<p>Many of the earth’s ecosystems are experiencing large species losses due to human impacts such as habitat destruction and fragmentation, climate change, species invasions, pollution, and overfishing. Due to the complex interactions between species in food webs the extinction of one species could lead to a cascade of further extinctions and hence cause dramatic changes in species composition and ecosystem processes. The complexity of ecological systems makes it difficult to study them empirically. The systems often consist of large species numbers with lots of interactions between species. Investigating ecological communities within a theoretical approach, using mathematical models and computer simulations, is an alternative or a complement to experimental studies. This thesis is a collection of theoretical studies. We use model food webs in order to explore how biodiversity (species number) affects the response of communities to species loss (Paper I-III) and to environmental variability (Paper IV).</p><p>In paper I and II we investigate the risk of secondary extinctions following deletion of one species. It is shown that resistance against additional species extinctions increases with redundancy (number of species per functional group) (Paper I) in the absence of competition between basal species but decreases with redundancy in the presence of competition between basal species (Paper II). It is further shown that food webs with low redundancy run the risk of losing a greater proportion of species following a species deletion in a deterministic environment but when demographic stochasticity is included the benefits of redundancy are largely lost (Paper II). This finding implies that in the construction of nature reserves the advantages of redundancy for conservation of communities may be lost if the reserves are small in size. Additionally, food webs show higher risks of further extinctions after the loss of basal species and herbivores than after the loss of top predators (Paper I and II).</p><p>Secondary extinctions caused by a primary extinction and mediated through direct and indirect effects, are likely to occur with a time delay since the manifestation of indirect effects can take long time to appear. In paper III we show that the loss of a top predator leads to a significantly earlier onset of secondary extinctions in model communities than does the loss of a species from other trophic levels. If local secondary extinctions occur early they are less likely to be balanced by immigration of species from local communities nearby implying that secondary extinctions caused by the loss of top predators are less likely to be balanced by dispersal than secondary extinctions caused by the loss of other species. As top predators are vulnerable to human-induced disturbances on ecosystems in the first place, our results suggest that conservation of top predators should be a priority. Moreover, in most cases time to secondary extinction is shown to increase with species richness indicating the decay of ecological communities to be slower in species-rich than in species-poor communities.</p><p>Apart from the human-induced disturbances that often force species towards extinction the environment is also, to a smaller or larger extent, varying over time in a natural way. Such environmental stochasticity influences the dynamics of populations. In paper IV we compare the responses of food webs of different sizes to environmental stochasticity. Species-rich webs are found to be more sensitive to environmental stochasticity. Particularly, species-rich webs lose a greater proportion of species than species-poor webs and they also begin losing species faster than species-poor webs. However, once one species is lost time to final extinction is longer in species-rich webs than in species-poor webs. We also find that the results differ depending on whether species respond similarly to environmental fluctuations or whether they are totally uncorrelated in their response. For a given species richness, communities with uncorrelated species responses run a considerable higher risk of losing a fixed proportion of species compared with communities with correlated species responses.</p>

Many of the earth’s ecosystems are experiencing large species losses due to human impacts such as habitat destruction and fragmentation, climate change, species invasions, pollution, and overfishing. Due to the complex interactions between species in food webs the extinction of one species could lead to a cascade of further extinctions and hence cause dramatic changes in species composition and ecosystem processes. The complexity of ecological systems makes it difficult to study them empirically. The systems often consist of large species numbers with lots of interactions between species. Investigating ecological communities within a theoretical approach, using mathematical models and computer simulations, is an alternative or a complement to experimental studies. This thesis is a collection of theoretical studies. We use model food webs in order to explore how biodiversity (species number) affects the response of communities to species loss (Paper I-III) and to environmental variability (Paper IV). In paper I and II we investigate the risk of secondary extinctions following deletion of one species. It is shown that resistance against additional species extinctions increases with redundancy (number of species per functional group) (Paper I) in the absence of competition between basal species but decreases with redundancy in the presence of competition between basal species (Paper II). It is further shown that food webs with low redundancy run the risk of losing a greater proportion of species following a species deletion in a deterministic environment but when demographic stochasticity is included the benefits of redundancy are largely lost (Paper II). This finding implies that in the construction of nature reserves the advantages of redundancy for conservation of communities may be lost if the reserves are small in size. Additionally, food webs show higher risks of further extinctions after the loss of basal species and herbivores than after the loss of top predators (Paper I and II). Secondary extinctions caused by a primary extinction and mediated through direct and indirect effects, are likely to occur with a time delay since the manifestation of indirect effects can take long time to appear. In paper III we show that the loss of a top predator leads to a significantly earlier onset of secondary extinctions in model communities than does the loss of a species from other trophic levels. If local secondary extinctions occur early they are less likely to be balanced by immigration of species from local communities nearby implying that secondary extinctions caused by the loss of top predators are less likely to be balanced by dispersal than secondary extinctions caused by the loss of other species. As top predators are vulnerable to human-induced disturbances on ecosystems in the first place, our results suggest that conservation of top predators should be a priority. Moreover, in most cases time to secondary extinction is shown to increase with species richness indicating the decay of ecological communities to be slower in species-rich than in species-poor communities. Apart from the human-induced disturbances that often force species towards extinction the environment is also, to a smaller or larger extent, varying over time in a natural way. Such environmental stochasticity influences the dynamics of populations. In paper IV we compare the responses of food webs of different sizes to environmental stochasticity. Species-rich webs are found to be more sensitive to environmental stochasticity. Particularly, species-rich webs lose a greater proportion of species than species-poor webs and they also begin losing species faster than species-poor webs. However, once one species is lost time to final extinction is longer in species-rich webs than in species-poor webs. We also find that the results differ depending on whether species respond similarly to environmental fluctuations or whether they are totally uncorrelated in their response. For a given species richness, communities with uncorrelated species responses run a considerable higher risk of losing a fixed proportion of species compared with communities with correlated species responses.

Produktnedläggning är ett sätt för företag att få bort produkter som inte presterar tillfredsställande. Tidigare studier har visat att företag med ordentliga rutiner kring produktavveckling har kunnat tillgodogöra sig flera fördelar i form av bland annat bättre lönsamhet och försäljning. Ändå har forskning visat att de flesta företag inte har några formella rutiner för nedläggning av produkter och att produktnedläggning inte ses som lika viktigt som andra produktaktiviteter. Av den anledningen studeras i denna uppsats hur väl utvecklade rutiner två utvalda företag har för avveckling av produkter. Syftet med uppsatsen är att undersöka hur två utvalda företags rutiner för produktnedläggning ser ut. Resultaten jämförs sedan med den teoretiska referensramen samt mellan företagen i fråga för att urskilja likheter och olikheter. Till denna uppsats har en kvalitativ metod använts för att klargöra hur företag går tillväga vid nedläggning av produkter. Genom intervjuer med AB Karl Hedin och Spendrups Bryggeri AB har empirisk data samlats in för att möjliggöra jämförelser företagen emellan samt med den teori som sammanställts.     De två studerade företagen har helt skilda förfaranden kring produktavvecklingar. Spendrups har en högre grad av formalitet i sina nedläggningsprocesser där hela kedjan från uppkomsten av en produkt till en eventuell avveckling sker i samråd mellan projektledare, företagsledning och produktansvariga. AB Karl Hedin har inga utformade rutiner kring produktavveckling utan hanterar frågan på respektive ort.  Vad som orsakar produktnedläggning hos respektive företag är dålig lönsamhet och försäljning tillsammans med flera andra individuella faktorer. / Product deletion is a method that companies can use to abandon products that are not performing satisfying. Studies have shown that companies with routines for product elimination have achieved several benefits in terms of higher sales volume and profitability. Nonetheless, research has proved that most companies do not have formal procedures for product deletion and that it is not considered quite as important as other product activities. For that reason, this essay will examine how highly developed the routines for product deletion are in two selected companies. The purpose of the study is to observe the procedures for product deletion in two selected companies. The findings will then be compared between companies in the survey and related to the theory to define similarities and differences. A qualitative method has been used to clarify how companies proceed when to abandon products. Empirical data has been collected by interviewing AB Karl Hedin and Spendrups Bryggeri AB for comparison to the theory and between the companies in our study in order to distinguish similarities and differences. The companies in the study have different routines when it comes to deleting products. Spendrups has a higher level of formality in their elimination procedures where the top management together with project managers and product managers collaborate all the way from the birth of the product to a possible deletion. AB Karl Hedin has no formal routines for product abandonment. These questions are dealt with at each separate district. What cause the companies to eliminate a product are mainly low profitability and sales volume among several individual factors.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). The understanding of the genetics and inheritance of TOF is limited. Although about 15% of cases are associated with a 22q11.2 deletion, the majority have no known aetiology. Even in 22q11.2 Deletion Syndrome (22q11DS), factors that increase the likelihood of CHD expression are poorly understood. We aimed to determine the prevalence and phenotypes of CHD in relatives of adults with TOF. We also investigated the prevalence of CHD in relatives without a 22q11.2 deletion of individuals with 22q11DS. Offspring of patients with TOF had the greatest prevalence of CHD. Diverse cardiac phenotypes, including left heart obstructive lesions, were found in families. We also found that unaffected relatives of individuals with 22q11DS had a greater prevalence of complex CHD over population expectations, suggesting that modifier genetic factors may be involved in expression of CHD in 22q11DS.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). The understanding of the genetics and inheritance of TOF is limited. Although about 15% of cases are associated with a 22q11.2 deletion, the majority have no known aetiology. Even in 22q11.2 Deletion Syndrome (22q11DS), factors that increase the likelihood of CHD expression are poorly understood. We aimed to determine the prevalence and phenotypes of CHD in relatives of adults with TOF. We also investigated the prevalence of CHD in relatives without a 22q11.2 deletion of individuals with 22q11DS. Offspring of patients with TOF had the greatest prevalence of CHD. Diverse cardiac phenotypes, including left heart obstructive lesions, were found in families. We also found that unaffected relatives of individuals with 22q11DS had a greater prevalence of complex CHD over population expectations, suggesting that modifier genetic factors may be involved in expression of CHD in 22q11DS.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 115-127.

The past two decades have witnessed an accelerated effort to understand the nature of schizophrenia and related psychotic disorders, but no causative gene(s) has been discovered yet. Family, twin, and adoption studies indicate that genetic factors are clearly implicated in the etiology of these disorders (Cardno and Gottesman, 2000; Cardno et al., 2002; McGuffin et al., 2003; Weinberger, 2005). Several aspects of 22q11 Deletion Syndrome (22qDS) - the most common chromosomal microdeletion found in humans - create a unique opportunity for susceptibility gene identification. For instance, the reported risk of psychotic disorders in 22qDS is 25-fold higher than in the general population (Murphy et al., 1999) and genome-wide linkage studies in families with schizophrenia without 22qDS indicate that the 22q11.2 region is a strong susceptibility locus for psychosis (Badner and Gershon, 2002; Lewis et al., 2003). This thesis aims to identify genetic factors associated with the development of psychosis in 22qDS by i) investigating the relationship between the length of the 22q11.2 deletions and the presence of a psychotic disorder in patients with 22qDS; ii) studying diagnostic molecular methods that improve detection of 22q11.2 deletions and duplications; and iii) exploring the relationship between 22qDS-psychotic phenotype and gene expression patterns. The central hypothesis was that psychosis in 22qDS would not be associated with haploinsufficiency (having one copy of the gene), but rather, it would be associated with distinct 22q11.2 gene expression profiles. Chapter 2 showed that 22q11.2 deletion size did not appear to be associated with the development of psychosis in adults with 22qDS. In Chapter 3, a molecular method that detects and size 22q11.2 deletions and duplications of various sizes was shown to be superior to the traditional molecular diagnostic technique used for molecular diagnostic of 22qDS. Finally, in Chapter 4, decreased gene expression of three genes located in the 22q11.2 region (SNAP29, COMT and BID) was significantly associated with psychosis in adults with 22qDS. Focusing on genes located in the 22q11.2 region has helped revealing genetic alterations associated with the frequent development of psychosis in 22qDS. Future studies focusing on investigating the heterogeneity of the psychotic presentation in 22qDS and further elucidating potential genetic mechanisms likely to explain the gene expression changes in the 22q11.2 region demonstrated here will help advance the scientific understanding of the etiology of psychosis.

The past two decades have witnessed an accelerated effort to understand the nature of schizophrenia and related psychotic disorders, but no causative gene(s) has been discovered yet. Family, twin, and adoption studies indicate that genetic factors are clearly implicated in the etiology of these disorders (Cardno and Gottesman, 2000; Cardno et al., 2002; McGuffin et al., 2003; Weinberger, 2005). Several aspects of 22q11 Deletion Syndrome (22qDS) - the most common chromosomal microdeletion found in humans - create a unique opportunity for susceptibility gene identification. For instance, the reported risk of psychotic disorders in 22qDS is 25-fold higher than in the general population (Murphy et al., 1999) and genome-wide linkage studies in families with schizophrenia without 22qDS indicate that the 22q11.2 region is a strong susceptibility locus for psychosis (Badner and Gershon, 2002; Lewis et al., 2003). This thesis aims to identify genetic factors associated with the development of psychosis in 22qDS by i) investigating the relationship between the length of the 22q11.2 deletions and the presence of a psychotic disorder in patients with 22qDS; ii) studying diagnostic molecular methods that improve detection of 22q11.2 deletions and duplications; and iii) exploring the relationship between 22qDS-psychotic phenotype and gene expression patterns. The central hypothesis was that psychosis in 22qDS would not be associated with haploinsufficiency (having one copy of the gene), but rather, it would be associated with distinct 22q11.2 gene expression profiles. Chapter 2 showed that 22q11.2 deletion size did not appear to be associated with the development of psychosis in adults with 22qDS. In Chapter 3, a molecular method that detects and size 22q11.2 deletions and duplications of various sizes was shown to be superior to the traditional molecular diagnostic technique used for molecular diagnostic of 22qDS. Finally, in Chapter 4, decreased gene expression of three genes located in the 22q11.2 region (SNAP29, COMT and BID) was significantly associated with psychosis in adults with 22qDS. Focusing on genes located in the 22q11.2 region has helped revealing genetic alterations associated with the frequent development of psychosis in 22qDS. Future studies focusing on investigating the heterogeneity of the psychotic presentation in 22qDS and further elucidating potential genetic mechanisms likely to explain the gene expression changes in the 22q11.2 region demonstrated here will help advance the scientific understanding of the etiology of psychosis.

The effects of a mutation in one gene can occasionally be suppressed by mutation in another gene. Genetic suppression indicates functional relationships and provides clues about the mechanism and order of action in genetic pathways. Here I explored the existing yeast deletion collection to identify suppressor relationships. The collection was released in 2000 and it is known that some strains in the collection have acquired mutations. Whole genome sequencing of 48 yeast deletion strains corresponding to 26 genome integrity genes was performed. High-throughput sequencing revealed a broad mutational spectrum including point mutations, indels, and copy number variations. I identified and experimentally validated two new suppressor mutations (sgs1 mutations in both top3Δ and rmi1Δ strains) corresponding to gene pairs with previously known suppressor relationships. Thus, high-throughput sequencing and analysis of yeast deletion strains can identify suppressor mutations. The resulting genome sequences also provide a baseline for future laboratory evolution experiments.

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