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Denna studie undersöker cellstorlekens inverkan på metabola processer, med särskilt fokus på skillnader mellan senescenta och icke-senescenta celler under varierande glukosförhållanden. Genom fluorescerande färgning, avbildning och flödescytometri analyserades nukleär och cellulär morfologi, DNA-innehåll, glukosupptag och cellvolym i cellinjerna HeLa Kyoto och DU-145. Resultaten visar signifikanta morfologiska förändringar i senescenta celler, inklusive ökad nukleär och cellulär storlek, högre aspektförhållanden och minskad nukleär konvexitet. Senescens associeras med minskat glukosupptag och förändrad metabolisk aktivitet, där större celler uppvisar lägre metabola hastigheter. Dessa fynd indikerar att cellulär senescens väsentligt påverkar metaboliska processer och morfologi, oberoende av glukoskoncentration. Forskningen förbättrar vår förståelse av cellulär metabolism och senescens, och erbjuder potentiella implikationer för terapeutiska strategier mot metabola störningar och cancer. Framtida studier bör undersöka de specifika mekanismerna bakom dessa förändringar och deras bredare tillämpningar inom medicinsk vetenskap.

Tesis por compendio / [ES] En las últimas dos décadas, la producción de caqui en España ha aumentado exponencialmente y la superficie de cultivo se ha multiplicado casi por ocho. En la actualidad, la producción de caqui está centralizada en el cultivar 'Rojo Brillante', que es mundialmente apreciado. Sin embargo, esta centralización supone una importante limitación comercial. En la presente Tesis se abordan dos objetivos principales: 1) Optimización de la tecnología pre y postcosecha con el fin de garantizar la calidad del caqui 'Rojo Brillante' durante la frigoconservación y el transporte a mercados internacionales. 2) Evaluación del comportamiento bajo condiciones mediterráneas de variedades introducidas de otras regiones productoras con el fin de ampliar el rango varietal de caqui. El primer objetivo de esta Tesis se logró a través de los estudios presentados en los Capítulos I al V. El segundo objetivo se abordó en los Capítulos VI y VII. En el Capítulo I se esclarecieron las causas del pardeamiento interno del fruto en los envíos a los mercados internacionales. La temperatura a la que se expone la fruta inmediatamente tras la aplicación del tratamiento de desastringencia con altas concentraciones de CO2 se identificó como el principal factor implicado en esta alteración. Los resultados obtenidos mostraron que esta alteración se puede evitar mediante la implementación de un período de atemperado de 24 h después del tratamiento con CO2, antes de conservar las frutas a bajas temperaturas. En el Capítulo II se evaluó la eficacia de un tratamiento de desastringencia recientemente patentado basado en la aplicación de una nueva cera que contiene etanol en su formulación. Los resultados mostraron que esta cera podría ser una alternativa al tratamiento convencional de desastringencia con altas concentraciones de CO2 cuando la fruta se envía a mercados lejanos a bajas temperaturas. La aplicación de la nueva cera antes de conservación en frío provocó la pérdida de astringencia de la fruta tras 30 días a 0 °C, preservando la firmeza y la calidad interna. Los resultados del Capítulo III demostraron que la realización de dos aplicaciones de ácido giberélico (AG) en precosecha permite retrasar el proceso de maduración de la fruta en el árbol con respecto a una sola aplicación. La combinación de AG en precosecha y 1-metilciclopropeno (1-MCP) en postcosecha resultó en una mayor calidad del fruto durante la frigoconservación en comparación con la aplicación únicamente de 1-MCP. Además, la fruta tratada con múltiples aplicaciones de AG mostró una firmeza ligeramente mayor tras de conservación a baja temperatura. En el Capítulo IV se demostró que, paralelamente al retraso de la maduración, el tratamiento con AG también retrasa la senescencia del cáliz, incrementando la calidad externa del fruto. La senescencia del cáliz durante la maduración del fruto se relacionó con una disminución de los parámetros de fluorescencia de clorofila (Fo, Fm y Fv/Fm). En el Capítulo V se estudiaron las condiciones óptimas de almacenamiento del caqui producido bajo cultivo ecológico. Según los resultados, no se deben almacenar los frutos cosechados con firmeza inferior a 30 N. La calidad del fruto durante la conservación dependió de las condiciones de almacenamiento, momento de aplicación del tratamiento de deastringencia y estado de madurez inicial. Por último, en los Capítulos VI y VII se abordó la evaluación bajo condiciones mediterráneas de 14 variedades de caquis no-astringentes procedentes de otros países. Se identificaron las variedades tempranas y tardías que pueden ser potencialmente interesantes para ampliar el período de cosecha en nuestra región. Los estudios postcosecha mostraron que todas las variedades estudiadas presentan una buena aptitud para ser comercializadas en los mercados nacionales y europeos. Sin embargo, la sensibilidad a los daños por frío que presentaron algunas de las variedades estudiadas podría limitar su comercialización a países de ultramar. Además, se observó que la respuesta al tratamiento con 1-MCP, para el control de los daños por frío, dependió en gran medida de la variedad. / [CA] En les últimes dues dècades, la producció de caqui a Espanya ha augmentat exponencialment i la superfície de cultiu s'ha multiplicat quasi per huit vegades. En l'actualitat, la producció de caqui està centralitzada en el la cultivar 'Rojo Brillante', que és mundialment apreciat. Malgrat això, aquesta centralització suposa d'una banda una important limitació comercial, ja que la producció es concentra en un període de collita relativament curt i, d'altra banda implica un alt risc fitosanitari. En la present Tesi s'aborden dos objectius principals: 1) Optimització de la tecnologia pre i postcollita amb la finalitat de garantir la qualitat del caqui 'Rojo brillante' durant la frigoconservació i el transport a mercats internacionals. 2) Avaluació del comportament de varietats introduïdes d'altres regions productores sota condicions mediterrànies amb la finalitat d'ampliar el rang varietal de caqui. En el Capítol I es van esclarir les causes de l l'enfosquiment intern. La temperatura a la qual s'exposa la fruita immediatament després de l'aplicació del tractament de desastringència amb altes concentracions de CO¿ es va identificar com el principal factor implicat en aquesta alteració. Els resultats obtinguts van mostrar que aquesta alteració es pot evitar mitjançant la implementació d'un període de temperat de 24 h després del tractament amb CO¿, abans de transferir la fruita a baixes temperatures. En el Capítol II es va avaluar l'eficàcia d'un tractament de desastringència recentment patentat basat en l'aplicació d'una nova cera que conté etanol en la seua formulació en caquis 'Rojo Brillante' i 'Triumph'. Els resultats van mostrar que aquesta cera podria ser una alternativa al tractament convencional de desastringència amb altes concentracions de CO¿ quan la fruita s'envia a mercats llunyans a baixes temperatures. L'aplicació de la nova cera abans de conservació en fred va provocar la pèrdua d'astringència de la fruita després de 30 dies a 0 °C, preservant la fermesa i la qualitat interna. Els resultats del Capítol III van demostrar que l'aplicació de dos tractaments d'àcid giberèlic (AG) en precollita permet retardar el procés de maduració de la fruita en l'arbre respecte a una sola aplicació. La combinació de AG en precollita i 1-metilciclopropeno (1-MCP) en postcollita va incrementar la qualitat del fruit durant la frigoconservació en comparació amb l'aplicació únicament de 1-MCP. A més, la fruita tractada amb múltiples aplicacions de AG va mostrar una fermesa lleugerament major després de conservació a baixa temperatura; no obstant això, una sola aplicació de AG també va ser eficaç per a previndre la manifestació de danys per fred en la fruita. En el Capítol IV es va demostrar que, paral·lelament al retard de la maduració, el tractament amb AG també retarda la senescència del calze, incrementant la qualitat externa del fruit. La senescència del calze durant la maduració del fruit es va relacionar amb una disminució dels paràmetres de fluorescència de clorofil·la (Fo, Fm i Fv/Fm). En el Capítol V es van estudiar les condicions òptimes d'emmagatzematge del caqui produït baix cultiu ecològic. D'acord amb els resultats obtinguts, no s'han d'emmagatzemar els fruits collits amb fermesa inferior a 30 N. La conservació del fruit va dependre de les condicions d'emmagatzematge, moment d'aplicació del tractament de desastringència i estat de maduresa de la fruita. Finalment, en els Capítols VI i VII es va abordar l'avaluació de 14 varietats de caquis no-astringents. Es van identificar les varietats primerenques i tardanes que poden ser potencialment interessants per a ampliar el període de collita. D'altra banda, els estudis postcollita van mostrar que totes les varietats estudiades presenten una bona aptitud per a ser comercialitzades en els mercats nacionals i europeus. No obstant això, la sensibilitat als danys per fred que van presentar algunes de les varietats estudiades podria limitar la seua comercialització a països d'ultramar. A més, es va observar que la resposta al tractament amb 1-MCP, per al control dels danys per fred, va dependre en gran manera de la varietat. / [EN] In the last two decades, persimmon production in Spain has increased exponentially and the cultivation area has expanded almost eight-fold. The current production of persimmon is focused on the cultivar 'Rojo Brillante', which is appreciated worldwide due to the high quality of the fruit. Nevertheless, centralized production of this single cultivar implies a major commercial limitation as its high volume of production is concentrated in a relative short harvesting period. Furthermore, it also implies a high phytosanitary risk. In this context, this Thesis addresses two main objectives: 1) Optimization of pre- and postharvest technology in order to guarantee the quality of 'Rojo Brillante' persimmon after cold storage and transportation to overseas markets. 2) Evaluation of the behavior of foreign varieties of persimmon under Mediterranean conditions in order to extend the varietal range. The first objective of this Thesis was tackled through the studies presented in Chapters I to V. The second objective was covered in Chapters VI and VII. Chapter I dealt with the causes of internal browning disorder manifested after cold shipment of 'Rojo Brillante' persimmons to overseas markets. The temperature to which fruit is exposed immediately after CO2 deastringency treatment was identified as the main factor involved in this alteration. Our results showed that this disorder can be avoided by implementing an attemperation period of 24 h after the CO2 treatment, before transferring fruit to cold storage. In Chapter II, the effectiveness of a recently patented deastringency treatment based on applying a new wax containing ethanol was assayed in 'Rojo Brillante' and 'Triumph' persimmons. The use of this new ethanol-based wax could be a potential alternative to the conventional CO2 deastringency treatment when the fruit are sent to distant overseas markets at low temperatures. Application of the new wax before cold storage led to loss of fruit astringency after 30 days at 0 °C while preserving fruit firmness and internal quality. The results of Chapter III demonstrated that two applications of gibberellic acid (GA) made it possible to delay the fruit maturity process on the tree more than with just a single application. The combination of GA and 1-methylciclopropene (1-MCP) preserved the fruit quality better than with the application of 1-MCP alone during cold storage. Moreover, the fruit treated by multiple GA applications showed a slightly higher firmness after cold storage. However, a single GA application was also effective in preventing the manifestation of chilling injury (CI) in fruit. Chapter IV demonstrated that in parallel to delaying maturity, the GA treatment also delayed calyx senescence, which meant that the fruit preserved a good appearance. The calyx lobe senescence during fruit ripening was linked to a decrease in all Chlorophyll Fluorescence Imaging (CFI) parameters (Fo, Fm, and Fv/Fm). Chapter V addressed the optimization of storage conditions for organic persimmons. According to our results, fruit harvested with a firmness lower than 30 N must not be stored. Fruit harvested with a higher level of firmness could be stored for up to three weeks depending on the storage conditions, the moment of application of the CO2 deastringency treatment, and the stage of fruit maturity. The longest storage period (3 weeks) was achieved when fruit were harvested with a firmness of around 45 N, submitted to CO2 treatment and then stored at 15 °C. Finally, 14 foreign varieties grown under Mediterranean conditions were evaluated to identify early- and late-season varieties with potential to extend the harvesting period. This is presented in Chapters VI and VII. In general, all the evaluated varieties fulfilled the quality criteria to be commercialized in domestic and European markets. However, sensitivity to CI was variety dependent and response to 1-MCP treatment was also observed to depend on the variety. / This study has been supported by the Instituto Nacional de Tecnología Agraria y Alimentaria de España (INIA) and Fondo Europeo de Desarrollo Regional (FEDER) through the projects RTA 2013-00043-C02-01 and RTA2017-00045-C02-01. In addition, it has been supported by the Valencian Institute for Agricultural Research (Project N° 51910). This study has also been founded by the Consellería de Educación, Investigación, Cultura y Deporte de la Comunidad Valenciana (project GV/2016/183). Ayoub Fathi Najafabadi thanks the INIA for grant FPI-INIA #43 (CPD2015-0151). The authors thank Fomesa Fruitech S.L.U. and Natural Hand S. L. for their technical support, Cooperativa Agrícola Ntra Sra de Loreto for its technical support and for making the plots and fruit used in this study available and Plant Production Department (Instituto Valenciano de Investigaciones Agrarias) for providing the fruit weight data and the photographs of the different varieties. / Fathi Najafabadi, A. (2021). Optimization of postharvest Technology for "Rojo brillante" Persimmon and Introduction of New Varieties in the Mediterranean Area [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/171252 / Compendio

Studies of mating systems and social organisation have been central to understanding of the evolution of social behaviour. The European badger Meles meles is a good species in which to study these processes, as its complex social system provides an opportunity to investigate how both natural and kin selection shape the evolution of mating systems and social structure. In this thesis, I use behavioural and genetic data to describe the mating system and social organisation of a high-density badger population and examine the occurrence of cooperative breeding. I genotyped 915 (85%) badgers trapped in Wytham Woods (1987–2005), 630 of which were cubs, and assigned both parents to 331 cubs with 95% confidence. This revealed a polygynandrous mating system, with up to five mothers and five fathers per social group. Mounting behaviour was also polygynandrous and I show the strongest evidence to date for multiple-paternity litters. I demonstrate, for the first time, that groups consisted of close and distant kin: approximately one third of group members were first-order kin, and overall group members had slightly lower relatedness levels than half-siblings. Within groups, adult and yearling females had higher pairwise relatedness than males, and neighbouring groups contained relatives. These findings result from the high level (42%) of extra-group paternities, 86% of which were assigned to neighbouring males. For the first time I show that females avoided inbreeding by mating with extra-group males; however, incestuous matings did occur. Promiscuous and repeated mountings were observed, which may reduce male–male aggression and infanticide, but may also promote sperm competition, genetic diversity, and / or genetic compatibility. Just under a third of adult males and females were assigned parentage each year and I quantify, for the first time, reproductive skew within badger groups. Correlations between relatedness, group productivity, and reproductive skew were not consistent with the predictions of incomplete-control models; rather, resource availability may play a role. Older and younger badgers displayed reduced annual breeding success, with male success increasing initially with experience. The Restraint, Constraint, and Selection Hypotheses did not explain the age-related breeding pattern in females. Variance in lifetime breeding success (LBS) was greater for males. Males that only bred within or only outside of their groups had half the LBS of males that did both. Females that were assigned maternity probably bred cooperatively and allonursed non-offspring, which has not been demonstrated previously. No benefit was established, however, in terms of litter size, probability of offspring breeding, or offspring lifetime breeding success, with more mothers in a group. In conclusion, badger social groups are fostered through kinship ties. Polygynandry and repeated mounting may have evolved originally to reduce male–male aggression and infanticide by males, through paternity masking. Although plural breeding occurs, group living appears to be costly. Motivation to disperse may be reduced through high-levels of extra-group paternities, which may also reduce inbreeding. Cooperative breeding among mothers may represent a low-cost behaviour with indirect benefits due to high levels of relatedness between female group-members. Badger sociality therefore represents an early stage in the evolution of social behaviour.

Le H2O2 est reconnu comme un signal dans l’activation des mécanismes de défense en réponse à divers stress, et son accumulation est donc régulée étroitement par le système antioxydant des plantes. Puisque la signalisation par le H2O2 peut être transmise par des processus thiol-dépendants, le statut du glutathion pourrait jouer un rôle important. Le rôle de ce composé en tant que molécule antioxydante est bien établi; cependant, son importance en tant que signal reste à élucider. Afin d’étudier cette question, ce travail a utilisé un mutant, cat2, ayant un défaut dans son métabolisme du H2O2 peroxysomal qui engendre, d’une manière conditionnelle, une oxydation et une accumulation du glutathion. Les modifications du glutathion dans cat2 sont accompagnées par l’activation à la fois de réponses dépendantes de l’acide salicylique (SA) ainsi que l’expression de gènes associés à l’acide jasmonique (JA). L’activation des deux voies phytohormonales par le stress oxydant intracellulaire est largement empêchée en bloquant génétiquement l’accumulation du glutathion dans un double mutant, cat2 cad2, qui porte une mutation additionnelle dans la voie de synthèse du glutathion. Les phénotypes contrastants de cat2 cad2 et cat2 gr1, dans lequel la perte de l’activité GR1 aggrave le stress oxydant, suggèrent que des processus glutathion-dépendants relient le H2O2 et l’activation des réponses de pathogenèse SA-dépendantes par un effet qui est additionnel aux fonctions antioxydantes du glutathion. Des comparaisons directes de cat2 cad2 et cat2 npr1 indiquent que les effets de bloquer l’accumulation du glutathion sur l’induction des voies SA et JA chez cat2 ne sont pas causés par une déficience dans la fonction de la NPR1. L’autophagie a été impliquée dans des processus comme la sénescence, et interagirait à la fois avec le stress oxydant et avec la signalisation par le SA. Afin d’explorer des relations entre autophagie et stress oxydant, des mutants atg ont été sélectionnés et croisés avec le cat2. Des analyses phénotypiques ont révélé que l’étendue de lésions SA-dépendantes observée chez cat2 cultivé en jours longs est similaire chez trois double mutants cat2 atg, alors que l’augmentation de la disponibilité en H2O2 peroxysomal liée à la mutation cat2 retarde la sénescence précoce observée chez les mutants atg. Dans son ensemble, le travail suggère que (1) des nouvelles fonctions glutathion-dépendantes sont importantes pour relier la disponibilité en H2O2 intracellulaire et activation des voies de signalisation SA et JA, et (2) que le H2O2 produit par la photorespiration pourrait jouer un rôle antagoniste dans les phénotypes de sénescence précoce observée chez les mutants atg. / H2O2 is a recognized signal in activation of defence mechanisms in response to various stresses, and its accumulation is thus tightly controlled by plant antioxidant systems. Because H2O2 signals may be transmitted by thiol-dependent processes, glutathione status could play an important role. While the antioxidant role of this compound is long established, the importance of glutathione in signaling remains unclear. To study this question, this work exploited a stress mimic mutant, cat2, which has a defect in metabolism of peroxisomal H2O2 that conditionally leads to oxidation and accumulation of glutathione. In cat2, changes in glutathione are accompanied by activation of both salicylic acid (SA)-dependent responses and jasmonic acid (JA)-associated genes in a time-dependent manner. This up-regulation of both phytohormone signaling pathway by intracellular oxidative stress can be largely prevented by genetically blocking glutathione accumulation in a double mutant, cat2 cad2, that additionally carries a mutation in the pathway of glutathione synthesis. Contrasting phenotypes between cat2 cad2 and cat2 gr1, in which loss of GR1 activity exacerbates oxidative stress, suggest that glutathione-dependent processes couple H2O2 to activation of SA-dependent pathogenesis responses through an effect that is additional to glutathione antioxidant functions. Direct comparison of cat2 cad2 and cat2 npr1 double mutants suggests that the effects of blocking glutathione accumulation on cat2-triggered up-regulation of both SA and JA pathways are not mediated by defective NPR1 function. Autophagy has been implicated in processes such as senescence, and may interact with oxidative stress and SA signaling. To explore relationships between autophagy and oxidative stress, selected atg mutants were crossed with cat2. Phenotypic analysis revealed that SA-dependent lesion spread observed in cat2 grown in long days is similar in three cat2 atg double mutants, whereas increased peroxisomal H2O2 availability in cat2 delays an oxidative stress related-senescence triggered by atg in short days. Overall, the work suggests that (1) novel glutathione-dependent functions are important to couple intracellular H2O2 availability to the activation of both SA and JA signaling pathways and (2) H2O2 produced through photorespiration may play an antagonistic role in the early senescence phenotype observed in atg mutants.

Au cours du vieillissement, la rigidification des artères élastiques entraine une augmentation de l'amplitude de la pression pulsée centrale, qui se propage dans la microcirculation cérébrale. De façon chronique, l’élévation anormale de la pression pulsée endommage les fonctions vasculaires et cérébrales, pouvant être impliquée dans le développement d’une déficience cognitive d’origine vasculaire. Ceci est supporté par l’observation d’anomalies cérébrovasculaires chez les individus atteints de démence vasculaire et de la maladie d’Alzheimer. De plus, les individus exposés aux facteurs de risque vasculaires (hypertension, obésité, diabète, athérosclérose), démontrent une vascularisation fragilisée, une augmentation de la pression pulsée centrale et présentent un déclin cognitif. Il est donc probable qu’en association avec l’âge, les facteurs de risque vasculaires favorisent de façon mécanistique la propagation de la pression pulsée dans la circulation cérébrale et révèlent de façon prématurée le déclin cognitif. Le lien mécanistique entre l’augmentation de la pression pulsée cérébrale, les facteurs de risque vasculaires, les dommages cérébrovasculaires et l’incidence de la démence reste à être plus clairement investigué. La présente thèse vise ainsi à étudier l’hypothèse biomécanique du rôle délétère de la pression pulsée dans la détérioration des fonctions cérébrovasculaires et cognitives, avec l’âge et en association avec les facteurs de risque vasculaires, en élucidant la cascade des événements pathologiques depuis l’élévation de la pression pulsée centrale jusqu’à l’incidence de la démence. Afin de vérifier notre hypothèse, nous avons entrepris dans une première étude d’étudier chez la souris WT, l’impact de l’augmentation in vivo d’un stress mécanique pulsatile central (par chirurgie TAC) sur la vasculature cérébrale, le tissu cérébral et les fonctions cognitives. Ce stress a été induit en parallèle dans le modèle de souris transgénique APP/PS1 de la maladie d’Alzheimer. Nous avons pu démontrer que les vaisseaux cérébraux des souris WT et APP/PS1 sont vulnérables au stress mécanique de la pression pulsée, caractérisé par une diminution de la réponse vasodilatatrice des artères piales, une raréfaction des capillaires due à une apoptose, l’incidence de micro-hémorragies, une rupture de la barrière hémato-encéphalique et une hypoperfusion cérébrale. Ces dommages cumulatifs à la microcirculation cérébrale sont associés à une inflammation cérébrale et à une diminution des performances d’apprentissage et de mémoire de travail et spatiale des souris. De plus, le phénotype Alzheimer des souris APP/PS1 est exacerbé en présence du stress vasculaire, exprimé par l’augmentation des dépôts béta-amyloïdes, ainsi que la dysfonction endothéliale cérébrale et l’inflammation cérébrale déjà présentes dans ce modèle. Dans une deuxième étude, nous avons caractérisé les fonctions cérébrovasculaires et cognitives des souris transgéniques LDLR-/-;hApoB100+/+ avec l’ajout ou non d’un stress mécanique pulsatile central in vivo (par chirurgie TAC). Ces souris présentent des facteurs de risques des maladies cardiovasculaires (hypertension et dyslipidémie) menant au développement d’athérosclérose et miment un vieillissement artériel central accéléré (rigidité aortique et des carotides, dysfonction endothéliale, augmentation de la pression pulsée). Nous avons démontré que les souris LDLR-/-;hApoB100+/+ exhibent des anomalies cérébrovasculaires structurelles et fonctionnelles, dont une atrophie cérébrale, une dysfonction endothéliale cérébrale, une hypoperfusion cérébrale, une augmentation de la perméabilité de la barrière hémato-encéphalique, des micro-hémorragies corticales, la présence d’inflammation, de sénescence et de stress oxydant au niveau vasculaire et parenchymateux. L’ensemble de ces altérations majoritairement vasculaires, sont associées à une diminution des performances cognitives et sont exacerbées en présence d’un stress vasculaire additif. Nos deux études chez la souris démontrent qu’en présence d’une pression pulsée élevée, les dommages à la microvasculature cérébrale conduisent à une perte fonctionnelle de l’homéostasie cérébrale et à un déclin cognitif, dont l’incidence est accélérée soit dans un modèle de démence ou soit de vieillissement artériel central et en présence de facteurs de risque des maladies cardiovasculaires. Nos études fournissent la démonstration mécanistique d’un continuum entre une augmentation de pression pulsée et un déclin cognitif vasculaire. / With advancing age, the large elastic arteries undergo significant stiffening, resulting in increased central pulse pressure waves that penetrates deeper the cerebral microcirculation and may result in cerebrovascular and neuronal tissue damages, likely contributing to the development of cognitive impairment from vascular injury origin. This is compatible with strong evidence between impaired cerebrovascular structure and function in the brain of patients with vascular dementia or Alzheimer’s disease. In addition, elderly individuals are subjected in their lifetime to multiple vascular risk factors (hypertension, obesity, diabetes, atherosclerosis), all of which are known to be deleterious to the vascular function, are associated with an increase in central pulse pressure and with cognitive decline. Therefore, it is likely that with age, risk factors for vascular diseases may mechanistically promote the propagation of pulse pressure into the cerebrovascular system and reveal prematurely the brain susceptibility to cognitive decline. The present thesis was conducted to study the biomechanical hypothesis of the deleterious role of the pulse pressure in the deterioration of cerebrovascular and cognitive functions, with age and in association with vascular risk factors, by elucidating the cascade of pathological events linking the increase in central pulse pressure to the expression of dementia. To validate our hypothesis, we first studied in mice the impact of the in vivo increase of central pulsatile mechanical stress (achieved by trans-aortic constriction surgery) on the cerebral vasculature, brain tissue and cognitive functions. This stress was also induced in the APP/PS1 transgenic mouse model of Alzheimer's disease. We have shown that cerebral vessels of WT and APP/PS1 mice are vulnerable to the mechanical stress of the increased pulse pressure, which is characterized by a decrease in the vasodilatory response of the pial arteries, a rarefaction of the capillaries due to apoptosis, the incidence of micro-hemorrhages, a rupture of the blood-brain barrier and cerebral hypoperfusion. These cumulative damages to the cerebral microcirculation are associated with brain inflammation and poorer learning and working and spatial memory performances in mice. The Alzheimer's phenotype of APP/PS1 mice was exacerbated in the presence of elevated pulse pressure, as shown by the increase in beta-amyloid deposits, the decreased in endothelial cerebral vasodilatory responses and brain inflammation, which are already present in this model. In a second study, we sought to characterize the cerebrovascular and cognitive functions in the transgenic mouse model LDLR-/-;hApoB100+/+, subjected or not in vivo to a central pulsatile mechanical stress (by trans-aortic constriction surgery). These mice exhibit risk factors for cardiovascular diseases (hypertension and dyslipidemia), develop atherosclerosis and mimic premature central arterial aging (aortic and carotid stiffness, endothelial dysfunction, increased pulse pressure). We reported that LDLR-/-;hApoB100+/+ mice were characterized by structural and functional brain vascular abnormalities, including cerebral hypoperfusion, increased permeability of the blood-brain barrier, endothelial cerebral dysfunction, microhemorrhages, but also cerebral atrophy and the presence of inflammation, senescence and high oxidative stress at the vascular and parenchymal level. In addition, all these alterations, which are mainly vascular, were associated with a decrease in the cognitive performance of mice. Also, these vascular, parenchymal and cognitive changes were exacerbated in the presence of the vascular stress induced by transverse aortic constriction. Altogether, our two studies in mice demonstrated that, in the presence of an increase in pulse pressure, the damages to the micro-cerebrovascular system lead to loss of cerebral homeostasis and to cognitive decline, which are accelerated in a model of dementia or a model of central vascular aging and in presence or vascular risk factors. Our studies highlight the mechanistic demonstration of a continuum between an increase in pulse pressure and vascular cognitive decline.

Northern Canadian peatlands contain vast deposits of carbon. It is with growing urgency that we seek a better understanding of their assimilative capacity. Assimilative capacity and peat accumulation in raised bogs are linked to primary productivity of resident Sphagnum species. Understanding moisture-mediated photosynthesis of Sphagnum spp. is central to understanding peat production rates. The relationship between depth to water table fluctuation and spectral reflectance of Sphagnum moss was investigated using multispectral imaging at a recovering raised bog on the southwest coast of British Columbia, Canada. Burns Bog is a temperate oceanic ombrotrophic bog. Three ecohydrological indicator species of moss were chosen for monitoring: S. capillifolium, S. papillosum, and S. cuspidatum. Three spectral vegetation indices (SVIs) were used to characterize Sphagnum productivity: the normalized difference vegetation index 660, the chlorophyll index, and the photochemical reflectance index. In terms of spectral sensitivity and the appropriateness of SVIs to species and field setting, we found better performance for the normalized difference vegetation index 660 in the discrimination of moisture mediated species-specific reflectance signals. The role that spatiotemporal scale and spectral mixing can have on reflectance signal fidelity was tested. We were specifically interested in the relationship between changes in the local water table and Sphagnum reflectance response, and whether shifting between close spatial scales can affect the statistical strength of this relationship. We found a loss of statistical significance when shifting from the species-specific cm2 scale to the spectrally mixed dm2 scale. This spatiospectral uncoupling of the moisture mediated reflectance signal has implications for the accuracy and reliability of upscaling from plot based measurements. In terms of species-specific moisture mediated reflectance signals, we were able to effectively discriminate between the three indicator species of Sphagnum along the hummock-to-hollow gradient. We were also able to confirm Sphagnum productivity and growth outside of the vascular growing season, establishing clear patterns of reflectance correlated with changes in the local moisture regime. The strongest relationships for moisture mediated Sphagnum productivity were found in the hummock forming species S. capillifolium. Each indicator Sphagnum spp. of peat has distinct functional traits adapted to its preferred position along the ecohydrological gradient. We also discovered moisture mediated and species-specific reflectance phenologies. These phenospectral characteristics of Sphagnum can inform future monitoring work, including the creation of a regionally specific phenospectral library. It’s recommended that further close scale multispectral monitoring be carried out incorporating more species of moss, as well as invasive and upland species of concern. Pervasive vascular reflectance bias in remote sensing products has implications for the reliability of peatland modelling. Avoiding vascular bias, targeted spectral monitoring of Sphagnum indicator species provides a more reliable measure for the modelling of peatland productivity and carbon assimilation estimates. / Graduate