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  • 1.
    Elväng, Annelie
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Melik, Wessam
    Södertörns högskola, Institutionen för livsvetenskaper, Kemi. Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Bertrand, Yann
    Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Lönn, Mikael
    Södertörns högskola, Institutionen för livsvetenskaper, Biologi. Södertörns högskola, Institutionen för livsvetenskaper, Miljövetenskap.
    Johansson, Magnus
    Södertörns högskola, Institutionen för livsvetenskaper, Kemi. Södertörns högskola, Institutionen för livsvetenskaper, Internationell hälsa.
    Sequencing of a Tick-Borne Encephalitis Virus from Ixodes ricinus Reveals a Thermosensitive RNA Switch Significant for Virus Propagation in Ectothermic Arthropods.2011Ingår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 11, nr 6, s. 649-658Artikel i tidskrift (Refereegranskat)
    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.

  • 2.
    Rukavishnikov, Grigory
    et al.
    Bekhterev National Medical Research Center for Psychiatry and Neurology, Russia.
    Leonova, Lubov
    Bekhterev National Medical Research Center for Psychiatry and Neurology, Russia.
    Kasyanov, Evgeny
    Bekhterev National Medical Research Center for Psychiatry and Neurology, Russia.
    Leonov, Vadim
    Södertörns högskola.
    Neznanov, Nikholay
    Bekhterev National Medical Research Center for Psychiatry and Neurology, Russia; Pavlov First Saint-Petersburg State Medical University, Russia.
    Mazo, Galina
    Bekhterev National Medical Research Center for Psychiatry and Neurology, Russia.
    Antimicrobial activity of antidepressants on normal gut microbiota: Results of the in vitro study2023Ingår i: Frontiers in Behavioral Neuroscience, E-ISSN 1662-5153, Vol. 17, artikel-id 1132127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Currently, there is little published data on the effects of antidepressants on normal gut microbiota and the consequences of such effects on treatment outcomes. The aim of the study: was to evaluate the growth kinetics of normal human gut microorganisms with antidepressants most common in routine clinical practice. Materials and methods: Research objects were species of microorganisms representing normal gut microbiota: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Candida albicans ATCC 24433, Bifidobacterium 791, Enterococcus faecalis ATCC 29212, Lactobacillus rhamnosus ATCC 53103. All microorganisms were cultivated in Schaedler broth (HiMedia) under aerobic/anaerobic conditions. The active substances of all studied antidepressants (fluvoxamine, fluoxetine, escitalopram, duloxetine, venlafaxine, mirtazapine) were extracted from ground preparations by dimethyl sulfoxide and centrifuged. Each solution of antidepressants was added to a Schaedler broth containing a certain microorganism's strain and diluted to final concentrations-200 μg/ml, 500 μg/ml, and 700 μg/ml. For a quantitative assessment of the effect, the specific growth rates (μ, h-1) of microorganisms were calculated as the slope of the initial part of the growth curve in coordinates (lnA, t). To evaluate the antidepressant effects on representatives of the normal microbiota in vitro, the following parameters were chosen: specific growth rate and IC50. Results: All antidepressants had an inhibitory effect on the growth of all studied microorganisms. Fluvoxamine and venlafaxine had the least effect on the growth activity of all studied microorganisms. Fluoxetine showed a pronounced effect on growth activity against E. coli, E. feacalis, S. aureus, and the least effect against C. albicans. Escitalopram had a greater effect on the growth rate of E. coli, E. feacalis, B. bifidum, L. rhamnosus, and C. albicans, which puts it among the leaders in terms of its effect on the growth activity of the microorganisms we studied. Mirtazapine, according to the results of our experiment, showed the greatest activity against L. rhamnosus and C. albicans. Conclusions: Our results confirm the effects of antidepressants on the growth activity of the normal gut microbiota individual strains. Further study of the antimicrobial activity of antidepressants may become one of the new directions for optimizing the personalized therapy of patients with depression.

  • 3.
    Wigerius, Michael
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper, Kemi. Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Melik, Wessam
    Södertörns högskola, Institutionen för livsvetenskaper, Kemi. Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Elväng, Annelie
    Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Johansson, Magnus
    Södertörns högskola, Institutionen för livsvetenskaper, Kemi. Södertörns högskola, Institutionen för livsvetenskaper, Internationell hälsa.
    Rac1 and Scribble are targets for the arrest of neurite outgrowth by TBE virus NS52010Ingår i: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 44, nr 3, s. 260-271Artikel i tidskrift (Refereegranskat)
    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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