10 research outputs found
Selecção, genética e evolução do crescimento e do tamanho
A considerable body of work in recent decades in the field of evolutionary quantitative
genetics has been motivated by the paradox of stasis. Mismatches between observed dynamics
of size in wild populations and evolutionary predictions must arise from deficient
understanding of the theoretical grounds underlying the evolution in a particular system,
and/or the adoption of methodological tools making assumptions that are unrealistic. Although
different in their nature, these classes of explanation are difficult to tear apart, as
very often quantitative genetics (statistical) tools make either implicit or explicit assumptions
about biology and ecology. In this thesis, I investigate inheritance and/or selection
mechanisms when conventional applications of theory are expected to lead to biased or
erroneous predictions of evolutionary change in size. Specifically, I adopt a methodology
to handle genetic constraints in a fairly phenotypic perspective, which facilitates quantification
of bias that would exist if such constraint was not accounted for (Chapter 3). I use
this methodology to tear apart the selection in Soay sheep body mass that occurs directly
through its effect on fitness and indirectly through its effect on pregnancy during the first
year of life. Next, I provide analytical proofs of several issues with applications of integral
projection models (IPMs) that incorporate inheritance and development, concluding
that these will predict no evolutionary change regardless of whether it should, will, or has
occurred (Chapter 4). Another main topic of this thesis is the development of a two-sex
individual-based model (IBM) of horn length (Chapter 6), equivalent to an IPM, that uses
quantitative genetics theory to model trait transmission (with development functions estimated
in Chapter 5). This IBM, parameterised using data from the bighorn sheep (Ovis
canadensis) of Ram Mountain, is used to quantify the evolutionary response to trophy hunting,
while accounting for a large number of ecological complexities.O paradoxo da estase morfológica (paradox of stasis) tem motivado avanços consideráveis
na área da genética quantitativa evolutiva nas últimas décadas. Discrepâncias
entre tendências temporais do tamanho de organismos em populações selvagens e previsões
baseadas em teoria evolutiva devem-se necessariamente a uma compreensão deficiente
dos fundamentos teóricos subjacentes à evolução num determinado sistema e/ou
à adopção de ferramentas metodológicas com pressupostos que não são realistas. Embora
difiram na sua natureza, estas duas explicações são difíceis de distinguir, uma vez
que, muitas vezes, as ferramentas (estatísticas) da genética quantitativa têm pressupostos,
implícitos ou explícitos, sobre biologia e ecologia. Na presente tese, eu investigo
mecanismos de hereditariedade e/ou selecção em casos para os quais se prevê que
aplicações teóricas convencionais gerem previsões enviesadas ou erróneas acerca da
evolução do tamanho dos organismos. Especificamente, adopto uma metodologia para
lidar com constrangimentos genéticos numa perspectiva bastante fenotípica, o que facilita
a quantificação do viés que existiria se tal constrangimento não fosse tido em conta
(Capítulo 3). Esta metodologia permite distinguir a selecção do peso corporal de ovelhas
da raça Soay (Ovies aries) que ocorre directamente, através do efeito do peso na
fitness (ou valor adaptativo), e indiretamente, através do seu efeito na probabilidade de
gravidez durante o primeiro ano de vida. No Capítulo 4, apresento provas analíticas de
várias questões com aplicações típicas de modelos de projeção integral (integral projection
models, IPMs) que incorporam hereditariedade e desenvolvimento de caracteres, concluindo
que estas aplicações são incapazes de prever alterações evolutivas, ainda que
estas tenham ocorrido ou se espere que ocorram. Outro tópico importante desta tese é
o desenvolvimento de um modelo baseado em indivíduos (individual-based model, IBM),
concebido e parameterizado para o comprimento dos cornos da população de ovelhas
de raça bighorn (Ovies canadensis) residente em Ram Mountain, no Canada (Capítulo 6).
Este modelo, desenvolvido para ambos os sexos e equivalente a um IPM, usa teoria da
genética quantitativa para modelar a transmissão genética de caracteres (com funções
de desenvolvimento estimadas no Capítulo 5). Desta forma, esta abordagem permite a
quantificação da resposta evolutiva à caça ao troféu, contabilizado, ao mesmo tempo, um
grande número de complexidades ecológicas.
ixPrograma Doutoral em Biologi
Modelo de prognóstico do tempo necessário ao controlo da dor oncológica
Tese de mestrado em Bioestatística, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2012A dor e dos sintomas mais angustiantes e prevalentes do cancro, ocorrendo em mais de 60% dos doentes com cancro metastático ou avançado. Entender as características associadas a complexidade do tratamento da dor oncológica tem sido nas últimas duas décadas, e continua a ser, um objectivo por cumprir.
Neste trabalho são desenvolvidos seis modelos de tempo de vida acelerado para o tempo até controlar a dor oncológica. São consideradas três distribuições para o tempo, nomeadamente as distribuições Weibull, log-logística e log-normal, e adoptadas duas regras de decisão alternativas no processo de seleção dos preditores. Os seis modelos são avaliados relativamente a sua capacidade preditiva, através de medidas que quantificam a capacidade preditiva global, a discriminação e a calibração. Estas medidas são calculadas para a amostra original mas também para amostras bootstrap, permitindo assim a obtenção de valores corrigidos para o optimismo (validação interna). A capacidade preditiva e utilizada como critério de seleção de um dos modelos, que constitui um índice de prognóstico e serve de base a criação de três grupos de prognóstico da dificuldade em atingir a analgesia em doentes oncológicos.In cancer patients, pain is one of the most feared and prevalent symptoms, occurring in more than 60% of the patients with metastatic or advanced stage disease. Understanding the characteristics related to the complexity of cancer pain treatment has been in the past two decades, and still is, an unfulfilled goal.
Six accelerated failure time models of the time to achieve pain control are developed. Weibull, log-logistic and log-normal distributions are considered as well as two alternative stopping rules in the predictors selection process. These six models are evaluated with respect to their predictive accuracy, through measures assessing discrimination, calibration and overall accuracy. Such measures are calculated from the original data set as well as from bootstrap samples, allowing for the optimism correction (internal validation). Predictive accuracy is set as a criterion to select one of the models to constitute a prognostic index and to create three prognostic groups including patients with different levels of difficulty to attain stabilized cancer pain
Selection, genetics and evolution of growth and size
A considerable body of work in recent decades in the field of evolutionary quantitative genetics has
been motivated by the paradox of stasis. Mismatches between observed dynamics of size in wild
populations and evolutionary predictions must arise from deficient understanding of the theoretical
grounds underlying the evolution in a particular system, and/or the adoption of methodological tools making assumptions that are unrealistic. Although different in their nature, these classes of explanation are difficult to tear apart, as very often quantitative genetics (statistical) tools make either implicit
or explicit assumptions about biology and ecology. In this thesis, I investigate inheritance and/or
selection mechanisms when conventional applications of theory are expected to lead to biased or
erroneous predictions of evolutionary change in size. Specifically, I adopt a methodology to handle
genetic constraints in a fairly phenotypic perspective, which facilitates quantification of bias that
would exist if such constraint was not accounted for (Chapter 3). I use this methodology to tear apart
the selection in Soay sheep body mass that occurs directly through its effect on fitness and indirectly
through its effect on pregnancy during the first year of life. Next, I provide analytical proofs of several
issues with applications of integral projection models (IPMs) that incorporate inheritance and development,
concluding that these will predict no evolutionary change regardless of whether it should,
will, or has occurred (Chapter 4). Another main topic of this thesis is the development of a two-sex
individual-based model (IBM) of horn length (Chapter 6), equivalent to an IPM, that uses quantitative
genetics theory to model trait transmission (with development functions estimated in Chapter 5).
This IBM, parameterised using data from the bighorn sheep (Ovis canadensis) of Ram Mountain, is
used to quantify the evolutionary response to trophy hunting, while accounting for a large number of
ecological complexities
Síndrome de Guillain-Barré em idade pediátrica. Protocolo de actuação
O protocolo de actuação na Síndrome de Guillain-Barré em idade pediátrica foi elaborado com o intuito de rever as mais recentes recomendações internacionais e de traçar linhas orientadoras de actuação. É constituído por duas partes: a primeira é a introdução teórica, resultante da revisão bibliográfica, e a segunda o Protocolo de actuação. Tratando-se de uma patologia para a qual ainda não existe um consenso, sobretudo no que respeita ao tratamento, optou-se por incluir as várias opções de tratamento recomendadas, permitindo a cada Unidade aplicar aquela com a qual possui mais experiência
The 2020S tooth fairy: from loose tooth to neuronal cell cultures, a method to establish neurologic Lysosomal Storage Diseases in vitro – an update
Lysosomal storage disorders (LSD) are a group of rare diseases caused mutations in genes that encode lysosomal enzymes, membrane proteins or transporters. This leads to an accumulation of undegraded substrates, which ultimately causes a broad range of highly debilitating clinical symptoms affecting multiple organs/systems, including the central nervous system. Yet, most therapies for LSD are limited to treating non-neurological signs. Thus, there is an urgent need for the development of new ones that can tackle the neuronal pathogenesis. Fortunately, the portfolio of innovative therapeutic approaches under development has been growing tremendously and the need for proper models grows alongside.
To address this concern, we propose the development and characterization of innovative patient-derived cell models for early onset neurodegenerative LSD using dental pulp stem cells (DPSC) from deciduous “baby” teeth. DPSCs hold potential to give rise to a variety of cells including functionally active neurons. Nevertheless, to the best of our knowledge, this sort of technology hasn’t yet been applied to samples obtained from LSD patients. This will be a total innovation in the field and we believe it holds potential to set a new trend for investigating LSD as it relies on a non-invasive, cost effective approach that can be set as a routine in any lab with standard cell culture conditions.
Here we present an update on this project, summarizing its rationale and current results, while giving an overview of the whole protocol and discussing its potential applications.
Briefly, over the last months, we have successfully implemented the protocol for the establishment of control DPSC cultures in our lab and are currently working on the differentiation protocol, which will allow the formation of mixed neuronal and glial cultures. We are also actively working with patients’ associations and a team of expert pediatricians from the major reference centers for treatment of LSD to identify potential volunteers for baby teeth collection, having already approached several families, who are now actively involved in the project and willing to send us deciduous baby teeth, as soon as they fall.
Acknowledgments
This work is partially supported by the Portuguese Society for Metabolic Disorders (SPDM - Bolsa SPDM de apoio à investigação Dr. Aguinaldo Cabral 2018; 2019DGH1629/SPDM2018I&D) and Sanfilippo Children's Foundation (2019DGH1656/SCF2019I&D).N/
revista do Mestrado em Teorias da arte da Faculdade de Belas Artes da Universidade de Lisboa
info:eu-repo/semantics/publishedVersio
Da produção à preservação informacional: desafios e oportunidades
This book focus in the study of past information systems, current information management and digital preservation. It results from a set of text sources, whose approaches reflect the challenges and opportunities in the world of information, treated by specialists dealing with it on a professional and academic level. The objective of this collection of text sources is to be a motto to new contributions to the archival field, potentiating experiences in the work context and new studies in the approached thematics
Characterization of a large cluster of HIV-1 A1 infections detected in Portugal and connected to several Western European countries
HIV-1 subtypes associate with differences in transmission and disease progression. Thus, the existence of geographic hotspots of subtype diversity deepens the complexity of HIV-1/AIDS control. The already high subtype diversity in Portugal seems to be increasing due to infections with sub-subtype A1 virus. We performed phylogenetic analysis of 65 A1 sequences newly obtained from 14 Portuguese hospitals and 425 closely related database sequences. 80% of the A1 Portuguese isolates gathered in a main phylogenetic clade (MA1). Six transmission clusters were identified in MA1, encompassing isolates from Portugal, Spain, France, and United Kingdom. The most common transmission route identified was men who have sex with men. The origin of the MA1 was linked to Greece, with the first introduction to Portugal dating back to 1996 (95% HPD: 1993.6-1999.2). Individuals infected with MA1 virus revealed lower viral loads and higher CD4+ T-cell counts in comparison with those infected by subtype B. The expanding A1 clusters in Portugal are connected to other European countries and share a recent common ancestor with the Greek A1 outbreak. The recent expansion of this HIV-1 subtype might be related to a slower disease progression leading to a population level delay in its diagnostic.Supported by FEDER, COMPETE, and FCT by the projects NORTE-01-0145-FEDER-000013, POCI-01-0145-FEDER-007038 and IF/00474/2014; FCT PhD scholarship PDE/BDE/113599/2015; FCT contract FCT IF/00474/2014; European Funds through grant BEST HOPE (project funded through HIVERA, grant 249697) and by FCT PTDC/DTP-EPI/7066/2014. Global Health and Tropical Medicine Center are funded through FCT (UID/Multi/04413/2013). We would like to acknowledge all the patients and health care professionals from the Portuguese hospitals that contributed in some way to this study