| 21. |
- Nilsson, Jonas, 1970, et al.
(författare)
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Targeting the glycoproteome.
- 2013
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Ingår i: Glycoconjugate journal. - : Springer Science and Business Media LLC. - 1573-4986 .- 0282-0080. ; 30:2, s. 119-36
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Tidskriftsartikel (refereegranskat)abstract
- Despite numerous original publications describing the structural complexity of N- and O-linked glycans on glycoproteins, only very few answer the basic question of which particular glycans are linked to which amino acid residues along the polypeptide chain. Such structural information is of fundamental importance for understanding the biological roles of complex glycosylations as well as deciphering their non-template driven biosynthesis. This review focuses on presenting and commenting on recent strategies, specifically aimed at identifying the glycoproteome of cultured cells and biological samples, using targeted and global enrichment procedures and utilizing the high resolution power, high through-put capacity and complementary fragmentation techniques of tandem mass spectrometry. The goal is to give an update of this emerging field of protein and glyco-sciences and suggest routes to bridge the data gap between the two aspects of glycoprotein characteristics, i.e. glycan structures and their attachment sites.
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| 22. |
- Thorek, D L J, et al.
(författare)
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Prostate-specific kallikrein-related peptidases and their relation to prostate cancer biology and detection. Established relevance and emerging roles.
- 2013
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 110:3, s. 484-92
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Tidskriftsartikel (refereegranskat)abstract
- Kallikreins are a family of serine proteases with a range of tissue-specific and essential proteolytic functions. Among the best studied are the prostate tissue-specific KLK2 and KLK3 genes and their secreted protease products, human kallikrein 2, hk2, and prostate-specific antigen (PSA). Members of the so-called classic kallikreins, these highly active trypsin-like serine proteases play established roles in human reproduction. Both hK2 and PSA expression is regulated by the androgen receptor which has a fundamental role in prostate tissue development and progression of disease. This feature, combined with the ability to sensitively detect different forms of these proteins in blood and biopsies, result in a crucially important biomarker for the presence and recurrence of cancer. Emerging evidence has begun to suggest a role for these kallikreins in critical vascular events. This review discusses the established and developing biological roles of hK2 and PSA, as well as the historical and advanced use of their detection to accurately and non-invasively detect and guide treatment of prostatic disease.
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| 23. |
- Andersson, Sandra, et al.
(författare)
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The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115911-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.
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| 24. |
- Halim, Adnan, et al.
(författare)
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LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins.
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:2, s. 573-584
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Tidskriftsartikel (refereegranskat)abstract
- The GalNAc O-glycosylation on Ser/Thr residues of extracellular proteins has not been well characterized from a proteomics perspective. We previously reported a sialic acid capture-and-release protocol to enrich tryptic N- and O-glycopeptides from human cerebrospinal fluid glycoproteins using nanoLC-ESI-MS/MS with collision-induced dissociation (CID) for glycopeptide characterization. Here, we have introduced peptide N-glycosidase F (PNGase F) pre-treatment of CSF samples to remove the N-glycans facilitating the selective characterization of O-glycopeptides and enabling the use of an automated CID-MS2/MS3 search protocol for glycopeptide identification. We used electron capture and transfer dissociation (ECD/ETD) to pinpoint the glycosylation site(s) of the glycopeptides, identified as predominantly core 1 like HexHexNAc-O- glycans attached to 1-4 Ser/Thr residues. We characterized 108 O-glycosylations and found Pro residues preferentially in the n-1, n+1 and/or n+3 positions in relation to the Ser/Thr attachment site (n). The characterization of glycans and glycosylation sites in glycoproteins from human clinical samples provides a basis for future studies addressing the biological and diagnostic importance of specific protein glycosylations in relation to human disease.
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| 25. |
- Karlsson, Roger, 1975, et al.
(författare)
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Strain-level typing and identification of bacteria using mass spectrometry-based proteomics.
- 2012
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Ingår i: Journal of proteome research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 11:5, s. 2710-20
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Tidskriftsartikel (refereegranskat)abstract
- Because of the alarming expansion in the diversity and occurrence of bacteria displaying virulence and resistance to antimicrobial agents, it is increasingly important to be able to detect these microorganisms and to differentiate and identify closely related species, as well as different strains of a given species. In this study, a mass spectrometry proteomics approach is applied, exploiting lipid-based protein immobilization (LPI), wherein intact bacterial cells are bound, via membrane-gold interactions, within a FlowCell. The bound cells are subjected to enzymatic digestion for the generation of peptides, which are subsequently identified, using LC-MS. Following database matching, strain-specific peptides are used for subspecies-level discrimination. The method is shown to enable a reliable typing and identification of closely related strains of the same bacterial species, herein illustrated for Helicobacter pylori .
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| 26. |
- Khezri, Banafsheh, et al.
(författare)
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Estimation of the possible economic effects of a sequential testing strategy with NT-proBNP before echocardiography in primary care
- 2014
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Ingår i: Clinical Laboratory. - 1433-6510. ; 60:7-8, s. 881-886
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The object of the study was to estimate the possible economic effects of a sequential testing strategy with NT-proBNP from a primary care payer perspective.METHODS:The study data were collected from primary care physicians in the County of Uppland from 2005 through 2012. Two different cut-off levels were used for negative NT-proBNP in the rule-out test: 300 and 400 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.RESULTS:The female patients were slightly older than the males. Based on the data from 2012, the estimated costs for NT-proBNP tests and echocardiographies per county were reduced by EUR 300000/100000 inhabitants with the 300 pg/mL cut-off and EUR 350000/100000 inhabitants with the 400 pg/mL.CONCLUSIONS:The use of NT-proBNP as a rule-out test in a sequential testing strategy reduced the cost for diagnostic work-up of primary care patients with suspected heart failure.
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| 27. |
- Nilsson-Ehle, Herman, 1950, et al.
(författare)
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Vitaminer och spårämnen.
- 2012
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Ingår i: Laurells Klinisk kemi i praktisk medicin. - 2012 - 9., [rev. och utök.] uppl. / redaktion: Peter Nilsson-Ehle, Maria Berggren Söderlund, Elvar Theodorsson ; redaktionskommitté: Charlotte Becker, Kjell Grankvist, Anders Grubb, Göran Lindstedt, Per Simonsson.. - Lund : Studentlitteratur AB. - 9789144047874
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Bokkapitel (refereegranskat)
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| 28. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Cerebrospinal fluid profiles of amyloid β-related biomarkers in Alzheimer's disease.
- 2012
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Ingår i: Neuromolecular medicine. - : Springer Science and Business Media LLC. - 1559-1174 .- 1535-1084. ; 14:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid cascade hypothesis on the pathogenesis of Alzheimer's disease (AD) states that amyloid β (Aβ) accumulation in the brain is a key factor that initiates the neurodegenerative process. Aβ is generated from amyloid precursor protein (APP) through sequential cleavages by BACE1 (the major β-secretase in the brain) and γ-secretase. The purpose of this study was to characterize APP metabolism in vivo in AD patients versus cognitively healthy subjects by examining alterations in cerebrospinal fluid (CSF) biomarkers. We measured BACE1 activity and concentrations of α- and β-cleaved soluble APP (sAPPα and sAPPβ, respectively) and Aβ40 in CSF, biomarkers that all reflect the metabolism of APP, in 75 AD patients and 65 cognitively healthy controls. These analytes were also applied in a multivariate model to determine whether they provided any added diagnostic value to the core CSF AD biomarkers Aβ42, T-tau, and P-tau. We found no significant differences in BACE1 activity or sAPPα, sAPPβ, and Aβ40 concentrations between AD patients and controls. A multivariate model created with all analytes did not improve the separation of AD patients from controls compared with using the core AD biomarkers alone, highlighting the strong diagnostic performance of Aβ42, T-tau, and P-tau for AD. However, AD patients in advanced clinical stage, as determined by low MMSE score (≤20), had lower BACE1 activity and sAPPα, sAPPβ, and Aβ40 concentrations than patients with higher MMSE score, suggesting that these markers may be related to the severity of the disease.
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