| 1. |
- Hagström, Åke, et al.
(author)
-
Composition and Seasonality of Membrane Transporters in Marine Picoplankton
- 2021
-
In: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 12
-
Journal article (peer-reviewed)abstract
- In this study, we examined transporter genes in metagenomic and metatranscriptomic data from a time-series survey in the temperate marine environment of the Baltic Sea. We analyzed the abundance and taxonomic distribution of transporters in the 3 mu m-0.2 mu m size fraction comprising prokaryotes and some picoeukaryotes. The presence of specific transporter traits was shown to be guiding the succession of these microorganisms. A limited number of taxa were associated with the dominant transporter proteins that were identified for the nine key substrate categories for microbial growth. Throughout the year, the microbial taxa at the level of order showed highly similar patterns in terms of transporter traits. The distribution of transporters stayed the same, irrespective of the abundance of each taxon. This would suggest that the distribution pattern of transporters depends on the bacterial groups being dominant at a given time of the year. Also, we find notable numbers of secretion proteins that may allow marine bacteria to infect and kill prey organisms thus releasing nutrients. Finally, we demonstrate that transporter proteins may provide clues to the relative importance of biogeochemical processes, and we suggest that virtual transporter functionalities may become important components in future population dynamics models.
|
|
| 2. |
|
|
| 3. |
- Lundgren, Ewa, et al.
(author)
-
Primary hyperparathyroidism revisited in menopausal women with serum calcium in upper normal range at population-based screening 8 years ago
- 2002
-
In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 26:8, s. 931-936
-
Journal article (peer-reviewed)abstract
- Abstract. Population-based screening showed 2.1% prevalence of primaryhyperparathyroidism (pHPT) in postmenopausal women. Individualswith total serum (s)-calcium levels of 2.55 mmol/L or more at screeningwere diagnosed with pHPT when subsequent analysis supported inappropriatelyelevated intact parathormone (PTH) levels in relation to evennormal s-calcium levels. The arbitrary diagnostic criteria were validatedby parathyroidectomy. Herein we reinvestigated biochemical signs ofpHPT in women not diagnosed with pHPT due to s-calcium 2.50 to 2.54mmol/L (group A, n 160) at screening or due to appropriate PTH levelson two occasions after screening (group B, n 70). Altogether, 99 womenin group A and 47 in group B underwent reinvestigation 8.8 years afterscreening when they were 65 to 84 years old. The s-calcium levels averaged2.56 mmol/L and had increased in group A (mean 0.04 mmol/L) anddecreased in group B (mean 0.05 mmol/L). A total of 48 and 18 females(48%, 38%), respectively, met the previously validated criteria of pHPT.Altogether 21% of them were hypercalcemic (range 2.60 –3.12 mmol/L).Subgroup analysis showed that PTH had not increased with time (n 47)and that atherogenic blood lipids, but not glucose levels, were similar inpHPT patients and matched controls (n 37). Assuming the existence ofpHPT already at screening, the prevalence of pHPT could be adjusted to3.4%. Even the most liberal diagnostic criteria utilized at pHPT screeningseemed to underdiagnose the disease by inefficient cutoff limits for scalciumand PTH. Because one-fifth of the women with pHPT progressedto hypercalcemia, long-term follow-up is advocated for those with scalciumin the upper normal range.
|
|
| 4. |
- Malyukova, Alena, et al.
(author)
-
Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia
- 2024
-
In: Genome Biology. - 1474-7596 .- 1474-760X. ; 25:1
-
Journal article (peer-reviewed)abstract
- Background: Targeted therapies exploiting vulnerabilities of cancer cells hold promise for improving patient outcome and reducing side-effects of chemotherapy. However, efficacy of precision therapies is limited in part because of tumor cell heterogeneity. A better mechanistic understanding of how drug effect is linked to cancer cell state diversity is crucial for identifying effective combination therapies that can prevent disease recurrence. Results: Here, we characterize the effect of G2/M checkpoint inhibition in acute lymphoblastic leukemia (ALL) and demonstrate that WEE1 targeted therapy impinges on cell fate decision regulatory circuits. We find the highest inhibition of recovery of proliferation in ALL cells with KMT2A-rearrangements. Single-cell RNA-seq and ATAC-seq of RS4;11 cells harboring KMT2A::AFF1, treated with the WEE1 inhibitor AZD1775, reveal diversification of cell states, with a fraction of cells exhibiting strong activation of p53-driven processes linked to apoptosis and senescence, and disruption of a core KMT2A-RUNX1-MYC regulatory network. In this cell state diversification induced by WEE1 inhibition, a subpopulation transitions to a drug tolerant cell state characterized by activation of transcription factors regulating pre-B cell fate, lipid metabolism, and pre-BCR signaling in a reversible manner. Sequential treatment with BCR-signaling inhibitors dasatinib, ibrutinib, or perturbing metabolism by fatostatin or AZD2014 effectively counteracts drug tolerance by inducing cell death and repressing stemness markers. Conclusions: Collectively, our findings provide new insights into the tight connectivity of gene regulatory programs associated with cell cycle and cell fate regulation, and a rationale for sequential administration of WEE1 inhibitors with low toxicity inhibitors of pre-BCR signaling or metabolism.
|
|
| 5. |
- Pilheden, Mattias, et al.
(author)
-
Duplex sequencing uncovers recurrent low-frequency cancer-associated mutations in infant and childhood KMT2A-rearranged acute leukemia
- 2022
-
In: HemaSphere. - : Wolters Kluwer. - 2572-9241. ; 6:10
-
Journal article (peer-reviewed)abstract
- Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3D835H or NRASG13D/G12S mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
|
|
| 6. |
- Qadri, Sami, et al.
(author)
-
Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease
- 2022
-
In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:5, s. e2008-e2020
-
Journal article (peer-reviewed)abstract
- Context: Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity. Objective: To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD. Design: Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3). Setting: Tertiary referral center. Patients: We recruited overweight/obese patients from endocrinology (n = 307) and hepatology (n = 71) clinics undergoing a liver biopsy [median body mass index (BMI) 40.3 (interquartile range 36.0-44.7) kg/m(2)]. Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cutoffs for NFS. Main Outcome Measures: Biomarker area under the receiver operating characteristic (AUROC), sensitivity, specificity, and predictive values to identify histological stage >= F3 fibrosis or nonalcoholic steatohepatitis with >= F2 fibrosis [fibrotic nonalcoholic steatohepatitis (NASH)]. Results: The scores with an AUROC >= 0.85 to identify >= F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cutoffs for NFS to rule in/out >= F3 fibrosis in groups with BM Is <30.0, 30.0 to 39.9, and >= 40.0 kg/m(2). This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose >= F3 fibrosis. Conclusions: In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cutoffs.
|
|
| 7. |
|
|
| 8. |
- Rivano Eckerdal, Johanna, et al.
(author)
-
Qualitative questionnaires as a method for information studies research
- 2017
-
In: Information Research. - 1368-1613. ; 22:1
-
Journal article (peer-reviewed)abstract
- Introduction. We present qualitative questionnaires, originally an ethnological method for documenting and collecting material about everyday life, as a fruitful method for information studies. Method. Since the early 20th century qualitative questionnaires, on various themes, have been sent out to informants. The answers to qualitative questionnaires consist of memories, opinions and experiences. Most archives working with questionnaires have regular informants who have enrolled because they are interested in sharing their knowledge of and views on everyday life. The paper starts with a brief presentation of the development of the method followed by a discussion about how answers to qualitative questionnaires may be analysed to benefit the most from the specifics of this tool. Examples from two studies based on material from the Mass Observation Archive, University of Sussex, and the Folklife Archives, Lund University, are introduced. The examples are chosen to illustrate two possible ways to adopt this method: to re-use an existing questionnaire and to create a new one. Conclusion. Qualitative questionnaires generate a rich material, useful for researchers from many disciplines. The material provided by the respondents is highly informative of various aspects of everyday life, past and present, and merits more attention from scholars
|
|
| 9. |
- Sixtensson, Johanna, et al.
(author)
-
Risk, discomfort and disruption: experiences of (im)mobilitiesin public spaces among Swedish youth racialised as non-white
- 2024
-
In: Journal of Youth Studies. - : Taylor & Francis. - 1367-6261 .- 1469-9680.
-
Journal article (peer-reviewed)abstract
- Mobility can be understood as both an everyday part of, and a normative imperative in, young people’s lives. It is also an unequally distributed resource. Based on interviews and focus groups with people in their teens, this article analyses how young people racialised as non-white experience (im)mobility in public spaces in Sweden. Drawing on Sarah Ahmed’s theorising, the article discusses how spaces are experienced in the racialised social-spatial order of Stockholm and Malmö. The analysis shows that the negative reactions of others, such as ‘looks’ and ‘comments’, in places perceived as white (Swedish) makes the young people feel unwelcome and disrupt their mobility. The young people’s experiences correspond to overall societal patterns of racialisation and segregation within these cities and Sweden as a whole. The analysis also shows that the young people express aversion towards visiting certain spaces or talk about complete withdrawal from spaces seen as risky. To analyse such responses of ‘being stopped’ we introduce the concepts of ‘socio-spatial reluctance’ and ‘socio-spatial withdrawal’. The article concludes that youth spatial mobilities must be understood as restricted by racialised structures, which affect not only where this category of young people feel safe to go but also what they can do.
|
|
| 10. |
|
|
