247 resultados para Angiogenesis patterns


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Aim This study compares the direct, macroecological approach (MEM) for modelling species richness (SR) with the more recent approach of stacking predictions from individual species distributions (S-SDM). We implemented both approaches on the same dataset and discuss their respective theoretical assumptions, strengths and drawbacks. We also tested how both approaches performed in reproducing observed patterns of SR along an elevational gradient.Location Two study areas in the Alps of Switzerland.Methods We implemented MEM by relating the species counts to environmental predictors with statistical models, assuming a Poisson distribution. S-SDM was implemented by modelling each species distribution individually and then stacking the obtained prediction maps in three different ways - summing binary predictions, summing random draws of binomial trials and summing predicted probabilities - to obtain a final species count.Results The direct MEM approach yields nearly unbiased predictions centred around the observed mean values, but with a lower correlation between predictions and observations, than that achieved by the S-SDM approaches. This method also cannot provide any information on species identity and, thus, community composition. It does, however, accurately reproduce the hump-shaped pattern of SR observed along the elevational gradient. The S-SDM approach summing binary maps can predict individual species and thus communities, but tends to overpredict SR. The two other S-SDM approaches the summed binomial trials based on predicted probabilities and summed predicted probabilities - do not overpredict richness, but they predict many competing end points of assembly or they lose the individual species predictions, respectively. Furthermore, all S-SDM approaches fail to appropriately reproduce the observed hump-shaped patterns of SR along the elevational gradient.Main conclusions Macroecological approach and S-SDM have complementary strengths. We suggest that both could be used in combination to obtain better SR predictions by following the suggestion of constraining S-SDM by MEM predictions.

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BACKGROUND: We studied human cytomegalovirus (CMV) donor-to-recipient transmission patterns in organ transplantation by analyzing genomic variants on the basis of CMV glycoprotein B (gB) genotyping. METHODS: Organ transplant recipients were included in the study if they had CMV viremia, if they had received an organ from a CMV-seropositive donor, and if there was at least 1 other recipient of an organ from the same donor who developed CMV viremia. Genotypes (gB1-4) were determined by real-time polymerase chain reaction. RESULTS: Forty-seven recipients of organs from 21 donors developed CMV viremia. Twenty-three recipients had a pretransplant donor/recipient (D/R) CMV serostatus of D(+)/R(+), and 24 had a serostatus of D(+)/R(-). The prevalences of genotypes in recipients were as follows: for gB1, 51% (n = 24); for gB2, 19% (n = 9); for gB3, 9% (n = 4); for gB4, 0% (n = 0); and for mixed infection, 21% (n = 10). Recipients of an organ from a common donor had infection with CMV of the same gB genotype in 12 (57%) of 21 instances. Concordance between genotypes was higher among seronegative (i.e., D(+)/R(-)) recipients than among seropositive (D(+)/R(+)) recipients, although discordances resulting from the transmission of multiple strains were seen. In seropositive recipients, transmission of multiple strains from the donor could not be differentiated from reactivation of a recipient's own strains. CONCLUSION: Our analysis of strain concordance among recipients of organs from common donors showed that transmission of CMV has complex dynamic patterns. In seropositive recipients, transmission or reactivation of multiple CMV strains is possible.

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Aim. Stressful life events are an important contributor to the onset and course of depression. Coping strategies and interpersonal patterns have been found to mediate the effects of stress [1]. Methods. This study examined the relationship between coping patterns and interpersonal interactions in early psychotherapy sessions of 25 female patients with major depression. Transcripts were rated for coping patterns using the Coping Patterns Rating Scale (CPRS; [2]). Interpersonal patterns were assessed using the Structural Analysis of Social Behavior (SASB; [3]). Results. Significant correlations were found between coping patterns and markers of interpersonal functioning in selected contexts. Discussion. The implications of these findings in understanding an important aspect of vulnerability to depression and enhancing treatment outcome are discussed.

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Understanding the distribution and composition of species assemblages and being able to predict them in space and time are highly important tasks io investigate the fate of biodiversity in the current global changes context. Species distribution models are tools that have proven useful to predict the potential distribution of species by relating their occurrences to environmental variables. Species assemblages can then be predicted by combining the prediction of individual species models. In the first part of my thesis, I tested the importance of new environmental predictors to improve species distribution prediction. I showed that edaphic variables, above all soil pH and nitrogen content could be important in species distribution models. In a second chapter, I tested the influence of different resolution of predictors on the predictive ability of species distribution models. I showed that fine resolution predictors could ameliorate the models for some species by giving a better estimation of the micro-topographic condition that species tolerate, but that fine resolution predictors for climatic factors still need to be ameliorated. The second goal of my thesis was to test the ability of empirical models to predict species assemblages' characteristics such as species richness or functional attributes. I showed that species richness could be modelled efficiently and that the resulting prediction gave a more realistic estimate of the number of species than when obtaining it by stacking outputs of single species distribution models. Regarding the prediction of functional characteristics (plant height, leaf surface, seed mass) of plant assemblages, mean and extreme values of functional traits were better predictable than indices reflecting the diversity of traits in the community. This approach proved interesting to understand which environmental conditions influence particular aspects of the vegetation functioning. It could also be useful to predict climate change impacts on the vegetation. In the last part of my thesis, I studied the capacity of stacked species distribution models to predict the plant assemblages. I showed that this method tended to over-predict the number of species and that the composition of the community was not predicted exactly either. Finally, I combined the results of macro- ecological models obtained in the preceding chapters with stacked species distribution models and showed that this approach reduced significantly the number of species predicted and that the prediction of the composition is also ameliorated in some cases. These results showed that this method is promising. It needs now to be tested on further data sets. - Comprendre la manière dont les plantes se répartissent dans l'environnement et s'organisent en communauté est une question primordiale dans le contexte actuel de changements globaux. Cette connaissance peut nous aider à sauvegarder la diversité des espèces et les écosystèmes. Des méthodes statistiques nous permettent de prédire la distribution des espèces de plantes dans l'espace géographique et dans le temps. Ces modèles de distribution d'espèces, relient les occurrences d'une espèce avec des variables environnementales pour décrire sa distribution potentielle. Cette méthode a fait ses preuves pour ce qui est de la prédiction d'espèces individuelles. Plus récemment plusieurs tentatives de cumul de modèles d'espèces individuelles ont été réalisées afin de prédire la composition des communautés végétales. Le premier objectif de mon travail est d'améliorer les modèles de distribution en testant l'importance de nouvelles variables prédictives. Parmi différentes variables édaphiques, le pH et la teneur en azote du sol se sont avérés des facteurs non négligeables pour prédire la distribution des plantes. Je démontre aussi dans un second chapitre que les prédicteurs environnementaux à fine résolution permettent de refléter les conditions micro-topographiques subies par les plantes mais qu'ils doivent encore être améliorés avant de pouvoir être employés de manière efficace dans les modèles. Le deuxième objectif de ce travail consistait à étudier le développement de modèles prédictifs pour des attributs des communautés végétales tels que, par exemple, la richesse en espèces rencontrée à chaque point. Je démontre qu'il est possible de prédire par ce biais des valeurs de richesse spécifiques plus réalistes qu'en sommant les prédictions obtenues précédemment pour des espèces individuelles. J'ai également prédit dans l'espace et dans le temps des caractéristiques de la végétation telles que sa hauteur moyenne, minimale et maximale. Cette approche peut être utile pour comprendre quels facteurs environnementaux promeuvent différents types de végétation ainsi que pour évaluer les changements à attendre au niveau de la végétation dans le futur sous différents régimes de changements climatiques. Dans une troisième partie de ma thèse, j'ai exploré la possibilité de prédire les assemblages de plantes premièrement en cumulant les prédictions obtenues à partir de modèles individuels pour chaque espèce. Cette méthode a le défaut de prédire trop d'espèces par rapport à ce qui est observé en réalité. J'ai finalement employé le modèle de richesse en espèce développé précédemment pour contraindre les résultats du modèle d'assemblage de plantes. Cela a permis l'amélioration des modèles en réduisant la sur-prédiction et en améliorant la prédiction de la composition en espèces. Cette méthode semble prometteuse mais de nouveaux tests sont nécessaires pour bien évaluer ses capacités.

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Myocardial angiogenesis induction with vascular growth factors constitutes a potential strategy for patients whose coronary artery disease is refractory to conventional treatment. The importance of angiogenesis in bone formation has led to the development of growth factors derived from bovine bone protein. Twelve pigs (mean weight, 73 +/- 3 kg) were chosen for the study. In the first group (n = 6, growth factor group) five 100 micrograms boluses of growth factors derived from bovine bone protein, diluted in Povidone 5%, were injected in the lateral wall of the left ventricle. In the second group (n = 6, control group), the same operation was performed but only the diluting agent was injected. All the animals were sacrificed after 28 days and the vascular density of the left lateral wall (expressed as the number of vascular structures per mm2) as well as the area of blood vessel profiles per myocardial area analysed were determined histologically with a computerised system. The growth factor group had a capillary density which was significantly higher than that of the control group: 12.6 +/- 0.9/mm2 vs 4.8 +/- 0.5/mm2 (p < 0.01). The same holds true for the arteriolar density: 1 +/- 0.2/mm2 vs 0.3 +/- 0.1/mm2 (p < 0.01). The surface ratios of blood vessel profiles per myocardial area were 4900 +/- 800 micron 2/mm2 and 1550 +/- 400 micron 2/mm2 (p < 0.01) respectively. In this experimental model, bovine bone protein derived growth factors induce a significant neovascularisation in healthy myocardium, and appear therefore as promising candidates for therapeutic angiogenesis.

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Photodynamic therapy (PDT) is a minimally invasive form of treatment, which is clinically approved for the treatment of angiogenic disorders, including certain forms of cancer and neovascular eye diseases. Although the concept of PDT has existed for a long time now, it has never made a solid entrance into the clinical management of cancer. This is likely due to secondary tissue reactions, such as inflammation and neoangiogenesis. The recent development of clinically effective angiogenesis inhibitors has lead to the initiation of research on the combination of PDT with such angiostatic targeted therapies. Preclinical studies in this research field have shown promising results, causing a revival in the field of PDT. This review reports on the current research efforts on PDT and vascular targeted combination therapies. Different combination strategies with angiogenesis inhibition and vascular targeting approaches are discussed. In addition, the concept of increasing PDT selectivity by targeted delivery of photosensitizers is presented. Furthermore, the current insights on sequencing the therapy arms of such combinations will be discussed in light of vascular normalization induced by angiogenesis inhibition.

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BACKGROUND: Adherence to combination antiretroviral therapy (cART) is a dynamic process, however, changes in adherence behavior over time are insufficiently understood. METHODS: Data on self-reported missed doses of cART was collected every 6 months in Swiss HIV Cohort Study participants. We identified behavioral groups associated with specific cART adherence patterns using trajectory analyses. Repeated measures logistic regression identified predictors of changes in adherence between consecutive visits. RESULTS: Six thousand seven hundred nine individuals completed 49,071 adherence questionnaires [median 8 (interquartile range: 5-10)] during a median follow-up time of 4.5 years (interquartile range: 2.4-5.1). Individuals were clustered into 4 adherence groups: good (51.8%), worsening (17.4%), improving (17.6%), and poor adherence (13.2%). Independent predictors of worsening adherence were younger age, basic education, loss of a roommate, starting intravenous drug use, increasing alcohol intake, depression, longer time with HIV, onset of lipodystrophy, and changing care provider. Independent predictors of improvements in adherence were regimen simplification, changing class of cART, less time on cART, and starting comedications. CONCLUSIONS: Treatment, behavioral changes, and life events influence patterns of drug intake in HIV patients. Clinical care providers should routinely monitor factors related to worsening adherence and intervene early to reduce the risk of treatment failure and drug resistance.

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A methodology of exploratory data analysis investigating the phenomenon of orographic precipitation enhancement is proposed. The precipitation observations obtained from three Swiss Doppler weather radars are analysed for the major precipitation event of August 2005 in the Alps. Image processing techniques are used to detect significant precipitation cells/pixels from radar images while filtering out spurious effects due to ground clutter. The contribution of topography to precipitation patterns is described by an extensive set of topographical descriptors computed from the digital elevation model at multiple spatial scales. Additionally, the motion vector field is derived from subsequent radar images and integrated into a set of topographic features to highlight the slopes exposed to main flows. Following the exploratory data analysis with a recent algorithm of spectral clustering, it is shown that orographic precipitation cells are generated under specific flow and topographic conditions. Repeatability of precipitation patterns in particular spatial locations is found to be linked to specific local terrain shapes, e.g. at the top of hills and on the upwind side of the mountains. This methodology and our empirical findings for the Alpine region provide a basis for building computational data-driven models of orographic enhancement and triggering of precipitation. Copyright (C) 2011 Royal Meteorological Society .

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The microenvironment hosting a tumor actively participates in regulating tumor cell proliferation, migration, and invasion. Among the extracellular matrix proteins enriched in the stroma of carcinomas are the tenascin family members tenascin-C and tenascin-W. Whereas tenascin-C overexpression in gliomas is known to correlate with poor prognosis, the status of tenascin-W in brain tumors has not been investigated so far. In the present study, we analyzed protein levels of tenascin-W in 38 human gliomas and found expression of tenascin-W in 80% of the tumor samples, whereas no tenascin-W could be detected in control, nontumoral brain tissues. Double immunohistochemical staining of tenascin-W and von Willebrand factor revealed that tenascin-W is localized around blood vessels, exclusively in tumor samples. In vitro, the presence of tenascin-W increased the proportion of elongated human umbilical vein endothelial cells (HUVECs) and augmented the mean speed of cell migration. Furthermore, tenascin-W triggered sprouting of HUVEC spheroids to a similar extent as the proangiogenic factor tenascin-C. In conclusion, our study identifies tenascin-W as a candidate biomarker for brain tumor angiogenesis that could be used as a molecular target for therapy irrespective of the glioma subtype.-Martina, E., Degen, M., Rüegg, C., Merlo, A., Lino, M. M., Chiquet-Ehrismann, R., Brellier, F. Tenascin-W is a specific marker of glioma-associated blood vessels and stimulates angiogenesis in vitro.

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Males in many animal species differ greatly from females in morphology, physiology and behaviour. Ants, bees and wasps have a haplodiploid mechanism of sex determination whereby unfertilized eggs become males while fertilized eggs become females. However, many species also have a low frequency of diploid males, which are thought to develop from diploid eggs when individuals are homozygous at one or more sex determination loci. Diploid males are morphologically similar to haploids, though often larger and typically sterile. To determine how ploidy level and sex-locus genotype affect gene expression during development, we compared expression patterns between diploid males, haploid males and females (queens) at three developmental timepoints in Solenopsis invicta. In pupae, gene expression profiles of diploid males were very different from those of haploid males but nearly identical to those of queens. An unexpected shift in expression patterns emerged soon after adult eclosion, with diploid male patterns diverging from those of queens to resemble those of haploid males, a pattern retained in older adults. The finding that ploidy level effects on early gene expression override sex effects (including genes implicated in sperm production and pheromone production/perception) may explain diploid male sterility and lack of worker discrimination against them during development.

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MicroRNAs (miRNAs) constitute an important class of gene regulators. While models have been proposed to explain their appearance and expansion, the validation of these models has been difficult due to the lack of comparative studies. Here, we analyze miRNA evolutionary patterns in two mammals, human and mouse, in relation to the age of miRNA families. In this comparative framework, we confirm some predictions of previously advanced models of miRNA evolution, e.g. that miRNAs arise more frequently de novo than by duplication, or that the number of protein-coding gene targeted by miRNAs decreases with evolutionary time. We also corroborate that miRNAs display an increase in expression level with evolutionary time, however we show that this relation is largely tissue-dependent, and especially low in embryonic or nervous tissues. We identify a bias of tag-sequencing techniques regarding the assessment of breadth of expression, leading us, contrary to predictions, to find more tissue-specific expression of older miRNAs. Together, our results refine the models used so far to depict the evolution of miRNA genes. They underline the role of tissue-specific selective forces on the evolution of miRNAs, as well as the potential co-evolution patterns between miRNAs and the protein-coding genes they target.

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Summary : Clinical evidence indicates that tumors recurring within previously irradiated fields are highly invasive and metastatic, suggesting a role of the tumor stroma in this effect. Angiogenesis plays a critical role in tumor progression. Ionizing radiation is known to induce apoptosis of angiogenic endothelial cells, while the effect on quiescent endothelial cells and de novo angiogenesis is not well characterized. We recently observed that irradiation of normal tissue prevents tumor- and growth factor-induced angiogenesis. The main aim of my thesis work was to characterize the mechanisms of radiation-mediated inhibition of angiogenesis. To this purpose we used a combination of in vivo and ex vivo studies on irradiated healthy tissue, and in vitro irradiation experiments using angiogenesis models and isolated endothelial cells. We found that irradiation did not induce endothelial cell apoptosis and did not disrupt quiescent vessels within irradiated skin. Radiation reduced the recruitment of leukocytes to angiogenic Matrigel plugs, but this effect was rather secondary to decreased angiogenesis, as exogenous addition of leucocytes to Matrigel plugs did not rescue the angiogenesis defects. To ascertain the direct effect of radiation on endothelial cells, we used the mouse aortic ring assay to test the sprouting capacity of irradiated endothelial cells ex vivo and in vitro, and found that irradiation completely suppressed endothelial cell sprouting. Using HUVEC cells, we showed that irradiation of quiescent confluent endothelial cells did not induce cell death but suppressed subsequent migration and cell proliferation and induced senescence. By Western blotting, we observed a rapid and sustained increase in p21 levels, previously shown to be activated by p53 in response to double strand break, and mediating senescence in human cells. Current experiments focus on the mechanism of sustained p21 upregulation and its role in reduced migration. Inhibition of endothelial cell migration and proliferation by radiation may explain reduced angiogenesis in tumors growing in previously irradiated fields.

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Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors, but individual exposure data remain scarce. While ground UV irradiance is monitored via different techniques, it is difficult to translate such observations into human UV exposure or dose because of confounding factors. A multi-disciplinary collaboration developed a model predicting the dose and distribution of UV exposure on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a simulation tool that estimates solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by various body locations is computed for direct, diffuse and reflected radiation separately. Dosimetric measurements obtained in field conditions were used to assess the model performance. The model predicted exposure to solar UV adequately with a symmetric mean absolute percentage error of 13% and half of the predictions within 17% range of the measurements. Using this tool, solar UV exposure patterns were investigated with respect to the relative contribution of the direct, diffuse and reflected radiation. Exposure doses for various body parts and exposure scenarios of a standing individual were assessed using erythemally-weighted UV ground irradiance data measured in 2009 at Payerne, Switzerland as input. For most anatomical sites, mean daily doses were high (typically 6.2-14.6 Standard Erythemal Dose, SED) and exceeded recommended exposure values. Direct exposure was important during specific periods (e. g. midday during summer), but contributed moderately to the annual dose, ranging from 15 to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose.

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OBJECTIVES: The aim of this study was to evaluate new electrocardiographic (ECG) criteria for discriminating between incomplete right bundle branch block (RBBB) and the Brugada types 2 and 3 ECG patterns. BACKGROUND: Brugada syndrome can manifest as either type 2 or type 3 pattern. The latter should be distinguished from incomplete RBBB, present in 3% of the population. METHODS: Thirty-eight patients with either type 2 or type 3 Brugada pattern that were referred for an antiarrhythmic drug challenge (AAD) were included. Before AAD, 2 angles were measured from ECG leads V(1) and/or V(2) showing incomplete RBBB: 1) α, the angle between a vertical line and the downslope of the r'-wave, and 2) β, the angle between the upslope of the S-wave and the downslope of the r'-wave. Baseline angle values, alone or combined with QRS duration, were compared between patients with negative and positive results on AAD. Receiver-operating characteristic curves were constructed to identify optimal discriminative cutoff values. RESULTS: The mean β angle was significantly smaller in the 14 patients with negative results on AAD compared to the 24 patients with positive results on AAD (36 ± 20° vs. 62 ± 20°, p < 0.01). Its optimal cutoff value was 58°, which yielded a positive predictive value of 73% and a negative predictive value of 87% for conversion to type 1 pattern on AAD; α was slightly less sensitive and specific compared with β. When the angles were combined with QRS duration, it tended to improve discrimination. CONCLUSIONS: In patients with suspected Brugada syndrome, simple ECG criteria can enable discrimination between incomplete RBBB and types 2 and 3 Brugada patterns.