| 1. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 2. |
- Enqvist, Johan, 1982-
(författare)
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Stewardship in an urban world : Civic engagement and human–nature relations in the Anthropocene
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Never before have humans wielded a greater ability to alter and disrupt planetary processes. Our impact is becoming so noticeable that a new geological epoch has been proposed – the Anthropocene – in which Earth systems might no longer maintain the stable and predictable conditions of the past 12 millennia. This is particularly evident in the rapid expansion of urban areas, where a majority of humans now live and where environmental changes such as rising temperatures and habitat loss are happening faster than elsewhere. In light of this, questions have been raised about what a more responsible relationship between humans and the rest of the planet might look like. Scholars in sustainability science employ the concept of ‘stewardship’ in searching for an answer; however, with multiple different applications and definitions, there is a need to better understand what stewardship is or what novelty it might add to sustainability research. This thesis investigates stewardship empirically through two case studies of civic engagement for protecting nature in cities – Bengaluru, India and New York City, USA. Further, the thesis also proposes a conceptual framework for how to understand stewardship as a relation between humans and the rest of nature, based on three dimensions: care, knowledge and agency. This investigation into stewardship in the urban context uses a social–ecological systems approach to guide the use of mixed theory and methods from social and natural sciences. The thesis is organized in five papers. Paper I reviews defining challenges in managing urban social–ecological systems and proposes that these can more effectively be addressed by collaborative networks where public, civic, other actors contribute unique skills and abilities. Paper II and Paper III study water resource governance in Bengaluru, a city that has become dependent on external sources while its own water bodies become degraded and depleted.Paper II analyzes how locally based ‘lake groups’ are able to affect change through co-management arrangements, reversing decades of centralization and neglect of lakes’ role in Bengaluru’s water supply.Paper III uses social–ecological network analysis to analyze how patterns in lake groups’ engagements and collaborations show better fit with ecological connectivity of lakes.Paper IV employs sense of place methods to explore how personal bonds to a site shapes motivation and goals in waterfront stewardship in New York City. Finally,Paper V reviews literature on stewardship and proposes a conceptual framework to understand and relate different uses and underlying epistemological approaches in the field. In summary, this thesis presents an empirically grounded contribution to how stewardship can be understood as a human–nature relation emergent from a deep sense ofcare and responsibility, knowledge and learning about how to understand social–ecological dynamics, and theagency and skills needed to influence these dynamics in a way that benefits a greater community of humans as others. Here, the care dimension is particularly important as an underappreciated aspect of social–ecological relations, and asset for addressing spatial and temporal misalignment between management institutions and ecosystem. This thesis shows that care for nature does not erode just because green spaces are degraded by human activities – which may be crucial for promoting stewardship in the Anthropocene.
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| 3. |
- Enqvist, Johan, 1982-
(författare)
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Urban environmental stewardship : Roles and reasons for civic engagements in governance of social-ecological systems
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stewardship as a concept is increasingly brought forward as a goal to reach sustainability goals of ensuring human wellbeing within the limits of Earth’s life support systems. Scholarship on the required capacities for planetary stewardship is growing rapidly, as are the insights. This thesis focuses on contributing with knowledge about what stewardship implies in terms of civic engagement in environmental issues, particularly in contexts where these can be particularly challenging: rapidly changing cities. Paper I describes the internal functioning of a citizen network engaged in various environmental issues in Bangalore, India. Analyzing social network structure and desired outcomes, it shows that while the loose structure inhibits efficiency, it encourages inclusiveness and builds legitimacy among members. Despite a reduced capacity to actively mobilize members, the network facilitates ecosystem monitoring and serves as an information platform to connect diverse groups across the city. Paper II describes how local engagement to restore Bangalorean lakes can influence city-level governance of water supply. Following key events in the 1960s, Bangalore has become increasingly dependent on a single source of water and seems unable to explore other supply approaches for its rapidly growing population. The study shows that the system’s trap-like dynamics can be rewired by citizen-based lake groups by incentivizing authorities to break long-standing centralization trends. By re- acknowledging the water bodies’ multifunctional role as man-made water harvesting units, groups have gathered local support and improved monitoring to protect lakes after restoration. Together, the two papers show that civic involvement in urban environmental stewardship can improve governance by complementing and acting as a watchdog over public authorities.
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| 4. |
- Johansson, Mikaela
(författare)
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Metaproteogenomics-guided enzyme discovery : Targeted identification of novel proteases in microbial communities
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Industrial biotechnology is a large and growing industry as it is part of establishing a “greener” and more sustainable bioeconomy-based society. Using enzymes as biocatalysts is a viable alternative to chemicals and energy intense industrial processes and is en route to a more sustainable industry. Enzymes have been used in different areas for ages and are today used in many industrial processes such as biofuels production, food industry, tanning, chemical synthesis, pharmaceuticals etc. Enzymes are today a billion-dollar industry in itself and the demand for novel catalysts for various present and future processes of renewable resources are high and perfectly in line with converting to a more sustainable society.Most enzymes used in industry today have been identified from isolated and pure cultured microorganisms with identified desirable traits and enzymatic capacities. However, it is known that less than 1% of all microorganisms can be can be obtained in pure cultures. Thus, if we were to rely solely on pure culturing, this would leave the 99% of the microorganisms that constitutes the “microbial dark matter” uninvestigated for their potential in coding for and producing valuable novel enzymes. Therefore, to investigate these “unculturable” microorganisms for novel and valuable enzymes, pure-culture independent methods are needed.During the last two decades there has been a fast and extensive development in techniques and methods applicable for this purpose. Especially important has been the advancements made in mass spectrometry for protein identification and next generation sequencing of DNA. With these technical developments new research fields of proteomics and genomics have been developed, by which the complete protein complement of cells (the proteome) and all genes (the genome) of organisms can be investigated. When these techniques are applied to microbial communities these fields of research are known as meta-proteomics and meta-genomics.However, when applied to complex microbial communities, difficulties different from those encountered in their original usage for analysis of single multicellular organisms or cell linages arises, and when used independently both methods have their own limitations and bottlenecks. In addition, both metaproteomics and metagenomics are largely non-targeting techniques. Thus, if the purpose is still to - somewhat contradictory – use these non-targeting methods for targeted identification of novel enzymes with certain desired activities and properties from within microbial communities, special measures need to be taken.The work presented in this thesis describes the development of a method that combinesmetaproteomics and metagenomics (i.e. metaproteogenomics) for the targeted discovery of novel enzymes with desired activities, and their correct coding genes, from within microbial communities. Thus, what is described is a method that can be used to circumvent the pure-culturing problem so that a much larger fraction of the microbial dark matter can be specifically investigated for the identification of novel valuable enzymes.
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| 5. |
- Hamrén, Bengt, 1971-
(författare)
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Safety and Efficacy Modelling in Anti-Diabetic Drug Development
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A central aim in drug development is to ensure that the new drug is efficacious and safe in the intended patient population. Mathematical models describing the pharmacokinetic-pharmacodynamic (PK-PD) properties of a drug are valuable to increase the knowledge about drug effects and disease and can be used to inform decisions. The aim of this thesis was to develop mechanism-based PK-PD-disease models for important safety and efficacy biomarkers used in anti-diabetic drug development. Population PK, PK-PD and disease models were developed, based on data from clinical studies in subjects with varying degrees of renal function, non-diabetic subjects with insulin resistance and patients with type 2 diabetes mellitus (T2DM), receiving a peroxisome proliferator-activated receptor (PPAR) α/γ agonist, tesaglitazar. The PK model showed that a decreased renal elimination of the metabolite in renally impaired subjects leads to increased levels of metabolite undergoing interconversion and subsequent accumulation of tesaglitazar. Tesaglitazar negatively affects the glomerular filtration rate (GFR), and since renal function affects tesaglitazar exposure, a PK-PD model was developed to simultaneously describe this interrelationship. The model and data showed that all patients had decreases in GFR, which were reversible when discontinuing treatment. The PK-PD model described the interplay between fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c) and haemoglobin in T2DM patients. It provided a mechanistically plausible description of the release and aging of red blood cells (RBC), and the glucose dependent glycosylation of RBC to HbA1c. The PK-PD model for FPG and fasting insulin, incorporating components for β-cell mass, insulin sensitivity and impact of disease and drug treatment, realistically described the complex glucose homeostasis in the heterogeneous patient population. The mechanism-based PK, PK-PD and disease models increase the understanding about T2DM and important biomarkers, and can be used to improve decision making in the development of future anti-diabetic drugs.
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