Mayaro virus and dengue virus 1 and 4 natural infection in culicids from Cuiabá, state of Mato Grosso, Brazil

This study aimed to verify the diversity of Culicidae species and their frequency of infection with flaviviruses and alphaviruses in Cuiabá, state of Mato Grosso, Brazil. Mosquitoes were captured with Nasci aspirators and hand net in 200 census tracts, identified alive at species level and pooled in one-20 (11,090 mosquitoes, 14 species). Female pools (n = 610) were subjected to multiplex seminested-reverse transcription-polymerase chain reaction (RT-PCR) for 11 flavivirus and five alphavirus. Positive pools were tested by single RT-PCR followed by nucleotide sequencing, by RT-PCR for E1 gene [Mayaro virus (MAYV)] and by inoculation in Vero cells (MAYV) or C6/36 cells (flaviviruses). One/171 Aedes aegypti was positive for dengue virus (DENV)-1, 12/403 Culex quinquefasciatus, and four/171Ae. aegypti for MAYV, which was isolated from two pools containing two nonengorged females of Ae. aegypti and two ofCx. quinquefasciatus. DENV-4 was detected in 58/171 pools of Ae. aegytpi, 105/403 Cx. quinquefasciatus, two/five Psorophora sp., two/11 Psorophora varipes/Psorophora albigenu, one/one Sabethes chloropterus, two/five Culex bidens/Culex interfor, and one/one Aedes sp. DENV-4 was isolated from two pools containing three and 16 nonengorged Cx. quinquefasciatus females. Phylogenetic analysis revealed MAYV belongs to genotype L, clustering with human samples of the virus previously identified in the city. Cuiabá has biodiversity and ecosystem favourable for vector proliferation, representing a risk for arbovirus outbreaks.

Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals.

Photoaging and photocarcinogenesis are primarily due to solar ultraviolet (UV) radiation, which alters DNA, cellular antioxidant balance, signal transduction pathways, immunology, and the extracellular matrix (ECM). The DNA alterations include UV radiation induced thymine-thymine dimers and loss of tumor suppressor gene p53. UV radiation reduces cellular antioxidant status by generating reactive oxygen species (ROS), and the resultant oxidative stress alters signal transduction pathways such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB)/p65, the janus kinase (JAK), signal transduction and activation of transcription (STAT) and the nuclear factor erythroid 2-related factor 2 (Nrf2). UV radiation induces pro-inflammatory genes and causes immunosuppression by depleting the number and activity of the epidermal Langerhans cells. Further, UV radiation remodels the ECM by increasing matrixmetalloproteinases (MMP) and reducing structural collagen and elastin. The photoprotective strategies to prevent/treat photoaging and photocarcinogenesis include oral or topical agents that act as sunscreens or counteract the effects of UV radiation on DNA, cellular antioxidant balance, signal transduction pathways, immunology and the ECM. Many of these agents are phytochemical derivatives and include polyphenols and non-polyphenols. The flavonoids are polyphenols and include catechins, isoflavones, proanthocyanidins, and anthocyanins, whereas the non-flavonoids comprise mono phenolic acids and stilbenes. The natural sources of polyphenols include tea, cocoa, grape/wine, soy, pomegranate, and Polypodium leucotomos. The non-phenolic phytochemicals include carotenoids, caffeine and sulphoraphance (SFN). In addition, there are other phytochemical derivatives or whole extracts such as baicalin, flavangenol, raspberry extract, and Photomorphe umbellata with photoprotective activity against UVB radiation, and thereby carcinogenesis.

On Strong Citizens: A Sociological View on Cognitions and Contentious Participation

The present thesis is about cognitions of left-wing activists and the role they play to better understand contentious participation. It compares activists of three post-industrial social movement organizations in Switzerland, i.e. Solidarity across Borders defending migrant's rights, the Society of Threatened People promoting collective human rights and Greenpeace protecting the environment. It makes use of an innovative mixed methods design combining survey and interview data. The main theoretical contribution is to conceptualize an analytical tool enabling to grasp the cognitive map of these activists by putting forward the concept of strong citizen, summing up their relation to society and politics. The relation to society consists of an extensive relation to others and an interconnected vision of society. Consequently, their primary concerns include the handing of common goods and the equal treatment of individuals with regard to common goods. The relation to politics incorporates a critical and vigilant citizen. They are critical towards political authorities and they appreciate political action by organized groups of the civil society. The thesis states that only by having such worldviews activists are able to construct an injustice, agency and identity frame for the claims of their organizations. Thus, the present work delivers a parsimonious answer to the question of where an injustice, agency and identity frame comes from. It does so by a systematic analysis of four specific arguments. First, it empirically demonstrates that these activists have - at the aggregate level - specific cognitive resources compared to the general population. Second, it describes the content of this specific cognitive outlook by evaluating the appropriateness of the strong citizen concept. Third, it looks at variations between activist's communities and shows that activists of more challenging protest issues are stronger citizens than activists of more mainstream protests. Finally, cognitions are not the only part of the story if one looks at contentious participation. Other factors, i.e. social networks and biographical availability, matter too. Therefore, I test if cognitions are able to contribute in explaining differences between activists' communities if one controls for other factors. In sum, this thesis is thus a first step to demonstrate why one should be concerned about activists' cognitions. - Cette thèse s'intéresse aux cognitions des activistes de gauche et à leur rôle dans le phénomène de la participation contestataire. Des activistes de trois organisations post- industrielles en Suisse sont comparé, à savoir Solidarité sans Frontières qui défend les droits des migrants, la Société des Peuples menacés qui promeut les droits des collectivités minoritaires et Greenpeace qui oeuvre pour la protection de l'environnement. Cette recherche utilise un « mixed methods design » en combinant de manière innovant des données de sondage et d'entretiens. Ma principale contribution théorique réside dans la conceptualisation d'un outil analytique qui permet de saisir la « carte cognitive » des activistes, à travers le concept de « strong citizen » qui se réfère à la relation spécifique qu'entretiennent certains individus avec la société et la politique. Ces individus sont caractérisés par une vision inclusive et interconnectée de la société, ainsi que par une conception politique du citoyen comme critique et vigilant. Mon argument principal est celui selon lequel seuls les individus possédant ce type particulier de cognitions sont capable de construire un cadre d'injustice, d'« agency » et d'identité. Cette thèse apporte donc quelques éléments de réponse à la question de l'origine de ces cadres cognitifs qui sont cruciales pour la participation. Pour ce faire, quatre aspects spécifiques sont analysés de manière systématique. Premièrement, je démontre empiriquement, au niveau agrégé, que ces activistes possèdent effectivement des ressources cognitives spécifiques - en comparaison avec la population générale. Deuxièmement, j'analyse le contenu de ces cognitions, ce qui me permet notamment d'évaluer la pertinence et l'adéquation du concept de « strong citizen ». Troisièmement, en m'intéressant cette fois aux variations entre communautés d'activistes, je démontre que ceux réunis autour d'enjeux protestataires très revendicatifs sont, d'un point de vue cognitif, plus proches de la figure du « strong citizen » que ceux mobilisés sur des enjeux plus consensuels. Finalement, d'autres facteurs, à savoir les réseaux sociaux et la disponibilité biographique, sont intégrés à l'analyse afin de mesurer le réel pouvoir explicatif des cognitions dans l'explication des différences observées entre communautés d'activistes. A travers ces analyses, cette thèse met en avant l'importance du rôle des cognitions dans l'étude de la participation contestataire.

Health effects of occupational exposure to traffic particles and noise

Exposure to fine particles and noise has been linked to cardiovascular diseases and elevated cardiovascular mortality affecting the worldwide population. Residence and/or work in proximity to emission sources as for example road traffic leads to an elevated exposure and a higher risk for adverse health effects. Highway maintenance workers spend most of their work time in traffic and are exposed regularly to particles and noise. The aims of this thesis were to provide a better understanding of the workers' mixed exposure to particles and noise and to assess cardiopulmonary short term health effects in relation to this exposure. Exposure and health data were collected in collaboration with 8 maintenance centers of the Swiss Road Maintenance Services located in the cantons Bern, Fribourg and Vaud in western Switzerland. Repeated measurements with 18 subjects were conducted during 50 non-consecutive work shifts between Mai 2010 and February 2012, equally distributed over all seasons. In the first part of this thesis we tested and validated measurements of ultrafine particles with a miniature diffusion size classifier (miniDiSC) - a novel particle counting device that was used for the exposure assessment during highway maintenance work. We found that particle numbers and average particle size measured by the miniDiSC were highly correlated with data from the P-TRAK, a condensation particle counter (CPC), as well as from a scanning mobility particle sizer (SMPS). However, the miniDiSC measured significantly more particles than the P-TRAK and significantly less than the SMPS in its full size range. Our data suggests that the instrument specific cutoffs were the main reason for the different particle counts. The first main objective of this thesis was to investigate the exposure of highway maintenance workers to air pollutants and noise, in relation to the different maintenance activities. We have seen that the workers are regularly exposed to high particle and noise levels. This was a consequence of close proximity to highway traffic and the use of motorized working equipment such as brush cutters, chain saws, generators and pneumatic hammers during which the highest exposure levels occurred. Although exposure to air pollutants were not critical if compared to occupational exposure limits, the elevated exposure to particles and noise may lead to a higher risk for cardiovascular diseases in this worker population. The second main objective was to investigate cardiopulmonary short-term health effects in relation to the particle and noise exposure during highway maintenance work. We observed a PM2.5 related increase of the acute-phase inflammation markers C-reactive protein and serum amyloid A and a decrease of TNFa. Heart rate variability increased as a consequence of particle as well as noise exposure. Increased high frequency power indicated a stronger parasympathetic influence on the heart. Elevated noise levels during recreational time, after work, were related to increased blood pressure. Our data confirmed that highway maintenance workers are exposed to elevated levels of particles and noise as compared to the average population. This exposure poses a cardiovascular health risk and it is therefore important to make efforts to better protect the workers health. The use of cleaner machines during maintenance work would be a major step to improve the workers' situation. Furthermore, regulatory policies with the aim of reducing combustion and non-combustion emissions from road traffic are important for the protection of workers in traffic environments and the entire population.

Role of Endogenous GLP-1 and GIP in Beta Cell Compensatory Responses to Insulin Resistance and Cellular Stress.

Role of GLP-1 and GIP in beta cell compensatory responses to beta cell attack and insulin resistance were examined in C57BL/6 mice lacking functional receptors for GLP-1 and GIP. Mice were treated with multiple low dose streptozotocin or hydrocortisone. Islet parameters were assessed by immunohistochemistry and hormone measurements were determined by specific enzyme linked immunoassays. Wild-type streptozotocin controls exhibited severe diabetes, irregularly shaped islets with lymphocytic infiltration, decreased Ki67/TUNEL ratio with decreased beta cell and increased alpha cell areas. GLP-1 and GIP were co-expressed with glucagon and numbers of alpha cells mainly expressing GLP-1 were increased. In contrast, hydrocortisone treatment and induction of insulin resistance increased islet numbers and area, with enhanced beta cell replication, elevated mass of beta and alpha cells, together with co-expression of GLP-1 and GIP with glucagon in islets. The metabolic responses to streptozotocin in GLP-1RKO and GIPRKO mice were broadly similar to C57BL/6 controls, although decreases in islet numbers and size were more severe. In contrast, both groups of mice lacking functional incretin receptors displayed substantially impaired islet adaptations to insulin resistance induced by hydrocortisone, including marked curtailment of expansion of islet area, beta cell mass and islet number. Our observations cannot be explained by simple changes in circulating incretin concentrations, suggesting that intra-islet GLP-1 and GIP make a significant contribution to islet adaptation, particularly expansion of beta cell mass and compensatory islet compensation to hydrocortisone and insulin resistance.

CD44 attenuates activation of the hippo signaling pathway and is a prime therapeutic target for glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor that, by virtue of its resistance to chemotherapy and radiotherapy, is currently incurable. Identification of molecules whose targeting may eliminate GBM cells and/or sensitize glioblastoma cells to cytotoxic drugs is therefore urgently needed. CD44 is a major cell surface hyaluronan receptor and cancer stem cell marker that has been implicated in the progression of a variety of cancer types. However, the major downstream signaling pathways that mediate its protumor effects and the role of CD44 in the progression and chemoresponse of GBM have not been established. Here we show that CD44 is upregulated in GBM and that its depletion blocks GBM growth and sensitizes GBM cells to cytotoxic drugs in vivo. Consistent with this observation, CD44 antagonists potently inhibit glioma growth in preclinical mouse models. We provide the first evidence that CD44 functions upstream of the mammalian Hippo signaling pathway and that CD44 promotes tumor cell resistance to reactive oxygen species-induced and cytotoxic agent-induced stress by attenuating activation of the Hippo signaling pathway. Together, our results identify CD44 as a prime therapeutic target for GBM, establish potent antiglioma efficacy of CD44 antagonists, uncover a novel CD44 signaling pathway, and provide a first mechanistic explanation as to how upregulation of CD44 may constitute a key event in leading to cancer cell resistance to stresses of different origins. Finally, our results provide a rational explanation for the observation that functional inhibition of CD44 augments the efficacy of chemotherapy and radiation therapy.

Cultural self-identification(s) and personal social networks among first and second-generation immigrants

L’estudi examina les relacions entre (1) les xarxes socials personals de la població immigrant resident a Barcelona i (2) les seves identitats culturals múltiples. L’objectiu principal de l’estudi és entendre com el contingut i l’estructura de les relacions socials dels immigrants facilita o dificulta (1) tenir un sentiment de pertinença a les noves cultures d’acollida, la catalana i la espanyola, i (2) la integració d’aquestes noves identitats socioculturals amb la seva identitat d’origen en una nova identitat bicultural cohesiva. El nostre plantejament inicial era que els immigrants amb xarxes socials més diverses des del punt de vista de la seva composició cultural tindrien més recursos socials i experiències cognitives més diverses , factors que afavoreixen les identificacions múltiples i la participació cívica. Els resultats de l’estudi mostren que el grau d’identificació dels participants amb la seva cultura ètnica o d’origen és força alt i, en certa mesura, més alt en comparació amb les cultures d’acollida ( catalana, cívica i espanyola). Tanmateix, el vincle dels participants amb les cultures d’acollida (p. ex., la cultura catalana) és prou rellevant per a indicar una orientació bicultural (catalana i ètnica). Les anàlisis de correlacions revelen que sentir-se català no impedeix sentir-se part de la comunitat etnocultural d’origen. A més, existeix una interrelació entre l'orientació cultural catalana i la identificació amb les comunitats cíviques locals. De la mateixa manera, tenir competències en llengua catalana no va en detriment de les competències en llengua castellana. Les anàlisis també mostren que factors com l’orientació cultural catalana, l’ús del català i la identificació amb la cultura catalana tenen una correlació positiva amb el grau de chohesio de la indentitat bicultural, afavoreixen el benestar psicològic i disminueixen l’estrès aculturatiu. L’anàlisi de les xarxes socials mostra que la identificació amb la cultura catalana, l’orientació cultural catalana i la integració de la identitat són factors clau per tenir xarxes socials més diverses des del punt de vista ètnic i lingüístic, amb menys membres del col•lectiu d’origen, i amb subgrups o “cliques” culturalment més heterogenis. La identificació espanyola també prediu, en mesura més reduïda, la diversitat de les xarxes. Els nostres resultats contribueixen a la recerca actual i les teories sobre interculturalitat i identitat cultural.

Plant traits co-vary with altitude in grasslands and forests in the European Alps

Biological traits that are advantageous under specific ecological conditions should be present in a large proportion of the species within an ecosystem, where those specific conditions prevail. As climatic conditions change, the frequency of certain traits in plant communities is expected to change with increasing altitude. We examined patterns of change for 13 traits in 120 exhaustive inventories of plants along five altitudinal transects (520-3100 m a.s.l.) in grasslands and in forests in western Switzerland. The traits selected for study represented the occupation of space, photosynthesis, reproduction and dispersal. For each plot, the mean trait values or the proportions of the trait states were weighted by species cover and examined in relation to the first axis of a PCA based on local climatic conditions. With increasing altitude in grasslands, we observed a decrease in anemophily and an increase in entomophily complemented by possible selfing; a decrease in diaspores with appendages adapted to ectozoochory, linked to a decrease in achenes and an increase in capsules. In lowlands, pollination and dispersal are ensured by wind and animals. However, with increasing altitude, insects are mostly responsible for pollination, and wind becomes the main natural dispersal vector. Some traits showed a particularly marked change in the alpine belt (e.g., the increase of capsules and the decrease of achenes), confirming that this belt concentrates particularly stressful conditions to plant growth and reproduction (e.g. cold, short growing season) that constrain plants to a limited number of strategies. One adaptation to this stress is to limit investment in dispersal by producing capsules with numerous, tiny seeds that have appendages limited to narrow wings. Forests displayed many of the trends observed in grasslands but with a reduced variability that is likely due to a shorter altitudinal gradient.

Phylogeny of shrews (Soricidae) : taxonomic and biogeographic implications

Résumé Les Soricidae sont l'une des plus grandes familles de mammifères avec plus de 300 espèces décrites. Elle a été récemment divisée en trois sous-familles, les Soricidae, qui sont distribuées dans la région Holarctique, les Crocidurinae en Afrique et en Eurasie, et les Myosoricinae en Afrique. La diversité spécifique de cette famille a conduit à des interprétations taxonomiques multiples, qui sont à l'origine de polémiques entre spécialistes, et même les premiers résultats moléculaires ont été fortement contradictoires. Le but de cette thèse est donc d'appliquer des meilleures techniques sur des échantillons mieux ciblés, afin de résoudre les contradictions taxonomiques et comprendre l'histoire de cette famille. Par le biais de marqueurs génétiques mitochondriaux et nucléaires, j'ai étudié: (i) Les relations taxonomiques à différent niveaux hiérarchiques au sein des Soricidae, c'est-à dire, entre les sous-familles, tribus, et genres, ainsi qu'au sein de deux complexes d'espèces largement distribués, et d'une espèce européenne, le but étant d'établir la congruence entre les données génétiques et les interprétations morphologiques classiques. (ii) Les relations biogéographiques, soit l'origine potentielle des différentes sous-familles, tribus, et genres, le nombre d'échanges intercontinentaux, ainsi que la structure phylogéographique à un niveau (péri)-spécifique, afin d'établir l'histoire de la diversification de cette famille. Les analyses combinées d'ADN mitochondrial et nucléaire ont montré un rapport clair entre les taxa à un niveau taxonomique élevé, mettant en évidence les rapports entre les sous-familles, les tribus, et les genres. Bien que Myosorex constitue un groupe monophylétique distinct, sa définition en tant que sous-famille séparée ne peut pas être reconnue. Ainsi, nous proposons d'attribuer un niveau de tribu pour ce clade (inclus dans les Crocidurinae). Nous avons également montré l'inclusion du genre Anourosorex dans les Soricinae et non en position basale dans les Soricidae. Au sein des Crocidurinae, Suncus s'est révélé être paraphylétique, et le genre Diplomesodon devrait être considéré d'un point de vue génétique comme invalide, puisque il se trouve au sein du clade du genre Crocidura. À un niveau taxonomique plus bas, nous avons montré la monophylie de deux complexes d'espèces largement distribués, le groupe de C. suaveolens et de C. olivieri. Néanmoins à l'intérieur de ceux-ci, des différences majeures avec la classification morphologique se sont révélées. Par exemples, C. sibirica n'est pas une espèce valide, les analyses de phylogénie moléculaire ne montrant pas de variations génétiques entre celle-ci et un échantillon de la localité type de C. suaveolens. D'un point de vue biogéographique, les fluctuations climatiques et les activités tectoniques des 20 derniers millions d'années ont fortement influencé la diversité actuelle des Soricidae. À un niveau taxonomique élevé, l'apparition de connexions de terre temporaires entre le Vieux et le Nouveau Monde au Miocène moyen ont mené à plusieurs colonisations indépendantes de l'Amérique par les Soricinae. Celles-ci ónt conduit à une diversification d'une tribu (Notiosoricini), ainsi que de genres (par ex: Cryptotis, Blarina) et d'un sous-genre (Otisorex) endémique au Néarctique. Dans le Vieux Monde, les barrières entre l'Afrique et Eurasie étaient plus perméables, menant à plusieurs échanges bidirectionnels de Crocidurinae. La diversification des clades principaux s'est produite au Miocène, certains clades étant endémiques d'Afrique ou d'Eurasie, tandis que d'autres se sont diversifiés à travers le Vieux Monde. À un niveau spécifique ou péri-spécifique, la fluctuation climatique du Pliocène et les glaciations du Pléistocène ont fortement divisé les populations dans tout le Paléarctique, menant à des entités génétiques distinctes. En Europe, les populations du groupe de C. suaveolens ont été divisées en une lignée Sud-Ouest et une Sud-Est, alors qu'au Proche-Orient et au Moyen-Orient, la diversité de clades est plus importante. En conclusion, mes études ont révélé que du Miocène à nos jours, la diversification des Soricidae a été provoquée par la colonisation de nouveaux habitats (dispersion), ainsi que par l'isolement des populations par diverses barrières (vicariance). Abstract The Soricidae is one of the largest mammalian families with more than 300 species described. It has been recently divided into three subfamilies, the Soricinae, which are distributed in the Holartic region, the Crocidurinae in Africa and Eurasia, and the Myosoricinae in Africa. The specific diversity of this family have led to multiple systematic interpretations and controversies between authors. Fortunately, today, cytotaxonomic, allozymic and molecular studies have permitted to clarify some uncertainties. Nevertheless, the Soricidae remains still poorly known. In this thesis, we aim at understanding with the use of mitochondrial and nuclear markers: (i) the taxonomic relationships at different hierarchical levels within Soricidae, i.e., between the subfamilies, tribes, and genera, as well as within two largely distributed species complexes, and within a European species, the goal being to establish congruence between the genetic data and traditional morphological interpretations; (ii) the biogeographic relationships, especially the potential origin of the different subfamilies, tribes, and genera, the number of transcontinental exchanges, as well as the phylogeographic structure at a (peri)-specific level, in order to establish the history of the genetic diversification of this family. The combined analyses of mitochondrial and nuclear DNA highlight for the first time a clear relationship between taxa at a high taxonomical level, permitting to distinguish the relationships between subfamilies, tribes, and genera. Although Myosorex formed a distinct monophyletic group, its definition as a distinct sub-family cannot be advocated. Thus, we propose to attribute a tribe level for this Glade (included within the Crocidurinae). Additionally, this combination of genes pleads in favour of the inclusion of the genus Anourosorex within the Soricinae and not in a basal position within the Soricidae. Within the Crocidurinae, Suncus appeared to be paraphyletic, and Diplomesodon should be considered from a genetic point of view as invalid, and is presently considered as Crocidura. At a lower taxonomic level, we showed the monophyly of two widely distributed species complexes, the C. suaveolens group and the C. olivieri group. Nevertheless within those, we showed major differences compared to morphological classification. For examples, C. sibirica revealed to not be a valid species, the molecular phylogenetic analyses failed to evidence genetical variations between it and samples of the type locality of C. suaveolens. In a biogeographic point of view, the climatic fluctuations and the tectonic plate activities of the last 20 Myr have strongly influenced the actual diversity of the family. At a high taxonomic level, the successive land bridge connections between the Old and the New World, which occurred during the Middle Miocene, have led to several independent colonisations of America by Soricinae, and a subsequent diversification of endemic Nearctic's tribe (Notiosoricini), genera (e.g. Cryptotis, Blaring) and sub-genus (Otisorex) within the Soricinae. Within the Old World, the barriers between Africa and Eurasia were more permeable, leading to several bidirectional exchanges within the Crocidurinae. The diversification of major clades occurred through the Miocene, some clades being endemic to Africa or Eurasia, whereas others diversified through the Old World. At a species level or a peri-specific level, the Pliocene climatic fluctuation and the Pleistocene glaciations have strongly divided the populations throughout the Palaearctic, leading to well defined genetic entities. In Europe, populations of the C. suaveolens group were split in a classical south-western and south-eastern lineage. In contrast, the Near East and the Middle East reveal many differentiated clades. In conclusion, our studies revealed that, from the Miocene to present, the diversification and speciation events within the Soricidae were caused by natural colonisation of new habitats (dispersion) and isolation of populations by various barriers (vicariance).

Proteostasis of aging and stem cells

Estudi realitzat a partir d’una estada a la the Salk Institute, Estats Units, entre 2010 i 2012. L'estabilitat del genoma és essencial per a la supervivència de les cèl • lules mare, però, l'estabilitat del proteoma pot tenir un paper igualment important en la identitat de cèl • lules mare i la seva funció. La nostra hipòtesi és que les cèl • lules mare tenen la capacitat de proteostasis augmentada en comparació amb els seus homòlegs diferenciats i ens varem preguntar si l'activitat del proteasoma és diferent a les cèl • lules mare embrionàries humanes (hESCs). En particular, els nostres resultats mostren que les poblacions de cèl• lules mare presenten una activitat del proteasoma que es correlaciona amb majors nivells de la subunitat 19S del proteasoma PSMD11/RPN-6 i un corresponent augment del ensamblatge del 26S/30S proteasoma. L'expressió ectòpica de PSMD11 és suficient per augmentar l'activitat del proteasoma. Sorprenentment, varem trobar que la llarga vida del GLP-1 C. elegans mutant té també un augment dramàtic en l'activitat del proteasoma associat a nivells augmentats en l'expressió de RPN-6. El factor de transcripció DAF-16 és essencial per l'augment de la longevitat de GLP-1 i els cucs mutants que trobem DAF-16 necessari per a l'augment d'expressió de RPN-6 i, per tant, per l'activació de l'activitat del proteasoma en GLP-1 mutant animals. Una possibilitat interessant és que els gens que regulen la vida i la resistència a l'estrès en C. elegans poden també regular la funció hESCs de mamífer, cèl • lules que son considerades immortals. Aquests resultats ens van portar a la conclusió de que FOXO4, un factor de transcripció sensible a la insulina/IGF-1, regula l'activitat del proteasoma en hESCs, el que suggereix un paper per FOXO4 en la funció d’aquestes cèl • lules. En efecte, FOXO4 es necessari per a la diferenciació en llinatges neuronals de les hESCs. Els nostres resultats estableixen una nova regulació de laproteostasis en hESCs que uneix la longevitat i la resistència a l'estrès en invertebrats amb la funció i identitat de les hESCs.

Combining palaeodistribution modelling and phylogeographical approaches for identifying glacial refugia in Alpine Primula

Aim We investigated the late Quaternary history of two closely related and partly sympatric species of Primula from the south-western European Alps, P. latifolia Lapeyr. and P. marginata Curtis, by combining phylogeographical and palaeodistribution modelling approaches. In particular, we were interested in whether the two approaches were congruent and identified the same glacial refugia. Location South-western European Alps. Methods For the phylogeographical analysis we included 353 individuals from 28 populations of P. marginata and 172 individuals from 15 populations of P. latifolia and used amplified fragment length polymorphisms (AFLPs). For palaeodistribution modelling, species distribution models (SDMs) were based on extant species occurrences and then projected to climate models (CCSM, MIROC) of the Last Glacial Maximum (LGM), approximately 21 ka. Results The locations of the modelled LGM refugia were confirmed by various indices of genetic variation. The refugia of the two species were largely geographically isolated, overlapping only 6% to 11% of the species' total LGM distribution. This overlap decreased when the position of the glacial ice sheet and the differential elevational and edaphic distributions of the two species were considered. Main conclusions The combination of phylogeography and palaeodistribution modelling proved useful in locating putative glacial refugia of two alpine species of Primula. The phylogeographical data allowed us to identify those parts of the modelled LGM refugial area that were likely source areas for recolonization. The use of SDMs predicted LGM refugial areas substantially larger and geographically more divergent than could have been predicted by phylogeographical data alone

Endocarditis prophylaxis revisited: experimental evidence of efficacy and new Swiss recommendations. Swiss Working Group for Endocarditis Prophylaxis.

Because of its severity, it is agreed that infectious endocarditis should be prevented whenever possible. Determining adequate prophylactic measures involves establishing (a) the patients at risk, (b) the procedures that might provoke bacteraemia, (c) the most effective prophylactic regimen, and (d) a balance between the risks of side effects from prophylaxis and of developing infectious endocarditis. Patients at risk and procedures inducing bacteraemia have been identified by clinical studies. On the other hand, the efficacy of prophylactic antibiotics has been based on animal studies. Randomised, placebo-controlled studies do not exist in humans because they would require large patient numbers and would raise ethical issues due to the severity of the disease. Case-control studies have indicated that infectious endocarditis prophylaxis is effective, but prevents only a limited number of cases. Animal experiments have revealed several key issues for human application. First, antibiotics do not prevent the early stages of valve colonisation, but rather kill the microorganisms after their attachment to the cardiac lesions. Second, the duration of antibiotic presence in the serum is critical. Under experimental conditions, the drugs must remain above their minimal inhibitory concentration for the organisms for > or = 10 h, to allow time for bacterial clearance from the valves. Third, antibiotic-induced killing is not the only mechanism allowing bacterial clearance. Other factors, such as platelet microbicidal proteins, may act in concert with the drugs to sterilise the lesions. Recommendations for prophylaxis have recently been revised in Europe and the USA. New information has improved the definition of groups at risk. Since most cases of infectious endocarditis are not preceded by medical procedures, primary prevention of infectious endocarditis should target infected foci responsible for spontaneous bacteraemia (e.g. poor dental hygiene). The purpose of this article is to update the existing recommendations in Switzerland, under the perspective of changing epidemiology, the availability of new drugs, and harmonisation with recommendations in other countries.

Predicting global change impacts on plant species' distributions: Future challenges

Given the rate of projected environmental change for the 21st century, urgent adaptation and mitigation measures are required to slow down the on-going erosion of biodiversity. Even though increasing evidence shows that recent human-induced environmental changes have already triggered species' range shifts, changes in phenology and species' extinctions, accurate projections of species' responses to future environmental changes are more difficult to ascertain. This is problematic, since there is a growing awareness of the need to adopt proactive conservation planning measures using forecasts of species' responses to future environmental changes. There is a substantial body of literature describing and assessing the impacts of various scenarios of climate and land-use change on species' distributions. Model predictions include a wide range of assumptions and limitations that are widely acknowledged but compromise their use for developing reliable adaptation and mitigation strategies for biodiversity. Indeed, amongst the most used models, few, if any, explicitly deal with migration processes, the dynamics of population at the "trailing edge" of shifting populations, species' interactions and the interaction between the effects of climate and land-use. In this review, we propose two main avenues to progress the understanding and prediction of the different processes A occurring on the leading and trailing edge of the species' distribution in response to any global change phenomena. Deliberately focusing on plant species, we first explore the different ways to incorporate species' migration in the existing modelling approaches, given data and knowledge limitations and the dual effects of climate and land-use factors. Secondly, we explore the mechanisms and processes happening at the trailing edge of a shifting species' distribution and how to implement them into a modelling approach. We finally conclude this review with clear guidelines on how such modelling improvements will benefit conservation strategies in a changing world. (c) 2007 Rubel Foundation, ETH Zurich. Published by Elsevier GrnbH. All rights reserved.

Evolutionary history and its relevance in understanding and conserving southern African biodiversity

Abstract : Understanding how biodiversity is distributed is central to any conservation effort and has traditionally been based on niche modeling and the causal relationship between spatial distribution of organisms and their environment. More recently, the study of species' evolutionary history and relatedness has permeated the fields of ecology and conservation and, coupled with spatial predictions, provides useful insights to the origin of current biodiversity patterns, community structuring and potential vulnerability to extinction. This thesis explores several key ecological questions by combining the fields of niche modeling and phylogenetics and using important components of southern African biodiversity. The aims of this thesis are to provide comparisons of biodiversity measures, to assess how climate change will affect evolutionary history loss, to ask whether there is a clear link between evolutionary history and morphology and to investigate the potential role of relatedness in macro-climatic niche structuring. The first part of my thesis provides a fine scale comparison and spatial overlap quantification of species richness and phylogenetic diversity predictions for one of the most diverse plant families in the Cape Floristic Region (CFR), the Proteaceae. In several of the measures used, patterns do not match sufficiently to argue that species relatedness information is implicit in species richness patterns. The second part of my thesis predicts how climate change may affect threat and potential extinction of southern African animal and plant taxa. I compare present and future niche models to assess whether predicted species extinction will result in higher or lower V phylogenetic diversity survival than what would be experienced under random extinction processes. l find that predicted extinction will result in lower phylogenetic diversity survival but that this non-random pattern will be detected only after a substantial proportion of the taxa in each group has been lost. The third part of my thesis explores the relationship between phylogenetic and morphological distance in southern African bats to assess whether long evolutionary histories correspond to equally high levels of morphological variation, as predicted by a neutral model of character evolution. I find no such evidence; on the contrary weak negative trends are detected for this group, as well as in simulations of both neutral and convergent character evolution. Finally, I ask whether spatial and climatic niche occupancy in southern African bats is influenced by evolutionary history or not. I relate divergence time between species pairs to climatic niche and range overlap and find no evidence for clear phylogenetic structuring. I argue that this may be due to particularly high levels of micro-niche partitioning. Résumé : Comprendre la distribution de la biodiversité représente un enjeu majeur pour la conservation de la nature. Les analyses se basent le plus souvent sur la modélisation de la niche écologique à travers l'étude des relations causales entre la distribution spatiale des organismes et leur environnement. Depuis peu, l'étude de l'histoire évolutive des organismes est également utilisée dans les domaines de l'écologie et de la conservation. En combinaison avec la modélisation de la distribution spatiale des organismes, cette nouvelle approche fournit des informations pertinentes pour mieux comprendre l'origine des patterns de biodiversité actuels, de la structuration des communautés et des risques potentiels d'extinction. Cette thèse explore plusieurs grandes questions écologiques, en combinant les domaines de la modélisation de la niche et de la phylogénétique. Elle s'applique aux composants importants de la biodiversité de l'Afrique australe. Les objectifs de cette thèse ont été l) de comparer différentes mesures de la biodiversité, 2) d'évaluer l'impact des changements climatiques à venir sur la perte de diversité phylogénétique, 3) d'analyser le lien potentiel entre diversité phylogénétique et diversité morphologique et 4) d'étudier le rôle potentiel de la phylogénie sur la structuration des niches macro-climatiques des espèces. La première partie de cette thèse fournit une comparaison spatiale, et une quantification du chevauchement, entre des prévisions de richesse spécifique et des prédictions de la diversité phylogénétique pour l'une des familles de plantes les plus riches en espèces de la région floristique du Cap (CFR), les Proteaceae. Il résulte des analyses que plusieurs mesures de diversité phylogénétique montraient des distributions spatiales différentes de la richesse spécifique, habituellement utilisée pour édicter des mesures de conservation. La deuxième partie évalue les effets potentiels des changements climatiques attendus sur les taux d'extinction d'animaux et de plantes de l'Afrique australe. Pour cela, des modèles de distribution d'espèces actuels et futurs ont permis de déterminer si l'extinction des espèces se traduira par une plus grande ou une plus petite perte de diversité phylogénétique en comparaison à un processus d'extinction aléatoire. Les résultats ont effectivement montré que l'extinction des espèces liées aux changements climatiques pourrait entraîner une perte plus grande de diversité phylogénétique. Cependant, cette perte ne serait plus grande que celle liée à un processus d'extinction aléatoire qu'à partir d'une forte perte de taxons dans chaque groupe. La troisième partie de cette thèse explore la relation entre distances phylogénétiques et morphologiques d'espèces de chauves-souris de l'Afrique australe. ll s'agit plus précisément de déterminer si une longue histoire évolutive correspond également à des variations morphologiques plus grandes dans ce groupe. Cette relation est en fait prédite par un modèle neutre d'évolution de caractères. Aucune évidence de cette relation n'a émergé des analyses. Au contraire, des tendances négatives ont été détectées, ce qui représenterait la conséquence d'une évolution convergente entre clades et des niveaux élevés de cloisonnement pour chaque clade. Enfin, la dernière partie présente une étude sur la répartition de la niche climatique des chauves-souris de l'Afrique australe. Dans cette étude je rapporte temps de divergence évolutive (ou deux espèces ont divergé depuis un ancêtre commun) au niveau de chevauchement de leurs niches climatiques. Les résultats n'ont pas pu mettre en évidence de lien entre ces deux paramètres. Les résultats soutiennent plutôt l'idée que cela pourrait être I dû à des niveaux particulièrement élevés de répartition de la niche à échelle fine.

Labeling Regulations and Segregation of First- and, Second-Generation Genetically Modified Products: Innovation Incentives and Welfare Effects, April 2005

We review some of the most significant issues and results on the economic effects of genetically modified (GM) product innovation, with emphasis on the question of GM labeling and the need for costly segregation and identity preservation activities. The analysis is organized around an explicit model that can accommodate the features of both first-generation and second-generation GM products. The model accounts for the proprietary nature of GM innovations and for the critical role of consumer preferences vis-à-vis GM products, as well as for the impacts of segregation and identity preservation and the effects of a mandatory GM labeling regulation. We also investigate briefly a novel question in this setting, the choice of “research direction”when both cost-reducing and quality-enhancing GM innovations are feasible.