No description available.

No description available.

The development of radiata pine (Pinus radiata D. Don.) clones was compared in monoclonal and clonal mixture plots planted in an experiment established at Dalethorpe, Canterbury, New Zealand with ten radiata pine clones in September 1993. Clones were deployed in a randomised complete block plot design with three replications. Each replication contained ten treatments of monoclonal plots and one in which all the clones were intimately mixed in equal proportions. Clones significantly differed in initial morphologies, survival and stem slenderness. Sturdiness and initial heights were found to be the best predictors of initial survivals. The study revealed that mode of deployment did not affect overall productivity, but individual clones exhibited significantly different productivities between modes of deployment. All clones contributed similarly to overall productivity in the monoclonal mode of deployment, whereas the contribution of clones in the clonal mixture mode of deployment was disproportionate. A minority of the clones contributed a majority of overall productivity in the clonal mixture mode of deployment. The inclusion of competition index as an independent variable in a distance-dependent individual tree diameter increment model explained a significant amount of variability in diameter growth. The use of an inverse-squared distance to neighbouring plants in the competition index provided a slightly superior fit to the data compared to one that employed a simple inverse of distance. Addition of genotype information in the competition index further improved the fit of the model. Clones experienced different levels of competition in monoclonal and clonal mixture modes of deployment. Competition in monoclonal plots remained uniform over time, whereas some clones experienced greater competition in clonal mixture plots which led to greater variability in their tree sizes. This study indicated that single tree plot progeny test selections and early selections may miss out some good genotypes that can grow rapidly if deployed monoclonally. Stand level modelling revealed that clones differed significantly in modeled yield patterns and model asymptotes. Clones formed two distinct groups having significantly different yield models. The study also demonstrated that models developed from an initial few years’ data were biased indicators of their relative future performances. Evaluation of effectiveness of the 3-PG hybrid model using parameter values obtained from destructive sampling and species-specific values from different studies revealed that it is possible to calibrate this model for simulating the productivity of clones, and predictions from this model might inform clonal selections at different sites under differing climatic conditions. Destructive sampling at age 5 years revealed that clones significantly differed in foliage and stem biomass. The differences in productivities of clones were mainly due to differences in biomass partitioning and specific leaf areas. Clones significantly differed in dynamic wood stiffness, stem-slenderness, branch diameter, branch index and branch angle at an initial stocking of 1250 stems/ha. Mode of deployment affected stem slenderness, which is sometimes related to stiffness. Although dynamic stiffness was correlated with stem slenderness and stem slenderness exhibited a significant influence on stiffness, clones did not exhibit statistically significant differences in dynamic stiffness. Increasing initial stocking from 833 stems/ha to 2500 stems/ha resulted in a 56 % decrease in branch diameter and a 17 % increase in branch angle. Trees in the monoclonal mode of deployment exhibited greater uniformity with respect to tree size, stem-slenderness, and competition experienced by clones compared to those in the clonal mixture mode of deployment. Susceptibility of one clone to Woolly aphid suggested that greater risks were associated with large scale deployment of susceptible clones in a monoclonal mode of deployment. This study also indicated that if the plants were to be deployed in a monoclonal mode then block plot selections would have greater potential to enhance productivity.

Submitted by Marco Antônio de Ramos Chagas (mchagas@ufv.br) on 2017-07-11T18:06:56Z No. of bitstreams: 1 texto completo.pdf: 518257 bytes, checksum: a284ae16f3d43e9016579dfb01f9d2c4 (MD5) / Made available in DSpace on 2017-07-11T18:06:56Z (GMT). No. of bitstreams: 1 texto completo.pdf: 518257 bytes, checksum: a284ae16f3d43e9016579dfb01f9d2c4 (MD5) Previous issue date: 2001-04-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A base da silvicultura clonal para o gênero Eucalyptus está na utilização de clones de alta produtividade, normalmente identificados nas avaliações dos testes clonais. Em geral, quanto maior o número de clones avaliados por unidade de tempo, maior a possibilidade de sucesso com a seleção. Entretanto, as etapas de avaliação e seleção são as mais caras e demoradas do programa de melhoramento, dificultando a elaboração e a execução de extensos programas de seleção de clones. Assim, o presente trabalho teve como objetivos: a avaliação da influência da idade, do espaçamento e do local sobre o tamanho da parcela experimental em testes clonais, considerando-se os coeficientes de variação experimentais, coeficientes de variação fenotípicos e produtividade em volume; e a determinação do tamanho da parcela experimental, por meio do Método de Máxima Curvatura Modificado, do Coeficiente de Correlação Intraclasse e da Análise Visual. A partir de quatro testes clonais, estabelecidos em área da International Paper do Brasil Ltda., analisaram -se as características altura, dap e volume dos quatro testes clonais, dispostos em delineamento em blocos ao acaso, com quatro repetições e parcela experimental quadrada de 25 plantas (5 x 5). Após a simulação de diferentes tamanhos de parcela: 2, 3, 4, 5, 9, 10, 15, 20 e 25 plantas/parcela, procedeu-se às análises do efeito do tamanho da parcela na produtividade, na precisão experimental e na variação do coeficiente fenotípico. Determinou-se, também, o tamanho da parcela pelos Métodos de Máxima Curvatura Modificado, do Coeficiente de Correlação Intraclasse e da Análise Visual. De forma geral, o tamanho da parcela não alterou a estimativa de produção volumétrica dos clones nas diferentes idades analisadas. No entanto, o coeficiente de variação experimental (CV exp ) e o coeficiente de variação fenotípico (CV f ) apresentaram maiores valores nas idades mais avançadas e com tendência de queda com o aumento do número de plantas na parcela, independentemente da idade. O espaçamento de plantio pode alterar o tamanho da parcela, pois, quanto maior o espaçamento, menores o CV exp e o CV f . O comportamento da parcela foi pouco influenciado pelas avaliações realizadas nos diferentes locais. O tamanho mínimo da parcela experimental indicado pelos Métodos de Máxima Curvatura Modificado e pelo Coeficiente de Correlação Intraclasse variou de 1 a 8,6 plantas/parcela; já na análise visual, variou de 5 a 15 plantas por parcela, nos diferentes testes clonais e nas características analisadas. Com base no presente estudo, pôde-se concluir que, em programas iniciais para seleção de clones, parcela de 5 a 10 plantas indica boa precisão experimental, sendo recomendada, principalmente, em situação com limitações de mudas, teste de grande número de clones e avaliações de cunho preliminar e em idade precoce. No entanto, vale ressaltar que, para um melhor conhecimento do clone para uso comercial, parcelas quadradas maiores e, ou, plantios-piloto são os mais indicados. / The base of clonal forestry for the Eucalyptus gender is the use of high production clones, normally identified in clonal test evaluations. In general, the higher the number of evaluated clones per time unit, the greater the possibility of a successful selection. However, the evaluation and selection stages are the most expensive and time-consuming of the enhancement program, creating difficulties for working out and carrying out extensive clone selection programs. Therefore, the present study had the objectives: evaluation of age influence, spacing and site on the experimental parcel size in clonal tests, considering the coefficient of variation experimental, the coefficient of variation phenotype and the volume productivity, as well as the determination of the experimental parcel size, by means of the Maximum Modified Curvation, the Interclass Correlation coefficient and Visual Analysis methods. Based on four clonal tests, established in the area of International Paper of Brazil Ltda., the characteristics height, diameter at breast height and volume were tested in the four clonal tests, set up in design of random blocks in four repetitions, in experimental square parcels of 25 plants (5x5). After the simulation of different parcel sizes: 2, 3, 4, 5, 10, 15, 20 and 25 plants/parcel, the influence of the parcel size on the productivity, the experimental accuracy and the variation of the phenotype coefficient were tested. The parcel size was also determined by the Maximum Modified Curvation, the Interclass Correlation Coefficient and the Visual Analysis methods. In the main, the parcel size did not influence the volume production estimative of the clones at the different analyzed ages. However, the coefficient of variation experimental (CV exp ) and the coefficient of variation phenotype (CV ph ) presented higher values at more advanced ages, with a sinking tendency when the number of plants in the parcel was reduced, independent of the age. The plant spacing can change the parcel size, since the greater the spacing, the lower the CV exp and CV ph . The parcel behavior was little influenced by the evaluations performed in the different sites. The minimum size of the experimental parcel indicated by the Maximum Modified Curvation and the Interclass Correlation Coefficient methods ranged from 1 to 8.6 plants per parcel, while for the Visual Analysis it varied from 5 to 15 plants per parcel in the different clone tests and the analyzed characteristics. Based on the present study, the conclusion can be drawn that in initial clone selection programs, parcels of 5 to 10 plants provide good experimental accuracy, especially recommended when there is only a limited number of seedlings available, a high number of test clones and evaluations of preliminary type and at an early age. However, it must be emphasized that in order to obtain more knowledge about a clone for commercial use, larger square parcels and/or, pilot plantings are the most indicated. / Dissertação importada do Alexandria

La LMMJ est un syndrome myéloprolifératif et myélodysplasique rare du jeune enfant, initiée par des mutations classiquement décrites comme mutuellement exclusives de RAS (NRAS, KRAS) ou de régulateurs de la voie RAS (PTPN11, NF1 ou CBL). Ces mutations, somatiques ou constitutionnelles, entraînent l’hyperactivation de cette voie de signalisation et une hypersensibilité spécifique au GM-CSF. La LMMJ est une hémopathie sévère dont le seul traitement est l’allogreffe de moelle osseuse. Cependant sa présentation et son évolution sont particulièrement hétérogènes puisqu’une transformation en leucémie aiguë myéloide survient chez un tiers des patients quand d’autres présentent des formes plus indolentes, voire des rémissions spontanées en l’absence de greffe. Cette hétérogénéité n’est que partiellement liée à la mutation initiatrice et pourrait s’expliquer par la présence de mutations additionnelles et/ou par une variabilité dans la cellule initiatrice de la leucémie, qui n’a jamais été précisément caractérisée.La caractérisation génétique de 118 LMMJ nous a permis de montrer que les anomalies génétiques additionnelles sont peu nombreuses dans les LMMJ sporadiques, et exceptionnelles dans les LMMJ syndromiques sauf en cas de neurofibromatose de type-1. Ces anomalies se concentrent sur deux grands systèmes, la voie RAS et le PRC2, et leur présence s’accompagne d’un pronostic défavorable (particulièrement en cas de mutations multiples de la voie RAS). L’absence d’anomalie additionnelle permet à l’inverse de distinguer un sous-groupe de patients qui présentent une forte probabilité de survie à long terme sans greffe et pour lesquels une soultion attentiste serait à privilégier. Une collaboration avec l’équipe de D Bonnet (Crick Institute) nous a ensuite permis d’établir un modèle murin de xénotransplantation dans des souris immunodéficientes de type NSG ou NSG-S et de montrer que la capacité de propagation de la leucémie est bien portée par la fraction souche, mais s’étend aussi chez certains patients à des fractions plus différenciées. Le profil génétique des 15 xénogreffes étudiées reproduit fidèlement l’architecture clonale des LMMJ natives, tant dans les souris NSG que NSG-S. L’architecture clonale des LMMJ est dans la majorité des cas compatible avec une acquisition linéaire des altérations, mais une architecture complexe est parfois observée, avec coexistence de clones distincts, dont les plus faiblement représentés sont susceptibles de devenir dominants lors de la rechute. Le séquençage de sous-populations isolées a montré que l’ensemble des mutations (initiatrice et additionnelles) est présent dès les fractions les plus immatures (HSC/MPP/MLP). Le séquençage de colonies obtenues par culture des progéniteurs en méthylcellulose révèle que les mutations coexistent dans les mêmes cellules, sans qu’il soit possible de hiérarchiser leur ordre de survenue, témoignant d’un avantage sélectif majeur de leur association dès la cellule souche. Au total, nos résultats remettent en cause le dogme de l’exclusivité mutuelle des mutations activant RAS dans les LMMJ, confirment le rôle central et initiateur de cette voie oncogénique dans la leucémogénèse et suggérent un effet-dose de l’activation de RAS, en particulier en cas de mutation de NRAS. La présence d’altérations multiples ciblant la voie RAS marque des LMMJ agressives et rapidement évolutives. La mise en évidence d’une fréquente dérégulation du PRC2 offre de nouvelles perspectives therapeutiques (comme l’utilisation des inhibiteurs de bromodomaine). La mise en place d’un modèle de souris xénotransplantée devrait de plus faciliter les études biologiques et la mise en place d’évaluations précliniques. / JMML is a rare myeloproliferative and myelodysplastic neoplasm of early childhood, initiated by mutations classically described as mutually exclusive of RAS (NRAS, KRAS) or RAS pathway regulators (PTPN11, NF1 or CBL). These mutations, either germline or somatically aquired, lead to an hyperactivation of the RAS signalling pathway and a to a specific hypersensitivity to GM-CSF. JMML is a severe hemopathy, and the only curative treatment is allogenic bone marrow transplantation. However, its presentation and evolution are particularly heterogeneous since transformation into acute myeloid leukaemia occurs in about one third of patients, when others present more indolent forms, or even spontaneous remissions in the absence of transplantation. This heterogeneity is only partially accounted for by the initiating mutation and could be related to the presence of additional mutations, or some variability in the leukemia initiating cell, which has never been precisely characterized so far.Establishing the genetic landscape of 118 LMMJ allowed us to show that additional genetic abnormalities are scarse in sporadic JMML and exceptional in syndromic JMML, except in the case of type-1 neurofibromatosis. These additional abnormalities mainly target two major biologic components, the RAS pathway and the PRC2, and their presence is associated with an unfavourable prognosis (particularly in the case of multiple mutations targeting the RAS pathway). On the other hand, the absence of any additional abnormality allows to delineate a subgroup of patients who have a high probability of long-term survival in the absence of bone marrow transplantation, and for whom a wait-and-see approach would be preferable. A collaboration with D. Bonnet’s group (Crick Institute) allowed us to establish a mouse model of xenotransplantation in immunodeficient NSG or NSG-S mice and to demonstrate that the leukemia propagating cell is present in the stem cell fractions (HSC, CD34+/CD38-…) but also extends in certain patients to more differentiated fractions, such as CMP. The genetic profile of xenografts established from 15 JMML faithfully reproduced the clonal architecture of the native leukemia, either in NSG or NSG-S mice. The clonal architecture of JMML is linear in the great majority of cases, with linear acquisition of alterations, but a complex architecture is sometimes observed, with coexistence of distinct clones, the weakest of which being susceptible to become dominant at relapse. Sequencing of sorted cell populations showed that all mutations (initiating and additional) are present in the most immature fractions (HSC/MPP/MLP). The sequencing of colonies obtained by culturing progenitors into methylcellulose revealed that mutations coexist in the same cells, their order of appearance being often impossible to determine, showing a major selective advantage of their association from the most immature compartment. In conclusion, our findings confirm the central role of RAS activation in JMML leukemogenesis. The identification of multiple alterations targeting the RAS pathway challenges the dogma of the mutual exclusivity of these mutations and defines a subset of aggressive and rapidly evolving JMML, suggesting a dose-effect of RAS activation, particularly in case with NRAS mutation. Recurrent deregulation of PRC2 in JMML may offer new therapeutic approaches, such as bromodomain inhibitors. The implementation of a xenotransplanted mouse model should also facilitate biological studies and the implementation of preclinical evaluations.

Indiana University-Purdue University Indianapolis (IUPUI) / Hematopoietic stem and progenitor cells (HSCs/HPCs) transplantation is a curative treatment for a variety of hematologic and non-hematologic diseases. Successful HSC transplantation requires infusing patients with a sufficient number of long-term engrafting HSCs. As a result, research efforts have focused on optimizing the collection process. Previous work established that harvesting mouse bone marrow HSCs under low oxygen tension similar to that reported for the bone marrow niche in situ (physioxia), results in enhanced HSC recovery and function. However, collecting bone marrow cells under physioxia is not a clinically viable approach. Here, I demonstrated that the collection and processing of peripheral blood mobilized with G-CSF alone or G-CSF and Plerixafor under physioxia resulted in a greater number of phenotypically defined long-term engrafting HSCs. Using high-resolution single cell sequencing to explore the molecular programs governing HSCs under physioxia, I identified increased expression of genes involved in HSC self-renewal and maintenance. In contrast, HSCs under ambient air upregulated genes implicated in HSC differentiation, apoptosis, and inflammatory pathways. Furthermore, wild-type HSCs under physioxia revealed a significant reduction in gene expression and activity of the epigenetic modifier Tet2. Consequently, I evaluated the phenotyping, engraftment potential and gene expression of preleukemic Tet2-/- bone marrow cells under physioxia and ambient air. Unlike wild-type HSCs, Tet2-/- HSCs/HPCs were unresponsive to changes in oxygen tension. Notably, we observed similar phenotypes, functions, and self-renewal and quiescence gene expression in wild-type HSCs under physioxia and Tet2- /- HSCs under physioxia or ambient air. These findings imply that the preserved stemness and enhanced engraftment of HSCs under physioxia may in part be a result of Tet2 downregulation. Understanding the mechanisms regulating wild-type and preleukemic HSCs under physioxia will have therapeutic implications for optimizing HSC transplantation and mitigating the growth advantage of preleukemic stem cells. / 2022-12-15

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No description available.

Orientador: Bruno Ettore Pavan / Resumo: Os plantios clonais são comumente utilizados para obter ganhos na produtividade. No entanto, a uniformidade genética, quando em extensas áreas, pode comprometer o desempenho silvicultural do eucalipto. Uma alternativa seria o emprego da mistura de clones em áreas comerciais. Este trabalho foi realizado com o objetivo de comparar a auto e alocompetição entre clones comerciais de Eucalyptus spp., e estimar as capacidades de exercer ou sofrer competição. O experimento foi implantado em delineamento de blocos casualizados, com 12 clones comerciais no espaçamento de 3,6 m x 2,5 m, com 5 plantas por parcela e 3 repetições. Foram avaliados aos 3 e 5 anos os caracteres altura de planta, diâmetro à altura do peito, volume e incremento médio anual. Com os dados médios da parcela foram efetuadas as análises estatísticas e estimados os parâmetros de competição. Houve diferenças entre a auto e a alocompetição para incremento médio anual e volume em ambas as idades avaliadas. O desempenho médio dos clones em auto e alocompetição foram semelhantes, não ocasionando prejuízos para a produção de madeira. A mistura clonal pode ser empregada sempre que for vantajosa do ponto de vista de manejo ou industrial. Os clones diferiram quanto à sua capacidade de exercer ou sofrer competição. / Mestre

Orientador: Maria de Lourdes Ribeiro de Souza da Cunha / Resumo: Infecções causadas por Staphylococcus aureus representam um dos principais problemas de saúde pública, com elevadas taxas de morbidade e mortalidade principalmente entre indivíduos com deficiência de sistema imunológico como os diabéticos, em especial aqueles que fazem uso diário de insulina. Além da alta patogenicidade e facilidade de aquisição de resistência aos antimicrobianos, o patógeno tem grande habilidade de colonizar indivíduos de forma assintomática, favorecendo sua disseminação e tornando esses indivíduos fonte de risco para infecções. O estudo teve como objetivo analisar a prevalência e fatores de risco para o carreamento nasal e orofaríngeo, bem como caracterizar o perfil de resistência, virulência e tipagem molecular de S. aureus sensível à meticilina (MSSA) e S. aureus resistente à meticilina (MRSA) isolados de indivíduos diabéticos insulino-dependentes do município de Botucatu, SP. S. aureus foram obtidos da nasofaringe e orofaringe de 312 indivíduos diabéticos insulino-dependentes da comunidade e analisados quanto à presença do gene mecA, genes das enterotoxinas (sea, seb, e sec-1), esfoliatinas A e B (eta e etb), toxina 1 da síndrome do choque tóxico (tst), leucocidina Panton–Valentine (pvl), hemolisinas alfa (hla) e delta (hld) e biofilme (operon icaADBC) através da técnica da reação em cadeia da polimerase (PCR) e a tipagem do SCCmec através de PCRmultiplex. O perfil de sensibilidade à oxacilina, cefoxitina, linezolida, quinupristina/dalfopristina e sulfam... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Infections caused by Staphylococcus aureus is a major public health problem and infections with this microorganism are associated with high morbidity and mortality rates, especially among individuals with immune deficiency disorders such as diabetes and particularly those who take insulin daily. In addition to its high pathogenicity and ability to acquire antimicrobial resistance, asymptomatic infection with this pathogen is common, favoring its dissemination and rendering these individuals a source of infection. The objective of this study was to analyze the prevalence and risk factors for nasal and oropharyngeal carriage, as well as to characterize the resistance profile, virulence, clonal profile and sequence type of methicillin-susceptible (MSSA) and methicillin-resistant S. aureus (MRSA) isolated from insulin-dependent diabetic individuals in the city of Botucatu, SP, Brazil. Staphylococcus aureus was collected from the nasopharynx and oropharynx of 312 community insulin-dependent diabetic individuals. The isolates were analyzed for the presence of the mecA, enterotoxin (sea, seb and sec-1), exfoliatin A and B (eta and etb), toxic shock syndrome toxin 1 (tst), Panton-Valentine leukocidin (pvl), alpha and delta hemolysin (hla and hld), and biofilm (icaADBC operon) genes by the polymerase chain reaction (PCR). SCCmec typing was performed by multiplex PCR. The susceptibility profile against oxacillin, cefoxitin, linezolid, quinupristin/dalfopristin and sulfamethoxazole/trim... (Complete abstract click electronic access below) / Doutor