| 1. |
- Agarwal, Vaibhav, et al.
(författare)
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Binding of Streptococcus pneumoniae endopeptidase O (PepO) to complement component C1q modulates the complement attack and promotes host cell adherence.
- 2014
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 289:22, s. 15833-15844
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Tidskriftsartikel (refereegranskat)abstract
- The Gram-positive species Streptococcus pneumoniae is a human pathogen causing severe local and life-threatening invasive diseases associated with high mortality rates and death. We demonstrated recently that pneumococcal endopeptidase O (PepO) is an ubiquitously expressed, multifunctional plasminogen and fibronectin binding protein facilitating host cell invasion and evasion of innate immunity. In this study we found that PepO interacts directly with the complement C1q protein, thereby attenuating the classical complement pathway and facilitating pneumococcal complement escape. PepO binds both free C1q and C1 complex in a dose-dependent manner based on ionic interactions. Our results indicate that recombinant PepO specifically inhibits the classical pathway of complement activation in both hemolytic and complement deposition assays. This inhibition is due to direct interaction of PepO with C1q, leading to a strong activation of the classical complement pathway and results in consumption of complement components. In addition, PepO binds the classical complement pathway inhibitor C4BP, thereby regulating downstream complement activation. Importantly, pneumococcal surface-exposed PepO-C1q interaction mediates bacterial adherence to host epithelial cells. Taken together, PepO facilitates C1q-mediated bacterial adherence, while its localized release consumes complement as a result of its activation following binding of C1q, thus representing an additional mechanism of human complement escape by this versatile pathogen.
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| 2. |
- Andersson, Marie, 1977, et al.
(författare)
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Mortality rates, cause and risk factors in people with spina bifida, register-based study over five decades
- 2024
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Ingår i: ACTA PAEDIATRICA. - 0803-5253 .- 1651-2227. ; 113:8, s. 1916-1926
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Tidskriftsartikel (refereegranskat)abstract
- AimCare for people with spina bifida can be improved. This may be done by evaluating mortality rates and causes of death.MethodsBetween 1973 and 2021, 1735 people with spina bifida appeared in registers of the Swedish population. Survival rates and causes of death were calculated according to age and decade.ResultsOver almost 50 years, the prevalence of spina bifida decreased from 5.2 to 1.2 per 10 000 births. Mortality fell sharply during the first year of life, with survival rising from 75% to 94%. For children aged 2-18 years and adults, mortality rates were low and differences between decades were minimal. Causes of childhood deaths were congenital abnormalities, hydrocephalus and infections, the latter two also in adults. Adult causes also included self-inflicted injuries and substance abuse, with suicidal or unclear intent, both more common than in the general population. Bladder malignancies were also more frequent, although after reconstructive bladder surgery, mortality rates were similar.ResultsOver almost 50 years, the prevalence of spina bifida decreased from 5.2 to 1.2 per 10 000 births. Mortality fell sharply during the first year of life, with survival rising from 75% to 94%. For children aged 2-18 years and adults, mortality rates were low and differences between decades were minimal. Causes of childhood deaths were congenital abnormalities, hydrocephalus and infections, the latter two also in adults. Adult causes also included self-inflicted injuries and substance abuse, with suicidal or unclear intent, both more common than in the general population. Bladder malignancies were also more frequent, although after reconstructive bladder surgery, mortality rates were similar.ConclusionSurvival in the first year of life increased in children with spina bifida, whereas there was no difference in survival rates between adults born between 1973 and 1999. For adults, proactive prevention methods regarding self-inflicted injury, substance abuse and bladder cancer are warranted.
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| 3. |
- Bergström, Magdalena, 1973-
(författare)
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Att åldras med långvariga alkoholproblem : hur medelålders och äldre kvinnor och män begripliggör sitt drickande, sig själva och sina liv
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to describe and analyze how late middle-aged and elderly women and men make sense of what it means to age with long-term drinking problems.I have conducted life story-inspired interviews with six women and 13 men who have alcohol problems which have been ongoing for at least 20 years. The analysis of the data has been inspired by thematic narrative analysis. For doing the analysis, I have used theories about meaning making and life stories, as well as theories about how people give meaning to their alcohol use. The interview person’s experiences of their present everyday life are connected to their pasts as well as to their expectations for the future. The interview persons make sense of themselves and their lives in relation to metanarratives that provides them with predefined ways to understand their social reality.The interview persons everyday lives can be seen in the light of their past, there the long-term drinking problems have resulted in severe consequences for their social networks, their physical and mental health as well as their financial situations. The alcohol use was often seen as both a solution to, and a cause of, their problems. Considering that most of the interview persons were suffering from severe health problems, several of them did not expect to live much longer. This, together with the fact that they were becoming older, evoked existential questions about how they wanted to spend their remaining time. In order to avoid an alcohol related death, several interview persons had started to question their alcohol use and a few had made actual attempts to overcome their drinking problems. Others had no hope of changing their life situations or cutting down their alcohol use.The interview persons are living in a time characterized by metanarratives about active and successful ageing. Research show, however, that drinking problems among late middle-aged and elderly people are increasing. People aging with long-term drinking problems are often overlooked when it comes to getting access to treatment programs for problematic alcohol use, and they seldom fit into organized activities for elderly people. Social interventions are, however, important for making the everyday lives less difficult for people ageing with long-term drinking problems and to provide added support to those who wish to change their drinking habits.
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| 4. |
- Blom, Magdalena
(författare)
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The atypical Rho GTPase RhoD and its role in cellular dynamics
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite its discovery 20 years ago, the accumulated knowledge about the Rho member RhoD is scarce. Instead, the vast majority of studies concerning Rho GTPases has focused on the three classical members RhoA, Cdc42 and Rac1. In contrast, RhoD is considered an atypical Rho GTPase, with an aberrant GTP/GDP cycling and an unknown regulation. Like most Rho GTPases, altered RhoD protein levels result in actin cytoskeleton reorganization. We found that increased RhoD protein levels lead to a less dynamic actin cytoskeleton, while RhoD silencing leads to more pronounced actin-containing structures, such as stress fibers, cortical actin and ruffles, depending on cell type. Actin-dependent processes, such as cell migration and cell proliferation, are significantly affected in absence of RhoD in fibroblasts. Moreover, we have shown that endogenous RhoD, as well as its interaction partner WHAMM, localize to the Golgi apparatus. Silencing or overexpression of RhoD or WHAMM leads to a dispersion of the Golgi apparatus, suggesting a role of these proteins in Golgi homeostasis. In addition, protein transport from the ER to the plasma membrane is delayed both when overexpressing and silencing RhoD and WHAMM, as measured by the VSV-G protein transport assay. One of the first described functions of RhoD was its regulatory role in endosome fusion and trafficking. We found that the localization to vesicles is independent of the nucleotide-bound status of RhoD. However, only the GTP-bound RhoD can localize to the plasma membrane. In contrast, RhoD must be inactivated for fusion of RhoD positive vesicles. Deleting the unique N-terminal of RhoD leads to an altered distribution and characteristics of RhoD positive vesicles. Taken together, this thesis elucidates the role of RhoD in three different dynamic cellular processes; reorganization of the actin cytoskeleton, Golgi homeostasis and vesicle transport and fusion.
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| 5. |
- Blom, Magdalena, et al.
(författare)
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The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration
- 2017
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 352:2, s. 255-264
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Tidskriftsartikel (refereegranskat)abstract
- RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration.
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| 6. |
- Bäckström, Erik, 1983-, et al.
(författare)
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Storing keV negative ions for an hour : The lifetime of the metastable 2P1/2 level in 32S−
- 2015
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 114:14
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Tidskriftsartikel (refereegranskat)abstract
- We use a novel electrostatic ion storage ring to measure the radiative lifetime of the upper level in the 3p 5 P 2 o 1/2 →3p 5 P 2 o 3/2 spontaneous radiative decay in S − 32 to be 503±54 sec . This is by orders of magnitude the longest lifetime ever measured in a negatively charged ion. Cryogenic cooling of the storage ring gives a residual-gas pressure of a few times 10 −14 mbar at 13 K and storage of 10 keV sulfur anions for more than an hour. Our experimental results differ by 1.3σ from the only available theoretical prediction.
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| 7. |
- Chartkunchand, Kiattichart C., et al.
(författare)
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Dianion diagnostics in DESIREE : High-sensitivity detection of C-n(2-) from a sputter ion source
- 2018
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 89:3
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Tidskriftsartikel (refereegranskat)abstract
- A sputter ion source with a solid graphite target has been used to produce dianions with a focus on carbon cluster dianions, C-n(2-), with n = 7-24. Singly and doubly charged anions from the source were accelerated together to kinetic energies of 10 keV per atomic unit of charge and injected into one of the cryogenic (13 K) ion-beam storage rings of the Double ElectroStatic Ion Ring Experiment facility at Stockholm University. Spontaneous decay of internally hot C-n(2-) dianions injected into the ring yielded C-n(2-) anions with kinetic energies of 20 keV, which were counted with a microchannel plate detector. Mass spectra produced by scanning the magnetic field of a 90 degrees analyzing magnet on the ion injection line reflect the production of internally hot C-7(2-) - C-24(2-) dianions with lifetimes in the range of tens of microseconds to milliseconds. In spite of the high sensitivity of this method, no conclusive evidence of C-6(2-) was found while there was a clear C-7(2-) signal with the expected isotopic distribution. This is consistent with earlier experimental studies and with theoretical predictions. An upper limit is deduced for a C-6(2-) signal that is two orders-of-magnitude smaller than that for C-7(2-). In addition, CnO2- and CnCu2- dianions were detected.
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| 8. |
- Chartkunchand, Kiattichart C., et al.
(författare)
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Radiative lifetimes of the bound excited states of Pt-
- 2016
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Ingår i: Physical Review A - Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 94:3
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 American Physical Society.The intrinsic radiative lifetimes of the 5d106sS1/22 and 5d96s2 D3/22 bound excited states in the platinum anion Pt- have been studied at cryogenic temperatures at the Double ElectroStatic Ion Ring Experiment (DESIREE) facility at Stockholm University. The intrinsic lifetime of the higher-lying 5d106s S1/22 state was measured to be 2.54±0.10s, while only a lifetime in the range of 50-200 ms could be estimated for the 5d96s2 D3/22 fine-structure level. The storage lifetime of the Pt- ion beam was measured to be a little over 15 min at a ring temperature of 13K. The present study reports the lifetime of an atomic negative ion in an excited bound state with an electron configuration different from that of the ground state.
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| 9. |
- Heimersson, Sara, 1984, et al.
(författare)
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LCA on wastewater and sludge management for local decision-making in Gothenburg – are new LCA method developments enough?
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper describes an LCA study that was made to inform decision-makers in Gothenburg about two different sludge management options. Incineration of anaerobically digested sludge with recovery of a phosphorus fertiliser product seemed preferable to using pasteurised anaerobically digested sludge in agriculture. Aspects under the control of the decision-makers were important for overall results, and caused the main differences between the studied systems, indicating considerable potential for local improvement efforts. Applying a human toxicity characterisation method with a more sludge specific fate model were important, but not crucial, for the results. However, the results are connected to large uncertainties and remaining challenges are discussed in the paper.
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| 10. |
- Jusko, Monika, et al.
(författare)
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Staphylococcal Proteases Aid in Evasion of the Human Complement System.
- 2014
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 6:1, s. 31-46
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component by aureolysin (Aur). We demonstrate here that four major extracellular proteases of S. aureus are potent complement inhibitors. Incubation of human serum with the cysteine proteases staphopain A and staphopain B, the serine protease V8 and the metalloproteinase Aur resulted in a drastic decrease in the hemolytic activity of serum, whereas two staphylococcal serine proteases D and E, had no effect. These four proteases were found to inhibit all pathways of complement due to the efficient degradation of several crucial components. Furthermore, S. aureus mutants lacking proteolytic enzymes were found to be more efficiently killed in human blood. Taken together, the major proteases of S. aureus appear to be important for pathogen-mediated evasion of the human complement system. © 2013 S. Karger AG, Basel.
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