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Neupane, R., Källsten, M., Lehmann, F. & Bergquist, J. (2018). Effect of mobile phase composition on the analysis of aggregates of antibody drug conjugates (ADCs) using size exclusion chromatography. Analytical Methods, 10(9), 938-941
Open this publication in new window or tab >>Effect of mobile phase composition on the analysis of aggregates of antibody drug conjugates (ADCs) using size exclusion chromatography
2018 (English)In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 10, no 9, p. 938-941Article in journal (Refereed) Published
Abstract [en]

In this study, the effect of mobile phase composition for size exclusion chromatography (SEC) on antibody drug conjugate (ADC) aggregate analysis was investigated. The use of organic components as well as high ionic strength during aggregate analysis was demonstrated to be advantageous.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2018
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-350281 (URN)10.1039/c7ay02696j (DOI)000426696100001 ()
Funder
Swedish Research Council, SRC 2015-4870Swedish Foundation for Strategic Research , ID14-0081
Available from: 2018-05-09 Created: 2018-05-09 Last updated: 2018-05-09Bibliographically approved
Patriarca, C., Bergquist, J., Sjöberg, P. J., Tranvik, L. & Hawkes, J. A. (2018). Online HPLC-ESI-HRMS Method for the Analysis and Comparison of Different Dissolved Organic Matter Samples. Environmental Science and Technology, 52(4), 2091-2099
Open this publication in new window or tab >>Online HPLC-ESI-HRMS Method for the Analysis and Comparison of Different Dissolved Organic Matter Samples
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2018 (English)In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 52, no 4, p. 2091-2099Article in journal (Refereed) Published
Abstract [en]

Natural dissolved organic matter (DOM) is an ultracomplex mixture that is essential to global carbon cycling but is poorly understood because of its complexity. The most powerful tool for the DOM characterization is high-resolution mass spectrometry (HRMS) generally combined to direct infusion (DI) as sample introduction. Liquid chromatography (LC) represents a compelling alternative to DI; however, state-of-the-art techniques involve only offline LC-HRMS approaches, which have important logistical drawbacks that make DOM analysis more challenging. This study introduces a new method based on online coupling of liquid chromatography to high resolution mass spectrometry, able to overcome the disadvantages of usual approaches. It is characterized by high reproducibility (% Bray–Curtis dissimilarity among replicates ≈ 2.5%), and it reduces transient complexity and contaminant interferences, thus increasing the signal-to-noise ratio (S/N), leading to the identification of an overall larger number of formulas in the mixture. Moreover, the application of an in silico fractionation prior to the statistical analysis allows an easy, flexible, fast, and detailed comparison of DOM samples from a variety of sources with a single chromatographic run.

National Category
Analytical Chemistry
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-341015 (URN)10.1021/acs.est.7b04508 (DOI)000426143300045 ()
Funder
Knut and Alice Wallenberg Foundation, 2013.0091Swedish Research Council, SRC 2015-4870Swedish Research Council, SRC 2014-04264
Available from: 2018-02-06 Created: 2018-02-06 Last updated: 2018-04-19Bibliographically approved
Wei, X., Zhang, Y., Yu, S., Li, S., Jiang, W., Zhu, Y., . . . Song, F. (2018). PDLIM5 identified by label-free quantitative proteomics as a potential novel biomarker of papillary thyroid carcinoma. Biochemical and Biophysical Research Communications - BBRC, 499(2), 338-344
Open this publication in new window or tab >>PDLIM5 identified by label-free quantitative proteomics as a potential novel biomarker of papillary thyroid carcinoma
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2018 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 499, no 2, p. 338-344Article in journal (Refereed) Published
Abstract [en]

In order to better understand the mechanisms underlying the development of papillary thyroid carcinoma (PTC), and to identify new potential biomarkers, high-resolution label-free mass spectrometry was performed on PTC tissues and adjacent normal thyroid tissues from six patients. In this process, 2788 proteins were identified, out of which 49 proteins presented significant differences between PTC tissues and adjacent normal thyroid tissues. Gene ontology revealed that the majority of these proteins are involved in the catalytic activity and binding. We selected three proteins with differential expressions: PDZ and LIM domain 5 (PDLIM5), PDLIM1 and ALDH1A1; Protein expressions were further verified by RT-PCR and western blot. Among these, expression of PDLIM5 and PDLIM1 was up-regulated, while that of ALDH1A1 was down-regulated in PTC tissues. Next, we confirmed their expression through quantitative dot blot (QDB) technique. We found that knockdown of PDLIM5 expression in the B-CPAP cell line could inhibit the migration, invasion and proliferation of PTC cells. In addition, PDLIM5 knockdown reduced Ras and Phospho-ERK1/2 expression. Thus, we suggested that PDLIM5 promotes PTC via activation of the Ras-ERK pathway. Our research provides new molecular insight into the function of PDLIM5, which may assist in studying the mechanism of PTC. In addition, PDLIM5 could be further explored as a potential candidate for PTC treatment.

Keywords
Papillary thyroid cancer, PDZ and UM domain 5, Proteomics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-353360 (URN)10.1016/j.bbrc.2018.03.159 (DOI)000430159400036 ()29574154 (PubMedID)
Available from: 2018-06-12 Created: 2018-06-12 Last updated: 2018-06-12Bibliographically approved
Neupane, R. & Bergquist, J. (2017). Analytical techniques for the characterization of Antibody Drug Conjugates: Challenges and prospects. European journal of mass spectrometry, 23(6), 417-426
Open this publication in new window or tab >>Analytical techniques for the characterization of Antibody Drug Conjugates: Challenges and prospects
2017 (English)In: European journal of mass spectrometry, ISSN 1469-0667, E-ISSN 1751-6838, Vol. 23, no 6, p. 417-426Article in journal (Refereed) Published
Abstract [en]

Antibody drug conjugates are increasingly being researched for the treatment of cancer. Accurate and reliable characterization of ADCs is inevitable for their development as potential therapeutic agent. Different analytical techniques have been used in order to decipher heterogeneous nature of antibody drug conjugates, enabling successful characterization. This review will summarize specially three major analytical tools i.e. UV-Vis spectroscopy, liquid chromatography, and mass spectrometry used in characterization of antibody drug conjugates. In this review, major challenges during analysis due to the inherent features of analytical techniques and antibody drug conjugates are summarized along with the modifications intended to address each challenge.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2017
Keywords
Antibody drug conjugate, hydrophobic interaction chromatography, mass spectrometry, reversed phase liquid chromatography, size exclusion chromatography, UV-Vis spectroscopy
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-345121 (URN)10.1177/1469066717733919 (DOI)000423263100014 ()29183195 (PubMedID)
Funder
Swedish Research Council, 2015-4870
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-03-12Bibliographically approved
Ma'ayeh, S. Y., Liu, J., Peirasmaki, D., Hörnaeus, K., Bergström Lind, S. K., Grabherr, M., . . . Svärd, S. (2017). Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells. PLoS Neglected Tropical Diseases, 11(12), Article ID e0006120.
Open this publication in new window or tab >>Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells
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2017 (English)In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 12, article id e0006120Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Giardia intestinalis is a non-invasive protozoan parasite that causes giardiasis in humans, the most common form of parasite-induced diarrhea. Disease mechanisms are not completely defined and very few virulence factors are known.

METHODOLOGY:

To identify putative virulence factors and elucidate mechanistic pathways leading to disease, we have used proteomics to identify the major excretory-secretory products (ESPs) when Giardia trophozoites of WB and GS isolates (assemblages A and B, respectively) interact with intestinal epithelial cells (IECs) in vitro.

FINDINGS:

The main parts of the IEC and parasite secretomes are constitutively released proteins, the majority of which are associated with metabolism but several proteins are released in response to their interaction (87 and 41 WB and GS proteins, respectively, 76 and 45 human proteins in response to the respective isolates). In parasitized IECs, the secretome profile indicated effects on the cell actin cytoskeleton and the induction of immune responses whereas that of Giardia showed anti-oxidation, proteolysis (protease-associated) and induction of encystation responses. The Giardia secretome also contained immunodominant and glycosylated proteins as well as new candidate virulence factors and assemblage-specific differences were identified. A minor part of Giardia ESPs had signal peptides (29% for both isolates) and extracellular vesicles were detected in the ESPs fractions, suggesting alternative secretory pathways. Microscopic analyses showed ESPs binding to IECs and partial internalization. Parasite ESPs reduced ERK1/2 and P38 phosphorylation and NF-κB nuclear translocation. Giardia ESPs altered gene expression in IECs, with a transcriptional profile indicating recruitment of immune cells via chemokines, disturbances in glucose homeostasis, cholesterol and lipid metabolism, cell cycle and induction of apoptosis.

CONCLUSIONS:

This is the first study identifying Giardia ESPs and evaluating their effects on IECs. It highlights the importance of host and parasite ESPs during interactions and reveals the intricate cellular responses that can explain disease mechanisms and attenuated inflammatory responses during giardiasis.

National Category
Analytical Chemistry Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-338331 (URN)10.1371/journal.pntd.0006120 (DOI)000419108500030 ()29228011 (PubMedID)
Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-02-02Bibliographically approved
Roomp, K., Kristinsson, H., Schvartz, D., Ubhayasekera, K., Sargsyan, E., Manukyan, L., . . . Bergsten, P. (2017). Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism. PLoS ONE, 12(4), Article ID e0176391.
Open this publication in new window or tab >>Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0176391Article in journal (Refereed) Published
Abstract [en]

Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/or confirm reported mechanisms of lipotoxicity. To this end isolated human pancreatic islets, exposed to chronically elevated palmitate concentrations for 0, 2 and 7 days, were functionally characterized and their levels of multiple targeted lipid and untargeted protein species determined. Glucosestimulated insulin secretion from the islets increased on day 2 and decreased on day 7. At day 7 islet insulin content decreased and the proinsulin to insulin content ratio doubled. Amounts of cholesterol, stearic acid, C16 dihydroceramide and C24: 1 sphingomyelin, obtained from the lipidomic screen, increased time-dependently in the palmitate-exposed islets. The proteomic screen identified matching changes in proteins involved in lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in the islets. Furthermore, proteins associated with immature secretory granules were decreased when palmitate exposure time was increased despite their high affinity for cholesterol. Proteins associated with mature secretory granules remained unchanged. Pathway analysis based on the protein and lipid expression profiles implicated autocrine effects of insulin in lipotoxicity. Taken together the study demonstrates that combining different omics approaches has potential in mapping of multiple simultaneous cellular events. However, it also shows that challenges exist for effectively combining lipidomics and proteomics in primary cells. Our findings provide insight into how saturated fatty acids contribute to islet cell dysfunction by affecting the granule maturation process and confirmation in human islets of some previous findings from rodent islet and cell-line studies.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-323459 (URN)10.1371/journal.pone.0176391 (DOI)000400383600072 ()28448538 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme
Available from: 2017-06-07 Created: 2017-06-07 Last updated: 2017-11-29Bibliographically approved
Andersson, C. R., Bergquist, J., Theodorsson, E. & Strom, J. O. (2017). Comparisons between commercial salivary testosterone enzyme-linked immunosorbent assay kits. Scandinavian Journal of Clinical and Laboratory Investigation, 77(8), 582-586
Open this publication in new window or tab >>Comparisons between commercial salivary testosterone enzyme-linked immunosorbent assay kits
2017 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 8, p. 582-586Article in journal (Refereed) Published
Abstract [en]

Introduction: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined. Aim of study: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec). Methods: Saliva was collected from 50 participants (25 men and 25 women). Each sample was analysed by the four ELISA kits. Results: The correlations between the ELISA kits from Demeditec, DRG and Salimetrics were moderate to high with r-values >.77; however, proportional errors between the methods calls for caution. The ELISA kit from IBL malfunctioned and no results from this kit was obtained. Conclusions: Results from studies using the ELISA kits from Demeditec, DRG and Salimetrics are generally comparable; however, translation using the formulae presented in the current study could increase the accuracy of these comparisons.

Keywords
Androgens, immunoassay, methods, saliva, testosterone
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-343341 (URN)10.1080/00365513.2017.1339231 (DOI)000416756100004 ()28644096 (PubMedID)
Funder
Swedish Research Council, 2015-4870
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-03-15Bibliographically approved
Samgina, T. Y., Artemenko, K. A., Bergquist, J., Trebse, P., Torkar, G., Tolpina, M. D. & Lebedev, A. T. (2017). Differentiation of frogs from two populations belonging to the Pelophylax esculentus complex by LC-MS/MS comparison of their skin peptidomes. Analusis, 409(7), 1951-1961
Open this publication in new window or tab >>Differentiation of frogs from two populations belonging to the Pelophylax esculentus complex by LC-MS/MS comparison of their skin peptidomes
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2017 (English)In: Analusis, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 7, p. 1951-1961Article in journal (Refereed) Published
Abstract [en]

LC-MS/MS was applied to establish the composition of the skin peptidome of a Slovenian green frog belonging to the Pelophylax esculentus complex. As this was similar to the peptidome of the Moscow population of Pelophylax ridibundus, it allowed us to identify the Slovenian frog from the Pelophylax esculentus complex as Pelophylax ridibundus. The sequences of six new peptides from the brevinin 2 family are reported for the first time on the basis of manual interpretation of their tandem mass spectra. The structural similarity of the brevinin 2 peptides from the Moscow and Slovenian populations of Pelophylax ridibundus enables peptides from this family to be utilized as biomarkers for Pelophylax ridibundus inter- and intraspecies differentiation, and the proposed approach can be used as an analytical tool for differentiating the corresponding species and populations. The potential biological activities of the novel peptides were estimated by 2D mass mapping. The results allowed us to classify all of the available peptides belonging to the brevinin 2 family.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG, 2017
Keywords
Natural products, Frog peptides, Brevinins, Green frogs, Tandem mass spectrometry, Peptide sequencing
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-319540 (URN)10.1007/s00216-016-0143-3 (DOI)000394377200023 ()28012108 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2017-11-29Bibliographically approved
Fallahsharoudi, A., de Kock, N., Johnsson, M., Bektic, L., Ubhayasekera, S. J., Bergquist, J., . . . Jensen, P. (2017). Genetic and Targeted eQTL Mapping Reveals Strong Candidate Genes Modulating the Stress Response During Chicken Domestication. G3: Genes, Genomes, Genetics, 7(2), 497-504
Open this publication in new window or tab >>Genetic and Targeted eQTL Mapping Reveals Strong Candidate Genes Modulating the Stress Response During Chicken Domestication
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2017 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 7, no 2, p. 497-504Article in journal (Refereed) Published
Abstract [en]

The stress response has been largely modified in all domesticated animals, offering a strong tool for genetic mapping. In chickens, ancestral Red Junglefowl react stronger both in terms of physiology and behavior to a brief restraint stress than domesticated White Leghorn, demonstrating modified functions of the hypothalamic-pituitary-adrenal (HPA) axis. We mapped quantitative trait loci (QTL) underlying variations in stress-induced hormone levels using 232 birds from the 12th generation of an advanced intercross between White Leghorn and Red Junglefowl, genotyped for 739 genetic markers. Plasma levels of corticosterone, dehydroepiandrosterone (DHEA), and pregnenolone (PREG) were measured using LC-MS/MS in all genotyped birds. Transcription levels of the candidate genes were measured in the adrenal glands or hypothalamus of 88 out of the 232 birds used for hormone assessment. Genes were targeted for expression analysis when they were located in a hormone QTL region and were differentially expressed in the pure breed birds. One genome-wide significant QTL on chromosome 5 and two suggestive QTL together explained 20% of the variance in corticosterone response. Two significant QTL for aldosterone on chromosome 2 and 5 (explaining 19% of the variance), and one QTL for DHEA on chromosome 4 (explaining 5% of the variance), were detected. Orthologous DNA regions to the significant corticosterone QTL have been previously associated with the physiological stress response in other species but, to our knowledge, the underlying gene(s) have not been identified. SERPINA10 had an expression QTL (eQTL) colocalized with the corticosterone QTL on chromosome 5 and PDE1C had an eQTL colocalized with the aldosterone QTL on chromosome 2. Furthermore, in both cases, the expression levels of the genes were correlated with the plasma levels of the hormones. Hence, both these genes are strong putative candidates for the domestication-induced modifications of the stress response in chickens. Improved understanding of the genes associated with HPA-axis reactivity can provide insights into the pathways and mechanisms causing stress-related pathologies.

Place, publisher, year, edition, pages
GENETICS SOCIETY AMERICA, 2017
Keywords
animal domestication, quantitative trait genes, corticosterone, aldosterone
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-319644 (URN)10.1534/g3.116.037721 (DOI)000394357100015 ()27974436 (PubMedID)
Funder
Swedish Research Council, 621-2011-4731 621-2011-4423, 2015-4870EU, European Research Council, 322206
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-11-29Bibliographically approved
Bowden, J. A., Heckert, A., Ulmer, C. Z., Jones, C. M., Koelmel, J. P., Abdullah, L., . . . Zhou, S. (2017). Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma. Journal of Lipid Research, 58(12), 2275-2288
Open this publication in new window or tab >>Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
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2017 (English)In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 58, no 12, p. 2275-2288Article in journal (Refereed) Published
Abstract [en]

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

Keywords
fatty acyls, glycerolipids, lipids, phospholipids, quality control, quantitation, sphingolipids, Standard Reference Material 1950, sterols, National Institute of Standards and Technology
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-344222 (URN)10.1194/jlr.M079012 (DOI)000416963900004 ()28986437 (PubMedID)
Funder
Swedish Research Council, 2015-4870Swedish Heart Lung Foundation, HLF 20140469; HLF 20150640
Available from: 2018-03-06 Created: 2018-03-06 Last updated: 2018-03-06Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-4597-041x

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