uu.seUppsala universitets publikationer
Ändra sökning
Avgränsa sökresultatet
2345678 201 - 250 av 420
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 201.
    Kask, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Hörnaeus, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Åberg, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Jorsback, A.
    GE Healthcare, Uppsala, Sweden..
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Proteomic, functional and receptor studies of growth differentiation factor 15, GDF-152018Ingår i: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 114, s. S76-S76Artikel i tidskrift (Övrigt vetenskapligt)
  • 202.
    Kask, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jorsback, Anneli
    Winkvist, Maria
    Alfredsson, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Ek, Bo
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Siegbahn, Agneta
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Identification of Novel Downstream Molecules of Tissue Factor Activation by Comparative Proteomic Analysis2014Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, nr 2, s. 477-488Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tissue factor (TF) is both an initiator of blood coagulation and a signaling receptor. Using a proteomic approach, we investigated the role of TF in cell signaling when stimulated by its ligand, activated factor VII (FVIIa). From a 2-D difference gel electrophoresis (DIGE) study we found forty one spots that were differentially regulated over time in FVIIa stimulated cells or in comparison to nonstimulated cells. Mass spectrometry identifies 23 out of these as 13 different proteins. One of them, elongation factor 2 (EF-2), was investigated in greater detail by Western blot, a protein synthesis assay and cell cycle analysis. When tissue factor was stimulated by FVIIa, the phosphorylation of EF-2 increased which inactivates this protein. Analyzing the effect using site inactivated FVIIa (FVIIai), as well as the protease activated receptor 2 (PAR-2) agonist SLIGKV, indicated that the inactivation was not PAR-2 dependent. A panel of tissue factor mutants was analyzed further to try to pinpoint what part of the cytoplasmic domain that is needed for this effect. Performing a protein synthesis assay in two different cell lines we could confirm that protein synthesis decreased upon stimulation by FVIIa. Cell cycle analysis showed that FVIIa also promotes a higher degree of cell proliferation.

  • 203.
    Kaukoranta, Päivi
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Engman, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Hedberg, Christian
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi.
    Andersson, Pher G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Iridium Catalysts with Chiral Imidazole-Phosphine Ligands for Asymmetric Hydrogenation of Vinyl Fluorides and other Olefins2008Ingår i: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 350, nr 7-8, s. 1168-1176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    New chiral bidentate imidazole-phosphine ligands have been prepared and evaluated for the iridium-catalysed asymmetric hydrogenation of olefins. The imidazole-phosphine-ligated iridium catalysts hydrogenated trisubstituted olefins with the same sense of enantiodiscrimination as known iridium catalysts possessing oxazole and thiazole as N-donors. The imidazole-based catalysts were shown to hydrogenate vinyl fluorides, in some cases with the highest ee values published to date.

  • 204.
    Kronschläger, Martin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Oftalmiatrik.
    Forsman, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Yu, Zhaohua
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Oftalmiatrik.
    Talebizadeh, Nooshin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Oftalmiatrik.
    Löfgren, Stefan
    Meyer, Linda M
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Söderberg, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Oftalmiatrik.
    Pharmacokinetics for topically applied caffeine in the rat2014Ingår i: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 122, s. 94-101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.

  • 205.
    Kumar, Rohan J
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Molekylär biomimetik.
    Karlsson, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Kemisk fysik.
    Streich, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Kemisk fysik.
    Rolandini Jensen, Alice
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Kemisk fysik.
    Jäger, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Molekylär biomimetik.
    Becker, Hans-Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Kemisk fysik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Johansson, Olof
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Molekylär biomimetik.
    Hammarström, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Kemisk fysik.
    Vectorial Electron Transfer in Donor-Photosensitizer-Acceptor Triads Based on Novel Bis-tridentate Ruthenium Polypyridyl Complexes2010Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 16, nr 9, s. 2830-2842Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The first examples of rodlikedonor–photosensitizer–acceptor arrays based on bis-2,6-di(quinolin-8-yl)pyridineRuII complexes 1a and 3a for photoinduced electron transfer have been synthesized and investigated. The complexes are synthesized in a convergent manner and are isolated as linear, single isomers. Time-resolved absorption spectroscopy reveals long-lived, photoinduced charge-separated states(tCSS (1a)=140 ns, tCSS (3a)=200 ns) formed by stepwise electron transfer.The overall yields of charge separation (Yield 50% for complex 1a and Yield 95% for complex 3a) are unprecedented for bis-tridentate RuII polypyridyl complexes.This is attributed to the longlived excited state of the [Ru(dqp)2]2+ complex combined with fast electron transfer from the donor moiety following the initial charge separation. The rodlike arrangement of donor and acceptor gives controlled, vectorial electron transfer, free from the complications of stereoisomeric diversity. Thus, such arrays provide an excellent system for the study of photoinduced electron transfer and, ultimately, the harvesting of solar energy.

  • 206.
    Kushnir, Mark M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Beta-methylamino-L-alanine analysis by liquid chromatography tandem mass spectrometry with iTRAQ as the derivative2009Ingår i: European journal of mass spectrometry, ISSN 1469-0667, E-ISSN 1751-6838, Vol. 15, nr 3, s. 439-443Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amino acid BMMA is produced by cyanobacteria and has been linked to the development of neurodegenerative diseases. We developed a method for quantitative analysis of BMAA in biological samples and plant extracts. The method is utilizing iTRAQ and LC-MS/MS detection using multiple reaction monitoring mode. The method uses 50 pL of sample and has a   Limit of quantitation of 300 ng mL(-1), within-run run imprecision  below 1%. Using this method we analyzed human serum samples, human cerebrospinal fluid samples and extract of the cycad seed. No BMAA could be detected in the human samples. Content of BMAA in the seed was 50 mg kg(-1).

  • 207.
    Kushnir, Mark M
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för analytisk kemi.
    Naessen, Tord
    Kirilovas, Dmitrijus
    Chaika, Andrey
    Nosenko, Jelena
    Mogilevkina, Iryna
    Rockwood, Alan L
    Carlstrom, Kjell
    Bergquist, Jonas
    Steroid profiles in ovarian follicular fluid samples using high sensitivity tandem mass spectrometry methodsIngår i: Artikel i tidskrift (Refereegranskat)
  • 208.
    Kushnir, Mark M
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Naessen, Tord
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Kirilovas, Dmitrijus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Chaika, Andrey
    Nosenko, Jelena
    Mogilevkina, Iryna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Rockwood, Alan L
    Carlström, Kjell
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Steroid profiles in ovarian follicular fluid from regularly menstruating women and women after ovarian stimulation2009Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 55, nr 3, s. 519-526Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Information on the concentrations of steroids in ovarian follicular fluid (FF) from regularly menstruating (RM) women has been limited because of the absence of methods for the simultaneous quantification of multiple steroids in small volumes of FF. We studied steroid profiles in FF during the early follicular phase of the menstrual cycle and after ovarian stimulation for in vitro fertilization (IVF), and compared concentrations with published values obtained by immunoassay (IA). METHODS: We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure 13 steroids in 40-microL aliquots of FF samples from 21 RM women and from 5 women after ovarian stimulation for IVF. Relationships between concentrations of steroids and their ratios (representations of the enzyme activities) were evaluated within and between subgroups. RESULTS: The concentrations of testosterone (Te), androstenedione (A4), and estradiol (E2) measured by LC-MS/MS were lower than those previously reported in studies with IAs. In RM women, androgens were the most abundant class of steroids, with A4 being the major constituent. The concentrations of 17-hydroxyprogesterone (17OHP), total androgens, and estrogens were 200- to 1000-fold greater in FF than in serum. Compared with RM women, FF samples from women undergoing ovarian stimulation had significantly higher concentrations of E2 (P = 0.021), pregnenolone (P = 0.0022), 17OHP (P = 0.0007), and cortisol (F) (P = 0.0016), and significantly higher ratios of F to cortisone (P = 0.0006), E2 to estrone (P = 0.0008), and E2 to Te (P = 0.0013). CONCLUSIONS: The data provide the first MS-based concentration values for 13 steroids in ovarian FF from RM women, from estrogen- and androgen-dominant follicles, and from women after ovarian stimulation for IVF.

  • 209.
    Kushnir, Mark M.
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Naessén, Tord
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Wånggren, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Rockwood, Alan L.
    Crockett, David K.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Protein and Steroid Profiles in Follicular Fluid after Ovarian Hyperstimulation as Potential Biomarkers of IVF Outcome2012Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 11, nr 10, s. 5090-5100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Controlled ovarian hyperstimulation is performed to assist with generation of multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our study was to evaluate differences in protein and steroid profiles in ovarian follicular fluid (hFF) samples obtained during oocy-te retrieval from women undergoing IVF treatment and to identify physiological pathways associated with the proteins. The hFF samples were depleted of abundant proteins, fractionated by ultrafiltration, digested, and analyzed by nano-LC QTOF. Concentrations of 15 endogenous steroids were determined in the samples using LC-MS/MS methods. The total number of proteins identified in the samples was 75, of which 4, 7, and 2 were unique to the samples from women with viable pregnancy, miscarriage, and no pregnancy, respectively. Identified proteins were associated with the acute response signaling, coagulation system, intrinsic and extrinsic prothrombin activation, complement system, neuroprotective role of THOP1, FXR/RXR activation, role of tissue factor, and growth hormone pathways. A greater number of proteins associated with biosynthesis was found in hFF samples corresponding to the oocytes resulting in pregnancy. The abundance of seven proteins was found to be associated with steroidogenesis. The obtained data will contribute to better understanding of the pathogenesis and development of noninvasive markers for assessment of oocytes viability.

  • 210. Kushnir, Mark M.
    et al.
    Roberts, William L.
    Rockwood, Alan L.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Bunker, Ashley M.
    Meikle, A. Wayne
    Are Estradiol results determined by the tandem mass spectrometry assay clinically useful for children?: reply2009Ingår i: American Journal of Clinical Pathology, ISSN 0002-9173, E-ISSN 1943-7722, Vol. 131, nr 5, s. 747-749Artikel i tidskrift (Refereegranskat)
  • 211.
    Kushnir, Mark M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Rockwood, A. L.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    LC-MS/MS in clinical laboratories2013Ingår i: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 5, nr 1, s. 5-6Artikel i tidskrift (Refereegranskat)
  • 212.
    Kushnir, Mark M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Rockwood, Alan L.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Liquid chromatography-tandem mass spectrometry applications in endocrinology2010Ingår i: Mass spectrometry reviews (Print), ISSN 0277-7037, E-ISSN 1098-2787, Vol. 29, nr 3, s. 480-502Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been recognized as a primary methodology for the accurate analysis of endogenous steroid hormones in biological samples. This review focuses on the use of LC-MS/MS in clinical laboratories to assist with the diagnosis of diverse groups of endocrine and metabolic diseases. Described analytical methods use on-line and off-line sample preparation and analytical derivatization to enhance analytical sensitivity, specificity, and clinical utility. Advantages of LC-MS/MS as an analytical technique include high specificity, possibility to simultaneously measure multiple analytes, and the ability to assess the specificity of the analysis in every sample. All described analytical methods were extensively validated, utilized in routine diagnostic practice, and were applied in a number of clinical and epidemiological studies, including a study of the steroidogenesis in ovarian follicles.

  • 213.
    Kushnir, Mark M
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för analytisk kemi.
    Rockwood, Alan L
    Bergquist, Jonas
    Varshavsky, Marina
    Roberts, William L
    Yue, Bingfang
    Bunker, Ashely M
    Meikle, A Wayne
    High sensitivity tandem mass spectrometry assay for serum estrone and estradiol2008Ingår i: American Journal of Clinical Pathology, ISSN 0002-9173, E-ISSN 1943-7722, Vol. 129, nr 4, s. 530-539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High-sensitivity measurement of serum estrogens is important in adult and pediatric endocrinology and oncology. We developed a high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of estrone (E-1) and estradiol (E-2). Aliquots of 200 mu L of serum were spiked with internal standard, extracted, derivatized with dansyl chloride, and analyzed by LC-MS/MS using 2-dimensional chromatographic separation. Total imprecision for the method was less than 11%; the limit of quantitation was 1 pg/mL. Reference intervals were established with samples from more than 900 healthy postmenopausal women, men, girls, and boys. Concentrations of estrogens in children reached adult levels by Tanner stage 3. In men and postmenopausal women, the median concentrations of total estrogens (E-1 + E-2) were 39 and 22 pg/mL, and the median E-2/E-1 ratios were 0.98 and 0.55, respectively. The method requires a small sample volume and has adequatesensitivity and specificity for analyzing estrogens in samples from postmenopausal women, men, and children.

  • 214.
    Kushnir, Mark M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Rockwood, Alan L.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Varshavsky, Marina
    Roberts, William L.
    Yue, Bingfang
    Bunker, Ashley M.
    Meikle, A. Wayne
    High-Sensitivity Tandem Mass Spectrometry Assay for Serum Estrone and Estradiol2008Ingår i: American Journal of Clinical Pathology, ISSN 0002-9173, E-ISSN 1943-7722, Vol. 129, nr 4, s. 530-539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High-sensitivity measurement of serum estrogens is important in adult and pediatric endocrinology and oncology. We developed a high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of estrone (E-1) and estradiol (E-2). Aliquots of 200 mu L of serum were spiked with internal standard, extracted, derivatized with dansyl chloride, and analyzed by LC-MS/MS using 2-dimensional chromatographic separation. Total imprecision for the method was less than 11%; the limit of quantitation was 1 pg/mL. Reference intervals were established with samples from more than 900 healthy postmenopausal women, men, girls, and boys. Concentrations of estrogens in children reached adult levels by Tanner stage 3. In men and postmenopausal women, the median concentrations of total estrogens (E-1 + E-2) were 39 and 22 pg/mL, and the median E-2/E-1 ratios were 0.98 and 0.55, respectively. The method requires a small sample volume and has adequate sensitivity and specificity for analyzing estrogens in samples from postmenopausal women, men, and children.

  • 215.
    Kushnir, Mark M.
    et al.
    ARUP Institute for Clinical and Experimental Pathology and Department of Pathology, University of Utah, Salt Lake City, UT, USA.
    Rockwood, Alan L.
    ARUP Institute for Clinical and Experimental Pathology and Department of Pathology, University of Utah, Salt Lake City, UT, USA.
    Roberts, William L.
    ARUP Institute for Clinical and Experimental Pathology and Department of Pathology, University of Utah, Salt Lake City, UT, USA.
    Yue, Bingfang
    ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Meikle, A. Wayne
    ARUP Institute for Clinical and Experimental Pathology. Department of Pathology and Department of Medicine, University of Utah, Salt Lake City, UT, USA.
    Liquid chromatography tandem mass spectrometry for analysis of steroids in clinical laboratories2011Ingår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 44, nr 1, s. 77-88Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Liquid chromatography tandem mass spectrometry is one of the most specific techniques available in clinical laboratories. In the past, immunoassays were the primary methodology for analysis of steroids in biological samples because they are rapid and easy to perform. However, these methods were shown to suffer from the lack of specificity for measuring many of the diagnostically important steroids. LC-MS/MS overcomes many of the limitations of immunoassays, enhances diagnostic utility of the testing, and expands diagnostic capabilities in endocrinology. In addition to the superior quality of the measurements, LC-MS/MS allows high throughput testing using small sample volume with minimal sample preparation, and frees the laboratory from dependence on suppliers of assay specific reagents. LC-MS/MS is being widely employed for routine measurement of steroids, and the methodology plays an important role in the standardization and harmonization of measurements among clinical laboratories.

  • 216.
    Kushnir, Mark
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi. Analytisk kemi.
    Rockwood, Alan
    Roberts, W.L.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi. Analytisk kemi.
    Varshavsky, M.
    Yuc, B.
    Bunker, A.M.
    Meikle, A.W.
    High sensitivity tandem mass spectrometry test for serum estrogens2007Ingår i: Clin.Chem 53 (6) A183-A183 D-74 Suppl. S, 2007Konferensbidrag (Övrigt vetenskapligt)
  • 217.
    Källsten, Malin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zhao, Hongxing
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Konzer, Anne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Sara Bergström
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    A comparative study of phosphopeptide-selective techniques for a sub-proteome of a complex biological sample.2016Ingår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 408, nr 9, s. 2347-2356Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Phosphorylation of proteins is important for controlling cellular signaling and cell cycle regulatory events. The process is reversible and phosphoproteins normally constitute a minor part of the global proteome in a cell. Thus, sample preparation techniques tailored for phosphoproteome studies are continuously invented and evaluated. This paper aims at evaluating the performances of the most popular techniques for phospho-enrichments in sub-proteome analysis, such as viral proteomes expressed in human cells during infection. A two-species sample of Adenovirus type 2 infected human cells was used, and in-solution digestion, strong cation exchange (SCX), and electrostatic repulsion hydrophilic interaction chromatography (ERLIC) fractionation, and subsequent enrichment by TiO2, were compared with SDS-PAGE fractionation and in-gel digestion. Evaluation was focused on phosphopeptide detection in the sub-proteome. The results showed that the SCX+TiO2 or ERLIC+TiO2 combinations had the highest enrichment efficiencies, but SDS-PAGE fractionation and in-gel digestion resulted in the highest number of identified proteins and phosphopeptides. Furthermore, the study demonstrates the usefulness of applying as many orthogonal techniques as possible in deep phosphoproteome analysis, since the overlap between approaches was low.

  • 218.
    Källsten, Malin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Ghorasaini, Mohan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hartmann, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Lehmann, Fredrik
    Oncopeptides AB.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Kovac, Lucia
    Recipharm OT Chemistry AB.
    Lind, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Magnetic beads for desalting of monoclonal antibodies and antibody-drug conjugatesManuskript (preprint) (Övrigt vetenskapligt)
  • 219.
    Källsten, Malin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Recipharm OT Chem AB, Uppsala, Sweden.
    Hartmann, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Artemenko, Konstantin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergström Lind, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lehmann, Fredrik
    Recipharm OT Chem AB, Uppsala, Sweden.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Qualitative analysis of antibody-drug conjugates (ADCs): an experimental comparison of analytical techniques of cysteine-linked ADCs.2018Ingår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 143, nr 22, s. 5487-5496Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibody-drug conjugates (ADCs) are an emerging type of biotherapeutics that utilize multiple tissue-specific antibodies combined with a range of linker designs to enable the transportation and selective release of cytotoxic drugs in close proximity to tumours. Consisting of antibodies conjugated to small drug molecules through a variety of linkers, ADCs are chemically complex analytes. Here we present a unique experimental comparison of four techniques for ADC analysis: hydrophobic interaction chromatography (HIC-UV/Vis), reversed phase liquid chromatography mass spectrometry (RPLC-MS), using either a QToF or an Orbitrap analyser, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Four different ADCs consisting of Trastuzumab, monomethyl auristatin E (MMAE) and a peptidic linker moiety differing in their respective stoichiometric ratios in regard to drug-to-antibody ratio (DAR) were used for the comparison. We found that the determined DAR from all techniques was comparable, while the accuracy of the molecular weights for the conjugated light and heavy chain differed more extensively. This indicates that the choice of a mass analyser is more crucial for determining the accurate weights of the light and heavy chains than to evaluate the DAR of a given batch. However, ambiguous DAR assignment in HIC-UV/Vis or bias for either the light or heavy chain fragments in the mass spectrometry-based techniques can influence the obtained average DAR value and the use of complementary techniques is advisable. Out of the four techniques evaluated, HIC-UV/Vis and MALDI required less time to obtain an average DAR value and would therefore be good for initial screenings in the early stages of the discovery phase of new ADCs.

    Ladda ner fulltext (pdf)
    fulltext
  • 220.
    Källsten, Malin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hartmann, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Kovac, Lucia
    Recipharm OT Chemistry AB.
    Lehmann, Fredrik
    Oncopeptides AB.
    Lind, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Investigating the Impact of Sample Preparation on Mass Spectrometry-Based Drug-To-Antibody Ratio Determination for Cysteine- and Lysine-Linked Antibody-Drug ConjugatesManuskript (preprint) (Övrigt vetenskapligt)
  • 221.
    Källsten, Malin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Recipharm OT Chem AB, Virdings Alle 32b, S-75450 Uppsala, Sweden.
    Pijnappel, Matthijs
    Recipharm OT Chem AB, Virdings Alle 32b, S-75450 Uppsala, Sweden.
    Hartmann, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Lehmann, Fredrik
    Oncopeptides AB, Luntmakargatan 46, SE-11137 Stockholm, Sweden.
    Kovac, Lucia
    Recipharm OT Chem AB, Virdings Alle 32b, S-75450 Uppsala, Sweden.
    Lind, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Application of triple quadrupole mass spectrometry for the characterization of antibody-drug conjugates2019Ingår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 411, nr 12, s. 2569-2576Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibody-drug conjugates (ADCs) are an inherently heterogeneous class of biotherapeutics, the development of which requires extensive characterization throughout. During the earliest phases of preclinical development, when synthetic routes towards the desired conjugate are being assessed, the main interest lies in the determination of the average drug-to-antibody ratio (DAR) of a given batch as well as information about different conjugation species. There has been a trend in mass spectrometry (MS)-based characterization of ADCs towards the use of high-resolving mass spectrometry for many of these analyses. Considering the high cost for such an instrument, the evaluation of cheaper and more accessible alternatives is highly motivated. We have therefore tested the applicability of a quadrupole mass analyzer for the aforementioned characterizations. Eight ADCs consisting of trastuzumab and varying stoichiometries of Mc-Val-Cit-PABC-monomethyl auristatin E conjugated to native cysteines were synthesized and served as test analytes. The average DAR value and molecular weights (Mw) of all detected chains from the quadrupole mass analyzer showed surprisingly high agreement with results obtained from a time-of-flight (TOF) mass analyzer and hydrophobic interaction chromatography (HIC)-derived values for all investigated ADC batches. Acquired Mw were within 80ppm of TOF-derived values, and DAR was on average within 0.32 DAR units of HIC-derived values. Quadrupole mass spectrometers therefore represent a viable alternative for the characterization of ADC in early-stage development.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 222.
    Källsten, Malin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Visanu, Diana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Pijnappel, Matthijs
    Recipharm OT Chemistry AB.
    Lehmann, Fredrik
    Oncopeptides AB.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lind, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Kovac, Lucia
    Recipharm OT Chemistry AB.
    The potential use of supercharging agents for improved mass spectrometric analysis of monoclonal antibodies and antibody-drug conjugatesManuskript (preprint) (Övrigt vetenskapligt)
  • 223. Lambert, Gavin
    et al.
    Elam, Mikael
    Friberg, Peter
    Lundborg, Christopher
    Gao, Sinsia
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi. Analytisk kemi.
    Nitescu, Petre
    Acute response to intracisternal bupivacaine in patients with refractory pain of the head and neck2006Ingår i: J. Physiol, nr 570.2, s. 421-428Artikel i tidskrift (Refereegranskat)
  • 224.
    Leito, Ivo
    et al.
    Univ Tartu, Inst Chem, Ravila 14a, EE-50411 Tartu, Estonia.
    Teearu, Anu
    Univ Tartu, Inst Chem, Ravila 14a, EE-50411 Tartu, Estonia.
    Bobacka, Johan
    Abo Akad Univ, Analyt Chem Lab, Johan Gadolin Proc Chem Ctr, Biskopsgatan 8, SF-20500 Turku, Finland.
    Randon, Jerome
    Univ Claude Bernard Lyon 1, CNRS, UMR 5280, Univ Lyon,Inst Sci Analyt, 5 Rue Doua, F-69100 Villeurbanne, France.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    EACH (Excellence in Analytical Chemistry), an Erasmus Mundus Joint Programme: progress and success2019Ingår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 411, nr 23, s. 5913-5921Artikel i tidskrift (Övrigt vetenskapligt)
  • 225.
    Lennartsson, Anna-Karin
    et al.
    The Institute of Stress Medicine, Gothenburg AND The Department of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Kushnir, Mark M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Billig, Håkan
    The Department of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Jonsdottir, Ingibjörg H
    The Institute of Stress Medicine, Gothenburg AND The Department of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Sex steroid levels temporarily increase in response to acute psychosocial stress in healthy men and women2012Ingår i: International Journal of Psychophysiology, ISSN 0167-8760, E-ISSN 1872-7697, Vol. 84, nr 3, s. 246-253Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is well known that acute psychosocial stress activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). However, the effect of acute psychosocial stress on the hypothalamic-pituitary-gonadal (HPG) axis and levels of sex steroids are less known. The aim of this study was to investigate the effect of acute psychosocial stress on serum concentrations of sex steroids in healthy men and women. Twenty men and 19 women (age 30-50years) underwent Trier Social Stress Test (TSST), a tool for investigating psychobiological stress responses in a laboratory setting. Blood samples were collected before, directly after the stress test, and after 30 minutes of the recovery. Concentrations of androgens were measured with high specificity LC-MS/MS method; concentrations of cortisol, estradiol and sex hormone-binding globulin where determined using immunoassays. In both men and women we observed significantly elevated levels of testosterone, estradiol, androstenedione and sex hormone binding globulin along with significantly increased adrenocorticotropic hormone (ACTH), serum cortisol, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) as a response to the stressor. Thus, even though the HPG axis and the production of sex steroids may be inhibited during prolonged periods of stress, the sex steroid levels may increase in the initial phase of the acute psychosocial stress.

  • 226. Lennartsson, Anna-Karin
    et al.
    Kushnir, Mark M.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Jonsdottir, Ingibjorg H.
    DHEA and DHEA-S response to acute psychosocial stress in healthy men and women2012Ingår i: Biological Psychology, ISSN 0301-0511, E-ISSN 1873-6246, Vol. 90, nr 2, s. 143-149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study investigates the effect of acute psychosocial stress on serum concentrations of DHEA and DHEA-S in healthy men and women. Twenty men and 19 women (age 30-50 years) underwent Trier Social Stress Test (TSST). Physiological measurements were performed before, directly after the stress test and after 30 mins of recovery. In both men and women, significantly elevated DHEA and DHEA-S levels were observed in response to the stressor. There was a large inter-individual variation in the magnitude of the response, especially for DHEA but no statistical difference between men and women. Magnitude of the change in the levels of DHEA was found to be positively associated with the magnitude of the changes in ACTH, cortisol and heart rate. Furthermore, the results of this study suggest that the capacity to secrete DHEA and DHEA-S during acute psychosocial stress declines with age.

  • 227.
    Li, Meishan
    et al.
    Department of Physiology and Pharmacology AND Department of Clinical Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Sweden.
    Ogilvie, Hannah
    Department of Physiology and Pharmacology AND Department of Clinical Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Sweden.
    Ochala, Julien
    Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences and Medicine, King’s College London, UK.
    Artemenko, Konstantin A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Iwamoto, Hiroyuki
    Japan Synchrotron Radiation Research Institute, Japan.
    Yagi, Naoto
    Japan Synchrotron Radiation Research Institute, Japan.
    Bergquist, Jonas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Larsson, Lars
    Department of Physiology and Pharmacology AND Department of Clinical Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Sweden.
    Aberrant post-translational modifications compromise human myosin motor function in old age2015Ingår i: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 14, nr 2, s. 228-235Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Novel experimental methods, including a modified single fiber in vitro motility assay, X-ray diffraction experiments, and mass spectrometry analyses, have been performed to unravel the molecular events underlying the aging-related impairment in human skeletal muscle function at the motor protein level. The effects of old age on the function of specific myosin isoforms extracted from single human muscle fiber segments, demonstrated a significant slowing of motility speed (P < 0.001) in old age in both type I and IIa myosin heavy chain (MyHC) isoforms. The force-generating capacity of the type I and IIa MyHC isoforms was, on the other hand, not affected by old age. Similar effects were also observed when the myosin molecules extracted from muscle fibers were exposed to oxidative stress. X-ray diffraction experiments did not show any myofilament lattice spacing changes, but unraveled a more disordered filament organization in old age as shown by the greater widths of the 1, 0 equatorial reflections. Mass spectrometry (MS) analyses revealed eight age-specific myosin post-translational modifications (PTMs), in which two were located in the motor domain (carbonylation of Pro79 and Asn81) and six in the tail region (carbonylation of Asp900, Asp904, and Arg908; methylation of Glu1166; deamidation of Gln1164 and Asn1168). However, PTMs in the motor domain were only observed in the IIx MyHC isoform, suggesting PTMs in the rod region contributed to the observed disordering of myosin filaments and the slowing of motility speed. Hence, interventions that would specifically target these PTMs are warranted to reverse myosin dysfunction in old age.

    Ladda ner fulltext (pdf)
    fulltext
  • 228.
    Liljegren, Gustav
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen.
    Dahlin, Andreas P.
    Zettersten, Camilla
    Bergquist, Jonas
    Nyholm, Leif
    On-line coupling of a microelectrode array equipped poly(dimethylsiloxane) microchip with an integrated graphite electrospray emitter to electrospray ionisation mass spectrometryManuskript (Övrigt vetenskapligt)
  • 229. Liljegren, Gustav
    et al.
    Dahlin, Andreas P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen.
    Zettersten, Camilla
    Bergquist, Jonas
    Nyholm, Leif
    On-line coupling of a microelectrode array equipped poly(dimethylsiloxane) microchip with an integrated graphite electrospray tip to electrospray mass spectrometryIngår i: Artikel i tidskrift (Refereegranskat)
  • 230.
    Liljegren, Gustav
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen. Institutionen för materialkemi, Oorganisk kemi. Analytisk kemi.
    Dahlin, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen. Institutionen för materialkemi, Oorganisk kemi. Analytisk kemi.
    Zettersten, Camilla
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen. Institutionen för materialkemi, Oorganisk kemi. Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen. Institutionen för materialkemi, Oorganisk kemi. Analytisk kemi.
    Nyholm, Leif
    Institutionen för materialkemi, Oorganisk kemi. Oorganisk kemi.
    On-line coupling of a microelectrode array equipped poly(dimethylsiloxane) microchip with an integrated graphite electrospray emitter for electrospray ionisation mass spectrometry2005Ingår i: Lab on a Chip, nr 5, s. 1008-1016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A novel method for the manufacturing of microchips for on-chip combinations of electrochemistry (EC) and sheathless electrospray ionisation mass spectrometry (ESI-MS) is described. The technique, which does not require access to clean-room facilities, is based on the incorporation of an array of gold microcoil electrodes into a poly(dimethylsiloxane) (PDMS) microflow channel equipped with an integrated graphite based sheathless ESI emitter. Electrochemical measurements, which were employed to determine the electroactive area of the electrodes and to test the microchips, show that the manufacturing process was reproducible and that the important interelectrode distance in the electrochemical cell could to be adequately controlled. The EC-ESI-MS device was evaluated based on the ESI-MS detection of the oxidation products of dopamine. The results demonstrate that the present on-chip approach enables full potentiostatic control of the electrochemical cell and the attainment of very short transfer times between the electrochemical cell and the electrospray emitter. The transfer times were 0.6 and 1.2 s for flow rates of 1.0 and 0.5 uL min-1, respectively, while the electrochemical conversion efficiency of the electrochemical cell was found to be 30% at a flow rate of 0.5 uL min-1. To decouple the electrochemical cell from the ESI-MS high voltage and to increase the user-friendliness, the on-line electrochemistry-ESI-MS experiments were performed using a wireless Bluetooth battery-powered instrument with the chip floating at the potential induced by the ESI high voltage. The described on-chip EC-ESI-MS device can be used for fundamental electrochemical investigations as well as for applications based on the use of electrochemically controlled sample pretreatment, preconcentration and ionisation steps prior to ESI-MS.

  • 231.
    Lind, Anne-Li
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Yu, Di
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Freyhult, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Bodolea, Constantin
    Department of Anaesthesia and Intensive Care, University of Medicine and Pharmacy, Cluj, Napoca, Romania..
    Ekegren, Titti
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Gustafsson, Mats G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Katila, Lenka
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 2, artikel-id e0149821Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.

    Ladda ner fulltext (pdf)
    fulltext
  • 232.
    Lind, Sara Bergström
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Artemenko, Konstantin A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Elfineh, Lioudmila
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zhao, Yanhong
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Post translational modifications in adenovirus type 22013Ingår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 447, nr 1-2, s. 104-111Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have combined 2-D SOS-PAGE with liquid chromatography-high resolving mass spectrometry (LC-MS) to explore the proteome of the adenovirus type 2 (Ad2) at the level of post translational modifications (PTMs). The experimental design included in-solution digestion, followed by titanium dioxide enrichment, as well as in-gel digestion of polypeptides after separation of Ad2 capsid proteins by 1-D and 2-D SOS-PAGE. All samples were analyzed using LC-MS with subsequent manual verification of PTM positions. The results revealed new phosphorylation sites that can explain the observed trains of protein spots observed for the pIII, pIIIa and ply proteins. The pin protein was found to be the most highly modified protein with now 18 verified sites of phosphorylation, three sites of nitrated tyrosine and one sulfated tyrosine. Nitrated tyrosines were also identified in pII. Lysine acetylations were detected in pII and pVI. The findings make the Ad2 virion much more complex than hitherto believed. 

  • 233.
    Lindberg, Peter
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Signalbehandling.
    Dahlin, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Bergström, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Thorslund, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Materialvetenskap.
    Andrén, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nikolajeff, Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Materialvetenskap.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Sample pretreatment on a microchip with an integrated electrospray emitter2006Ingår i: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 27, nr 11, s. 2075-2082Artikel i tidskrift (Refereegranskat)
  • 234.
    Liu, Fang
    et al.
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China.;Binzhou Med Univ, Dept Radiol, Affiliated Hosp, Binzhou 256603, Shandong, Peoples R China..
    Zhang, Yuan
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Men, Tingting
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Jiang, Xingyue
    Binzhou Med Univ, Dept Radiol, Affiliated Hosp, Binzhou 256603, Shandong, Peoples R China..
    Yang, Chunhua
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Li, He
    Binzhou Med Univ, Yantai Affiliated Hosp, Dept Gastr & Intestine, Yantai 264003, Shandong, Peoples R China..
    Wei, Xiaodan
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Yan, Dong
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Feng, Gangming
    China Agr Univ, Yantai Inst, Yantai 264670, Shandong, Peoples R China..
    Yang, Jianke
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Wang, Bin
    Binzhou Med Univ, Dept Radiol, Affiliated Hosp, Binzhou 256603, Shandong, Peoples R China..
    Jiang, Wenguo
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Mi, Jia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Tian, Geng
    Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 264003, Shandong, Peoples R China..
    Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor B signaling pathway2017Ingår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 13, s. 22059-22075Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues. Notably, several significant proteins are in the PDGF-B signaling pathway, including peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which were validated by western blot. Furthermore, upstream regulators including PDGF-B, PDGFR-beta, Akt, eIF4E and p70s6K were found significantly increased in the gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the proliferation of gastric cancer cells in vitro. The administration of exogenous PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B knockdown cells. Taken together, our findings suggested that PDGF-B signaling pathway plays an important role in the regulation of gastric cancer proliferation and the inhibition of this pathway may be a potential approach for treatment of gastric cancer.

  • 235.
    Ljungdahl, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Hanrieder, Jörg
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Andersson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Analysis of neuropeptides by MALDI imaging mass spectrometry2013Ingår i: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1023, s. 121-136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is one of the most effective tools for localizing small molecules and compounds directly in thin tissue sections. MALDI IMS should be used when the distribution of molecular species is not known and to localize changes due to a disease process or a treatment. In recent years it has become increasingly clear that many pathological processes are not readily correlated to dramatic changes in protein levels. MALDI IMS can aid the localization of areas where the cellular concentration of proteins may be high enough to play an important biological role, but when the precise location is unknown. Here, we present a MALDI IMS protocol and data analysis of molecular imaging of multiple rat brain sections.

  • 236.
    Ljungdahl, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Hanrieder, Jörg
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Fälth, Maria
    Unit Cancer Genome Research, Division of Molecular Genetics, German Cancer Research Center (DKFZ), Germany.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Andersson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Imaging Mass Spectrometry Reveals Elevated Nigral Levels of Dynorphin Neuropeptides in L-DOPA-Induced Dyskinesia in Rat Model of Parkinson's Disease2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 9, s. e25653-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS) was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm) nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors. This suggests that mu and/or delta subtype-selective opioid receptor antagonists may be clinically relevant for reducing L-DOPA-induced dyskinesia in Parkinson's disease.

    Ladda ner fulltext (pdf)
    fulltext
  • 237.
    Ljungvall, Karl
    et al.
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden..
    Magnusson, Ulf
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden..
    Korvela, Marcus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Norrby, Mattias
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden..
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Persson, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Heavy metal concentrations in female wild mink (Neovison vison) in Sweden: Sources of variation and associations with internal organ weights2017Ingår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 36, nr 8, s. 2030-2035Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The American mink is an invasive species in Sweden, and it is legally hunted all year. Therefore, the mink is well suited as a sentinel species for environmental monitoring. In the present study female mink (n = 91) from 6 different areas in Sweden were analyzed for the concentrations of silver, cadmium, mercury and lead in liver tissue using inductively coupled plasma mass spectrometry. The wet concentrations in liver tissue were 42.6 +/- 52.7 ng/g for silver, 99.5 +/- 100 ng/g for cadmium, 652 +/- 537 ng/g formercury, and 196 +/- 401 ng/g for lead (expressed as mean + standard deviation). There were associations between the sample area and the concentrations of silver, lead, and mercury. The concentrations of lead and cadmium varied with season of capture and lead, cadmium, and mercury were positively associated with increasing age. Relative liver weight was positively associated with concentrations of mercury and negatively associated with lead and cadmium. Relative kidney weight was negatively associated with lead concentrations. In summary, it is of importance to take age and season of capture into account when assessing levels of heavy metals in wild mink. Also, liver and kidneys seem to be potential targets for heavy metal toxicity in wild female mink in Sweden.

    Ladda ner fulltext (pdf)
    fulltext
  • 238.
    Llano-Diez, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Renaud, Guillaume
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Andersson, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gonzales Marrero, Humberto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Cacciani, Nicola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Corpeno, Rebeca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Artemenko, Konstantin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Mechanisms underlying intensive care unit muscle wasting and effects of passive mechanical loading2012Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, nr 5, s. R209-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ABSTRACT: INTRODUCTION: Critical ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decreased quality of life of survivors. Critical illness myopathy (CIM) is a frequently observed neuromuscular disorder in ICU patients. Sepsis, systemic corticosteroid hormone treatment and post-synaptic neuromuscular blockade have been forwarded as the dominating triggering factors. Recent experimental results from our group using a unique experimental rat ICU model have shown that the "mechanical silencing" associated with the ICU condition is the primary triggering factor. This study aims at (1) unraveling the mechanisms underlying CIM, and (2) evaluating the effects of a specific intervention aiming at reducing the mechanical silencing in sedated and mechanically ventilated ICU patients. METHODS: Muscle gene/protein expression, post-translational modifications (PTMs), muscle membrane excitability, muscle mass measurements, and contractile properties at the single muscle fiber level were explored in seven deeply sedated and mechanically ventilated ICU patients (not exposed to systemic corticosteroid hormone treatment, post-synaptic neuromuscular blockade or sepsis) subjected to unilateral passive mechanical loading 10 hours per day (2.5 hours, 4 times) for 9 +/- 1 days. RESULTS: These patients developed a phenotype considered pathognomonic of CIM, i.e., severe muscle wasting and a preferential myosin loss (P<0.001). In addition, myosin PTMs specific to the ICU condition were observed in parallel with an increased sarcolemmal expression and cytoplasmic translocation of nNOS. Passive mechanical loading for 9 +/- 1 resulted in a 35% higher specific force (P<0.001) compared with the unloaded leg, although it was not sufficient to prevent the loss of muscle mass. CONCLUSIONS: Mechanical silencing is suggested to be a primary mechanism underlying CIM, i.e., triggering the myosin loss, muscle wasting and myosin PTMs. The higher nNOS expression found in the ICU patients and its cytoplasmic translocation are forwarded as a probable mechanism underlying these modifications. The positive effect of passive loading on muscle fiber function strongly supports the importance of early physical therapy and mobilization in deeply sedated and mechanically ventilated ICU patients.

  • 239.
    Lundqvist, Maria J.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Kvantkemi.
    Persson, Petter
    Abrahamsson, Maria
    Hammarström, Leif
    Wolpher, Henriette
    Johansson, Olof
    Åkermark, Björn
    Eriksson, Lars
    Bergquist, Jonas
    Norrby, Per-Ola
    Ruthenium complexes of bipyridyl(pyridyl)alkane ligands: Effect of methylene or iso-propylene bridge on structural and photophysical propertiesManuskript (Övrig (populärvetenskap, debatt, mm))
  • 240.
    Ma'ayeh, Showgy Y.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Liu, Jingyi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Peirasmaki, Dimitra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Hörnaeus, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergström Lind, Sara K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Grabherr, Manfred
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Svärd, Staffan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells2017Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, nr 12, artikel-id e0006120Artikel i tidskrift (Refereegranskat)
    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.

    Ladda ner fulltext (pdf)
    fulltext
  • 241.
    Magnusson, Kristina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för biologisk beroendeforskning.
    Hallberg, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för biologisk beroendeforskning.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Nyberg, Fred
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för biologisk beroendeforskning.
    Enzymatic conversion of dynorphin A in the rat brain is affected by administration of nandrolone decanoate2007Ingår i: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 28, nr 4, s. 851-858Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The misuse of anabolic androgenic steroids (AAS) seems to produce profound effects on the central nervous system, leading to aggressive behavior and increased sensitivity to other drugs of abuse. The present study addresses the effect on the enzymatic transformation, here called dynorphin converting enzyme-like activity. The formation of the mu/delta opioid peptide receptor-preferring Leu-enkephalin-Arg6 from the kappa opioid peptide receptor-preferring dynorphin A was measured in rats treated with nandrolone decanoate. Significant variations in enzymatic transformation were observed in several brain regions. An altered receptor activation profile in these regions may be one contributory factor behind AAS-induced personality changes.

  • 242. Maksimov, Vladimir
    et al.
    Nakamura, Miyuki
    Wildhaber, Thomas
    Nanni, Paolo
    Ramström, Margareta
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hennig, Lars
    The H3 chaperone function of NASP is conserved in Arabidopsis.2016Ingår i: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 88, nr 3, s. 425-436Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Histones are abundant cellular proteins but, if not incorporated into chromatin, they are usually bound by histone chaperones. Here, we identify Arabidopsis NASP as a chaperone for histones H3.1 and H3.3. NASP interacts in vitro with monomeric H3.1 and H3.3 as well as with histone H3.1-H4 and H3.3-H4 dimers. However, NASP does not bind to monomeric H4. NASP shifts the equilibrium between histone dimers and tetramers towards tetramers but does not interact with tetramers in vitro. Arabidopsis NASP promotes [H3-H4]2 tetrasome formation, possibly by providing preassembled histone tetramers. However, NASP does not promote disassembly of in vitro preassembled tetrasomes. In contrast to its mammalian homolog, Arabidopsis NASP is a predominantly nuclear protein. In vivo, NASP binds mainly monomeric H3.1 and H3.3. Pulldown experiments indicated that NASP may also interact with the histone chaperone MSI1 and a HSC70 heat shock protein.

  • 243.
    Malmström, David
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Axén, Jakob
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Viberg, Peter
    Nanosep, Lund.
    Spégel, Peter
    Department of Clinical Sciences, Melecular Metabolism, Lund University Diabetes Centre, Malmö University Hospital.
    Continuous full filling capillary electrochromatography-electrospraying chromatographic nanoparticles2011Ingår i: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 32, nr 2, s. 261-267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The influence of instrumental parameters affecting the ionization in continuous full filling capillary electrochromatography/electrospray ionization mass spectrometry (CFF-CEC/ESI-MS) was investigated. The investigated parameters were the BGE and sheath liquid ion strength and organic modifier content, the nebulizer gas pressure, and the concentration of nanoparticles in the BGE. It was found that the nebulizer pressure had the largest influence on the separation efficiency and apparent retention. It was shown that even the lowest pressure investigated was sufficient to guide the nanoparticle flow away from the mass spectrometer inlet. A nebulizer pressure of 5 psi was found to be optimal; increasing the pressure significantly decreased the separation efficiency due to the generation of a hydrodynamic flow. Generally, the ion strength of both the BGE and the sheath liquid were found to have very moderate effects on the separation of a homologous series of dialkyl phthalates, whereas the ionization efficiency was found to be unaffected by the nanoparticles and the separation efficiency was found to increase with increasing concentrations up to 3.8 mg/mL, whereafter it was observed to drop. The optimized method was linear over a wide concentration range and presented LOD and LOQ more than threefold lower than those previously reported using CFF-CEC/ESI-MS.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 244.
    Manell, Hannes
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kristinsson, Hjalti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ubhayasekera, Sarojini Jayantha Kumari
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mörwald, Katharina
    Paracelsus Medical University.
    Staaf, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Cadamuro, Janne
    Paracelsus Medical University.
    Zsoldos, Fanni
    Paracelsus Medical University.
    Göpel, Sven
    AstraZeneca.
    Sargsyan, Ernest
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Weghuber, Daniel
    Paracelsus Medical University.
    Forslund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance2019Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, nr 7, s. 880-891Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To delineate mechanisms for fasting hyperglucagonemia in childhood obesity bystudying the associations between fasting plasma glucagon concentrations and plasmalipid parameters and fat compartments.

    Methods: Cross-sectional study of children and adolescents with obesity (n=147) and leancontrols (n=43). Differences in free fatty acids (FFA), triglycerides, insulin and fatcompartments (quantified by magnetic resonance imaging) across quartiles of fastingplasma glucagon concentration were analysed. Differences in OGTT glucagonresponse was tested in high vs low FFAs, triglycerides and insulin. Human islets ofLangerhans were cultured at 5.5 mmol/l glucose and in the absence or presence of aFFA mixture with total FFA concentration of 0.5 mmol/l and glucagon secretionquantified.

    Results: In children with obesity, the quartile with the highest fasting glucagon had higherinsulin (201±174 vs 83±39 pmol/l, p<0.01), FFAs (383±52 vs 338±109 μmol/l,p=0.02), triglycerides (1.5±0.9 vs 1.0±0.7 mmol/l, p<0.01), visceral adipose tissuevolume (1.9±0.8 vs 1.2±0.3 dm3, p<0.001) and a higher prevalence of impairedglucose tolerance (41% vs 8%, p=0.01) than the lowest quartile. During OGTT,children with obesity and high insulin had a worse suppression of glucagon during thefirst 10 minutes after glucose intake. Glucagon secretion was 2.6-fold higher in isletstreated with FFAs than in those not treated with FFAs.4

    Conclusion: Hyperglucagonemia in childhood obesity is associated with hyperinsulinemia, highplasma FFAs, high plasma triglycerides, visceral adiposity and impaired glucosetolerance. The glucagonotropic effect of FFAs on isolated human islets provides apotential mechanism linking high fasting plasma FFAs and glucagon levels.

  • 245.
    Manukyan, Levon
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Ubhayasekera, Sarojini J.K.A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergquist,, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sargsyan, Ernest
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Palmitate-induced impairments of beta-cell function are linked with generation of specific ceramide species via acylation of sphingosine2015Ingår i: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 156, nr 3, s. 802-812Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prolonged exposure to palmitate impairs beta-cell function and mass. One of the proposed mechanisms is alteration in ceramide generation. In the present study, exposure to palmitate induced the level of palmitoyl transferase and ceramide synthases, enzymes of the ceramide de novo and salvage pathways, and doubled total ceramide levels, which was associated with decreased insulin secretion and augmented apoptosis in MIN6 cells and human islets. By inhibiting enzymes of the pathways pharmacologically with ISP-1 or fumonisin B1 or by siRNA we showed that Cer(14:0), Cer(16:0), Cer(20:1) and Cer(24:0) species, generated by the salvage pathway, are linked to the harmful effect of palmitate on beta-cells. Oleate attenuates negative effects of palmitate on beta-cells. When oleate was included during culture of MIN6 cells with palmitate the palmitate-induced up-regulation of the enzymes of the de novo and salvage pathways was prevented resulting in normalized levels of all ceramide species except Cer(20:1). Our data suggest that enhanced ceramide generation in response to elevated palmitate levels involves both de novo and salvage pathways. However, the negative effects of palmitate on beta-cells are attributed to generation of ceramide species Cer(14:0), Cer(16:0) and Cer(24:0) via acylation of sphingosine.

    Ladda ner fulltext (pdf)
    fulltext
  • 246. Mehdi, Saher
    et al.
    Derkacheva, Maria
    Ramström, Margareta
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Kralemann, Lejon
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hennig, Lars
    The WD40 Domain Protein MSI1 Functions in a Histone Deacetylase Complex to Fine-Tune Abscisic Acid Signaling2016Ingår i: The Plant Cell, ISSN 1040-4651, E-ISSN 1532-298X, Vol. 28, nr 1, s. 42-54Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    MSI1 belongs to a family of histone binding WD40-repeat proteins. Arabidopsis thaliana contains five genes encoding MSI1-like proteins, but their functions in diverse chromatin-associated complexes are poorly understood. Here, we show that MSI1 is part of a histone deacetylase complex. We copurified HISTONE DEACETYLASE19 (HDA19) with MSI1 and transcriptional regulatory SIN3-like proteins and provide evidence that MSI1 and HDA19 associate into the same complex in vivo. These data suggest that MSI1, HDA19, and HISTONE DEACETYLATION COMPLEX1 protein form a core complex that can integrate various SIN3-like proteins. We found that reduction of MSI1 or HDA19 causes upregulation of abscisic acid (ABA) receptor genes and hypersensitivity of ABA-responsive genes. The MSI1-HDA19 complex fine-tunes ABA signaling by binding to the chromatin of ABA receptor genes and by maintaining low levels of acetylation of histone H3 at lysine 9, thereby affecting the expression levels of ABA receptor genes. Reduced MSI1 or HDA19 levels led to increased tolerance to salt stress corresponding to the increased ABA sensitivity of gene expression. Together, our results reveal the presence of an MSI1-HDA19 complex that fine-tunes ABA signaling in Arabidopsis.

  • 247.
    Moberg, My
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Bylund, Dan
    A generic stepwise optimization strategy for liquid chromatography electrospray ionization tandem mass spectrometry methods2006Ingår i: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 41, nr 10, s. 1334-1345Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The feasibility and advantages of using sophisticated chemometric tools in combination with the execution of thoroughly planned experiments to determine experimental conditions for optimal performance of an LC-ESI-MS/MS analysis is demonstrated. A stepwise strategy is proposed, which provides a controlled optimization procedure of the chromatographic quality (in terms of separation among the sample constituents) and maximizes the mass spectrometric signal of the selected product ions. Design of experiments (DOE) and response surface methodology are applied throughout the procedure. The stepwise approach has the advantage of dealing with the different optimization criteria separately, i.e. first ensuring sufficient chromatographic separation, then maximizing the amount of precursor ion entering the mass spectrometer, and finally generating high amounts of selected product ions. The experiments are performed on a linear ion trap mass spectrometer. Retention mapping using the band-tracking model is applied during LC development, which facilitates the optimization of segmented gradients. A set of different siderophores, strong iron chelates, is used as the model substances.

  • 248.
    Momeni, N
    et al.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Brudin, L
    Department of Clinical Physiology, Kalmar County Hospital, Kalmar, Sweden.
    Behnia, F
    Department of Occupational Therapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
    Sivberg, B
    Department of Health Sciences, Lund University, Lund, Sweden.
    Joghataei, M T
    Cellular and Molecular Research Centre, Tehran Medical University, Tehran, Iran.
    Persson, B L
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    A novel blood-based biomarker for detection of autism spectrum disorders2012Ingår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 2, artikel-id e91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autism spectrum disorders (ASD) are classified as neurological developmental disorders. Several studies have been carried out to find a candidate biomarker linked to the development of these disorders, but up to date no reliable biomarker is available. Mass spectrometry techniques have been used for protein profiling of blood plasma of children with such disorders in order to identify proteins/peptides that may be used as biomarkers for detection of the disorders. Three differentially expressed peptides with mass–charge (m/z) values of 2020±1, 1864±1 and 1978±1 Da in the heparin plasma of children with ASD that were significantly changed as compared with the peptide pattern of the non-ASD control group are reported here. This novel set of biomarkers allows for a reliable blood-based diagnostic tool that may be used in diagnosis and potentially, in prognosis of ASD.

    Ladda ner fulltext (pdf)
    fulltext
  • 249.
    Morell, Arvid
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lennmyr, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Jonsson, Ove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Tovedal, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Zemgulis, Vitas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Myrdal Einarsson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Thelin, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bjørnerud, Atle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Influence of blood/tissue differences in contrast agent relaxivity on tracer based MR perfusion measurements2015Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 28, nr 2, s. 135-147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    Perfusion assessment by monitoring the transport of a tracer bolus depends critically on conversion of signal intensity into tracer concentration. Two main assumptions are generally applied for this conversion; (1) contrast agent relaxivity is identical in blood and tissue, (2) change in signal intensity depends only on the primary relaxation effect. The purpose of the study was to assess the validity and influence of these assumptions.

    MATERIALS AND METHODS:

    Blood and cerebral tissue relaxivities r1, r2, and r2* for gadodiamide were measured in four pigs at 1.5 T. Gadolinium concentration was determined by inductively coupled plasma atomic emission spectroscopy. Influence of the relaxivities, secondary relaxation effects and choice of singular value decomposition (SVD) regularization threshold was studied by simulations.

    RESULTS:

    In vivo relaxivities relative to blood concentration [in s-1 mM-1 for blood, gray matter (GM), white matter (WM)] were for r1 (2.614 ± 1.061, 0.010 ± 0.001, 0.004 ± 0.002), r2 (5.088 ± 0.952, 0.091 ± 0.008, 0.059 ± 0.014), and r2* (13.292 ± 3.928, 1.696 ± 0.157, 0.910 ± 0.139). Although substantial, by a nonparametric test for paired samples, the differences were not statistically significant. The GM to WM blood volume ratio was estimated to 2.6 ± 0.9 by r1, 1.6 ± 0.3 by r2, and 1.9 ± 0.2 by r2*. Secondary relaxation was found to reduce the tissue blood flow, as did the SVD regularization threshold.

    CONCLUSION:

    Contrast agent relaxivity is not identical in blood and tissue leading to substantial errors. Further errors are introduced by secondary relaxation effects and the SVD regularization.

  • 250.
    Musunuri, Sravani
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Richard, Bernhard Clemens
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Shevchenko, Ganna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Micellar extraction possesses a new advantage for the analysis of Alzheimer's disease brain proteome2015Ingår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 407, nr 4, s. 1041-1057Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Integral membrane proteins (MPs), such as transporters, receptors, and ion channels, are of great interest because of their participation in various vital cellular functions including cell-cell interactions, ion transport, and signal transduction. However, studies of MPs are complicated because of their hydrophobic nature, heterogeneity, and low abundance. Cloud-point extraction (CPE) with the non-ionic surfactant Triton X-114 was performed to simultaneously extract and phase separate hydrophobic and hydrophilic proteins from Alzheimer's disease (AD) and unaffected control brain tissue. Quantitative proteomics analysis of temporal neocortex samples of AD patients and controls was performed using a shotgun approach based on stable isotope dimethyl labeling (DML) quantification technique followed by nanoLC-MS/MS analysis. A total of 1096 unique proteins were identified and quantified, with 40.3 % (211/524) predicted as integral MPs with at least one transmembrane domain (TMD) found in the detergent phase, and 10 % (80/798) in the detergent-depleted phase. Among these, 62 proteins were shown to be significantly altered (p-value < 0.05), in AD versus control samples. In the detergent fraction, we found 10 hydrophobic transmembrane proteins containing up to 14 putative TMDs that were significantly up- or down-regulated in AD compared with control brains. Changes in four of these proteins, alpha-enolase (ENOA), lysosome-associated membrane glycoprotein 1 (LAMP1), 14-3-3 protein gamma (1433G), and sarcoplasmic/endoplasmic reticulum calcium ATPase2 (AT2A2) were validated by immunoblotting. Our results emphasize that separating hydrophobic MPs in CPE contributes to an increased understanding of the underlying molecular mechanisms in AD. Such knowledge can become useful for the development of novel disease biomarkers.

2345678 201 - 250 av 420
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf