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- Muthukrishnan, Uma, 1984-, et al.
(författare)
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The exosome membrane localization of histones is independent of DNA and upregulated in response to stress
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Extracellular histones contribute to many acute and chronic diseases but also populate the secretomes of healthy cells and biofluids. However, a secretory pathway for histones has not been described. Here we report that core and linker histones localize to multivesicular bodies and are secreted via exosomes. Histones are tightly associated with the exosome membrane, with N-terminal domains exposed, in a DNA-independent manner. Furthermore, rapid upregulation of exosomal histones occurs following heat stress, accompanied by enhanced vesicle secretion and a shift towards a population of smaller vesicles. Proteomic analyses identified the downregulation of endosomal sorting complex required for transport (ESCRT) complex as a possible mechanism underlying increased histone secretion.We show for the first time that membrane-associated histones are actively secreted from intact cells via the multivesicular body/exosomal pathway. We demonstrate a novel pathway for extracellular histone release that may have a role in both health and disease.
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| 4. |
- Boström, Tove, et al.
(författare)
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Investigating the correlation of protein and mRNA levels in human cell lines using quantitative proteomics and transcriptomics
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- An important topic of discussion in proteomics is the degree of correlation of RNA and protein levels in cells, tissues and organs. In this study, the difference in protein and mRNA levels for a number of selected gene targets were investigated across six human cell lines using quantitative proteomics and next generation sequencing-based transcriptomics. The copy numbers of 32 proteins were determined using an absolute quantitative proteomics approach (PrEST-SILAC), where heavy isotope-labeled protein fragments were used as internal standards. A cross evaluation of protein copy numbers determined by mass spectrometry and staining profiles using immunohistochemistry showed good correlation. The mRNA levels were determined using RNA sequencing based on digital counting of sequencing reads and the levels determined as FPKM values. Comparison of the relative variations in mRNA and protein levels for individual genes across the six cell lines showed correlation between protein and mRNA levels, including six genes with high variability in expression levels in the six cell lines resulting in an average correlation of 0.9 (Spearman's rank coefficient). In summary, the analysis of the selected protein targets supports the conclusion that the translation rate across cell lines correlates for a particular gene, suggesting that individual protein levels can be predicted from the respective mRNA levels by defining the relation between protein and mRNA, specific for each human gene.
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| 6. |
- Johansson, Henrik J., et al.
(författare)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2018
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Ingår i: Molecular & Cellular Proteomics. - : American Society for Biochemistry and Molecular Biology. - 1535-9476 .- 1535-9484. ; 18:8, suppl. 2, s. S40-S40
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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| 7. |
- Kälin, Gregor
(författare)
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Scattering Amplitudes in Supersymmetric Quantum Chromodynamics and Gravity
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Quantum field theory is a theoretical framework for the description of nature in terms of fundamental particles, fields and their interactions. In the quantum regime, elementary scattering processes are observables in many experiments and studied in theoretical physics. The theoretical understanding of scattering amplitudes is often based on a perturbative analysis in powers of the coupling strength of the fundamental forces. Whereas the computation of scattering amplitudes has been dominated by Feynman diagram constructions for a long time, new methods have lead to a multitude of novel results in the last 20-30 years. Thereafter discoveries of new representations, dualities and construction methods have enormously increased our understanding of the mathematical structure of scattering amplitudes.In this thesis we focus on a particular structure of gauge theory amplitudes known as the color-kinematics duality. Closely tied to this duality is the double copy construction of gravitational amplitudes, and a set of identities among basic building blocks of the gauge theory, the BCJ identities. Using methods developed for the study of this duality, we obtain new results for scattering amplitudes in non-maximal supersymmetric Yang-Mills coupled to massless fundamental matter at one and two loops. We immediately construct amplitudes in supergravity theories via the double copy. Furthermore, we include methods and results for the integration of gauge theory amplitudes and the ultraviolet structure of supergravity amplitudes.In a second part we present ideas related to the identification of basic building blocks that underlie the construction of scattering amplitudes. A decomposition of gauge theory amplitudes into color- and kinematic-dependent contributions exposes a set of primitive objects. Relations among these objects allow us to identify a minimal set of independent kinematic building blocks.
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| 8. |
- Olofsson, Pia H., 1962-, et al.
(författare)
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Increased transmucosal uptake of E. coli K12 in porcine small bowel following experimental short term abdominal compartment syndrome
- 2009
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Abdominal compartment syndrome (ACS) may lead to bacterial translocation and possibly be of importance for development of multiorgan failure. However, the underlying mechanisms have not been fully elucidated. In a porcine model we recently demonstrated preserved intestinal mucosal blood flow during experimental short duration ACS. In the present study we used the same model to determine mucosal barrier function and morphology in the small bowel and colon of pigs before and after short term ACS. Methods: The study comprised 12 anaesthetized pigs exposed to experimental ACS and 6 control animals. Via laparotomy, samples of small bowel and colon were taken out for studies before short term ACS, where the abdomen was inflated with CO2 and IAP was increased stepwise by 10 mm Hg at 10-minute intervals up to 50 mm Hg, and again 10 minutes after exsufflation. Mucosal microcirculation was measured by laser Doppler flowmetry, and mucosal tissues were mounted in modified Ussing chambers for assessment of barrier function (E. coli K12 uptake and 51Cr-EDTA permeability). Specimens were also fixed in formaldehyde, stained with eosin-hematoxylin and evaluated blindly using an 8-grade scale for assessment of mucosal damage. Results: Transmucosal passage of E. coli was three-fold increased in the small bowel after ACS (22.6 [18.2 – 54.4] units) vs. baseline (8.1 [2.0 – 13.9]; P< 0.050) with a significant correlation to alterations of mucosal microcirculation. In the colon bacterial passage was unchanged, whereas 51Cr-EDTA permeability after ACS increased to 181% of baseline (P<0.05) and was correlated to significant mucosal histopathological changes (P<0.03). Conclusion: Short term ACS with reperfusion induced significant dysfunction of the intestinal mucosal barrier. The response patterns concerning barrier dysfunction differed between small bowel and colonic mucosa, with increased bacterial passage and paracellular permeability, respectively.
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| 9. |
- Speranzon, Alberto, 1975-
(författare)
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Coordination, Consensus and Communication in Multi-robot Control Systems
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Analysis, design and implementation of cooperative control strategies for multi-robot systems under communication constraints is the topic of this thesis. Motivated by a rapidly growing number of applications with networked robots and other vehicles, fundamental limits on the achievable collaborative behavior are studied for large teams of autonomous agents. In particular, a problem is researched in detail in which the group of agents is supposed to agree on a common state without any centralized coordination. Due to the dynamics of the individual agents and their varying connectivity, this problemis an extension of the classical consensus problemin computer science. It captures a crucial component of many desirable features of multi-robot systems, such as formation, flocking, rendezvous, synchronizing and covering. Analytical bounds on the convergence rate to consensus are derived for several systemconfigurations. It is shown that static communication networks that exhibit particular symmetries yield slow convergence, if the connectivity of each agent does not scale with the total number of agents. On the other hand, some randomly varying networks allow fast convergence even if the connectivity is low. It is furthermore argued that if the data being exchanged between the agents are quantized, it may heavily degrade the performance. The extent to which certain quantization schemes are more suitable than others is quantified through relations between the number of agents and the required total network bit rate. The design of distributed coordination and estimation schemes based on the consensus algorithm is presented. A receding horizon coordination strategy utilizing subgradient optimization is developed. Robustness and implementation aspects are discussed. A new collaborative estimation method is also proposed. The implementation of multi-robot control systems is difficult due to the high systemcomplexity. In the final part of this thesis, a hierarchical control architecture appropriate for a class of coordination tasks is therefore suggested. It allows a formal verification of the correctness of the implemented control algorithms.
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| 10. |
- Sun, Jielin, et al.
(författare)
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Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12
- 2008
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Ingår i: Nature Genetics. - London : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 40:10, s. 1153-1155
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 10-9 for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.
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