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Sökning: WFRF:(Andersen Peter M) > Stockholms universitet

  • Resultat 1-10 av 16
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1.
  • Hansen, Eline P., et al. (författare)
  • Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite-host cross talk
  • 2019
  • Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalent porcine helminth, Ascaris suum, compromises pig health and reduces farm productivity worldwide. The closely related human parasite, A. lumbricoides, infects more than 800 million people representing a disease burden of 1.31 million disability-adjusted life years. The infections are often chronic in nature, and the parasites have a profound ability to modulate their hosts' immune responses. This study provides the first in-depth characterisation of extracellular vesicles (EVs) from different developmental stages and body parts of A. suum and proposes the role of these vesicles in the host-parasite interplay. The release of EVs from the third- (L3) and fourth-stage (L4) larvae and adults was demonstrated by transmission electron microscopy (TEM), and sequencing of EV-derived RNA identified a number of microRNAs (miRNAs) and transcripts of potential host immune targets, such as IL-13, IL-25 and IL-33, were identified. Furthermore, proteomics of EVs identified several proteins with immunomodulatory properties and other proteins previously shown to be associated with parasite EVs. Taken together, these results suggest that A. suum EVs and their cargo may play a role in host-parasite interactions. This knowledge may pave the way to novel strategies for helminth infection control and knowledge of their immune modulatory potential.
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2.
  • Kotak, R., et al. (författare)
  • Dust and The Type II-Plateau Supernova 2004et
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 704:1, s. 306-323
  • Tidskriftsartikel (refereegranskat)abstract
    • We present mid-infrared (MIR) observations of the Type II-plateau supernova (SN) 2004et, obtained with the Spitzer Space Telescope between 64 and 1406 days past explosion. Late-time optical spectra are also presented. For the period 300-795 days past explosion, we argue that the spectral energy distribution (SED) of SN 2004et comprises (1) a hot component due to emission from optically thick gas, as well as free-bound radiation; (2) a warm component due to newly formed, radioactively heated dust in the ejecta; and (3) a cold component due to an IR echo from the interstellar-medium dust of the host galaxy, NGC 6946. There may also have been a small contribution to the IR SED due to free-free emission from ionized gas in the ejecta. We reveal the first-ever spectroscopic evidence for silicate dust formed in the ejecta of a supernova. This is supported by our detection of a large, but progressively declining, mass of SiO. However, we conclude that the mass of directly detected ejecta dust grew to no more than a few times 10-4 M sun. We also provide evidence that the ejecta dust formed in comoving clumps of fixed size. We argue that, after about two years past explosion, the appearance of wide, box-shaped optical line profiles was due to the impact of the ejecta on the progenitor circumstellar medium and that the subsequent formation of a cool, dense shell was responsible for a later rise in the MIR flux. This study demonstrates the rich, multifaceted ways in which a typical core-collapse supernova and its progenitor can produce and/or interact with dust grains. The work presented here adds to the growing number of studies that do not support the contention that SNe are responsible for the large mass of observed dust in high-redshift galaxies.
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3.
  • Sinding, Mikkel-Holger S., et al. (författare)
  • Arctic-adapted dogs emerged at the Pleistocene-Holocene transition
  • 2020
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 368:6498
  • Tidskriftsartikel (refereegranskat)abstract
    • Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an similar to 9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an similar to 33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.
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4.
  • Bergh, Johan, 1983-, et al. (författare)
  • Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping
  • 2015
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:14, s. 4489-4494
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.
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5.
  • Byström, Roberth, et al. (författare)
  • SOD1 Mutations Targeting Surface Hydrogen Bonds Promote Amyotrophic Lateral Sclerosis without Reducing Apo-state Stability
  • 2010
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:25, s. 19544-19552
  • Tidskriftsartikel (refereegranskat)abstract
    • In good accord with the protein aggregation hypothesis for neurodegenerative diseases, ALS-associated SOD1 mutations are found to reduce structural stability or net repulsive charge. Moreover there are weak indications that the ALS disease progression rate is correlated with the degree of mutational impact on the apoSOD1 structure. A bottleneck for obtaining more conclusive information about these structure-disease relationships, however, is the large intrinsic variability in patient survival times and insufficient disease statistics for the majority of ALS- provoking mutations. As an alternative test of the structure- disease relationship we focus here on the SOD1 mutations that appear to be outliers in the data set. The results identify several ALS- provoking mutations whose only effect on apoSOD1 is the elimination or introduction of a single charge, i.e. D76V/Y, D101N, and N139D/K. The thermodynamic stability and folding behavior of these mutants are indistinguishable from the wild-type control. Moreover, D101N is an outlier in the plot of stability loss versus patient survival time by having rapid disease progression. Commonto the identified mutations is that they truncate conserved salt-links and/or H-bond networks in the functional loops IV or VII. The results show that the local impact of ALS- associated mutations on the SOD1 molecule can sometimes overrun their global effects on apo-state stability and net repulsive charge, and point at the analysis of property outliers as an efficient strategy for mapping out new ALS- provoking features.
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6.
  • Chrysafi, Anna, et al. (författare)
  • Quantifying Earth system interactions for sustainable food production via expert elicitation
  • 2022
  • Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 5:10, s. 830-842
  • Tidskriftsartikel (refereegranskat)abstract
    • Several safe boundaries of critical Earth system processes have already been crossed due to human perturbations; not accounting for their interactions may further narrow the safe operating space for humanity. Using expert knowledge elicitation, we explored interactions among seven variables representing Earth system processes relevant to food production, identifying many interactions little explored in Earth system literature. We found that green water and land system change affect other Earth system processes strongly, while land, freshwater and ocean components of biosphere integrity are the most impacted by other Earth system processes, most notably blue water and biogeochemical flows. We also mapped a complex network of mechanisms mediating these interactions and created a future research prioritization scheme based on interaction strengths and existing knowledge gaps. Our study improves the understanding of Earth system interactions, with sustainability implications including improved Earth system modelling and more explicit biophysical limits for future food production.
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7.
  • Hansen, Benni W., et al. (författare)
  • In situ and experimental evidence for effects of elevated pH on protistan and metazoan grazers
  • 2019
  • Ingår i: Journal of Plankton Research. - : Oxford University Press (OUP). - 0142-7873 .- 1464-3774. ; 41:3, s. 257-271
  • Tidskriftsartikel (refereegranskat)abstract
    • Plankton succession was studied in a hyper-eutrophic stratified estuary, Mariager Fjord, Denmark. Above the pycnocline (15 m) pH increased from 8.5 to 9.2 and the oxygen increased to super saturation after 5 d of sunny weather due to high primary production. The protistan grazers were dominated by heterotrophic dinoflagellates and mixotrophic and heterotrophic ciliates. Metazooplankton was dominated by meroplankton, rotifers and the copepod, Acartia tonsa, all with a relatively low biomass. Cirriped nauplii occupied the upper strata while polychaete larvae populated the whole water column. Bivalve larvae occurred occasionally above the pycnocline even at very high pH. In pH challenge experiments, the mixotrophic ciliate Mesodinium rubrum was the least pH tolerant species, followed by Strombidium spp., which did not cope well with seawater pH > 8.5. Some heterotrophic dinoflagellates were more tolerant with net growth at pH > 9. The predominant rotifer Synchaeta sp. tolerated up to pH 9.5 and the copepod survived pH 10 but stopped producing eggs at pH 9.5 with unaffected egg hatching success. The polychaete and cirriped larvae tolerated pH 9.5, but bivalve larvae showed decreased survival already at pH 8.5. In situ distribution patterns and pH challenge experiments suggest that pH indeed contribute to structuring zooplankton distribution.
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8.
  • Jong, Wouter SP, et al. (författare)
  • A structurally informed autotransporter platform for efficient heterologous protein secretion and display
  • 2012
  • Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859 .- 1475-2859. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The self-sufficient autotransporter (AT) pathway, ubiquitous in Gram-negative bacteria, combines a relatively simple protein secretion mechanism with a high transport capacity. ATs consist of a secreted passenger domain and a β-domain that facilitates transfer of the passenger across the cell-envelope. They have a great potential for the extracellular expression of recombinant proteins but their exploitation has suffered from the limited structural knowledge of carrier ATs. Capitalizing on its crystal structure, we have engineered the Escherichia coli AT Hemoglobin protease (Hbp) into a platform for the secretion and surface display of heterologous proteins, using the Mycobacterium tuberculosis vaccine target ESAT6 as a model protein.RESULTS: Based on the Hbp crystal structure, five passenger side domains were selected and one by one replaced by ESAT6, whereas a β-helical core structure (β-stem) was left intact. The resulting Hbp-ESAT6 chimeras were efficiently and stably secreted into the culture medium of E. coli. On the other hand, Hbp-ESAT6 fusions containing a truncated β-stem appeared unstable after translocation, demonstrating the importance of an intact β-stem. By interrupting the cleavage site between passenger and β-domain, Hbp-ESAT6 display variants were constructed that remain cell associated and facilitate efficient surface exposure of ESAT6 as judged by proteinase K accessibility and whole cell immuno-EM analysis. Upon replacement of the passenger side domain of an alternative AT, EspC, ESAT6 was also efficiently secreted, showing the approach is more generally applicable to ATs. Furthermore, Hbp-ESAT6 was efficiently displayed in an attenuated Salmonella typhimurium strain upon chromosomal integration of a single encoding gene copy, demonstrating the potential of the Hbp platform for live vaccine development.CONCLUSIONS: We developed the first structurally informed AT platform for efficient secretion and surface display of heterologous proteins. The platform has potential with regard to the development of recombinant live vaccines and may be useful for other biotechnological applications that require high-level secretion or display of recombinant proteins by bacteria.
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9.
  • Jong, Wouter S. P., et al. (författare)
  • An autotransporter display platform for the development of multivalent recombinant bacterial vector vaccines
  • 2014
  • Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859 .- 1475-2859. ; 13, s. -162
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Autotransporter pathway, ubiquitous in Gram-negative bacteria, allows the efficient secretion of large passenger proteins via a relatively simple mechanism. Capitalizing on its crystal structure, we have engineered the Escherichia coli autotransporter Hemoglobin protease (Hbp) into a versatile platform for secretion and surface display of multiple heterologous proteins in one carrier molecule. Results: As proof-of-concept, we demonstrate efficient secretion and high-density display of the sizeable Mycobacterium tuberculosis antigens ESAT6, Ag85B and Rv2660c in E. coli simultaneously. Furthermore, we show stable multivalent display of these antigens in an attenuated Salmonella Typhimurium strain upon chromosomal integration. To emphasize the versatility of the Hbp platform, we also demonstrate efficient expression of multiple sizeable antigenic fragments from Chlamydia trachomatis and the influenza A virus at the Salmonella cell surface. Conclusions: The successful efficient cell surface display of multiple antigens from various pathogenic organisms highlights the potential of Hbp as a universal platform for the development of multivalent recombinant bacterial vector vaccines.
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10.
  • Lok, Veeleah, et al. (författare)
  • Changes in anxiety and depression during the COVID-19 pandemic in the European population : A meta-analysis of changes and associations with restriction policies
  • 2023
  • Ingår i: European psychiatry. - 0924-9338 .- 1778-3585. ; 66:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background. Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population.Methods. We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression.Results. Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress.Conclusions. Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.
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