Macrophages are the largest cells in the immune system and they regulate inflammatory signalling and inform cell fate decisions. Many signals, including those mediated by Tumor Necrosis Factor alpha (TNFα) converge on a few key intracellular signalling pathways, including the Nuclear Factor kappa B (NFκB) network. The NFκB signalling pathway plays a vital role in the regulation of many different cellular responses, including the production of TNFα itself, which is required to sustain and propagate immune responses to, for example, infection or tissue damage. In this thesis we report on studies-both experimental and theoretical-of the NFκB signalling pathway in macrophages. Our collaborators stimulated these cells with various doses of Lipopolysaccharide (LPS), a molecule that forms the major component of the outer membrane of Gram-negative bacteria: in these experiments it serves as a proxy for bacterial infection. The macrophages, studied in vitro, respond as they are believed to do in tissues, by secreting certain signalling molecules called cytokines: the level of secretion proved to depend on the strength of the LPS stimulus. Further, heterogeneity of macrophage signalling was observed in response to a range of LPS doses. Within individual macrophages LPS stimulation results in oscillatory behaviour of NFκB localisation-NFκB shuttles in and out of the nucleus-with an amplitude (peak nuclear concentration) that also depends on the LPS dose. Heterogeneity was also observed in cells that were stimulated with the same dose intensity. This raises an important question about how immune cells coordinate inflammatory activity in the presence of this variability. In this thesis we aim to achieve an understanding of the system through the qualitative analysis of mathematical models of it. This work explores both the parametric sensitivity and bifurcation analyses for two mathematical models of NFκB in macrophages. Parametric sensitivity analysis is used to investigate the role of parameters on the model's output, especially on certain features of the signal-peak amplitudes, inter-peak intervals and areas beneath curves-that are commonly measured in single-cell experiments. Local bifurcation analysis is conducted in order to show all the possible behaviours produced when varying parameters.

I april 2022 presenterade Riksskogstaxeringen (RT) preliminära digitaliserade data om provträd, inklusive åldersbestämningar, från den första Riksskogstaxeringen 1923–1929. Motsvarande data har tidigare funnits tillgängliga digitalt för provträd från inventeringarna efter 1983. Tillsammans med de nya preliminära uppgifterna finns därför nu möjlighet att studera trädpopulationens utveckling i Sverige under de senaste 90 åren. Syftet med denna studie var att analysera hur den svenska trädpopulationen har utvecklats baserat på de tre mätperioderna 1926, 1985 och 2018. Det gjordes genom en kvantitativ analys av RT:s data med fokus på variablerna trädslag, brösthöjdsålder och diameter. Resultaten visar att störst förändringar skedde mellan 1985 och 2018. 2018 var tall för första gången det vanligaste trädslaget. Mellan 1926 och 2018 ökar antalet barrträd i varje diameterklass. De gamla och grova träden blir fler både i avseende på barr och löv. För lövträden ses en markant ökning av bok och ek mellan 1985 och 2018.

Background: On the 21st of April 2021, the EU Commission declared the adoption of Directive (EU) 2022/2464. This directive will significantly increase reporting requirements for companies within its scope. To this date, these sustainability standards are the most comprehensive yet and they aim to foster sustainability reporting quality. However, the concept of quality is multidimensional and empirical evidence related to SRQ and mandatory reporting standards are ambiguous. However, this new directive has not yet been researched thoroughly. Considering it will disrupt the way companies conduct their sustainability reporting, it would foster a research contribution to explore the effects the directive will have on SRQ.  Purpose: This thesis seeks to measure the compliance with, and quality of, the cross- cutting and topical standards derived from Directive (EU) 2022/2464 in large Swedish companies.  Method: The applied research method is quantitative with a deductive approach, where a hypothesis was generated based on existing literature on sustainability reporting quality. Data was collected from annual and sustainability reports of 45 companies. To measure CSRD compliance and the quality index, content analysis has been used. This facilitates transposition of qualitative information to quantitative data. The data was analysed using the statistical program SPSS.  Results: The results from the study show a significant positive relationship between compliance with CSRD and all the dependent variables of measuring the quality of sustainability reporting. Furthermore, the study shows that the average degree of compliance with CSRD requirements is currently 34% in the population, where the highest achieved score was 58% and the lowest achieved score was 7%.

As they are not only the home of many threatened species, but also one of the main actors in the global carbon cycle, peatlands are highly valuable ecosystems. Human disturbance, in particular drainage for forestry and agriculture, has substantially changed the state of the world’s peatlands and will continue to do so. Lowering the water table by drainage has many hydrological and biological effects, including an increased growth of trees and shrubs as well as reduced growth of the key peat moss genus Sphagnum, leading to peat degradation and release of carbon dioxide. The effects of drainage are sometimes used as predictions for how peatlands will respond to climate change, and undrained mires are thus expected to become more like drained ones in the future. The accuracy of that assumption has, to my knowledge, not been tested on a large scale. Here, I use data from two Swedish national monitoring programs to analyze how the vegetation on drained and undrained mires has changed in recent decades. The results showed an increased tree growth but a decreased establishment of new trees on both drained and undrained mires, implying that contrary to common belief there is no current large-scale afforestation of open mires in Sweden. Sphagnum had, surprisingly, increased on both drained and undrained mires, while other functional groups showed varying results. The tree growth rate was faster on drained mires, but in most other analyses the response to time did not differ depending on drainage regime. Thereby, this study found limited support for the hypothesis that undrained mires are becoming more like drained mires with climate change.

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 and miR-181b regulate NFI-A expression via a post-transcriptional regulatory mechanism by recruiting RNA-binding proteins HuR and Ago1 to stabilize NFI-A mRNA, thus increasing its protein levels. Studies in our laboratory also showed that inflammatory mediator S100A9 accumulates in the nucleus in Gr1+CD11b+ myeloid precursors in the later phases of sepsis and is necessary for their expansion and programming into immunosuppressive MDSCs. We demonstrate here that nuclear S100A9 associates with specific transcription factors that activate miR-21 and miR-181b expressions. In our final manuscript, we uncover another layer of the mechanisms of MDSC expansion and programming. We found that long non-coding RNA (lncRNA) Hotairm1 binds to and recruits S100A9 to the nucleus to program Gr1+CD11b+ myeloid precursors into MDSCs in the later phases of sepsis. Together, our results reveal three regulatory layers involving NFI-A, S100A9 and Hotairm1 in the pathway leading to MDSCs development in sepsis and suggest that therapeutically targeting these molecular switches might improve sepsis survival.

Des changements de croissance ont été documentés pour le XXe siècle dans de nombreuses régions en Europe. Cependant une évaluation exhaustive des changements de productivité, à une large échelle géographique, avec une analyse de leur hétérogénéité spatiale et de la diversité interspécifique de la réponse fait encore défaut. L'objectif de cette thèse est d'évaluer les changements récents de la productivité forestière aux échelles nationale, régionale et locale en France, et de rechercher leurs causes environnementales, à partir d'une approche de modélisation statistique de l'accroissement en surface terrière du peuplement (∆G) et d'indicateurs environnementaux. Nous avons utilisé les données de l'inventaire forestier national français pour 8 espèces dont la niche écologique et la distribution diffèrent (Fagus sylvatica, Quercus robur, Quercus petraea, Quercus pubescens, Picea abies, Abies alba, Pinus sylvestris and Pinus halepensis), observées en peuplements purs et réguliers. Nous présentons les facteurs ayant un effet sur la productivité des différentes espèces à l'échelle nationale, ainsi que des cartes de productivité suggérant que l'aire de distribution des espèces n'est pas toujours limitée par les conditions environnementales. Entre 1980 et 2005, nous observons des tendances positives, modales ou non significatives de la productivité pour toutes les espèces à l'exception des deux espèces méditerranéennes dont la productivité a diminué, soulignant ainsi la variabilité interspécifique de ces changements. Nous observons également de fortes variations spatiales des changements de productivité, autant dans leur intensité que dans leur signe, aux échelles régionale et intra-régionale. Ces résultats remettent en question la pertinence d'une évaluation moyenne à large échelle et soulignent le caractère contextuel des estimations. Nous mettons en évidence le rôle du réchauffement climatique récent dans les tendances observées. Ce travail fournit une évaluation plurispécifique et multi-échelle de la réaction de la productivité des espèces arborées à un environnement changeant. Nous avons souligné le caractère spécifique des changements de productivité et leur caractère contextuel, du fait de différences dans l'autécologie des espèces et de variations spatiales des facteurs limitants. Une étude approfondie de l'effet des facteurs environnementaux et de leurs interactions complexes est nécessaire pour la prédiction de la productivité future des espèces. / Growth trends have been reported in many regions of Europe over the twentieth century. However, an integrated assessment of productivity changes, including focus on a wide geographical scale, analysis of spatial heterogeneity, and the inter-specific diversity of growth responses is still lacking. The aim of this Ph.D work was to assess recent changes in forest productivity on a national, regional and local scale in France, and to investigate their potential environmental causes, based on statistical modeling approaches of stand basal area increment (BAI), and environmental indicators. We used the French NFI data for 8 species of contrasted ecological niches and distributions (Fagus sylvatica, Quercus robur, Quercus petraea, Quercus pubescens, Picea abies, Abies alba, Pinus sylvestris and Pinus halepensis), taken in pure and even-aged stands. We identified the main factors influencing tree species productivity on a national scale, and produced productivity maps suggesting that species distribution ranges are not always limited by environmental conditions. Between 1980 and 2005, the productivity trends reported were positive, modal or non-significant for all species, except the two Mediterranean species for which productivity decreased, highlighting inter-specific differences in these changes. We observed strong variations of productivity changes, both in intensity and sign, on a regional and intra-regional scale. These results question the relevance of wide-scale average assessments and highlight their context-dependence. The role of recent climatic warming in featuring the BAI trends was highlighted. This work provides an enriched scale- and species-dependent assessment of tree species reaction to a changing environment. We emphasized the species- and context dependence of productivity changes, due to differences in species autecology and spatial variations in the limiting factors. Further focus on the effect of environmental factors and their complex interactions is needed for the prediction of species future productivity.