| 1. |
- Malmström, Erik, et al.
(author)
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The importance of fibroblasts in remodelling of the human uterine cervix during pregnancy and parturition.
- 2007
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In: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 13, s. 333-341
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Journal article (peer-reviewed)abstract
- It is well established that fibroblasts play a crucial role in pathophysiological extracellular matrix remodelling. The aim of this project is to elucidate their role in normal physiological remodelling. Specifically, the remodelling of the human cervix during pregnancy, resulting in an enabled passage of the child, is used as the model system. Fibroblast cultures were established from cervices of non-pregnant women, women after 36 weeks of pregnancy and women directly after partus. The cells were immunostained and quantified by western blots for differentiation markers. The cultures were screened for cytokine and metalloproteinase production and characterized by global proteome analysis. The cell cultures established from partal donors differ significantly from those from non-pregnant donors, which is in accordance with in vivo findings. A decrease in alpha-smooth actin and prolyl-4hydroxylase and an increase in interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMP)-1 and MMP-3 were observed in cultures from partal donors. 2D-gel electrophoresis followed by mass spectrometry showed that the expression of 59 proteins was changed significantly in cultures of partal donors. The regulated proteins are involved in protein kinase C signalling, Ca2+ binding, cytoskeletal organization, angiogenesis and degradation. Our data suggest that remodelling of the human cervix is orchestrated by fibroblasts, which are activated or recruited by the inflammatory processes occurring during the ripening cascade.
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| 2. |
- Raghavan, Maanasa, et al.
(author)
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The genetic prehistory of the New World Arctic
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6200, s. 1020-
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Journal article (peer-reviewed)abstract
- The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (similar to 3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.
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| 3. |
- Bergfeldt, Nora, et al.
(author)
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Identification of microbial pathogens in Neolithic Scandinavian humans
- 2024
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In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
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Journal article (peer-reviewed)abstract
- With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.
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| 4. |
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| 5. |
- Eriksson, Anna, et al.
(author)
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Optimized Protocol for On-Target Phosphopeptide Enrichment Prior to Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry Using Mesoporous Titanium Dioxide
- 2010
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 82:11, s. 4577-4583
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Journal article (peer-reviewed)abstract
- A novel on-target phosphopeptide enrichment method is presented that allows specific enrichment and direct analysis by matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS) of phosphorylated peptides. Spots consisting of a thin film of anatase titanium dioxide are sintered onto a conductive glass surface. Enrichment and analysis can be performed on the modified target with minimal sample handling. The protocol leads to an enrichment efficiency that is superior to what has been reported before for similar methods. The method was tested using beta-casein as a model phosphorylated protein as well as with a custom peptide mixed with its phosphorylated form. A very low detection limit, a significantly improved phosphoprofiling capability, and a simple experimental approach provide a powerful tool for the enrichment, detection, and analysis of phosphopeptides.
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| 6. |
- Gerstner, Christina, et al.
(author)
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Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted alpha-Enolase T Cell Epitope in Rheumatoid Arthritis
- 2016
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 7
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Journal article (peer-reviewed)abstract
- Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from alpha-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified alpha-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLFRAAVPSGAS), the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFCitAAVPSGAS) elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the posttranslational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes, this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue.
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| 7. |
- Holmberg, Lars, et al.
(author)
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Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations
- 2024
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In: BJU INTERNATIONAL. - : Blackwell Publishing. - 1464-4096 .- 1464-410X.
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Journal article (peer-reviewed)abstract
- ObjectivesTo investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guerin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC).Patients and MethodsWe analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs.ResultsThe cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk.ConclusionsThese data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.
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| 10. |
- Patel, Mitesh, et al.
(author)
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Change of Body Movement Coordination during Cervical Proprioceptive Disturbances with Increased Age.
- 2010
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In: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 56, s. 284-290
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Journal article (peer-reviewed)abstract
- Background: To date, there are very few studies on postural stability in older adults using body movement recordings to capture the postural movement pattern. Moreover, the importance of proprioception at key areas such as the calf or neck on the postural movement pattern in older adults has rarely been investigated. Objective: To investigate whether the body movement coordination strategy to calf or neck vibration was affected by aging. Methods: Body movement measurements were taken at five locations (ankle, knee, hip, shoulder and head) from 18 younger (mean age 29.1 years) and 16 older (mean age 71.5 years) adult subjects using a 3D movement measuring system while subjected to 50 s of pseudo-random calf or neck vibratory stimulation pulses with eyes open or closed. The positions from the knee, hip, shoulder and head markers were correlated against one another to give an indication of the body coordination. Results: During quiet standing, older adults had greater correlation between the head and trunk than the young. There was an age effect in the body movement coordination strategy. Older adults had a different movement pattern with neck vibration involving mainly more independent knee movements, indicating balance difficulty. Conclusions: Neck vibration affects the movement pattern in older adults more compared with younger adults and calf vibration, suggesting that, the regulation of body orientation in older adults is more difficult, especially during cervical proprioceptive disturbances.
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