EMBO/sd-character-level-ner huggingface dataset:
Figure 8Semi-quantitative PCR of miR-132 and western blot analysis of ITPKB, phosphorylated (pERK1/2) and total ERK1/2, phosphorylated (AT8 , AT270) and total TAU, phosphorylated sphingosine kinase 1 (pSphK1), BACE1, full length APP (flAPP), APP CTFs and sAPPβ in human AD hippocampi (AD) compared to non demented control samples (ND). Sample size, n=39 for AD and n=15 for ND. Values were normalized to ND and presented as mean ± SEM. The Student's t-test was used.
Figure 3An autoradiograph showing radiolabeled PAR2-5A bands that were formed in reactions of OAS1 with the activator (pIC) and the acceptor PAR (lanes 11-14). Lanes 1-2 OAS1 only, lanes 3-6 OAS1 with activator pIC; lanes 7-10 OAS1 with substrate PAR; lane 15 negative control without OAS1. 32P-α-ATP was added to all reactions. Top: specificity of anti-2',5'A, as shown by ELISA. Synthetic 2',5'-p3A3, PAR2-5A #1, PAR2-5A #2 (2 different preparations of PAR2-5A). PAR and 3',5'-pA3 were used as competitors. Bottom: Dot-blot of synthetic PAR and 2-5A-PAR. In vitro synthesized PAR and PAR-2-5-A were applied in 1:2 dilutions (left to right) to nylon membrane and probed with anti-2-5A or anti-PAR. Immunostaining of PAR-2-5A synthesized in vitro. Reaction mixtures were resolved by electrophoresis in a polyacrylamide-8 M urea denaturing gel, transferred to a charged nylon membrane, and probed with mouse anti-PAR 10H (left panel) or rabbit anti-2-5A after stripping (right panel). XC: Xylene Cyanol (apparent size 150 nucleotides), BPB: Bromophenol Blue (apparent size 35 nucleotides). Lane 1, purified PARP1 alone; lane 2, PAR reaction: PARP1, activated DNA, NAD+, and histone; lane 3, 2-5A reaction: OAS1, pIC, ATP; lane 4, 2-5A and PAR reactions: OAS1, pIC, ATP and PARP1, activated DNA, NAD, histone. After incubation at 37oC for 60 min, the proteins were removed by digestion with proteinase K. Western analysis of PARP1 auto-modified with PAR in vitro in the absence or presence of OAS1. Reaction mixtures were resolved by SDS-PAGE, transferred to a charged nylon membrane, and probed with mouse anti-PARP1. Reactions were set up as in (C), but without proteinase K digestion. Lane 1, PARP1 alone; lane 2, PAR reaction: PARP1, activated DNA and NAD; lane 3, 2-5A reaction: OAS1, pIC, and ATP; lane 4, 2-5A and PAR reactions: OAS1, pIC, and ATP with PARP1, activated DNA, NAD and histone; lane 5, 2-5A and PAR reactions without ATP. The large smeary signals are due to PAR chains attached to PARP1 and the smaller sharp bands are free PARP1. The same blot was probed with anti-PAR, anti-2-5A and anti-OAS1. Western analysis of 2-5A precipitated with anti-PAR antibodies from lysates of H2O2-treated HME cells. Cells were treated with 500 M H2O2 for 12 min, and lysates were incubated with control (mouse IgG3) or mouse anti-PAR. Samples were probed with anti-PAR, anti-2-5A or anti-PARP1 antibodies. Flow-thr.: flow-through, WCL: whole cell lysate, IP: immuno-precipitate. Right panels (IP) show exposures for 10 x longer than left panels (WCL, flow-thr). Apparent MW (kDa) is indicated on the right. Experiments were repeated two times with similar results. Western analysis of 2-5A precipitated with anti-PAR antibodies from lysates of HME control, KO1 and TKO cells, and control cells pre-incubated with olaparib, treated with H2O2 for 12 min. Samples were probed with anti-PAR or anti-2-5A antibodies. Ponceau staining of the membrane is shown as loading control. Experiments were repeated four times with similar results.
IGF2R binding to CD20 is relevant for myogenic differentiation.Figure 2Bioinformatic prediction of IGF2R and CD20 cross-reactivity. Cartoon representation of the interaction of IGF2 (yellow) and IGF2R domain 11 complex from Xray structure (PDB code 2v5p). IGF2R domain 11 AB, CD, EF, HI loops and residues (shown in sticks format) involved in the hydrophobic interactions are shown (a). Bioinformatic prediction of IGF2R and CD20 cross-reactivity. Cartoon representation of the IGF2R domain 11- CD20 (lime) complex obtained from docking simulations and residues involved in hydrophobic interactions are shown in stick format (b). Bioinformatic prediction of IGF2R and CD20 cross-reactivity. The structure of IGF2R (in red) and IGF2 (green) are shown compared to docking poses of epitope 3. These data show that the helical region (residues 178-184) of the epitope mediates binding to the receptor as well as IGF2. The C-terminal helix of epitope 3 partially overlaps the first α-helix of IGF2. Cluspro-dock IGF2R-CD20 binding epitope poses corresponding to PDB codes 2v5p-2oslP, 2v5p-2oslQ and 2v5p-3pp4P are coloured in yellow, blue and cyan, respectively (c). (d) Over-expressing CD20 in C2C12 myoblasts that co-expressed CD20 (in green) and IGF2R (in red). DAPI-labelled nuclei are shown in blue. Scale bars=75 μm. (e) Representative CD20 and IGF2R immunoprecipitation products immunoblotted for IGF2R and CD20, respectively, in UNTREATED and shCD20-treated C2C12 cell membranes and whole lysates of proteins. The immunoprecipitation output is shown as IP neg. (f) Myotubes immunofluorescence of cells in proliferation medium (P.M.) and after 2, 4 and 6 days of myogenic differentiation in serum free medium. Control (untreated), shCD20-treated C2C12 cells, C2C12 and HSkM myoblasts pre-treated with anti-IGF2R for 24 hours were stained. Desmin-positive myotubes are shown in green. Scale bars=75 μm. (g) Fusion index quantification after 6 days of differentiation. One-way ANOVA. **p<0.01; ***p<0.001; ****p<0.0001. Each experiment was performed in triplicate wells. All values are expressed as mean±SEM. (h) Representative WB of anti-myogenin, anti-Myf5, anti-MyHC and anti-β-actin in total protein lysates obtained from untreated, shCD20-treated C2C12 cells, and C2C12 and HSkM myoblasts pre-treated with anti-IGF2R for 24 hours; cells were collected under P.M. and after 2, 4 and 6 days of myogenic differentiation. Densitometric analysis of WB data expressed as the ratio of the indicated antibody/β-actin in arbitrary units. Two-way ANOVA test. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 in comparison to the results obtained in untreated cells at the corresponding time point. ##p<0.01; ###p<0.001; ####p<0.0001 in comparison to the results obtained in shCD20-treated C2C12 cells at the corresponding time point. Each experiment was performed in triplicate wells. All values are expressed as the mean±SEM.
/- dendritic cells and antigen cross-presentation.Figure 3TAP1-/- BMDC transduced with vector control (A) or hβ2m (C) were incubated with varying concentrations of Epoxomicin for 6hr in absence or presence of exogenously added Kb-binding SIINFEKL peptide and analyzed for surface expression of Kb by flow cytometry. Representative plots are shown (A, C). The impact of Epoxomicin on cell surface Kb was analyzed by plotting Kb surface expression on cells incubated with Epoxomicin, normalized to that on cell incubated without Epoxomicin (n=3) (B, D). The effect of Epoxomicin on cross-presentation of OVA-coated beads by TAP1-/- BMDC expressing hβ2m was determined by incubating the BMDC with OVA coated latex beads in the presence of varying doses of Epoxomicin and 10μM gB peptide. After 6hrs the cells were fixed, incubated with B3Z cells and IL-2 production was measured
Pex14-containing vesicular structures mature into peroxisomes upon reintroduction of PEX3.Figure 4.(A) FM images of pex3 cells with Pex14-mCherry upon Pex3-eGFP reintroduction after shifting cells from MM-Glu with ammonium sulfate to MM-M/G with methylamine. (B-E) Live cell FM images of pex3 atg1 cells upon Pex3 reintroduction. Shown are pex3 atg1 cells producing Pex14-mCherry and PAMOPEX3-eGFP (B), PAMOPEX3.PEX10-GFP (C), PAMOPEX3.PMP47-GFP (D), or PAMOPEX3.PTEFGFP-SKL (E). Cells were grown similar to the method in A. The arrows in B-D indicate the first detectable GFP signal. Bars, 2.5 µm.
SHARPIN-deficiency leads HoipK778R/K778R mice to embryonic lethality, which is rescued by TNFR1 knockout.Figure 4Numbers of weaned mice of the indicated genotypes from crosses of Hoip+/K778R; Sharpin+/cpdm mice. Number of the embryos of the indicated genotype at E12.5 and E13.5 from crosses of HoipK778R/K778R; Sharpin+/cpdm mice. Gross appearance images of HoipK778R/K778R; Sharpin+/+, HoipK778R/K778R; Sharpin+/cpdm and HoipK778R/K778R; Sharpincpdm/cpdm embryos at E13.5. Representative pictures from 7 embryos each. Scale bars: 1 mm. Gross appearance images of Hoip+/K778R;Sharpincpdm/cpdm;Tnfr1+/-and HoipK778R/+; Sharpincpdm/cpdm ; Tnfr1-/- female mice at 6 weeks of age, and a female HoipK778R/K778R; Sharpincpdm/cpdm ; Tnfr1-/- mouse at 8 weeks of age. H&E staining, Keratin 14 (KRT14) and Cleaved Caspase 3 immunostaining of dorsal skin sections from mice of the indicated genotypes at 4 or 8 weeks of age. Scale bars: 50 µm.
Figure 6Kaplan-Meier survival plots for mice with indicated genotypes, number of mice, and median survival. Right panel, analysis of survival differences using the Log-rank (Mantel-Cox) test. Spectra of malignant tumors found in mice with indicated genotypes (p53-/- n=16; p53EE/- n=24; p53EE/EE n=37; p53+/- n=28; p53EE/+ n=17). p53 immunohistochemistry (IHC) in representative spontaneous tumors; scale bars 25 µm. Kaplan-Meier survival plots for Eµ-Myc transgenic mice with different p53 genotype. Kaplan-Meier survival plots for wild-type recipient mice transplanted with AML1/ETO9a + NrasG12D-transduced fetal liver cells (5 donors/genotype). p53 IHC for representative samples from (D) and (E) illustrates constitutive stabilization of p53EE in cancer cells; scale bars 25 µm.
A DSB in the promoter of ABCB1 causes gene upregulation and Taxol-resistanceA) Graphical representation of the ABCB1 genomic region and the location of the gRNA targeting the gene.Figure 1A) Graphical representation of the ABCB1 genomic region and the location of the gRNA targeting the gene. RPE-1 cells were infected with a Lentivirus carrying one of the gRNAs and after 7 days of puromycin selection one million cells were plate with 8nM of Taxol for Colony Outgrowth Assay. Taxol resistant cells were counted and plotted in the graph. n=3. B) Crystal violet staining of viability assay on RPE-1 Parental cells and Taxol resistant clones obtained from A. For the clones' nomenclature, sg# represents the sgRNA from where they are derived and C# the clone number. C) Western Blot showing the levels of the PgP and control (α-TUBB) in RPE-1 parental and Taxol resistant clones. D) ABCB1 mRNA levels determined by qRT-PCR and normalized to GAPDH expression levels. Each dot represents a technical replicate (n=3). E) Representative smRNA-FISH images of RPE-1 Parental and clones for the ABCB1 gene and DAPI. The images are projections of 0,5μm sections and a total 5 μm in thickness. Scale bar, 15μm.
Figure 1Schematic representation for the generation of ArCK cells. Time 0 is defined by the estimated onset of Mps1 inhibitor-induced chromosome mis-segregation. Representative images of euploid control or ArCK cells interacting with NK cells. The NK cell-mediated killing was measured at a 2.5:1 (NK cells: target cells) ratio and was recorded by live cell imaging for 36 hours at a 30-min interval. TO-PRO-3 (1 μM) was added to the medium at the same time of NK cell addition to measure cell membrane integrity. Phase contrast (top) and TO-PRO-3 signal (bottom) from the same field were presented. Arrowheads indicate ArCK cell death. All images were acquired at the same exposure time and light intensity. Scale bar 20 μM. Measurement of NK cell-mediated killing of ArCK and euploid control cells (Ctrl) at a 2.5:1 (NK cells: target cells) ratio. 50 randomly chosen target cells were followed for 36 hours by live cell imaging per condition per replicate. The cumulative cell death was calculated. n=3 biological replicates; mean± SEM. The statistical significance was determined using nonparametric Kolmogorov-Smirnov test (KS test) as described in the method section; p< 0.0001. Measurement of euploid control (Ctrl) and ArCK cell proliferation without NK cells. Live cell imaging of target cells without NK cells was performed using the same condition as described in the method section. For each condition, 50 cells were randomly chosen at the beginning of the movie as the initial population (indicated by the dashline, ninitial = 50). The cumulative cell number was recorded. Dot plot of individual data points and mean were presented; n=2 biological replicates. NK cell-mediated cytotoxicity across various NK cell to target cell ratios. Either euploid control (Ctrl) or ArCK cells were co-cultured with NK cells at the indicated NK cell: target cell ratios. The cumulative killing of target cells was measured. n=3 biological replicates; mean± SEM. p< 0.0001 for all four NK cell: target cell ratios, KS test.
RanQ69L partially rescues the IPZ-induced MI spindle disassembly (A) The rescue of the effects of 15 µM IPZ on MI spindles was examined in mouse oocytes expressing histone H2B-mCherry from microinjected mRNA, co-stained with SiR-tubulin and noninjected or injected with mRNAs coding for RanQ69L or hTPX2.Figure 5(A) The rescue of the effects of 15 µM IPZ on MI spindles was examined in mouse oocytes expressing histone H2B-mCherry from microinjected mRNA, co-stained with SiR-tubulin and noninjected or injected with mRNAs coding for RanQ69L or hTPX2. Maximum intensity z-stack projections from confocal live-cell movies 30 min after GVBD, at metaphase I and anaphase I. Time in hh: mm is relative to GVBD. Scale bars, 10 µm. (B-C) The frequency of GVBD (B) and anaphase I entry (C) quantified by live confocal imaging of oocytes stained and treated Fisher's exact test, oocyte numbers are shown in brackets. (D) Changes in spindle volume over time after GVBD. Means ± SDs, mixed-design ANOVA, oocyte numbers are shown in brackets.
Co-incubation of B16F10 melanoma with platelets results in Asm secretion and activation and ceramide release to mediate metastasis.Figure 2A Platelets were isolated from wild-type (WT) or Asm-deficient (Asm−/−) mice by density-gradient centrifugation, and 1 × 107 platelets were incubated with 1 × 105 B16F10 cells. The samples were lysed, and Asm activity was determined. In unstimulated samples (time point of co-incubation 0 s), tumor cells and platelets were admixed after lysis. B The formation of ceramide was determined by a diacylglycerol (DAG) kinase assay (upper panel) and mass spectrometry (lower panel). In unstimulated samples (time point of co-incubation 0 s), tumor cells and platelets were admixed after lysis. C, D For determination of the secretion of Asm by platelets into the supernatants (C), tumor cells and wild-type (WT) or Asm-deficient (Asm−/−) platelets were co-incubated for 20 s, the samples were pelleted, the supernatants were removed and acidified, and the Asm activity was measured in the presence or absence of Zn2+. For measurement of surface Asm and ceramide, samples were co-incubated as indicated (C, D) and pelleted; the supernatants were discarded, incubated with anti-Asm antibodies, washed, and lysed; and Asm immunocomplexes were immobilized and subjected to immunocomplex enzyme assays. Surface ceramide was measured by incubation of intact cells with DAG kinase in the presence of [32P]γATP followed by extraction and measurement of [32P]-ceramide. Omission of one cell type indicated by "−" here and thereafter. E Treatment of B16F10tumor cells for 2 min with 1 U/ml ASM or 10 μM C16ceramide restores in vivo metastasis in Asm-deficient mice. After treatment, the cells were injected intravenously into Asm-deficient (Asm−/−) mice. Controls were left untreated prior to injection. The number of metastases was determined 14 days after tumor cell injection.
BRAVO and WOX5 reinforce each other at the root stem cell niche.Figure 2Confocal images of PI-stained 6-day-old roots. GFP-tagged expression is shown in yellow. A-C) pBRAVO:GFP in WT (A), bravo-2 (B) and wox5-1 (C) knockout backgrounds. D-G) pWOX5:GFP in the WT (D), bravo-2 (E), wox5-1 (F) and bravo-2 wox5-1 (G) knockout backgrounds. Scale bar: 50 µm. Quantification of the GFP fluorescent signal of the roots in A-C (H) and D-G (I). Boxplot indicating the average pixel intensity of the GFP in the stem cell niche (n>25, 3 biological replicates, *p-value < 0.05 Student´s t- test for each genotype versus the WT in the same condition). Quantification was done by integrating the GFP signal in each root across defined areas that included the whole SCN (Appendix Figure S7). In the boxplot, box width represents the interquartile range (IQR=Q3-Q1), with the horizontal line denoting the median, while whiskers extend from Q1-1.5IQR to Q3+1.5IQR. White dots are the outliers and black dots are the experimental observations.
Figure 2A Anti-TK Western blot of ubiquitinated titin samples. B Reconstruction of the 3D-structure of the full-length kinase region of titin, A168-M1, achieved by overlapping the structure of A170-M1 in this work and that of the A168-A170 previous reported (PDB 2NZI). The presence of a flexible hinge region at the A170-NL junction can be predicted since the crystal structure of A170-M1 shows only few and weak interactions between A170 and TK. Otherwise, the A168-M1 titin segment is highly structured. Lysine residues ubiquitinated by MuRF1 (as identified by mass spectrometry) are marked in magenta. Sites found in denervated limb muscle from mice are boxed (Lang et al, 2017) and sites found in other in vivo studies are underlined
Figure 6A Summary of enriched Gene Ontology terms more potently upregulated by Gadd45a. The p-values represent the modified Fisher Exact corrected EASE score. B Heatmaps depicting the relative fold change of gene expression at 8 dpi by DNA microarray. Red and green colors indicate increased and decreased expression, respectively. C qPCR analysis of endogenous Oct4, Nanog or endogenous Sox2expression level during reprogramming with SKO plus Flag, wild-type Gadd45a or G39A Gadd45a. (**p≤0.01; ***p≤0.001; n=3)
Figure 6The CBioportal was used to query the DNA and RNA HR gene alterations found in the TCGA primary PCa data set. HR genes queried were BRCA1, BRCA2, RAD51, MRE11A, RAD50, NBN, RBBP8, EXO1, RPA1, RPA2, RPA3, XRCC3, BLM, RMI1, RMI2, TOP3A, GEN1, SLX4. Default settings were used Expression levels of indicated HR pathway genes in primary PCa vs normal patient samples. Violin plots represent FPKM normalized counts obtained from matched tumor and normal RNA-Seq data from TCGA (n=52) with p-values generated using paired t-tests The CBioportal was used to query the DNA and RNA HR gene alterations as above using the PCF-SU2C advanced PCa data set The CBioportal was used to query the DNA and RNA HR gene alterations as above using the PCF-SU2C advanced PCa data set, and the data are presented on a per patient basis
Divergent pathways promoted by PGE2 synergistically activate the transcription factor MEF2.Figure 8 Schematic representation of the PGE2 triggered signal transduction pathways converging on HDAC5 and subsequently MEF2. PGE2 activates MEF2 through EP3 receptor and the βγ subunit of Gi/o proteins. One pathway implicates activation of PKD and concomitant phosphorylation of HDAC5. The phosphorylated HDAC5 is exported from the nucleus, which results in de-repression of MEF2 and activation of the embryonic gene programs. In addition, hand in hand activation of Tiam1, Rac1 and PAK2 kinase occurs, which pathway also contributes to the nuclear export of HDAC5 and is responsible for synergistic activation of MEF2
Figure 6A Positive correlation of Fe (up) and Zn (down) content in Md/Mx and Md/Mb under Fe deficient and Fe replete conditions. Values are means ± SD, n = 3 (biological replicates). B Zn content in leaves of Md/Mx and Md/Mb under Fe deficient and Fe replete conditions. Values are means ± SD, n= 3 (biological replicates). Asterisks indicate statistically significant differences (***, P < 0.001, Student's t-test), ns = no significant difference. C Suppression of Zn2+ sensitivity in S. cerevisiae strain K667 (pmc1 vcx1 cnb1) determined by expressing sMdCAX3 (N-terminally truncated) and full-length MdCAX3 with or without MdCXIP1. Growth of a dilution series of yeast cells expressing the various plasmids on selection medium lacking histidine (−Ura) and spotted onto YPD medium containing 10 mM ZnSO4. The W303-1A expression of pYES2 (empty vector) were used as a positive control. D Cellular localization of Zn2+ (blue) in Mx and MdCAX3-suppressed Mx roots under Fe deficient conditions. Arrowhead indicates the cytoplasm. Scale Bars: 20 μm. E Fluorescence intensity detection at the position indicated by the long and narrow arrow in the Fig 6D. F Shoot phenotype of Md/Mx and Md/Mb under Fe deficient and Fe replete conditions. Scale Bar: 2 cm.
Analysis of autophagosomal maturation in HCV-infected cells.Fig 1(A) Western-blot analysis of HCV-infected cells at various time-points post-infection (p.i.) (m.o.i. = 1). Numbers under Rubicon and UVRAG panels indicate their protein levels at different time points relative to their levels in mock-infected cells (i.e., 0 hour p.i.). (B) Fluorescence imaging of HCV infected cells. Stable Huh7.5 cells that expressed mRFP-GFP-LC3 were infected with HCV and fixed at the time points indicated for the analysis of RFP and GFP puncta. Nuclei were stained with DAPI. The boxed areas were enlarged and shown to the right. (C) Upper panel, levels of RFP and GFP puncta after HCV infection relative to those in mock-infected cells, which were arbitrarily defined as 1. Lower panel, percentages of RFP puncta that were positive for GFP (i.e., Yellow/Red ratio). The results represent the average of >50 cells that were analyzed. (D) Fluorescence imaging of RFP, GFP and LAMP1 in HCV-infected cells expressing mRFP-GFP-LC3. The lysosomal marker LAMP1 was stained in blue color. DAPI was not used to stain the nuclei. The colocalization of RFP and GFP will generate the yellow color, and the colocalization of RFP with LAMP without GFP will generate the purple color. The boxed areas were enlarged and shown to the right.
a, Detection of wild-type (+) and Ambra1 gene-trap transcripts (gt) from total E14.figf1a, Detection of wild-type (+) and Ambra1 gene-trap transcripts (gt) from total E14.5 embryos analysed by northern blotting. Size marker, 28S ribosomal RNA. b, Immunoblot analysis of E14.5embryobrain extracts using antibodies against Ambra1 (left panel) and β-gal (right panel). Specific bands (arrowheads) and unspecific signals (asterisk) are indicated. Molecular weights are measured in kilodaltons (kDa). The fusion protein can be revealed only by means of the more sensitive anti-β-gal antibody. c-f, Expression of Ambra1 in the mouse embryonic nervous system. β-gal-staining on whole-mount Ambra1+/gt mouseembryos at E8.5 (c), E11.5 (d) and on a cross-section of E11.5spinal cord (e) is shown. Fb, forebrain; Hb, hindbrain; Mb, midbrain. f, Matching expression of the endogenous gene was revealed by whole-mount Ambra1 mRNA in situ hybridization analysis in E11.5 wild-type embryos. g-l, Electron scanning microscopy analysis of E11.5 (g) and E12.5 (h) Ambra1gt/gt embryos. Note the failure of the neural tube closure, the extensive midbrain/hindbrain exencephaly (Ex) with a closed telencephalon (T), and the lumbosacral spina bifida (Sb). i, j, E14.5 wild-type (i) and Ambra1gt/gt (j) embryos are characterized by prominent exencephaly. k, l, Histological analysis of E12.5 wild-type (k) and Ambra1gt/gt (l) embryos on cross-section. Note the absence of a normal ventricular system, the extensive overgrowth of the proliferative neuroepithelium in the diencephalon (Di) and spinal cord (Sc), and the enlarged fifth ganglia (VG) in the Ambra1gt/gt embryo. m-p, TUNEL (TdT-mediated dUTP nick end labelling) staining of E10.5brain (m, n) and E9.5spinal cord (o, p) in wild-type (m, o) and Ambra1gt/gt (n, p) embryo sections. q-t, Analysis of cell proliferation in wild-type (q, s) and Ambra1gt/gt (r, t) embryos on transverse sections of E8.5cephalic neural folds in prospective hindbrain region (mitoses, arrows in q, r) and on sagittal sections of E10.5forebrain (BrdU uptake, s, t).