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- Nilsson, Emma A
(författare)
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FOXC2 and CAPN10 as candidate genes for obesity, insulin resistance and type 2 diabetes
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The worldwide prevalence of obesity and type 2 diabetes is increasing rapidly. Both disorders depend on genetic and environmental factors. The studies included in this thesis investigated the possible association of the FOXC2 and CAPN10 genes with obesity, insulin resistance, type 2 diabetes, and related phenotypes. FOXC2 encodes a forkhead transcription factor, which was identified as a key regulator of adipocyte metabolism in mice overexpressing FOXC2 in adipose tissue. The exact function of FOXC2 in humans remains unknown. FOXC2 mRNA levels in both visceral fat and skeletal muscle correlated with measures of insulin sensitivity and FOXC2 mRNA expression was significantly higher in visceral compared to subcutaneous fat in humans. FOXC2 mRNA levels were upregulated in response to insulin in cultured human adipocytes. A common variant in the 5' untranslated region of the gene (C-512T) was identified. The C-allele was associated with higher triglyceride levels and higher HOMA-IR indeces in female sibling pairs as well as with obesity, and the Metabolic Syndrome in males. However, no association was found between this polymorphism and type 2 diabetes. CAPN10, encoding the cysteine protease calpain-10, was the first type 2 diabetes susceptibility gene discovered by a genome-wide scan and positional cloning. We found that CAPN10 mRNA expression is a heritable trait. Furthermore, a polymorphism in the gene (SNP-43) was associated with reduced CAPN10 mRNA levels in both subcutaneous fat and skeletal muscle. Subjects with normal glucose tolerance, but not subjects with impaired glucose tolerance, upregulated CAPN10 mRNA levels in response to fat during a hyperinsulinemic euglycemic clamp. These results suggest that the C-allele at FOXC2 C-512T and low FOXC2 mRNA expression predispose individuals to obesity and insulin resistance but not to type 2 diabetes. CAPN10 mRNA expression is a heritable trait and influenced by variation at SNP-43. Although CAPN10 SNP-43 is not associated with obesity, low CAPN10 mRNA expression, or inability to upregulate CAPN10 mRNA levels in response to elevated FFA and insulin, may predispose towards insulin resistance and type 2 diabetes.
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- Nilsson, Emma
(författare)
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Arkitekturens kroppslighet. Staden som terräng
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Beginning with the notion that spatial and material qualities of architecture set limits and create conditions for how we make use of it, the overall aim and ambition of this thesis is to develop this notion and to contribute to a deeper understanding of the relationships that are produced between the materiality of architecture and a bodily appropriation of it. To investigate this the thesis establishes two concepts: corporality and terrain. The concept of corporality recognizes that a body is dependent on the situations it is made active by, that is the body techniques and materialities involved. The same individual can articulate a wide range of body techniques and body materialities. Some experiences can be carried and activated in new ways as part of a new corporality, but which ones these are and how they are transplanted depends on the techniques and materialities that come with a certain corporality. This highlights the dependency on spatial relations in order for different corporalities to be put into motion. The concept of terrain describes the encounter between a corporality and a surrounding environment. An environment can accommodate several overlapping terrains, and their extensions do not necessarily coincide with the environment or each other. A terrain assembles actors with a wide time-spatial distribution, and the relations between corporality and environment are shaped by many different conditions and with many different prerequisites. Terrains are continuously articulated, but depending on differences in modes of production, a terrain can also become more or less manifest. The thesis discuss the production of terrains, in relation to some significant differences as to how this production takes place, and how terrains are made visible in terms of body cultural affinities. Architects do not create terrains, they establish the prerequisites for them, but architecture is significant to the temporal and spatial coordination of different terrains, and the ways they are articulated. The thesis show that such coordination can be achieved by identifying which architectural configurations articulate already known and familiar terrains. Architects can also use the concept to examine terrains that are being produced by a given environment and thereby making visible and ensure the yet unknown terrains and body cultures.
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- Nilsson, Emma C, 1979-
(författare)
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Cellular receptors for viruses with ocular tropism
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several viruses from different virus families are known to cause ocular infections, e.g. members of the Adenoviridae, Picornaviridae and the Herpesviridae families. These infections are spread by contact and in the case of adenoviruses (Ads) and picornaviruses they are also highly contagious. The ocular infections caused by Ads and picornaviruses are called epidemic keratoconjunctivitis (EKC) and acute hemorrhagic conjunctivitis (AHC), respectively. Historically, EKC is caused mainly by three types of Ads from species D: Ad8, Ad19 and Ad37. The infection is characterized by keratitis and conjunctivitis but also involves pain, edema, lacrimation and blurred vision. AHC is caused mainly by two types of picornaviruses: coxsackievirus A24v (CVA24v) and enterovirus 70 (EV70), and is characterized by pain, redness, excessive tearing, swelling and subconjunctival hemorrhages. In addition, blurred vision, keratitis, malaise, myalgia, fever, headache and upper respiratory tract symptoms can also be experienced. Both infections are problematic in many parts of the world, affecting millions of people every year. Despite the great need, the only treatment available today is supportive treatment; no antiviral drugs are available to combat these common viral infections. Ad37 has previously been reported to use sialic acid (SA) as its cellular receptor. Since there is no antiviral treatment available against EKC we wanted to evaluate the inhibitory effect of SA-based antiviral compounds on Ad37 binding to and infection of ocular cells. We found that multivalent compounds consisting of SA linked to a globular carrier molecule, in this case human serum albumin, efficiently blocked Ad37 binding and infection at low concentrations. Further attempts were then made to improve the effect by chemically modifying SA monosaccharides. However, no enhanced inhibitory effect was accomplished and the conclusion was that the best inhibitors are based on unmodified SA. We next hypothesized that development of efficient SA-based binding inhibitors may require detailed knowledge about the structure of the SA-containing receptor. Using a battery of biological and biochemical experiments, including glycan array, binding and infection assays, X-ray crystallography and surface plasmon resonance (SPR); we identified a specific glycan involved in the binding and infection of Ad37. This glycan turned out to be a branched, di-SA-containing motif corresponding to the glycan motif of the ganglioside GD1a. However, the ganglioside itself did not function as a cellular receptor, as shown by a number of binding and infection assays. Instead, the receptor consisted of one or more glycoproteins that contain the GD1a glycan motif. This glycan docked with both its SAs into the trimeric Ad37 knob resulting in a very strong interaction as compared to most other protein-glycan interactions. Hopefully, this finding will aid development of more potent inhibitors of Ad37 binding and infection. The receptor for CVA24v, one of the main causative agents of AHC, has been unknown until now. We showed that this ocular virus, like Ad37, is also able to use SA as a receptor on corneal cells but not on conjunctival cells. This suggested that CVA24v may use two different receptors. As for Ad37, the receptor used by CVA24v on corneal cells also appears to be one or more sialic acid-containing glycoproteins. We believe that these findings may be a starting point for design and development of candidate drugs for topical treatment of AHC.
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- Nilsson, Emma, 1982
(författare)
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Effects of cognitive tasks on car drivers’ behaviors and physiological responses
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The effects of drivers’ engagement in cognitive tasks (i.e., non-visual, cognitively loading activities unrelated to the task of driving) are debated and unclear. Numerous experiments show impaired driver behaviors, yet naturalistic studies typically do not find an increased crash risk. In the future, autonomous driving (AD) is expected to improve traffic safety while allowing safe engagement in cognitive (and other) tasks. Having the opportunity to perform non-driving related tasks while traveling may then motivate drivers to use AD, provided they can actually engage in the tasks. Unfortunately, research on drivers’ engagement in cognitive tasks suffers severe methodological limitations since reliable and unintrusive measures of cognitive load are lacking. The aim of this thesis is therefore to advance the understanding of task-induced cognitive load in the context of traffic safety. This aim is split into two objectives: A) to better understand how drivers’ involvement in cognitive tasks can affect safety-relevant driver behaviors and decisions and B) to provide methodological guidance about assessing cognitive load in drivers using physiological measures. To accomplish Objective A, effects of cognitive tasks on driver behaviors were studied during routine driving and in a safety-critical event in a driving simulator. Also, drivers’ ability to engage in a non-driving related task while using AD in real traffic was explored. In line with the cognitive control hypothesis (Engström et al., 2017), it was found that cognitive tasks negatively affected driver behaviors in situations where cognitive control was needed, for example in intersections—but not in a lead vehicle braking scenario where responses were triggered automatically by visual looming. It was also found that although the number of off-path glances decreased during cognitive load, the timing of the remaining glances was unaffected. Clearly, cognitive load has different effects on different mechanisms. When using AD, drivers were indeed capable of engaging in a non-driving related task—suggesting that AD will be able to fulfill drivers’ desire to perform such tasks while traveling, which may motivate AD usage and thus improve traffic safety (given that AD is truly safer than manual driving). Finally, a simulator study addressing Objective B showed that the measurability of cognitive load was greatly improved by recognizing that multiple coexisting mental responses give rise to different physiological responses. This approach can provide less context-dependent measurements and allows for a better, more detailed understanding of the effects of cognitive tasks. These findings can help improve traffic safety—both by being used in system development, and as part of the systems themselves.
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- Nilsson, Emma
(författare)
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Genetic epidemiological studies of adverse pregnancy outcomes and the role of schizophrenia
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purposes of this thesis were to investigate the importance of genetic and environmental factors in the development of adverse pregnancy outcomes and to investigate the role of schizophrenia as a risk factor for and a consequence of adverse pregnancy outcomes. In the first study we investigated the importance of genetic and environmental factors for pre-eclampsia and gestational hypertension and whether the diseases share genetic etiology. Swedish population-based registers were used and 1,188,207 births were included. We found that full sisters and mother-daughters were more similar for pre-eclampsia and gestational hypertension than half-sisters. Moreover, a full sister to a woman with pre-eclampsia had a significantly increased risk of gestational hypertension. The heritability estimates were 31% for pre-eclampsia, 20% for gestational hypertension, and 28% for pregnancy-induced hypertension. In sum, we found a genetic component in the liability of both pre-eclampsia and gestational hypertension. The co-morbidity indicates that pre-eclampsia and gestational hypertension may share parts of their genetic etiology. The aims of the second and third studies were to examine risks of adverse pregnancy outcomes among mothers and fathers with schizophrenia and to investigate if the increased risks among women with schizophrenia were due to maternal, paternal, genetic and/or environmental factors. Two million births from Swedish population-based registers were included. Maternal factors (e.g., smoking) explained most of the risks for adverse pregnancy outcomes and women with an episode of schizophrenia during pregnancy had the highest risks. Increased risks for low birth weight, small-for-gestational age, and infant death among offspring to fathers with schizophrenia were observed. In conclusion, mothers with schizophrenia have increased risks for adverse pregnancy outcomes. The risks were highest for women admitted to psychiatric care during pregnancy. The increased risks among offspring to fathers with schizophrenia suggest that, in addition to maternal risk behavior, non-optimal social and/or economical circumstances are of importance. In the fourth study we investigated if the previously found association between low birth weight and subsequent development of schizophrenia is mediated by familial factors. We used data from obstetric records in a cohort analysis of 11,360 same-sexed twins, and conducted co-twin control analyses on 90 pairs discordant for schizophrenia. The results from the cohort analyses showed that low birth weight and small head circumference were associated with later development of schizophrenia. The associations remained in the within-pair analyses. We concluded that the association between low birth weight and schizophrenia is partly a function of reduced fetal growth and that fetal growth restriction seems to be associated with risk of schizophrenia independently of familial factors. This thesis has examined adverse pregnancy outcomes using register-based samples and genetic epidemiological methods. We found a genetic comorbidity between pre-eclampsia and gestational hypertension, which should be considered in the future search for susceptibility genes and in the identification of intervention strategies. Maternal as well as paternal schizophrenia influence the risk of adverse pregnancy outcomes. These results prompt for better surveillance of families at risk. Further, we found that fetal growth restriction is an independent risk factor for subsequent development of schizophrenia. Adverse pregnancy outcomes represent some of the most challenging targets in epidemiology and elucidation of the underlying mechanisms and identification of markers of early insult that predisposes to adult diseases are important.
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| 8. |
- Ohlsson-Nevo, Emma, 1960-
(författare)
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Colorectal cancer : patients’ and next-of-kin’s experiences and the effects of a psycho-educational program
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To test whether a psycho-educational program affects mental wellbeing in persons treated for colorectal cancer and their next-of-kin.Design: A prospective, longitudinal, randomized controlled trial.Setting: Surgical clinic at a university hospital in Sweden.Sample: 105 colorectal cancer patients and 71 next-of-kin were allocated to a psychoeducational program or to standard care.Methods: Mental wellbeing was evaluated with the Mood Adjective Check List and The Hospital Anxiety and Depression Scale at baseline and at 1, 6, and 12 months. The program consisted of seven meetings, including lecture and time for reflection with other patients/nextof-kin.Main Research Variable: Overall mood, activity, calmness, pleasantness, anxiety, and depression.Findings: The psycho-educational program increased overall mood, calmness, and pleasantness among patients after one month but had no effect on activity, anxiety, or depression. The program had no effect on the overall mood, activity, calmness, pleasantness, anxiety, or depression among next-of-kin.Conclusion: The psycho-educational program had a short-term effect on overall patient mood, calmness, and pleasantness but not on next-of-kin. Implications for Nursing: A psycho-educational program including lecture and time for reflection can be used with a colorectal cancer patient population to improve some aspects of their mental wellbeing.
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- Rosendal, Ebba, 1993-
(författare)
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Host-pathogen interactions during tick-borne flavivirus infection : pathogenesis, tropism and tools
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tick-borne encephalitis virus (TBEV) is a neurotropic member of the genus Flavivirus. It may transmit to humans through the bite of an infected tick or consumption of unpasteurized dairyproducts, and causes tick-borne encephalitis (TBE). TBE constitutes a significant health burden in Eurasia, with more than 10,000 cases reported every year. In this thesis, I have investigated the role of the innate immune response in restricting infection in the central nervous system (CNS), identified virulence factors and developed a new model system to study the structural proteins of TBEV.Viral tropism is important for understanding underlying mechanisms of pathology. In the first part,we combined whole-brain imaging with single nuclei RNA-sequencing after infection of wildtype (WT) and interferon (IFN) α/β receptor knockout (Ifnar-/-) mice by Langat virus (LGTV), a low-virulent model for TBEV. We found that absence of type I IFN signaling changes viral tropism and leads to an impaired inflammatory response. For neurons, astrocytes, and microglia we also compared the response to LGTV infection in vivo with the response of primary monocultures infected in vitro. Primary cells are often used for mechanistic studies of neurotropic viruses, but we found limited overlap in altered pathways between in vivo and in vitro, which emphasizes the role of cellular crosstalk in shaping the transcriptional response to infection in the brain.The second part addresses viral determinants of pathogenicity. By comparing disease progression induced by different TBEV strains in a mouse model, we identified TBEV 93/783 as a highly virulentstrain belonging to the European subtype. We could show that two unusual amino acid substitutions in the envelope (E) protein of 93/783 enhanced neurovirulence and contributed to pathogenesis. To facilitate further studies of the structural proteins of TBEV, we generated and thoroughlycharacterized a chimeric virus with the pre-membrane (prM) and ecto-E protein of TBEV 93/783 in the genetic background of LGTV. The chimeric virus shows similar growth kinetics as the parental LGTV in vitro but is less pathogenic in our mouse model. Meanwhile, it remained neurovirulent and structurally similar to TBEV, making it a useful tool for studying the structural proteins of TBEV under lower biosafety conditions. Taken together, these findings deepen our understanding of what determines the outcome of tick-borne flavivirus infection and the utility of the available model systems for studying disease mechanisms.
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