Conditional Involvement of CONSTITUTIVE PHOTOMORPHOGENIC1 in the Degradation of Phytochrome A.

All higher plants possess multiple phytochrome photoreceptors, with phytochrome A (phyA) being light labile and other members of the family being relatively light stable (phyB-phyE in Arabidopsis [Arabidopsis thaliana]). phyA also differs from other members of the family because it enables plants to deetiolate in far-red light-rich environments typical of dense vegetational cover. Later in development, phyA counteracts the shade avoidance syndrome. Light-induced degradation of phyA favors the establishment of a robust shade avoidance syndrome and was proposed to be important for phyA-mediated deetiolation in far-red light. phyA is ubiquitylated and targeted for proteasome-mediated degradation in response to light. Cullin1 and the ubiquitin E3 ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) have been implicated in this process. Here, we systematically analyze the requirement of cullins in this process and show that only CULLIN1 plays an important role in light-induced phyA degradation. In addition, the role of COP1 in this process is conditional and depends on the presence of metabolizable sugar in the growth medium. COP1 acts with SUPPRESSOR OF PHYTOCHROME A (SPA) proteins. Unexpectedly, the light-induced decline of phyA levels is reduced in spa mutants irrespective of the growth medium, suggesting a COP1-independent role for SPA proteins.

Spatial pattern of floral morphology: a possible insight into the effects of pollinators on plant distribution

Pollination syndromes involve convergent evolution towards phenotypes composed of specific scents, colours or floral morphologies that attract or restrict pollinator access to reward. How these traits might influence the distributions of plant species in interaction with pollinators has rarely been investigated. We sampled 870 vegetation plots in the western Swiss Alps and classified the plant species into seven blossom types according to their floral morphology (wind, disk, funnel, tube, bilabiate, head or brush). We investigated the environmental features of plots with functional diversity (FD) lower than expected by chance alone to detect potential pollination filtering and related the proportions of the seven blossom types to a combination of environmental descriptors. From these results, we inferred the potential effect of the pollinator on the spatial distribution of plant species. The vegetation plots with significantly lower FD of blossom types than expected by chance were found at higher altitudes, and the proportions of blossom types were strongly patterned along the same gradient. These results support a biotic filtering effect on plant species assemblages through pollination: disk blossoms became dominant at higher altitudes, resulting in a lower FD. In harsh conditions at high altitudes, pollinators usually decrease in activity, and the openness of the disk blossom grants access to any available pollinator. Inversely, bilabiate blossoms, which are mostly pollinated by bees, were more abundant at lower elevations, which are characterised by greater abundance and diversity of bees. Generalisation through openness of the blossom could be advantageous at high elevations, while specialisation could be a successful alternative strategy at lower elevations. The approach used in this study is purely correlative, and further investigations should be conducted to infer the nature of the causal relationship between plant and pollinator distributions.

Etude de la distribution de Formica exsecta Nyl. à l 'aide d 'un système d 'information géographique

La distribution de Formica exsecta semble être conditionnée par un bon ensoleillement (pour le développement du couvain) et par le type de végétation (ressources alimentaires). Par la combinaison de ces facteurs à l'aide du SIG, Ramona Maggini a planifié l'échantillonage de 240 stations dans le PNS pour l'analyse de la distribution de cette espèce

Intraspecific competition reveals conditional fitness effects of single gene polymorphism at the Arabidopsis root growth regulator BRX.

Intraspecific genetic variation for morphological traits is observed in many organisms. In Arabidopsis thaliana, alleles responsible for intraspecific morphological variation are increasingly being identified. However, the fitness consequences remain unclear in most cases. Here, the fitness effects of alleles of the BRX gene are investigated. A brx loss-of-function allele, which was found in a natural accession, results in a highly branched but poorly elongated root system. Comparison between the control accession Sav-0 and an introgression of brx into this background (brxS) indicated that, surprisingly, brx loss of function did not negatively affect fitness in pure stands. However, in mixed, well-watered stands brxS performance and reproductive output decreased significantly, as the proportion of Sav-0 neighbors increased. Additional comparisons between brxS and a brxS line that was complemented by a BRX transgene confirmed a direct effect of the loss-of-function allele on plant performance, as indicated by restored competitive ability of the transgenic genotype. Further, because plant height was very similar across genotypes and because the experimental setup largely excluded shading effects, the impaired competitiveness of the brx loss-of-function genotype likely reflects below-ground competition. In summary, these data reveal conditional fitness effects of a single gene polymorphism in response to intraspecific competition in Arabidopsis.

In vitro and in vivo tumor models for studies of distribution of radiolabelled monoclonal antibodies and fragments.

Colon carcinoma multicellular spheroids were incubated in vitro with radiolabelled MAbs. The more rapid penetration of fragments as compared to intact MAbs was clearly demonstrated. For the study of antibody localization in tumors in vivo, the model of nude mice with ligated kidneys was used. Although very artificial, this model allowed to demonstrate that, without urinary excretion, Fab fragments accumulated more rapidly into the tumor than intact MAbs and disappeared faster from the blood. This difference was less striking for F(ab')2 fragments. In the liver a decreased accumulation of both types of fragments as compared to intact MAbs was observed. Concerning radioimmunotherapy we think that Fab fragments are not useful because of their too short half-life in the circulation and in tumor and because they will probably be too toxic for the kidneys. Intact MAbs and F(ab')2 fragments have each their advantages. Intact MAbs show highest tumor accumulation in mice without ligated kidney, however, they remain mostly on the periphery of tumor nodules, as shown by autoradiography. F(ab')2 fragments have been found to penetrate deeper into the tumor and to accumulate less in the liver. It might be therefore an advantage to combine intact MAbs with F(ab')2 fragments, so that in the tumor two different regions could be attacked whereas in normal tissues toxicity could be distributed to different organs such as to the liver with intact MAbs and to the kidney with F(ab')2 fragments.

Robust response transformations based on optimal prediction

Nonlinear regression problems can often be reduced to linearity by transforming the response variable (e.g., using the Box-Cox family of transformations). The classic estimates of the parameter defining the transformation as well as of the regression coefficients are based on the maximum likelihood criterion, assuming homoscedastic normal errors for the transformed response. These estimates are nonrobust in the presence of outliers and can be inconsistent when the errors are nonnormal or heteroscedastic. This article proposes new robust estimates that are consistent and asymptotically normal for any unimodal and homoscedastic error distribution. For this purpose, a robust version of conditional expectation is introduced for which the prediction mean squared error is replaced with an M scale. This concept is then used to develop a nonparametric criterion to estimate the transformation parameter as well as the regression coefficients. A finite sample estimate of this criterion based on a robust version of smearing is also proposed. Monte Carlo experiments show that the new estimates compare favorably with respect to the available competitors.

The HSR on chromosome 1 of the house mouse, Mus domesticus: distribution and frequency in Switzerland.

A total of 357 house mice (Mus domesticus) from 83 localities uniformly distributed throughout Switzerland were screened for the presence of a homogenously staining region (HSR) on chromosome 1. Altogether 47 mice from 11 localities were HSR/+ or HSR/HSR. One sample of 11 individuals all had an HSR/HSR karyotype. Almost all mice with the variant were collected from the Rhone valley (HSR frequency: 61%) and Val Bregaglia (HSR frequency: 81%). For samples from most of the area of Switzerland, the HSR was absent. There was no strong association between the geographic distribution of the HSR and the areas of occurrence of metacentrics. However, at Chiggiogna the HSR was found on Rb (1.3). Possible explanations for the HSR polymorphism are discussed.

Methods for integration site distribution analyses in animal cell genomes.

The question of where retroviral DNA becomes integrated in chromosomes is important for understanding (i) the mechanisms of viral growth, (ii) devising new anti-retroviral therapy, (iii) understanding how genomes evolve, and (iv) developing safer methods for gene therapy. With the completion of genome sequences for many organisms, it has become possible to study integration targeting by cloning and sequencing large numbers of host-virus DNA junctions, then mapping the host DNA segments back onto the genomic sequence. This allows statistical analysis of the distribution of integration sites relative to the myriad types of genomic features that are also being mapped onto the sequence scaffold. Here we present methods for recovering and analyzing integration site sequences.

Integration of high-resolution geophysical data for the characterization of alluvial aquifers : new approaches and implications for hydrological predictions

Abstract Accurate characterization of the spatial distribution of hydrological properties in heterogeneous aquifers at a range of scales is a key prerequisite for reliable modeling of subsurface contaminant transport, and is essential for designing effective and cost-efficient groundwater management and remediation strategies. To this end, high-resolution geophysical methods have shown significant potential to bridge a critical gap in subsurface resolution and coverage between traditional hydrological measurement techniques such as borehole log/core analyses and tracer or pumping tests. An important and still largely unresolved issue, however, is how to best quantitatively integrate geophysical data into a characterization study in order to estimate the spatial distribution of one or more pertinent hydrological parameters, thus improving hydrological predictions. Recognizing the importance of this issue, the aim of the research presented in this thesis was to first develop a strategy for the assimilation of several types of hydrogeophysical data having varying degrees of resolution, subsurface coverage, and sensitivity to the hydrologic parameter of interest. In this regard a novel simulated annealing (SA)-based conditional simulation approach was developed and then tested in its ability to generate realizations of porosity given crosshole ground-penetrating radar (GPR) and neutron porosity log data. This was done successfully for both synthetic and field data sets. A subsequent issue that needed to be addressed involved assessing the potential benefits and implications of the resulting porosity realizations in terms of groundwater flow and contaminant transport. This was investigated synthetically assuming first that the relationship between porosity and hydraulic conductivity was well-defined. Then, the relationship was itself investigated in the context of a calibration procedure using hypothetical tracer test data. Essentially, the relationship best predicting the observed tracer test measurements was determined given the geophysically derived porosity structure. Both of these investigations showed that the SA-based approach, in general, allows much more reliable hydrological predictions than other more elementary techniques considered. Further, the developed calibration procedure was seen to be very effective, even at the scale of tomographic resolution, for predictions of transport. This also held true at locations within the aquifer where only geophysical data were available. This is significant because the acquisition of hydrological tracer test measurements is clearly more complicated and expensive than the acquisition of geophysical measurements. Although the above methodologies were tested using porosity logs and GPR data, the findings are expected to remain valid for a large number of pertinent combinations of geophysical and borehole log data of comparable resolution and sensitivity to the hydrological target parameter. Moreover, the obtained results allow us to have confidence for future developments in integration methodologies for geophysical and hydrological data to improve the 3-D estimation of hydrological properties.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI.

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied. In vitro study. University based hospital. Fifty-four women undergoing intracytoplasmic sperm injection (ICSI). Oocytes were retrieved, fertilized in vitro using ICSI, and the resulting embryos transferred. Serum was collected immediately prior to oocyte retrieval. Adiponectin isoforms (high molecular weight (HMW), medium and low molecular weight) were determined in serum and FF. Total adiponectin and the different isoform levels were compared with leptin and ovarian steroid concentrations. Adiponectin isoforms in serum and FF. Adiponectin isoform distribution differed between serum and FF; the HMW fraction made up half of all adiponectin in the serum but only 23.3% in the FF. Total and HMW adiponectin in both serum and FF correlated negatively with the body mass index and the concentration of leptin. No correlations were observed for total adiponectin or its isoforms with estradiol, progesterone, anti-Mullerian hormone, inhibin B, or the total follicle stimulating hormone (FSH) dose administered during the ovarian stimulation phase. This study shows for the first time that adiponectin isoform distribution varies between the serum and FF compartments in gonadotropin stimulated patients. A trend towards higher HMW adiponectin serum levels in successful ICSI cycles compared to implantation failures was observed; studies with larger patient groups are required to confirm this observation.

Distribution de la morphologie des tumeurs incidentes dans le canton de Vaud [Morphologic distribution of tumors occuring in the canton of Vaud].

After a short presentation of the methodological aspects of cancer registration and morphological coding, the results concerning cancer of the upper digestive tract, lung, testis and ovary were discussed. Some distributions of the main histological types are analysed by age, sex, site and multiple primaries. Known statistical associations are described between morphology and sex for lung cancer and between morphology and controlateral tumor for ovary.

Predicting species distribution: offering more than simple habitat models

n the last two decades, interest in species distribution models (SDMs) of plants and animals has grown dramatically. Recent advances in SDMs allow us to potentially forecast anthropogenic effects on patterns of biodiversity at different spatial scales. However, some limitations still preclude the use of SDMs in many theoretical and practical applications. Here, we provide an overview of recent advances in this field, discuss the ecological principles and assumptions underpinning SDMs, and highlight critical limitations and decisions inherent in the construction and evaluation of SDMs. Particular emphasis is given to the use of SDMs for the assessment of climate change impacts and conservation management issues. We suggest new avenues for incorporating species migration, population dynamics, biotic interactions and community ecology into SDMs at multiple spatial scales. Addressing all these issues requires a better integration of SDMs with ecological theory.

Unfolding nature "in silico" : overcoming practical and metodological limitations of species distribution models

Abstract : The existence of a causal relationship between the spatial distribution of living organisms and their environment, in particular climate, has been long recognized and is the central principle of biogeography. In turn, this recognition has led scientists to the idea of using the climatic, topographic, edaphic and biotic characteristics of the environment to predict its potential suitability for a given species or biological community. In this thesis, my objective is to contribute to the development of methodological improvements in the field of species distribution modeling. More precisely, the objectives are to propose solutions to overcome limitations of species distribution models when applied to conservation biology issues, or when .used as an assessment tool of the potential impacts of global change. The first objective of my thesis is to contribute to evidence the potential of species distribution models for conservation-related applications. I present a methodology to generate pseudo-absences in order to overcome the frequent lack of reliable absence data. I also demonstrate, both theoretically (simulation-based) and practically (field-based), how species distribution models can be successfully used to model and sample rare species. Overall, the results of this first part of the thesis demonstrate the strong potential of species distribution models as a tool for practical applications in conservation biology. The second objective this thesis is to contribute to improve .projections of potential climate change impacts on species distributions, and in particular for mountain flora. I develop and a dynamic model, MIGCLIM, that allows the implementation of dispersal limitations into classic species distribution models and present an application of this model to two virtual species. Given that accounting for dispersal limitations requires information on seed dispersal, distances, a general methodology to classify species into broad dispersal types is also developed. Finally, the M~GCLIM model is applied to a large number of species in a study area of the western Swiss Alps. Overall, the results indicate that while dispersal limitations can have an important impact on the outcome of future projections of species distributions under climate change scenarios, estimating species threat levels (e.g. species extinction rates) for a mountainous areas of limited size (i.e. regional scale) can also be successfully achieved when considering dispersal as unlimited (i.e. ignoring dispersal limitations, which is easier from a practical point of view). Finally, I present the largest fine scale assessment of potential climate change impacts on mountain vegetation that has been carried-out to date. This assessment involves vegetation from 12 study areas distributed across all major western and central European mountain ranges. The results highlight that some mountain ranges (the Pyrenees and the Austrian Alps) are expected to be more affected by climate change than others (Norway and the Scottish Highlands). The results I obtain in this study also indicate that the threat levels projected by fine scale models are less severe than those derived from coarse scale models. This result suggests that some species could persist in small refugias that are not detected by coarse scale models. Résumé : L'existence d'une relation causale entre la répartition des espèces animales et végétales et leur environnement, en particulier le climat, a été mis en évidence depuis longtemps et est un des principes centraux en biogéographie. Ce lien a naturellement conduit à l'idée d'utiliser les caractéristiques climatiques, topographiques, édaphiques et biotiques de l'environnement afin d'en prédire la qualité pour une espèce ou une communauté. Dans ce travail de thèse, mon objectif est de contribuer au développement d'améliorations méthodologiques dans le domaine de la modélisation de la distribution d'espèces dans le paysage. Plus précisément, les objectifs sont de proposer des solutions afin de surmonter certaines limitations des modèles de distribution d'espèces dans des applications pratiques de biologie de la conservation ou dans leur utilisation pour évaluer l'impact potentiel des changements climatiques sur l'environnement. Le premier objectif majeur de mon travail est de contribuer à démontrer le potentiel des modèles de distribution d'espèces pour des applications pratiques en biologie de la conservation. Je propose une méthode pour générer des pseudo-absences qui permet de surmonter le problème récurent du manque de données d'absences fiables. Je démontre aussi, de manière théorique (par simulation) et pratique (par échantillonnage de terrain), comment les modèles de distribution d'espèces peuvent être utilisés pour modéliser et améliorer l'échantillonnage des espèces rares. Ces résultats démontrent le potentiel des modèles de distribution d'espèces comme outils pour des applications de biologie de la conservation. Le deuxième objectif majeur de ce travail est de contribuer à améliorer les projections d'impacts potentiels des changements climatiques sur la flore, en particulier dans les zones de montagnes. Je développe un modèle dynamique de distribution appelé MigClim qui permet de tenir compte des limitations de dispersion dans les projections futures de distribution potentielle d'espèces, et teste son application sur deux espèces virtuelles. Vu que le fait de prendre en compte les limitations dues à la dispersion demande des données supplémentaires importantes (p.ex. la distance de dispersion des graines), ce travail propose aussi une méthode de classification simplifiée des espèces végétales dans de grands "types de disperseurs", ce qui permet ainsi de d'obtenir de bonnes approximations de distances de dispersions pour un grand nombre d'espèces. Finalement, j'applique aussi le modèle MIGCLIM à un grand nombre d'espèces de plantes dans une zone d'études des pré-Alpes vaudoises. Les résultats montrent que les limitations de dispersion peuvent avoir un impact considérable sur la distribution potentielle d'espèces prédites sous des scénarios de changements climatiques. Cependant, quand les modèles sont utilisés pour évaluer les taux d'extinction d'espèces dans des zones de montages de taille limitée (évaluation régionale), il est aussi possible d'obtenir de bonnes approximations en considérant la dispersion des espèces comme illimitée, ce qui est nettement plus simple d'un point dé vue pratique. Pour terminer je présente la plus grande évaluation à fine échelle d'impact potentiel des changements climatiques sur la flore des montagnes conduite à ce jour. Cette évaluation englobe 12 zones d'études réparties sur toutes les chaines de montages principales d'Europe occidentale et centrale. Les résultats montrent que certaines chaines de montagnes (les Pyrénées et les Alpes Autrichiennes) sont projetées comme plus sensibles aux changements climatiques que d'autres (les Alpes Scandinaves et les Highlands d'Ecosse). Les résultats obtenus montrent aussi que les modèles à échelle fine projettent des impacts de changement climatiques (p. ex. taux d'extinction d'espèces) moins sévères que les modèles à échelle large. Cela laisse supposer que les modèles a échelle fine sont capables de modéliser des micro-niches climatiques non-détectées par les modèles à échelle large.