Influência de eventos históricos e recentes na filogeografia e estrutura genética de Neothraupis fasciata (Aves : Thraupidae), uma ave endêmica do Cerrado

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2016.

On the solution of bivariate population balance equations for aggregation: X-discretization of space for expansion and contraction of computational domain

A new structured discretization of 2D space, named X-discretization, is proposed to solve bivariate population balance equations using the framework of minimal internal consistency of discretization of Chakraborty and Kumar [2007, A new framework for solution of multidimensional population balance equations. Chem. Eng. Sci. 62, 4112-4125] for breakup and aggregation of particles. The 2D space of particle constituents (internal attributes) is discretized into bins by using arbitrarily spaced constant composition radial lines and constant mass lines of slope -1. The quadrilaterals are triangulated by using straight lines pointing towards the mean composition line. The monotonicity of the new discretization makes is quite easy to implement, like a rectangular grid but with significantly reduced numerical dispersion. We use the new discretization of space to automate the expansion and contraction of the computational domain for the aggregation process, corresponding to the formation of larger particles and the disappearance of smaller particles by adding and removing the constant mass lines at the boundaries. The results show that the predictions of particle size distribution on fixed X-grid are in better agreement with the analytical solution than those obtained with the earlier techniques. The simulations carried out with expansion and/or contraction of the computational domain as population evolves show that the proposed strategy of evolving the computational domain with the aggregation process brings down the computational effort quite substantially; larger the extent of evolution, greater is the reduction in computational effort. (C) 2011 Elsevier Ltd. All rights reserved.

On the solution of bivariate population balance equations for aggregation: Pivotwise expansion of solution domain

The solution of a bivariate population balance equation (PBE) for aggregation of particles necessitates a large 2-d domain to be covered. A correspondingly large number of discretized equations for particle populations on pivots (representative sizes for bins) are solved, although at the end only a relatively small number of pivots are found to participate in the evolution process. In the present work, we initiate solution of the governing PBE on a small set of pivots that can represent the initial size distribution. New pivots are added to expand the computational domain in directions in which the evolving size distribution advances. A self-sufficient set of rules is developed to automate the addition of pivots, taken from an underlying X-grid formed by intersection of the lines of constant composition and constant particle mass. In order to test the robustness of the rule-set, simulations carried out with pivotwise expansion of X-grid are compared with those obtained using sufficiently large fixed X-grids for a number of composition independent and composition dependent aggregation kernels and initial conditions. The two techniques lead to identical predictions, with the former requiring only a fraction of the computational effort. The rule-set automatically reduces aggregation of particles of same composition to a 1-d problem. A midway change in the direction of expansion of domain, effected by the addition of particles of different mean composition, is captured correctly by the rule-set. The evolving shape of a computational domain carries with it the signature of the aggregation process, which can be insightful in complex and time dependent aggregation conditions. (c) 2012 Elsevier Ltd. All rights reserved.

Spatial expansion and population structure of the neotropical malaria vector, Anopheles darlingi (Diptera: Culicidae)

Extensive population structuring is known to occur in Anopheles darlingi, the primary malaria vector of the Neotropics. We analysed the phylogeographic structure of the species using the mitochondrial cytochrome oxidase I marker. Diversity is divided into six main population groups in South America: Colombia, central Amazonia, southern Brazil, south-eastern Brazil, and two groups in north-east Brazil. The ancestral distribution of the taxon is hypothesized to be central Amazonia, and there is evidence of expansion from this region during the late Pleistocene. The expansion was not a homogeneous front, however, with at least four subgroups being formed due to geographic barriers. As the species spread, populations became isolated from each other by the Amazon River and the coastal mountain ranges of south-eastern Brazil and the Andes. Analyses incorporating distances around these barriers suggest that the entire South American range of An. darlingi is at mutation-dispersal-drift equilibrium. Because the species is distributed throughout such a broad area, the limited dispersal across some landscape types promotes differentiation between otherwise proximate populations. Moreover, samples from the An. darlingi holotype location in Rio de Janeiro State are substantially derived from all other populations, implying that there may be additional genetic differences of epidemiological relevance. The results obtained contribute to our understanding of gene flow in this species and allow the formulation of human mosquito health protocols in light of the potential population differences in vector capacity or tolerance to control strategies. (C) 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 97, 854-866.

Using traditional heuristic algorithms on an initial genetic algorithm population applied to the transmission expansion planning problem

This paper analyses the impact of choosing good initial populations for genetic algorithms regarding convergence speed and final solution quality. Test problems were taken from complex electricity distribution network expansion planning. Constructive heuristic algorithms were used to generate good initial populations, particularly those used in resolving transmission network expansion planning. The results were compared to those found by a genetic algorithm with random initial populations. The results showed that an efficiently generated initial population led to better solutions being found in less time when applied to low complexity electricity distribution networks and better quality solutions for highly complex networks when compared to a genetic algorithm using random initial populations.

Anti-IL-2 Treatment Impairs the Expansion of T-reg Cell Population during Acute Malaria and Enhances the Th1 Cell Response at the Chronic Disease

Plasmodium chabaudi infection induces a rapid and intense splenic CD4(+) T cell response that contributes to both disease pathogenesis and the control of acute parasitemia. The subsequent development of clinical immunity to disease occurs concomitantly with the persistence of low levels of chronic parasitemia. The suppressive activity of regulatory T (T-reg) cells has been implicated in both development of clinical immunity and parasite persistence. To evaluate whether IL-2 is required to induce and to sustain the suppressive activity of T-reg cells in malaria, we examined in detail the effects of anti-IL-2 treatment with JES6-1 monoclonal antibody (mAb) on the splenic CD4(+) T cell response during acute and chronic P. chabaudi AS infection in C57BL/6 mice. JES6-1 treatment on days 0, 2 and 4 of infection partially inhibits the expansion of the CD4(+)CD25(+)Foxp3(+) cell population during acute malaria. Despite the concomitant secretion of IL-2 and expression of high affinity IL-2 receptor by large CD4(+) T cells, JES6-1 treatment does not impair effector CD4+ T cell activation and IFN-gamma production. However, at the chronic phase of the disease, an enhancement of cellular and humoral responses occurs in JES6-1-treated mice, with increased production of TNF-alpha and parasite-specific IgG2a antibodies. Furthermore, JES6-1 mAb completely blocked the in vitro proliferation of CD4(+) T cells from non-treated chronic mice, while it further increased the response of CD4(+) T cells from JES6-1-treated chronic mice. We conclude that JES6-1 treatment impairs the expansion of T-reg cell population during early P. chabaudi malaria and enhances the Th1 cell response in the late phase of the disease.

Expansion of a recurrent V beta 5.3+ T-cell population in newly diagnosed and untreated HLA-DR2 multiple sclerosis patients.

We have used a PCR-based technology to study the V beta 5 and V beta 17 repertoire of T-cell populations in HLA-DR2 multiple sclerosis (MS) patients. We have found that the five MS DR2 patients studied present, at the moment of diagnosis and prior to any treatment, a marked expansion of a CD4+ T-cell population bearing V beta 5-J beta 1.4 beta chains. The sequences of the complementarity-determining region 3 of the expanded T cells are highly homologous. One shares structural features with that of the T cells infiltrating the central nervous system and of myelin basic protein-reactive T cells found in HLA-DR2 MS patients. An homologous sequence was not detectable in MS patients expressing DR alleles other than DR2. However, it is detectable but not expanded in healthy DR2 individuals. The possible mechanisms leading to its in vivo proliferation at the onset of MS are discussed.

Dynamique d’une population faunique en expansion sous différents scénarios climatiques : le dindon sauvage (Meleagris gallopavo)

Les changements climatiques récents ont mené à l’expansion de la répartition de plusieurs espèces méridionales, mais ont aussi causé l’extinction locale d’espèces se retrouvant à la limite de leur tolérance environnementale. Ces populations en expansion peuvent favoriser différentes stratégies d’histoire de vie en répondant à différents facteurs limitants. Dans cette thèse, je vise à déterminer et quantifier l’effet du climat et des évènements extrêmes sur le cycle de vie complet d’une espèce en expansion (le dindon sauvage) pour comprendre les changements au niveau populationnel ainsi que les mécanismes impliqués dans l’expansion de la distribution d’une espèce. J’ai défini les évènements extrêmes de pluie, d’épaisseur de neige au sol et de température, comme un évènement dont la fréquence est plus rare que le 10e et 90e percentile. En utilisant l’approche « Measure-Understand-Predict » (MUP), j’ai tout d’abord suivi trois populations le long d’un gradient latitudinal de sévérité hivernale pour mesurer l’effet de variables météorologiques sur la dynamique des populations. La survie des dindons sauvages diminuait drastiquement lorsque l’accumulation de neige au sol dépassait 30 cm pour une période de 10 jours et diminuait également avec la température. Au printemps, la persistance de la neige affectait négativement le taux d’initiation de la nidification et l’augmentation de la pluie diminuait la survie des nids. Dans une deuxième étape, j’ai examiné l’impact des évènements climatiques extrêmes et des processus démographiques impliqués dans l’expansion du dindon, liés à la théorie des histoires de vie pour comprendre la relation entre la dynamique de ces populations en expansions avec le climat. J’ai démontré que la fréquence des évènements extrêmes hivernaux et, d’une façon moins importante, les évènements extrêmes estivaux limitaient l’expansion nordique des dindons sauvages. J’ai appuyé, à l’aide de données empiriques et de modélisation, les hypothèses de la théorie classique des invasions biologiques en montrant que les populations en établissement priorisaient les paramètres reproducteurs tandis que la survie adulte était le paramètre démographique affectant le plus la dynamique des populations bien établies. De plus, les populations les plus au nord étaient composées d’individus plus jeunes ayant une espérance de vie plus faible, mais avaient un potentiel d’accroissement plus élevé que les populations établies, comme le suggère cette théorie. Finalement, j’ai projeté l’impact de la récolte sur la dynamique des populations de même que le taux de croissance de cette espèce en utilisant les conditions climatiques futures projetées par les modèles de l’IPCC. Les populations en établissement avaient un taux de récolte potentiel plus élevé, mais la proportion de mâles adultes, possédant des caractéristiques recherchées par les chasseurs, diminuait plus rapidement que dans les populations établies. Dans le futur, la fréquence des évènements extrêmes de pluie devrait augmenter tandis que la fréquence des évènements extrêmes de température hivernale et d’accumulation de neige au sol devraient diminuer après 2060, limitant probablement l’expansion nordique du dindon sauvage jusqu’en 2100. Cette thèse améliore notre compréhension des effets météorologiques et du climat sur l’expansion de la répartition des espèces ainsi que les mécanismes démographiques impliqués, et nous a permis de prédire la probabilité de l’expansion nordique de la répartition du dindon sauvage en réponse aux changements climatiques.

Expansion and chondrogenic potential of human articular chondrocytes on macroporous microcarriers

Regenerative medicine techniques are currently being investigated to replace damaged cartilage. Critical to the success of these techniques is the ability to expand the initial population of cells while minimising de-differentiation to allow for hyaline cartilage to form. Three-dimensional culture systems have been shown to enhance the differentiation of chondrocytes in comparison to two-dimensional culture systems. Additionally, bioreactor expansion on microcarriers can provide mechanical stimulation and reduce the amount of cellular manipulation during expansion. The aim of this study was to characterise the expansion of human chondrocytes on microcarriers and to determine their potential to form cartilaginous tissue in vitro. High-grade human articular cartilage was obtained from leg amputations with ethics approval. Chondrocytes were isolated by collagenase digestion and expanded in either monolayers (104 cells/cm2) or on CultiSpher-G microcarriers (104 cells/mg) for three weeks. Following expansion, monolayer cells were passaged and cells on microcarriers were either left intact or the cells were released with trypsin/EDTA. Pellets from these three groups were formed and cultured for three weeks to establish the chondrogenic differentiation potential of monolayer-expanded and microcarrier-expanded chondrocytes. Cell viability, proliferation, glycosaminoglycan (GAG) accumulation, and collagen synthesis were assessed. Histology and immunohistochemistry were also performed. Human chondrocytes remained viable and expanded on microcarriers 10.2±2.6 fold in three weeks. GAG content significantly increased with time, with the majority of GAG found in the medium. Collagen production per nanogram DNA increased marginally during expansion. Histology revealed that chondrocytes were randomly distributed on microcarrier surfaces yet most pores remained cell free. Critically, human chondrocytes expanded on microcarriers maintained their ability to redifferentiate in pellet culture, as demonstrated by Safranin-O and collagen II staining. These data confirm the feasibility of microcarriers for passage-free cultivation of human articular chondrocytes. However, cell expansion needs to be improved, perhaps through growth factor supplementation, for clinical utility. Recent data indicate that cell-laden microcarriers can be used to seed fresh microcarriers, thereby increasing the expansion factor while minimising enzymatic passage.

A brief history of haemotopoietic stem cell Ex vivo expansion

Haematopoiesis is the process by which a hierarchy of mature and progenitor blood cells are formed. These cell populations are all derived from multipotent haematopoietic stem cells (HSC), which reside in the bone marrow ‘niche’ of adult humans. Over the lifetime of a healthy individual, this HSC population replenishes between 1010-1011 blood cells on a daily basis. Dysregulation of this system can lead to a number of haematopoietic diseases, including aplastic anaemias and leukaemias, which result in, or require for disease resolution, bone marrow cell depletion. In 1956, E. Donnall Thomas demonstrated that haematopoiesis could be restored by transplanting bone marrow-derived cells from one man into his identical twin brother, who was suffering from advanced leukaemia. His success drew significant interest in academic research and medicine communities, and 12 years later, the first successful allogeneic transplant was performed. To this day, HSCs remain the most studied and characterised stem cell population. In fact, HSCs are the only stem cell population routinely utilised in the clinic. As such, HSCs function as a model system both for the biological investigation of stem cells, as well as for their clinical application. Herein, we briefly review HSC transplantation, strategies for the ex vivo cultivation of HSCs, recent clinical outcomes, and their impact on the future direction of HSC transplantation therapy.

Colonoscopy requirements of population screening for colorectal cancer in New Zealand

Aim: To estimate the colonoscopy burden of introducing population screening for colorectal cancer in New Zealand. Methods: Screening for colorectal cancer using biennial immunochemical faecal occult blood tests offered to people aged 50-74 years of age was modelled using population estimates from Statistics New Zealand for 2011-2031. Modelling to determine colonoscopy requirements was based on participation and test positivity rates from published results of screening programmes. Estimates of the number of procedures required for ongoing adenoma surveillance were calculated using screening literature results of adenoma yield, and New Zealand Guidelines for Adenoma Surveillance. Sensitivity analysis was undertaken on key parameters. Results: For a test positivity of 6.4%, biennial screening using immunochemical faecal occult blood testing with a 60% participation rate, would require 18,000 colonoscopies nationally, increasing to 28,000 by 2031. The majority of procedures are direct referrals from a positive FOBT, with surveillance colonoscopy numbers building over time. Conclusion: Colonoscopy requirements for immunochemical faecal occult blood based population screening for colorectal cancer are high. Significant expansion of services is required and careful management of surveillance procedures to ensure timely delivery of initial colonoscopies whilst maintaining symptomatic services. A model re-run informed by data from the screening pilot will allow improved estimates for the New Zealand setting.

Rapid Global Expansion of the Fungal Disease Chytridiomycosis into Declining and Healthy Amphibian Populations.

The fungal disease chytridiomycosis, caused by Batrachochytrium dendrobatidis, is enigmatic because it occurs globally in both declining and apparently healthy (non-declining) amphibian populations. This distribution has fueled debate concerning whether, in sites where it has recently been found, the pathogen was introduced or is endemic. In this study, we addressed the molecular population genetics of a global collection of fungal strains from both declining and healthy amphibian populations using DNA sequence variation from 17 nuclear loci and a large fragment from the mitochondrial genome. We found a low rate of DNA polymorphism, with only two sequence alleles detected at each locus, but a high diversity of diploid genotypes. Half of the loci displayed an excess of heterozygous genotypes, consistent with a primarily clonal mode of reproduction. Despite the absence of obvious sex, genotypic diversity was high (44 unique genotypes out of 59 strains). We provide evidence that the observed genotypic variation can be generated by loss of heterozygosity through mitotic recombination. One strain isolated from a bullfrog possessed as much allelic diversity as the entire global sample, suggesting the current epidemic can be traced back to the outbreak of a single clonal lineage. These data are consistent with the current chytridiomycosis epidemic resulting from a novel pathogen undergoing a rapid and recent range expansion. The widespread occurrence of the same lineage in both healthy and declining populations suggests that the outcome of the disease is contingent on environmental factors and host resistance.