7 results on '"Lisa Böhme"'
Search Results
2. Comparison of target enrichment strategies for ancient pathogen DNA
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Anja Furtwängler, Judith Neukamm, Lisa Böhme, Ella Reiter, Melanie Vollstedt, Natasha Arora, Pushpendra Singh, Stewart T Cole, Sascha Knauf, Sébastien Calvignac-Spencer, Ben Krause-Kyora, Johannes Krause, Verena J Schuenemann, and Alexander Herbig
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ancient DNA ,high-throughput sequencing ,hybridization capture ,Mycobacterium leprae ,pathogen DNA ,target enrichment ,Biology (General) ,QH301-705.5 - Abstract
In ancient DNA research, the degraded nature of the samples generally results in poor yields of highly fragmented DNA; targeted DNA enrichment is thus required to maximize research outcomes. The three commonly used methods – array-based hybridization capture and in-solution capture using either RNA or DNA baits – have different characteristics that may influence the capture efficiency, specificity and reproducibility. Here we compare their performance in enriching pathogen DNA of Mycobacterium leprae and Treponema pallidum from 11 ancient and 19 modern samples. We find that in-solution approaches are the most effective method in ancient and modern samples of both pathogens and that RNA baits usually perform better than DNA baits.
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- 2020
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3. The Chk1 inhibitor SAR-020106 sensitizes human glioblastoma cells to irradiation, to temozolomide, and to decitabine treatment
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Ina Patties, Sonja Kallendrusch, Lisa Böhme, Eva Kendzia, Henry Oppermann, Frank Gaunitz, Rolf-Dieter Kortmann, and Annegret Glasow
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Glioblastoma ,Chk1 inhibitor ,SAR-020106 ,Decitabine ,Irradiation ,Temozolomide ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Glioblastoma is the most common and aggressive brain tumour in adults with a median overall survival of only 14 months after standard therapy with radiation therapy (IR) and temozolomide (TMZ). In a novel multimodal treatment approach we combined the checkpoint kinase 1 (Chk1) inhibitor SAR-020106 (SAR), disrupting homologue recombination, with standard DNA damage inducers (IR, TMZ) and the epigenetic/cytotoxic drug decitabine (5-aza-2′-deoxycitidine, 5-aza-dC). Different in vitro glioblastoma models are monitored to evaluate if the impaired DNA damage repair may chemo/radiosensitize the tumour cells. Methods Human p53-mutated (p53-mut) and -wildtype (p53-wt) glioblastoma cell lines (p53-mut: LN405, T98G; p53-wt: A172, DBTRG) and primary glioblastoma cells (p53-mut: P0297; p53-wt: P0306) were treated with SAR combined with TMZ, 5-aza-dC, and/or IR and analysed for induction of apoptosis (AnnexinV and sub-G1 assay), cell cycle distribution (nuclear PI staining), DNA damage (alkaline comet or gH2A.X assay), proliferation inhibition (BrdU assay), reproductive survival (clonogenic assay), and potential tumour stem cells (nestinpos/GFAPneg fluorescence staining). Potential treatment-induced neurotoxicity was evaluated on nestin-positive neural progenitor cells in a murine entorhinal-hippocampal slice culture model. Results SAR showed radiosensitizing effects on the induction of apoptosis and on the reduction of long-term survival in p53-mut and p53-wt glioblastoma cell lines and primary cells. In p53-mut cells, this effect was accompanied by an abrogation of the IR-induced G2/M arrest and an enhancement of IR-induced DNA damage by SAR treatment. Also TMZ and 5-aza-dC acted radioadditively albeit to a lesser extent. The multimodal treatment achieved the most effective reduction of clonogenicity in all tested cell lines and did not affect the ratio of nestinpos/GFAPneg cells. No neurotoxic effects were detected when the number of nestin-positive neural progenitor cells remained unchanged after multimodal treatment. Conclusion The Chk1 inhibitor SAR-020106 is a potent sensitizer for DNA damage-induced cell death in glioblastoma therapy strongly reducing clonogenicity of tumour cells. Selectively enhanced p53-mut cell death may provide stronger responses in tumours defective of non-homologous end joining (NHEJ). Our results suggest that a multimodal therapy involving DNA damage inducers and DNA repair inhibitors might be an effective anti-tumour strategy with a low risk of neurotoxicity.
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- 2019
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4. Genome-wide study of a Neolithic Wartberg grave community reveals distinct HLA variation and hunter-gatherer ancestry
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Tobias L. Lenz, Frederica Pierini, Lisa Böhme, Joanna H. Bonczarowska, Janina Dose, Almut Nebel, Johannes Müller, Sabine Schade-Lindig, Rodrigo Barquera, Clara Drummer, Oliver Kohlbacher, Alexander Immel, Andre Franke, Martin Furholt, John Meadows, Julian Susat, David Ellinghaus, András Szolek, Stefan Schreiber, Christoph Rinne, Katharina Fuchs, Jan Christian Kässens, Ben Krause-Kyora, and Johannes Krause
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0301 basic medicine ,Population genetics ,QH301-705.5 ,Human Migration ,Population ,Medicine (miscellaneous) ,Human leukocyte antigen ,Biology ,Genome ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Article ,Evolution, Molecular ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,Residence Characteristics ,Germany ,Animals ,Humans ,DNA, Ancient ,Biology (General) ,education ,Hunter-gatherer ,History, Ancient ,education.field_of_study ,Genome, Human ,Racial Groups ,Genetic Variation ,Agriculture ,Feeding Behavior ,Europe ,030104 developmental biology ,Genetics, Population ,Human leukocyte antigen gene ,Archaeology ,Evolutionary biology ,Western europe ,Predatory Behavior ,Molecular evolution ,General Agricultural and Biological Sciences ,030217 neurology & neurosurgery ,Genome-Wide Association Study ,Coevolution - Abstract
The Wartberg culture (WBC, 3500-2800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We performed genome-wide analyses of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3300-3200 cal. BCE). The results showed that the farming population of Niedertiefenbach carried a surprisingly large hunter-gatherer ancestry component (34–58%). This component was most likely introduced during the cultural transformation that led to the WBC. In addition, the Niedertiefenbach individuals exhibited a distinct human leukocyte antigen gene pool, possibly reflecting an immune response that was geared towards detecting viral infections., Alexander Immel et al. performed genome-wide analyses of 42 individuals from a collective burial in Niedertiefenbach, Germany from the Wartberg Culture. The authors find that this population had a large hunter-gatherer ancestry component and a distinct HLA pool, which indicates immune defenses against viral pathogens.
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- 2021
5. Targeted analysis of polymorphic loci from low-coverage shotgun sequence data allows accurate genotyping of HLA genes in historical human populations
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Ben Krause-Kyora, Onur Özer, Almut Nebel, Joanna H. Bonczarowska, Federica Pierini, Tobias L. Lenz, Lisa Böhme, Marcel Nutsua, Andre Franke, and Julian Susat
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Genetic Markers ,0301 basic medicine ,Genotype ,Population genetics ,Denmark ,Adaptive immunity ,Population ,lcsh:Medicine ,Evolutionary biology ,Human leukocyte antigen ,Computational biology ,Biology ,Polymorphism, Single Nucleotide ,Genome ,Article ,Evolutionary genetics ,Pattern Recognition, Automated ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,Immunogenetics ,Humans ,Sequencing ,DNA, Ancient ,1000 Genomes Project ,lcsh:Science ,education ,Genotyping ,Alleles ,education.field_of_study ,Multidisciplinary ,Genome, Human ,Palaeontology ,lcsh:R ,Haplotype ,Histocompatibility Antigens Class II ,High-Throughput Nucleotide Sequencing ,Genetics, Population ,030104 developmental biology ,Ancient DNA ,Haplotypes ,Genetic marker ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
The highly polymorphic human leukocyte antigen (HLA) plays a crucial role in adaptive immunity and is associated with various complex diseases. Accurate analysis of HLA genes using ancient DNA (aDNA) data is crucial for understanding their role in human adaptation to pathogens. Here, we describe the TARGT pipeline for targeted analysis of polymorphic loci from low-coverage shotgun sequence data. The pipeline was successfully applied to medieval aDNA samples and validated using both simulated aDNA and modern empirical sequence data from the 1000 Genomes Project. Thus the TARGT pipeline enables accurate analysis of HLA polymorphisms in historical (and modern) human populations.
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- 2020
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6. Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe
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Clara Drummer, Janina Dose, Oliver Kohlbacher, Ben Krause-Kyora, Lisa Böhme, Alexander Immel, Jan Christian Kässens, Almut Nebel, Martin Furholt, David Ellinghaus, Iain Mathieson, Tobias L. Lenz, Katharina Fuchs, Rodrigo Barquera, Julian Susat, Johannes Müller, Andre Franke, Johannes Krause, András Szolek, John Meadows, Joanna H. Bonczarowska, Federica Pierini, Christoph Rinne, and Schade-Lindig S
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education.field_of_study ,Human leukocyte antigen gene ,Genetic heterogeneity ,Evolutionary biology ,Western europe ,Population ,Human leukocyte antigen ,Allele ,Biology ,education ,Genome - Abstract
The Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.
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- 2019
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7. Emerging Opportunities Provided by Technology to Advance Research in Child Health Globally
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Alastair van Heerden PhD, Jukka Leppanen PhD, Mary Jane Rotheram-Borus PhD, Carol M. Worthman PhD, Brandon A. Kohrt PhD, Sarah Skeen PhD, Sonja Giese BSc (Hon), Rob Hughes MB ChB, MPH, Lisa Bohmer MPH, and Mark Tomlinson PhD
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Pediatrics ,RJ1-570 - Abstract
Current approaches to longitudinal assessment of children’s developmental and psychological well-being, as mandated in the United Nations Sustainable Development Goals, are expensive and time consuming. Substantive understanding of global progress toward these goals will require a suite of new robust, cost-effective research tools designed to assess key developmental processes in diverse settings. While first steps have been taken toward this end through efforts such as the National Institutes of Health’s Toolbox, experience-near approaches including naturalistic observation have remained too costly and time consuming to scale to the population level. This perspective presents 4 emerging technologies with high potential for advancing the field of child health and development research, namely (1) affective computing, (2) ubiquitous computing, (3) eye tracking, and (4) machine learning. By drawing attention of scientists, policy makers, investors/funders, and the media to the applications and potential risks of these emerging opportunities, we hope to inspire a fresh wave of innovation and new solutions to the global challenges faced by children and their families.
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- 2020
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