| 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. |
- Filipowicz, Natalia, et al.
(författare)
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Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
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| 3. |
- Gisslander, Karl, et al.
(författare)
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Data quality and patient characteristics in European ANCA-associated vasculitis registries : data retrieval by federated querying
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - 0003-4967. ; 83:1, s. 112-120
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. Methods Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. Results A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. Conclusions In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
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| 4. |
- Koczkowska, Magdalena, et al.
(författare)
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Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband's long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis. Although comprehensive cytogenetic analysis showed seemingly near perfect balance between 45, X and 48, XYYY cell populations, scRNA-seq revealed widespread differences in genotype distribution among immune cell fractions, specifically in monocytes, B- and T-cells. These results were confirmed at DNA level by digital-droplet PCR on flow-sorted immune cell types. Furthermore, deregulation of predominantly autosomal genes was observed, including TCL1A overexpression in 45, X B-lymphocytes and other known genes associated with hematological malignancies. Together with the standard hematological results, showing increased fractions of monocytes and CD4+/CD8+T lymphocytes ratio, long-term personalized hemato-oncological surveillance was recommended in the reported patient.
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| 5. |
- Płódowska, Magdalena, et al.
(författare)
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Hypothermia differentially modulates the formation and decay of NBS1, γH2AX and 53BP1 foci in U2OS cells exposed to gamma radiation
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- In studies on the mechanism of DNA damage response where ionizing radiation is used as the DNA damaging agent, cells are often exposed to ionizing radiation on melting ice (corresponding to 0.8 °C). The purpose of this procedure is to inhibit cellular processes i.e. DNA repair. Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage, but its mechanisms of action are poorly understood. The aim of the study was to analyze the effect of hypothermia at the level of formation and decay of NBS1, γH2AX, and 53BP1 foci, micronuclei, survival, cell cycle progression and oxidative stress in U2OS cells. The results show that hypothermia alone induced oxidative stress and foci. When applied in combination with radiation but only during the exposure time, it potentiated the formation of γH2AX and 53BP1 but not of NBS1 foci. When applied during irradiation and subsequent repair time, 53BP1 and NBS1 foci formed and decayed, but the levels were markedly lower than when repair was carried out at 37 °C. The frequency of micronuclei was elevated in cells irradiated at 0.8 °C, but only when analysed 20 h after irradiation which is likely due to a reduced G2 cell cycle block. Hypothermia reduced cell survival, both with and without radiation exposure. The temperature effect should be considered when cooling cells on melting ice to inhibit DNA repair in the induction of DNA damage.
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| 6. |
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| 7. |
- Scholz, Marek, et al.
(författare)
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Conceptual design of the high resolution neutron spectrometer for ITER
- 2019
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Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 59:6
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Tidskriftsartikel (refereegranskat)abstract
- A high resolution neutron spectrometer (HRNS) system has been designed as a neutron diagnostic tool for ITER. The HRNS is dedicated to measurements of time resolved neutron energy spectra for both deuterium and deuterium-tritium (DT) plasmas. The main function of the HRNS is to determine the fuel ion ratio n(t)/n(d) in the plasma core with 20% uncertainty and a time resolution of 100ms for a range of ITER operating scenarios from 0.5 MW to 500 MW in fusion power. Moreover, neutron spectroscopy measurements should also be possible in the initial deuterium phase of ITER experiments. A supplementary function of the HRNS is to provide information on the fuel ion temperature. Furthermore, the HRNS can be used as an additional line-of-sight (LOS) for the radial neutron camera. To meet these requirements, a set of four spectrometers positioned after each other along a single LOS has been designed. The detector techniques employed include a thin foil proton recoil spectrometer (TPR), a neutron diamond detector (NDD), a back-scattering time-of-flight system (bToF) and a forward timeof-flight system (fToF). The TPR system, positioned closest to the plasma, provides data at high fusion powers. For plasma conditions producing intermediate fusion power two neutron spectrometers are installed: NDD and bToF. The NDD is installed as the second instrument along the HRNS LOS after the TPR. The fToF spectrometer is dedicated for low tritium densities and pure deuterium operation. The paper summarizes the current state of the art of neutron spectroscopy useful in plasma diagnostics and the possibility of installing a dedicated HRNS for ITER in the designated diagnostic port. We conclude that the proposed HRNS system can fulfil the ITER measurement requirements over a broad range of plasma operational scenarios, including full power DT, start-up, ramp-down and pure D operations.
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| 8. |
- Wojcik, Krzysztof P., et al.
(författare)
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Giant superconducting proximity effect on spintronic anisotropy
- 2019
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- We investigate theoretically the interplay of proximity effects due to the presence of a superconductor and normal ferromagnetic leads on the formation of the spintronic quadrupolar exchange field in a large-spin molecule. We show that the spintronic anisotropy can be enhanced by a few orders of magnitude and tuned by changing the strength of coupling to the superconductor. Especially large anisotropy is generated in the vicinity of the charge parity changing transition of the molecule. We also provide predictions of measurable spectral properties being the hallmarks of these phenomena.
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