| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
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| 3. |
- Aad, G., et al.
(författare)
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Observation of Single-Top-Quark Production in Association with a Photon Using the ATLAS Detector
- 2023
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 131:18
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Tidskriftsartikel (refereegranskat)abstract
- This Letter reports the observation of single top quarks produced together with a photon, which directly probes the electroweak coupling of the top quark. The analysis uses 139 fb−1 of 13 TeV proton-proton collision data collected with the ATLAS detector at the Large Hadron Collider. Requiring a photon with transverse momentum larger than 20 GeV and within the detector acceptance, the fiducial cross section is measured to be 688±23(stat) , to be compared with the standard model prediction of at next-to-leading order in QCD.
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| 4. |
- Battisti, Umberto Maria, et al.
(författare)
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Exploration of Novel Urolithin C Derivatives as Non-Competitive Inhibitors of Liver Pyruvate Kinase
- 2023
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Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- The inhibition of liver pyruvate kinase could be beneficial to halt or reverse non-alcoholic fatty liver disease (NAFLD), a progressive accumulation of fat in the liver that can lead eventually to cirrhosis. Recently, urolithin C has been reported as a new scaffold for the development of allosteric inhibitors of liver pyruvate kinase (PKL). In this work, a comprehensive structure-activity analysis of urolithin C was carried out. More than 50 analogues were synthesized and tested regarding the chemical features responsible for the desired activity. These data could pave the way to the development of more potent and selective PKL allosteric inhibitors.
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| 5. |
- Brusini, Irene, et al.
(författare)
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MRI-derived brain age as a biomarker of ageing in rats : validation using a healthy lifestyle intervention
- 2022
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 109, s. 204-215
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Tidskriftsartikel (refereegranskat)abstract
- The difference between brain age predicted from MRI and chronological age (the so-called BrainAGE) has been proposed as an ageing biomarker. We analyse its cross-species potential by testing it on rats undergoing an ageing modulation intervention. Our rat brain age prediction model combined Gaussian process regression with a classifier and achieved a mean absolute error (MAE) of 4.87 weeks using cross-validation on a longitudinal dataset of 31 normal ageing rats. It was then tested on two groups of 24 rats (MAE = 9.89 weeks, correlation coefficient = 0.86): controls vs. a group under long-term environmental enrichment and dietary restriction (EEDR). Using a linear mixed-effects model, BrainAGE was found to increase more slowly with chronological age in EEDR rats ( p = 0 . 015 for the interaction term). Cox re-gression showed that older BrainAGE at 5 months was associated with higher mortality risk ( p = 0 . 03 ). Our findings suggest that lifestyle-related prevention approaches may help to slow down brain ageing in rodents and the potential of BrainAGE as a predictor of age-related health outcomes.
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| 6. |
- Liu, Suli, et al.
(författare)
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A Chromosome-centric Human Proteome Project (C-HPP) to Characterize the Sets of Proteins Encoded in Chromosome 17
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 49-61
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Tidskriftsartikel (refereegranskat)abstract
- We report progress assembling the parts list for chromosome 17 and illustrate the various processes that we have developed to integrate available data from diverse genomic and proteomic knowledge bases. As primary resources, we have used GPMDB, neXtProt, PeptideAtlas, Human Protein Atlas (HPA), and GeneCards. All sites share the common resource of Ensembl for the genome modeling information. We have defined the chromosome 17 parts list with the following information: 1169 protein-coding genes, the numbers of proteins confidently identified by various experimental approaches as documented in GPMDB, neXtProt, PeptideAtlas, and HPA, examples of typical data sets obtained by RNASeq and proteomic studies of epithelial derived tumor cell lines (disease proteome) and a normal proteome (peripheral mononuclear cells), reported evidence of post-translational modifications, and examples of alternative splice variants (ASVs). We have constructed a list of the 59 "missing" proteins as well as 201 proteins that have inconclusive mass spectrometric (MS) identifications. In this report we have defined a process to establish a baseline for the incorporation of new evidence on protein identification and characterization as well as related information from transcriptome analyses. This initial list of "missing" proteins that will guide the selection of appropriate samples for discovery studies as well as antibody reagents. Also we have illustrated the significant diversity of protein variants (including post-translational modifications, PTMs) using regions on chromosome 17 that contain important oncogenes. We emphasize the need for mandated deposition of proteomics data in public databases, the further development of improved PTM, ASV, and single nucleotide variant (SNV) databases, and the construction of Web sites that can integrate and regularly update such information. In addition, we describe the distribution of both clustered and scattered sets of protein families on the chromosome. Since chromosome 17 is rich in cancer-associated genes, we have focused the clustering of cancer-associated genes in such genomic regions and have used the ERBB2 amplicon as an example of the value of a proteogenomic approach in which one integrates transcriptomic with proteomic information and captures evidence of coexpression through coordinated regulation.
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| 7. |
- Vestberg, Robert, et al.
(författare)
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A General Strategy for Highly Efficient Nanoparticle Dispersing Agents Based on Hybrid Dendritic Linear Block Copolymers
- 2009
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 47:5, s. 1237-1258
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Tidskriftsartikel (refereegranskat)abstract
- A modular approach to the synthesis of a library of hybrid dendriticlinear copolymers was developed based on RAFT polymerization from monodisperse dendritic macroRAFT agents. By accurately controlling the molecular weight of the linear block, generation number of the dendrimer and the nature of the dendritic chains ends, the performance of these hybrid block copolymers as dispersing agents was optimized for a range of nanoparticles. For titanium dioxide nanoparticles, dispersion in a poly(methyl methacrylate) matrix was maximized with a second generation dendrimer containing four carboxylic acid end groups, and the quality of dispersion was observed to be superior to commercial dispersing agents for TiO2. This approach also allowed novel hybrid dendritic-linear dispersing agents to be prepared for the dispersion of Au and CdSe nanoparticles based on disulphide and phosphine oxide end groups, respectively.
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| 8. |
- Öberg Hed, Kim, 1982-
(författare)
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Advanced polymeric scaffolds for functional materials in biomedical applications
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Advancements in the biomedical field are driven by the design of novel materials with controlled physical and bio-interactive properties. To develop such materials, researchers rely on the use of highly efficient reactions for the assembly of advanced polymeric scaffolds that meet the demands of a functional biomaterial. In this thesis two main strategies for such materials have been explored; these include the use of off-stoichiometric thiol-ene networks and dendritic polymer scaffolds. In the first case, the highly efficient UV-induced thiol-ene coupling (TEC) reaction was used to create crosslinked polymeric networks with a predetermined and tunable excess of thiol or ene functionality. These materials rely on the use of readily available commercial monomers. By adopting standard molding techniques and simple TEC surface modifications, patterned surfaces with tunable hydrophobicity could be obtained. Moreover, these materials are shown to have great potential for rapid prototyping of microfluidic devices. In the second case, dendritic polymer scaffolds were evaluated for their ability to increase surface interactions and produce functional 3D networks. More specifically, a self-assembled dendritic monolayer approach was explored for producing highly functional dendronized surfaces with specific interactions towards pathogenic E. coli bacteria. Furthermore, a library of heterofunctional dendritic scaffolds, with a controllable and exact number of dual-purpose azide and ene functional groups, has been synthesized. These scaffolds were explored for the production of cell interactive hydrogels and primers for bone adhesive implants. Dendritic hydrogels decorated with a selection of bio-relevant moieties and with Young’s moduli in the same range as several body tissues could be produced by facile UV-induced TEC crosslinking. These gels showed low cytotoxic response and relatively rapid rates of degradation when cultured with normal human dermal fibroblast cells. When used as primers for bone adhesive patches, heterofunctional dendrimers with high azide-group content led to a significant increase in the adhesion between a UV-cured hydrophobic matrix and the wet bone surface (compared to patches without primers).
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