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  2. Detailansicht für Treffer 2 öffnen
    Figure 6. Disruption of the PICK AH compromises binding strength and alters synaptic localization and clustering of PICK1 in hippocampal neurons. ; (a) PICK1 V121E,L125E amphipathic helix mutations depicted on PICK1 domain overview. (b) Normalized malemide stained PICK1 V121E,L125E binding as a function of concentration towards LKV. Kd*=0.28 ± 0.12 μM, Bmax: 95 ± 9%. Malemide stained PICK1 WT as dashed line for comparison. (c–d) Flp-In T-REx 293 eYFP-PICK1 WT or eYFP-PICK1 V121E, L125E cells transiently expressing LKV with (black bars;+Tet) and without (white bars; −Tet) similar to the data shown in Figure 3h–g. Data are means ± S.E, n = 6. (*p≤0.05, Students t-test, correction for multiple comparisons). (e) Model of PICK1 scaffolding. After the initial binding using one PDZ domain, PICK1 will be able to maintain avidity via both the second PDZ domain and the AH (grey box). The AH interaction, however, is dependent on the PDZ interaction. Under conditions yielding the second interaction relatively unfavorable state (2) will be slightly favored. This will allow for an additional PICK1 molecule to bind the free receptor site. If the concentration and intrinsic affinity is sufficiently high this state (3) can be maintained. (f) Representative images of hippocampal neurons, DIV 20–22, expressing GFP-PICK1WT (upper panel) or GFP-PICK1 V121E, L125E (lower panel) stained for GFP (left column) and PSD-95 (middle column), and the overlay is shown in the right column. Scale bar is 20 µm. (g) Quantification of the expression level of GFP-PICK1 WT and GFP-PICK1 V121E, L125E measured as the mean intensity of GFP in the soma. (h) Quantification of the number of dendritic PICK1 clusters (see Materials and method section for definition) relative to the number of PSD-95 clusters. (i) Quantification of PSD-95 clusters relative to dendritic length. (j) Quantification of the fraction of PICK1 clusters colocalized with PSD-95. All values are normalized to the corresponding mean value for GFP-PICK1 wt. (***p
    2019
    unknown
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  3. Detailansicht für Treffer 3 öffnen
    Figure 5. PICK1 switch scaffolding mode dependent on intrinsic PDZ affinity. ; (a) Schematic representation of the experimental setup. Both PICK1 WT (blue) and PICK1 A87L (red) are labeled. Exchange is allowed before binding of PICK1 WT/A87L heterodimers. (b) Representative images of heterodimeric binding as a function of concentration. (c–e) Normalized concentration dependent binding to either LKV (solid lines) or LKI (dashed lines), and quantified in both the WT (blue) and A87L (red) channel as function of linear and logarithmic concentration. LKV PICK1 WT/A87L: Kd*=24 ± 21 nM, Bmax: 51 ± 2%. LKI PICK1 WT/A87L Kd*=123 ± 21 nM, Bmax: 56 ± 2% (see Tables 1–3 for explanation of Bmax values) (n = 3), (****p≤0.0001). (f) Schematic summary of conclusions made from figures c-e. Fitted Bmax values are shown on the y-axis, for PICK1 WT/WT and PICK1 WT/A87L to SCMS expressing LKV and LKI together with avidity and proposed binding mode (g–h) Flp-In T-REx 293 eYFP-PICK1 cells transiently expressing LKV, LKI, LKA or LKV +A with (black bars;+Tet) and without (white bars; −Tet) tetracycline-induced expression of eYFP-PICK1 were surface-labeled with anti-FLAG M1 antibody prior to stimulation of internalization with agonist (10 μM Isoproteronol for 20 min). Subsequently, cells were treated with the antagonist (10 μM Alprenolol, 60 min) to allow recycling to the plasma membrane. Surface receptor immunoreactivity was determined by surface ELISA. Internalization (g) refers to the fractional reduction of surface receptor in response to 25 min of agonist exposure compared with non-treated cells (100%). Recycling (h) refers to the fractional recovery of surface receptor following antagonist incubation for 1 hr. These values were all normalized to the respective signal of non-interacting β2-LKV + A, with and without tetracycline induction, respectively. Data are means ±S.E, n = 6. (***p0.05, One way ANOVA, Bonferroni’s post test compared to LKV +A). Scale bars 10 μm.
    2019
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  4. Detailansicht für Treffer 4 öffnen
    Figure 3. The intrinsic PDZ affinity does not translate directly to avidity but determines maximal binding. ; (b) Normalized binding derived from SCMS as a function of PICK1 concentration to LKV (black) (Kd*=37 ± 5 nM, Bmax = 100%), LKI (dark grey) (Kd*=29 ± 4 nM, Bmax = 56 ± 2%), LKA (light grey) (Kd*=59 ± 11 nM, Bmax = 41 ± 4%) LKV +A (white) (Kd*not fitted, Bmax = 21 ± 3). n = 8, 7, 5 and 3, respectively (**p
    2019
    unknown
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  5. Detailansicht für Treffer 5 öffnen
    Table 2. PICK1 Mutants binding to LKV.
    2019
    unknown
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  6. Detailansicht für Treffer 6 öffnen
    Figure 4. Schematic representation of the thermodynamic model for homobivalent ligand-target interactions and thereon-based simulated saturation and dissociation curves. ; (a) Thermodynamic scheme for homobivalent ligand, ‘aa’- target, ‘AA’, interactions (see also Figure 4—figure supplement 1 for full scheme). The different binding modes in panel a are designated by ‘AAaa’ for the partially bound complexes (green), by ‘aAAa’ for the bivalently bound complex (red) and by ‘aaAAaa’ for ‘ternary’ complex with two partly bound ligands (blue). The rebinding kinetics is dependent the local concentration, [L], that is calculated as that of one molecule within a half-sphere with radius, r. Moreover, the rate constant is modified by f due to steric hindrance, restricted rational freedom and entropic cost. An f of 185 enables good qualitative simulation of our data (see also Figure 4—figure supplement 3 for behavior at other values of f). (b) Simulated saturation binding curve for binding of species. Input parameters: k1 = 1.85⋅105 M−1min−1, k-1 = 0.0085 min-−1, k2 = 0.136 min−1 (i.e. a composite rate constant such as defined in the figure). Total incubation time is 120 min. Analysis of the total signal according to a variable slope sigmoidal dose-response paradigm yields half-maximal signal at 50 nM. Note for these parameters the blue ‘ternary’ complex outpaces the red bivalent complex at bulk concentration of PICK1 above 100 nM. (c,d) Simulated dissociation curves after 120 min pre-incubation with 200 nM (c) and 20 nM (d) of the same homobivalent ligand as in panel c (corresponding to the affinity difference between LKV and LKI). [aa] is set and kept at 0 for simulating the ‘washout phase’.
    2019
    unknown
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  7. Detailansicht für Treffer 7 öffnen
    Perspektiven der bayerischen Landwirtschaft. LKV Magazin.
    Mennig, P. ; Sauer, J.
    2022
    unknown
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  8. Detailansicht für Treffer 8 öffnen
    Perspektiven der bayerischen Landwirtschaft. LKV Magazin. ; Prospects for Bavarian agriculture. LKV magazine.
    Mennig, P. ; Sauer, J.
    2021
    unknown
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  9. Detailansicht für Treffer 9 öffnen
    Zum Schicksal sog. „Anpassungsverhandlungen“ nach brandenburgischem Hochschulrecht Nachlese zu Knopp, LKV 2007, 152 ff., und Ausblick
    Knopp, Lothar
    In: 10 Jahre Hochschulrecht im Wandel ; page 199-209; (2012)
    Buch
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  10. Detailansicht für Treffer 10 öffnen
    Landes- und Kommunalverwaltung ::LKV.
    In: http://lawcat.berkeley.edu/record/539161, 1991
    academicJournal
    Wie komme ich dran?
  11. Detailansicht für Treffer 11 öffnen
    Landes- und Kommunalverwaltung ::LKV.
    In: http://lawcat.berkeley.edu/record/539161, 1991
    academicJournal
    Wie komme ich dran?
  12. Detailansicht für Treffer 12 öffnen
    Phosphodiesterase-5 inhibition mimics intermittent reoxygenation and improves cardioprotection in the hypoxic myocardium.
    Milano, G ; Bianciardi, P ; et al.
    2011
    Zeitungsartikel
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  13. Detailansicht für Treffer 13 öffnen
    Eine konstruktionsbasierte Beschreibung von Mehrwortverbindungen mit Lokalisierungsverben im Deutschen
    De Knop, Sabine ; USL-B - Séminaire des Sciences du Langage (SeSLa)
    2022
    Online Buch
    Zugriff:
    Volltext
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  14. Detailansicht für Treffer 14 öffnen
    Eine konstruktionsbasierte Beschreibung von Mehrwortverbindungen mit Lokalisierungsverben im Deutschen
    De Knop, Sabine ; USL-B - Séminaire des Sciences du Langage (SeSLa)
    2022
    Online Buch
    Zugriff:
    Volltext
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  15. Detailansicht für Treffer 15 öffnen
    ОЦЕНКА РЕЖУЩИХ СПОСОБНОСТЕЙ НИТРИДБОРОВЫХ ВЫСОКОПОРИСТЫХ КРУГОВ ПРИ ПЛОСКОМ ШЛИФОВАНИИ ДЕТАЛЕЙ ИЗ СТАЛИ 13X15H5AM3 ПО МАКРОГЕОМЕТРИИ ПОВЕРХНОСТИ С ИСПОЛЬЗОВАНИЕМ ИСКУССТВЕННОГО ИНТЕЛЛЕКТА
    СОЛЕР ЯКОВ, ИОСИФОВИЧ ; НГУЕН МАНЬ, ТИЕМ ; et al.
    2016
    academicJournal
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  16. Detailansicht für Treffer 16 öffnen
    Homothetic Vectors of Bianchi Type I Spacetimes in Lyra Geometry and General Relativity
    Ali, Ahmad T ; Khan, Suhail ; et al.
    2015
    academicJournal
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  17. Detailansicht für Treffer 17 öffnen
    Plectrocnemia kirmikhia Melnitsky, Ivanov & Perkovsky 2021, sp. nov.
    Melnitsky, Stanislav I. ; Ivanov, Vladimir D. ; et al.
    In: A new species of Plectrocnemia (Trichoptera: Polycentropodidae) from Rovno amber, pp. 106-109 in Zootaxa 5006(1) 107-108, 2021
    unknown
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  18. Detailansicht für Treffer 18 öffnen
    Institutions and mechanism of regional integration in the South Central Coast ; Thể chế và động cơ liên kết vùng ở vùng Duyên hải Nam Trung Bộ
    Nguyễn Quốc Toàn
    In: Science and Technology Development Journal: Economics-Law and Management; Vol. 2 No. 2 (2018); 21 ; Tạp chí Phát triển Khoa học & Công nghệ: Khoa học - Kinh tế - Luật và Khoa học Quản lý; Tập. 2 Số. 2 (2018); 21, 2020
    academicJournal
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  19. Detailansicht für Treffer 19 öffnen
    Anwendung soziologischer Methoden zur Motivation von Landwirten, Impfungen durchzuführen, mit speziellem Fokus auf der Impfung gegen BVD
    Zehrer, Gabriele Heidi
    2017
    Online academicJournal
    Zugriff:
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    Volltext
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  20. Detailansicht für Treffer 20 öffnen
    Status-Quo-Analyse der Herdengesundheit und –fruchtbarkeit in ökologisch geführten bayerischen Milchviehbetrieben
    Deger, Leopold
    2016
    Online academicJournal
    Zugriff:
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    Volltext
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