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Schwalbe, E.

Publications and source records attributed to Schwalbe, E..

2 recordsLinked to original sources
bioRxiv2020

The Effects of Inter-Individual Biological Differences and Taphonomic Alteration on Human Bone Protein Profiles: Implications for the Development of PMI/AAD Estimation Methods

Bone proteomics studies using animal proxies and skeletonized human remains have delivered encouraging results in the search for potential biomarkers for precise and accurate post-mortem interval (PMI) and the age-at-death (AAD) estimation in medico-legal investigations. At present, however, the effects of inter-individual biological differences and taphonomic alteration on recovered human bone protein profiles are not well understood. This study investigated the human bone proteome in four human body donors studied throughout decomposition outdoors. The effects of ageing phenomena (in vivo and post-mortem), and intrinsic and extrinsic variables on the variety and abundancy of the bone proteome were assessed. Results identified a new potential biomarker for PMI estimation, as well as three potential biomarkers for AAD estimation. The results also suggest that bone mineral density (BMD) may be an important variable affecting the survival and extraction of proteins. Highlights- CO3, CO9, COBA2, CO3A1, MGP, PGS2 and TTHY are potential biomarkers for post-mortem interval estimation in skeletonized human remains - FETUA, ALBU and OLFL3 are potential biomarkers for age-at-death estimation in human remains - Taphonomic and biological variables play a significant role in survival and extraction rates of proteins in bone - Bone mineral density may affect survival of proteins in bone, probably due to the effects of the mineral matrix on the movement of decomposer microbes - Higher bone mineral density may affect the survival and the extraction rate of collagen and mineral-binding proteins

biochemistry↗
bioRxiv2019

Epigenetic dysregulation underpins tumorigenesis in a cutaneous tumor syndrome.

Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes 1,2. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel driver mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic and methylation profiling suggest that mutated DNMT3A drives tumorigenesis mechanistically through Wnt/{beta}-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm the phenomenon of benign pulmonary metastases from primary skin lesions. In malignant tumors, additional epigenetic modifiers MBD4, CREBBP, KDM6A and EP300 were mutated. We thus present epigenetic dysregulation as a driver in CCS tumorigenesis and propose this may account for the diverse histophenotypic patterns despite the paucity of mutations seen. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.

cancer biology↗