Browsing by Subject "MASS-SPECTROMETRY"

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  • Puurunen, Jenni; Sulkama, Sini; Tiira, Katriina; Araujo, Cesar; Lehtonen, Marko; Hanhineva, Kati; Lohi, Hannes (2016)
    Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent and multifactorial neuropsychiatric disorder in the human population worldwide. Complex etiology and clinical heterogeneity have challenged the research, diagnostics and treatment of the disease. Hyperactive and impulsive behaviour has also been observed in dogs, and they could offer a physiologically relevant model for human ADHD. As a part of our ongoing study to understand the molecular etiology of canine anxiety traits, this study was aimed to pilot an approach to identify metabolic biomarkers in canine ADHD-like behaviours for research, diagnostics and treatment purposes. Methods: We collected fresh plasma samples from 22 German Shepherds with varying ADHD-like behaviours. All dogs were on the same controlled diet for 2 weeks prior to sampling. A liquid chromatography combined with mass spectrometry (LC-MS)-based non-targeted metabolite profiling was performed to identify plasma metabolites correlating with the ADHD-like behaviour of the dogs. Results: 649 molecular features correlated with ADHD-like behavioural scores (p(raw) <0.05), and three of them [sn-1 LysoPC(18: 3), PC(18: 3/18: 2) and sn-1 LysoPE(18: 2)] had significant correlations also after FDR correction (pFDR <0.05). Phospholipids were found to negatively correlate with ADHD-like behavioural scores, whereas tryptophan metabolites 3-indolepropionic acid (IPA) and kynurenic acid (KYNA) had negative and positive correlations with ADHD-like behavioural scores, respectively. Conclusions: Our study identified associations between canine ADHD-like behaviours and metabolites that are involved in lipid and tryptophan metabolisms. The identified metabolites share similarity with earlier findings in human and rodent ADHD models. However, a larger replication study is warranted to validate the discoveries prior to further studies to understand the biological role of the identified metabolites in canine ADHD-like behaviours.
  • Itokazu, Yutaka; Tajima, Nobuyoshi; Kerosuo, Laura; Somerharju, Pentti; Sariola, Hannu; Yu, Robert K.; Kakela, Reijo (2016)
    The central nervous system (CNS) harbors multiple glial fibrillary acidic protein (GFAP) expressing cell types. In addition to the most abundant cell type of the CNS, the astrocytes, various stem cells and progenitor cells also contain GFAP+ populations. Here, in order to distinguish between two types of GFAP expressing cells with or without the expression of the A2B5 antigens, we performed lipidomic analyses on A2B5+/GFAP+ and A2B5-/GFAP+ cells from rat spinal cord. First, A2B5+/GFAP- progenitors were exposed to the leukemia inhibitory factor (LIF) or bone morphogenetic protein (BMP) to induce their differentiation to A2B5+/GFAP+ cells or A2B5-/GFAP+ astrocytes, respectively. The cells were then analyzed for changes in their phospholipid, sphingolipid or acyl chain profiles by mass spectrometry and gas chromatography. Compared to A2B5+/GFAP- progenitors, A2B5-/GFAP+ astrocytes contained higher amounts of ether phospholipids (especially the species containing arachidonic acid) and sphingomyelin, which may indicate characteristics of cellular differentiation and inability for multipotency. In comparison, principal component analyses revealed that the lipid composition of A2B5+/GFAP+ cells retained many of the characteristics of A2B5+/GFAP- progenitors, but their lipid profile was different from that of A2B5-/GFAP+ astrocytes. Thus, our study demonstrated that two GFAP+ cell populations have distinct lipid profiles with the A2B5+/GFAP+ cells sharing a phospholipid profile with progenitors rather than astrocytes. The progenitor cells may require regulated low levels of lipids known to mediate signaling functions in differentiated cells, and the precursor lipid profiles may serve as one measure of the differentiation capacity of a cell population.
  • Rooijers, Koos; Kolmeder, Carolin; Juste, Catherine; Dore, Joel; de Been, Mark; Boeren, Sjef; Galan, Pilar; Beauvallet, Christian; de Vos, Willem M.; Schaap, Peter J. (2011)
  • Simmons, Suzanne C.; Jaemsae, Hannaleena; Silva, Dilson; Cortez, Celia M.; McKenzie, Edward A.; Bitu, Carolina C.; Salo, Sirpa; Nurmenniemi, Sini; Nyberg, Pia; Risteli, Juha; deAlmeida, Carlos E. B.; Brenchley, Paul E. C.; Salo, Tuula; Missailidisi, Sotiris (2014)
  • Knuuttila, Matias; Mehmood, Arfa; Huhtaniemi, Riikka; Yatkin, Emrah; Häkkinen, Merja R.; Oksala, Riikka; Laajala, Teemu D.; Ryberg, Henrik; Handelsman, David J.; Aittokallio, Tero; Auriola, Seppo; Ohlsson, Claes; Laiho, Asta; Elo, Laura L.; Sipila, Petra; Makela, Sari I.; Poutanen, Matti (2018)
    The development of castration-resistant prostate cancer (CRPC) is associated with the activation of intratumoral androgen biosynthesis and an increase in androgen receptor (AR) expression. We recently demonstrated that, similarly to the clinical CRPC, orthotopically grown castration-resistant VCaP (CR-VCaP) xenografts express high levels of AR and retain intratumoral androgen concentrations similar to tumors grown in intact mice. Herein, we show that antiandrogen treatment (enzalutamide or ARN-509) significantly reduced (10-fold, P <0.01) intratumoral testosterone and dihydrotestosterone concentrations in the CR-VCaP tumors, indicating that the reduction in intratumoral androgens is a novel mechanism by which antiandrogens mediate their effects in CRPC. Antiandrogen treatment also altered the expression of multiple enzymes potentially involved in steroid metabolism. Identical to clinical CRPC, the expression levels of the full-length AR (twofold, P <0.05) and the AR splice variants 1 (threefold, P <0.05) and 7 (threefold, P <0.01) were further increased in the antiandrogen-treated tumors. Nonsignificant effects were observed in the expression of certain classic androgen-regulated genes, such as TMPRSS2 and KLK3, despite the low levels of testosterone and dihydrotestosterone. However, other genes recently identified to be highly sensitive to androgen-regulated AR action, such as NOV and ST6GalNAc1, were markedly altered, which indicated reduced androgen action. Taken together, the data indicate that, besides blocking AR, antiandrogens modify androgen signaling in CR-VCaP xenografts at multiple levels.
  • Hattula, Katarina; Hirschberg, Daniel; Kalkkinen, Nisse; Butcher, Sarah J.; Ora, Ari (2014)
  • Skurnik, Mikael; Jaakkola, Salla; Mattinen, Laura; von Ossowski, Lotta; Nawaz, Ayesha; Pajunen, Maria; Happonen, Lotta J. (2021)
    Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1.
  • Happonen, Lotta J.; Pajunen, Maria I.; Jun, Jin Woo; Skurnik, Mikael (2021)
    Yersinia enterocolitica is a food-borne Gram-negative pathogen responsible for several gastrointestinal disorders. Host-specific lytic bacteriophages have been increasingly used recently as an alternative or complementary treatment to combat bacterial infections, especially when antibiotics fail. Here, we describe the proteogenomic characterization and host receptor identification of the siphovirus vB_YenS_phi R2-01 (in short, phi R2-01) that infects strains of several Yersinia enterocolitica serotypes. The phi R2-01 genome contains 154 predicted genes, 117 of which encode products that are homologous to those of Escherichia bacteriophage T5. The phi R2-01 and T5 genomes are largely syntenic, with the major differences residing in areas encoding hypothetical phi R2-01 proteins. Label-free mass-spectrometry-based proteomics confirmed the expression of 90 of the phi R2-01 genes, with 88 of these being either phage particle structural or phage-particle-associated proteins. In vitro transposon-based host mutagenesis and phi R2-01 adsorption experiments identified the outer membrane vitamin B12 receptor BtuB as the host receptor. This study provides a proteogenomic characterization of a T5-type bacteriophage and identifies specific Y. enterocolitica strains sensitive to infection with possible future applications of phi R2-01 as a food biocontrol or phage therapy agent.
  • Pussila, Marjaana; Sarantaus, Laura; Dermadi Bebek, Denis; Valo, Satu; Reyhani, Nima; Ollila, Saara; Päivärinta, Essi Mari-Anna; Peltomäki, Päivi T; Mutanen, Marja; Nyström, Minna (2013)
  • Anton, Dea; Bender, Ingrid; Kaart, Tanel; Roasto, Mati; Heinonen, Marina; Luik, Anne; Puessa, Tonu (2017)
    Polyphenols of fruits and vegetables form an important part of human dietary compounds. Relatively little is known about accumulation of phenolics during fruits ripening process. The goal of this work was to study the changes in antioxidant activity and in content of 30 polyphenols during ripening of tomato fruits. Five organically and conventionally grown tomato cultivars were investigated at three different ripening stages. Phenolic compounds were extracted with methanol and extracts were analyzed by HPLC-DAD-MS/MS. During ripening, four different changing patterns were observed: (1) high level in green fruits with minimal changes; (2) continuous increase with maximum level in red-ripe fruits; (3) decrease; (4) increase and achieving maximum level at half-ripe stage. Similar change patterns were found for organic and conventional fruits. The accumulation patterns of phenolic compounds were similar in standard-type tomatoes but differed in several cases in cherry-type cultivar. Although contents of some polyphenols decreased during ripening, total phenolics and free radical scavenging activity increased in all studied cultivars and in case of both cultivationmodes. The changes in content of phenolic compounds during ripening were greatly influenced by cultivars, but cultivation mode had only minor impact on dynamics in polyphenols contents in tomato fruits.
  • Lovric, Alen; Graner, Marit; Bjornson, Elias; Arif, Muhammad; Benfeitas, Rui; Nyman, Kristofer; Ståhlman, Marcus; Pentikäinen, Markku O.; Lundbom, Jesper; Hakkarainen, Antti; Siren, Reijo; Nieminen, Markku S.; Lundbom, Nina; Lauerma, Kirsi; Taskinen, Marja-Riitta; Mardinoglu, Adil; Boren, Jan (2018)
    Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation of metabolic syndrome, accompanied with excessive fat accumulation in the liver and other vital organs. Ectopic fat accumulation was previously associated with negative effects at the systemic and local level in the human body. Thus, we aimed to identify and assess the predictive capability of novel potential metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using the inflammation-associated proteome, lipidome and metabolome. Myocardial and hepatic triglycerides were measured with magnetic spectroscopy while function of left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose tissue were measured with magnetic resonance imaging. Measured ectopic fat depots were profiled and predicted using a Random Forest algorithm, and by estimating the Area Under the Receiver Operating Characteristic curves. We have identified distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate, diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0, glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14), and myocardium (CE20:3, LAPTGF-beta 1, glutamate and glucose). Our analyses highlighted non-invasive biomarkers that accurately predict ectopic fat depots, and reflect their distinct metabolic signatures in subjects with NAFLD.
  • Duporte, Geoffroy; Riva, Matthieu; Parshintsev, Jevgeni; Heikkinen, Enna; Barreira, Luis M. F.; Myllys, Nanna; Heikkinen, Liine; Hartonen, Kari; Kulmala, Markku; Ehn, Mikael; Riekkola, Marja-Liisa (2017)
    Amines are recognized as key compounds in new particle formation (NPF) and secondary organic aerosol (SOA) formation. In addition, ozonolysis of a-pinene contributes substantially to the formation of biogenic SOAs in the atmosphere. In the present study, ozonolysis of a-pinene in the presence of dimethylamine (DMA) was investigated in a flow tube reactor. Effects of amines on SOA formation and chemical composition were examined. Enhancement of NPF and SOA formation was observed in the presence of DMA. Chemical characterization of gas and particle-phase products by high-resolution mass spectrometric techniques revealed the formation of nitrogen containing compounds. Reactions between ozonolysis reaction products of a-pinene, such as pinonaldehyde or pinonic acid, and DMA were observed. Possible reaction pathways are suggested for the formation of the reaction products. Some of the compounds identified in the laboratory study were also observed in aerosol samples (PM1) collected at the SMEAR II station (Hyytiala, Finland) suggesting that DMA might affect the ozonolysis of a-pinene in ambient conditions.
  • Riva, M.; Ehn, M.; Li, D.; Tomaz, S.; Bourgain, F.; Perrier, S.; George, C. (2019)
    While acknowledged as key components in the formation of new particles in the atmosphere, the accurate characterization of gaseous (highly) oxygenated organic compounds remains challenging and requires analytical developments. Earlier studies have successfully used the nitrate ion (NO3) based chemical ionization (CI) coupled to atmospheric pressure interface time-of-flight mass spectrometry (CI-APi-TOF) for monitoring these compounds. Despite many breakthroughs in recent years, the CI-APi-TOF has many limitations, preventing for instance the unambiguous ion identification of overlapping peaks. To tackle this analytical challenge, we developed a CI interface coupled to an ultrahigh-resolution Orbitrap mass spectrometer (CI-Orbitrap). We show that the CI-Orbitrap has similar sensitivity and selectivity as the CI-APi-TOF, but with over an order of magnitude higher mass resolving power (up to 140 000). Equally importantly, the CI-Orbitrap allows tandem mass spectrometry, providing the possibility for structural elucidation of the highly oxygenated organic molecules (HOM). As a proof of concept, we characterized HOM formed during the ozonolysis of two biogenic compounds (alpha-pinene and limonene), under different environmental conditions in a flow reactor. The CI-Orbitrap exhibited high sensitivity to both HOM and radical species, while easily separating ions of different elemental composition in cases where the more common TOF applications would not have been able to distinguish all ions. Our tandem mass spectrometry analyses revealed distinct fingerprint spectra for all the studied HOM. Overall, the CI-Orbitrap is an extremely promising instrument, and it provides a much-needed extension to ongoing research on HOM, with potential to impact also many other fields within atmospheric chemistry.
  • Fang, Jiaxi; Wang, Yang; Kangasluoma, Juha; Attoui, Michel; Junninen, Heikki; Kulmala, Markku; Petäjä, Tuukka; Biswas, Pratim (2017)
    Few studies reported the formation of Ti-containing clusters in the initial stages of TiO2 flame synthesis. The conversion from synthesis precursor to TiO2 monomers was commonly assumed to take place through global reaction such as thermal decomposition and/or hydrolysis at high temperatures. More recent studies have been able to identify stable intermediates of Ti-containing monomers, most commonly Ti(OH)(4), as the final step before the formation of TiO2. However, no larger Ti-containing cluster formation mechanisms or interactions between these monomers have been tracked. To investigate cluster formation pathways of TiO2 during flame synthesis, Charged clusters were measured in an atmospheric pressure interface time-of-flight (APi-TOF) mass spectrometer. TiO2 nanoparticles were synthesized by adding titanium tetraisopropoxide (TTIP) precursor to a premixed CH4/O-2/N-2 flat flame aerosol reactor. Pure TiO2 clusters were not detected by the APi-TOF. Results from measured mass spectra and mass defect plots show that for positively charged clusters, the abstraction of CH2 groups occurs simultaneously with the clustering of larger intermediate organometallic species. For negatively charged clusters, NOx formation pathways in the flame may play a role during the initial stages of TiO2 formation, since a lot of Ti-containing clusters were attached with nitrate-related species. These research findings provide insights on quantum dot synthesis and molecular doping where rapid dilution of the flame synthesized nanoparticles is needed to better control the particle size and chemical composition. The possible influences of and potential artifacts brought by the dilution system on observing the incipient particle formation in flames were also discussed.
  • Kolmeder, Carolin A.; de Been, Mark; Nikkilä, Janne; Ritamo, Ilja; Mättö, Jaana; Valmu, Leena; Salojärvi, Jarkko; Palva, Airi; Salonen, Anne; de Vos, Willem M. (2012)
  • Viinamaki, Jenni; Ojanpera, Ilkka (2016)
    There is a constant demand for the quantification of drug metabolites within post-mortem toxicology. Especially electrospray ionization-mass spectrometry techniques necessitate that calibration is carried out using primary reference standards due to the non-uniform ionization efficiency between parent drugs and their metabolites. As reference standards for metabolites are not readily available and their costs are high, alternative methods for immediate quantification are required. In this study, ultra-high performance liquid chromatography coupled with photodiode array detection and corona charged aerosol detection was utilized for the concurrent quantification of 23 drug metabolites using the corresponding parent drug for calibration. Based on this secondary calibration, the quantitative results for the N-demethylated metabolites by each detector were similar to those obtained by the ordinary calibration using reference standards. For O-demethylated metabolites, the differences in detector response caused somewhat larger biases using the secondary calibration. Using the validated secondary calibration, the blood sample data gathered from 633 post-mortem cases was retrospectively reprocessed to discover the combined metabolite-parent concentrations and metabolite to parent ratios for six toxicologically relevant drugs. These results, representing all causes of death, were compared to published data from therapeutic drug monitoring and post-mortem toxicology. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Shishido, Tania Keiko; Popin, Rafael Vicentini; Jokela, Jouni; Wahlsten, Matti; Fiore, Marli Fatima; Fewer, David P.; Herfindal, Lars; Sivonen, Kaarina (2020)
    Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. We tested 62 cyanobacterial strains isolated from various Brazilian biomes for antileukemic and antimicrobial activities. Extracts from 39 strains induced selective apoptosis in acute myeloid leukemia (AML) cancer cell lines. Five of these extracts also exhibited antifungal and antibacterial activities. Chemical and dereplication analyses revealed the production of nine known natural products. Natural products possibly responsible for the observed bioactivities and five unknown, chemically related chlorinated compounds present only in Brazilian cyanobacteria were illustrated in a molecular network. Our results provide new information on the vast biosynthetic potential of cyanobacteria isolated from Brazilian environments.
  • Mesihää, Samuel; Ketola, Raimo A.; Pelander, Anna; Rasanen, Ilpo; Ojanpera, Ilkka (2017)
    Gas chromatography coupled to atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (GC-APCI-QTOFMS) was evaluated for the identification of new psychoactive substances (NPS). An in-house high mass resolution GC-APCI-QTOFMS test library was developed for 29 nitrogen-containing drugs belonging mostly to synthetic stimulants. The library was based on 12 intra-day measurements of each compound at three different collision energies, 10, 20 and 40 eV. The in-house library mass spectra were compared to mass spectra from a commercial library constructed by liquid chromatography-electrospray ionization (LC-ESI) QTOFMS. The reversed library search scores between the in-house GC-APCI library and the commercial LC-ESI library were compared once a week during a 5-week period by using data measured by GC-APCI-QTOFMS. The protonated molecule was found for all drugs in the full scan mode, and the drugs were successfully identified by both libraries in the targeted MS/MS mode. The GC-APCI library score averaged over all collision energies was as high as 94.4/100 with a high repeatability, while the LC-ESI library score was also high (89.7/100) with a repeatability only slightly worse. These results highlight the merits of GC-APCI-QTOFMS in the analysis of NPS even in situations where the reference standards are not immediately available, taking advantage of the accurate mass measurement of the protonated molecule and product ions, and comparison to existing soft-ionization mass spectral libraries.
  • Scifo, Enzo; Szwajda, Agnieszka; Debski, Janusz; Uusi-Rauva, Kristiina; Kesti, Tapio; Dadlez, Michal; Gingras, Anne-Claude; Tyynelä, Jaana; Baumann, Marc H.; Jalanko, Anu; Lalowski, Maciej (2013)
  • Zhang, Lu; Diaz-Diaz, Norberto; Zarringhalam, Kourosh; Hermansson, Martin; Somerharju, Pentti; Chuang, Jeffrey (2012)