| 1. |
- Tomic, Tajana Tesan, et al.
(författare)
-
MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression
- 2020
-
Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 16:6
-
Tidskriftsartikel (refereegranskat)abstract
- Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B:p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A. The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors. © 2020 Tomic et al.
|
|
| 2. |
|
|
| 3. |
- Einarsdottir, Sigrun, et al.
(författare)
-
Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
- 2022
-
Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
-
Tidskriftsartikel (refereegranskat)abstract
- Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
|
|
| 4. |
- Ellis, Vincenzo A., et al.
(författare)
-
Explaining prevalence, diversity and host specificity in a community of avian haemosporidian parasites
- 2020
-
Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 129:9, s. 1314-1329
-
Tidskriftsartikel (refereegranskat)abstract
- Many hypotheses attempt to explain parasite–host associations, but rarely are they examined together in a single community. For hosts, key traits are the proportion of infected individuals (prevalence) and the diversity of parasites infecting them. A key parasite trait is host specificity, ranging from specialists infecting one or a few closely related species to generalists infecting many species. We tested 10 hypotheses to explain host-parasite associations; five ‘host-centric’ (e.g. prevalence is related to host abundance) and five ‘parasite-centric’ (e.g. parasite abundance is related to host specificity). We analyzed a community of 67 locally transmitted avian haemosporidian parasite lineages (genera Plasmodium, Haemoproteus or Leucocytozoon), sampled from 2726 birds (64 species) in southern Sweden. Among host-centric hypotheses, Haemoproteus and Leucocytozoon prevalence and Haemoproteus diversity were related to host habitat preferences, whereas there were no relationships with host abundance or body mass. Haemoproteus and Leucocytozoon prevalences were more similar among closely related than among distantly related host species. Haemoproteus prevalence and diversity were lower in host species with few close relatives (‘evolutionarily distinct’ hosts). Among parasite-centric hypotheses, most lineages, even relative generalists, infected closely related host species more often than expected by chance. However, the host species of Haemoproteus and Leucocytozoon lineages overlapped less among lineages than expected by chance. Specialists did not reach higher prevalences than generalists on single host species. However, the abundance of Haemoproteus lineages was related to host specificity with generalists more common than specialists; this was driven by three closely related generalists. Host specificity of parasites was unrelated to the abundance or evolutionarily distinctiveness of their hosts. Parasite communities are likely structured by many factors and cannot be explained by hypotheses focusing solely on hosts or parasites. However, we found consistent effects of host phylogenetic relationships, plausibly a result of evolutionarily conserved host immune systems limiting parasite distributions.
|
|
| 5. |
- Lethin, Connie, et al.
(författare)
-
Predicting caregiver burden in informal caregivers caring for persons with dementia living at home – A follow-up cohort study
- 2020
-
Ingår i: Dementia. - London : Sage Publications. - 1471-3012 .- 1741-2684. ; 9:3, s. 640-660
-
Tidskriftsartikel (refereegranskat)abstract
- Longitudinal studies of caregiver burden when caring for persons with dementia living at home are sparse. The aim of the study was to identify factors associated with caregiver burden and predicting increased burden related to caregivers, persons with dementia and formal care. Data were collected through interviews with 1223 caregivers in eight European countries. Bivariate and multivariate regression analyses were performed. Factors associated with caregiver burden included extensive informal care provision, decreased well-being and reduced quality of life for the caregiver and reduced cognition, decreased quality of life, severe neuropsychiatric symptoms and depression in the person with dementia and caregivers’ negative experience of quality of care. Factors predicting an increased burden were diminished caregiver well-being, severe neuropsychiatric symptoms of the person with dementia and caregivers’ negative perception of quality of care. The knowledge gained in this study may be useful in developing more adequate service systems and interventions to improve dementia care. © 2018, The Author(s) 2018.
|
|
| 6. |
- Pape Møller, Anders, et al.
(författare)
-
Interaction of climate change with effects of conspecific and heterospecific density on reproduction
- 2020
-
Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 129:12, s. 1807-1819
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the relationship between temperature and the coexistence of great tit Parus major and blue tit Cyanistes caeruleus, breeding in 75 study plots across Europe and North Africa. We expected an advance in laying date and a reduction in clutch size during warmer springs as a general response to climate warming and a delay in laying date and a reduction in clutch size during warmer winters due to density‐dependent effects. As expected, as spring temperature increases laying date advances and as winter temperature increases clutch size is reduced in both species. Density of great tit affected the relationship between winter temperature and laying date in great and blue tit. Specifically, as density of great tit increased and temperature in winter increased both species started to reproduce later. Density of blue tit affected the relationship between spring temperature and blue and great tit laying date. Thus, both species start to reproduce earlier with increasing spring temperature as density of blue tit increases, which was not an expected outcome, since we expected that increasing spring temperature should advance laying date, while increasing density should delay it cancelling each other out. Climate warming and its interaction with density affects clutch size of great tits but not of blue tits. As predicted, great tit clutch size is reduced more with density of blue tits as temperature in winter increases. The relationship between spring temperature and density on clutch size of great tits depends on whether the increase is in density of great tit or blue tit. Therefore, an increase in temperature negatively affected the coexistence of blue and great tits differently in both species. Thus, blue tit clutch size was unaffected by the interaction effect of density with temperature, while great tit clutch size was affected in multiple ways by these interactions terms.
|
|
| 7. |
- Persson Lindell, Olof, et al.
(författare)
-
Clinical decision support for familial hypercholesterolemia (CDS-FH) : Rationale and design of a cluster randomized trial in primary care
- 2022
-
Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 247, s. 132-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder with high risk of premature atherosclerotic cardiovascular disease and death. Clinical decision support (CDS) systems have the potential to aid in the identification and management of patients with FH. Prior studies using computer-based systems to screen patients for FH have shown promising results, but there has been no randomized controlled trial conducted. The aim of the current cluster randomized study is to evaluate if a CDS can increase the identification of FH.Methods: We have developed a CDS integrated in the electronic health records that will be activated in patients with elevated cholesterol levels (total cholesterol > 8 mmol/L or low-density lipoprotein-cholesterol > 5.5 mmol/L, adjusted for age, ongoing lipid lowering therapy and presence of premature coronar y arter y disease) at increased risk for FH. When activated, the CDS will urge the physician to send an automatically generated referral to the local lipid clinic for further evaluation. To evaluate the effects of the CDS, all primary care clinics will be cluster randomized 1:1 to either CDS intervention or standard care in a Swedish region with almost 500,000 inhabitants. The primary endpoint will be the number of patients diagnosed with FH at 30 months. Resource use and long-term health consequences will be estimated to assess the cost-effectiveness of the intervention.Conclusion : Despite increasing awareness of FH, the condition remains underdiagnosed and undertreated. The present study will investigate whether a CDS can increase the number of patients being diagnosed with FH.
|
|
| 8. |
- Törnell, Andreas, 1994, et al.
(författare)
-
Rapid cytokine release assays for analysis of SARS-CoV-2-specific T cells in whole blood.
- 2022
-
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 226:2, s. 208-216
-
Tidskriftsartikel (refereegranskat)abstract
- Waning of IgG antibodies against SARS-CoV-2 complicates diagnosis of past infection. Durability of T cell memory against SARS-CoV-2 remains unclear, and most current T cell protocols are unsuited for large-scale automation.Whole blood samples from 31 patients with verified past COVID-19 and 46 controls, out of which 40 received SARS-CoV-2 vaccine were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon-γ (IFN-γ) in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti-receptor-binding domain S1 IgG.Induction of IFN-γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (AUC=0.93, AUC=0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5/17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC-peptide-induced T cell memory responses remained in 13/17 (76%) subjects >180 days after infection (P=0.012 vs. NC-IgG, McNemar test). After two vaccine doses, 18/18 donors exhibited S1-specific T cell memory.Cytokine release assays for the monitoring of T cell memory in whole blood may be useful for evaluation of complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T cell immunity.
|
|
| 9. |
|
|
| 10. |
|
|
