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    Axon Medchem LLC tp003
    Tp003, supplied by Axon Medchem LLC, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/tp003/tp003/pm31163180-64-0-3
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    Article Title: Increased sensitivity to psychostimulants and GABAergic drugs in Lsamp-deficient mice.
    Article Snippet: Accepted Manuscript Increased sensitivity to psychostimulants and GABAergic drugs in Lsamp-deficient mice Aleksandr Bregin, Timur Mazitov, Ingrid Aug, Mari-Anne Philips, Jürgen Innos, Eero Vasar PII: S0091-3057(19)30115-7 DOI: https://doi.org/10.1016/j.pbb.2019.05.010 Reference: PBB 72728 To appear in: Pharmacology, Biochemistry and Behavior Received date: 11 March 2019 Revised date: 30 May 2019 Accepted date: 31 May 2019 Please cite this article as: A. Bregin, T. Mazitov, I. Aug, et al., Increased sensitivity to psychostimulants and GABAergic drugs in Lsamp-deficient mice, Pharmacology, Biochemistry and Behavior, https://doi.org/10.1016/j.pbb.2019.05.010 This is a PDF file of an unedited manuscript that has been accepted for publication.. As a service to our customers we are providing this early version of the manuscript.. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form.



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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and TP003 promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.

    Journal: Pharmacological research

    Article Title: Pharmacological chaperones restore proteostasis of epilepsy-associated GABA A receptor variants.

    doi: 10.1016/j.phrs.2024.107356

    Figure Lengend Snippet: Fig. 4. Hispidulin and TP003 promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.

    Article Snippet: Hispidulin (catalog#: 2174), CL218872 (catalog#: 1709), ZK93423 (catalog#: 1994), Bretazenil (catalog#: 3568), CGS20625 (catalog#: 2467), and TP003 (catalog#: 4414) were purchased from Tocris Bioscience.

    Techniques: Functional Assay, Expressing, Clinical Proteomics, Membrane, Control, Comparison

    Fig. 6. Hispidulin and TP003 inhibit the ERAD of the misfolding-prone α1(G251D) variant. a HEK293T cells stably expressing α1(G251D)β2γ2 receptors were treated with DMSO, Hispidulin (10 µM), and TP003 (5 µM) for 24 h. Then cycloheximide (100 μg / mL) (CHX), a potent protein synthesis inhibitor, was added to the cell culture media for the indicated time before cell lysis and Western blot analysis. Quantification of the normalized remaining α1 protein band intensity was shown on the right (n = 3). b Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the protein levels of selected ERAD factors in HEK293T cells stably expressing α1 (G251D)β2γ2 receptors (n = 3). c Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the interactions between α1(G251D) and selected ERAD factors in HEK293T cells stably expressing α1(G251D)β2γ2 receptors. Quantification of the ratio of proteins of interest / α1(G251D) post immunoprecipitation is shown in the right panels (n = 3). IP: immunoprecipitation. Each data point is reported as mean ± SEM. ANOVA followed by post-hoc Tukey test was used to evaluate the statistical significance. Statistical significance was labelled for the comparison to the DMSO treatment group. NS, not significant; *, p < 0.05; **, p < 0.01; ***, p < 0.001.

    Journal: Pharmacological research

    Article Title: Pharmacological chaperones restore proteostasis of epilepsy-associated GABA A receptor variants.

    doi: 10.1016/j.phrs.2024.107356

    Figure Lengend Snippet: Fig. 6. Hispidulin and TP003 inhibit the ERAD of the misfolding-prone α1(G251D) variant. a HEK293T cells stably expressing α1(G251D)β2γ2 receptors were treated with DMSO, Hispidulin (10 µM), and TP003 (5 µM) for 24 h. Then cycloheximide (100 μg / mL) (CHX), a potent protein synthesis inhibitor, was added to the cell culture media for the indicated time before cell lysis and Western blot analysis. Quantification of the normalized remaining α1 protein band intensity was shown on the right (n = 3). b Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the protein levels of selected ERAD factors in HEK293T cells stably expressing α1 (G251D)β2γ2 receptors (n = 3). c Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the interactions between α1(G251D) and selected ERAD factors in HEK293T cells stably expressing α1(G251D)β2γ2 receptors. Quantification of the ratio of proteins of interest / α1(G251D) post immunoprecipitation is shown in the right panels (n = 3). IP: immunoprecipitation. Each data point is reported as mean ± SEM. ANOVA followed by post-hoc Tukey test was used to evaluate the statistical significance. Statistical significance was labelled for the comparison to the DMSO treatment group. NS, not significant; *, p < 0.05; **, p < 0.01; ***, p < 0.001.

    Article Snippet: Hispidulin (catalog#: 2174), CL218872 (catalog#: 1709), ZK93423 (catalog#: 1994), Bretazenil (catalog#: 3568), CGS20625 (catalog#: 2467), and TP003 (catalog#: 4414) were purchased from Tocris Bioscience.

    Techniques: Variant Assay, Stable Transfection, Expressing, Cell Culture, Lysis, Western Blot, Immunoprecipitation, Comparison

    Fig. 8. Proposed mechanism of action of Hispidulin and TP003 on rescuing α1 DAV trafficking. Hispidulin and TP003 act as pharmacological chaperones to bind GABAA receptor variants to stabilize them in the ER. Pharmacological chaperone treatment enhances the assembly of the variants and their forward trafficking to the Golgi and plasma membrane. The effect of Hispidulin and TP003 is also reflected from the enhanced folding and reduced degradation of the variants. Consistently, the interactions between the variants and pro-folding chaperones (BiP and calnexin) and a trafficking factor (LMAN1) are enhanced, whereas the interactions be tween the variants and ERAD factors (Grp94 and VCP) are reduced by pharmacological chaperone treatment.

    Journal: Pharmacological research

    Article Title: Pharmacological chaperones restore proteostasis of epilepsy-associated GABA A receptor variants.

    doi: 10.1016/j.phrs.2024.107356

    Figure Lengend Snippet: Fig. 8. Proposed mechanism of action of Hispidulin and TP003 on rescuing α1 DAV trafficking. Hispidulin and TP003 act as pharmacological chaperones to bind GABAA receptor variants to stabilize them in the ER. Pharmacological chaperone treatment enhances the assembly of the variants and their forward trafficking to the Golgi and plasma membrane. The effect of Hispidulin and TP003 is also reflected from the enhanced folding and reduced degradation of the variants. Consistently, the interactions between the variants and pro-folding chaperones (BiP and calnexin) and a trafficking factor (LMAN1) are enhanced, whereas the interactions be tween the variants and ERAD factors (Grp94 and VCP) are reduced by pharmacological chaperone treatment.

    Article Snippet: Hispidulin (catalog#: 2174), CL218872 (catalog#: 1709), ZK93423 (catalog#: 1994), Bretazenil (catalog#: 3568), CGS20625 (catalog#: 2467), and TP003 (catalog#: 4414) were purchased from Tocris Bioscience.

    Techniques: Clinical Proteomics, Membrane