ORCID Profile
0000-0002-4747-4938
Current Organisation
IT University of Copenhagen
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Cold Spring Harbor Laboratory
Date: 10-09-2018
DOI: 10.1101/407692
Abstract: Ancient DNA (aDNA) sequencing has enabled unprecedented reconstruction of speciation, migration, and admixture events for extinct taxa 1 . Outside the permafrost, however, irreversible aDNA post-mortem degradation 2 has so far limited aDNA recovery within the ˜0.5 million years (Ma) time range 3 . Tandem mass spectrometry (MS)-based collagen type I (COL1) sequencing provides direct access to older biomolecular information 4 , though with limited phylogenetic use. In the absence of molecular evidence, the speciation of several Early and Middle Pleistocene extinct species remain contentious. In this study, we address the phylogenetic relationships of the Eurasian Pleistocene Rhinocerotidae 5-7 using ˜1.77 million years (Ma) old dental enamel proteome sequences of a Stephanorhinus specimen from the Dmanisi archaeological site in Georgia (South Caucasus) 8 . Molecular phylogenetic analyses place the Dmanisi Stephanorhinus as a sister group to the woolly ( Coelodonta antiquitatis ) and Merck’s rhinoceros ( S. kirchbergensis ) clade. We show that Coelodonta evolved from an early Stephanorhinus lineage and that this genus includes at least two distinct evolutionary lines. As such, the genus Stephanorhinus is currently paraphyletic and its systematic revision is therefore needed. We demonstrate that Early Pleistocene dental enamel proteome sequencing overcomes the limits of ancient collagen- and aDNA-based phylogenetic inference, and also provides additional information about the sex and taxonomic assignment of the specimens analysed. Dental enamel, the hardest tissue in vertebrates, is highly abundant in the fossil record. Our findings reveal that palaeoproteomic investigation of this material can push biomolecular investigation further back into the Early Pleistocene.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.YEXMP.2015.11.009
Abstract: Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion, and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk. Tumor s les were obtained from colon cancer patients. Biopsies from tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction or in formalin and paraffin embedded (FFPE) for immunohistochemical staining. CDX2 mRNA expression was evaluated by RT-qPCR. FFPE sections were stained for MLH1, MSH2, MSH6, PMS2, and CDX2. A total of 191 patient s les were included in the study and analyzed by immunohistochemistry. Of these s les, 97 were further evaluated by RT-qPCR. There was no significant difference in CDX2 mRNA expression between tumor and normal tissues. CDX2 mRNA expression was significantly lower in right-sided tumors (p<0.05), poorly differentiated tumors (p<0.05), and MMR-deficient tumors (p<0.05). Similarly, CDX2 protein expression was more often low or absent in right-sided tumors (p<0.01), poorly differentiated tumors (p<0.001), and MMR-deficient tumors (p<0.001). Low CDX2 protein or mRNA expression was not associated with recurrence risk. We found that CDX2 downregulation is associated with MMR deficiency, right-sided tumors, and poor differentiation at both the mRNA and protein level. Whether CDX2 plays an active role in tumor progression in MSI/MMR-deficient tumors remains to be elucidated.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2019
Publisher: Springer Science and Business Media LLC
Date: 17-05-2022
DOI: 10.1038/S41467-022-29923-Z
Abstract: The Pleistocene presence of the genus Homo in continental Southeast Asia is primarily evidenced by a sparse stone tool record and rare human remains. Here we report a Middle Pleistocene hominin specimen from Laos, with the discovery of a molar from the Tam Ngu Hao 2 (Cobra Cave) limestone cave in the Annamite Mountains. The age of the fossil-bearing breccia ranges between 164–131 kyr, based on the Bayesian modelling of luminescence dating of the sedimentary matrix from which it was recovered, U-series dating of an overlying flowstone, and U-series–ESR dating of associated faunal teeth. Analyses of the internal structure of the molar in tandem with palaeoproteomic analyses of the enamel indicate that the tooth derives from a young, likely female, Homo in idual. The close morphological affinities with the Xiahe specimen from China indicate that they belong to the same taxon and that Tam Ngu Hao 2 most likely represents a Denisovan.
Publisher: American Chemical Society (ACS)
Date: 10-05-2012
DOI: 10.1021/PR3000249
Abstract: Advances in proteomics are continually driven by the introduction of new mass spectrometric instrumentation with improved performances. The recently introduced quadrupole Orbitrap (Q Exactive) tandem mass spectrometer allows fast acquisition of high-resolution higher-energy collisional dissociation (HCD) tandem mass spectra due to the parallel mode of operation, where the generation, filling, and storage of fragment ions can be performed while simultaneously measuring another ion packet in the Orbitrap mass analyzer. In this study, data-dependent acquisition methods for "fast" or "sensitive" scanning were optimized and assessed by comparing stable isotope labeled yeast proteome coverage. We discovered that speed was the most important parameter for s le loads above 125 ng, where a 95 ms HCD scanning method allowed for identification and quantification of more than 2000 yeast proteins from 1 h of analysis time. At s le loads below 125 ng, a 156 ms HCD acquisition method improved the sensitivity, mass accuracy, and quality of data and enabled us to identify 30% more proteins and peptides than the faster scanning method. A similar effect was observed when the LC gradient was extended to 2 or 3 h for the analysis of complex mammalian whole cell lysates. Using a 3 h LC gradient, the sensitive method enabled identification of more than 4000 proteins from 1 μg of tryptic HeLa digest, which was almost 200 more identifications compared to the faster scanning method. Our results demonstrate that peptide identification on a quadrupole Orbitrap is dependent on s le amounts, acquisition speed, and data quality, which emphasizes the need for acquisition methods tailored for different s le loads and analytical preferences.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2019
Publisher: Springer Science and Business Media LLC
Date: 22-06-2014
DOI: 10.1038/NG.3014
Publisher: Elsevier BV
Date: 06-2009
Publisher: Elsevier BV
Date: 09-2016
Publisher: Springer Science and Business Media LLC
Date: 06-11-2019
DOI: 10.1038/S41586-019-1732-Z
Abstract: Central to understanding cellular behaviour in multi-cellular organisms is the question of how a cell exits one transcriptional state to adopt and eventually become committed to another. Fibroblast growth factor-extracellular signal-regulated kinase (FGF -ERK) signalling drives differentiation of mouse embryonic stem cells (ES cells) and pre-implantation embryos towards primitive endoderm, and inhibiting ERK supports ES cell self-renewal
Publisher: American Chemical Society (ACS)
Date: 26-10-2010
DOI: 10.1021/PR100637Q
Abstract: Mass spectrometry (MS)-based proteomics now enables the analysis of thousands of phosphorylation sites in single projects. Among a wide range of analytical approaches, the combination of high resolution MS scans in an Orbitrap analyzer with low resolution MS/MS scans in a linear ion trap has proven to be particularly successful ("high-low" strategy). Here we investigate if the improved sensitivity of higher energy collisional dissociation (HCD) on an LTQ-Orbitrap Velos instrument allows a "high-high" strategy. A high resolution MS scan was followed by up to 10 HCD MS/MS scans, and we achieved cycle times of about 3 s making the method compatible with chromatographic time scales. Fragment mass accuracy increased about 50-fold compared to the "high-low" strategy. Unexpectedly, the HCD approach mapped up to 16,000 total phosphorylation sites in one day's measuring time--the same or better than the standard high-low strategy. Reducing the target values from a standard of 30,000 to 5000 ions did not severely affect identification rates but did decrease identification and localization scores for phosphorylation sites. We conclude that HCD in the new configuration is now a viable method for large-scale phosphoproteome analysis alongside collisional induced dissociation, (CID) and electron capture/transfer dissociation (ECD/ETD).
Publisher: Elsevier BV
Date: 12-2012
Publisher: Cold Spring Harbor Laboratory
Date: 09-01-2020
DOI: 10.1101/2020.01.08.897595
Abstract: The study of human cardiac pathologies often relies on research conducted in model organisms to gain molecular insight into disease and to develop novel treatment strategies however, translating findings from model organisms back to human can present a significant challenge, in part due to a lack of knowledge about the differences across species in cardiac protein abundances and their interactions. Here we set out to bridge this knowledge gap by presenting a global analysis of cardiac protein expression profiles in humans and commonly used model organisms. Using quantitative mass spectrometry-based proteomics, we measured the abundance of ~7,000 proteins in s les from the separate chambers of human, pig, horse, rat, mouse and zebrafish hearts. This knowledgebase of cardiac protein signatures is accessible through an online database at: atlas.cardiacproteomics.com. Quantitative comparison of the protein profiles support the pig as model organism of choice for arrhythmogenic right ventricular cardiomyopathy whereas comparison of profiles from the two-chambered zebrafish heart suggests a better resemblance to the right side of mammalian hearts. This proteomics resource facilitates translational prospect of cardiac studies from model organisms to humans by enabling direct comparison of disease-linked protein networks across species.
Publisher: American Chemical Society (ACS)
Date: 21-05-2012
DOI: 10.1021/PR3003886
Publisher: Elsevier BV
Date: 02-2021
Publisher: Proceedings of the National Academy of Sciences
Date: 02-07-2012
Abstract: γ-Hydroxybutyric acid (GHB) binding to brain-specific high-affinity sites is well-established and proposed to explain both physiological and pharmacological actions. However, the mechanistic links between these lines of data are unknown. To identify molecular targets for specific GHB high-affinity binding, we undertook photolinking studies combined with proteomic analyses and identified several GABA A receptor subunits as possible candidates. A subsequent functional screening of various recombinant GABA A receptors in Xenopus laevis oocytes using the two-electrode voltage cl technique showed GHB to be a partial agonist at αβδ- but not αβγ-receptors, proving that the δ-subunit is essential for potency and efficacy. GHB showed preference for α4 over α(1,2,6)-subunits and preferably activated α4β1δ (EC 50 = 140 nM) over α4β(2/3)δ (EC 50 = 8.41/1.03 mM). Introduction of a mutation, α4F71L, in α4β1(δ)-receptors completely abolished GHB but not GABA function, indicating nonidentical binding sites. Radioligand binding studies using the specific GHB radioligand [ 3 H]( E , RS )-(6,7,8,9-tetrahydro-5-hydroxy-5 H -benzocyclohept-6-ylidene)acetic acid showed a 39% reduction ( P = 0.0056) in the number of binding sites in α4 KO brain tissue compared with WT controls, corroborating the direct involvement of the α4-subunit in high-affinity GHB binding. Our data link specific GHB forebrain binding sites with α4-containing GABA A receptors and postulate a role for extrasynaptic α4δ-containing GABA A receptors in GHB pharmacology and physiology. This finding will aid in elucidating the molecular mechanisms behind the proposed function of GHB as a neurotransmitter and its unique therapeutic effects in narcolepsy and alcoholism.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2022
DOI: 10.1038/S42003-022-04190-2
Abstract: Recent improvements in the analysis of ancient biomolecules from human remains and associated dental calculus have provided new insights into the prehistoric diet and genetic ersity of our species. Here we present a multi-omics study, integrating metagenomic and proteomic analyses of dental calculus, and human ancient DNA analysis of the petrous bones of two post-Last Glacial Maximum (LGM) in iduals from San Teodoro cave (Italy), to reconstruct their lifestyle and the post-LGM resettlement of Europe. Our analyses show genetic homogeneity in Sicily during the Palaeolithic, representing a hitherto unknown Italian genetic lineage within the previously identified Villabruna cluster. We argue that this lineage took refuge in Italy during the LGM, followed by a subsequent spread to central-western Europe. Analysis of dental calculus showed a diet rich in animal proteins which is also reflected on the oral microbiome composition. Our results demonstrate the power of this approach in the study of prehistoric humans and will enable future research to reach a more holistic understanding of the population dynamics and ecology.
Publisher: Springer Science and Business Media LLC
Date: 14-04-2013
DOI: 10.1038/NG.2610
Publisher: Public Library of Science (PLoS)
Date: 19-04-2021
DOI: 10.1371/JOURNAL.PBIO.3001144
Abstract: Delineating human cardiac pathologies and their basic molecular mechanisms relies on research conducted in model organisms. Yet translating findings from preclinical models to humans present a significant challenge, in part due to differences in cardiac protein expression between humans and model organisms. Proteins immediately determine cellular function, yet their large-scale investigation in hearts has lagged behind those of genes and transcripts. Here, we set out to bridge this knowledge gap: By analyzing protein profiles in humans and commonly used model organisms across cardiac chambers, we determine their commonalities and regional differences. We analyzed cardiac tissue from each chamber of human, pig, horse, rat, mouse, and zebrafish in biological replicates. Using mass spectrometry–based proteomics workflows, we measured and evaluated the abundance of approximately 7,000 proteins in each species. The resulting knowledgebase of cardiac protein signatures is accessible through an online database: atlas.cardiacproteomics.com . Our combined analysis allows for quantitative evaluation of protein abundances across cardiac chambers, as well as comparisons of cardiac protein profiles across model organisms. Up to a quarter of proteins with differential abundances between atria and ventricles showed opposite chamber-specific enrichment between species these included numerous proteins implicated in cardiac disease. The generated proteomics resource facilitates translational prospects of cardiac studies from model organisms to humans by comparisons of disease-linked protein networks across species.
No related grants have been discovered for Jesper Olsen.