| 1. |
|
|
| 2. |
- Rosa, Fábio F, et al.
(author)
-
Single-cell transcriptional profiling informs efficient reprogramming of human somatic cells to cross-presenting dendritic cells
- 2022
-
In: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 7:69, s. 1-18
-
Journal article (peer-reviewed)abstract
- Type 1 conventional dendritic cells (cDC1s) are rare immune cells critical for the induction of antigen-specific cytotoxic CD8+ T cells, although the genetic program driving human cDC1 specification remains largely unexplored. We previously identified PU.1, IRF8, and BATF3 transcription factors as sufficient to induce cDC1 fate in mouse fibroblasts, but reprogramming of human somatic cells was limited by low efficiency. Here, we investigated single-cell transcriptional dynamics during human cDC1 reprogramming. Human induced cDC1s (hiDC1s) generated from embryonic fibroblasts gradually acquired a global cDC1 transcriptional profile and expressed antigen presentation signatures, whereas other DC subsets were not induced at the single-cell level during the reprogramming process. We extracted gene modules associated with successful reprogramming and identified inflammatory signaling and the cDC1-inducing transcription factor network as key drivers of the process. Combining IFN-γ, IFN-β, and TNF-α with constitutive expression of cDC1-inducing transcription factors led to improvement of reprogramming efficiency by 190-fold. hiDC1s engulfed dead cells, secreted inflammatory cytokines, and performed antigen cross-presentation, key cDC1 functions. This approach allowed efficient hiDC1 generation from adult fibroblasts and mesenchymal stromal cells. Mechanistically, PU.1 showed dominant and independent chromatin targeting at early phases of reprogramming, recruiting IRF8 and BATF3 to shared binding sites. The cooperative binding at open enhancers and promoters led to silencing of fibroblast genes and activation of a cDC1 program. These findings provide mechanistic insights into human cDC1 specification and reprogramming and represent a platform for generating patient-tailored cDC1s, a long-sought DC subset for vaccination strategies in cancer immunotherapy.
|
|
| 3. |
- Warsi, Sarah, et al.
(author)
-
Schlafen2 is a regulator of quiescence in adult murine hematopoietic stem cells
- 2022
-
In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 107:12, s. 2884-2896
-
Journal article (peer-reviewed)abstract
- Even though hematopoietic stem cells (HSC) are characterized by their ability to self-renew and differentiate, they primarily reside in quiescence. Despite the immense importance of this quiescent state, its maintenance and regulation is still incompletely understood. Schlafen2 (Slfn2) is a cytoplasmic protein known to be involved in cell proliferation, differentiation, quiescence, interferon response, and regulation of the immune system. Interestingly, Slfn2 is highly expressed in primitive hematopoietic cells. In order to investigate the role of Slfn2 in the regulation of HSC we have studied HSC function in the elektra mouse model, where the elektra allele of the Slfn2 gene contains a point mutation causing loss of function of the Slfn2 protein. We found that homozygosity for the elektra allele caused a decrease of primitive hematopoietic compartments in murine bone marrow. We further found that transplantation of elektra bone marrow and purified HSC resulted in a significantly reduced regenerative capacity of HSC in competitive transplantation settings. Importantly, we found that a significantly higher fraction of elektra HSC (as compared to wild-type HSC) were actively cycling, suggesting that the mutation in Slfn2 increases HSC proliferation. This additionally caused an increased amount of apoptotic stem and progenitor cells. Taken together, our findings demonstrate that dysregulation of Slfn2 results in a functional deficiency of primitive hematopoietic cells, which is particularly reflected by a drastically impaired ability to reconstitute the hematopoietic system following transplantation and an increase in HSC proliferation. This study thus identifies Slfn2 as a novel and critical regulator of adult HSC and HSC quiescence.
|
|
| 4. |
- Adielsson, Anna, et al.
(author)
-
Outcome prediction for patients assessed by the medical emergency team : a retrospective cohort study
- 2022
-
In: BMC Emergency Medicine. - : Springer Science and Business Media LLC. - 1471-227X. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background: Medical emergency teams (METs) have been implemented to reduce hospital mortality by the early recognition and treatment of potentially life-threatening conditions. The objective of this study was to establish a clinically useful association between clinical variables and mortality risk, among patients assessed by the MET, and further to design an easy-to-use risk score for the prediction of death within 30 days.Methods: Observational retrospective register study in a tertiary university hospital in Sweden, comprising 2,601 patients, assessed by the MET from 2010 to 2015. Patient registry data at the time of MET assessment was analysed from an epidemiological perspective, using univariable and multivariable analyses with death within 30 days as the outcome variable. Predictors of outcome were defined from age, gender, type of ward for admittance, previous medical history, acute medical condition, vital parameters and laboratory biomarkers. Identified factors independently associated with mortality were then used to develop a prognostic risk score for mortality.Results: The overall 30-day mortality was high (29.0%). We identified thirteen factors independently associated with 30-day mortality concerning; age, type of ward for admittance, vital parameters, laboratory biomarkers, previous medical history and acute medical condition. A MET risk score for mortality based on the impact of these individual thirteen factors in the model yielded a median (range) AUC of 0.780 (0.774-0.785) with good calibration. When corrected for optimism by internal validation, the score yielded a median (range) AUC of 0.768 (0.762-0.773).Conclusions: Among clinical variables available at the time of MET assessment, thirteen factors were found to be independently associated with 30-day mortality. By applying a simple risk scoring system based on these individual factors, patients at higher risk of dying within 30 days after the MET assessment may be identified and treated earlier in the process.
|
|
| 5. |
- Aebi, Stefan, et al.
(author)
-
Locally advanced breast cancer.
- 2022
-
In: Breast. - : Elsevier BV. - 1532-3080. ; 62:Suppl. 1
-
Journal article (peer-reviewed)abstract
- Locally advanced breast cancer (LABC) is defined here as inoperable breast adenocarcinoma without distant metastases. Patients with LABC require a multidisciplinary approach. Given the risk of distant metastasis, staging exams are necessary. The incidence of LABC (stages IIIB and IIIC) has decreased in recent years. LABC has rarely been investigated separately: patients with LABC have participated both in clinical trials of palliative and of neoadjuvant therapy. Most trials did not analyze responses and long-term outcomes independently; thus, the treatment of patients with LABC is extrapolated from studies of patients with less or more advanced disease. Pathologic confirmation and molecular profiling are essential for the choice of neoadjuvant chemotherapy. Preoperative endocrine therapy may be considered in certain clinical situations; the addition of a CDK4/6 inhibitor is being investigated. HER2 positive LABCs are targeted with anti-HER2 agents combined with chemotherapy. PD-1 and PD-L1 antibodies in 'triple-negative' LABC are promising. Excellent responses to neoadjuvant therapy enable conservative surgery in many patients; however, inflammatory breast cancer may still indicate mastectomy. Postoperative radiotherapy is usually indicated. Target volumes include breast/chest wall, axillary, supraclavicular and internal mammary nodal basins. Preoperative radiation therapy can be useful in patients without response to systemic therapies. Palliative surgery for poor responders after neoadjuvant systemic and radiation therapy can be considered. Multidisciplinary teams can optimize local control and prevent relapses. However, modest improvement in survival was achieved between 2000 and 2014 underscoring the unmet need in patients with LABC who will benefit from specific research efforts in this disease entity.
|
|
| 6. |
- Bengtsson, F., et al.
(author)
-
Alkali ion diffusion and structure of chemically strengthened TiO2 doped soda-lime silicate glass
- 2022
-
In: Journal of Non-Crystalline Solids. - : Elsevier BV. - 0022-3093 .- 1873-4812. ; 586, s. 121564-121564
-
Journal article (peer-reviewed)abstract
- Diffusion kinetics and structural properties of chemically strengthened titania-doped soda-lime silicate glasses were studied by depth-resolved X-ray photoelectron spectroscopy, Raman spectroscopy and spectrophotometry. The glasses were ion exchanged, whereby Na+ in the glass was replaced by K+ in a molten salt bath, at four different treatment temperatures between 350 and 500 °C. The alkali diffusion coefficient, DK-Na, and corresponding activation energy were calculated to be between 3.26×10−12 and 4.47×10−11 cm2s−1 and between 101.1 kJmol−1 and 105.6 kJmol−1, respectively. DK-Na was observed to decrease as the TiO2 concentration was increased. Raman analysis showed Q3-silicate species with different bond lengths, which was attributed to surface compressive stresses, and increasing Si-O-Si bond angle with increasing ion exchange temperature. Ti3+ ions exist as a minor species in the glasses and its concentration depends on the TiO2 content. Deconvolution of the optical absorption spectra reveals Jahn-Teller compressive distortion of the Ti3+ octahedral coordination.
|
|
| 7. |
- Bengtsson, Felix, et al.
(author)
-
Dataset: Alkali Ion diffusion and structure of chemically strengthened TiO2 doped soda-lime silicate glass
- 2022
-
Other publicationabstract
- Diffusion kinetics and structural properties of chemically strengthened titania-doped soda-lime silicate glasses were studied by depth-resolved X-ray photoelectron spectroscopy, Raman spectroscopy and spectrophotometry.Chemical strengthening (CS) is frequently used to strengthen thin glasses. CS of glass is based on ion exchange of larger ions from a molten salt into glass. Both the ion and counter ion are conventionally monovalent alkali ions.Diffusion kinetics and structural properties of chemically strengthened titania-doped (TiO2) soda-lime silicate (SLS) glasses were studied by depth-resolved X-ray photoelectron spectroscopy, Raman spectroscopy and spectrophotometry. The glasses were ion exchanged, whereby Na+ in the glass was replaced by K+ in a molten salt bath, at four different treatment temperatures between 350 and 500 °C.The following samples were prepared and analyzed by X-ray Photoelectron Spectroscopy (XPS): (1) SLS, (2) 4.7% TiO2, and (3) 9.9% TiO2. The ion exchange procedure was performed for 5 h at four different temperatures below Tg (350, 400, 450 and 500 °C). Before XPS measurements, the samples were wet-etched using hydrofluoric (HF) acid to produce samples with six different etching depths.The Raman scattered light was detected in the backscattering configuration employing linear polarization and 2400 lines/mm grating, and a 100x objective lens. Depth profile spectra were collected at six different depths of 0, 10, 20, 30, 40, and 50 µm for each glass sample, employing 12 scans with a 10 s exposure time for each scan.Spectrophotometric measurements were conducted before and after K+/Na+ ion-exchange treatmeatment for 5 h at 500 °C, collected between 300 and 2500 nm.
|
|
| 8. |
- Börjesson, Stefan, 1979-, et al.
(author)
-
Detection of an IMI-2 carbapenemase-producing Enterobacter asburiae at a Swedish feed mill
- 2022
-
In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
-
Journal article (peer-reviewed)abstract
- Occurrence of multidrug resistant Enterobacteriaceae in livestock is of concern as they can spread to humans. A potential introduction route for these bacteria to livestock could be animal feed. We therefore wanted to identify if Escherichia spp., Enterobacter spp., Klebsiella spp., or Raoutella spp. with transferable resistance to extended spectrum cephalosporins, carbapenems or colistin could be detected in the environment at feed mills in Sweden. A second aim was to compare detected isolates to previous described isolates from humans and animals in Sweden to establish relatedness which could indicate a potential transmission between sectors and feed mills as a source for antibiotic resistant bacteria. However, no isolates with transferable resistance to extended-cephalosporins or colistin could be identified, but one isolate belonging to the Enterobacter cloacae complex was shown to be carbapenem-resistant and showing carbapenemase-activity. Based on sequencing by both short-read Illumina and long-read Oxford Nanopore MinIon technologies it was shown that this isolate was an E. asburiae carrying a bla IMI-2 gene on a 216 Kbp plasmid, designated pSB89A/IMI-2, and contained the plasmid replicons IncFII, IncFIB, and a third replicon showing highest similarity to the IncFII(Yp). In addition, the plasmid contained genes for various functions such as plasmid segregation and stability, plasmid transfer and arsenical transport, but no additional antibiotic resistance genes. This isolate and the pSB89A/IMI-2 was compared to three human clinical isolates positive for bla IMI-2 available from the Swedish antibiotic monitoring program Swedres. It was shown that one of the human isolates carried a plasmid similar with regards to gene content to the pSB89A/IMI-2 except for the plasmid transfer system, but that the order of genes was different. The pSB89A/IMI-2 did however share the same transfer system as the bla IMI-2 carrying plasmids from the other two human isolates. The pSB89A/IMI-2 was also compared to previously published plasmids carrying bla IMI-2, but no identical plasmids could be identified. However, most shared part of the plasmid transfer system and DNA replication genes, and the bla IMI-2 gene was located next the transcription regulator imiR. The IS3-family insertion element downstream of imiR in the pSB89A was also related to the IS elements in other bla IMI-carrying plasmids.
|
|
| 9. |
- Capo, Eric, et al.
(author)
-
Expression Levels of hgcAB Genes and Mercury Availability Jointly Explain Methylmercury Formation in Stratified Brackish Waters
- 2022
-
In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:18, s. 13119-13130
-
Journal article (peer-reviewed)abstract
- Neurotoxic methylmercury (MeHg) is formed by microbial methylation of inorganic divalent Hg (Hg-II) and constitutes severe environmental and human health risks. The methylation is enabled by hgcA and hgcB genes, but it is not know nif the associated molecular-level processes are rate-limiting or enable accurate prediction of MeHg formation in nature. In this study, we investigated the relationships between hgc genes and MeHg across redox-stratified water columns in the brackish Baltic Sea. We showed, for the first time, that hgc transcript abundance and the concentration of dissolved Hg-II-sulfide species were strong predictors of both the Hg-II methylation rate and MeHg concentration, implying their roles as principal joint drivers of MeHg formation in these systems. Additionally, we characterized the metabolic capacities of hgc(+) microorganisms by reconstructing their genomes from metagenomes (i.e., hgc(+) MAGs), which highlighted the versatility of putative Hg-II methylators in the water column of the Baltic Sea. In establishing relationships between hgc transcripts and the Hg-II methylation rate, we advance the fundamental understanding of mechanistic principles governing MeHg formation in nature and enable refined predictions of MeHg levels in coastal seas in response to the accelerating spread of oxygen-deficientzones.
|
|
| 10. |
- Frisk, Anders, et al.
(author)
-
Kropp
- 2022
-
In: Hur kan vi förstå rörelse?. - Stockholm : Liber. - 9789147145393 ; , s. 60-105
-
Book chapter (other academic/artistic)abstract
- Rörelseövning 1. Böja - sträcka - vridaRörelseövning 2. BallongövningAvslutningReferenser
|
|
