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  1. Article ; Online: The APOE-TOMM40 Humanized Mouse Model: Characterization of Age, Sex, and PolyT Variant Effects on Gene Expression.

    Gottschalk, William K / Mahon, Scott / Hodgson, Dellila / Barrera, Julio / Hill, Delaney / Wei, Angela / Kumar, Manish / Dai, Kathy / Anderson, Lauren / Mihovilovic, Mirta / Lutz, Michael W / Chiba-Falek, Ornit

    Journal of Alzheimer's disease : JAD

    2023  Volume 94, Issue 4, Page(s) 1563–1576

    Abstract: Background: The human chromosome 19q13.32 is a gene rich region and has been associated with multiple phenotypes, including late onset Alzheimer's disease (LOAD) and other age-related conditions.: Objective: Here we developed the first humanized ... ...

    Abstract Background: The human chromosome 19q13.32 is a gene rich region and has been associated with multiple phenotypes, including late onset Alzheimer's disease (LOAD) and other age-related conditions.
    Objective: Here we developed the first humanized mouse model that contains the entire TOMM40 and APOE genes with all intronic and intergenic sequences including the upstream and downstream regions. Thus, the mouse model carries the human TOMM40 and APOE genes and their intact regulatory sequences.
    Methods: We generated the APOE-TOMM40 humanized mouse model in which the entire mouse region was replaced with the human (h)APOE-TOMM40 loci including their upstream and downstream flanking regulatory sequences using recombineering technologies. We then measured the expression of the human TOMM40 and APOE genes in the mice brain, liver, and spleen tissues using TaqMan based mRNA expression assays.
    Results: We investigated the effects of the '523' polyT genotype (S/S or VL/VL), sex, and age on the human TOMM40- and APOE-mRNAs expression levels using our new humanized mouse model. The analysis revealed tissue specific and shared effects of the '523' polyT genotype, sex, and age on the regulation of the human TOMM40 and APOE genes. Noteworthy, the regulatory effect of the '523' polyT genotype was observed for all studied organs.
    Conclusion: The model offers new opportunities for basic science, translational, and preclinical drug discovery studies focused on the APOE genomic region in relation to LOAD and other conditions in adulthood.
    MeSH term(s) Humans ; Animals ; Mice ; Apolipoproteins E/genetics ; Genotype ; Phenotype ; Introns ; Gene Expression ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Genetic Predisposition to Disease ; Mitochondrial Precursor Protein Import Complex Proteins
    Chemical Substances Apolipoproteins E ; TOMM40 protein, human ; Mitochondrial Precursor Protein Import Complex Proteins
    Language English
    Publishing date 2023-07-13
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-230451
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  2. Book: Gruene Chemie - Sparkling Science

    Mihovilovic, Marko

    Abstract: Das Projekt Gruene Chemie zielt darauf ab, bereits SchuelerInnen fuer eine neue 'gruene Chemie' im Hinblick auf umweltvertraegliche und nachhaltige Produktionsverfahren zu begeistern, indem sie in aktuelle wissenschaftliche Arbeiten an der TU Wien ... ...

    Title variant Green chemistry - sparkling science
    Institution Technische Universitaet Wien, Institut fuer Angewandte Synthesechemie, Getreidemarkt 9/163, 1060, Wien, AT
    Abstract Das Projekt Gruene Chemie zielt darauf ab, bereits SchuelerInnen fuer eine neue 'gruene Chemie' im Hinblick auf umweltvertraegliche und nachhaltige Produktionsverfahren zu begeistern, indem sie in aktuelle wissenschaftliche Arbeiten an der TU Wien eingebunden werden sollen. Ziel ist es, sie nachhaltig fuer Naturwissenschaften im Allgemeinen und chemische Disziplinen im Speziellen gewinnen zu koennen. Dazu ist ein umfassendes Programm aus experimentellen Arbeiten, Auswertung der Versuche, Verfassung von Berichten und schliesslich Kommunikation der Resultate und Themenfelder geplant. Dabei sollen insbesondere auch LehrerInnen eingebunden werden, um die neuen Entwicklungen spaeter im eigenen Lehrbetrieb weitervermitteln zu koennen. Die einzelnen Individualprojekte sind thematisch zwischen mehreren beteiligten Forschungsgruppen angesiedelt und sollen kooperativ betreut werden.
    Keywords Nachhaltige Chemie ; Umweltvertraeglichkeit ; Produktionstechnik ; Naturwissenschaft ; Kommunikation ; Nachhaltige Entwicklung ; Schulausbildung ; Chemie ; Informationsvermittlung ; Wien
    Language German
    Document type Book
    Remark Projektbeginn: 01.07.2008 Projektende: 31.12.2010 Foerdernummer:
    Database Environmental research database (UFORDAT) of the German Federal Environment Agency (UBA)

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  3. Book: Effektives Redesign von oxidativen Enzymen fuer gruene Chemie

    Mihovilovic, Marko
    Title variant The effective redesign of oxidative enzymes for green chemistry
    Institution Technische Universitaet Wien, Institut fuer Angewandte Synthesechemie, Getreidemarkt 9/163, 1060, Wien, AT
    Keywords Nachhaltige Chemie ; Oxidation ; Enzym
    Document type Book
    Remark project start: 02/01/2008 project end: 02/01/2013 grant ID:
    Database Environmental research database (UFORDAT) of the German Federal Environment Agency (UBA)

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  4. Article ; Online: Measurement of the α-Particle Monopole Transition Form Factor Challenges Theory: A Low-Energy Puzzle for Nuclear Forces?

    Kegel, S / Achenbach, P / Bacca, S / Barnea, N / Beričič, J / Bosnar, D / Correa, L / Distler, M O / Esser, A / Fonvieille, H / Friščić, I / Heilig, M / Herrmann, P / Hoek, M / Klag, P / Kolar, T / Leidemann, W / Merkel, H / Mihovilovič, M /
    Müller, J / Müller, U / Orlandini, G / Pochodzalla, J / Schlimme, B S / Schoth, M / Schulz, F / Sfienti, C / Širca, S / Spreckels, R / Stöttinger, Y / Thiel, M / Tyukin, A / Walcher, T / Weber, A

    Physical review letters

    2023  Volume 130, Issue 15, Page(s) 152502

    Abstract: We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron scattering experiment in a broad Q^{2} range (from 0.5 to ...

    Abstract We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron scattering experiment in a broad Q^{2} range (from 0.5 to 5.0  fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.
    Language English
    Publishing date 2023-04-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.130.152502
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  5. Article ; Online: Targeting α6GABA

    Lee, Ming Tatt / Mouri, Akihiro / Kubota, Hisayoshi / Lee, Hsin-Jung / Chang, Man-Hsin / Wu, Chen-Yi / Knutson, Daniel E / Mihovilovic, Marko / Cook, James / Sieghart, Werner / Nabeshima, Toshitaka / Chiou, Lih-Chu

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2022  Volume 150, Page(s) 113022

    Abstract: ... ...

    Abstract GABA
    MeSH term(s) Animals ; Disease Models, Animal ; Humans ; Methamphetamine/adverse effects ; Mice ; Phencyclidine/adverse effects ; Rats ; Receptors, GABA-A ; Schizophrenia/chemically induced ; Schizophrenia/drug therapy ; gamma-Aminobutyric Acid/therapeutic use
    Chemical Substances Receptors, GABA-A ; Methamphetamine (44RAL3456C) ; gamma-Aminobutyric Acid (56-12-2) ; Phencyclidine (J1DOI7UV76)
    Language English
    Publishing date 2022-04-25
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2022.113022
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  6. Article ; Online: Erratum to "Defined concatenated α6α1β3γ2 GABAA receptor constructs reveal dual action of pyrazoloquinolinone allosteric modulators" [Bioorg. Med. Chem. 27 (2019) 3167-3178].

    Simeone, X / Iorio, M T / Siebert, D C B / Rehman, S / Schnürch, M / Mihovilovic, M D / Ernst, M

    Bioorganic & medicinal chemistry

    2020  Volume 28, Issue 8, Page(s) 115417

    Language English
    Publishing date 2020-03-14
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2020.115417
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  7. Article: The Role of Upregulated APOE in Alzheimer's Disease Etiology.

    Gottschalk, William K / Mihovilovic, Mirta / Roses, Allen D / Chiba-Falek, Ornit

    Journal of Alzheimer's disease & Parkinsonism

    2016  Volume 6, Issue 1

    Language English
    Publishing date 2016-02-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2711981-6
    ISSN 2161-0460
    ISSN 2161-0460
    DOI 10.4172/2161-0460.1000209
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  8. Article: Thymic epithelial cell line expresses transcripts encoding alpha-3, alpha-5 and beta-4 subunits of acetylcholine receptors, responds to cholinergic agents and expresses choline acetyl transferase. An in vitro system to investigate thymic cholinergic mechanisms.

    Mihovilovic, M / Butterworth-Robinette, J

    Journal of neuroimmunology

    2001  Volume 117, Issue 1-2, Page(s) 58–67

    Abstract: Transcriptional and immunocytological characterization of thymic epithelial (TE) cell line TE750 shows that these cells, like primary TE cell cultures, transcribe alpha-3, alpha-5 and beta-4 acetylcholine receptor (AcChR) subunit genes while expressing ... ...

    Abstract Transcriptional and immunocytological characterization of thymic epithelial (TE) cell line TE750 shows that these cells, like primary TE cell cultures, transcribe alpha-3, alpha-5 and beta-4 acetylcholine receptor (AcChR) subunit genes while expressing cortical, medullary and epithelial differentiation thymic markers. Incubation of TE750 cells with nicotine decreases cell adherence and growth as measured through direct cytological observation and nucleic acid quantification, respectively. Physostigmine, a traditional cholinesterase inhibitor that also activates nicotinic AcChRs, reproduces the effects of nicotine. Strengthening the hypothesis that cholinergic receptors mediate the effects of physostigmine, acetylcholinesterase (AcChase) activity is not detected in TE750 cells. Also, like thymocytes, TE750 cells express choline acetyltransferase (ChAT), indicating that the natural transmitter AcCh can be produced locally within the thymic parenchyma. Taken together these findings indicate that TE750 cells in culture represent a suitable in vitro system for the analysis of cholinergic mechanisms operational in the thymic epithelium.
    MeSH term(s) Cell Line ; Choline O-Acetyltransferase/metabolism ; Cholinergic Agents/pharmacology ; Epithelial Cells/physiology ; Humans ; Immunohistochemistry ; Nicotine/pharmacology ; Physostigmine/pharmacology ; Protein Subunits ; RNA, Messenger/analysis ; Receptors, Cholinergic/genetics ; Thymus Gland/cytology ; Thymus Gland/innervation
    Chemical Substances Cholinergic Agents ; Protein Subunits ; RNA, Messenger ; Receptors, Cholinergic ; Nicotine (6M3C89ZY6R) ; Physostigmine (9U1VM840SP) ; Choline O-Acetyltransferase (EC 2.3.1.6)
    Language English
    Publishing date 2001-05-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 8335-5
    ISSN 1872-8421 ; 0165-5728
    ISSN (online) 1872-8421
    ISSN 0165-5728
    DOI 10.1016/s0165-5728(01)00314-9
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    Zs.A 1646: Show issues Location:
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  9. Article ; Online: Statistics of DNA capture by a solid-state nanopore.

    Mihovilovic, Mirna / Hagerty, Nicholas / Stein, Derek

    Physical review letters

    2013  Volume 110, Issue 2, Page(s) 28102

    Abstract: A solid-state nanopore can electrophoretically capture a DNA molecule and pull it through in a folded configuration. The resulting ionic current signal indicates where along its length the DNA was captured. A statistical study using an 8-nm-wide nanopore ...

    Abstract A solid-state nanopore can electrophoretically capture a DNA molecule and pull it through in a folded configuration. The resulting ionic current signal indicates where along its length the DNA was captured. A statistical study using an 8-nm-wide nanopore reveals a strong bias favoring the capture of molecules near their ends. A theoretical model shows that bias to be a consequence of configurational entropy rather than a search by the polymer for an energetically favorable configuration. We also quantified the fluctuations and length dependence of the speed of simultaneously translocating polymer segments from our study of folded DNA configurations.
    MeSH term(s) DNA/chemistry ; Electrophoresis ; Models, Chemical ; Nanopores ; Nucleic Acid Conformation
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2013-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.110.028102
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  10. Article ; Online: Defined concatenated α6α1β3γ2 GABA

    Simeone, X / Iorio, M T / Siebert, D C B / Rehman, S / Schnürch, M / Mihovilovic, M D / Ernst, M

    Bioorganic & medicinal chemistry

    2019  Volume 27, Issue 14, Page(s) 3167–3178

    Abstract: Pyrazoloquinolinones (PQs) have been extensively studied as modulators of ... ...

    Abstract Pyrazoloquinolinones (PQs) have been extensively studied as modulators of GABA
    MeSH term(s) Binding Sites ; Humans ; Ligands ; Quinolones/chemistry ; Receptors, GABA-A/chemistry
    Chemical Substances Ligands ; Quinolones ; Receptors, GABA-A
    Language English
    Publishing date 2019-06-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2019.06.006
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