Change search
Refine search result
2345678 201 - 250 of 3709
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 201.
    Awah, Nancy
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Studies on Plasmodium falciparum asexual blood stage antigens: RAP-2/RSP-2 and Pf332 in focus2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The life cycle of the malaria parasite is very complex and provides a number of potential targets for vaccination. In this thesis, data on two plasmodial asexual blood stage antigens (RAP-2 and Pf332) are presented.

    A partial aim of the work presented herein was to investigate the mechanisms responsible for the destruction of erythroid cells in anaemia, and more specifically to define the role of the rhoptry associated protein (RAP)-2 and other members of the RAP complex, RAP-1 and -3 in processes resulting in anaemia. Antibodies to the RAP complex were shown to have the potential to mediate the destruction of RAP-2-tagged erythroid cells by phagocytosis or by complement activation and lysis. In addition, antibodies to RAP-1 and RAP-2 could induce the apoptotic death of RAP-2- tagged erythroblasts. The frequency and functionality of naturally occurring RAP-2 antibodies in the sera of anaemic and non-anaemic Cameroonian children were also investigated. All sera tested contained RAP-2-reactive antibodies by both immunofluorescence and flow cytometry. The anaemic group of children had higher levels of IgG than the non-anaemic ones, while the levels of IgM were similar. With respect to IgG subclasses, higher levels of IgG3 were seen in the non-anaemic individuals as compared to anaemic subjects. The non-anaemic individuals recognised a greater proportion of RAP-2-tagged RBCs and activated complement to a greater extent than the anaemic ones.

    Earlier studies observed that humans continuously exposed to malaria, recognised Pf332 extensively. Further studies revealed that Pf332 antibodies were able to inhibit parasite growth and cytoadherence in vitro. Making use of Pf332-C231, a sub-fragment of Pf332, we studied the effects/mode of action of C231-specific antibodies on P. falciparum parasite growth and development in vitro. The antibodies appeared to act mainly on late stage parasites by two main mechanisms: 1) through the induction of abnormal/pyknotic parasites, and, 2) RBC lysis (disintegration of RBCs), thus limiting parasite growth and development. The antibody isotype in this context was IgG. Following the removal of immune pressure, parasites resumed growth, albeit at a much slower rate. The results suggest that during natural infections, antibodies to C231 could play a role in parasite control.

    In summary, these data suggest that antibodies to both antigens could be instrumental in immune responses leading to disease control, but could also mediate pathology.

  • 202.
    Awah, Nancy
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Balogun, Halima
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Achidi, E.
    Mariuba, L. A.
    Nogueira, P. A.
    Orlandi, P.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Gysin, J.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Antibodies to the Plasmodium falciparum rhoptry protein RAP-2/RSP-2 in relation to anaemia in Cameroonian children2011In: Parasite immunology (Print), ISSN 0141-9838, E-ISSN 1365-3024, Vol. 33, no 2, p. 104-115Article in journal (Refereed)
    Abstract [en]

    Previous studies have implicated reactive antibodies to the low molecular weight rhoptry-associated proteins (RAP-1, RAP-2/RSP-2 and RAP-3) in erythroid cell destruction during Plasmodium falciparum infection. In this pilot study, the frequency, specificity and functional capacity of naturally acquired anti-RAP-2/RSP-2 antibodies were investigated in the sera of anaemic and nonanaemic malaria-infected Cameroonian children. All sera recognized RAP-2/RSP-2 by FACS, irrespective of the clinical status of the subjects. However, the anaemic children showed higher levels of IgG antibodies than the nonanaemic group, while both groups showed similar levels of IgM antibodies. Only few individuals had detectable levels of RAP-2/RSP-2-specific IgG1 and IgG3 subclass antibodies, while no IgG2 and IgG4 subclass antibodies were detected in these subjects. By ELISA, the anaemic group tended to show higher levels of antibodies to RAP-2/RSP-2 regarding all antibody classes tested, except for IgG4 and IgE. Unexpectedly, sera from the nonanaemic group activated complement to a greater extent than those from the anaemic group. These results need to be confirmed in extended studies but indicate that the effector functions of the RAP-2/RSP-2-reactive antibodies may be more important than their amounts. Such antibodies could play a role in both immunity and pathogenesis during P. falciparum infection.

  • 203. Axelsson, J
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Gustavsson, P
    Rudman, A
    Selection into shift and night work2013Conference paper (Refereed)
  • 204.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sleep, appearance and social interactions2014Conference paper (Other academic)
  • 205.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sömn och fysisk aktivitet2016In: FYSS 2017: fysisk aktivitet i sjukdomsprevention och sjukdomsbehandling, Stockholm: Läkartidningen förlag AB , 2016, 3, p. 171-183Chapter in book (Other academic)
  • 206. Axelsson, John
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Akerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Donofrio, Paolo
    Lekander, Mats
    Ingre, Michael
    Sleepiness and performance in response to repeated sleep restriction and subsequent recovery during semi-laboratory conditions.2008In: Chronobiol Int, ISSN 1525-6073, Vol. 25, no 2, p. 297-308Article in journal (Refereed)
    Abstract [en]

    Sleepiness and performance in response to repeated sleep restriction and subsequent recovery during semi-laboratory conditions.

    Axelsson J, Kecklund G, Akerstedt T, Donofrio P, Lekander M, Ingre M.

    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. john.axelsson@ki.se

    There is an ongoing debate of how best to measure the effects of sleep loss in a reliable and feasible way, partly because well controlled laboratory studies and field studies have come to different conclusions. The aims of the present study were to investigate both sleepiness and performance in response to long-term sleep restriction and recovery in a semi-laboratory environment, investigate order effects (i.e., whether levels return to baseline) in a study with seven days of recovery, and characterize individual differences in tolerance to restricted sleep. Nine healthy men (age 23-28 yrs) participated in the protocol, which included one habituation day (sleep 23:00-07:00 h), two baseline days (23:00-07:00 h), five days with restricted sleep (03:00-07:00 h), and seven recovery days (23:00-07:00 h). Participants went outdoors at least twice each day. Reaction-time tests were performed at 08:00, 14:00, and 20:00 h each day in the laboratory. Sleepiness was self-rated by the Karolinska Sleepiness Scale (KSS)after each test. The mixed-effect regression models showed that each day of restricted sleep resulted in an increase of sleepiness by 0.64+/- .05 KSS units (a nine-step scale, p < .001), increase of median reaction times of 6.6+/- 1.6 ms ( p = .003), and increase of lapses/test of 0.69 +/- .16 ms ( p < .001). Seven days of recovery allowed participants to return to the baseline for sleepiness and median reaction time, but not for lapses.The individual differences were larger for performance measures than for sleepiness; the between-subject standard deviation for the random intercept was in the magnitude of the effects of 1.1 days of restricted sleep for sleepiness, 6.6 days of restricted sleep for median reaction time, and 3.2 days for lapses. In conclusion, the present study shows that sleepiness is closely related to sleep pressure, while performance measures, to a larger extent, appear determined by specific individual traits. Moreover, it is suggested to measure sleepiness in a standardized situation so as to minimize the influences of contextual factors.

  • 207.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Tigerström, L
    Does rapid eye movement (REM) sleep prepare the brain for wakening?2014In: Journal of sleep research, Special issue: 22nd Congress of the European Sleep Research Society, 16-20 September, 2014, Tallinn, Estonia, 2014Conference paper (Other academic)
  • 208.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Karshikoff, Bianca
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Hedman, E.
    Is health anxiety related to disease avoidance?2015Conference paper (Refereed)
  • 209. Axelsson, John
    et al.
    Rehman, Javaid-Ur
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Ekman, Rolf
    Miller, Gregory E
    Höglund, Caroline Olgart
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans2013In: PloS one, ISSN 1932-6203, Vol. 8, no 12, p. e82291-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion.

    METHODS: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed.

    RESULTS: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day.

    CONCLUSIONS: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

  • 210. Axelsson, John
    et al.
    Sundelin, Tina
    Karolinska Institutet, Sweden.
    Ingre, Michael
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Van Someren, Eus J. W.
    Olsson, Andreas
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Beauty sleep: experimental study on the perceived health and attractiveness of sleep deprived people2010In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 341, article id c6614Article in journal (Refereed)
    Abstract [en]

    Our findings show that sleep deprived people appear less healthy, less attractive, and more tired compared with when they are well rested. This suggests that humans are sensitive to sleep related facial cues, with potential implications for social and clinical judgments and behaviour. Studies are warranted for understanding how these effects may affect clinical decision making and can add knowledge with direct implications in a medical context.

  • 211.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Sundelin, Tina
    Olsson, Mats J.
    Sorjonen, Kimmo
    Axelsson, Charlotte
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Universitätsklinikum Essen, Germany.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Identification of acutely sick people and facial cues of sickness2018In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 285, no 1870, article id 20172430Article in journal (Refereed)
    Abstract [en]

    Detection and avoidance of sick individuals have been proposed as essential components in a behavioural defence against disease, limiting the risk of contamination. However, almost no knowledge exists on whether humans can detect sick individuals, and if so by what cues. Here, we demonstrate that untrained people can identify sick individuals above chance level by looking at facial photos taken 2 h after injection with a bacterial stimulus inducing an immune response (2.0 ng kg-1 lipopolysaccharide) or placebo, the global sensitivity index being d' = 0.405. Signal detection analysis (receiver operating characteristic curve area) showed an area of 0.62 (95% confidence intervals 0.60-0.63). Acutely sick people were rated by naive observers as having paler lips and skin, a more swollen face, droopier corners of the mouth, more hanging eyelids, redder eyes, and less glossy and patchy skin, as well as appearing more tired. Our findings suggest that facial cues associated with the skin, mouth and eyes can aid in the detection of acutely sick and potentially contagious people.

  • 212.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institute, Sweden.
    Vyazovskiy, Vladyslav V.
    Banking Sleep and Biological Sleep Need2015In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 38, no 12, p. 1843-1845Article in journal (Refereed)
  • 213.
    Axelsson, Sara
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Eriksson, Kåre
    Department of Occupational and Environmental Medicine, University Hospital of Northern Sweden, Umeå, Sweden.
    Hagström, Katja
    Department of Environmental Science, Örebro University, Örebro.
    Bryngelsson, Ing-Liss
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    HPLC/neg-ESI-MS determination of resin acids in urine from Swedish wood pellets production plants workers and correlation with air concentrations2012In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650Article in journal (Refereed)
  • 214.
    Axelsson, Viktoria
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Evaluation of neurotoxic properties of gliotoxin2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The occurrence of mould in food and animal feed is a severe problem due to the secondary metabolites, called mycotoxins, which can possess toxic activity. Aspergillus fumigatus is a common fungus found in improperly stored animal feed and the abundance of spores of the fungus is frequently spread into the air. Gliotoxin has been identified as one of the most toxic second metabolites produced by A. fumigatus. Although A. fumigatus is known to produce mycotoxins that induce neurological syndromes, the neurotoxic properties of gliotoxin have not previously been studied. In this thesis a neurotoxic activity of gliotoxin was demonstrated by using differentiated human neuroblastoma SH-SY5Y cells as a surrogate for the nervous system. The major findings were as follows:

    i. Gliotoxin is highly toxic to SH-SY5Y cells and there is a correlation between the toxicity and the cellular redox status.

    ii. Gliotoxin reduces the number of neurites, but does not affect the cell bodies morphologically, at non-cytotoxic concentrations. This indicates that the toxin may induce peripheral axonopathy in vivo.

    iii. The intracellular free Ca2+ concentration is increased after exposure to gliotoxin, an effect that is the most ubiquitous feature of neuronal cell death. Simultaneously, calpains and caspases, proteases known to be involved in neuronal death and axonal degeneration, are activated.

    iv. The observed irreversible neurite degenerative effects of gliotoxin are mainly dependent on caspase activation, whereas calpains are involved in the gliotoxin-induced cytotoxicity.

    v. Gliotoxin induces a decreased rate of protein synthesis at non-cytotoxic concentration, which may contribute to the degeneration of neurites.

    vi. We did also succeed in developing an in vitro method for determination of toxic activity in animal feed. This study was done in collaboration with National Veterinary Institute (SVA) in Uppsala, and the method is today established and in use at Department of Animal Feed, SVA.

  • 215.
    Axelsson, Viktoria
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Holback, Sofia
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Sjögren, Maria
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Gustafsson, Helena
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells.2006In: Biochem Biophys Res Commun, ISSN 0006-291X, Vol. 345, no 3, p. 1068-74Article in journal (Refereed)
    Abstract [en]

    In this study, a significant increase by 50% in intracellular free calcium concentration ([Ca(2+)](i)) was observed in differentiated human neuroblastoma (SH-SY5Y) cells after exposure to 0.25microM of the fungal metabolite gliotoxin for 72h. Further, the involvement of caspases and calpains was demonstrated to underlie the gliotoxin-induced cytotoxic and neurite degenerative effects. The caspase inhibitor Z-VAD-fmk almost completely reduced the neurite degeneration from 40% degeneration of neurites to 5% as compared to control. Inhibition of calpains with calpeptin significantly attenuated gliotoxin-induced cytotoxicity, determined as reduction in total cellular protein content, from 43% to 14% as compared to control cells. Western blot analyses of alphaII-spectrin breakdown fragments confirmed activity of the proteases, and that alphaII-spectrin was cleaved by caspases in gliotoxin-exposed cells. These results show that calpains and caspases have a role in the toxicity of gliotoxin in differentiated SH-SY5Y cells and that the process may be Ca(2+)-mediated.

  • 216.
    Aydin, Juhanes
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Senthil, Kumar K
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sayah, Mahmoud J
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Wallner, Olov A
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabó, Kálmán J
    Synthesis and catalytic application of chiral 1,1'-Bi-2-naphthol- and biphenanthrol-based pincer complexes: selective allylation of sulfonimines with allyl stannane and allyl trifluoroborate.2007In: Journal of Organic Chemistry, Vol. 72, no 13, p. 4689-4697Article in journal (Refereed)
    Abstract [en]

    New easily accessible 1,1'-bi-2-naphthol- (BINOL-) and biphenanthrol-based chiral pincer complex catalysts were prepared for selective (up to 85% enantiomeric excess) allylation of sulfonimines. The chiral pincer complexes were prepared by a flexible modular approach allowing an efficient tuning of the selectivity of the catalysts. By employment of the different enantiomeric forms of the catalysts, both enantiomers of the homoallylic amines could be selectively obtained. Both allyl stannanes and allyl trifluoroborates can be employed as allyl sources in the reactions. The biphenanthrol-based complexes gave higher selectivity than the substituted BINOL-based analogues, probably because of the well-shaped chiral pocket generated by employment of the biphenanthrol complexes. The enantioselective allylation of sulfonimines presented in this study has important implications for the mechanism given for the pincer complex-catalyzed allylation reactions, confirming that this process takes place without involvement of palladium(0) species.

  • 217.
    Aydin, Juhanes
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabó, Kálmán
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium-pincer complex catalyzed C-C coupling of allyl nitriles with tosyl imines via regioselective allylic C-H bond functionalization2008In: Organic Letters, ISSN 1523-7060, Vol. 10, no 13, p. 2881-2884Article in journal (Refereed)
    Abstract [en]

    A mechanistically new palladium-pincer complex catalyzed allylation of sulfonimines is presented. This reaction involves C-H bond functionalization of allyl nitriles under mild conditions. The reaction proceeds with a high regioselectivity, without allyl rearrangement of the product. Modeling studies indicate that the carbon-carbon bond formation process proceeds via (η1-allyl)palladium pincer complex intermediates.

  • 218. Aydin-Schmidt, Berit
    et al.
    Thorsell, Walborg
    Stockholm University, Faculty of Science, Department of Zoology.
    Wahlgren, Mats
    Carolus Linnaeus, the ash, worm-wood and other anti-malarial plants2010In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, no 11-12, p. 941-942Article in journal (Refereed)
    Abstract [en]

    In 1735 Carolus Linnaeus wrote that quinine was the preferred treatment for malaria but that the bark of the ash (Fraxinus excelsior) and worm-wood (Artemisia absinthium) also had effects on the disease. We here report that lipo- and hydrophilic extracts of the bark of the ash inhibit the in vitro growth of the asexual stages of P. falciparum. The data suggests that the knowledge of the treatment of malaria was already available in Europe some 300 years ago.

  • 219.
    Ayesa, Susana
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lindquist, Charlotta
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Agback, Tatiana
    Benkestock, Kurt
    Classon, Björn
    Henderson, Ian
    Hewitt, Ellen
    Jansson, Katarina
    Kallin, Anders
    Sheppard, Dave
    Samuelsson, Bertil
    Solid-phase parallel synthesis and SAR of 4-amidofuran-3-one inhibitors of cathepsin S: Effect of sulfonamides P3 substituents on potency and selectivity.2009In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 17, no 3, p. 1307-1324Article in journal (Refereed)
    Abstract [en]

    Highly potent and selective 4-amidofuran-3-one inhibitors of cathepsin S are described. The synthesis and structure–activity relationship of a series of inhibitors with a sulfonamide moiety in the P3 position is presented. Several members of the series show sub-nanomolar inhibition of the target enzyme as well as an excellent selectivity profile and good cellular potency. Molecular modeling of the most interesting inhibitors describes interactions in the extended S3 pocket and explains the observed selectivity towards cathepsin K.

  • 220.
    Azad, Azade
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Leander, Lina
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Children's Reporting About Sexual Versus Physical Abuse: Patterns of Reporting, Avoidance and Denial2015In: Psychiatry, Psychology and Law, ISSN 1321-8719, E-ISSN 1934-1687, Vol. 22, no 6, p. 890-902Article in journal (Refereed)
    Abstract [en]

    This study analysed the reporting patterns of 22 sexually abused children and 23 physically abused children (all cases had been verified). Police interviews with the children were analysed in relation to the amount and type of information reported, as well as the frequency of denial and avoidance of critical information. Physically and sexually abused children reported more neutral information from the abusive acts per se than information regarding sexual or physically violent acts. The children were also high in avoidance and denial regarding information about the abuse. The physically abused children reported more severe information about physically abusive acts compared with the amount of information the sexually abused children reported about severe sexual acts. An explanation for this may have been the shameful and taboo nature of sexual abuse. It is important to undertake further investigation of how the nature and type of abuse, to which child witnesses have been exposed, may affect the reporting pattern. Such information may broaden our knowledge about how to conduct and evaluate child interviews.

  • 221.
    Baars, Louise
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Protein targeting, translocation and insertion in Escherichia coli: Proteomic analysis of substrate-pathway relationships2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Approximately 10% of the open reading frames in the genome of the Gram-negative bacterium E. coli encodes secretory proteins, and 20% encodes integral inner membrane proteins (IMPs). These proteins are sorted to their correct cellular compartments (the periplasm and the outer and inner membranes) by specialized targeting and translocation/insertion systems. So far, a very limited set of model proteins have been used to study proteins sorting requirements in E. coli. The main objective of all the papers presented in this thesis was to determine the targeting and translocation/insertion requirements of more E. coli proteins. In papers I and II, this was done using focused approaches. Selected model proteins (lipoproteins and putative outer membrane proteins) were expressed from plasmids and their targeting and translocation were analysed in vitro by crosslinking experiments and/or in vivo by pulse-chase analysis in different E. coli mutant strains. In papers III a comparative sub-proteome analysis was carried out to define the role of the cytoplasmic chaperone SecB in protein targeting. In paper IV, a similar approach was used to study how protein translocation and insertion is affected upon depletion of the essential Sec-translocon component SecE. The ‘global’ approach used in paper III and IV allowed us to study protein targeting and translocation/insertion requirements on a proteome level. This led to the identification of several novel SecB substrates and a large number of potential Sec-translocon independent IMPs.

  • 222. Babor, Thomas
    et al.
    Stenius, Kerstin
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD).
    Health services: Treatment of substance use disorders within health services2010In: ATLAS on substance use (2010): Resources for the prevention and treatment of substance use disorders / [ed] Wolrd Health Organization, WHO Library Cataloguing-in-Publication Data , 2010, p. 23-25Chapter in book (Other academic)
    Abstract [en]

    http://www.who.int/substance_abuse/publications/treatment/en/index.html

  • 223. Backeström, Anna
    et al.
    Eriksson, Sture
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Olsson, Tommy
    Rolandsson, Olov
    Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study2015In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 7, article id 20Article in journal (Refereed)
    Abstract [en]

    Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. Results: A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. Conclusions: This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

  • 224. Bagger-Sjöbäck, Dan
    et al.
    Strömbäck, Karin
    Hakizimana, Pierre
    Plue, Jan
    Stockholm University, Faculty of Science, Department of Physical Geography.
    Larsson, Christina
    Hultcrantz, Malou
    Papatziamos, Georgios
    Smeds, Henrik
    Danckwardt-Lillieström, Niklas
    Hellström, Sten
    Johansson, Ann
    Tideholm, Bo
    Fridberger, Anders
    A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, article id e0115657Article in journal (Refereed)
    Abstract [en]

    Background Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies. Methods We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo. Findings One year after surgery, high-frequency hearing had improved 2.7 +/- 3.8 dB in the placebo group (67 patients analysed) and 2.4 +/- 3.7 dB in the treated group (72 patients; means +/- 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy.

  • 225.
    Bajinskis, Ainars
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Lindegren, Helene
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Johansson, Lotta
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Low-Dose/Dose-Rate gamma Radiation Depresses Neural Differentiation and Alters Protein Expression Profiles in Neuroblastoma SH-SY5Y Cells and C17.2 Neural Stem Cells2011In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 175, no 2, p. 185-192Article in journal (Refereed)
    Abstract [en]

    The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose gamma-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs gamma rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate gamma rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism. (C) 2011 by Radiation Research Society

  • 226.
    Bajinskis, Ainars
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Natarajan, Adayapalam T.
    Erixon, Klaus
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    DNA double strand breaks induced by the indirect effect of radiation are more efficiently repaired by non-homologous end joining compared to homologous recombination repair2013In: Mutation research. Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, E-ISSN 1879-3592, Vol. 756, no 1-2, p. 21-29Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the relative involvement of three major DNA repair pathways, i.e., non-homologous end joining (NHEJ), homologous recombination (HRR) and base excision (BER) in repair of DNA lesions of different complexity induced by low- or high-LET radiation with emphasis on the contribution of the indirect effect of radiation for these radiation qualities. A panel of DNA repair-deficient CHO cell lines was irradiated by Cs-137 gamma-rays or radon progeny alpha-particles. Irradiation was also performed in the presence of 2 M DMSO to reduce the indirect effect of radiation and the complexity of the DNA damage formed. Clonogenic survival and micronucleus assays were used to estimate efficiencies of the different repair pathways for DNA damages produced by direct and indirect effects. Removal of the indirect effect of low-LET radiation by DMSO increased clonogenic survival and decreased MN formation for all cell lines investigated. A direct contribution of the indirect effect of radiation to DNA base damage was suggested by the significant protection by DMSO seen for the BER deficient cell line. Lesions formed by the indirect effect are more readily repaired by the NHEJ pathway than by HRR after irradiation with gamma-rays or alpha-particles as evaluated by cell survival and the yields of MN. The results obtained with BER- and NHEJ-deficient cells suggest that the indirect effect of radiation contributes significantly to the formation of repair substrates for these pathways.

  • 227.
    Bakali, Amin
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Herman, Maria Dolores
    Johnson, Kenneth A.
    Kelly, Amélie A.
    Wieslander, Åke
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Hallberg, B. M.
    Nordlund, Pär
    Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site2007In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 27, p. 19644-19652Article in journal (Refereed)
    Abstract [en]

    The human lipid kinase family controls cell proliferation, differentiation, and tumorigenesis and includes diacylglycerol kinases, sphingosine kinases, and ceramide kinases. YegS is an Escherichia coli protein with significant sequence homology to the catalytic domain of the human lipid kinases. We have solved the crystal structure of YegS and shown that it is a lipid kinase with phosphatidylglycerol kinase activity. The crystal structure reveals a two-domain protein with significant structural similarity to a family of NAD kinases. The active site is located in the interdomain cleft formed by four conserved sequence motifs. Surprisingly, the structure reveals a novel metal binding site composed of residues conserved in most lipid kinases.

  • 228. Ball, Frank
    et al.
    Britton, Tom
    Stockholm University, Faculty of Science, Department of Mathematics.
    House, Thomas
    Isham, Valerie
    Mollison, Denis
    Pellis, Lorenzo
    Tomba, Gianpaolo Scalia
    Seven challenges for metapopulation models of epidemics, including households models2015In: Epidemics, ISSN 1755-4365, E-ISSN 1878-0067, Vol. 10, p. 63-67Article in journal (Refereed)
    Abstract [en]

    This paper considers metapopulation models in the general sense, i.e. where the population is partitioned into sub-populations (groups, patches,...), irrespective of the biological interpretation they have, e.g. spatially segregated large sub-populations, small households or hosts themselves modelled as populations of pathogens. This framework has traditionally provided an attractive approach to incorporating more realistic contact structure into epidemic models, since it often preserves analytic tractability (in stochastic as well as deterministic models) but also captures the most salient structural inhomogeneity in contact patterns in many applied contexts. Despite the progress that has been made in both the theory and application of such metapopulation models, we present here several major challenges that remain for future work, focusing on models that, in contrast to agent-based ones, are amenable to mathematical analysis. The challenges range from clarifying the usefulness of systems of weakly-coupled large sub-populations in modelling the spread of specific diseases to developing a theory for endemic models with household structure. They include also developing inferential methods for data on the emerging phase of epidemics, extending metapopulation models to more complex forms of human social structure, developing metapopulation models to reflect spatial population structure, developing computationally efficient methods for calculating key epidemiological model quantities, and integrating within- and between-host dynamics in models.

  • 229. Ball, Frank
    et al.
    Britton, Tom
    Stockholm University, Faculty of Science, Department of Mathematics.
    Sirl, David
    Household epidemic models with varying infection response2011In: Journal of Mathematical Biology, ISSN 0303-6812, E-ISSN 1432-1416, Vol. 63, no 2, p. 309-337Article in journal (Refereed)
    Abstract [en]

    This paper is concerned with SIR (susceptible -> infected -> removed) household epidemic models in which the infection response may be either mild or severe, with the type of response also affecting the infectiousness of an individual. Two different models are analysed. In the first model, the infection status of an individual is predetermined, perhaps due to partial immunity, and in the second, the infection status of an individual depends on the infection status of its infector and on whether the individual was infected by a within- or between-household contact. The first scenario may be modelled using a multitype household epidemic model, and the second scenario by a model we denote by the infector-dependent-severity household epidemic model. Large population results of the two models are derived, with the focus being on the distribution of the total numbers of mild and severe cases in a typical household, of any given size, in the event that the epidemic becomes established. The aim of the paper is to investigate whether it is possible to determine which of the two underlying explanations is causing the varying response when given final size household outbreak data containing mild and severe cases. We conduct numerical studies which show that, given data on sufficiently many households, it is generally possible to discriminate between the two models by comparing the Kullback-Leibler divergence for the two fitted models to these data.

  • 230.
    Balogun, Halima A.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Immunological characteristics of recombinant fragments of the Plasmodium falciparum blood-stage antigen Pf3322011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Effective malaria vaccine might help improve control strategies against malaria, but the complexity of interactions between the parasite and its hosts poses challenges. The asexual blood stage P. falciparum antigen Pf332 has potentials as one of the proteins in understanding the complex host-parasite interactions. The interest in Pf332 as a target for parasite neutralizing antibodies, evolved from previous studies demonstrating that Pf332-reactive antibodies inhibits parasite growth in vitro. The presence of natural P. falciparum infection also indicated that Pf332 has the ability to induce protective antibodies.

    In paper I, we identified and characterized the immunogenicity of a C-terminal region of Pf332. Immunological analyses carried out with this fragment revealed that rabbit anti-C231 antibodies possess parasite in vitro inhibitory capabilities. In paper II, the functional activity of C231 specific antibodies was confirmed with human-affinity purified antibodies, where the antibodies inhibited late stage parasite development, by the presence of abnormal parasites and disintegrated red cell membranes.

    Epidemiological data from malaria endemic area of Senegal (Paper III & IV), showed that antibodies were reactive with two different fragments of Pf332 (C231 and DBL). Distribution of anti-C231 antibodies in the IgG subclasses, gave similar levels of IgG2 and IgG3. The levels of anti-C231 antibodies were associated with protection from clinical malaria, but with DBL reactive antibodies IgG3 was associated with protection from clinical malaria.

    We hereby conclude that antigen Pf332 contains immunogenic epitopes, and is a potential target for parasite neutralizing antibodies. The Pf332 protein should thus be considered as a candidate antigen for inclusion in a subunit P. falciparum malaria vaccine.

  • 231.
    Balogun, Halima
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Awah, Nancy
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Farouk, S.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Pf332-C231- reactive antibodies affect growth and development of intraerythrocytic Plasmodium falciparum parasitesArticle in journal (Refereed)
  • 232.
    Balogun, Halima
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Awah, Nancy
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Nilsson, S.
    Rousillhon, C.
    Rogier, C.
    Trape, J. F.
    Chen, Q.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Pattern of antibodies to the Duffy binding-like domain of Plasmodium falciparum antigen Pf332 in Senegalese individualsManuscript (preprint) (Other academic)
  • 233. Bal-Price, Anna
    et al.
    Crofton, Kevin M.
    Sachana, Magdalini
    Shafer, Timothy J.
    Behl, Mamta
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Hargreaves, Alan
    Landesmann, Brigitte
    Lein, Pamela J.
    Louisse, Jochem
    Monnet-Tschudi, Florianne
    Paini, Alicia
    Rolaki, Alexandra
    Schrattenholz, Andre
    Sunol, Cristina
    van Thriel, Christoph
    Whelan, Maurice
    Fritsche, Ellen
    Putative adverse outcome pathways relevant to neurotoxicity2015In: Critical reviews in toxicology, ISSN 1040-8444, E-ISSN 1547-6898, Vol. 45, no 1, p. 83-91Article, review/survey (Refereed)
    Abstract [en]

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.

  • 234.
    Baltzer, Maria
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Backhans, Mona
    Melinder, Karin
    Involvement and structure: A qualitative study of organizational change and sickness absence among women in the public sector in Sweden2011In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 11, p. 318-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Organizational changes in modern corporate life have become increasingly common and there are indications that they often fail to achieve their ends. An earlier study of 24,036 employees showed that those who had repeatedly been exposed to large increases in staffing during 1991-1996 had an excess risk of both long-term sickness absence and hospital admission during 1997-1999, while moderate expansion appeared to be protective. The former was most salient among female public sector employees. We used qualitative interviews to explore work environment factors underlying the impact of organizational changes (moderate and large expansions in staffing) on sickness absence from an employee perspective. METHOD: We interviewed 21 strategically selected women from the earlier study using semi-structured telephone interviews focusing on working conditions during the organizational changes. We identified 22 themes which could explain the association between organizational changes and sickness absence. We then used Qualitative Comparative Analysis (QCA) to reduce the number of themes and discover patterns of possible causation. RESULTS: The themes that most readily explained the outcomes were Well Planned Process of Change (a clear structure for involvement of the employees in the changes), Agent of Change (an active role in the implementation of the changes), Unregulated Work (a lack of clear limits and guidelines regarding work tasks from the management and among the employees), and Humiliating Position (feelings of low status or of not being wanted at the workplace), which had been salient throughout the analytic process, in combination with Multiple Contexts (working in several teams in parallel) and Already Ill (having already had a debilitating illness at the beginning of 1991), which may indicate degree of individual exposure and vulnerability. Well Planned Process of Change, Agent of Change and Multiple Contexts are themes that were associated with low sickness absence. Unregulated Work, Humiliating Position and Already Ill were associated with high sickness absence. CONCLUSIONS: These findings suggest that promising areas for future research and improvement in change management could be the structured involvement of the employees in the planning of organizational changes, and the development of methods to avoid highly unregulated working conditions.

  • 235. Bao, Cuiping
    et al.
    Yang, Xilin
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Med Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Tianjin, Peoples R China.
    Luo, Hongbin
    Xu, Zhongliang
    Su, Cheng
    Qi, Xiuying
    Diabetes mellitus and incidence and mortality of kidney cancer: A meta-analysis2013In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 27, no 4, p. 357-364Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes is associated with increased risk of a spectrum of cancers, but there are few meta-analyses on the association between diabetes and kidney cancer. We performed a meta-analysis of case-control studies and cohort studies to address the incidence and mortality of kidney cancer in diabetes. Methods: Studies were identified by searching PubMed database and manual assessment of the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effect model. Study quality was assessed using the Newcastle-Ottawa scale. Results: A total of 24 studies were included. We found that diabetes was significantly associated with increased risk of kidney cancer (RR=1.40, 95% CI = 1.16 to 1.69), and the results were consistent between case-control and cohort studies. A slightly stronger positive relation was observed in women (RR = 1.47, 95% CI=1.18 to 1.83) than in men (RR=1.28, 95% CI=1.10 to 1.48). Additional analyses indicated that the increased risk of kidney cancer was independent of alcohol consumption, body mass index (BMI)/obesity and smoking. However, there was no association between diabetes and mortality of kidney cancer (RR=1.12, 95% CI=0.99 to 1.20), without heterogeneity (P = 0.419, I-2 = 1.8%). Conclusions: Diabetes mellitus may increase the risk of kidney cancer in both women and men.

  • 236. Barbeiro, A. R.
    et al.
    Ureba, Ana
    Stockholm University, Faculty of Science, Department of Physics. Universidad de Sevilla, Spain; Instituto de Biomedicina de Sevilla, IBIS, Spain; Karolinska Institutet, Sweden.
    Baeza, J. A.
    Linares, R.
    Perucha, M.
    Jimenez-Ortega, E.
    Velazquez, S.
    Mateos, J. C.
    Leal, A.
    3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166767Article in journal (Refereed)
    Abstract [en]

    A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.

  • 237. Barbosa, Cristina
    et al.
    Feio, Paulo
    Fernandes, Ana
    Thorslund, Mats
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    GOVERNANCE STRATEGIES TO AN AGEING SOCIETY - LOCAL ROLL IN MULTI LEVEL PROCESSES2016In: Journal of Comparative Politics, ISSN 1337-7477, E-ISSN 1338-1385, Vol. 9, no 1, p. 4-18Article in journal (Refereed)
    Abstract [en]

    Demographic ageing marks strategic orientations and public policies. It's a challenge to societies, public and private institutions and Welfare State. The goal of this study is to understand the local governance strategies to an ageing population and the role of the local in multilevel governance processes. A qualitative methodology it was followed that supports analysis and understanding of both local ageing policies. The samples are case studies of two contexts, Portugal and Sweden, respectively city councils of Lisbon and Nacka, where stakeholders were interviewed. Different concepts and visions influence local ageing policies. Vertical coordination is easier to follow in Portugal, but without concrete laws, and in Sweden, horizontal coordination is emphasized between providers and municipalities. Local public intervention in ageing seeks renewed actions and this study allows to conclude that a perfect local policy doesn't exist. However in many aspects, can be complementary.

  • 238.
    Barclay, Kieron
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. London School of Economics and Political Science, UK; Max Planck Institute for Demographic Research, Germany.
    Myrskylä, Mikko
    Tynelius, Per
    Berglind, Daniel
    Rasmussen, Finn
    Birth order and hospitalization for alcohol and narcotics use in Sweden2016In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 167, p. 15-22Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have shown that birth order is an important predictor of later life health as well as socioeconomic attainment. In this study, we examine the relationship between birth order and hospitalization for alcohol and narcotics use in Sweden. Methods: We study the relationship between birth order and hospitalization related to alcohol and narcotics use before and after the age of 20 using Swedish register data for cohorts born 1987-1994. We apply Cox proportional hazard models and use sibling fixed effects, eliminating confounding by factors shared by the siblings. Results: Before age 20 we find that later born siblings are hospitalized for alcohol use at a higher rate than first-borns, and there is a monotonic increase in the hazard of hospitalization with increasing birth order. Second-borns are hospitalized at a rate 47% higher than first-borns, and third-borns at a rate 65% higher. Similar patterns are observed for hospitalization for narcotics use. After age 20 the pattern is similar, but the association is weaker. These patterns are consistent across various sibling group sizes. Conclusions: Later born siblings are more likely to be hospitalized for both alcohol and narcotics use in Sweden. These birth order effects are substantial in size, and larger than the estimated sex differences for the risk of hospitalization related to alcohol and drug use before age 20, and previous estimates for socioeconomic status differences in alcohol and drug abuse.

  • 239. Barghadouch, Amina
    et al.
    Kristiansen, Maria
    Smith Jervelund, Signe
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Montgomery, Edith
    Norredam, Marie
    Refugee children have fewer contacts to psychiatric healthcare services: an analysis of a subset of refugee children compared to Danish-born peers2016In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 51, no 8, p. 1125-1136Article in journal (Refereed)
    Abstract [en]

    Studies show a high level of mental health problems among refugee children. This study examined whether a subset of refugee children living in Denmark accessed psychiatric healthcare services more than those born in the country. This study compared 24,427 refugee children from Asia, The Middle East, Sub-Saharan Africa and former Yugoslavia, who obtained residency in Denmark between 1 January 1993 and 31 December 2010 with 146,562 Danish-born children, matched 1:6 on age and sex. The study looked at contacts with psychiatric hospitals as well as psychologists and psychiatrists in private practice. Between 1 January 1996 and 30 June 2012, 3.5 % of the refugee children accessed psychiatric healthcare services compared to 7.7 % of the Danish-born children. The rate ratio of having any first-time psychiatric contact was 0.42 (95 % CI 0.40-0.45) among refugee boys and 0.35 (95 % CI 0.33-0.37) among refugee girls, compared to Danish-born children. Figures were similar for those accessing private psychologists or psychiatrists, emergency room, inpatient and outpatient services. Refugee children used fewer psychiatric healthcare services than Danish-born children. This may indicate that refugee children experience barriers in accessing psychiatric healthcare systems and do not receive adequate assessment of their mental health and subsequent referral to specialist services.

  • 240. Barisic, Ivan
    et al.
    Schoenthaler, Silvia
    Ke, Rongqin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Noehammer, Christa
    Wiesinger-Mayr, Herbert
    Multiplex detection of antibiotic resistance genes using padlock probes2013In: Diagnostic microbiology and infectious disease, ISSN 0732-8893, E-ISSN 1879-0070, Vol. 77, no 2, p. 118-125Article in journal (Refereed)
    Abstract [en]

    The elucidation of resistance mechanisms is of central importance to providing and maintaining efficient medical treatment. However, molecular detection methods covering the complete set of resistance genes with a single test are still missing. Here, we present a novel 100-plex assay based on padlock probes in combination with a microarray that allows the simultaneous large-scale identification of highly diverse beta-lactamases. The specificity of the assay was performed using 70 clinical bacterial isolates, recovering 98% of the beta-lactamase nucleotide sequences present. Additionally, the sensitivity was evaluated with PCR products and genomic bacterial DNA, revealing a detection limit of 10(4) DNA copies per reaction when using PCR products as the template. Pre-amplification of genomic DNA in a 25-multiplex PCR further facilitated the detection of beta-lactamase genes in dilutions of 10(7) cells/mL. In summary, we present an efficient, highly specific, and highly sensitive multiplex detection method for any gene.

  • 241. Barlind, Jonas G.
    et al.
    Buckett, Linda K.
    Crosby, Sharon G.
    Davidsson, Ojvind
    Emtenas, Hans
    Ertan, Anne
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Jurva, Ulrik
    Lemurell, Malin
    Gutierrez, Pablo Morentin
    Nilsson, Karolina
    O'Mahony, Gavin
    Petersson, Annika U.
    Redzic, Alma
    Wagberg, Fredrik
    Yuan, Zhong-Qing
    Identification and design of a novel series of MGAT2 inhibitors2013In: Bioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, E-ISSN 1090-2120, Vol. 23, no 9, p. 2721-2726Article in journal (Refereed)
    Abstract [en]

    [Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to naive, p < 0.01) in plasma triacylglycerol (TAG) concentration.

  • 242. Barnevik Olsson, Martina
    et al.
    Holm, Anette
    Westerlund, Joakim
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Cognitive psychology. Gothenburg University, Sweden.
    Lundholm Hedvall, Åsa
    Gillberg, Christopher
    Fernell, Elisabeth
    Children with borderline intellectual functioning and autism spectrum disorder: developmental trajectories from 4 to 11 years of age2017In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 13, p. 2519-2526Article in journal (Refereed)
    Abstract [en]

    Background: Studies on autism have tended to focus either on those with intellectual disability (ie, those with intellectual quotient [IQ] under 70) or on the group that is referred to as high-functioning, that is, those with borderline, average or above average IQ. The literature on cognition and daily functioning in autism spectrum disorder combined specifically with borderline intellectual functioning (IQ 70-84) is limited. Methods: From a representative group of 208 preschool children diagnosed with autism spectrum disorder, those 50 children in the group with borderline intellectual functioning at ages 4.5-6.5 years were targeted for follow-up at a median age of 10 years. A new cognitive test was carried out in 30 children. Parents were interviewed with a semi-structured interview together with the Vineland Adaptive Behavior Scales (n=41) and the Autism-Tics, attention-deficit/hyperactivity disorder (AD/HD) and other comorbidities inventory (A-TAC) (n=36). Results: Most children of interviewed parents presented problems within several developmental areas. According to A-TAC and the clinical interview, there were high rates of attention deficits and difficulties with regulating activity level and impulsivity. Vineland Adaptive Behavior Scales composite scores showed that at school age, a majority of the children had declined since the previous assessment at ages between 4.5 and 6.5 years. Almost half the tested group had shifted in their IQ level, to below 70 or above 84. Conclusion: None of the children assessed was without developmental/neuropsychiatric problems at school-age follow-up. The results support the need for comprehensive follow-up of educational, medical and developmental/neuropsychiatric needs, including a retesting of cognitive functions. There is also a need for continuing parent/family follow-up and support.

  • 243. Barnevik Olsson, Martina
    et al.
    Westerlund, Joakim
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Gothenburg University, Sweden.
    Lundstrom, Sebastian
    Giacobini, MaiBritt
    Fernell, Elisabeth
    Gillberg, Christopher
    Recovery from the diagnosis of autism - and then?2015In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 11, p. 999-1005Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to follow up the 17 children, from a total group of 208 children with autism spectrum disorder (ASD), who recovered from autism. They had been clinically diagnosed with ASD at or under the age of 4 years. For 2 years thereafter they received intervention based on applied behavior analysis. These 17 children were all of average or borderline intellectual functioning. On the 2-year follow-up assessment, they no longer met criteria for ASD. Methods: At about 10 years of age they were targeted for a new follow-up. Parents were given a semistructured interview regarding the child's daily functioning, school situation, and need of support, and were interviewed using the Vineland Adaptive Behavior Scales (VABS) and the Autism - Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC) telephone interview. Results: The vast majority of the children had moderate-to-severe problems with attention/activity regulation, speech and language, behavior, and/or social interaction. A majority of the children had declined in their VABS scores. Most of the 14 children whose parents were A-TAC-interviewed had problems within many behavioral A-TAC domains, and four (29%) had symptom levels corresponding to a clinical diagnosis of ASD, AD/HD, or both. Another seven children (50%) had pronounced subthreshold indicators of ASD, AD/HD, or both. Conclusion: Children diagnosed at 2-4 years of age as suffering from ASD and who, after appropriate intervention for 2 years, no longer met diagnostic criteria for the disorder, clearly needed to be followed up longer. About 3-4 years later, they still had major problems diagnosable under the umbrella term of ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations). They continued to be in need of support, educationally, from a neurodevelopmental and a medical point of view. According to parent interview data, a substantial minority of these children again met diagnostic criteria for ASD.

  • 244.
    Barragan, Antonio
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Karolinska Institutet, Sweden.
    Weidner, Jessica M.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Karolinska Institutet, Sweden.
    Jin, Z.
    Korpi, E. R.
    Birnir, B.
    GABAergic signalling in the immune system2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 4, p. 819-827Article, review/survey (Refereed)
    Abstract [en]

    The GABAergic system is the main inhibitory neurotransmitter system in the central nervous system (CNS) of vertebrates. Signalling of the transmitter c-aminobutyric acid (GABA) via GABA type A receptor channels or G-protein-coupled type B receptors is implicated in multiple CNS functions. Recent findings have implicated the GABAergic system in immune cell functions, inflammatory conditions and diseases in peripheral tissues. Interestingly, the specific effects may vary between immune cell types, with stage of activation and be altered by infectious agents. GABA/GABA-A receptor-mediated immunomodulatory functions have been unveiled in immune cells, being present in T lymphocytes and regulating the migration of Toxoplasma-infected dendritic cells. The GABAergic system may also play a role in the regulation of brain resident immune cells, the microglial cells. Activation of microglia appears to regulate the function of GABAergic neurotransmission in neighbouring neurones through changes induced by secretion of brain-derived neurotrophic factor. The neurotransmitter-driven immunomodulation is a new but rapidly growing field of science. Herein, we review the present knowledge of the GABA signalling in immune cells of the periphery and the CNS and raise questions for future research.

  • 245. Barregard, Lars
    et al.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cooke, Marcus S.
    Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine2013In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 18, no 18, p. 2377-2391Article in journal (Refereed)
    Abstract [en]

    Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.

  • 246.
    Barrett, Damon
    Stockholm University, Faculty of Law, Department of Law. University of Essex, UK.
    The Child's Right to Protection from Drugs: Understanding History to Move Forward2017In: Health and Human Rights: An International Journal, ISSN 1079-0969, E-ISSN 2150-4113, Vol. 19, no 1, p. 263-268Article in journal (Refereed)
  • 247. Bartelink, Eric J.
    et al.
    Sholts, Sabrina B.
    Milligan, Colleen F.
    Van Deest, Traci L.
    Wärmländer, Sebastian K. T. S.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Linköping University, Sweden.
    A Case of Contested Cremains Analyzed Through Metric and Chemical Comparison2015In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 60, no 4, p. 1068-1073Article in journal (Refereed)
    Abstract [en]

    Since the 1980s, cremation has become the fastest growing area of the U.S. funeral industry. At the same time, the number of litigations against funeral homes and cremation facilities has increased. Forensic anthropologists are often asked to determine whether the contents of an urn are actually cremated bone, and to address questions regarding the identity of the remains. This study uses both metric and chemical analyses for resolving a case of contested cremains. A cremains weight of 2021.8 g was predicted based on the decedent's reported stature and weight. However, the urn contents weighed 4173.5 g. The urn contents also contained material inconsistent with cremains (e.g., moist sediment, stones, ferrous metal). Analysis using XRD and SEM demonstrated that the urn contained thermally altered bone as well as inorganic material consistent with glass fiber cement. Although forensically challenging, cremains cases such as this one can be resolved using a multidisciplinary approach.

  • 248.
    Bartonek, Frida
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    The role of self-esteem for the relation between school performance and psychosomatic health in adolescence: Sex differences and gender theoretical interpretations2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    While socioeconomic inequalities in health seem to level out during adolescence, circumstances related to school appears to have increased in importance. Such circumstances include, for example, school performance. The primary aim of this study is to examine the relationship between school performance and psychosomatic health. The moderating role of self-esteem and the presence of any sex differences will additionally be investigated. Data from the Stockholm School Survey in 2004, covering a total sample of 5 135 adolescents in 9th grade, were used. Based on linear regression, a significant association between school marks and psychosomatic health was found where higher school performance was linked to better health. Moreover, lower self-esteem was linked to more health complaints. Self-esteem moderated the association between school marks and psychosomatic health but only among boys, for whom the effect of having both high marks and high self-esteem was not as beneficial for health as expected. While differences by sex were found in the distribution of school marks, self-esteem and psychosomatic health, none were found in the associations between self-esteem and school performance and psychosomatic health (the only exception being the moderating role of self-esteem among boys).

  • 249.
    Basmarke-Wehelie, Rahma
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Sjölinder, Hong
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Jurkowski, Wiktor
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Arnqvist, Anna
    Umea Univ, Dept Med Biochem & Biophys, Sweden.
    Engstrand, Lars
    Karolinska Inst, Swedish Inst Infect Dis Control, Sweden.
    Hagner, Matthias
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Wallin, Elin
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Guan, Na
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Kuranasekera, Hasanthi
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Aro, Helena
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Jonsson, Ann-Beth
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity2011In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 141, no 3, p. 918-928Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.

    METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.

    RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.

    CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.

  • 250. Bassyouni, Fatma A.
    et al.
    Saleh, Tamer S.
    ElHefnawi, Mahmoud M.
    Abd El-Moez, Sherein I.
    El-Senousy, Waled M.
    Abdel-Rehim, Mohamed E.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives2012In: Archives of pharmacal research, ISSN 0253-6269, E-ISSN 1976-3786, Vol. 35, no 12, p. 2063-2075Article in journal (Refereed)
    Abstract [en]

    Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1Hbenzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4aEuro(3),5aEuro(3)-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophorebased correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking using the MOE software and its validation.

2345678 201 - 250 of 3709
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf