dog's lymphoid organs and allowing both virus strains to enter these cells at the same efficiency. A75/17-V CDV replicated more slowly in CHODogSLAM cells than A75/17 CDV and syncytium formation was significantly decreased compared to A75/17 infected CHODogSLAM cells.. Cell culture adaptation lead to an attenuated virus strain both in vitro and in vivo with decreased polymerase activity and syncytium forming capability showing an important role of the polymerase in determining the phenoytpe of the virus. In addition, this reduced phenotype of A75/17-V CDV was shown to be due to the P mutations in the P protein only, showing an important function of the polycistronic P gene in the adaptation process. The role of the matrix protein was found not to have any effect on polymerase activity, however its participation in the adaptation process still needs to be elucidated. The accessory proteins V and C were shown to act on polymerase activity, but their functions in virus pathogenicity and in inhibiting the interferon system have not been studied in this thesis. The V proteins have an activating effect on the polymerase of both the A75/17 and the A75/17-V CDV strains. Although the C protein amino acid sequence was not changed during adaptation of wild-type canine distemper virus in Vero cells, the C protein was demonstrated to have opposite effects on polymerase activity of both virus strains suggesting a different interaction of the C protein with the proteins forming the polymerase complex, which could modulate polymeras activity. These effects were demonstrated by transfection experiments and studying recombinant viruses not expressing the C protein. Thus, the abrogation of the C protein decrease the activity of the wild-type polymerase. In contrast, the polymerase activity of the Vero cell- adapted virus is enhanced in the absence of the C protein and this has also been demonstrated with a recombinant virus, which grew faster in the first 48 hours of infection. Future studies will focus on the generation of recombinant wild-type viruses, which should be very helpful in understanding the molecular mechanisms underlying the adaptation process and the loss of pathogenicity.

Tectonic and metamorphic evolution of the Central Himalayan Domain in Southeast Zanskar (Kashmir, India)

La région du Zanskar, étudiée dans le cadre de ce travail, se situe au passage entre deux domaines himalayens fortement contrastés, la Séquence Cristalline du Haut Himalaya (HHCS), composée de roches métamorphiques et l'Himalaya Tethysien (TH), composé de séries sédimentaires. La transition entre ces deux domaines est marquée par une structure tectonique majeure, la Zone de Cisaillement du Zanskar (ZSZ), au sein de laquelle on observe une augmentation extrêmement rapide, mais néanmoins graduelle, du degré du métamorphisme entre le TH et le HHCS. Il a été établi que le HHCS n'est autre que l'équivalent métamorphique des séries sédimentaires de la base du TH. C'est principalement lors d'un épisode de mise en place de nappes à vergence sudouest, entre l'Eocène moyen et l'Oligocène, que les séries sédimentaires de la base du TH ont été entraînées en profondeur où elles ont subi un métamorphisme de type barrovien. Au début du Miocène, le HHCS à été exhumé en direction du sud-ouest sous forme d'une grande nappe, délimitée a sa base par le MCT (principal chevauchement central) et à son sommet par la Zone de Cisaillement du Zanskar. L'ensemble des zones barroviennes, de la zone à biotite jusqu'à la zone à disthène, a été cisaillée par les mouvements en faille normale au sommet du HHCS et se retrouve actuellement sur une épaisseur d'environ 1 kilomètre au sein de la ZSZ. La décompression associée à l'exhumation du HHCS a provoqué la fusion partielle d'une partie du HHCS et a donné naissance à des magmas de composition leucogranitiques. Grâce à la géothermobarometrie, et connaissant la géométrie de la ZSZ, il nous a été possible de déterminer que le rejet le long de cette structure d'extension est d'au moins 35?9 kilomètres. Une série d'arguments nous permet cependant de suggérer que ce rejet aurait pu être encore bien plus important (~100km). Les données géochronologiques nous permettent de contraindre la durée des mouvements d'extension le long de la ZSZ à 2.4?0.2 Ma entre 22.2?0.2 Ma et 19.8?0.1 Ma. Ce travail apporte de nouvelles données sur les processus métamorphiques, magmatiques et tectoniques liés aux phénomènes d'extension syn-orogeniques.<br/><br/>The southeastern part of Zanskar is located at the transition between two major Himalayan domains of contrasting metamorphic grade, the High Himalayan Crystalline Sequence (HHCS) and the Tethyan Himalaya (TH). The transition between the TH and the HHCS is marked by a very rapid, although perfectly gradual, decrease in metamorphic grade, which coincides with a major tectonic structure, the Zanskar Shear Zone (ZSZ). It is now an established fact that the relation between the HHCS and the TH is not one of basement-cover type, but that the metasedimentary series of the HHCS represent the metamorphic equivalent of the lowermost sedimentary series of the TH. This transformation of sedimentary series into metamorphic rocks, and hence the differentiation between the TH and the HHCS, is the consequence of crustal thickening associated to the formation of large scale southwest vergent nappes within the Tethyan Himalaya sedimentary series. This, Middle Eocene to Oligocene, episode of crustal thickening and associated Barrovian metamorphism is followed, shortly after, by the exhumation of the HHCS as a, large scale, south-west vergent, nappe. Foreword The exhumation of the HHCS nappe is marked by the activation of two contemporaneous structures, the Main Central Thrust at its base and the Zanskar Shear Zone at its top. Extensional movements along the ZSZ, caused the Barrovian biotite to the kyanite zones to be sheared and constricted within the ~1 km thick shear zone. Decompression associated with the exhumation of the HHCS induced the formation of leucogranitic magmas through vapour-absent partial melting of the highest-grade rocks. The combination of geothermobarometric data with a geometric model of the ZSZ allowed us to constrain the net slip at the top of the HHCS to be at least 35?9 kilometres. A set of arguments however suggests that these movements might have been much more important (~ 100 km). Geochronological data coupled with structural observations constrain the duration of ductile shearing along the ZSZ to 2.4?0.2 Ma between 22.2?0.2 Ma and 19.8?0.1 Ma. This study also addresses the consequences of synorogenic extension on the metamorphic, tectonic and magmatic evolution of the upper parts of the High Himalayan Crystalline Sequence.

Information System ProcessInnovation Adoption, Adaptation, Learning, and Unlearning: A Longitudinal Case Study

This thesis examines the history and evolution of information system process innovation (ISPI) processes (adoption, adaptation, and unlearning) within the information system development (ISD) work in an internal information system (IS) department and in two IS software house organisations in Finland over a 43-year time-period. The study offers insights into influential actors and their dependencies in deciding over ISPIs. The research usesa qualitative research approach, and the research methodology involves the description of the ISPI processes, how the actors searched for ISPIs, and how the relationships between the actors changed over time. The existing theories were evaluated using the conceptual models of the ISPI processes based on the innovationliterature in the IS area. The main focus of the study was to observe changes in the main ISPI processes over time. The main contribution of the thesis is a new theory. The term theory should be understood as 1) a new conceptual framework of the ISPI processes, 2) new ISPI concepts and categories, and the relationships between the ISPI concepts inside the ISPI processes. The study gives a comprehensive and systematic study on the history and evolution of the ISPI processes; reveals the factors that affected ISPI adoption; studies ISPI knowledge acquisition, information transfer, and adaptation mechanisms; and reveals the mechanismsaffecting ISPI unlearning; changes in the ISPI processes; and diverse actors involved in the processes. The results show that both the internal IS department and the two IS software houses sought opportunities to improve their technical skills and career paths and this created an innovative culture. When new technology generations come to the market the platform systems need to be renewed, and therefore the organisations invest in ISPIs in cycles. The extent of internal learning and experiments was higher than the external knowledge acquisition. Until the outsourcing event (1984) the decision-making was centralised and the internalIS department was very influential over ISPIs. After outsourcing, decision-making became distributed between the two IS software houses, the IS client, and itsinternal IT department. The IS client wanted to assure that information systemswould serve the business of the company and thus wanted to co-operate closely with the software organisations.

Evolution based on domain combinations: the case of glutaredoxins

Background: Protein domains represent the basic units in the evolution of proteins. Domain duplication and shuffling by recombination and fusion, followed by divergence are the most common mechanisms in this process. Such domain fusion and recombination events are predicted to occur only once for a given multidomain architecture. However, other scenarios may be relevant in the evolution of specific proteins, such as convergent evolution of multidomain architectures. With this in mind, we study glutaredoxin (GRX) domains, because these domains of approximately one hundred amino acids are widespread in archaea, bacteria and eukaryotes and participate in fusion proteins. GRXs are responsible for the reduction of protein disulfides or glutathione-protein mixed disulfides and are involved in cellular redox regulation, although their specific roles and targets are often unclear. Results: In this work we analyze the distribution and evolution of GRX proteins in archaea,bacteria and eukaryotes. We study over one thousand GRX proteins, each containing at least one GRX domain, from hundreds of different organisms and trace the origin and evolution of the GRX domain within the tree of life. Conclusion: Our results suggest that single domain GRX proteins of the CGFS and CPYC classes have, each, evolved through duplication and divergence from one initial gene that was present in the last common ancestor of all organisms. Remarkably, we identify a case of convergent evolution in domain architecture that involves the GRX domain. Two independent recombination events of a TRX domain to a GRX domain are likely to have occurred, which is an exception to the dominant mechanism of domain architecture evolution.

Use of physiological constraints to identify quantitative design principles for gene expression in yeast adaptation to heat shock

Background: Understanding the relationship between gene expression changes, enzyme activity shifts, and the corresponding physiological adaptive response of organisms to environmental cues is crucial in explaining how cells cope with stress. For example, adaptation of yeast to heat shock involves a characteristic profile of changes to the expression levels of genes coding for enzymes of the glycolytic pathway and some of its branches. The experimental determination of changes in gene expression profiles provides a descriptive picture of the adaptive response to stress. However, it does not explain why a particular profile is selected for any given response. Results: We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the physiological level that ultimately constrain changes in gene expression. Conclusion: Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.

Vécu et adaptation des couples âgés séparés par l'entrée en institution de l'un des conjoints.

Cette thèse de doctorat porte sur le vécu et l'adaptation des couples âgés séparés par l'entrée de l'un des conjoints en institution. Notre démarche se fonde sur le paradigme compréhensif en sciences humaines. Nous avons rencontré sept couples dont l'un des conjoints vivait dans un Etablissement Médico-Social (EMS) de Suisse Romande, alors que l'autre continuait de vivre dans la communauté. Pour chaque situation, nous avons mené une interview individuelle de chacun des conjoints ainsi qu'une interview de couple. Nous avons effectué une analyse thématique du discours des interviewés. En outre, adoptant une perspective à la fois scientifique et clinique, nous avons étudié la dynamique conjugale des couples. Enfin, nous avons élaboré une typologie des différentes trajectoires de ces couples, en mettant en évidence les liens entre la dynamique de couple antérieure à l'hébergement, le vécu du moment de l'hébergement et le vécu lors des interviews. Nous avons montré le rôle central de l'ambivalence, vis-à-vis de la relation conjugale ou vis-à-vis de l'hébergement, dans les difficultés d'adaptation des couples à leur nouvelle situation de vie. -- This thesis is about the experience and adaptation of older couples separated by the accommodation of one spouse in a specialised institution. Our approach is based on the comprehensive paradigm in human sciences. We have met seven couples, of which one spouse was living in an institution (EMS) in the French speaking part of Switzerland, as the other spouse was still living in the community. In every situations, we have interviewed each spouse individually and both spouses together. We have carried out a thematic analysis of the discourses. Moreover, taking a scientific as well as a clinical perspective, we have studied the spousal dynamics of the couples. Finally, we have elaborated a typology of couples' trajectories, from earlier spousal dynamics to their experience of the transition and their experience in the time of the interviews. We have showed the crucial role of ambivalence, towards the couple relation or towards the accommodation, in couples' difficulties to adapt to their new living situation.

Reinald Porchet, Pirrus, Garsion et sa fille: autour de quelques particularités d'adaptation dans "Le Siège d'Antioche avec la conquête de Jérusalem" (inédit) tiré de Baudri de Bourgueil

Considérations autour de la chanson de geste "Le Siège d'Antioche avec la conquête de Jérusalem", qui se dit tirée de la chronique de Baudri de Bourgueil. Mise au point sur la tradition manuscrite du texte et étude plus détaillée de passages illustrant comment le récit diffère de sa (ou plutôt, ses) source(s) latine(s) et de "La Chanson d'Antioche" du cycle de la Première Croisade.

Genomic evidence for role of inversion 3RP of Drosophila melanogaster in facilitating climate change adaptation.

Chromosomal inversion polymorphisms are common in animals and plants, and recent models suggest that alternative arrangements spread by capturing different combinations of alleles acting additively or epistatically to favour local adaptation. It is also thought that inversions typically maintain favoured combinations for a long time by suppressing recombination between alternative chromosomal arrangements. Here, we consider patterns of linkage disequilibrium and genetic divergence in an old inversion polymorphism in Drosophila melanogaster (In(3R)Payne) known to be associated with climate change adaptation and a recent invasion event into Australia. We extracted, karyotyped and sequenced whole chromosomes from two Australian populations, so that changes in the arrangement of the alleles between geographically separated tropical and temperate areas could be compared. Chromosome-wide linkage disequilibrium (LD) analysis revealed strong LD within the region spanned by In(3R)Payne. This genomic region also showed strong differentiation between the tropical and the temperate populations, but no differentiation between different karyotypes from the same population, after controlling for chromosomal arrangement. Patterns of differentiation across the chromosome arm and in gene ontologies were enhanced by the presence of the inversion. These data support the notion that inversions are strongly selected by bringing together combinations of genes, but it is still not clear if such combinations act additively or epistatically. Our data suggest that climatic adaptation through inversions can be dynamic, reflecting changes in the relative abundance of different forms of an inversion and ongoing evolution of allelic content within an inversion.