EMBO/sd-character-level-ner huggingface dataset:
Figure 3(A) Toxicity of wt sc mTNF and mutant Y86F after injection (↑) in naïve C56BL/6 mice. First injection was i.v., other injections were i.p. Mean rectal body temperature ± SEM and cumulative survival rates are shown (n = 4). For continuity of the temperature graphs, dead mice were included with a temperature of 20°C. (B) Plasma IL-6 concentrations measured via ELISA. Blood samples were taken 6 hours after i.v. injection of wt sc mTNF or mutant Y86F. (C) Immunohistochemical staining for PECAM-1 (red), ICAM-1 (green) and DNA (blue) of B16Bl6 tumors after p.l. treatment with 7µg wt mTNF or 50µg of mCD13-AFR. Scale bar is 50µm. (D) Expression of ICAM-1, E-selectin and VEGF-R2 in B16Bl6 tumor 6h after treatment, by qPCR analysis of whole tumor RNA. Error bars are SEM. ns, non-significant; *, p < 0.05; **, p < 0.01; ***, p < 0.001 by one-way ANOVA with Bonferroni's multiple comparison test. (E) Tumor growth and body weight change after daily p.l. injection of indicated (equimolar) doses of mCD13-AFR, non-targeted AFR (BcII10-AFR) or mCD13 VHH control (CD13-hIFNα2) in the B16Bl6 melanoma model. The line under the graph represents the treatment period. Tumor growth is shown as mean TSI, error bars are SEM (n = 5). ***, p < 0.001 by two-way ANOVA with Bonferroni's multiple comparison test. (F) B16Bl6 tumor growth after daily p.l. treatment with indicated doses of mCD13-AFR, Wortmannin (Wm), Birinapant (Bir) or combinations thereof. Wortmannin and Birinapant were given 1 hour before CD13-AFR. Tumor growth is shown as mean TSI + SEM (n = 4 for Wm and Bir, 5 for other groups). The line under the graph represents the treatment period. TSI of individual tumors of the indicated treatment groups at day 17 after tumor inoculation.
Regulation of Cbl by Aub in the GSCs is essential for their self-renewal (A-B) Immunostaining of germaria from aubHN2/QC42 (A) and aubHN2/QC42; CblMB/+ (B) females with anti-Vasa (green) and anti-Hts (red).Figure 7(A-B) Immunostaining of germaria from aubHN2/QC42 (A) females with anti-Vasa (green) and anti-Hts (red). DAPI (blue) was used to visualize DNA. The white arrow indicates the lack of GSCs; white arrowheads indicate GSCs. Scale bar: 10 μm. (A-B) Immunostaining of germaria from aubHN2/QC42; CblMB/+ (B) females with anti-Vasa (green) and anti-Hts (red). DAPI (blue) was used to visualize DNA. The white arrow indicates the lack of GSCs; white arrowheads indicate GSCs. Scale bar: 10 μm. (C) Quantification of mutant germaria with 0 to 1 GSC in the indicated genotypes. The number of scored germaria (n) is indicated. *** p-value <0.001, ** p-value <0.01, * p-value <0.05, using the χ2 test. (D) Model of Aub function in GSCs. Aub is required intrinsically in GSCs for their self-renewal and differentiation. Aub function in self-renewal depends on translational repression of Cbl mRNA in GSCs through the recruitment of the CCR4-NOT complex. In cystoblasts, this translational repression is decreased, likely through the implication of at least another factor (X). As is the case for other translational controls in the GSC lineage, Aub/CCR4-NOT acts in fine-tuning Cbl levels. Aub function in GSC differentiation depends on activation of the Chk2 DNA damage checkpoint, consistent with a role in transposable element (TE) repression to maintain genome integrity; Ago3 has the same role in GSC differentiation.
Figure 8Ingenuity Pathway Analysis (IPA) of AKG-induced transcriptome signature in adrenal chromaffin cell treated with AKG. The mRAN was extracted from adrenal chromaffin cells after 3-hrs incubation of vehicle or AKG (100 μM). (n = 3 per group). Immunoblots and quantification of p-IKK/IKK, p65, p-IκB/IκB and OXGR1 protein in adrenal chromaffin cells cultured with vehicle + NC, vehicle + siOXGR1, AKG (100 μM) + NC or AKG + siOXGR1 for 3 hrs (n = 3 per group). p65 translocation in adrenal chromaffin cells cultured with vehicle + NC, vehicle + siOXGR1, AKG (100 μM) + NC or AKG + siOXGR1 for 3 hrs (n = 3 per group). Scale bars, 100 μm. Immunoblots and quantification of p-IKK/IKK, p65 and p-IκB/IκB protein in adrenal chromaffin cells cultured with vehicle, AKG (100 μM), IKK inhibitor IKK16 or AKG + IKK16 for 3 hrs. E level in the medium from adrenal chromaffin cell cultured with vehicle, AKG (100 μM), IKK16 or AKG + IKK16 for 3 hrs (n = 10 per group).
Figure 2(A) left panel, map4k4-1 shows enhanced resistance to Pseudomonas syringae pv. tomato DC3000. The growth of Pst DC3000 after inoculation in the indicated genotypes (Col-0, white bars, map4k4-1, green bars). Bacterial titers were determined 2 hours (day 0) and 3 days after inoculation. Right panel, disease symptoms of wild-type and map4k4-1 at 3 days after inoculation. Values are the means ± SD, n = 6 (biological replicates), p < 0.01. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant. (B) map4k4-1 disease resistance phenotype was recovered to wild-type levels in two independent complementation lines, c867 and c872. Bacterial titers were determined as described above. Values are the means ± SD, n = 6 (biological replicates), p < 0.01. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant. (C) qRT-PCR analysis of PR1 expression levels in Col-0, map4k4-1 and c867 after mock (MgCl2) or Pst DC3000 inoculation, values are the means ± SD, n = 3 (biological replicates), p < 0.01. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant. (D) Flg22-protection assay. Col-0, map4k4-1 and c867 were pretreated with H2O or flg22 1 day before Pst DC3000 inoculation. The bacterial population was measured 3 days after infection. Values are the means ± SD, n = 6. **p < 0.01, Results are representative of three independent experiments. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant.
Figure 5(A) flg22 stimulates DDL PARylation. DDL-FLAG was transiently expressed in Arabidopsis protoplasts fed with 32P-NAD+. Protoplasts were treated without or with 100 nM flg22 for 30 min. PARylated DDL was immunoprecipitated with α-FLAG affinity beads, separated on 10% SDS-PAGE and visualized by autoradiography. PAR(DDL) indicates PARylated DDL proteins. A representative result from three repeats is shown. (B-C) DDL PARylation is reduced in parp1, parp2 and parp1,2 mutants. Protoplasts isolated from parp1or parp2 single mutants (B), or parp1,2 double mutants (C) were used for in vivo PARylation assay with 32P-NAD+. Protoplasts were treated with 100 nM flg22 for 30 min. The experiments were repeated twice with similar results.
HMGCL and βOHB favor metastatic dissemination of PDA cellsA Human ALU sequences quantification in lower chorioallantoic membrane (CAM) of chicken embryo injected with sg-CTRL or sg-HMGCL #2 PANC-1 cells.Figure 5A Human ALU sequences quantification in lower chorioallantoic membrane (CAM) of chicken embryo injected with sg-CTRL or sg-HMGCL #2 PANC-1 cells. Relative amount of metastasis is expressed as mean fold change relative to sg-CTRL ± SEM (n=8/group). Significance was defined by one-tailed Student's t-test. *: p<0.05. (B) Box-and-whisker plots of ketone bodies (KB) metagene score defined as first component of PCA of genes in primary tumors (n=728), in all metastases (n=76), and in liver metastases specifically (n=35). Box-and-whisker plot were defined with default parameters by median value (central band at the 50th percentile), interquartile ranges (IQR, box limited by 25th and 75th percentile) and whisker boundaries defined at 1.5x IQR. Significance was defined by Student's t-test. C Representative immunostaining of SMCT1 and MCT2 in metastatic livers of KIC mice (n=3 mice). Metastatic area (orange star) is separated from liver (green circle) by dotted lines. Scale bar: 100 µm. D-F Effect of βOHB treatment on liver metastatic incidence, size and status. Representative HPS staining of liver lobes from metastatic mice treated with βOHB (100mg/kg/day, i.p.) or 0.9% NaCl (i.p.) (n=8 mice/group). Metastatic areas are separated from liver by yellow dotted lines. Scale bar: 1mm and 500 µm for insets (D). Number and size of metastasis per lobe and classified in small, medium and large size (E). Pathological status of metastasis from mice treated with βOHB or NaCl (n=13 or 5 lobes/group, respectively). Data are expressed as percentage of total metastasis in all liver lobes presenting metastasis (F). G Representative images of mouse and human liver metastatic cells-derived organoids after 7 days of culture in medium alone (untreated) or supplemented with 1 or 10mM of βOHB. Scale bar: 1000 µm. H Working model: HMGCL and βOHB promote tumor expansion and dissemination. PDA tumor cells expressed HMGCL (left panel). In this setting, PDA can use βOHB from direct source as tumor surrounding βOHB, mimicked in our study by direct injection of βOHB, and indirect source from degradation of various nutrients. βOHB and HMGCL contribute to tumor growth and metastases formation. In metastases, ketone bodies genes are upregulated. When HMGCL is knock-out (right panel), contribution of βOHB in TCA cycle is reduced and tumor growth as well as dissemination capacity of tumor cells are strongly disturbed.
Silencing of PHD1 decreases p53 phosphorylation in response to chemotherapy in CRC cells.Figure 1Western blot for p53, phosphorylated p53 at Ser15 (p53 pS15), and vinculin (vinc) in HCT116 treated with 300 μM 5-FU for 8 h and silenced for PHD1, PHD2, or PHD3. qRT-PCR for PHD1, PHD2, and PHD3 in HCT116 silenced for PHD1 (*P = 0.0006 toward Scr), PHD2 (*P = 0.0004 toward Scr), or PHD3 (*P = 0.0075 toward Scr). A two-tailed unpaired t-test was performed with n = 3/group. Western blot of p53 pS15, p53, PHD1, and vinculin in HCT116 treated with 300 μM 5-FU for 8 h and silenced for PHD1 or a scrambled (Scr) control. qRT-PCR for PHD1 showing silencing efficacy with both siRNAs 1 (*P = 0.0017 toward Scr) and 2 (*P = 0.0023 toward Scr) compared to the scrambled control in HCT116. A two-tailed unpaired t-test was performed with n = 3/group. Western blot for p53, p53 pS15, and vinc in HCT116 silenced for PHD1 with two different constructs (constructs 1 and 2) upon exposure to 300 μM 5-FU for 8 h. Western blot for p53 pS15, p53, and vinculin in HCT116 silenced for PHD1 and treated with either 200 nM SN-38 or 20 μM oxaliplatin for 8 h. RNA levels of PHD1 in LIM1215 silenced for PHD1. (*P = 0.0099 toward Scr in a two-tailed unpaired t-test with n = 3/group.) Western blot for p53 pS15, p53, and vinc in LIM1215 upon silencing of PHD1 and treatment for 8 h with 200 μM 5-FU.
Figure 5Immunofluorescence analysis with anti-NeuN antibody in the retina of WT, Ndufs4-/-, Ndufs4-/-/miR-181a/b-1-/- and miR-181a/b-1-/- mice. RGCs are preserved in Ndufs4-/-/miR-181a/b-1-/- with respect to Ndufs4-/- mice. Scale bars are 50μm. Number of RGCs/mm (%). N=5. Graphical representation of the results of the optokinetic tracking assays reported as fold change of cycles/degree. Visual acuity is preserved in Ndufs4-/-/miR-181a/b-1-/- with respect to Ndufs4-/- mice. N≥8. Electroretinographic analysis reveals amelioration of b-wave patterns in Ndufs4-/-/miR-181a/b-1-/- with respect to Ndufs4-/-mice. N≥5.
Genome‐wide TE targets of RDR6‐RdDM A AGO6 enrichment and depletion of 21–22nt siRNAs for the entire genome in 100‐bp tiles for both wt Col and ddm1.Figure 4A AGO6 enrichment and depletion of 21-22nt siRNAs for the entire genome in 100‐bp tiles for both wt Col and ddm1. Tiles were categorized by annotation feature. B Of the tiles in (A) in both wt Col and ddm1, we determined the number of tiles with ≥ 2‐fold CHH methylation dependent on RDR6. C Distribution of AGO6 enrichment across TEs (solid lines) and genes (dashed lines) for different sizes of small RNAs in either the wt Col TE‐silenced epigenome or the ddm1 TE‐transcriptionally active epigenome. Dashed lines have the same color codes as the solid lines. 'Start' and 'Stop' represent the edges of the TE and the transcriptional start and stop sites of the genes. D-G Heatmaps of AGO6 enrichment of TE siRNA size classes in wt Col and ddm1 epigenomes. Analyzed were (D) the position of the TE on a chromosome and TE size, (E) the copy number of the TE, (F) the TE type and (G) the TE family name. The color of the TE family name in (G) corresponds to the TE type in (F). H Bisulfite sequencing of TE targets. Error bars represent Wilson score interval 95% confidence limits.
a) One hour after intraperitoneal injection of 30 mg kg−1 leupeptin to C57BL/6 mice, 25 mg kg−1 of imatinib (Ima) was injected intraperitoneally.f7(a) One hour after intraperitoneal injection of 30 mg kg−1 leupeptin to C57BL/6 mice, 25 mg kg−1 of imatinib (Ima) was injected intraperitoneally. Three hours later, tissue lysate was prepared from the liver and subjected to immunoblot analysis. (b) Imatinib (25 mg kg−1), trehalose (2 g kg−1) or PBS was injected intraperitoneally into 12-week-old diabetic Atg7+/−-ob/ob mice 3 times a week, and the blood glucose level was monitored. ***P0.001, ###P0.001; two-way ANOVA. (c) IPGTT were performed after treatment of Atg7+/−-ob/ob mice with imatinib or trehalose for 8 weeks. #P0.05; ##P or **P0.01; ###P or ***P0.001; Student's t-test. (d) ITT were performed after treatment of Atg7+/−-ob/ob mice with imatinib or trehalose for 8 weeks. #P0.05; ##P or **P0.01; ###P or ***P0.001; Student's t-test. (e) Regular insulin (Ins) was injected into the tail vein of Atg7+/−-ob/ob mice that were treated with imatinib or PBS for 8 weeks. Seven minutes later, tissue lysates were prepared and subjected to immunoblotting. (f) Tissue lysates prepared from the same mice without insulin injection were subjected to immunoblotting. Numbers below immunoblot bands indicate the fold changes normalized to control bands. ('*' indicates comparison between imatinib and control: '#' indicates comparison between trehalose and control).
Figure 6(A) SV-AUC data for 0.2 nM AF488-SPOP ΔBACK. Fluorescence scans were collected for 12 h and are plotted against distance from the axis of rotation (circles). The data were subjected to standard c(s) analysis in SEDFIT (Schuck, 2000) and the results of this fit are shown (solid lines, rainbow color scheme). (B) Sedimentation coefficient distributions for a selection of values from the dilution series are shown. (C) The isotherm of weighted-average s-values vs. concentration (black circles), was fit to a dimer self-association model and reveals a KD of 1.11 nM, [95% confidence interval 0.88, 1.40 nM] (solid line). (D) The BACK domain dimerizes with micromolar affinity. Experimental weight-average molar mass (Mw) from CG-MALS for SPOP mutBTB (black circles) was fitted to a self-association model (see text for details) for BACK-BACK dimerization (black line) yielding a KD of 36 ± 3 µM (average and standard deviation from 3 independent experiments). Fits to the monomer/dimer equilibrium model and to alternative monomer/trimer, tetramer and pentamer equilibrium models are depicted as black solid line and as dashed and grey lines, respectively. Residuals for all models are depicted in the lower panel.
Fig.Figure 4A Experimental timelines for CSDS, virus stereotaxic injections and behavioral study. B Imaging of GFP expression in the hippocampus 3 weeks after virus vector injection. Scale bar: 250 μm. C Expression of CD39 in the hippocampus of mice injected with LV-siCD39 (n = 6 mice/group. LV-siCD39 vs Control, P = 0.0006, Student's t test). D The social avoidance behavior for the stressed mice after knocking down CD39 (n = 15, 15, 14 mice. Interaction F2, 41 = 17.96, P < 0.0001; Target F1, 41 = 3.75e-005, P = 0.9951; Drug F2, 41 = 6.099, P = 0.0048; For Target CSDS - LV-GFP vs Ctrl - LV-GFP, P < 0.0001; CSDS - LV-siCD39 vs CSDS - LV-GFP, P < 0.0001. Two-way ANOVA with Tukey's post-test). E The immobility time in the TST of mice injected with LV- siCD39 (n = 11, 19, 15 mice. Treatment F 2, 42 = 5.807, P = 0.0059; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0069; CSDS - LV-siCD39 vs CSDS - LV-GFP, P = 0.0065. One-way ANOVA with Fisher's LSD test). F The immobility time spent in the FST of mice treatment with LV-siCD39 (n = 12, 19, 15 mice. Treatment F2, 43 = 5.237, P = 0.0092; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0095; CSDS - LV-siCD39 vs CSDS - LV-GFP, P = 0.0093. One-way ANOVA with Fisher's LSD test). G The ATPase hyperactivity of mice after knocking down CD39 in the hippocampal (n = 5, 6, 5 mice. Treatment F2, 13 = 8.45, P = 0.0044; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0016; CSDS - LV-CD39 vs CSDS - LV-GFP, P = 0.0166. One-way ANOVA with Fisher's LSD test). H The ATP level of mice after knocking down CD39 in the hippocampal (n = 5 mice/group. Treatment F2, 12 = 6.04, P = 0.0153; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0444; CSDS - LV-CD39 vs CSDS - LV-GFP, P = 0.0051. One-way ANOVA with Fisher's LSD test).
Figure 6A Visualization of CASPL4D1 proteins and lignin by mCherry and CADMAC fluorescence. Data information: pCASPL4D1::CASPL4D1-mCherry plants were pretreated with CADMAC and then inoculated with Pst DC3000 (AvrRpm1). mCh, mCherry; Chl, chlorophyll; hpi, hours post-inoculation. Scale bars, 20 μm (A) B Magnified views of CASPL4D1 and lignin localization. Images in boxes were enlarged in the 2nd to 4th columns. Arrows indicate lignin deposition between cells. Data information: pCASPL4D1::CASPL4D1-mCherry plants were pretreated with CADMAC and then inoculated with Pst DC3000 (AvrRpm1). mCh, mCherry; Chl, chlorophyll; hpi, hours post-inoculation. Scale bars 10 μm (B). C Relative fluorescence intensity profiles of CASPL1D1 (mCherry) and lignin (CADMAC) across transects indicated by dotted lines Data information: pCASPL4D1::CASPL4D1-mCherry plants were pretreated with CADMAC and then inoculated with Pst DC3000 (AvrRpm1). D A model showing morphological changes of CASPL- and lignin-deposited cells during the HR response.
Figure 8A-D Immunoprecipitation assay showing the interaction of GFP-tagged DDX6 (wild-type or the indicated mutants) with HA-tagged decapping factors and 4E-T in HEK293T cells. Inputs (1% for the HA-tagged proteins and 3.5% for the GFP-tagged proteins) and immunoprecipitates (20% and 7%, respectively) were analyzed by western blotting using anti-HA and anti-GFP antibodies. GFP-MBP served as negative control. E Immunoprecipitation assay showing the interaction of GFP-tagged NOT1 with HA-tagged DDX6 (wild-type or the indicated mutants) in HEK293T cells. Samples were analyzed as described in panels (A-D). F Control HeLa cells (transfected with a scrambled shRNA) or cells depleted of DDX6 were transfected with a mixture of three plasmids: the R-Luc-8xlet-7-poly(A) or the corresponding reporter carrying mutations in let-7-binding sites (R-Luc-Mut, Mut), a plasmid expressing F-Luc as a transfection control, and a plasmid expressing shRNA-resistant versions of GFP-DDX6 (wild-type or the indicated mutants) or MBP. For each condition, Renilla luciferase activity was measured, normalized to that of the F-Luc transfection control and set at 100% in cells expressing R-Luc-Mut. The left panel shows the normalized Renilla luciferase activities in control cells (i.e., cells treated with scrambled shRNA and expressing MBP). The right panel shows relative fold derepression for each condition for the R-Luc-8xlet-7-poly(A) after normalization. Mean values ± standard deviations from 4 independent experiments are shown. G Western blot showing the efficiency of the DDX6 knockdown. Dilutions of control cell lysates were loaded in lanes 1-4 to estimate the efficacy of the depletion. PABP served as a loading control. H Control HeLa cells (transfected with a scrambled shRNA) or cells depleted of 4E-T were transfected with a mixture of three plasmids: as described in (panel F). The left panel shows normalized Renilla luciferase activities in control cells (i.e., cells treated with scrambled shRNA). The right panel shows the relative fold derepression for the R-Luc-8xlet-7-poly(A) (after normalization) in 4E-T-depleted cells relative to control cells. Mean values ± standard deviations from 3 independent experiments are shown. I Western blot showing the efficiency of the 4E-T knockdown. Dilutions of control cell lysates were loaded in lanes 1-4 to estimate the efficacy of the depletion. Tubulin served as a loading control.
Figure 3(A) Representative images of immunostained larval NMJs and active zones from WT, hiw mutant, and hiw mutant driving an RNAi against dNmnat [#29402]. In the top 3 panels, greyscale images of entire terminal were acquired by staining for nerve marker HRP. Presynaptic Brp puncta (green) and postsynaptic dGluRIII clusters (magenta) were imaged to quantify N in each genotype. (B) Quantification of NMJ synaptic terminal surface area in each genotype. [WT n = 14, hiw n = 12 , hiw > dNmnat-RNAi n=12. 1-way ANOVA w/Tukey's multiple comparisons, DF=37, F=22.427, p < 0.0001. WT vs hiw p < 0.0001 (****), WT vs hiw > dNmnat-RNAi p < 0.0001 (****), hiw vs hiw > dNmnat-RNAi p = 0.2907 (NS)]. (C) Quantification of BRP puncta per NMJ [WT n = 14, hiw n = 12, hiw > dNmnat-RNAi n=12. 1-way ANOVA w/Tukey's multiple comparisons, DF=37, F=2.854, p = 0.0711. WT vs hiw p = 0.0573 (NS), WT vs hiw > dNmnat-RNAi p = 0.4529 (NS), hiw vs hiw > dNmnat-RNAi p = 0.5030 (NS)]. (D) Quantification of percentage of Brp puncta that were apposed to a dGluRIII clusters at each NMJ [WT n = 14, hiw n = 12, hiw > dNmnat-RNAi n=12. 1-way ANOVA w/Tukey's multiple comparisons, DF=37, F=2.093, p = 0.4716. WT vs hiw p = 0.2168 (NS), WT vs hiw > dNmnat-RNAi p = 0.1882 (NS), hiw vs hiw > dNmnat-RNAi p = 0.9966 (NS)]. (E) Representative electrophysiological traces from a synaptic facilitation experiment in which trains of 5 pulses were used to evoke consecutive action potentials at 100 ms ISI. Genotypes for these experiments were: WT (elav>UAS-RFP), hiw mutant (hiw; elav>UAS-RFP), or hiw depleted of dNmnat (hiw; elav>dNmnat-RNAi). (F) Quantification of the facilitation index, in which the amplitude of the 5th pulse is divided by the amplitude of the 1st pulse. [100 ms ISI: WT n=11, hiw n= 9, hiw>dNmnat-RNAi n= 12. 1-way ANOVA w/Tukey's multiple comparisons, DF = 31, F= 7.546, p =0.0023. WT vs hiw p =0.0020 (**), hiw vs hiw> dNmnat-RNAi p= 0.0229 (*), WT vs hiw> dNmnat-RNAi p= 0.5141 (NS). 50 ms ISI: WT n=11, hiw n= 9, hiw>dNmnat-RNAi n= 12. 1-way ANOVA w/Tukey's multiple comparisons, DF = 31, F= 5.587, p =0.0089. WT vs hiw p =0.0129 (*), hiw vs hiw> dNmnat-RNAi p= 0.0217 (*), WT vs hiw> dNmnat-RNAi p= 0.9546 (NS).]
Full-length TLN (but not APP) accumulates in a distinct compartment in PS1−/−hippocampal neurons.Figure 1.Full-length TLN (but not APP) accumulates in a distinct compartment in PS1−/−hippocampal neurons. Double-immunofluorescence staining for endogenous TLN (green, B36.1) and APP (red, mAb C1 6.1) in wild-type (top) and PS1−/− (bottom) hippocampal neurons (15-d culture). The inset shows an overview of the neuron. In wild-type neurons TLN labeling is essentially localized to the somatodendritic plasmalemma in contrast to APP, which is found in intracellular compartments. In addition, PS1 deficiency causes TLN, but not APP, to cluster in large somatic accumulations. Bars, 10 μm.