Understanding marine mammal populations and how they are affected by human activity and ocean conditions is vital, especially in tracking population declines and monitoring endangered species. However, tracking marine mammal populations and their distribution is challenging due to difficulties in observation and costs. Using surrounding plankton environmental DNA (eDNA) has the potential to provide an indirect measure of monitoring cetacean abundances based on ecological associations. This project aims to apply statistical methods to assess the relationship of visual abundances of common species of baleen whales with amplicon sequence variants (ASV) of plankton eDNA samples from the NOAA-CalCOFI Ocean Genomics (NCOG) project. Modeling this relationship of eDNA with marine mammal sightings may greatly aid the ability to predict the abundance of whales in the ocean. There are several key challenges associated with the analysis of this NCOG data. Plankton eDNA samples are an example of compositional data, where the proportions of each ASV must sum to one; this provides a challenging constraint for statistical analysis and interpretation. High dimensionality (the number of parameters exceeds the observations) and sparsity (many observed zeros) of the genetic sequencing data also pose challenges in estimating parameters. Finally, the model associations should be adjusted for related factors, including seasonality and oceanographic factors, the latter of which goes beyond this project's scope. This thesis develops and fits models to estimate cetacean abundance from plankton eDNA by leveraging methods of compositional data analysis and high-dimensional regression. This project applies log-ratio data transformations and corresponding log-contrast models to address the compositional aspect of eDNA reads. Regression methods involving high-dimensional data typically rely on dimensionality reduction or regularization. This project implements both reduction and regularization through sparse partial least squares (sPLS) regression. In addition to the data modeling objective of using plankton eDNA to predict baleen whale abundances, this project also identifies ecological correlations between whale abundance and plankton eDNA.

Os microRNAs (miRNAs) são pequenos RNAs endógenos não codantes de 21-24 nucleotídeos (nt) que regulam a expressão gênica de genes-alvos. Eles estão envolvidos em diversos aspectos de desenvolvimento da planta, tanto na parte aérea, quanto no sistema radicular. Entre os miRNAs, o miRNA156 (miR156) regula a família de fatores de transcrição SQUAMOSA Promoter-Binding Protein-Like (SPL) afetando diferentes processos do desenvolvimento vegetal. Estudos recentes mostram que a via gênica miR156/SPL apresenta efeito positivo tanto no aumento da formação de raízes laterais, quanto no aumento de regeneração de brotos in vitro a partir de folhas e hipocótilos em Arabidopsis thaliana. Devido ao fato de que a origem da formação de raiz lateral e a regeneração in vitro de brotos a partir de raiz principal compartilham semelhanças anatômicas e moleculares, avaliou-se no presente estudo se a via miR156/SPL, da mesma forma que a partir de explantes aéreos, também é capaz de influenciar na regeneração de brotos in vitro a partir de explantes radiculares. Para tanto foram comparados taxa de regeneração, padrão de distribuição de auxina e citocinina, análises histológicas e histoquímicas das estruturas regeneradas em plantas com via miR156/SPL alterada, incluindo planta mutante hyl1, na qual a produção desse miRNA é severamente reduzida. Além disso, foi avaliado o padrão de expressão do miR156 e específicos genes SPL durante a regeneração de brotos in vitro a partir da raiz principal de Arabidopsis thaliana. No presente trabalho observou-se que a alteração da via gênica miR156/SPL é capaz de modular a capacidade de regeneração de brotos in vitro a partir de raiz principal de Arabidopsis thaliana e a distribuição de auxina e citocinina presente nas células e tecidos envolvidos no processo de regeneração. Plantas superexpressando o miR156 apresentaram redução no número de brotos regenerados, além de ter o plastochron reduzido quando comparado com plantas controle. Adicionalmente, plantas contento o gene SPL9 resistente à clivagem pelo miR156 (rSPL9) apresentaram severa redução na quantidade de brotos, além de terem o plastochron alongado. Interessantemente, plantas mutantes hyl1-2 e plantas rSPL10 não apresentaram regeneração de brotos ao longo da raiz principal, mas sim intensa formação de raízes laterais e protuberâncias, respectivamente, tendo essa última apresentado indícios de diferenciação celular precoce. Tomados em conjunto os dados sugerem que o miR156 apresenta importante papel no controle do processo de regeneração de brotos in vitro. Entretanto, esse efeito é mais complexo em regeneração in vitro a partir de raízes do que a partir de cotilédones ou hipocótilos. / MicroRNAs (miRNAs) are endogenous small non-coding RNAs of 21-24 nucleotides (nt) in length that regulate target gene expression. They are involved in many aspects of plant development, both in the shoot and in the root systems. Among miRNAs, miRNA156 (miR156) regulates SQUAMOSA Promoter Binding-Like (SPL) transcription factor family affecting different plant development processes. Recent studies have shown that the miR156/SPL pathway has a positive effect both in the increase of lateral root formation and regeneration of shoots from leaves and hypocotyls in Arabidopsis thaliana. Because the origin of lateral root formation and in vitro shoot regeneration from primary root share similar anatomical and molecular features, in the present study was evaluated whether the miR156/SPL pathway, in the same manner that from aerial explants, is also able to influence the in vitro shoot regeneration from root explants. For this, it was compared regeneration rates, distribution pattern of auxin and cytokinin, histological and histochemical analyses of the structures regenerated in plants in with the miR156/SPL pathway is modified, including the mutant hyl1-1, in which the biosynthesis of this miRNA is severely reduced. Besides that, it was evaluated the expression pattern of miR156 and specific SPL target genes during in vitro shoot regeneration from primary roots of Arabidopsis it was observed that the alteration on the miR156/SPL pathway is capable to modulate in vitro shoot regeneration from the primary root of Arabidopsis and the distribution of auxin and cytokinin at the tissues and cells involved in the regeneration process. Plants overexpressing the miR156a have shown reduction in the number of regenerated shoots, and displayed a reduction in plastochron when compared with wild type plants. Additionally, plants expressing cleavage-resistant form of SPL9 (rSPL9) presented severe reduction in the amount of shoots, and extended plastochron. Interestingly, mutant hyl1-2 and plants rSPL10 did not show any shoot regeneration along the root, but high formation of lateral roots and protuberances, respectively, having rSPL10 presented evidence of precocious cell differentiation. Taken together, these data suggest that de miR156 and SPLs have an important role in the control the in vitro shoot regeneration process. However, its effect is somehow more complex in roots than in cotyledons or hypocotyls.

Os microRNAs (miRNAs) são pequenos RNAs endógenos não codantes de 21-24 nucleotídeos (nt) que regulam a expressão gênica de genes-alvos. Eles estão envolvidos em diversos aspectos de desenvolvimento da planta, tanto na parte aérea, quanto no sistema radicular. Entre os miRNAs, o miRNA156 (miR156) regula a família de fatores de transcrição SQUAMOSA Promoter-Binding Protein-Like (SPL) afetando diferentes processos do desenvolvimento vegetal. Estudos recentes mostram que a via gênica miR156/SPL apresenta efeito positivo tanto no aumento da formação de raízes laterais, quanto no aumento de regeneração de brotos in vitro a partir de folhas e hipocótilos em Arabidopsis thaliana. Devido ao fato de que a origem da formação de raiz lateral e a regeneração in vitro de brotos a partir de raiz principal compartilham semelhanças anatômicas e moleculares, avaliou-se no presente estudo se a via miR156/SPL, da mesma forma que a partir de explantes aéreos, também é capaz de influenciar na regeneração de brotos in vitro a partir de explantes radiculares. Para tanto foram comparados taxa de regeneração, padrão de distribuição de auxina e citocinina, análises histológicas e histoquímicas das estruturas regeneradas em plantas com via miR156/SPL alterada, incluindo planta mutante hyl1, na qual a produção desse miRNA é severamente reduzida. Além disso, foi avaliado o padrão de expressão do miR156 e específicos genes SPL durante a regeneração de brotos in vitro a partir da raiz principal de Arabidopsis thaliana. No presente trabalho observou-se que a alteração da via gênica miR156/SPL é capaz de modular a capacidade de regeneração de brotos in vitro a partir de raiz principal de Arabidopsis thaliana e a distribuição de auxina e citocinina presente nas células e tecidos envolvidos no processo de regeneração. Plantas superexpressando o miR156 apresentaram redução no número de brotos regenerados, além de ter o plastochron reduzido quando comparado com plantas controle. Adicionalmente, plantas contento o gene SPL9 resistente à clivagem pelo miR156 (rSPL9) apresentaram severa redução na quantidade de brotos, além de terem o plastochron alongado. Interessantemente, plantas mutantes hyl1-2 e plantas rSPL10 não apresentaram regeneração de brotos ao longo da raiz principal, mas sim intensa formação de raízes laterais e protuberâncias, respectivamente, tendo essa última apresentado indícios de diferenciação celular precoce. Tomados em conjunto os dados sugerem que o miR156 apresenta importante papel no controle do processo de regeneração de brotos in vitro. Entretanto, esse efeito é mais complexo em regeneração in vitro a partir de raízes do que a partir de cotilédones ou hipocótilos. / MicroRNAs (miRNAs) are endogenous small non-coding RNAs of 21-24 nucleotides (nt) in length that regulate target gene expression. They are involved in many aspects of plant development, both in the shoot and in the root systems. Among miRNAs, miRNA156 (miR156) regulates SQUAMOSA Promoter Binding-Like (SPL) transcription factor family affecting different plant development processes. Recent studies have shown that the miR156/SPL pathway has a positive effect both in the increase of lateral root formation and regeneration of shoots from leaves and hypocotyls in Arabidopsis thaliana. Because the origin of lateral root formation and in vitro shoot regeneration from primary root share similar anatomical and molecular features, in the present study was evaluated whether the miR156/SPL pathway, in the same manner that from aerial explants, is also able to influence the in vitro shoot regeneration from root explants. For this, it was compared regeneration rates, distribution pattern of auxin and cytokinin, histological and histochemical analyses of the structures regenerated in plants in with the miR156/SPL pathway is modified, including the mutant hyl1-1, in which the biosynthesis of this miRNA is severely reduced. Besides that, it was evaluated the expression pattern of miR156 and specific SPL target genes during in vitro shoot regeneration from primary roots of Arabidopsis it was observed that the alteration on the miR156/SPL pathway is capable to modulate in vitro shoot regeneration from the primary root of Arabidopsis and the distribution of auxin and cytokinin at the tissues and cells involved in the regeneration process. Plants overexpressing the miR156a have shown reduction in the number of regenerated shoots, and displayed a reduction in plastochron when compared with wild type plants. Additionally, plants expressing cleavage-resistant form of SPL9 (rSPL9) presented severe reduction in the amount of shoots, and extended plastochron. Interestingly, mutant hyl1-2 and plants rSPL10 did not show any shoot regeneration along the root, but high formation of lateral roots and protuberances, respectively, having rSPL10 presented evidence of precocious cell differentiation. Taken together, these data suggest that de miR156 and SPLs have an important role in the control the in vitro shoot regeneration process. However, its effect is somehow more complex in roots than in cotyledons or hypocotyls.

Medicines and vaccines have revolutionized disease prevention and treatment, offering numerous benefits. However, they also raise concerns about Adverse Drug Reactions (ADRs), which can have severe consequences. Summaries of Product Characteristics (SmPCs), provided by the European Medicines Agency (EMA), and Structured Product Labelings (SPLs), provided by the Food and Drug Administration (FDA), are valuable sources of information on drug-ADR relations. Understanding these relations is crucial as it contributes to establishing labeled datasets for known ADRs and advancing statistical assessment methods. Uppsala Monitoring Centre (UMC) has developed a text mining pipeline to extract known ADRs from SPLs. While the pipeline works effectively with SPLs, it faces challenges with SmPCs provided in PDF format. This study explores extending the scanner component of the pipeline by utilizing Python PDF extraction libraries to extract text from SmPCs and fine-tuning domain-specific pre-trained BERT-based models for Named Entity Recognition (NER), which is a Natural Language Processing (NLP) task, aiming to identify known ADRs from SmPCs. The investigation finds pypdfium2 [1] to be the optimal Python PDF extraction library, and fine-tuned PubMedBERT—a domain-specific language model pre-training from scratch [2]—for the NER task achieves the best performance in identifying ADRs from SmPCs. The model's performance, evaluated using entity-level evaluation metrics including Exact, Covering, and Overlap match metrics, achieves F1-scores of 0.9138, 0.9268, and 0.9671, respectively, indicating significantly good performance. Consequently, the extension model investigated in this study will be integrated into the existing pipeline by UMC professionals.

Les plantes médicinales constituent une source inexhaustible de composés (des produits naturels - PN) utilisé en médecine pour la prévention et le traitement de diverses maladies. L'introduction de nouvelles technologies et méthodes dans le domaine de la chimie des produits naturels a permis le développement de méthodes ‘high throughput’ pour la détermination de la composition chimique des extraits de plantes, l'évaluation de leurs propriétés et l'exploration de leur potentiel en tant que candidats médicaments. Dernièrement, la métabolomique, une approche intégrée incorporant les avantages des technologies d'analyse moderne et la puissance de la bioinformatique s’est révélé un outil efficace dans la biologie des systèmes. En particulier, l'application de la métabolomique pour la découverte de nouveaux composés bioactifs constitue un domaine émergent dans la chimie des produits naturels. Dans ce contexte, le genre Acronychia de la famille des Rutaceae a été choisi sur la base de son usage en médecine traditionnelle pour ses propriétés antimicrobienne, antipyrétique, antispasmodique et anti-inflammatoire. Nombre de méthodes chromatographiques modernes, spectrométriques et spectroscopiques sont utilisées pour l'exploration de leur contenu en métabolites suivant trois axes principaux constituant les trois chapitres de cette thèse. En bref, le premier chapitre décrit l’étude phytochimique d’Acronychia pedunculata, l’identification des métabolites secondaires contenus dans cette espèce et l'évaluation de leurs propriétés biologiques. Le deuxième chapitre vise au développement de méthodes analytiques pour l'identification des dimères d’acétophénones (marqueurs chimiotaxonomiques du genre) et aux stratégies utilisées pour la déréplication de ces différents extraits et la caractérisation chimique des composés par UHPLC-HRMSn. Le troisième chapitre se concentre sur l'application de méthodologies métabolomique (RMN et LC-MS) pour l'analyse comparative (entre les différentes espèces, origines, organes), pour des études chimiotaxonomiques (entre les espèces) et pour la corrélation des composés contenus avec une activité pharmacologique. / Medicinal plants constitute an unfailing source of compounds (natural products – NPs) utilised in medicine for the prevention and treatment of various deceases. The introduction of new technologies and methods in the field of natural products chemistry enabled the development of high throughput methodologies for the chemical composition determination of plant extracts, evaluation of their properties and the exploration of their potentials as drug candidates. Lately, metabolomics, an integrated approach incorporating the advantages of modern analytical technologies and the power of bioinformatics has been proven an efficient tool in systems biology. In particular, the application of metabolomics for the discovery of new bioactive compounds constitutes an emerging field in natural products chemistry. In this context, Acronychia genus of Rutaceae family was selected based on its well-known traditional use as antimicrobial, antipyretic, antispasmodic and anti-inflammatory therapeutic agent. Modern chromatographic, spectrometric and spectroscopic methods were utilised for the exploration of their metabolite content following three basic axes constituting the three chapters of this thesis. Briefly, the first chapter describes the phytochemical investigation of Acronychia pedunculata, the identification of secondary metabolites contained in this species and evaluation of their biological properties. The second chapter refers to the development of analytical methods for the identification of acetophenones (chemotaxonomic markers of the genus) and to the dereplication strategies for the chemical characterisation of extracts by UHPLC-HRMSn. The third chapter focuses on the application of metabolomic methodologies (LC-MS & NMR) for comparative analysis (between different species, origins, organs), chemotaxonomic studies (between species) and compound-activity correlations.