EMBO/sd-character-level-ner huggingface dataset:
Design of Bak variants with reduced pore-forming activity. Mutated amino acids are highlighted in red. (b) Bak∆TM_2 (blue frame): Combines R156Q and I80E, N86E, which target the interaction between the BH3 region and helix 1.
E Genetic suppression is consistent across genes encoding members of the same complex. Strongest suppression score across TS alleles for a gene (colour scale, as in (D)) in crosses to different wild strains (x-axis) for genes (y-axis) that encode members of the GPI-anchor trans-amidase complex (bottom) or the nuclear condensin complex (top). The G GPI16 gene suppression was not estimated in the NCYC110 strain due to chromosome II copy number variation ("X").
A Left, kymograph from sequential epifluorescence (20×) images showing cytosolic Ca2+ oscillations in speed‐fluctuating immature DC after slow motility phases (upper and lower panel) and a change in direction (lower panel). DCs were loaded with the Ca2+ dye Oregon GreenBAPTA 1‐AM, introduced in micro‐channels, and imaged every 10 s. Right, sequential epifluorescence (20×) images (1 image/20 s is shown). Instantaneous velocities and intracellular calcium oscillations were measured as described in Materials and Methods. Scale bar: 10 μm.
MDTF cells were transfected with an empty vector (pCDNA3.1) or a vector expressing myc-tagged human S100A9 whose expression was analysed by Western-blotting with anti-myc 48h post-transfection.
(D) Kinetics of internalization of p75NTR in wild type hippocampal neurons in the presence or absence of NGF. Shown is mean ± SEM of percentage internalization of total surface p75NTR (set to 100%). N=3 independent experiments each performed in duplicate; *, P<0.05 ± NGF (2-way ANOVA). (E) Linear transformation of p75NTR internalization kinetics IMAX denotes maximal internalization in %. T1/2 denotes time for half maximal internalization in minutes.
E Representative images showing AHR and DDA1 levels in brain metastases (generated by intracardiac inoculation of H2030-BrM) found at endpoint of vehicle and DEBIO-0932 treated animals. This result was reproduced in 2 independent staining with different brains. BB: bisbenzamide. Scale bars: low magnification (HSP90 and GFP), 50 µm; high magnification (DDA1), 6 µm (dotted lines).
(F) The bead-autophagosome fraction was lysed and subjected to immunoprecipitation with an anti-Ub IgG antibody (FK2) or control IgG. Co-immunoprecipitated molecules were examined by Western blotting using the indicated antibodies.
The effect of the arid2, arid3, and arid4 mutations on the silencing of solo LTR, SDC, and FWA as determined by qPCR. Showing are results of three biological replicates with standard deviations.
D. Mdm12 binds NBD-PE. Wild-type and monomeric (I5P mutant) Mdm12 were incubated with NBD-PE and separated from free NBD-PE in native PAGE. Coomassie staining (left) and fluorescent (right) detection indicates that Mdm12 directly interacts with NBD-PEin vitro.E. Quantitative data showing binding affinities for NBD-PE by Mdm12. The binding affinities of Mdm12 (monomer/dimer shown in Native PAGE and I5P mutant) for NBD-PE was measured with a NBD-PE concentration-dependent manner. All experiments were carried out three times and the means ± SD are given.
Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), or control (A-I) combined or not with a treatment with MG132 (H) followed by western blot analysis (A-F, H-I).
M Western blotting showing protein levels of MYC, PKM2, and LDHA in Dgcr8−/−ESCs stably expressing Myc shRNAs and further infected with Mbd2 siRNAs. A representative result is shown.
(D) HCT116 cells were transfected with control (mixture of control siLuci and siGFP) or GRWD1-targeting (mixture of siGRWD1-3 and 4 or siGRWD1-1) siRNAs for 24 h and then immunostained as above. Scale bar, 20 um.
F. Functional categories of downregulated genes in hTrmt13 knockdown MDA-MB-231 cells showing the p-value for the enrichment of biological process GO term.
I. Tau phosphorylation detected by antibody AT8 (pS202+pT205) in stratum pyramidale of area CA3 (arrowhead). Note that immunoreactivity increases with expression level.
L Co-immunoprecipitation of the DHHC2_WT-HA and DHHC2_WT-Myc co-expressed in HEK293T cells.
(D) KEGG Pathway analyses of over-lapped Differential expressed genes (DEGs) in both lncPSCA-overexpression cells and the DDX5-konckdown cells identified multiple pathways involved in cancer biology, with the P53 and MAPK signaling pathways as two of the most markedly changed pathways.
Immunohistochemical analysis of paraffin-embedded xenograft prostate tumor using CD31 (G) antibody. The total vessels number per mm2 was quantified. Scale bars: 0.1 mm. Data are presented as means ± SEM (n=4-5 mice per group). Data information: Student's t-test was used for the statistical analysis (*P<0.05).
(D, E) Imaging of luciferase activity in the liver of HIF1aAlbKO (D) and HIF2aAlbKO (E) mice after a hydrodynamic tail vein injection with a HRE-luc reporter plasmid or control (PBS) according to body weight followed by 6h normoxia or hypoxia. (F, G) Bioluminescent photon counts normalized to the PBS control group in liver of (F) HIF1aAlbKO and (G) HIF2aALbKO mice and their wild-type littermates 6h after normoxia of hypoxia. Data information: All bars represent mean ± SEM. Each individual data point represent individual mice. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. *** P<0.001; ** P≤ 0.01; * P≤ 0.05. N = normoxia, H = hypoxia. Signal around the perimeter of the Petri dishes represent aspecific luciferase signal.
C. Dissected flatmount of zebrafish embryos injected with Alx1DN, after Alcian blue staining. The embryos developed an absence of the frontonasal derived median portion of the anterior neurocranium (ANC) and a profound hypoplasia of the Meckel's and ventral cartilages. In the most severely affected zebrafish, a nearly abrogated ANC was observed. Scale bar: 200 µm.
Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding A-C/EBP or C/EBPζ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data with mean value from 8(C are shown on the right Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate
(B) HEK293A cells were transfected with control or p38α siRNA. At 72 h after transfection, cells were incubated in either full medium, EBSS, or EBSS containing leupeptin for 2 h. Cells lysates were analysed for LC3 lipidation using an anti‐LC3 antibody. The membrane was also probed with anti‐actin and anti‐p38α antibodies. LC3 lipidation was quantified as the amount of LC3II/LC3I (data are represented as mean ±s.e.m. n=5, full medium control versus p38α siRNA (**P=0.0056); EBSS control versus p38α siRNA (**P=0.048); EBSS with Leu control versus p38α siRNA (**P=0.04), Student's t‐test).
(E) Gene expression analysis by RT-qPCR of Stat3+/+ (blue) and Stat3-/- (red) cells cultured in 2i and treated with LIF for 1 hour, 4 hours or 4 days. Data are normalized to unstimulated 2i cultures. Beta-actin served as an internal control. Mean and s.e.m. of three independent experiments. Unpaired t-test: * P<0.05 ** P<0.01 *** P<0.001. See also Appendix Figure S1B.
Figure 8. Model showing distinct gene regulatory function of JNK signaling during EMT. Onset of EMT crucially relies on Smad-mediated (Valcourt et al, 2007; Xu et al, 2009) transcriptional changes and as cells advance through the mesenchymal fate, JNK pathway progressively becomes critical in gene regulation. We identified a set of transcription factors (Prkrir, Etv6, Srf, Hoxb9, Tsc22d1, Tcf12, Nr1h4, Zeb1, Pcbp4, Nfil3) that are induced by JNK signaling and function in progression and/or maintenance of the mesenchymal state Furthermore, JNK activity also represses another set of factors (Meox2, Hnf4a, Sfpi1, Lmo7, Cdx2) that promote an epithelial phenotype. Among these JNK regulated factors, in addition to the factors known to regulate EMT and carcinogenesis (Etv6 (Tognon et al, 2011), Srf (Bae et al, 2014), Hoxb9 (Hayashida et al, 2010), Tcf12 (Lee et al, 2012), Zeb1 (Burk et al, 2008; Sanchez-Tillo et al, 2013), Meox2 (Valcourt et al, 2007), Hnf4a (Santangelo et al, 2011), Sfpi1 (Rosenbauer et al, 2006; Walter et al, 2005), Lmo7 (Tanaka-Okamoto et al, 2009) and Cdx2 (Gross et al, 2008)), we also identified five novel transcription factors that are crucial for progression and/or maintenance of EMT (Nfil3, Nr1h4, Tsc22d1, Pcbp4 and Prkrir).
(F) Ceramides levels in isolated pancreatic islets of mice at 8 weeks of age with deletion of Abca12 in β-cells (mean±SEM n=10, 4 and 5 mice per genotype respectively).
(f, g) Immunoblots (IB) of p62 (g) in starved C38 and IB3-1 cells. Uncropped images of blots are shown in Supplementary Information, Fig. S10.
types.A, HEK293T cells were infected with HIV-luc/2019-nCoV pseudoviruses and then incubated with teicoplanin at various concentrations. The intracellular luciferase activity was measured at 48 h post-infection. The IC50 was calculated using GraphPad Prism software.B
B KEGG pathway analysis indicated the altered function of TGF-β/BMP signaling pathway
Immunoblots of p-AMPK, p-ACC and PGC1α and corresponding quantifications represent p-AMPK, p-ACC and PGC1α protein levels (G in C2C12 myocytes transfected by mGPDH plasmid with the AMPK inhibitor compound C (CC) 24 h after differentiation
The cumulative probability distribution of MP-SVs plotted against the tether length. The red dotted lines represent the mean MP tether length in resting wild-type for each sub-pool.
C-H 20 nM siRNA for NC and PKR were transfected into WT and lincRNA-EPS-/- iBMMs following infection with VSV (MOI 0.1) for 4 h, Mx1, Ifit2, and Isg15 mRNA level were measured by RT-qPCR (C, E, and G), and relative basal expression change rates of the antiviral ISGs in lincRNA-EPS-/- iBMMs were calculated compared with WT group (D, F, and H).
(c) GFP-tagged BRLF1 wild type, BRLF1 L578A or empty vector was transfected into 293T cells with GST-tagged POLR3F or POLR3G expressing plasmids for 48 h. Cells were collected and immunoprecipitation with GST-affinity beads was performed, and then whole cell lysates and immunoprecipitated complexes were analyzed as indicated.
Expression of CBFs target genes J) in EGR2-overexpressing plants. Two-week-old seedlings were treated at 4°C for the indicated period and subjected to qRT-PCR analysis. Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).
SDS-soluble and insoluble fractions were isolated from SH-SY5Y cells expressing WT or catalytic-inactive mutant OGT treated with 20 μM EA, and the fractions were analyzed by immunoblotting. Quantification of (F).
T cell-dependent immune responses. Prdm1ihCd2/+ (red dots) and wild-type (gray dots) mice at the age of 2 months were immunized with NP-KLH (in alum) and analyzed at day 14 after immunization b ELISA The serum titers of anti-NP-specific IgM, IgG1 and IgG2b antibodies were analyzed by ELISA using NP7-BSA- or NP24-BSA-coated plates for detecting high-affinity IgG1 or total IgM, IgG1 and IgG2b antibodies, respectivel Dot plots display the serum immunoglobulin titers of Prdm1ihCd2/+ (red dots) and wild-type (gray dots) mice. NP-specific IgG1 concentrations (μg/ml) were determined relative to a standard NP-binding IgG1 antibody, whereas IgM and IgG2b amounts are indicated as relative units (RU) by setting the WT data to 1
F STS-induced caspase 3/7 activity of HCT116 Bax/Bak DKO cells expressing Bax, Bax S184V, BakTBax or BakTBax S184V is displayed normalized to Bax activity. Data represent averages ± SEM. n ≥ 3.
(C) HeLa cells left unstimulated (CTR) or infected with Listeria TKO for 1 h, analysed by IF using antibodies against mTOR and LAMP2.
Time-lapse Airyscan imaging of ΔΨm in living HeLa cell, co-stained with MTG (ΔΨm-insensitive after loading) and TMRE (ΔΨm sensitive). Arrowhead points to a flickering event where a mitochondrion depolarizes (~9 sec) and repolarizes (~16 sec), showing that heterogeneous signal from TMRE (but not MTG) disappears and reappears. Scale bar = 500 nm. N = 4 independent experiments. Quantification of A. Plot shows average TMRE fluorescence intensity (FI) of cristae (dark red line) vs. matrix (light red line) during the time series. The drop in TMRE FI during the depolarization phase of the flickering is the ΔΨm-sensitive component of the TMRE signal. The remaining TMRE FI during depolarization can be considered as the ΔΨm-insensitive portion of TMRE signal. Note that the remaining TMRE FI after depolarization at the cristae and matrix are approximately identical, indicating that differences in TMRE FI between the cristae and matrix prior to depolarization are derived from differences in ΔΨm. N = 4 independent experiments.
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.
Real time PCR analysis of irg-1, irg-2 and irg-3 genes in N2 worms exposed to odor of undA mutant upon PA14. n = 3. * P ≤ 0.05, ** P ≤ 0.01 as determined by two-tailed unpaired t-test. Error bars indicate SEM.
sulA genes measured by quantitative PCR when WT and mutant strains are grown in M9 medium with or without supplementation of amino acids or dTMP. WT and mutant strains were grown for 4 hours of growth in the indicated medium at 37°C, while WT treated with different concentrations of Tmp were grown for 4 hours at 42°C. Brown bars (M9+AA) in the gray shaded area correspond to filamentation conditions and these are associated with pronounced upregulation of all three SOS genes. On the other hand, conditions with loss of filamentation (with dTMP or no supplementation) show much less expression. Error bars represent SD of 2-3 biological replicates (see Methods).
C) Diagram of the proline metabolism pathways. Proline biosynthesis genes are PYCRL, Pyrroline-5-Carboxylate Reductase Like; PYCR1, Pyrroline-5-Carboxylate Reductase 1; PYCR2, Pyrroline-5-Carboxylate Reductase 2; ALDH18A1, Aldehyde Dehydrogenase 18 Family Member A1 (Pyrroline-5-Carboxylate Synthetase).
a. mRNA expression on ex vivo isolated Tregs from MS patients and healthy controls (n=15).
(a) Representative confocal microscopy images showing HACE1 (green) localizing to the Ub+ protein aggregates (red) induced by puromycin treatment in HA-HACE1 MEF. Arrows indicate co-localized puncta. Scale bar, 10 μm.
Apoptotic fraction (Sub-G1 population) determined by propidium iodide staining of cells treated with PLK1i Graph represents the mean±SEM of three independent experiments.
(A) WT (SCY62), tag∆ste∆ (H1246), tag∆ (H1226) and ste∆ (H1112) cells expressing GFP−Atg8 were grown to mid-log phase in YPD and shifted to SD-N for 6 h. Cells were stained with BODIPY and visualized by fluorescence microscopy. Scale bar, 5 μm.
U2OS cells stably expressing HA-SHLD2∆720-904 (Left) or HA-SHLD2∆1-680 (Right) were processed as in (B). Immunofluorescence against endogenous HA and RPA32 epitope was subsequently performed to monitor RPA32 and SHLD2 accumulation at sites of damage. Shown are representative micrographs. Scale bar = 5µm.
The microtubule cytoskeleton is changed in COs upon ECE2 KO. Quantification of ac-tub in ventricles of ECE2 KO COs by measurement of the mean grey value in Fiji shows significant reduction upon ECE2 KO (n=number of analysed ventricles; *P = 0.019 in One Way ANOVA and Tukey Pairwise Multiple Comparison).
E Gli1/DNA binding. Double‐stranded oligonucleotide containing the canonical GliBS sequence (5′-TTGCCTACCTGGGTGGTCTCTCCACTT-3′) or mutated GliBS sequence used as control (5′-TTGCCTACCTCCCACTTCTCTCCACTT-3′) was used as probe (P) in EMSA experiments. The assay was performed using recombinant GST‐Gli1ZF‐WT (Gli1 zinc finger fragment: aa 242-424), GST‐Gli1ZF‐K350A and GST‐Gli1ZF‐K340A. The graph on the right indicates ratio (mean arbitrary units ± SD from three independent experiments) of GST‐Gli1ZF‐WT or GST‐Gli1ZF mutants bound to the labeled GliBS probe/GliBS‐free probe normalized to the amount of GST‐Gli1ZF‐WT/DNA binding (as described in ). *P 0.05 versus Gli1 WT.
The expression of SAMHD1 is negatively correlated with EV71 viral replication ability. HEK293T and RD cells were infected with EV71 at a MOI of 0.1, then the cells and supernatants were harvested at the indicated time points. Immunoblotting (IB) analysis of EV71 VP1 in cells, with tubulin as a loading control. EV71-VP1 protein in the supernatants was detected after ultracentrifugation.
D, viSNE layout of CyTOF single-cell events with points colored according to the CHIKV channel. By qualitative comparison monocytes, myeloid dendritic cells (mDCs), and B cells (labeled) have the highest CHIKV envelope protein (E2) expression on the cell surface.
A: Sequence of snapshots of the LimE-GFP distribution and stress T for an amoeboid cell and the GFP-myo distribution for a separate amoeboid cell. Corresponding speeds are 7.4µm/min and 4.5µm/min. The sequences show both the phases of protrusion and retraction. White arrows represent the direction of motion.
Dot-plot representing the percentage of proliferating cells from a sample of G2 patients before starting immunotherapy, activated ex vivo by A549-SC3 cells in the presence of the indicated antibodies. "Dual" represents the addition of both anti-PD-1 and anti-LAG-3 antibodies. Appropriate statistical comparisons are shown within the graph with two-way paired ANOVA. Data from CD28+ and CD28negative subsets are represented as indicated. for CD8 T cells.
DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool or siUBTD1single1; UBTD1 +YAP+TAZ, siUBTD1single1+siYAPsingle1+ siTAZsingle1 or siUBTD1single1+siYAPsingle2+ siTAZsingle2). (C) Quantification of DU145 cell migration in Transwell chamber inserts.
F, Frequency of RBPs and proteins with prion-like domains or ATPase activity found in TSN2_NS and TSN2_HS protein pools in comparison with yeast and human SG proteomes Jain et al., 2016().
H Quantification of double-positive endolysosomes at 300' (ATZ:sfGFP-KDEL n=14, ATZ:CNX n=8, ATZ:CLIMP63 n=10 cells. One-way ANOVA and Dunnett's multiple comparisons test, ** P<0.01 **** P<0.0001). Data information: Scale bars 10 μm.
(d) Absolute loadings of the drugs with the largest weights, annotated by target category
d) Representative images of dUnaG- or dEGFP-expressing CHO cells grown either under normoxia (21% oxygen), CoCl2-treatment or hypoxia (1% oxygen) for 12 hours. Scale bars= 50µm
D) Boxplots and individual points for times for each plate well profile for both WT and KO cells kept at 37°C or transferred to 18°C for 24h (top panel) or 5h (bottom panel) from biological repeats 1 and 2. Points are colored according to their distinct phase prior to 18°C exposure. Colored lines (bottom panel) show the change in the mean for the points from each phase. Boxplots display median (central line), interquartile range (IQR, box edges) and range (whiskers). Number of wells: top panel WT cells: 37°C (120), 18°C 24h (119); top panel KO cells: 37°C (120), 18°C 24h (120); bottom panel WT cells: 37°C (58), 18°C 5h (120); top panel KO cells: 37°C (60), 18°C 5h (120).
Degradation of long-lived proteins using metabolic labeling was performed as described in Supplementary Materials and Methods. The data represent the mean ± SEM of nine independent samples analyzed in three independent experiments. *P = 0.009 for WT and *P = 0.0013 for Ctns−/−, respectively. NS, not significant (unpaired t-test).
CftrF508del mice (a-d)(a) Confocal microscopy of LC3 (top) and p62 (bottom) in lung tissues from CftrF508del mice. Nuclei counterstained with DAPI (blue). Scale bar, 10 μm. Representative images of ten PBS-treated and ten NAC-treated mice. (b) Quantification of LC3 dots (per mm2 of tissue) in lung tissues from CftrF508del mice. Means ± s.d. Asterisk, P 0.001 versus PBS-treated mice; ANOVA.
B. Schematic of pairing between miRNAs (loaded into Ago2) and targets used in equilibrium binding experiments.
(E-M) C2C12 cells were transfected for 48 h with GFP, GFP‐Jumpy (Jumpy), GFP‐MTM1 (MTM1) or GFP‐MTMR2 (MTMR2), fixed and immunostained with anti‐p62 antibody (red). p62 puncta were quantitated by confocal fluorescence microscopy. Representative confocal images of GFP (E), GFP‐Jumpy (F), GFP‐MTM1 (G), GFP‐MTMR2 (H) transfected cells, immunostained for p62 (I), (J), (K) and (L), respectively. Scale bars, 5 μm. White lines represent outline of the cells. Quantitation of p62 puncta per cell (M). Bars, SEM (n=3 independent experiments, with an average of 30 cells per experiments).
Serum levels of triglycerides (TAG) and non-esterified free fatty acids (NEFA) in WT and DKO mice (n=5).
AP staining of the iPSC colonies in reprogramming with OSK combined with scramble control, inhibitors of miR-23a, miR-27a, miR-24 and let-7c respectively.
Superposition of the IgI3 domain from β protein (blue) onto predicted IgI3 domain structure of clade II sequence of S. pyogenes R28 protein (red).
CLSM images showing NCL localization (immunofluorescence), aluRNA (RNA FISH) and DNA (DAPI). Transfection of HeLa cells was done as in (A).
B) Distribution of cells across the different clusters per experimental group (n=2 mice pooled for all experimental groups, except for TAUtg-11M and TAUwt-11M with n=3 mice pooled).
D-E. Mitochondrial membrane potential (ΔΨM) was measured by flow cytometry in control and patient fibroblasts after treatment of 1μM STS for 24 h (E) and quantified in D from two independent experiments. Differences between the control and patient fibroblasts were analyzed by Student's t-test (two-sided): significant (*:0.05>p>0.01). Patient 1 (P1) versus control (C2): *: p=0.0414 (24h). Patient 2 (P2) versus control (C2): *: p=0.0461 (24h).
H. Above: Sample-wise co-regulation network of embryonic MΦ development. Pearson correlation threshold of 0.92 was used to generate the network. Below: scheme thereof.
(A) ACE2 protein abundance in different human tissues based on various studies processed by PaxDB, with expression levels presented as parts per million (ppm). The "Integrated" dataset corresponds to PaxDB estimation of average expression.
B) Cells transfected as in (A) were loaded with Alexa-647 transferrin for 15 minutes and the fluorescent transferrin chased out for the indicated time periods. At the end of the timecourse the cells were fixed and the transferrin content of GFP positive cells analysed by flow cytometry. Results are expressed as a percentage of Tfn fluorescence at t=0 and are the mean of 3 independent experiments, ± s.e.m.
(E) The FD20 epitope (red) is conserved between SARS-CoV-2, RaTG13, and SARS-CoV. Dots indicate identical residues and dashes indicate gaps. Brackets indicate sequence identity between the aligned RBD and SARS-CoV-2 RBD. NCBI accession codes for the sequences are as follows. RaTG13, QHR63300.2; SARS-CoV, NC_004718.3.
(A) Serum insulin of WT and Pdia4tg/tg (TG) mice on BKS or Leprdb/db background at the indicated ages, was measured using an ELISA kit. Data information: Data from 3 experiments more One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant. The number of mice (n) is indicated in parentheses.
(B) Immunoblots from cytosolic (cyt) and nuclear (nuc) fractionations of RPE-1 cells in early-G1 showing the presence of endogenous ACTN4 in nuclear fractions. Proteins were detected with antibodies against (α) ACTN4, α-Tubulin or Histone 3 as indicated
3D reconstructions of the MP-SV pool: AZ-membrane (blue), presynaptic density (PD, pink), non-tethered (yellow), tethered (orange), docked SVs (light orange). Scale bar, 100 nm. (B-D) Wild-type ribbon synapse upon inhibition (B), rest (C) and stimulation (D); (E-G) OtofPga/Pga ribbon synapse upon inhibition (E), rest (F) and stimulation (G).