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  • 1.
    Alam, Sadaf Sakina
    Södertörn University College, School of Life Sciences.
    Determination of gp120 & Trx80 dependent production of hydrogen peroxide in cell free & cell-dependent systems2009Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Hydrogen peroxide (H2O2), a reactive oxygen specie (ROS), is most commonly associated with oxidative stress causing cytotoxic effects on living cells. Oxidative stress has been implicated in various conditions including neurodegenerative diseases, autoimmune diseases and cancer. In addition H2O2 is produced as a defense mechanism against pathogens, as being released by activated phagocytes. In recent years, H2O2 has become established as an important regulator of signal transduction in eukaryotic cells. Hydrogen peroxide is generated both intracellularly and extracellularly in response to various stimuli including cytokines and growth factors. There are different mechanisms by which H2O2 is generated, facilitating signal transduction in cells; through NOX-system in miyochondria, via singlet oxygen, receptor/ligand interaction or by redox active metal ions. The HIV glycoprotein 120 (gp120) is associated with HIV dementia and it is known as a neurotoxin that causes neuronal damage. It has been proposed that free radicals may be involved in the pathogenesis caused by gp120. In addition the truncated form of thioredoxin (Trx80) is known to stimulate HIV replication in HIV infected cells, however, the exact mechanism is not known. A possible way both proteins may mediate their activity is by inducing H2O2 production. The aim of this study was to investigate H2O2 production induced by the proteins gp120 and Trx80. In order to detect H2O2 production an assay based on the fluorescent compound Amplex Red, was established. The assay was used to detect H2O2 released by gp120 and Trx80 in a cell-free environment, in a cell-system and in the presence of metal ions (copper ions) with a physiological reductant (ascorbate). We did not detect H2O2 production induced by gp120 and Trx80 respectively, using our assay, however, other ROS such as hydroxyl radicals may have been generated although they were not detectable with our method. Hence, further studies are needed in order to fully understand how gp120 and Trx80 mediate their activity.

  • 2.
    Alkemar, Gunnar
    Södertörn University, School of Life Sciences. Stockholms universitet, Wenner-Grens institut.
    Ribosome and ribosomal RNA Structure: An experimental and computational analysis of expansion segments in eukaryotic ribosomal RNA2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ribosomes are large ribonucleoprotein complexes which incorporate amino acids into peptide chains during translational process in all types of living cells. The eukaryotic ribosome is larger compared to its prokaryotic counterpart. The size differences are due to a larger protein part and that the rRNA contains eukaryote specific expansion segments (ES). Cryo-EM reconstruction has visualized many ES on the ribosomal surface which have given clues about function and structural features. However, the secondary structures of most ES are unknown or ill defined. In this thesis, the secondary and also to a certain extent the tertiary structures of several ES are determined by using computational methods and biochemical experimental techniques. The juxtaposition of ES6 close to ES3 in the Cryo-EM image of the yeast ribosome suggested that ES3 and ES6 might interact. A computational analysis of more than 2900 sequences shows that a complementary helical region of seven to nine contiguous base pairs can form between ES3 and ES6 in almost all analyzed sequences. Biochemical in situ experiments support the proposed interaction. Secondary structure models are presented for ES3 and ES6 in 18S rRNA and ES39 in 28S rRNA, where homologous structural elements could be modeled in the experimentally analyzed ribosomes from fungi, plants and mammals. The structure models were further supported by computational methods where the ES6 structure and the ES39 structure could be formed in more than 6000 and 900 sequences respectively. A tertiary structure model of ES3 and ES6 including the helical interaction is presented. An in vitro transcribed and folded ES6 sequence differed from that observed in situ, suggesting that chaperones, ribosomal proteins, and/or the tertiary rRNA interaction could be involved in the in vivo folding of ES6. An analysis of the similarities between ES39 structures suggests that it might be under selective constraint to preserve its secondary structure.

  • 3.
    Bräutigam, Lars
    et al.
    Södertörn University, School of Life Sciences, Molecular biology.
    Hillmer, Janine M.
    Södertörn University, School of Life Sciences, Molecular biology.
    Söll, Iris
    Södertörn University, School of Life Sciences, Molecular biology.
    Hauptmann, Giselbert
    Södertörn University, School of Life Sciences, Molecular biology.
    Localized Expression of Urocortin Genes in the Developing Zebrafish rain2010In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 518, no 15, p. 2978-2995Article in journal (Refereed)
    Abstract [en]

    The corticotropin-releasing hormone (CRH) family consists of four aralogous genes, CRH and urocortins (UCNs) 1, 2, and 3. In a previous tudy, we analyzed CRH in the teleost model organism zebrafish and its ranscript distribution in the embryonic brain. Here, we describe ull-length cDNAs encoding urotensin 1 (UTS1), the teleost UCN1 rtholog, and UCN3 of zebrafish. Major expression sites of uts1 in adult ebrafish are the caudal neurosecretory system and brain. By using T-PCR analysis, we show that uts1 mRNA is also present in ovary, aternally contributed to the embryo, and expressed throughout embryonic evelopment. Expression of ucn3 mRNA was detected in a range of adult issues and during developmental stages from 24 hours post fertilization nward. Analysis of spatial transcript distributions by whole-mount in itu hybridization revealed limited forebrain expression of uts1 and cn3 during early development. Small numbers of uts1-synthesizing eurons were found in subpallium, hypothalamus, and posterior iencephalon, whereas ucn3-positive cells were restricted to elencephalon and retina. The brainstem was the main site of uts1 and cn3 synthesis in the embryonic brain. uts1 Expression was confined to he midbrain tegmentum; distinct hindbrain cell groups, including locus oeruleus and Mauthner neurons; and the spinal cord. ucn3 Expression was ocalized to the optic tectum, serotonergic raphe, and distinct hombomeric cell clusters. The prominent expression of uts1 and ucn3 in rainstem is consistent with proposed roles of CRH-related peptides in tress-induced modulation of locomotor activity through monoaminergic rainstem neuromodulatory systems. J. Comp. Neurol. 518:2978-2995, 2010.

  • 4.
    Cortobius Fredriksson, Moa
    Södertörn University College, School of Life Sciences.
    ProBenefit: Implementing the Convention on Biological Diversity in the Ecuadorian Amazon2009Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Legislation on benefit sharing dates back to 1992 and the commandment of the UNConvention on Biological Diversity, hence implementation still has few cases to fall back on(CBD, 1992). The case study of the project ProBenefit presented by the thesis highlights howlack of deliberation can undermine a democratic process. The objective of the thesis is thatProBenefit’s attempt to implement the standards of the CBD on access and benefit sharingwill highlight not only problems met by this specific project, but difficulties that generallymeet democratic processes in contexts of high inequality. To define if the project ProBenefitsucceeded in carrying out a deliberative process the project will be analyzed by the criteria:access to information, representation, legitimacy and involvement.The population in the project area of ProBenefit had a long history of social marginalization,which made it hard for foreign projects to gain legitimacy. The lack of independentorganizations and the late establishment of the project, which resulted in time shortage, madeit impossible to prevent the distrust of the local population. The failure of the projectcoordinators to ensure active participation of all stakeholders resulted in a late and lowinvolvement of the local participants. The absence of independent organization also madedemocratic legitimacy of the process questionable. Even if ProBenefit had a vision ofdemocratic deliberation the project was unable to break down the prevailing unequal powerdistribution which resulted in an unsustainable process and failure. The conclusion of thethesis is that the attainment of deliberation foremost depends on how a project deals with theexisting distribution of power and how it succeeds in involving all stakeholders.

  • 5.
    Demir, Daniel
    et al.
    Södertörn University College, School of Business Studies.
    John, Joshua
    Södertörn University College, School of Business Studies.
    Lojalitet på en biografmarknad2009Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Biografmarknaden är i dagsläget i en situation där marknadsledaren har en monopolliknande ställning. Detta påverkar i hög grad de mindre biografernas existens då man inte kan konkurrera på samma villkor. Detta i sin tur leder till att biografbesökarna försvinner till de större biograferna med större produktutbud. Mindre biografer måste hitta nya lösningar för att kunna behålla sina kunder på en konkurrensutsatt marknad. Denna uppsats tar därför upp vilka faktorer som är viktiga för att kunna skapa lojala och återkommande kunder. 

    Syftet med uppsatsen är att göra en fallstudie för att analysera och utvärdera två stora och en liten biograf. Detta sker genom enkätundersökningar av biografbesökarna på de tre olika biograferna som är Heron City, Kistabiografen och Roxybiografen.

    Denna uppsats är skriven utifrån den mindre biografen Roxybiografens perspektiv för att se vilka faktorer som skapar lojala biografbesökare. Uppsatsen använder sig av en fallstudie för att skapa en stor förståelse och inblick för objektets situation.

    Det som framkommit av studien är att en mindre biograf måste differentiera sig genom att erbjuda något annat än vad konkurrenterna gör vilket är grundläggande för att en liten biograf ska överleva.

    Som underlag till denna undersökning ligger teorin involvement theory och marknadsföringsstrategier som kostnadsöverlägsenhet, differentiering och fokusering.

  • 6. Elmroth, K.
    et al.
    Nygren, Jonas
    Södertörn University, Avdelning Naturvetenskap. Karolinska Institute.
    Mårtensson, S.
    Ismail, I. H.
    Hammarsten, O.
    Cleavage of cellular DNA by calicheamicin γ12003In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 2, no 4, p. 363-374Article in journal (Refereed)
    Abstract [en]

    It is assumed that the efficient antitumor activity of calicheamicin γ1 is mediated by its ability to introduce DNA double-strand breaks in cellular DNA. To test this assumption we have compared calicheamicin γ1-mediated cleavage of cellular DNA and purified plasmid DNA. Cleavage of purified plasmid DNA was not inhibited by excess tRNA or protein indicating that calicheamicin γ1 specifically targets DNA. Cleavage of plasmid DNA was not affected by incubation temperature. In contrast, cleavage of cellular DNA was 45-fold less efficient at 0°C as compared to 37° due to poor cell permeability at low temperatures. The ratio of DNA double-strand breaks (DSB) to single-stranded breaks (SSB) in cellular DNA was 1:3, close to the 1:2 ratio observed when calicheamicin γ1 cleaved purified plasmid DNA. DNA strand breaks introduced by calicheamicin γ1 were evenly distributed in the cell population as measured by the comet assay. Calicheamicin γ1-induced DSBs were repaired slowly but completely and resulted in high levels of H2AX phosphorylation and efficient cell cycle arrest. In addition, the DSB-repair deficient cell line Mo59J was hyper sensitive to calicheamicin γ. The data indicate that DSBs is the crucial damage after calicheamicin γ1 and that calicheamicin γ1-induced DSBs are recognized normally. The high DSB:SSB ratio, specificity for DNA and the even damage distribution makes calicheamicin γ1 a superior drug for studies of the DSB-response and emphasizes its usefulness in treatment of malignant disease.

  • 7.
    Elväng, Annelie
    et al.
    Södertörn University, School of Life Sciences, Molecular biology.
    Melik, Wessam
    Södertörn University, School of Life Sciences, Chemistry. Södertörn University, School of Life Sciences, Molecular biology.
    Bertrand, Yann
    Södertörn University, School of Life Sciences, Molecular biology.
    Lönn, Mikael
    Södertörn University, School of Life Sciences, Biology. Södertörn University, School of Life Sciences, Environmental science.
    Johansson, Magnus
    Södertörn University, School of Life Sciences, Chemistry. Södertörn University, School of Life Sciences, International health.
    Sequencing of a Tick-Borne Encephalitis Virus from Ixodes ricinus Reveals a Thermosensitive RNA Switch Significant for Virus Propagation in Ectothermic Arthropods.2011In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 11, no 6, p. 649-658Article in journal (Refereed)
    Abstract [en]

    Tick-borne encephalitis virus (TBEV) is a flavivirus with major impact on global health. The geographical TBEV distribution is expanding, thus making it pivotal to further characterize the natural virus populations. In this study, we completed the earlier partial sequencing of a TBEV pulled out of a pool of RNA extracted from 115 ticks collected on Torö in the Stockholm archipelago. The total RNA was sufficient for all sequencing of a TBEV genome (Torö-2003), without conventional enrichment procedures such as cell culturing or suckling mice amplification. To our knowledge, this is the first time that the genome of TBEV has been sequenced directly from an arthropod reservoir. The Torö-2003 sequence has been characterized and compared with other TBE viruses. In silico analyses of secondary RNA structures formed by the two untranslated regions revealed a temperature-sensitive structural shift between a closed replicative form and an open AUG accessible form, analogous to a recently described bacterial thermoswitch. Additionally, novel phylogenetic conserved structures were identified in the variable part of the 3'-untranslated region, and their sequence and structure similarity when compared with earlier identified structures suggests an enhancing function on virus replication and translation. We propose that the thermo-switch mechanism may explain the low TBEV prevalence often observed in environmentally sampled ticks. Finally, we were able to detect variations that help in the understanding of virus adaptations to varied environmental temperatures and mammalian hosts through a comparative approach that compares RNA folding dynamics between strains with different mammalian cell passage histories.

  • 8.
    Engström, Hanna
    Södertörn University College, School of Life Sciences.
    Molecular and morphological analysis of genetic polymorphisms causing glabrousness in wild populations of Arabidopsis lyrata.2006Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    Trichome formation in Arabidopsis lyrata is a naturally occurring trait with phenotypic polymorphisms within wild populations. In Swedish accessions of A. lyrata, three genetic polymorphisms situated in the coding region of GL1, an important transcription factor in trichome production, have been identified, and these are candidates for being the cause of a glabrous phenotype. In this study a complementation test has been performed to clarify which mutation/mutations that are detrimental for trichome formation. A set of constructs has been transformed into A. thaliana, a close relative to A. lyrata, and subsequent generations of plants were examined for phenotype, genotype and gene expression. A SNP (Single Nucleotide Polymorphism) in the R3 MYB domain of GL1, resulting in a change of an alanine to aspartic acid, was identified as the critical polymorphism. The other two mutations, two indels, were harmless to protein function. The inserted constructs were under control of the native GL1 promoter. Plants that, because of the SNP, lacked trichome production, became totally glabrous.

  • 9. Gabriel, Jens Peter
    et al.
    Mahmood, Riyadh
    Kyriakatos, Alexandros
    Söll, Iris
    Södertörn University, School of Life Sciences, Molecular biology.
    Hauptmann, Giselbert
    Södertörn University, School of Life Sciences, Molecular biology.
    Calabrese, Ronald L.
    El Manira, Abdeljabbar
    Serotonergic Modulation of Locomotion in Zebrafish-Endogenous Release and Synaptic Mechanisms2009In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 29, no 33, p. 10387-10395Article in journal (Refereed)
    Abstract [en]

    Serotonin (5-HT) plays an important role in shaping the activity of the spinal networks underlying locomotion in many vertebrate preparations. At larval stages in zebrafish, 5-HT does not change the frequency of spontaneous swimming; and it only decreases the quiescent period between consecutive swimming episodes. However, it is not known whether 5-HT exerts similar actions on the locomotor network at later developmental stages. For this, the effect of 5-HT on the fictive locomotor pattern of juvenile and adult zebrafish was analyzed. Bath-application of 5-HT (1-20 mu M) reduced the frequency of the NMDA-induced locomotor rhythm. Blocking removal from the synaptic cleft with the reuptake inhibitor citalopram had similar effects, suggesting that endogenous serotonin is modulating the locomotor pattern. One target for this modulation was the mid-cycle inhibition during locomotion because the IPSPs recorded in spinal neurons during the hyperpolarized phase were increased both in amplitude and occurrence by 5-HT. Similar results were obtained for IPSCs recorded in spinal neurons clamped at the reversal potential of excitatory currents (0 mV). 5-HT also slows down the rising phase of the excitatory drive recorded in spinal cord neurons when glycinergic inhibition is blocked. These results suggest that the decrease in the locomotor burst frequency induced by 5-HT is mediated by a potentiation of mid-cycle inhibition combined with a delayed onset of the subsequent depolarization.

  • 10.
    Grönberg, Naima
    Södertörn University College, School of Life Sciences.
    Induction of pathogenesis-related genes, PR-17a and N-methyltransferase, in barley infested by the aphid Rhopalosiphum padi 2006Independent thesis Advanced level (degree of Magister)Student thesis
    Abstract [en]

    Plants produce a large diverse array of organic compounds that may function in protection against pathogens. Diverse antifungal compounds were reported to exist in barley (Hordeum vulgare L.); the indole alkaloid, gramine, and the pathogenesis-related proteins are some of them. Both the N-methyltransferase that is involved in gramine biosynthesis and PR-17a were studied in barley upon infestation by the bird cherry-oat aphid (Rhopalosiphum padi).

    The effect of infestation by R. padi on induction of PR-17a and N-methyltransferase was investigated in different barley lines, susceptible and resistant.

    The gene expression of PR-17a was down-regulated in the susceptible cv. Golf and to some extent up-regulated at the first days in var. Lina and then down-regulated. The PR-17a was induced by the aphid infestation in the resistant line CI16145; the gene expression was stronger in the infested plants than in the controls. The different responses in resistant and susceptible lines indicate that the induced PR-17a may play a role in the resistance against aphid infestation. PR-17a was up-regulated systemically in the base in barley after infestation by R. padi.

    In the susceptible varieties Lina and Golf, the accumulation of N-methyltransferase did not increase with time from 1 day to 7 days after infestation, as determined by western blots with antibody raised against NMT from barley. The NMT-gene was down-regulated after 7 days infestation in both variety Lina and Golf both locally in the first leaf and in the base. Barley line CI16145 had no accumulation of NMT as was seen by western blotting. There was no induction of NMT in barley upon aphid infestation.

  • 11.
    Grönkvist, Pamela
    Södertörn University College, School of Life Sciences.
    Effects of overexpression of syndecan-1 in mesenchymal tumor cells2011Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    BackgroundAll cells carry a transmembrane proteoglycan calledsyndecan. Syndecans influence many functions like cell migration, cell adhesionand cell proliferation and it is involved in cellular signaling andtumourigenesis.

    The common features of differentiation in twomesenchymal tumor cell types, malignant mesothelioma cells and fibrosarcoma cells,are connected to the synthesis of syndecans. By studying the overexpression ofsyndecan-1 we hope to discover new features of the syndecan-1 molecule that wecan add to the puzzle of mesenchymal tumors.

    Methods and findingsMalignant mesothelioma cells and fibrosarcoma cellswere cultured and transfected with full-length- and truncated syndecan-1 constructs.To detect the expression of syndecan-1 on RNA level Rt-Q-PCR was conductedfollowed by immunocytochemical analysis to establish the syndecan-1 expressionon protein level. The result showed a 2-7 fold increase of syndecan-1 in thetransfectants comparing to the control. The proliferation of transfectants was analyzedby cell proliferation assay and cell cycle analysis. All transfectants showed alower proliferation rate comparing to the controls and a slight increase inG0/G1 phase.

    Because of the high structural similarities ofsyndecan family members, I studied how overexpression of syndecan-1 affected theother syndecans using Rt-Q-PCR. Syndecan-2 and -4 were downregulated in thetransfectants carrying syndecan-1 ectodomain, whereas the truncated versionshad the opposite effect. The expression of syndecan-bound heparan sulfate wasstudied by FACS and indicated an upregulation for heparan sulfate whenmeasuring internal- and membrane bound syndecans simultanesly.

    ConclusionsIn this study I haveshown that overexpression of full-length syndecan-1 and the different truncatedvariants, had similar profound effects on mesenchymal cell proliferation. Syndecan-1also influences the other members of the syndecan family suggesting a complexregulation.

  • 12.
    Gustafsson, Kerstin
    et al.
    Södertörn University, School of Life Sciences, Environmental science. Södertörn University, School of Life Sciences, Biology.
    Blidberg, Eva
    Elfgren, Irene Karlsson
    Hellström, Anna
    Kylin, Henrik
    Gorokhova, Elena
    Direct and indirect effects of the fungicide azoxystrobin in outdoor rackish water microcosms2010In: Ecotoxicology, ISSN 0963-9292, E-ISSN 1573-3017, Vol. 19, no 2, p. 431-444Article in journal (Refereed)
    Abstract [en]

    The effects of the strobilurin fungicide azoxystrobin were studied in rackish water microcosms, with natural plankton communities and ediment. Two experiments were conducted: Experiment 1 (nominal conc. 0, 5 and 60 mu g/L, 24-L outdoor microcosms for 21 days) and a second, ollow-up, Experiment 2 (nominal conc. 0, 3, 7.5, 15 mu g/L, 4-L indoor icrocosms for 12 days). The microcosms represent a simplified brackish ater community found in shallow semi-enclosed coastal areas in gricultural districts in the Baltic Sea region. Measured water oncentrations of the fungicide (Experiment 1) were, on average, 83 and 2% of nominal concentrations directly after application, and 25 and 30% fter 21 days, for the low and high dose treatments, respectively, orresponding to mean DT50-values of 15.1 and 25.8 days, for low and igh dose treatments, respectively. In Experiment 1, direct toxic ffects on calanoid copepods at both test concentrations were observed. imilarly, in Experiment 2, the copepod abundance was significantly educed at all tested concentrations. There were also significant econdary effects on zooplankton and phytoplankton community structure, tanding stocks and primary production. Very few ecotoxicological tudies have investigated effects of plant protection products on Baltic rganisms in general and effects on community structure and function pecifically. Our results show that azoxystrobin is toxic to brackish ater copepods at considerably lower concentrations than previously eported from single species tests on freshwater crustaceans, and that irect toxic effects on this ecologically important group may lead to ascade effects altering lower food webs and ecosystem functioning.

  • 13.
    Havervall, Carolina
    Södertörn University College, School of Life Sciences.
    CXCL13: A Prognostic Marker in Multiple Sclerosis2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In the demyelinating autoimmune disease multiple sclerosis (MS) there is a great need for validated prognostic biomarkers that can give information about both prognosis and disease course. So far only clinical parameters have been shown to predict future outcome. CXCL13 is a potent B cell chemoattractant that has been suggested to be a potential biomarker candidate. The aim of this study was to investigate the usefulness of CXCL13 as a prognostic biomarker for MS.

    Clinical, paraclinical, laboratory and MRI data about a large group of MS patients and controls were collected. CXCL13 levels in cerebrospinal fluid (CSF) samples from these patients were determined by standard enzymelinked immunosorbent assay (ELISA).

    In general CXCL13 were increased in CSF in MS, especially in relapsing-remitting MS during relapses, i.e. with ongoing inflammations in the central nervous system. CXCL13 is a good candidate prognostic marker for MS, since newly diagnosed MS with high CXCL13 levels showed worsened disease course within five years. Most importantly, MS conversion occurred in higher rate in possible MS patients with high concentrations of CXCL13 in CSF, and in a shorter time point. This observation may support an early treatment decision in these patients.

    In conclusion, this study provides support for an association between CXCL13 levels in the CSF and later development of disease severity in MS.

  • 14.
    Jaensson, Alia
    Södertörn University, School of Life Sciences, Biology. Södertörn University, School of Life Sciences, Molecular biology.
    Pheromonal Mediated Behaviour and Endocrine Responses in Salmonids: The impact of Cypermethrin, Copper, and Glyphosate2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The effects of cypermethrin, copper and glyphosate on the endocrine system and subsequent response to female pheromones were investigated in mature male brown trout (Salmo trutta) parr.  Responses measured were the amount of strippable milt, blood plasma levels of both an androgen (11-ketotestosterone (11-KT)) and a progestin (17α,20β-dihydroxy-4-pregnen-3-one (17,20b-P)), and behavioural changes. This was done in a two phased investigation where parr were exposed to one of the following via ambient water: 1) 0.1 or 1.0 μg L-1 cypermethrin, 2) 10 or 100 μg L-1 copper (Cu2+), or 3) 150 μg L-1 glyphosate for a 96 hour period.  Phase one was a priming experiment exposing parr to a treatment followed by priming with PGF or ovarian fluid (OVF). Atlantic salmon (Salmo salar) parr were, also exposed to glyphosate during phase I. The second phase was centered on behavioural observations.  Exposed parr were placed in a 35,000 L stream aquarium together with two ovulated females and four anadromous males. After the experiments a blood sample was taken, milt volumes measured and testes weighed.  The plasma was analyzed for 11-KT and 17,20b-P concentrations using radioimmunoassay (RIA).

    Results from phase I-priming: 1.0 μg L-1 cypermethrin exposure lowered 17,20b-P and 11-KT; Copper exposure lowered milt volumes; glyphosate exposure lowered 11-KT in salmon and raised 17,20b-P in trout.  Results from phase II-behaviour: 1.0 μg L-1 cypermethrin exposure lowered 11-KT, milt and spawning behaviour; copper exposure lowered spawning behaviour and raised 11-KT; Glyphosate exposure lowered 11KT; continuous cypermethrin exposure raised 17,20b-P, 11-KT and gave a tendency towards increased aggression. It is concluded that low concentration exposure to the compounds examined can induce negative effects on male salmonid endocrine systems, either through a disruption in the olfactory system or through a direct effect.

  • 15.
    Kantrowitz, Joshua T.
    et al.
    Columbia Univ, Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA.
    Jakubovitz, Aaron
    Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
    Scaramello, Nayla
    Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
    Laukka, Petri
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen..
    Silipo, Gail
    Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
    Javitt, Daniel C.
    Columbia Univ, Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA.
    Are Schizophrenia Patients Amusical?: The Role of Pitch and Rhythm in Auditory Emotion Recognition Impairments in Schizophrenia2013In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 9, p. 18S-18SArticle in journal (Refereed)
  • 16.
    Khalil, Yasmin
    Södertörn University College, School of Life Sciences.
    Study on Hepatitis C virus (HCV) subtypes in Sweden before and after the universal screening of blood donors2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Since the discovery in 1989 of hepatitis C virus (HCV) as the infectious agent responsible for the vast majority of post-transfusion non-A non-B hepatitis, blood transfusions are no longer a source for HCV transmission in Sweden. Anti-HCV testing was implemented for all blood donations in 1992. Since then intravenous drug use (IDU) has become the major route of transmission in the western world. Six genotypes and more than 80 subtypes of HCV have now been identified world-wide. These genotypes and subtypes are determined by genetic divergences between the HCV strains. Subtypes 1a, 1b, 2b, 2c, and 3a have global spread, while the other subtypes have a more limited geographical distribution. Little was known on the prevalence of HCV among blood donors and on which genotypes and subtypes of HCV were circulating in Sweden before the testing of all blood donations was implemented. The prevalence of anti-HCV was therefore investigated in sera sent to the Swedish Institute for Infectious Disease Control (SMI) from 412 patients; 241 were sampled between 1970 and 1991 before the universal screening in 1992, while 171 were sampled between 1992 and 2002. The samples derived from 193 (47%) blood donors, (104 sampled before, and 89 after 1992), and from seven other groups of patients. Two groups had suspected known routes of infection, intravenous drug use (IDU) 33 patients and hemodialysis, 16 patients, while it was unknown for the other patients. Anti-HCV was detected in 120 (29%) samples. The highest frequency was found among IDUs, (91%). Before general screening was implemented, 2.8% of the blood donors were positive for hepatitis C, whereas 28% of those sampled after 1992 were anti-HCV positive. Those latter samples were sent to SMI due to anti-HCV reactivity in a primary test at the blood centre. HCV RNA could be detected by PCR in 56 (47%) of the anti-HCV positive samples, the subtype could be determined by sequencing in 45 (80%) of those. The subtypes found were 1a in 31 %, 1b in 18%, 2b in 22%, and 3a in 27%. One sample was of subtype 2c. There was a tendency of increase of genotype 2 and a decrease in subtype 1a with time. 1a was found in 38% of the samples collected before 1992, while it was only found in 19% of the samples from 1992 or later. On the other hand genotype 2 was found in 17% sera sampled before 1992 and in 37% of the samples collected 1992 or later. It is not known if this genotype has recently been introduced into Sweden. Further analysis on larger series of samples is needed to confirm these preliminary results.

  • 17.
    Krantz-Frid, Madelene
    Södertörn University College, School of Life Sciences.
    Ecotoxicological effects from three antifouling paints on the red macroalga Ceramium tenuicorne.2009Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Antifouling paints are applied on vessels to prevent growth of fouling organisms such hasbarnacles. Presently, there are a number of different paints available on the Swedish marketwith different strategies and active substances. The paints might work by either continuouslyreleasing biocides or physically by peeling off or provide an easily cleansed surface whereorganisms cannot attach. The physically working paints do not need to register an activesubstance since its purpose is not to affect living organisms by a chemical or biological modeof action. In this study, two commercially available paints, the copper-based Fabi 3959(International Paint Ltd) and physically eroding, biocide-free labelled Mille Light (HempelFärg AB) were compared to Hard Racing superior, containing copper and the forbiddensubstance Tributyltin. Fabi International is only allowed to be used on the Swedish west coastdue to 6% added as active substance while the biocide-free Mille Light is eligible for eastcoast usage. The toxic effect from respective paint was investigated by assembling a growthinhibition test with the red macro alga Ceramium tenuicorne. The results show that all thestudied paints had a negative effect on growth and therefore leaked substances inconcentrations high enough to be harmful to the alga. The toxic response differed with theeffect on growth being in the following order, Hard racing superior>Fabi >Mille Light.Implications regarding the current legalization involving biocide-free labelled antifoulingpaints are discussed.

  • 18.
    Lindgren, Malin
    et al.
    Södertörn University, School of Life Sciences.
    Riazi, Raha
    Stockholms universitet.
    Lesch, Christine
    Stockholms universitet.
    Willielinsson, Christine
    Stockholms universitet.
    Theopold, Ulrich
    Stockholms universitet.
    Dushay, Mitchell S.
    Södertörn University, School of Life Sciences.
    Fondue and transglutaminase in the Drosophila larval clot2008In: Journal of insect physiology, ISSN 0022-1910, E-ISSN 1879-1611, Vol. 54, no 3, p. 586-592Article in journal (Refereed)
    Abstract [en]

    Hemolymph coagulation is vital for larval hemostasis and important in immunity, yet the molecular basis of coagulation is not well understood in insects. Of the larval clotting factors identified in Drosophila, Fondue is not conserved in other insects, but is notable for its effects on the clot's physical properties.. a possible function in the cuticle, and for being a substrate of transglutaminase. Transglutaminase is the only mammalian clotting factor found in Drosophila, and as it acts in coagulation in other invertebrates, it is also likely to be important in clotting in Drosophila. Here we describe a Fondue-GFP fusion construct that labels the cuticle and clot, and show that chemical inhibition and RNAi knockdown of the Drosophila transglutaminase gene affect clot properties and composition in ways similar to knockdown of the fon gene. Thus, Fondue appears to be incorporated into the cuticle and is a key transglutaminase substrate in the clot. This is also the first direct functional confirmation that transglutaminase acts in coagulation in Drosophila.

  • 19.
    Lindström, Jonna
    Södertörn University College, School of Life Sciences.
    Dietary intake estimations of brominated flame retardants for Swedish children2008Independent thesis Advanced level (degree of Magister), 20 points / 30 hpStudent thesis
    Abstract [en]

    The dietary intake of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) have been estimated for Swedish children. A dietary survey performed in 2003, including 4, 8-9 and 11-12 year olds, and concentrations in individual food items were combined. The food included in the study was mainly of animal origin, consisting of fish and shellfish, dairy products, meat products, eggs, animal and vegetable fats and fats from miscellaneous food products. The medium-bound intake of PBDEs (9 congeners) were estimated to 23.0 ng/day, 30.9 ng/day and 27.7 ng/day for 4, 8-9 and 11-12 years olds respectively. The corresponding estimations for HBCD were 7.94 ng/day 10.7 ng/day and 9.46 ng/day for 4, 8-9 and 11-12 years olds respectively. These results show a higher daily intake for 8-9 year olds compared with the other age groups. However, when estimating the daily intake per kg bw, the intake decreases with age. BDE-47 contributed the most to the total intake of PBDEs, with approximately 40%. The food group contributing the most to the intake of PBDEs and HBCD was fish and shellfish, of which non-Baltic fatty fish was the largest contributor. There were no considerable differences between boys and girls in any of the aspects examined. The result from this study show a lower intake of PBDEs and HBCD in Swedish children compared with children in other studies made in Europe and the United States.

  • 20.
    Liuzza, Marco Tullio
    et al.
    Stockholms universitet.
    Lindholm, Torun
    Stockholms universitet.
    Hawley, Caitlin
    Stockholms universitet.
    Gustafsson Sendén, Marie
    Stockholms universitet.
    Ekström, Ingrid
    Stockholms universitet.
    Olsson, Mats J.
    Karolinska Institutet.
    Larsson, Maria
    Stockholms universitet.
    Olofsson, Jonas K.
    Stockholms universitet.
    The Body Odor Disgust Scale (BODS): Development and Validation of a Novel Olfactory Disgust Assessment2017In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 42, no 6, p. 499-508Article in journal (Refereed)
    Abstract [en]

    Disgust plays a crucial role in the avoidance of pathogen threats. In many species, body odors provide important information related to health and disease, and body odors are potent elicitors of disgust in humans. With this background, valid assessments of body odor disgust sensitivity are warranted. In the present article, we report the development and psychometric validation of the Body Odor Disgust Scale (BODS), a measure suited to assess individual differences in disgust reaction to a variety of body odors. Collected data from 3 studies (total n = 528) show that the scale can be used either as a unidimensional scale or as a scale that reflects two hypothesized factors: sensitivity to one's own body odors versus those of others. Guided by our results, we reduced the scale to 12 items that capture the essence of these 2 factors. The final version of the BODS shows an excellent internal consistency (Cronbach's alpha s > 0.9). The BODS subscales show convergent validity with other general disgust scales, as well as with other olfactory functions measures and with aspects of personality that are related to pathogen avoidance. A fourth study confirmed the construct validity of the BODS and its measurement invariance to gender. Moreover, we found that, compared with other general disgust scales, the BODS is more strongly related to perceived vulnerability to disease. The BODS is a brief and valid assessment of trait body odor disgust sensitivity.

  • 21.
    Löfmark, Sonja
    et al.
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institutet.
    Fang, Hong
    Karolinska Institutet.
    Hedberg, Maria
    Karolinska Institutet.
    Edlund, Charlotta
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institutet.
    Inducible metronidazole resistance and nim genes in clinical Bacteroides fragilis group isolates2005In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 49, no 3, p. 1253-1256Article in journal (Refereed)
    Abstract [en]

    Nitroimidazole resistance (nim) genes were detected in 2% of 1,502 clinical Bacteroides fragilis group strains isolated from 19 European countries, and a novel nim gene was identified. High metronidazole resistance could be induced in nim-positive strains, which emphasizes the importance of acknowledging metronidazole resistance in the clinical setting.

  • 22.
    Löfmark, Sonja
    et al.
    Karolinska Institute.
    Jernberg, Cecilia
    Södertörn University, School of Life Sciences. Karolinska Institute.
    Jansson, Janet K.
    Swedish University of Agricultural Sciences.
    Edlund, Charlotta
    Karolinska Institute / Medical Products Agency.
    Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. and resistance genes2006In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 58, no 6, p. 1160-1167Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim was to study the long-term consequences of 1 week clindamycin administration regarding selection and persistence of resistance, resistance determinants and diversity of the Bacteroides spp. in the intestinal microflora. Methods: A total of 1306 Bacteroides isolates were collected from constitutively cultured faecal samples during a 2 year period from eight healthy volunteers. The strains were identified by biochemical and genotyping methods. MIC values were determined by the agar dilution method and presence of resistance genes was screened by real-time PCR. Results: Ecological changes in the intestinal microflora persisting up to 24 months were recorded after a 7 day clindamycin administration to four healthy volunteers. Compared to a control group, not exposed to clindamycin, an enrichment and stabilization of resistant Bacteroides strains and resistance determinants were discovered up to 2 years after clindamycin exposure. Conclusions: The results indicate that even a short-term antibiotic administration can cause long-term alterations in the commensal microbiota of individual subjects, detectable 2 years after dosing. The recorded selection and persistence of resistant strains and resistance genes, illustrates the importance of increasing our knowledge of the role of the abundant intestinal microbial community as a reservoir for spread of resistance.

  • 23.
    Pettersson, Sara
    Södertörn University College, School of Life Sciences.
    Development of siRNA against the CYP1A1 gene for trap of endogenous Ah-receptor ligand2006Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    The aryl hydrocarbon receptor (Ah-receptor) is a member of the bHLH-PAS protein family. The Ah-receptor is a ligand dependent transcription factor, which activates a wide range of genes, most notably the xenobiotica metabolising genes, CYP1A1 and CYP1A2. The biological function of the Ah-receptor is still unknown and an endogenous ligand has yet not been identified. A possible Ah-receptor ligand is 6-formylindolo[3,2-b]carbazole (FICZ). FICZ has a high affinity for the Ah-receptor and is rapidly metabolised by CYP1A1, CYP1A2 and aldehydeoxidase (AOX). To try to trap FICZ or other possible endogenous Ah-receptor ligands, the metabolising enzymes CYP1A1, CYP1A2 and AOX were blocked. This was achieved through chemical blockage of CYP1A1 and CYP1A2 by ellepticin and through silencing with siRNA directed against CYP1A1 and CYP1A2. Successful blockage would be seen as an increase in Ah-receptor dependent XRE-luciferase activity. Chemical blockage of AOX with tungstate did not affect FICZ-dependent XRE-luciferase activation which could indicate that HepG2 cells lack AOX. The chemical blockage of CYP1A1 and CYP1A2 with ellepticin modified the XRE-luciferase response, but did not completely block Ah-receptor activation. In addition it is possible that ellepticin is a ligand for the Ah-receptor. The blockage of CYP1A1 by siRNA was successful; a silencing of CYP1A1 mRNA by at least 50 percent was detected. However due to lack of time it was not tested if the blockage of CYP1A1 and CYP1A2 was sufficient to trap Ah-receptor ligands.

  • 24.
    Rajput, Abdul Mateen
    Södertörn University College, School of Life Sciences.
    Histone modifications after DNA damage affect survival in Schizosaccharomyces pombe2010Independent thesis Advanced level (degree of Master (One Year)), 60 credits / 90 HE creditsStudent thesis
    Abstract [en]

    S. cerevisiae Ada2 and Bre1 has a role in histone post-translational modifications. Deletion of these genes causes deficiency in acetylation (Ada2) or ubiquitination (Bre1) of histones. Further, mutants lacking these genes or homologous genes showed different phenotypes in human and S. cerevisiae while treated with DNA damaging agents 4-NQO and MMS. Bre1 deficient cells showed 4-NQO sensitivity in S. cerevisiae and resistance in human cells. Since it has been shown that S. pombe is more close to mammals in chromatin regulation we wanted to examine S. pombe response against MMS and 4-NQO. By homologous recombination, genes were deleted and mutants were treated with different concentration of both the genotoxins. In accordance with a previous study, Ada2Δ showed sensitivity to MMS while Brl1Δ & Brl2Δ grew as wild type. Surprisingly, unlike S. cerevisiae, S. pombe showed resistance to 4-NQO and has a phenotype similar to the one found in human cells.

  • 25.
    Rustum, Cecilia
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Stockholms universitet, Institutionen för neurokemi.
    Dynamic aspects of nucleocytoplasmic trafficking2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cellular structures and compartmentalization is the result of a dynamic steady state exchange between its components. This thesis is focused in investigations of dynamic properties of green fluorescent protein (GFP)-labeled proteins in live cells using confocal laser microscopy in combination with bleaching techniques such as fluorescence recovery after photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP).

    Studies of dynamic properties of c-Myc in living cells showed that c-Myc is shuttling between the nucleus and the cytoplasm. c-Myc also enters the nucleoli during certain conditions. Nucleolar c-Myc is dynamically associated to structural component(s) of nucleoli, but can exchange with soluble pools in the nucleoplasm and cytoplasm.

    Photobleaching experiments showed that a significant fraction of HIV-1 Vpr is dynamically associated with the NE and rapidly exchanges between the nucleoplasm and the cytoplasm. The yeast two-hybrid system, pull-down experiments and co-immunoprecipitating was used to show that Vpr interacts specifically and directly with a domain in the N-terminal portion of the NPC protein hCG1. The results suggest that the specific interaction of HIV-1 Vpr with the nucleoporin hCG1 results in the dynamic retention of Vpr at the nuclear envelope.

    The distribution and dynamic properties of NPC proteins was investigated in NIH/3T3 cells, lacking the pore membrane protein gp210. Confocal laser scanning microscopy and FRAP experiments showed that the absence of gp210 from nuclear pores of NIH/3T3 cells did neither alter the distribution nor dynamic properties of POM121 and NUP107 (two NPC proteins stably integrated in the NPC).

    Degradation of the integral nuclear pore membrane protein POM121 during apoptosis was investigated in relation to other apoptotic events. POM121 cleavage, which is the earliest sign of dismantling of the nuclear membrane, is due to caspase-3-dependent cleavage at aspartate-531. Loss of nuclear compartmentalization in live cells undergoing apoptosis was monitored as appearance of GFP-NLS in the cytoplasm. The time of appearance of cytoplasmic GFP-NLS correlated with caspase-3-dependent cleavage of POM121. Both events occured concomitantly with collapsing of chromatin against the nuclear periphery, but preceded the onset of nucleosomal DNA fragmentation.

    Translocation ability of the cell-penetrating peptide, transportan, into living cells was investigated. Recombinantly expressed GFP was purified and conjugated to chemically synthesized transportan via a disulfide bond and added to tissues culture cells. Transportan was able to internalize a 27 kDa protein such as GFP in a native folded state into living cells.

  • 26.
    Schenk, Linda
    Södertörn University, School of Life Sciences. KTH, Filosofi.
    Setting occupational exposure limits: Practices and outcomes of toxicological risk assessment2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Occupational Exposure Limits (OELs) are used as an important regulatory instrument to protect workers’ health from adverse effects of chemical exposures. The main objective of this thesis is to study risk assessment practices in the setting of OEL in order to produce knowledge that will help improve the consistency and transparency of OELs.

    For the purpose of paper I a database of OELs for a total of 1341 substances was compiled. Of these, only 25 substances have OELs from all 18 included organisations while more than one third of the substances are only regulated by one organisation alone. The average level of OELs differs substantially between organisations; the US OSHA exposure limits are (on average) nearly 40 % higher than those of Poland.

    In paper II six EU member states’ OELs are compared to the European Commission’s OELs. Also within Europe there is a large difference concerning the average level of OELs (35%). The average level of lists tends to decrease over time, although there are exceptions to this. There are also indications that the exposure limits of EU member states are converging towards the European Commission’s OELs.

    The work presented in paper III identifies steps in the risk assessment that could account for the large differences in OELs for 14 different substances. Differences in the identification of the critical effect could explain the different level of the OELs for half of the substances. But the age of the data review could not account for all the differences in data selection, only one fifth of the documents referred to all available key studies. Also the evaluation of the key studies varied significantly.

    The aim of paper IV was to investigate how the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Commission uses assessment factors when proposing health-based indicative OELs. For only one third of the investigated OELs were explicit assessment factors given. On average the safety margin of the recommendations was 2.1 higher when an explicit assessment factor had been used. It is recommended that the SCOEL develop and adhere to a more articulate framework on the use of assessment factors.

    Paper V focuses on the Derived No-Effect Levels (DNELs) which are to be calculated under the new European Union REACH legislation. It is a comparison of the safety margins of 88 SCOEL recommendations with those of the corresponding worker-DNELs, derived according to the default approach as described in the REACH guidance document. Overall, the REACH safety margins were approximately six times higher than those derived from the SCOEL documentations but varied widely with REACH/SCOEL safety margin ratios ranging by two orders of magnitude, from 0.3 to 58.

  • 27.
    Schenk, Linda
    et al.
    Södertörn University, School of Life Sciences. KTH.
    Hansson, Sven Ove
    Ruden, Christina
    Södertörn University, School of Life Sciences. KTH.
    Gilek, Michael
    Södertörn University, School of Life Sciences.
    Are occupational exposure limits becoming more alike within the European Union?2008In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 28, no 7, p. 858-866Article in journal (Refereed)
    Abstract [en]

    The occupational exposure limits (OELs) established by seven different national regulatory agencies of EU member states are compared with those of the European Commission (EC). The comparison concerned: (1) what chemicals have been selected, (2) the average level of exposure limits for all chemicals, and (3) the similarity between the OELs of different EU member states and the OELs recommended by the European Commission. The average level of the exposure limits has declined during the past 10 years in four of the live countries in our study for which historical data were available to us. Poland has not changed its level noticeably and Germany has increased it. Since the first list of indicative OELs was established by the EC, a few of the EU exposure limits have been lowered. The similarity index indicates that the exposure limits of EU member states are converging towards the European Commission's recommended OELs. Still, the average level of OELs differs between organizations - the Estonian OELs are on average 35% higher than the Polish OELs.

  • 28.
    Schenk, Linda
    et al.
    Södertörn University, School of Life Sciences. KTH.
    Hansson, Sven Ove
    Ruden, Christina
    Södertörn University, School of Life Sciences. KTH.
    Gilek, Michael
    Södertörn University, School of Life Sciences.
    Occupational exposure limits: A comparative study2008In: Regulatory toxicology and pharmacology, ISSN 0273-2300, E-ISSN 1096-0295, Vol. 50, no 2, p. 261-270Article in journal (Refereed)
    Abstract [en]

    Occupational exposure limits (OELs) are used as an important regulatory instrument to protect workers' health from adverse effects of chemical exposures. The OELs mirror the outcome of the risk assessment and risk management performed by the standard setting actor. In this study we compared the OELs established by 18 different organisations or national regulatory agencies. The OELs were compared with respect to: (1) what chemicals have been selected and (2) the average level of exposure limits for all chemicals. Our database contains OELs for a total of 1341 substances; of these 25 substances have OELs from all 18 organisations while more than one-third of the substances are only regulated by one organisation. The average level of the exposure limits has declined during the past 10 years for 6 of the 8 organisations in our study for which historical data were available; it has increased for Poland and remained nearly unchanged for Sweden. The average level of OELs differs substantially between organisations; the US OSHA exposure limits are (on average) nearly 40 % higher than those of Poland. The scientific or policy-related motivations for these differences remain to be analysed.

  • 29.
    Schenk, Linda
    et al.
    KTH, Filosofi.
    Johanson, Gunnar
    Institute of Environmental Medicine, Karolinska Institutet.
    Use of Uncertainty Factors by the SCOEL in their derivation of health-based Occupational Exposure Limits2010In: Critical reviews in toxicology, ISSN 1040-8444, E-ISSN 1547-6898, Vol. 40, no 9, p. 791-798Article, review/survey (Refereed)
    Abstract [en]

    The aim of this study was to investigate how the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Commission uses uncertainty factors when proposing health-based indicative occupational exposure limit values (IOELVs). In total, 75 IOELVs in 62 summary documents published from 1991 to 2003 were analyzed. For 31 of the IOELVs, no explicit uncertainty factor (EUF) was stated. For these, we calculated an implicit safety margin (ISM) as the ratio between the point of departure (POD, derived from the NOAEL or LOAEL of the critical effect) and the proposed IOELV. We further analysed whether date of recommendation, type of critical effect, nature of POD or amount of available data influenced the magnitude of the EUFs and ISMs. The ISMs varied little (range 1-5), while the EUFs showed more variability (range 1-50). The EUFs remained unaffected over time and the ISMs decreased slightly. Significant differences in the magnitude of the EUFs, but not ISMs, were found between critical effects, however, contrary to expected the average EUFs and ISMs for irritation were similar to those for more severe systemic effects. The nature of the POD affected the ISMs and EUFs only slightly and less than expected. Both EUFs and ISMs showed a weak but significant negative correlation with the amount of available toxicological data, measured as the number of relevant publications in PubMed, whereas SCOEL statements on data sufficiency had no influence. Overall, the most striking difference was that between EUFs and ISMs, the former being on average 2.1 times higher.

  • 30.
    Svenaeus, Fredrik
    Södertörn University, School of Culture and Education, Centre for Studies in Practical Knowledge.
    Naturalisticand Phenomenological Theories of Health: Distinctions and Connections2013In: Human Experience and Nature: Examining the Relationship between Phenomenology and Naturalism / [ed] Havi Carel and Darian Meacham, Cambridge: Cambridge University Press, 2013Chapter in book (Refereed)
    Abstract [en]

    In this paper I present and compare the philosophies and ideas behind naturalistic theories of health on the one hand and phenomenological theories of health on the other. The basic difference between the two sets of theories is no doubt that whereas naturalistic theories claim to rest on value neutral concepts, such as normal biological function, the phenomenological suggestions for theories of health take their starting point in what is often named intentionality: meaningful stances taken by the embodied person in experiencing and understanding her situation and taking action in the world.

    Although naturalism and phenomenology are fundamentally different in their approach to understand and define health, they are not necessarily opposed when it comes to understanding the predicament of ill persons. Naturalism can afford phenomenology an important strategic importance in finding clues for medical investigations, just as phenomenology can envelop a naturalistic understanding of diseases. Furthermore, the two theories display similarities in their emphasis of embodiment as the central element of health theory and in their stress on the alien nature of the body displayed in illness. Theories of biology and phenomenology are, indeed, companionable and in many cases also mutually supportive in the realms of health and illness.

  • 31. Tikka, Pia
    et al.
    Kaipainen, Mauri
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Media Technology.
    Embodied Protonarratives Embedded in Systems of Contexts: A Neurocinematic Approach2015In: Neuroscience and Media: New Understandings and Representations / [ed] Grabowski, Michael, Routledge, 2015, p. 76-88Chapter in book (Other academic)
  • 32. Tikka, Pia
    et al.
    Kaipainen, Mauri
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Media Technology.
    Phenomenological Considerations on Time Consciousness under Neurocinematic Search Light2014In: Cinéma & cie : international film studies journal, ISSN 2036-461X, Vol. XIV, no 22-23Article in journal (Refereed)
    Abstract [en]

    Film narratives are intrinsically time-dependent designs. This article proposes a model of narrative nowness, based on Husserl's concepts of retention and protention on one hand, and Francisco Varela's neurophenomenological exploration of time consciousness on the other, relating this further to narrative experience and its neural epiphenomena. Only recently has brain research been equipped with the possibility of dealing with temporal frames relevant for time consciousness in the scope of whole narratives. The study of cinema using neuroscientific methods and insights is referred to as neurocinematics. We promote neurocinematics as a complementary method of traditional film research, rather than an approach of brain sciences in general. Neurocinematic methods may provide film studies with new tools for re-evaluating established filmmaking conventions and developing new ways to study, for instance, the film viewer's experience and related aspects of time consciousness.

  • 33.
    Tikka, Pia
    et al.
    Aalto University, Finland .
    Kaipainen, Mauri Y.
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Media Technology.
    From naturalistic neuroscience to modeling radical embodiment with narrative enactive systems2014In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 8, p. 794-Article in journal (Refereed)
    Abstract [en]

    Mainstream cognitive neuroscience has begun to accept the idea of embodied mind, which assumes that the human mind is fundamentally constituted by the dynamical interactions of the brain, body, and the environment. In today’s paradigm of naturalistic neurosciences, subjects are exposed to rich contexts, such as video sequences or entire films, under relatively controlled conditions, against which researchers can interpret changes in neural responses within a time window. However, from the point of view of radical embodied cognitive neuroscience, the increasing complexity alone will not suffice as the explanatory apparatus for dynamical embodiment and situatedness of the mind. We suggest that narrative enactive systems with dynamically adaptive content as stimuli,may serve better to account for the embodied mind engaged with the surrounding world. Among the ensuing challenges for neuroimaging studies is how to interpret brain data against broad temporal contexts of previous experiences that condition the unfolding experience of nowness. We propose means to tackle this issue, as well as ways to limit the exponentially growing combinatoria of narrative paths to a controllable number.

  • 34. Tikka, Pia
    et al.
    Väljamäe, Aleksander
    de Borst, Aline
    Pugliese, Roberto
    Ravaja, Niklas
    Kaipainen, Mauri
    Södertörn University, School of Communication, Media and it, Media technology.
    Takala, Tapio
    Enactive cinema paves way for understanding complex real-time social interaction in neuroimaging experiments2012In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 6, article id 298Article in journal (Refereed)
    Abstract [en]

    We outline general theoretical and practical implications of what we promote as enactive cinema for the neuroscientific study of online socio-emotional interaction. In a real-time functional magnetic resonance imaging (rt-fMRI) setting, participants are immersed in cinematic experiences that simulate social situations. While viewing, their physiological reactions - including brain responses - are tracked, representing implicit and unconscious experiences of the on-going social situations. These reactions, in turn, are analysed in real-time and fed back to modify the cinematic sequences they are viewing while being scanned. Due to the engaging cinematic content, the proposed setting focuses on living-by in terms of shared psycho-physiological epiphenomena of experience rather than active coping in terms of goal-oriented motor actions. It constitutes a means to parametrically modify stimuli that depict social situations and their broader environmental contexts. As an alternative to studying the variation of brain responses as a function of a priori fixed stimuli, this method can be applied to survey the range of stimuli that evoke similar responses across participants at particular brain regions of interest.

  • 35.
    Wigerius, Michael
    et al.
    Södertörn University, School of Life Sciences, Chemistry. Södertörn University, School of Life Sciences, Molecular biology.
    Melik, Wessam
    Södertörn University, School of Life Sciences, Chemistry. Södertörn University, School of Life Sciences, Molecular biology.
    Elväng, Annelie
    Södertörn University, School of Life Sciences, Molecular biology.
    Johansson, Magnus
    Södertörn University, School of Life Sciences, Chemistry. Södertörn University, School of Life Sciences, International health.
    Rac1 and Scribble are targets for the arrest of neurite outgrowth by TBE virus NS52010In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 44, no 3, p. 260-271Article in journal (Refereed)
    Abstract [en]

    Tick-borne encephalitis virus (TBEV) causes extensive CNS disease in humans known as TBE, however, relatively little is known of the molecular mechanisms for its progress. Here, we now show that TBEV produces defects in neuronal development of PC12 cells through a function of the viral NS5 protein. The methyltransferase domain of NS5 is critical and sufficient for restriction of nerve growth factor induced neurite outgrowth. This effect is reversed by expression of NS5 mutants unable to bind Scribble and unexpectedly, in Scribble depleted cells with binding-competent NS5. Furthermore, we also demonstrate that the Rho GTPase Rac1 and the guanine nucleotide-exchange factor, beta PIX are outcompeted by NS5 for binding to Scribble, linking to effects on neurite outgrowth by TBEV. Together, these findings provide the first experimental evidence that Rac1 and beta PIX are indirect targets of NS5 acting through the multifunctional polarity protein Scribble to oppose neuronal differentiation. In conclusion, our results offer a potential mechanism by which TBEV alters neuronal circuitry and opens new avenues for therapeutic interventions.

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