| 1. |
- Chylenski, Maciej, et al.
(författare)
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Patrilocality and hunter-gatherer-related ancestry of populations in East-Central Europe during the Middle Bronze Age
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The demographic history of East-Central Europe after the Neolithic period remains poorly explored, despite this region being on the confluence of various ecological zones and cultural entities. Here, the descendants of societies associated with steppe pastoralists form Early Bronze Age were followed by Middle Bronze Age populations displaying unique characteristics. Particularly, the predominance of collective burials, the scale of which, was previously seen only in the Neolithic. The extent to which this re-emergence of older traditions is a result of genetic shift or social changes in the MBA is a subject of debate. Here by analysing 91 newly generated genomes from Bronze Age individuals from present Poland and Ukraine, we discovered that Middle Bronze Age populations were formed by an additional admixture event involving a population with relatively high proportions of genetic component associated with European hunter-gatherers and that their social structure was based on, primarily patrilocal, multigenerational kin-groups. By analysing 91 Bronze Age genomes from East-Central Europe, the authors discovered that Middle Bronze Age populations were formed by an admixture event involving hunter-gatherers and that the social structure of resulting population was primarily patrilocal.
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| 2. |
- Elowsson Rendin, Linda, et al.
(författare)
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Matrisome Properties of Scaffolds Direct Fibroblasts in Idiopathic Pulmonary Fibrosis
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:16
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Tidskriftsartikel (refereegranskat)abstract
- In idiopathic pulmonary fibrosis (IPF) structural properties of the extracellular matrix (ECM) are altered and influence cellular responses through cell-matrix interactions. Scaffolds (decellularized tissue) derived from subpleural healthy and IPF lungs were examined regarding biomechanical properties and ECM composition of proteins (the matrisome). Scaffolds were repopulated with healthy fibroblasts cultured under static stretch with heavy isotope amino acids (SILAC), to examine newly synthesized proteins over time. IPF scaffolds were characterized by increased tissue density, stiffness, ultimate force, and differential expressions of matrisome proteins compared to healthy scaffolds. Collagens, proteoglycans, and ECM glycoproteins were increased in IPF scaffolds, however while specific basement membrane (BM) proteins such as laminins and collagen IV were decreased, nidogen-2 was also increased. Findings were confirmed with histology, clearly showing a disorganized BM. Fibroblasts produced scaffold-specific proteins mimicking preexisting scaffold composition, where 11 out of 20 BM proteins were differentially expressed, along with increased periostin and proteoglycans production. We demonstrate how matrisome changes affect fibroblast activity using novel approaches to study temporal differences, where IPF scaffolds support a disorganized BM and upregulation of disease-associated proteins. These matrix-directed cellular responses emphasize the IPF matrisome and specifically the BM components as important factors for disease progression.
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| 3. |
- Bahnan, Wael, et al.
(författare)
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Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
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| 4. |
- Ehinger, Anna, et al.
(författare)
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Histological grade provides significant prognostic information in addition to breast cancer subtypes defined according to St Gallen 2013
- 2017
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Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 56:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Background: The St Gallen surrogate definition of the intrinsic subtypes of breast cancer consist of five subgroups based on estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2), and Ki-67. PgR and Ki-67 are used for discriminating between the Luminal A-like and Luminal B-like (HER2-negative) subtypes. Histological grade (G) has prognostic value in breast cancer; however, its relationship to the St Gallen subtypes is not clear. Based on a previous pilot study, we hypothesized that G could be a primary discriminator for ER-positive/HER2-negative breast cancers that were G1 or G3, whereas Ki-67 and PgR could provide additional prognostic information specifically for patients with G2 tumors. To test this hypothesis, a larger patient cohort was examined. Patients and methods: Six hundred seventy-one patients (amp;gt;= 35 years of age, pT1-2, pN0-1) with ER-positive/HER2-negative breast cancer and complete data for PgR, Ki-67, G, lymph node status, tumor size, age, and distant disease-free survival (DDFS; median follow-up 9.2 years) were included. Results: Luminal A-like tumors were mostly G1 or G2 (90%) whereas Luminal B-like tumors were mostly G2 or G3 (87%) and corresponded with good and poor DDFS, respectively. In Luminal B-like tumors that were G1 (n = 23), no metastasis occurred, whereas 14 of 40 Luminal A-like tumors that were G3 metastasized. In the G2 subgroup, low PgR and high Ki-67 were associated with an increased risk of distant metastases, hazard ratio (HR) and 95% confidence interval (CI) 1.8 (0.95-3.4) and 1.5 (0.80-2.8), respectively. Conclusions: Patients with ER-positive/HER2-negative/G1 breast cancer have a good prognosis, similar to that of Luminal A-like, while those with ER-positive/HER2-negative/G3 breast cancer have a worse prognosis, similar to that of Luminal B-like, when assessed independently of PgR and Ki-67. Therapy decisions based on Ki-67 and PgR might thus be restricted to the subgroup G2.
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| 5. |
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| 6. |
- Eriksson, Irene, et al.
(författare)
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The Early Awareness and Alert System in Sweden : History and Current Status
- 2017
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 8
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Forskningsöversikt (refereegranskat)abstract
- The Swedish EAA System started as a regional initiative and rapidly grew to become a national level activity. An important feature of the system today is its complete integration into the national process for managed introduction and follow-up of new medicines. The system will continue to evolve as a response both to the changing landscape of health innovations and to new policy initiatives at the regional, national and international level.
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| 7. |
- Governa, Valeria, et al.
(författare)
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Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:9
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic strategies directed at the tumor surfaceome (TS), including checkpoint inhibitor blocking antibodies, antibody drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cells, provide a new armament to fight cancer. However, a remaining bottleneck is the lack of strategies to comprehensively interrogate patient tumors for potential TS targets. Here, we have developed a platform (tumor surfaceome mapping [TS-MAP]) integrated with a newly curated TS classifier (SURFME) that allows profiling of primary 3D cultures and intact patient glioma tumors with preserved tissue architecture. Moreover, TS-MAP specifically identifies proteins capable of endocytosis as tractable targets for ADCs and other modalities requiring toxic payload internalization. In high-grade gliomas that remain among the most aggressive forms of cancer, we show that cellular spatial organization (2D vs. 3D) fundamentally transforms the surfaceome and endocytome (e.g., integrins, proteoglycans, semaphorins, and cancer stem cell markers) with general implications for target screening approaches, as exemplified by an ADC targeting EGFR. The TS-MAP platform was further applied to profile the surfaceome and endocytome landscape in a cohort of freshly resected gliomas. We found a highly diverse TS repertoire between patient tumors, not directly associated with grade and histology, which highlights the need for individualized approaches. Our data provide additional layers of understanding fundamental to the future development of immunotherapy strategies, as well as procedures for proteomics-based target identification and selection. The TS-MAP platform should be widely applicable in efforts aiming at a better understanding of how to harness the TS for personalized immunotherapy.
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| 8. |
- Juras, Anna, et al.
(författare)
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Maternal genetic origin of the late and final Neolithic human populations from present-day Poland
- 2021
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Ingår i: American Journal of Physical Anthropology. - : Wiley. - 0002-9483 .- 1096-8644. ; 176:2, s. 223-236
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aim to identify maternal genetic affinities between the Middle to Final Neolithic (3850-2300 BC) populations from present-day Poland and possible genetic influences from the Pontic steppe.Materials and methods: We conducted ancient DNA studies from populations associated with Zlota, Globular Amphora, Funnel Beaker, and Corded Ware cultures (CWC). We sequenced genomic libraries on Illumina platform to generate 86 complete ancient mitochondrial genomes. Some of the samples were enriched for mitochondrial DNA using hybridization capture.Results: The maternal genetic composition found in Zlota-associated individuals resembled that found in people associated with the Globular Amphora culture which indicates that both groups likely originated from the same maternal genetic background. Further, these two groups were closely related to the Funnel Beaker culture-associated population. None of these groups shared a close affinity to CWC-associated people. Haplogroup U4 was present only in the CWC group and absent in Zlota group, Globular Amphora, and Funnel Beaker cultures.Discussion: The prevalence of mitochondrial haplogroups of Neolithic farmer origin identified in Early, Middle and Late Neolithic populations suggests a genetic continuity of these maternal lineages in the studied area. Although overlapping in time - and to some extent - in cultural expressions, none of the studied groups (Zlota, Globular Amphora, Funnel Beaker), shared a close genetic affinity to CWC-associated people, indicating a larger extent of cultural influence from the Pontic steppe than genetic exchange. The higher frequency of haplogroup U5b found in populations associated with Funnel Beaker, Globular Amphora, and Zlota cultures suggest a gradual maternal genetic influx from Mesolithic hunter-gatherers. Moreover, presence of haplogroup U4 in Corded Ware groups is most likely associated with the migrations from the Pontic steppe at the end of the Neolithic and supports the observed genetic distances.
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| 9. |
- Juras, Anna, et al.
(författare)
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Mitochondrial genomes from Bronze Age Poland reveal genetic continuity from the Late Neolithic and additional genetic affinities with the steppe populations
- 2020
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Ingår i: American Journal of Physical Anthropology. - : Wiley. - 0002-9483 .- 1096-8644. ; 172:2, s. 176-188
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In this work we aim to investigate the origins and genetic affinities of Bronze Age populations (2,400-1,100 BC) from the region of southern Poland and to trace maternal kinship patterns present in the burials of those populations by the use of complete mitochondrial genomes.Materials and methods: We performed ancient DNA analyses for Bronze Age individuals from present-day Poland associated with the Strzy(z) over dotow culture, the Mierzanowice culture, and the Trzciniec Cultural circle. To obtain complete mitochondrial genomes, we sequenced genomic libraries using Illumina platform. Additionally, hybridization capture was used to enrich some of the samples for mitochondrial DNA. AMS C-14-dating was conducted for 51 individuals to verify chronological and cultural attribution of the analyzed samples.Results: Complete ancient mitochondrial genomes were generated for 80 of the Bronze Age individuals from present-day Poland. The results of the population genetic analyses indicate close maternal genetic affinity between Mierzanowice, Trzciniec, and Corded Ware culture-associated populations. This is in contrast to the genetically more distant Strzy(z) over dotow people that displayed closer maternal genetic relation to steppe populations associated with the preceding Yamnaya culture and Catacomb culture, and with later Scythians. Potential maternal kinship relations were identified in burials of Mierzanowice and Trzciniec populations analyzed in this study.Discussion: Results revealed genetic continuity from the Late Neolithic Corded Ware groups to Bronze Age Mierzanowice and Trzciniec-associated populations, and possible additional genetic contribution from the steppe to the formation of the Strzy(z) over dotow-associated group at the end of 3rd millennium BC. Mitochondrial patterns indicated several pairs of potentially maternally related individuals mostly in Trzciniec-associated group.
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| 10. |
- Larsen, Kristoffer, et al.
(författare)
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Presence of activated mobile fibroblasts in bronchoalveolar lavage from patients with mild asthma
- 2004
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 170:10, s. 1049-1056
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Tidskriftsartikel (refereegranskat)abstract
- Activated fibroblasts are suggested to be involved in the deposition of extracellular matrix in the formation of peribronchial fibrosis in asthma. We report the novel finding of activated elongated fibroblasts accompanied by elevated numbers of eosinophils in bronchoalveolar lavage fluid from 5 out of 12 patients with mild asthma (= 42%), whereas no fibroblasts were observed in the control subjects without asthma (n = 17). The elongated fibroblasts migrated twice as far when compared with fibroblasts from corresponding bronchial biopsies from the same patients, accompanied by an induced expression of RhoA and Rac1, indicating that the increased expression of these proteins are linked to increased migratory capabilities. Moreover, the elongated fibroblasts had an elevated production of the proteoglycans biglycan, versican, perlecan, and decorin, which correlated to an active cytoplasm in these cells. Differential expression patterns between the two fibroblast groups in motility-regulating proteins, such as cofilin, nuclear chloride ion channel protein, and heat-shock protein 20, were identified by two-dimensional electrophoresis and mass spectrometry. These findings indicate the presence of activated and mobile fibroblasts accompanied by an induced inflammatory response outside the airway epithelium in patients with mild asthma, results that may play a role in formation of airway fibrosis.
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