927 resultados para Humanized niche
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Non-indigenous species can have strong impacts on biodiversity by affecting trophic relationships in their new environments. The piscivorous dice snake (Natrix tessellata) has been introduced to Geneva Lake, western Switzerland, where the endangered viperine snake (Natrix maura) is native. Local, dramatic declines in the viperine snake population might be associated with the appearance of the dice snake through dietary overlap between these 2 species, which mainly feed on bullhead (Cottus gobio). In response to this decline, a control program for dice snake was implemented in 2007 to reduce numbers of this introduced snake. In 2010, a new species of fish, the freshwater blenny (Salaria fluviatilis), which shares the same habitat as the bullhead, was introduced into Lake Geneva and has since reached high densities. We determined the impact of freshwater blenny on diet composition and body condition of dice snakes. In addition, we tested for effects of the control program on the body condition of dice snakes and viperine snakes. We collected 294 dice snakes between 2007 and 2013. Based on morphology and a genetic marker (cytochrome b gene), we determined the ®sh species contained in these snakes' stomachs. We found a drastic switch in dice snake diet following the arrival of freshwater blenny, as consumption of bullhead declined by 68% and was replaced by the blenny. In addition, the body condition of dice snakes increased significantly after the arrival of freshwater blenny. The body condition of both snake species was positively correlated with the number of dice snakes removed from the study area. This finding has important implications concerning the conservation of the endangered viperine snake, and suggests that the control program of dice snakes should be continued.
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Els marges de pedra seca són un dels ambients socioecològics més singulars del país i, al mateix temps, un dels hàbitats menys estudiats. La nostra recerca ha analitzat la biodiversitat de les margenades de Vandellòs i l’Hospitalet de l’Infant; mitjançant mostrejos de flora i de la fauna hem constatat l’elevada complexitat de la xarxa tròfica que s’estableix en aquest nínxol ecològic. En la vessant socioambiental, hem realitzat entrevistes a diferents entesos en la cultura de la pedra seca, les quals han permès determinar la importància dels marges per entendre una part de la història ambiental del país. Amb la recerca s’ha observat un clar retrocés del patrimoni de pedra seca a causa de la recessió del sector agrícola. L’aprofitament turístic de la cultura de la pedra seca i la implicació de les Administracions Públiques en la difusió d’aquest patrimoni, són claus per garantir-ne la pervivència en el futur.
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BACKGROUND: Certolizumab pegol (Cimzia, CZP) was approved for the treatment of Crohn's disease (CD) patients in 2007 in Switzerland as the first country worldwide. This prospective phase IV study aimed to evaluate the efficacy and safety of CZP over 26 weeks in a multicenter cohort of practice-based patients. METHODS: Evaluation questionnaires at baseline, week 6, and week 26 were completed by gastroenterologists in hospitals and private practices. Adverse events were evaluated according to World Health Organization (WHO) guidelines. RESULTS: Sixty patients (38F/22M) were included; 53% had complicated disease (stricturing or penetrating), 45% had undergone prior CD-related surgery. All patients had prior exposure to systemic steroids, 96% to immunomodulators, 73% to infliximab, and 43% to adalimumab. A significant decrease of the Harvey-Bradshaw Index (HBI) was observed under CZP therapy (12.2 ± 4.9 at week 0 versus 6.3 ± 4.7 at week 6 and 6.7 ± 5.3 at week 26, both P < 0.001). Response and remission rates were 70% and 40% (week 6) and 67% and 36%, respectively (week 26). The complete perianal fistula closure rate was 36% at week 6 and 55% at week 26. The frequency of adverse drug reactions attributed to CZP was 5%. CZP was continued in 88% of patients beyond week 6 and in 67% beyond week 26. CONCLUSIONS: In a population of CD patients with predominantly complicated disease behavior, CZP proved to be effective in induction and maintenance of response and remission. This series provides the first evidence of CZP's effectiveness in perianal fistulizing CD in clinical practice.
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BACKGROUND: Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine.¦OBJECTIVE: In this study we developed a human PBMC-engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms.¦METHODS: Nonobese diabetic (NOD)-scid-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically.¦RESULTS: Using the aeroallergens birch or grass pollen as model allergens and, for some donors, also hazelnut allergen, we show that allergen-specific human IgE in murine sera and allergen-specific proliferation and cytokine production of human CD4(+) T cells recovered from spleens after 3 weeks could only be measured in mice treated with PBMCs plus allergen. Importantly, these mice had the highest endoscopic scores evaluating translucent structure, granularity, fibrin, vascularity, and stool after oral or rectal allergen challenge and a strong histologic inflammation of the colon. Analyzing the underlying mechanisms, we demonstrate that allergen-associated colitis was dependent on IgE, human IgE receptor-expressing effector cells, and the mediators histamine and platelet-activating factor.¦CONCLUSION: These results demonstrate that allergic gut inflammation can be induced in human PBMC-engrafted mice, allowing the investigation of pathophysiologic mechanisms of allergic diseases of the intestine and evaluation of therapeutic interventions.
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The coloration of ectotherms plays an important role in thermoregulation processes. Dark individuals should heat up faster and be able to reach a higher body temperature than light individuals and should therefore have benefits in cool areas. In central Europe, montane local populations of adder (Vipera berus) and asp viper (Vipera aspis) exhibit a varying proportion of melanistic individuals. We tested whether the presence of melanistic V. aspis and V. berus could be explained by climatic conditions. We measured the climatic niche position and breadth of monomorphic (including strictly patterned individuals) and polymorphic local populations, calculated their niche overlap and tested for niche equivalency and similarity. In accordance with expectations, niche overlap between polymorphic local populations of both species is high, and even higher than that of polymorphic versus monomorphic montane local populations of V. aspis, suggesting a predominant role of melanism in determining the niche of ectothermic vertebrates. However, unexpectedly, the niche of polymorphic local populations of both species is narrower than that of monomorphic ones, indicating that colour polymorphism does not always enable the exploitation of a greater variability of resources, at least at the intraspecific level. Overall, our results suggest that melanism might be present only when the thermoregulatory benefit is higher than the cost of predation.
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Recent developments in metacommunity theory have raised awareness that processes occurring at regional scales might interfere with local dynamics and affect conditions for the local coexistence of competing species. Four main paradigms are recognized in this context (namely, neutral, patch-dynamics, species-sorting, and mass-effect), which differ according to the role assigned to ecological or life-history differences among competing species, as well as to the relative time scale of regional vs. local dynamics. We investigated the patterns of regional and local coexistence of two species of shrews (Crocidura russula and Sorex coronatus) sharing a similar diet (generalist insectivores) over four generations, in a spatially structured habitat at the altitudinal limit of their distributions. Local populations were small, and regional dynamics were strong, with high rates of extinction and recolonization. Niche analysis revealed significant habitat differentiation on a few important variables, including temperature and availability of winter resting sites. In sites suitable for both species, we found instances of local coexistence with no evidence of competitive exclusion. Patterns of temporal succession did not differ from random, with no suggestion of a colonization-competition trade-off. Altogether, our data provide support for the mass-effect paradigm, where regional coexistence is mediated by specialization on different habitat types, and local coexistence by rescue effects from source sites. The strong regional dynamics and demographic stochasticity, together with high dispersal rates, presumably contributed to mass effects by overriding local differences in specific competitive abilities.
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A new nematode, the type of a new genus and a new species Laurostrongylus hoineffae, parasitic in the cricetid rodent Gymnuromys roberti in Madagascar, is described. The species belongs to the Graphiidinae subfamily of Trichostrongylidae but some features point to its affinity to certain Libyostrongylinae, especially to two monospecific genera endemic in Madagascar Pararhabdonema and Cnizostrongylus. This ensemble of relict species seems thus to support the concept of a common ancestor for the Libyostrongylinae and Graphidiinae. The two subfamilies were supposed to originate in the Ethipian region. The presence of the three generain Madagascar could either indicate their Madagascan origin or, more likely, a continental origin with an insular niche allowing the preservation of the species.
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The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in ∼100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1α/β and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.
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The ability to model biodiversity patterns is of prime importance in this era of severe environmental crisis. Species assemblage along environmental gradient is subject to the interplay of biotic interactions in complement to abiotic environmental filtering. Accounting for complex biotic interactions for a wide array of species remains so far challenging. Here, we propose to use food web models that can infer the potential interaction links between species as a constraint in species distribution models. Using a plant-herbivore (butterfly) interaction dataset, we demonstrate that this combined approach is able to improve both species distribution and community forecasts. Most importantly, this combined approach is very useful in rendering models of more generalist species that have multiple potential interaction links, where gap in the literature may be recurrent. Our combined approach points a promising direction forward to model the spatial variation of entire species interaction networks. Our work has implications for studies of range shifting species and invasive species biology where it may be unknown how a given biota might interact with a potential invader or in future climate.
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INTRODUCTION: Two subcutaneous injections of adalimumab in severe acute sciatica significantly reduced the number of back operations in a short-term randomised controlled clinical trial. OBJECTIVE: To determine in a 3-year follow-up study whether the short-term benefit of adalimumab in sciatica is sustained over a longer period of time. METHODS: The primary outcome of this analysis was incident discectomy. Three years after randomisation, information on surgery could be retrieved in 56/61 patients (92%).A multivariate Cox proportional hazard models, adjusted for potential confounders, was used to determine factors predisposing to surgery. RESULTS: Twenty-three (41%) patients had back surgery within 3 years, 8/29 (28%) in the adalimumab group and 15/27 (56%) in the placebo group, p=0.04. Adalimumab injections reduced the need for back surgery by 61% (HR)=0.39 (95% CI 0.17 to 0.92). In a multivariate model, treatment with a tumour necrosis factor-α antagonist remained the strongest protective factor (HR=0.17, p=0.002). Other significant predictors of surgery were a good correlation between symptoms and MRI findings (HR=11.6, p=0.04), baseline intensity of leg pain (HR=1.3, p=0.06), intensity of back pain (HR=1.4, p=0.03) and duration of sickness leave (HR=1.01 per day, p=0.03). CONCLUSION: A short course of adalimumab in patients with severe acute sciatica significantly reduces the need for back surgery.
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Résumé Identification, localisation et activation des cellules souches hématopoiétiques dormantes in vivo Les cellules souches somatiques sont présentes dans la majorité des tissus régénératifs comme la peau, l'épithélium intestinal et le système hématopoiétique. A partir d'une seule cellule, elles ont les capacités de produire d'autres cellules souches du même type (auto-renouvellement) et d'engendrer un ensemble défini de cellules progénitrices différenciées qui vont maintenir ou réparer leur tissu hôte. Les cellules souches adultes les mieux caractérisées sont les cellules souches hématopoiétiques (HSC), localisées dans la moelle osseuse. Un des buts de mon travail de doctorat était de caractériser plus en profondeur la localisation des HSCs endogènes in vivo. Pour ce faire, la technique "label retaining assay", se basant sur la division peu fréquentes et sur la dormance des cellules souches, a été utilisée. Après un marquage des souris avec du BrdU (analogue à l'ADN) suivi d'une longue période sans BrdU, les cellules ayant incorporés le marquage ("label retaining cells" LCRs) ont pu être identifiées dans la moelle osseuse. Ces cellules LCRs étaient enrichies 300 fois en cellules de phenotype HSC et, en utilisant de la cytofluorométrie, il a pu être montré qu'environ 15% de toutes les HSCs d'une souris restent dormantes durant plusieures semaines. Ces HSCs dormantes à long terme ne sont probablement pas impliquées dans la maintenance de 'hématopoièse. Par contre, on assiste à l'activation rapide de ces HSCs dormantes lors d'une blessure, comme une ablation myéloide. Elles re-entrent alors en cycle cellulaire et sont essentielles pour une génération rapide des cellules progénitrices et matures qui vont remplacer les cellules perdues. De plus, la détection des LCRs, combinée avec l'utilisation du marqueur de HSCs c-kit, peut être utilisée pour la localisation des HSCs dormantes présentes dans la paroi endostéale de la cavité osseuse. De manière surprenante, les LCRs c-kit+ ont surtout étés trouvées isolées en cellule unique, suggérant que le micro-environement spécifique entourant et maintenant les HSCs, appelé niche, pourrait être très réduit et abriter une seule HSC par niche. Rôles complexes du gène supresseur de tumeur Pten dans le système hématopoiétique La phosphatase PTEN disparaît dans certains cancers héréditaires ou sporadiques humains, comme les gliomes, les cancers de l'utérus ou du sein. Pten inhibe la voie de signalisation de la PI3-kinase et joue un rôle clé dans l'apoptose, la croissance, la prolifération et la migration cellulaire. Notre but était d'étudier le rôle de Pten dans les HSC normale et durant la formation de leucémies. Pour ce faire, nous avons généré un modèle murin dans lequel le gène Pten peut être supprimé dans les cellules hématopoiétiques, incluant les HSCs. Ceci a été possible en croissant l'allèle conditionnelle ptenflox soit avec le transgène MxCre inductible par l'interféron α soit avec le transgène Scl-CreERt inductible par le tamoxifen. Ceci permet la conversion de l'allèle ptenflox en l'allèle nul PtenΔ dans les HSCs et les autres types cellulaires hématopoiétiques. Les souris mutantes Pten développent une splénomégalie massive causée par une expansion dramatiques de toutes les cellules myéloides. De manière interessante, alors que le nombre de HSCs dans la moelle osseuse diminue progressivement, le nombre des HSCs dans la rate augmente de manière proportionnelle. Etrangement, les analyses de cycle cellulaire ont montrés que Pten n'avait que peu ou pas d'effet sur la dormance des HSCs ou sur leur autorenouvellement. En revanche, une augmentation massive du niveau de la cytokine de mobilisation G-CSF a été détéctée dans le serum sanguin, suggérant que la suppression de Pten stimulerait la mobilisation et la migration des HSC de la moelle osseuse vers la rate. Finallement, la transplantation de moelle osseuse délétée en Pten dans des souris immuno-déficientes montre que Pten fonctionnerait comme un suppresseur de tumeur dans le système hématopoiétique car son absence entraîne la formation rapide de leucémies lymphocytaires. Summary Identification, localization and activation of dormant hematopoietic stun cells in vivo Somatic stem cells are present in most self-renewing tissues including the skin, the intestinal epithelium and the hematopoietic system. On a single cell basis they have the capacity to produce more stem cells of the same phenotype (self-renewal) and to give rise to a defined set of mature differentiated progeny, responsible for the maintenance or repair of the host tissue. The best characterized adult stem cell is the hematopoietic stem cell (HSC) located in the bone marrow. One goal of my thesis work was to further characterize the location of endogenous HSCs in vivo. To do this, a technique called "label retaining assay» was used which takes advantage of the fact that stem cells (including HSCs) divide very infrequently and can be dormant for months. After labeling mice with the DNA analogue BrdU followed by a long BrdU free "chase", BrdU "label retaining cells" (CRCs) could be identified in the bone marrow. These CRCs were 300-fold enriched for phenotypic HSCs and by using flow cytometry analysis it could be shown that about 15% of all HSCs in the mouse are dormant for many weeks. Our results suggest that these long-term dormant HSCs are unlikely to be involved in homeostatic maintenance. However they are rapidly activated and reenter the cell cycle in response to injury signals such as myeloid ablation. In addition, detection of LRCs in combination with the HSC marker c-Kit could be used to locate engrafted dormant HSCs close to the endosteal lining of the bone marrow cavities. Most surprisingly, c-Kit+LRCs were found predominantly as single cells suggesting that the specific stem cell maintaining microenvironment, called niche, has limited space and may house only single HSCs. Complex roles of the tumor suppressor gene Pten in the hematopoietic system. The phosphatase PTEN is lost in hereditary and sporadic forms of human cancers, including gliomas, endometrial and breast cancers. Pten inhibits the PI3-kina.se pathway and plays a key role in apoptosis, cell growth, proliferation and migration. Our aim was to study the role of Pten in normal HSCs and during leukemia formation. To do this, we generated a mouse model in which the Pten gene can be deleted in hematopoietic cells including HSCs. This was achieved by crossing the conditional ptenflox allele with either the interferona inducible MxCre or the tamoxifen inducible Scl-CreERT transgene. This allowed the conversion of the ptenflox allele into a pterr' null allele in HSCs and other hematopoietic cell types. As a result Pten mutant mice developed massive splenomegaly due to a dramatic expansion of all myeloid cells. Interestingly, while the number of bone marrow HSCs progressively decreased, the number of HSCs in the spleen increased to a similar extent. Unexpectedly, extensive cell cycle analysis showed that Pten had little or no effect on HSC dormancy or HSC self-renewal. Instead, dramatically increased levels of the mobilizing cytokine G-CSF were detected in the blood serum suggesting that loss-of Pten stimulates mobilization and migration of HSC from the BM to the spleen. Finally, transplantation of Pten deficient BM cells into immuno-compromised mice showed that Pten can function as a tumor suppressor in the hematopoietic system and that its absence leads to the rapid formation of T cell leukemia.
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Within only two decades olive oil developed from a niche product which could hardly be found in food stores outside the producing regions towards an integrated component in the diets of industrial countries. This paper discusses the impacts of the promotion of the “healthy Mediterranean diet” on land use and agro-ecosystems in the producing countries. It examines the dynamics of olive oil production, trade and consumption in the EU15 in the period 1972 to 2003 and the links between dietary patterns, trade and land use. It analyses the underlying socio-economic driving forces behind the increasing spatial disconnect between production and consumption of olive oil in the EU15 and in particular in Spain, the world largest producer during the last three decades. In the observed period olive oil consumption increased 16 fold in the non-producing EU15 countries. In the geographically limited producing regions like Spain, the 5 fold increase in export production was associated with the rapid industrialization of olive production, the conversion of vast Mediterranean landscapes to olive monocultures and a range of environmental pressures. High amounts of subsidies of the European Common Agricultural Policy and feedback loops within production and consumption systems were driving the transformation of the olive oil system. Our analysis indicates the process of change was not immediately driven by increases in demand for olive oil in non-producing countries, but rather by the institutional setting of the European Union and by concerted political interventions.
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Aim Understanding the stability of realised niches is crucial for predicting the responses of species to climate change. One approach is to evaluate the niche differences of populations of the same species that occupy regions that are geographically disconnected. Here, we assess niche conservatism along thermal gradients for 26 plant species with a disjunct distribution between the Alps and the Arctic. Location European Alps and Norwegian Finnmark. Methods We collected a comprehensive dataset of 26 arctic-alpine plant occurrences in two regions. We assessed niche conservatism through a multi-species comparison and analysed species rankings at cold and warm thermal limits along two distinct gradients corresponding to (1) air temperatures at 2 meters above ground level and (2) elevation distances to the treeline (TLD) for the two regions. We assessed whether observed relationships were close to those predicted under thermal limit conservatism. Results We found a weak similarity in species ranking at the warm thermal limits. The range of warm thermal limits for the 26 species was much larger in the Alps than in Finnmark. We found a stronger similarity in species ranking and correspondence at the cold thermal limit along the gradients of 2-m temperature and TLD. Yet, along the 2-m temperature gradient, the cold thermal limits of species in the Alps were lower on average than those in Finnmark. Main conclusion We found low conservatism of the warm thermal limits but a stronger conservatism of the cold thermal limits. We suggest that biotic interactions at the warm thermal limit likely modulate species responses more strongly than at the cold limit. The differing biotic context between the two regions is likely responsible for the observed differences in realised niches.
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Background: The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferatoractivated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents.Objectives: In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action.Methods: As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses.Results: DEHP-treated mice were protected from diet-induced obesity via PPARalpha-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPARbeta nor PPARgamma was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPARalpha-humanized mice. These species differences are associated with a different pattern of coregulator recruitment.Conclusion: These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPARalpha signaling and highlight the metabolic importance of the species-specific activation of PPARalpha by xenobiotic compounds. Editor's SummaryDiethylhexyl phthalate (DEHP) is an industrial plasticizer used in cosmetics, medical devices, food packaging, and other applications. Evidence that DEHP metabolites can activate peroxisome proliferatoractivated receptors (PPARs) involved in fatty acid oxidation (PPARalpha and PPARbeta) and adiposite function and insulin resistance (PPARgamma) has raised concerns about potential effects of DEHP on metabolic homeostasis. In rodents, PPARalpha activation also induces hepatic peroxisome proliferation, but this response to PPARalpha activation is not observed in humans. Feige et al. (p. 234) evaluated systemic and metabolic consequences of high-dose oral DEHP in combination with a high-fat diet in wild-type mice and genetically engineered mouse PPAR models. The authors report that mice exposed to DEHP gained less weight than controls, without modifying their feeding behavior; they also exhibited lower triglyceride levels, smaller adipocytes, and improved glucose tolerance compared with controls. These effects, which were observed in mice fed both high-fat and standard diets, appeared to be mediated by PPARalpha-dependent activation of hepatic fatty acid catabolism without apparent involvement of PPARbeta or PPARgamma. However, mouse models that expressed human (versus mouse) PPARalpha tended to gain more weight on a high-fat diet than their DHEP-unexposed counterparts. The authors conclude that findings support species-specific metabolic effects of DEHP mediated by PPARalpha activation.
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Despite opportunities for radiation provided by spatio-temporal isolation, the basic morphological plan of pulmonate snails has remained conservative. In consequence of the resulting dearth of morphological characters and their plasticity, there is a case for using biochemical characters such as exogenous chemicals released by the snails (e.g. amino acids) and their chemoreception niche as taxonomic aids to classify snails of medical importance. As these same chemicals are used by snails to distinguish conspecifics they could also be used as "environmental antibodies" in controlled release formulations (CRF's) designed to remove target snails in a specific, cost-effective and ecologically acceptable manner. The snails, surface-living bacteria, algae and macrophytic plants are considered as co-evolved, interactive modular systems with strong mutualistic elements. Recently, anthropogenic perturbations such as deforestation, and damming of flowing waters, have benefited these modules whereas others such as river canalization, acid deposition, accumulation of pesticide residues and eutrophication have harmed them. Research is needed to elucidate the factors which limit the growth of snails in primitive habitats, uninfluenced by man, as well as in those subject to harmful anthropogenic factors. The understanding thus gained could be applied to develop cost-effective primary health care strategies to reduce or prevent transmission of schistosomiasis and other water related diseases.