| 1. |
- Hultberg, Tove, et al.
(author)
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Ash dieback risks an extinction cascade
- 2020
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In: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 244
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Journal article (peer-reviewed)abstract
- Large-scale decline in populations of European ash (Fraxinus excelsior) are occurring throughout Europe due to the invasive fungus Hymenoscyphus fraxineus. This has grave ecological implications not only for ash trees, but also for the biodiversity supported by, and in some cases solely dependent on ash. Here we used data on the tree-species associations of biodiversity in Sweden, to predict extinction risks for ash-associated organisms, and the potential for combinations of other tree species to sustain ash-associated biodiversity. Of the 483 ash-associated species identified, 11% are exclusive to ash, and a further 23% prefer mainly ash. Notably, many ash-associated species are shared with wych elm (Ulmus glabra) which is similarly threatened by an invasive fungus. Considering the level of host association and the species' conservation status, 115 species were deemed at high risk of regional extinction. Using a mathematical optimization model we found that up to nine additional tree species would be needed to sustain all non-obligate ash dependent/preferring species in the absence of ash and elm. We discuss mitigation and adaption options to reduce the potential for an extinction cascade and conserve ash-associated biodiversity, but all pose unique challenges.
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| 2. |
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| 3. |
- Fagerberg, David, et al.
(author)
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Novel Leb-like Helicobacter pylori-binding glycosphingolipid created by the expression of human alpha-1,3/4-fucosyltransferase in FVB/N mouse stomach.
- 2009
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In: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 19:2, s. 182-91
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Journal article (peer-reviewed)abstract
- The "Le(b) mouse" was established as a model for investigations of the molecular events following Le(b)-mediated adhesion of Helicobacter pylori to the gastric epithelium. By the expression of a human alpha-1,3/4-fucosyltransferase in the gastric pit cell lineage of FVB/N transgenic mice, a production of Le(b) glycoproteins in gastric pit and surface mucous cells was obtained in this "Le(b) mouse," as demonstrated by binding of monoclonal anti-Le(b) antibodies. To explore the effects of the human alpha-1,3/4-fucosyltransferase on glycosphingolipid structures, neutral glycosphingolipids were isolated from stomachs of transgenic alpha-1,3/4-fucosyltransferase-expressing mice. A glycosphingolipid recognized by BabA-expressing H. pylori was isolated and characterized by mass spectrometry and proton NMR as Fuc alpha 2Gal beta 3(Fuc alpha 4)GalNAc beta 4 Gal beta 4 Glc beta 1Cer, i.e., a novel Le(b)-like glycosphingolipid on a ganglio core. In addition, two other novel glycosphingolipids were isolated from the mouse stomach epithelium that were found to be nonbinding with regard to H. pylori. The first was a pentaglycosylceramide, GalNAc beta 3 Gal alpha 3(Fuc alpha 2)Gal beta 4 Glc beta 1Cer, in which the isoglobotetrasaccharide has been combined with Fuc alpha 2 to yield an isoglobotetraosylceramide with an internal blood group B determinant. The second one was an elongated fucosyl-gangliotetraosylceramide, GalNAc beta 3(Fuc alpha 2)Gal beta 3GalNAc beta 4Gal beta 4 Glc beta 1Cer.
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| 4. |
- Faria, Vanda, et al.
(author)
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Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder : A Randomized Trial
- 2017
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 179-188
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Journal article (peer-reviewed)abstract
- Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).Methods: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram(20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.Findings: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n = 24) as compared to covert (n = 22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69–31.65, p < 0.0001) with more than three times higher response rate (50% vs. 14%; χ2(1) = 6.91, p = 0.009) and twice the effect size (d = 2.24 vs. d = 1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p ≤ 0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p = 0.0006) and attenuated amygdala (z threshold 2.70, p = 0.003) activity.Interpretation: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.
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| 5. |
- Hultberg, Jonas, et al.
(author)
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In-depth immune profiling reveals advanced B- and T-cell differentiation to be associated with Th1-driven immune dysregulation in common variable immunodeficiency
- 2023
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In: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 257
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Journal article (peer-reviewed)abstract
- Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by low levels of an-tibodies. In addition to infections, many patients also suffer from T-helper 1-driven immune dysregulation, which is associated with increased mortality. The aim of this study was to perform in-depth characterization of the T and the B cell compartments in a well-defined cohort of patients affected by CVID and correlate the findings to the level of clinical immune dysregulation. We used mass cytometry, targeted proteomics, flow cytometry and functional assays to delineate the immunological phenotype of 15 CVID-affected patients with different levels of immune dysregulation. Unbiased clustering of T cell mass cytometry data correlated with CVID-related immune dysregulation and plasma protein profiles. Expanded CXCR3+ T-bet-expressing B cells correlated with effector memory CD4+ T cell clusters, and increased plasma levels of CXCR3-ligands. Our findings indicate an interplay between B cells and T cells in CVID-related immune dysregulation and provide a better understanding of the underlying pathological mechanisms.
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| 6. |
- Hultberg, Jonas, et al.
(author)
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Plasma protein profiling reflects T(H)1-driven immune dysregulation in common variable immunodeficiency
- 2020
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In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 146:2, s. 417-428
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Journal article (peer-reviewed)abstract
- Background: Common variable immunodeficiency (CVID) is a disorder characterized by antibody deficiency. A significant fraction of the patients suffer from immune dysregulation, which leads to increased morbidity and mortality. The pathogenesis of this condition is poorly understood. Objective: Our aim was to find out whether the plasma protein signature in CVID is associated with clinical characteristics and lymphocyte aberrations. Methods: A highly sensitive proximity extension assay was used for targeted profiling of 145 plasma proteins in 29 patients with CVID. Phenotyping of peripheral lymphocytes was done by flow cytometry. The findings were correlated with the burden of immune dysregulation. Results: Unsupervised clustering of plasma protein profiles identified 2 distinct groups of patients with CVID that differed significantly in terms of the degree of complications due to immune dysregulation and in terms of the frequency of activated B- and T-cell subpopulations. Pathway analysis identified IFN-gamma and IL-1 beta as the top enriched upstream regulators associated with higher grade of immune dysregulation. In addition, CVID was found to be associated with increased plasma levels of the B-cell attracting chemokine CXCL13. Conclusion: Clustering based on plasma protein profiles delineated a subgroup of patients with CVID with activated T cells and clinical complications due to immune dysregulation. Thus, data indicate that CVID-associated immune dysregulation is a T(H)1-mediated inflammatory process driven by the IFN-gamma pathway.
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| 7. |
- Lindfors, Oskar, et al.
(author)
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Överdiagnostik – vad är det? : INTRODUKTION TILL BEGREPPET [What is overdiagnosis?]
- 2023
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In: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 120
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Research review (peer-reviewed)abstract
- A considerable amount of spending in health care is deemed wasteful. Overdiagnosis, i.e. the labelling of a person with a diagnosis that lacks net benefit, is an entity within the overarching concept of »too much medicine«. Overdiagnosis includes overdetection and overdefinition. Disease mongering is a type of overdefinition with economic drivers. Overtesting and overtreatment are other aspects of »too much medicine«, but are not overdiagnosis per se. Medical research tends to focus on benefits of diagnostics and therapy, whereas overdiagnosis and other harms receive less attention, leading to overestimation of benefits. The international network Choosing Wisely has been successful in changing the diagnostic mindset in several countries and a Swedish campaign is under way, yielding new possibilities to counteract »too much medicine« and the specific problem of overdiagnosis.
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| 8. |
- Nyström, Sofia, et al.
(author)
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Plasma Levels of mir-34a-5p Correlate with Systemic Inflammation and Low Naïve CD4 T Cells in Common Variable Immunodeficiency
- 2024
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In: Journal of Clinical Immunology. - : SPRINGER/PLENUM PUBLISHERS. - 0271-9142 .- 1573-2592. ; 44:1
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Journal article (peer-reviewed)abstract
- PurposeCommon variable immunodeficiency (CVID) is a primary antibody deficiency that commonly manifests as recurrent infections. Many CVID patients also suffer from immune dysregulation, an inflammatory condition characterized by polyclonal lymphocytic tissue infiltration and associated with increased morbidity and mortality. The genetic cause is unknown in most CVID patients and epigenetic alterations may contribute to the broad range of clinical manifestations. MicroRNAs are small non-coding RNAs that are involved in epigenetic modulation and may contribute to the clinical phenotype in CVID.MethodsHere, we determined the circulating microRNAome and plasma inflammatory proteins of a cohort of CVID patients with various levels of immune dysregulation and compared them to healthy controls. A set of deregulated microRNAs was validated by qPCR and correlated to inflammatory proteins and clinical findings.ResultsLevels of microRNA-34a correlated with 11 proteins such as CXCL9, TNF, and IL10, which were predicted to be biologically connected. Moreover, there was a negative correlation between mir-34 levels and the number of naive CD4 T cells in CVID.ConclusionCollectively, our data show that microRNAs correlate with the inflammatory response in CVID. Further investigations are needed to elucidate the role of miRNAs in the development of CVID-related immune dysregulation.
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| 9. |
- Vall, Maria, et al.
(author)
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Carbon dioxide adsorption on mesoporous magnesium carbonate
- 2019
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In: Energy Procedia. - : Elsevier. - 1876-6102. ; 158, s. 4671-4676
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Journal article (peer-reviewed)abstract
- Mesoporous magnesium carbonate (MMC) was synthesized and tested for its ability to separate CO2 from N2. The pure gas CO2 uptake of MMC was around 1.5 mmol/g at 101 kPa, 0 °C. The N2 uptake under the same conditions was less than 0.1 mmol/g. Al(NO3)3, Al2O3, K2CO3 and KNO3 were introduced into the porous structure of MMC as additives. All of the additives tested increased the CO2 uptake of MMC and increased its selectivity towards CO2. The incorporation of 5 wt.% K2CO3 increased the CO2 uptake of MMC up to over 3.2 mmol/g. The ideally adsorbed solution theory was used to calculate the CO2 selectivity of MMC and MMC with additives for a hypothetical gas mixture that contained 15% CO2: 85% N2. The CO2 selectivity at 101 kPa (0 °C) was around 60. MMC with 5 wt.% K2CO3 had a CO2 selectivity of over 150 under the same conditions. Vacuum swing cyclic CO2 adsorption/desorption showed that the CO2 uptake on MMC with 5 wt.% K2CO3 decreased after each cycle. Heat regeneration (up to 250 °C, for 10 minutes) could recover most of the lost CO2 capacity after each cycle. Heat regeneration indicatively improved the cyclic performance of this adsorbent. MMC with 5 wt.% K2CO3 was the best performing adsorbent in this study and can potentially be further developed into a good CO2 adsorbent for temperature swing adsorption (TSA) processes.
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| 10. |
- Vall, Maria, et al.
(author)
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Inorganic carbonate composites as potential high temperature CO2 sorbents with enhanced cycle stability
- 2019
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In: RSC Advances. - 2046-2069. ; 9:35, s. 20273-20280
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Journal article (peer-reviewed)abstract
- A calcium magnesium carbonate composite (CMC) material containing highly porous amorphous calcium carbonate (HPACC) and mesoporous magnesium carbonate (MMC) was synthesized. CMCs with varying HPACC : MMC mol ratios and high BET surface area (over 490 m2 g−1) were produced. The CMCs retained the morphology shared by HPACC and MMC. All these materials were built up of aggregated nanometer-sized particles. We tested the CO2 uptake properties of the synthesized materials. The CMCs were calcined at 850 °C to obtain the corresponding calcium magnesium oxide composites (CMOs) that contained CaO : MgO at different mol ratios. CMO with CaO : MgO = 3 : 1 (CMO-3) showed comparable CO2 uptake at 650 °C (0.586 g g−1) to CaO sorbents obtained from pure HPACC (0.658 g g−1) and the commercial CaCO3 (0.562 g g−1). Over 23 adsorption–desorption cycles CMOs also showed a lower CO2 uptake capacity loss (35.7%) than CaO from HPACC (51.3%) and commercial CaCO3 (79.7%). Al was introduced to CMO by the addition of Al(NO3)3 in the synthesis of CMC-3 to give ACMO after calcination. The presence of ∼19 mol% of Al(NO3)3 in ACMO-4 significantly enhanced its stability over 23 cycles (capacity loss of 5.2%) when compared with CMO-3 (calcined CMC-3) without adversely affecting the CO2 uptake. After 100 cycles, ACMO-4 still had a CO2 uptake of 0.219 g g−1. Scanning electron microscope images clearly showed that the presence of Mg and Al in CMO hindered the sintering of CaCO3 at high temperatures and therefore, enhanced the cycle stability of the CMO sorbents. We tested the CO2 uptake properties of CMO and ACMO only under ideal laboratory testing environment, but our results indicated that these materials can be further optimized as good CO2 sorbents for various applications.
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