Immunometabolic reprogramming during suppressive HIV-1 infection

Since the implementation of antiretroviral therapy (ART), infection with human immunodeficiency virus type-1 (HIV-1) has been transformed into a chronic lifelong condition. The main obstacle for a HIV-1 cure is the persistence of latently infected cells in viral reservoirs. The viral endurance can instigate detrimental changes on the function and activity of immune cells, creating a chronic inflammatory environment in people living with HIV-1 (PLWH) on successful long-term suppressive antiretroviral therapy (PLWHART). The continuous activation of immune cells may lead to an earlier onset of age-related diseases. Immunometabolism is an emerging field that studies how metabolic reprogramming has an impact on the activation, differentiation, and function of immune cells. Given that these underlying processes are likely to contribute to chronic inflammation in PLWH, the overall aim of this thesis was to evaluate how immunometabolism is reprogrammed during “controlled” HIV-1 infection, either by ART in PLWHART or in PLWH with natural control of infection, elite controllers (PLWHEC). In paper I, we integrated proteomic and transcriptomic data to investigate features distinct to the PLWHEC phenotype in a male cohort. We identified dysregulated hypoxia inducible factor (HIF) signalling and altered metabolism as unique characteristics of the male PLWHEC phenotype. As controlled HIV-1 infection still induce changes in the immune system we aimed to compare differences in the immune phenotype between PLWHEC and PLWHART and its relation to HIV-1 persistence in paper II. We identified a unique phenotype of decreased CCR6 expression on CD4+ and CD8+ T cells in PLWHEC compared to PLWHART and healthy controls (HC). Additionally, the CD4+CCR6+ cells exhibited a proteomic profile indicative of increased sensitivity towards cell death mechanisms in PLWHEC compared to PLWHART. A reduced proportion of integrated HIV-1 DNA in the reservoir of PLWHEC was found, although no difference in the amount of intact provirus. Continuing our evaluation of differences between PLWHEC and PLWHART we performed metabolo-transcriptomic analysis to understand and infer changes on a multisystem level in paper III. We detected a system level metabolic aberration mainly revolving around OXPHOS in PLWHART compared to PLWHEC. Using pharmacological modulation, we identified how this dysregulation of OXPHOS possibly affects HIV-1 reservoir dynamics and the immune senescence profile. Furthermore, to understand how HIV-1 chronicity affects long-lasting metabolic flexibility and adaptation we conducted plasma metabolomics to understand alterations during suppressive ART in a Swedish cohort in paper IV. We also aimed to characterize the cell populations that mainly contribute to changes in the metabolic environment. We detected aberrant energy metabolism in PLWHART, mainly revolving around the tricarboxylic acid cycle and amino acid synthesis. Cell-type specific evaluation showed that the main metabolic alterations occurred on monocytic cell populations, and that PLWHART exhibited dysregulated chemokine receptor expression of CCR2, CCR5, and CX3CR1 on myeloid cell lineages. In paper V, we wanted to evaluate if the altered metabolic environment was consistent on a global scale using two cohorts from low and middle-income countries (namely, Cameroon and India) using plasma metabolomics. We detected a dysregulation of amino acid metabolism and a switch towards glutaminolysis during long-term suppressive ART. In summary, the research covered in this thesis illuminates the importance of metabolic reprogramming during HIV-1 persistence in PLWH with controlled infection

Unexpected Counter-Movements to Nationalism: the Hidden Potential of Local Food Communities

 This article identifies a hitherto understudied element of local food communities, namely their potential as counter-movements to nationalist discourses, practices and policies. This potential should be particularly valuable in Eastern Europe, where European integration has been severely contested over the past years by political elites. We support our argument by a closer qualitative inquiry into two cases; one with urban-rural dimensions in the metropolitan area of Budapest and one in a more sparsely populated cross-border region at the Slovak-Hungarian border. Based on 18 interviews with coordinators, producers and consumers, numerous visits to both sites, and studying the organisations’ documents we conclude that the growth of local food communities contributes to strengthened solidarity in local communities. Although nationalist discourses on buying domestic are rarely contested explicitly, the lack of any reference to national movements and discourses testifies to the primary importance of the local

Mitträffling på tvåfältsvägar - En kvalitativ undersökning om branschens åsikter och metoder

In order to increase the traffic safety on two-lane roads the Swedish Road Administration introduced new milled rumble strips in the middle of the lane. These rumble strips are a way to attract drivers attention if they are about to unintentionally leave the lane. The milled rumble strips cause both internal and external noise and vibration internally in the vehicle. The Swedish Road Administration have had trouble lately getting these grooves made on the roads where they want to have new milled rumble strips in the centre of two-lane roads. The purpose of this work is to examine the work of milled rumble stripes in the middle of the lane on two-lane roads. The goal is that the work can be able to be of assistance to the Swedish Road Administration regarding what can be done to ensure that milled rumble strips can be carried out considerably more on roads in the future. This work has studied the methods regardning rumble strips where the cost aspect also has been interesting. Also rumble strips on roads with a thin layer coating and surface treatment has been specifically studied. The work is divided into two parts, the first part describes the problem and provides insight into the topic milled rumble strips. Milled rumble strips in the Nordic countries have been studied. The second part, which is also the investigative part of the work consists of qualitative interviews with people at the Swedish Road Administration and the contractors who work with precisely milled rumble strips on the road. The result shows that the Swedish Road Administration is on track to solve the difficulties of getting new rumble strips carried out. One thing that is difficult with the milled rumble strips is how it should be handled. Throughout, it should be more clearly what the rules are. The rules today are actually written the same regardless of the asphalt properties. There have been rumble strips on roads with both surface treatment and thin-layer coating, where both results and impact of the rumble strip varies. There is disagreement within the Swedish Road Administration regarding which coverings that it is possible to do milled rumble strips in or not, and it would be of interest to make a proper investigation of which ones that can or can not. An alternative to the milled rumble strips that makes it necessary to not take any account of the coating type, is possibly a reverse rumble strip in the middle of the lane of two-lane roads. The study shows that a traditional cold milling machine is used to perform both Sinusräffla and Målillaräffla and the cost varies between 10-22 SEK/rm

Methods of biopotentials software processing

Modern ITechnologies allows for limitless applications of DSP (digital signal processing) in the Biomedical Engineering, avoiding the once unavoidable analogue hardware conditioning and instrumentation pre-processing. This paper depicts two prominent applications of software processing in the fields of EEG and ECG

An Evaluation of the Potential of the Geoelectrical Resistivity Method for Mapping Gas Migration in Landfills

Methane is a powerful greenhouse gas and growing concern regarding global climate changes over the last years has pointed out the need to quantify and control the leaking of methane into the atmosphere. Landfill gas is regarded as one of the major sources for methane migration to the atmosphere. In this study we present research work with the objective to evaluate the use of geoelectrical resistivity to detect gas migration in landfills. Extensive field experiments were conducted at the Filborna landfill site in Helsingborg, Sweden, in August 2008. In general, the resistivity measurements showed results corresponding to results reported from previous investigations in waste. However, also large variations in resistivity were indicated. Relatively high variability and high mean resistivity in the surface-near layers clearly indicate influence on the resistivity in the upper zone of the landfill. The variability and high resistivity may partly be explained by appearance and migration of landfill gas

Development of 3D geoelectrical resistivity for mapping of gas migration in landfills

Methane is a powerful greenhouse gas and growing concern regarding global climate changes and landfill gas is regarded as one of the major sources for methane migration to the atmosphere. In this study we present research work with the objective to evaluate the use of 3D geoelectrical resistivity to detect gas migration in landfills. Extensive field experiments were conducted at the Filborna landfill site in Helsingborg, Sweden, in August 2008. In general, the resistivity measurements showed results corresponding to results reported from previous investigations in waste. In this paper we present results showing the influence of rainfall events on the resistivity, and the correlation between gas flux and resistivity near the surface