Contrôle traductionnel du rythme circadien de la bioluminescence chez le dinoflagellé Lingulodinium polyedrum

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Identification et caractérisation de candidats régulateurs du cycle cellulaire chez le dinoflagellé Lingulodinium polyedrum

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity.

Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC-resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy.

Wear and its effects on dental topography measures in howling monkeys (Alouatta palliata).

OBJECTIVES: Three dental topography measurements: Dirichlet Normal Energy (DNE), Relief Index (RFI), and Orientation Patch Count Rotated (OPCR) are examined for their interaction with measures of wear, within and between upper and lower molars in Alouatta palliata. Potential inferences of the "dental sculpting" phenomenon are explored. MATERIALS AND METHODS: Fifteen occluding pairs of howling monkey first molars (15 upper, 15 lower) opportunistically collected from La Pacifica, Costa Rica, were selected to sample wear stages ranging from unworn to heavily worn as measured by the Dentine Exposure Ratio (DER). DNE, RFI, and OPCR were measured from three-dimensional surface reconstructions (PLY files) derived from high-resolution CT scans. Relationships among the variables were tested with regression analyses. RESULTS: Upper molars have more cutting edges, exhibiting significantly higher DNE, but have significantly lower RFI values. However, the relationships among the measures are concordant across both sets of molars. DER and EDJL are curvilinearly related. DER is positively correlated with DNE, negatively correlated with RFI, and uncorrelated with OPCR. EDJL is not correlated with DNE, or RFI, but is positively correlated with OPCR among lower molars only. DISCUSSION: The relationships among these metrics suggest that howling monkey teeth adaptively engage macrowear. DNE increases with wear in this sample presumably improving food breakdown. RFI is initially high but declines with wear, suggesting that the initially high RFI safeguards against dental senescence. OPCR values in howling monkey teeth do not show a clear relationship with wear changes.

Introducing molaR: a New R Package for Quantitative Topographic Analysis of Teeth (and Other Topographic Surfaces)

© 2016 Springer Science+Business Media New YorkResearchers studying mammalian dentitions from functional and adaptive perspectives increasingly have moved towards using dental topography measures that can be estimated from 3D surface scans, which do not require identification of specific homologous landmarks. Here we present molaR, a new R package designed to assist researchers in calculating four commonly used topographic measures: Dirichlet Normal Energy (DNE), Relief Index (RFI), Orientation Patch Count (OPC), and Orientation Patch Count Rotated (OPCR) from surface scans of teeth, enabling a unified application of these informative new metrics. In addition to providing topographic measuring tools, molaR has complimentary plotting functions enabling highly customizable visualization of results. This article gives a detailed description of the DNE measure, walks researchers through installing, operating, and troubleshooting molaR and its functions, and gives an example of a simple comparison that measured teeth of the primates Alouatta and Pithecia in molaR and other available software packages. molaR is a free and open source software extension, which can be found at the doi:10.13140/RG.2.1.3563.4961(molaR v. 2.0) as well as on the Internet repository CRAN, which stores R packages.

Nitrate metabolism in the dinoflagellate Lingulodinium polyedrum

Les dinoflagellés sont des eucaryotes unicellulaires retrouvés dans la plupart des écosystèmes aquatiques du globe. Ces organismes amènent une contribution substantielle à la production primaire des océans, soit en tant que membre du phytoplancton, soit en tant que symbiontes des anthozoaires formant les récifs coralliens. Malheureusement, ce rôle écologique majeur est souvent négligé face à la capacité de certaines espèces de dinoflagellés à former des fleurs d'eau, parfois d'étendue et de durée spectaculaires. Ces floraisons d'algues, communément appelées "marées rouges", peuvent avoir de graves conséquences sur les écosystèmes côtiers, sur les industries de la pêche et du tourisme, ainsi que sur la santé humaine. Un des facteurs souvent corrélé avec la formation des fleurs d'eau est une augmentation dans la concentration de nutriments, notamment l’azote et le phosphore. Le nitrate est un des composants principaux retrouvés dans les eaux de ruissellement agricoles, mais également la forme d'azote bioaccessible la plus abondante dans les écosystèmes marins. Ainsi, l'agriculture humaine a contribué à magnifier significativement les problèmes associés aux marées rouges au niveau mondial. Cependant, la pollution ne peut pas expliquer à elle seule la formation et la persistance des fleurs d'eau, qui impliquent plusieurs facteurs biotiques et abiotiques. Il est particulièrement difficile d'évaluer l'importance relative qu'ont les ajouts de nitrate par rapport à ces autres facteurs, parce que le métabolisme du nitrate chez les dinoflagellés est largement méconnu. Le but principal de cette thèse vise à remédier à cette lacune. J'ai choisi Lingulodinium polyedrum comme modèle pour l'étude du métabolisme du nitrate, parce que ce dinoflagellé est facilement cultivable en laboratoire et qu'une étude transcriptomique a récemment fourni une liste de gènes pratiquement complète pour cette espèce. Il est également intéressant que certaines composantes moléculaires de la voie du nitrate chez cet organisme soient sous contrôle circadien. Ainsi, dans ce projet, j'ai utilisé des analyses physiologiques, biochimiques, transcriptomiques et bioinformatiques pour enrichir nos connaissances sur le métabolisme du nitrate des dinoflagellés et nous permettre de mieux apprécier le rôle de l'horloge circadienne dans la régulation de cette importante voie métabolique primaire. Je me suis tout d'abord penché sur les cas particuliers où des floraisons de dinoflagellés sont observées dans des conditions de carence en azote. Cette idée peut sembler contreintuitive, parce que l'ajout de nitrate plutôt que son épuisement dans le milieu est généralement associé aux floraisons d'algues. Cependant, j’ai découvert que lorsque du nitrate était ajouté à des cultures initialement carencées ou enrichies en azote, celles qui s'étaient acclimatées au stress d'azote arrivaient à survivre près de deux mois à haute densité cellulaire, alors que les cellules qui n'étaient pas acclimatées mourraient après deux semaines. En condition de carence d'azote sévère, les cellules arrivaient à survivre un peu plus de deux semaines et ce, en arrêtant leur cycle cellulaire et en diminuant leur activité photosynthétique. L’incapacité pour ces cellules carencées à synthétiser de nouveaux acides aminés dans un contexte où la photosynthèse était toujours active a mené à l’accumulation de carbone réduit sous forme de granules d’amidon et corps lipidiques. Curieusement, ces deux réserves de carbone se trouvaient à des pôles opposés de la cellule, suggérant un rôle fonctionnel à cette polarisation. La deuxième contribution de ma thèse fut d’identifier et de caractériser les premiers transporteurs de nitrate chez les dinoflagellés. J'ai découvert que Lingulodinium ne possédait que très peu de transporteurs comparativement à ce qui est observé chez les plantes et j'ai suggéré que seuls les membres de la famille des transporteurs de nitrate de haute affinité 2 (NRT2) étaient réellement impliqués dans le transport du nitrate. Le principal transporteur chez Lingulodinium était exprimé constitutivement, suggérant que l’acquisition du nitrate chez ce dinoflagellé se fondait majoritairement sur un système constitutif plutôt qu’inductible. Enfin, j'ai démontré que l'acquisition du nitrate chez Lingulodinium était régulée par la lumière et non par l'horloge circadienne, tel qu'il avait été proposé dans une étude antérieure. Finalement, j’ai utilisé une approche RNA-seq pour vérifier si certains transcrits de composantes impliquées dans le métabolisme du nitrate de Lingulodinium étaient sous contrôle circadien. Non seulement ai-je découvert qu’il n’y avait aucune variation journalière dans les niveaux des transcrits impliqués dans le métabolisme du nitrate, j’ai aussi constaté qu’il n’y avait aucune variation journalière pour n’importe quel ARN du transcriptome de Lingulodinium. Cette découverte a démontré que l’horloge de ce dinoflagellé n'avait pas besoin de transcription rythmique pour générer des rythmes physiologiques comme observé chez les autres eukaryotes.

Contrôle traductionnel du rythme circadien de la bioluminescence chez le dinoflagellé Lingulodinium polyedrum

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Identification et caractérisation de candidats régulateurs du cycle cellulaire chez le dinoflagellé Lingulodinium polyedrum

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Free Resolutions from Involutive Bases

We show that the theory of involutive bases can be combined with discrete algebraic Morse Theory. For a graded k[x0 ...,xn]-module M, this yields a free resolution G, which in general is not minimal. We see that G is isomorphic to the resolution induced by an involutive basis. It is possible to identify involutive bases inside the resolution G. The shape of G is given by a concrete description. Regarding the differential dG, several rules are established for its computation, which are based on the fact that in the computation of dG certain patterns appear at several positions. In particular, it is possible to compute the constants independent of the remainder of the differential. This allows us, starting from G, to determine the Betti numbers of M without computing a minimal free resolution: Thus we obtain a new algorithm to compute Betti numbers. This algorithm has been implemented in CoCoALib by Mario Albert. This way, in comparison to some other computer algebra system, Betti numbers can be computed faster in most of the examples we have considered. For Veronese subrings S(d), we have found a Pommaret basis, which yields new proofs for some known properties of these rings. Via the theoretical statements found for G, we can identify some generators of modules in G where no constants appear. As a direct consequence, some non-vanishing Betti numbers of S(d) can be given. Finally, we give a proof of the Hyperplane Restriction Theorem with the help of Pommaret bases. This part is largely independent of the other parts of this work.

Food for Pollinators: Quantifying the Nectar and Pollen Resources of Urban Flower Meadows

Planted meadows are increasingly used to improve the biodiversity and aesthetic amenity value of urban areas. Although many ‘pollinator-friendly’ seed mixes are available, the floral resources these provide to flower-visiting insects, and how these change through time, are largely unknown. Such data are necessary to compare the resources provided by alternative meadow seed mixes to each other and to other flowering habitats. We used quantitative surveys of over 2 million flowers to estimate the nectar and pollen resources offered by two exemplar commercial seed mixes (one annual, one perennial) and associated weeds grown as 300m2 meadows across four UK cities, sampled at six time points between May and September 2013. Nectar sugar and pollen rewards per flower varied widely across 65 species surveyed, with native British weed species (including dandelion, Taraxacum agg.) contributing the top five nectar producers and two of the top ten pollen producers. Seed mix species yielding the highest rewards per flower included Leontodon hispidus, Centaurea cyanus and C. nigra for nectar, and Papaver rhoeas, Eschscholzia californica and Malva moschata for pollen. Perennial meadows produced up to 20x more nectar and up to 6x more pollen than annual meadows, which in turn produced far more than amenity grassland controls. Perennial meadows produced resources earlier in the year than annual meadows, but both seed mixes delivered very low resource levels early in the year and these were provided almost entirely by native weeds. Pollen volume per flower is well predicted statistically by floral morphology, and nectar sugar mass and pollen volume per unit area are correlated with flower counts, raising the possibility that resource levels can be estimated for species or habitats where they cannot be measured directly. Our approach does not incorporate resource quality information (for example, pollen protein or essential amino acid content), but can easily do so when suitable data exist. Our approach should inform the design of new seed mixes to ensure continuity in floral resource availability throughout the year, and to identify suitable species to fill resource gaps in established mixes.

On (p, q) − equations with concave terms

We consider a (p, q)− equation (1 < q < p, p ≥ 2) with a parametric concave term and a (p − 1)− linear perturbation. We show that the problem have five nontrivial smooth solutions: four of constant sign and the fifth nodal. When q = 2 (i.e., (p, 2) equation) we show that the problem has six nontrivial smooth solutions, but we do not specify the sign of the sixth solution. Our approach uses variational methods, together with truncation and comparison techniques and Morse theory.

Relação coronal do implante com a crista óssea

Introdução: A reabilitação com implantes nas últimas décadas tem evoluído tendo em vista a obtenção de melhores resultados ao nível mecânico/funcional, mas também a nível estético. A relação coronal dos implantes com crista óssea é um dos pontos que tem sido estudado. Objectivo: Realizar uma revisão sobre a relação coronal dos implantes com a crista óssea, com objectivo de responder à seguinte questão “A posição sub-crestal dos implantes em relação à crista óssea é vantajosa?”. Para tal vão ser estudados alguns dos factores que podem influenciar esta decisão. Metodologia: Realizou-se pesquisa bibliográfica recorrendo às bases de dados da “MEDLINE/Pubmed”, “SciELO”, “Science Direct”, “B-on”, “Google Academic” e repositórios de várias universidades portuguesas e estrangeiras, com as palavras-chave: “Bone Cells” ”Bone remodeling”, “Bone Crest”, “Osseointegration”, “Implant Placement”, “Biologic Width” e “Platform Switching”,”Implant Placement Depth” e “Morse Cone”, tendo sido estas associadas entre si. Também foi realizada pesquisa manual em livros dos vários temas estudados. Conclusão: A colocação de implantes ao nível sub-crestal ainda apresenta alguma controvérsia, mas obedecendo a alguns factores, como a utilização de um implante e pilar específicos, pode tornar- se algo muito vantajoso numa perspectiva futura.

Tensões ósseas peri-implantares em implantes colocados justa e infra crestalmente

Este trabalho divide-se em duas partes distintas: uma longa e detalhada revisão bibliográfica acerca das temáticas anatomia peri-implantar, espaço biológico, osso alveolar, osteointegração, cone Morse e platform-switching e FEA (Finit Element Analisys) ; e um estudo sobre tensões peri-implantares em implantes do tipo cone Morse colocados infra e justa crestalmente. Foi possível concluir com este estudo laboratorial que os implantes colocados justacrestalmente apresentam melhores resultados biomecanicamente, ou seja, apresentam um menor volume de osso em tensão. Materiais e métodos: Foi realizada uma pesquisa bibliográfica na PubMed e Medline explorando os seguintes items: “osteointegração”, “saucerização”, “platform switching”, “cone Morse”, “osso alveolar”, “anatomina peri-implantar”, “espaço biológico”, “osteoclastos”, “osteoblastos”, “remodelação óssea”, “colocação de implantes justacrestalmente”, “colocação de implantes infra-crestalmente” e “análise de FEA”. Na bibliografia encontrada com as temáticas supra-citadas foi feita uma cuidadosa selecção de acordo com aquilo a que este trabalho se propunha. Simultaneamente, um modelo 3D de dois implantes, um de conexão externa hexagonal e outro de conexão interna do tipo cone Morse, exactamente iguais com exceção da já referida conexão, de 10mm de comprimento e 4mm de diâmetro, foram inseridos num bloco ósseo obtido através de uma CT e sujeitos a uma força axial de 150N e uma força oblíqua de 150N a 45º, tendo sido avaliados por uma análise de elementos finitos.

Étude descriptive des effets d’une action pédagogiques spécifique auprès d'un enfant de 5 ans éprouvant de sérieuses difficultés langagières

La présente recherche porte sur une expérience de rééducation, auprès d'un enfant de cinq ans présentant un assez lourd handicap dans ses performances langagières à son arrivée en classe maternelle. D'abord, une recherche théorique a été effectuée afin de mieux connaître les étapes précédant l’apparition du langage, c'est-à-dire l’étape prénatale, le stade sensori-moteur et le langage préverbal. La recherche théorique devait également s'attacher aux caractéristiques et aux effets du milieu dans lequel tout enfant grandit, milieu qui a une grande influence sur l’évolution de son langage, ainsi que sur son bagage culturel. Ensuite, il était possible d'étudier plus spécifiquement trois aspects du langage de l 'enfant, soit le système phonologique, l’extension du vocabulaire ainsi que l’apparition des fonctions syntaxiques.