EMBO/SourceData huggingface dataset:
Figure 5B, C. SCID male mice with PDX tumors were treated with vehicle (40% polyethylene glycol), JQ1 (50 mg/kg), CPI-637 (30 mg/kg), combination of JQ1 (50 mg/kg) and CPI-637 (30 mg/kg) or NEO2734 (30 mg/kg) five days a week for three consecutive weeks. Tumors isolated from mice at day 21 of drug treatment were photographed (B) and tumor growth are shown in (C). All data shown are means ± SEM. The P value comparing the tumor volume at day 21 post- treatment was calculated by the unpaired two-tailed Student's t-test; *** P < 0.001.PDX tumors in each treatment group were harvested for protein For western blot analysis, three tumors each group (n = 3) were used for protein extraction and mixed with equal ration to detect the indicated antibodies in (D).PDX tumors in each treatment group were harvested for RNA extraction. For RT-qPCR, three tumors each group (n = 3) were extracted RNA for RT-qPCR in (E). Data are shown as means ± SEM. The P value comparing vehicle with each treatment group was calculated by unpaired two-tailed Student's t-test and indicated in the graph.
Figure 6Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were harvested for western blot analysis with the indicated antibodies (A) Asterisk, SRC3 at expected molecular mass.Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were harvested for IFC with p-AKT-S473 antibody (B). E-cadherin antibody was used to indicate the cell membrane (red) and DAPI for nucleus (blue). Scale bars: 25 µm.Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were cultured for five days, followed by the treatment with JQ1 (2 µM), CPI-637 (2 µM), JQ1 (2 µM) + CPI-637 (2 µM) or NEO2734 (2 µM) for five more days. The representative images of organoids after the treatment are shown in (C)Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were cultured for five days, followed by the treatment with JQ1 (2 µM), CPI-637 (2 µM), JQ1 (2 µM) + CPI-637 (2 µM) or NEO2734 (2 µM) for five more days. the quantified data of the organoid diameter are shown in (D). Scale bars: 25 µm. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; n.s., not significant, * P < 0.05, ** P < 0.01, *** P < 0.001.E, F. 313HR (SPOP WT) and 573R (Q165P) organoids were cultured for 5 days, followed by the treatment with the indicated inhibitors for 5 days. The organoids were stained with Caspase-3 antibody (green) to detect apoptotic cells. E-cadherin antibody staining was used to define the cell membrane (red) and the nucleus was counterstained with DAPI (blue). The representative images of cleaved Caspase-3 IFC staining are shown in (E). Scale bars: 25 µm. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; * P < 0.05, *** P < 0.001.
Figure 7A. C4-2 PCa cells infected with virus expressing EV, SPOP Q165P or F133V were harvested for western blot analysis.B MTS was performed to compare the cell growth between EV, Q165P, F133V C4-2 groups after the treatment with indicated inhibitors (2 µM of JQ1, 2 µM of CPI-637, 2 µM NEO2734) for 72 h. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; n.s., not significant, * P < 0.05, ** P < 0.01, *** P < 0.001.C. Clonogenic survival assay was performed to determine the sensitivity of NEO2734 in SPOP mutant C4-2 cells. The survival curve showed IC50 for EV (1.01 µM), SPOP Q165P (0.621 µM) and SPOP F133V cells (0.395 µM).D, E. C4-2 cells expressing EV, Q165 or F133V constructs were treated with 1 µM of NEO2734 for 4 days and cultured for another 8 days before harvesting. The number of colonies with more than 50 cells was counted. Representative images of colonies are shown in (D) with quantification data in (E). All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; * P < 0.05, *** P < 0.001.F - H. A schematic depicts the procedure of the establishment of SPOP mutant xenograft models and inhibitor administration (F). When the tumor reached 100 mm3, mice were treated with vehicle (40% polyethylene glycol), JQ1 (50 mg/kg) or NEO2734 (30 mg/kg) five days a week for three consecutive weeks. Tumors isolated from mice at day 21 of treatment were photographed (G) and tumor growth are shown in (H). All data shown are means ± SEM. The P value comparing the tumor volume at day 21 post- treatment was calculated by the unpaired two-tailed Student's t-test; * P < 0.05, ** P < 0.01; *** P < 0.001.
Figure 1(B) Co-immunoprecipitation of HA-tagged Btz-WT or Btz-HD with Myc-tagged GFP or eIF4AIII from transfected S2R+ cells using Myc-Trap Magnetic Agarose beads. The upper Western blot is blotted with anti-Myc and the lower with anti-HA. Input samples are shown on the left and immunoprecipitates on the right. Btz-WT co-immunoprecipitates with eIF4AIII, but Btz-HD does not, although the protein is equally stable. The asterisk represents a likely cleavage product of Btz.(C-F) show stage 10 egg chambers stained with anti-Vasa (C-F) or anti-GFP (E', F'). (C) wild type; (D) germline clones homozygous for the null allele btz2; (E) btz2 germline clones rescued with Btz-WT; (F) btz2 germline clones rescued with Btz-HD. Posterior is to the right. Scale bars, 80 μm. Vasa localization to the posterior pole of the oocyte is lost in btz mutants and is rescued by the wild type but not the EJC interaction-defective transgene. Wild-type Btz-GFP, but not the mutant form, is also slightly enriched at the posterior pole.
Figure 2(L-N) electron micrographs showing cross-sections of larval muscle 6 in segment A3, with the dorsal surface to the right. Scale bars, 10 μm. (L) btz2/+; (M) Df(3R)BSC497/+; (N) btz2/ Df(3R)BSC497. Yellow arrows indicate examples of mitochondria interspersed between muscle fibers, and red arrows indicate mitochondria at the dorsal surface. Scale bars, 2 μm.(O) quantification of the ratio of the dorsal surface peak of ATP5 intensity to the second highest peak for the genotypes indicated. ***, p<0.001; **p<0.01; *p<0.05; ns, not significant by Mann-Whitney test. n=9 (btz/+), n=11 (Df/+, btz/Df), n=6 (btz/Df; G14>btz, C57-GAL4/+), n=4 (btz/Df; Btz-WT, C57>eIF4AIII RNAi), n=5 (btz/Df; Btz-HD), n=10 (C57>btz RNAi), or n=3 (C57>mago RNAi). Error bars show mean ± SEM.
Figure 3(A-J) confocal images of the NMJ on larval muscles 6 and 7 in segment A3, stained with anti-HRP (magenta) to label the nerve and anti-Dlg (green) as a postsynaptic marker of synaptic boutons. (A) w1118 control; (B) btz2/+; (C) btz2/Df(3R)BSC497; (D) UAS-btz/+; da-GAL4, btz2/Df(3R)BSC497; (E) BG380-GAL4/+; UAS-btz/+; btz2/Df(3R)BSC497; (F) 24B-GAL4/UAS-btz; btz2/Df(3R)BSC497; (G) BG380-GAL4/+; 24B-GAL4/UAS-btz; btz2/Df(3R)BSC497; (H) BG380-GAL4/+; UAS-btz RNAi/+; (I) mhc-GAL4/UAS-btz RNAi; (J) repo-GAL4/UAS-btz RNAi. Scale bar, 30 μm. Insets in (A, C) show enlargements of the boxed regions, illustrating the closer spacing of boutons in btz mutants.(K, L) quantifications of the number of boutons normalized to muscle surface area (x1000) in the indicated genotypes. ****, p<0.0001; ***, p<0.001; **, p<0.01; ns, not significant by unpaired t-test with Welch's correction. n=23 (w; da-GAL4, btz/Df), n=6 (btz/+), n=10 (Df/+, UAS-BtzGFP/+; btz/Df), n=8 (btz/Df), n=22 (da>btz-GFP; btz/Df), n=13 (BG380-GAL4; btz/Df; BG380+24B>Btz-GFP; btz/Df; da-GAL4/+), n=5 (BG380>Btz-GFP; btz/Df), n=11 (24B-GAL4; btz/Df; da>btz RNAi), n=12 (24B>Btz-GFP; btz/Df; btz RNAi/+), n=9 (BG380+24B-GAL4; btz/Df), n=15 (BG380-GAL4/+), n=14 (BG380>btz RNAi; repo>btz RNAi), n=16 (mhc-GAL4/+), n=28 (mhc>btz RNAi), or n=21 (repo-GAL4/+). Error bars show mean ± SEM. NMJ size is reduced in btz mutants and rescued by expressing UAS-btz with da-GAL4 or with the combination of the BG380-GAL4 and 24B-GAL4 drivers, but not with any single driver. Expressing UAS-btz RNAi with da-GAL4 or in motor neurons with BG380-GAL4, muscles with mhc-GAL4 or glia with repo-GAL4 also reduces NMJ size.
Figure 4(I) quantifications of the number of boutons normalized to muscle surface area (x1000) in the indicated genotypes. ****, p<0.0001; ***, p<0.001 by unpaired t-test or Mann-Whitney test. n=15 (BG380-GAL4), n=12 (BG380>btz RNAi; BG380>mago RNAi; BG380>eIF4AIII RNAi), n=16 (btz/+), n=13 (btz/Df), or n=10 (Btz-WT; btz/Df; Btz-HD; btz/Df). Error bars show mean ± SEM. NMJ size is reduced by knocking down btz in motor neurons, but slightly increased by knocking down mago or eIF4AIII. The size deficit in btz mutants is equally well rescued by the wild type or EJC interaction-defective btz transgenes.
Figure 5(L) quantifications of the number of boutons normalized to muscle surface area (x1000) in the indicated genotypes. ****, p<0.0001; ns, not significant by unpaired t-test or Mann-Whitney test. n=19 (UAS-daw RNAi/+), n=9 (BG380>daw RNAi; btz/Df; tub>daw), n=23 (mhc>daw RNAi), n=10 (repo>daw RNAi; tub>daw), n=12 (btz/Df; UAS-daw), or n=14 (btz/Df; tub>btz). Error bars show mean ± SEM. Knocking down daw in motor neurons, muscles or glia reduces NMJ size. Expressing UAS-daw with tub-GAL4 rescues NMJ size in btz mutants as efficiently as expressing UAS-btz, but has no significant effect on NMJ size in a wild-type background.
Figure 1Immunofluorescence labeling of QSOX1 and a Golgi marker (GM130) in epithelial cells isolated from murine colon. QSOX1 is green, GM130 is red, and DAPI staining of nuclei is blue in the merged image. Scale bar is 10 µm.Top, average colon length of WT and QSOX1 KO mice following indicated treatments. For untreated mice, colon lengths were calculated for 3 WT and 3 KO. For treated mice, lengths were calculated from 5 mice except for the DSS-treated WT, for which 3 mice were analyzed. Error bars are standard deviation. Statistical analysis was performed using Tukey multiple comparison of means (** p<0.01). Administration of QSOX1 inhibitory antibody MAb316.1 (αQSOX1), did not enhance the sensitivity of WT colons to DSS (p>0.4 for MAb316.1-treated WT vs. WT control antibody (IgG)-treated; p>0.5 for MAb316.1-treated WT vs. WT without antibody treatment). Bottom, representative images of colons following DSS treatment. Scale bar is 1 cm.
Figure 3Representative TEM micrographs of about a hundred collected from 3 mice of each genotype show large and well-packed goblet cell granules in WT and QSOX1 KO colons. Scale bar is 5 µm.Alcian blue and PAS staining of reduced guanidine-insoluble mucins from WT and QSOX1 KO mice, separated on a 6% polyacrylamide gel. Data information: each lane corresponds to a sample from one mouse.Muc5b fluorescent immunoblot of WT and QSOX1 KO lung lavage samples separated on agarose gels. Data information: each lane corresponds to a sample from one mouse.Western blot analysis of blood Vwf from WT and QSOX1 KO mice separated on agarose gels. Data information: each lane corresponds to a sample from one mouse.QSOX1 immunofluorescence (green) in control (siControl) and QSOX1 knockdown (siQSOX1) MDA-MB-231 cells. Blue is DAPI staining of nuclei. Scale bar is 20 µm. Data information: The results described in are representative of 3 experiments that were performed.Western blot analysis of the MUC2 N-terminal region and indicated cysteine mutants in supernatants of transfected cell cultures. No differences in disulfide-mediated dimerization were observed for any MUC2 variant between siC (siControl) and siQ (siQSOX1). Data information: The results described in G are representative of 3 experiments that were performed.
Figure 4Western blot analysis of colon epithelial cell lysates from WT and QSOX1 KO mice. Lysates were treated with PEG-mal 2 kDa or NEM as indicated above each blot and probed using antibodies to St6gal1. As for panel A but using antibodies to St3gal1. As for panel A but using antibodies to B3galt5. Data information: For the experiments in panels A-C, equal amounts of total protein were applied to each gel lane, and no reducing agent was added. Experiments were repeated 3 times with fresh new lysates, and representative blots are shown.QSOX1 oxidizes St6gal1 in vitro. MAb492.1 is a monoclonal antibody that inhibits human QSOX1 St6gal1 with one pair of free cysteines is modified by two PEG-mal additions (2PEG), whereas protein with two pairs of free cysteines acquires four PEG-mal additions (4PEG). The change in migration per two PEG-mal modifications appears greater than 4 kD as expected due to the differences in hydrodynamic properties and SDS binding of PEG vs. protein QSOX1 oxidation of St6gal1 mutants. The C350-C361 disulfide (the redox-active disulfide present in the C139A-C403A mutant) is oxidized rapidly, while the C142-C406 disulfide (present in the C350A-C361A mutant) is oxidized slowly. Data information: Experiments were repeated 3 times with fresh new lysates, and representative blots are shown.
Figure 1(A) Kinetics of cell numbers in Lineage-EPCR+CD150+CD48- (L-ESLAM) HSCs, Lineage-EPCR+CD150+CD48+ (CD150+CD48+) progenitor cells, and Lineage-EPCR+CD150-CD48+ (CD150-CD48+) progenitor cells after the administration of 5-FU (250 mg/kg, i.v.). The small graph is an enlargement of 0 to 8 days after the administration of 5-FU. (* or **) in the small graph represents the statistical analysis of HSC between 3 and 4 or 7 days, respectively.
Figure 3(A) A principal component analysis (PCA) using the ATAC-seq data of HSCs in the steady state (untreated), early phase (5-FU 6d), or late phase (5-FU 10d).
Figure 4mRNA (C) in Acly in HSCs after the administration of 5-FU.protein (D), and phosphorylation levels of Ser455 (E) in Acly in HSCs after the administration of 5-FU.The levels of intracellular Glu (G) in HSCs obtained from untreated or 5-FU-treated mice.total acetylated lysine (I) in HSCs obtained from untreated or 5-FU-treated mice.
Figure 5(B-C) The effects of CTPI-2 (B) or BMS303141 (BMS) (C) on H3K27ac in HSCs in the early phase after the administration of 5-FU.(D-E) The effects of CTPI-2 (D), BMS303141 (BMS) (E), A-485 (D), and TV-3664 (E) on HSC expansion in the early phase after the administration of 5-FU. Numbers in the dot plots represent the frequencies of the indicated fractions within total BM cells.
Figure 7Global H3K27ac (A), Acly levels (B) in CD48- HSCs and CD48+ progenitor cells (HPCs)in the late phase after the administration of 5-FU.acetylated lysine (C), and ΔΨm (D) in CD48- HSCs and CD48+ progenitor cells (HPCs)in the late phase after the administration of 5-FU.
Figure 8(C) The frequencies of the CD150+CD48- and CD48+ fractions within the lineage-EPCR+ fraction after a 4-day culture of HSCs in the late phase with or without BMS303141 (BMS; 100 μM), SB204990 (SB; 100 μM), an alternative Acly inhibitor, or CTPI-2 (50 μM). (D and E) Total cell number (D) or CD48+ cell number (E) after the 4-day culture of HSCs in the late phase with or without BMS303141 (BMS), SB204990 (SB), or CTPI-2. Numbers within the graph represent the inhibitory effects of each treatment (fold decrease by an inhibitor treatment).
Figure 1B, C. Cryosections of samples from patients with prostate carcinoma and SCC of the lung. Samples were processed as described in the methods section. Ve=vessel, Tu=tumor. Scale 50µm. See also Fig 1D for comparative semi-quantitative analysis of a panel of samples from patients with prostate carcinoma, lung SCC and non-lung SCC.D. Semi quantitative analysis of binding of the PSMA antibodies 10B3 and J591 to cryosections from different tumor entities. For definition of the H-score reflecting binding intensity, refer to the methods section. Statistical analysis was performed using the paired, non-parametric Wilcoxon test. Sample size (n) and the corresponding P-values are indicated in the graphs.
Figure 2E, F. Binding of the Fabsc- and IgGsc-molecules to PSMA-expressing LNCaP (E) or 22Rv1low (F) cells was assessed by flow cytometry, as described in the methods section. The EC50 values were calculated using GraphPad Prism software and are presented below the figure.G-I. Binding of the Fabsc- and IgGsc-molecules to CD3-expressing Jurkat-cells (G) and to CD4 T cells (H) and CD8 T cells (I) in PBMC preparations was assessed by flow cytometry. The results represent the average of three independent experiments performed with different PBMC donors. EC50 values are presented in the table below the figure.
Figure 3BsAb were incubated at the indicated concentrations with PBMC of healthy donors together with LNCaP- expressing high and low amounts of PSMA, respectively. After three days, cytokine release were determined by flow cytometry as described in the methods section. Mean values and standard deviations of triplicate measurements are indicated.BsAb were incubated at the indicated concentrations with PBMC of healthy donors together with 22Rv1low-cells expressing high and low amounts of PSMA, respectively. After three days, cytokine release were determined by flow cytometry as described in the methods section. Mean values and standard deviations of triplicate measurements are indicated.
Figure 4B PBMC of a healthy donor were incubated with the indicated concentrations of bsAbs, and after three days cytokine release (B) were measured using a 3H-thymidine uptake- and a Legendplex assay, respectively. Mean values and standard deviations from triplicate samples.
Figure 5C-F. 64Cu labeled bsAbs were injected into NSG mice carrying 22Rv1high tumors (5 animals per group), and uptake at the indicated locations was determined by PET quantification over time (C, D) and at termination of the experiment after 48 hours (E, F) as described in the methods section. Error bars represent standard deviation of the mean value.
Figure 6B, C. 106 LNCaP cells were injected s.c. into the right flank of NSG mice (5 per group) and treatment with PBMC and bsAbs was started when tumors had reached a diameter of 5mm. BsAbs (2µg per dose) were applied at day 1, 8 and 15 (IgGsc) and daily at day 1-3, day 8-10 and day 15-17 (Fabsc), PBMC were applied at day 1,8 and 15. Mean values and standard deviations of five mice per group are indicated.
Figure 1(E) Peptide competition assay with a WT LxxIxE peptide or a mutated variant that does not bind B56 (LxxAxA). Binding of YFP-B56α to indicated proteins was determined and quantified by LiCor.(G) ﻿YFP-B56α pull down from cells stably expressing the indicated LxxIxE binding pocket variants of B56α and subsequent immunoblotting of indicated proteins. Representative of 4 independent experiments.
Figure 2(B) IP of YFP-B56α from cells stably expressing the B56α WT, R222E, and 5A followed by immunoblotting of indicated proteins. Representative blots are shown (top). hSgo1 signals were normalized to YFP and plotted (bottom). Error bars represent SD (n=4).(C) Reciprocal IP of (B). YFP-hSgo1 expression construct was transfected into cells stably expressing FLAG-B56α WT, R222E and 5A, followed by YFP IP and immunoblotting of indicated proteins. Representative blots are shown (top). B56α signals were normalized to YFP and plotted (bottom). Error bars represent SD (n=4).(D) Representative images of chromosome spreads from the indicated conditions. Scale bar, 5μm. (E) Quantification of (D). The distance between the two peak intensities of CREST was measured for 5 kinetochore pairs and averaged for a single cell and plotted. The data are from 4 independent experiments and the mean and SD are indicated.(F) hSgo1 RNAi and rescue with the indicated B56α variants fused to YFP and the Cenp B centromere-targeting domain (CB). Representative images of chromosome spreads are shown. CB targets all the rescue constructs (green) to the centromere. Scale bar, 5μm. (G) Quantification of (F). The distance between the two peak intensities of YFP was measured for 5 kinetochore pairs and averaged for a single cell and plotted. The data are from 3 independent experiments and the mean and SD are indicated.
Figure 3(D) Localization of B56α in cells depleted of hSgo1 and expressing the indicated YFP-hSgo1 variants. Representative immunofluorescent images are shown. Scale bar, 5μm. (E) B56α signal intensity was quantified. B56α signal from each cell was determined from 5 kinetochore pairs and normalized to YFP-hSgo1 signal. Each circle represents an individual cell, and the average and SD are indicated.(F) Mitotic U2OS LacO Haspin CM cells expressing hSgo1-LacI-GFP variants or LacI-GFP (control) were stained for PP2A-C. Scale bar, 5μm. (G) PP2A-C signal intensity was quantified, normalized to GFP, and then plotted. Each circle represents an individual cell, and the mean fluorescent intensity is indicated. Representative of at least 3 independent experiments.
Figure 4(A) Representative images of chromosome spreads from hSgo1 RNAi treated cells stably expressing the indicated YFP-hSgo1 variants. All the YFP-hSgo1 rescue constructs (green) localize to the centromeres (CREST, red). Scale bar, 5μm. (B) The distance between the two peak intensities of CREST was measured for 5 kinetochore pairs from the chromosome spreads in (A) and averaged for a single cell. The data are from 3 independent experiments and the mean and SD are indicated.(C) IP of YFP-hSgo1 from cells stably expressing hSgo1 WT, 3A, and 4A followed by immunoblotting of cohesin components, Smc1 and Smc3. Representative blots are shown (top). Signals were quantification by LiCor, normalized to YFP and plotted (bottom). Error bars represent SD (n=4 for Smc1 and n=3 for Smc3).(F) hSgo1 RNAi and rescue with the indicated hSgo1 RNAi-resistant constructs was performed. Representative still images captured during the live cell imaging showing DIC and YFP-hSgo1 WT, 3A, and 4A localization during mitosis. Time (min) from nuclear envelop breakdown (NEBD) is indicated. Scale bar, 15μm.
Figure 1(A) LC-MS/MS extracted ion chromatograms of 28 modified ribonucleosides analyzed in parasite tRNA. Signal intensities of the modifications are scaled to that for m1A, the ribonucleoside with the highest MS signal
Figure 5LC-MS/MS analysis was performed on T1-digested tRNA and deconvolution yielded precise masses of the unmodified (3055.425 Da) and modified (3143.43 Da) oligos for Glu-tRNAGAA (BCollision-induced dissociation of the parent molecular ions for m/z 1046.477-3 from Glu-tRNAGA produced expected -c, -w and -y ions for the sequences CU[mcm5s2U]UCACCCLC-MS/MS analysis was performed on T1-digested tRNA and deconvolution yielded precise masses of th unmodified (1835.20 Da) and modified (1923.262 Da) oligos for Gln-tRNACAA (E)Collision-induced dissociation of the parent molecular ions fo m/z 1923.262 from Gln-tRNACAA produced expected -c, -w and -y ions for the sequence CC[mcm5s2U]CCAARatios of modified oligonucleotides from the anticodon stem-loop o (H)GluGA isoacceptors expressed as percentages of their sum totalRatios of modified oligonucleotides from the anticodon stem-loop o (G)GlnCARatios of modified oligonucleotides from the anticodon stem-loop o (I)GlyGGA isoacceptors expressed as percentages of their sum total
Figure 6(A, B) Comparison of arbitrary translation efficiency (TE) values of (A) late trophozoite stage (TP 40) and (B) schizont stage (TP 46) proteins across all experimental time points. The arbitrary TE is defined here as the normalized protein abundance per mRNA abundance to mimic the translational output per mRNA copy in a biological system. The top 5% up-regulated proteins (n = 100) at (A) late trophozoite stage (TP 40) and (B) schizont stage (TP 46) were used for this analysis. Differences among all groups were first tested by one-way ANOVA analysis, followed by Dunnett's test as multiple comparison post-test to find significant differences between pairs of (A) TP 40 or (B) TP 46 and other time points. P<0.01 is denoted as **. P<0.0001 is denoted as ****. Scatterplots of mRNA and protein fold-changes (log-transformed) at time points (C) 40 h and (D) 46 h in the erythrocytic cycle. Quadrants are designated with roman numerals. Data points falling into quadrant I are designated as high translationally efficient (HTE) proteins while those falling into quadrant IV are designated low translationally efficient (LTE) proteins