EMBO/sd-character-level-ner huggingface dataset:
left panels. Superimposed single-cell traces representative of the effect of 100 μM D-Asp on [Ca2+]i detected in MO3.13 cells (A in absence or in presence of 10 μM MK-801 or 150 μM APV right panels. Quantification of the oscillation index in MO3.13 cells (A in absence or in presence of 10 μM MK-801 or 150 μM APV Quantification of the initial [Ca2+]i increase elicited by D-Asp measured as ∆% of peak versus basal values in absence or in presence of 10 μM MK-801 or 150 μM AP in M03.13 cells (a MK-801 and APV were preincubated 10 minutes before registration Data information: The values represent the mean ± S.E.M from 3 independent experimental sessions. Level of significance was determined by using: in A and a, one way-ANOVA P<0.001 followed by Bonferroni post hoc test, *P<0.05 versus control (basal value), ˄P<0.05 versus D-Asp. Data are reported as mean of 23-30 cells in each group, n=3 biological replicate
L) In situ hybridization for ISLR/Islr with RNAscope probes in mouse colon tumors from AOM-DSS model (L). t indicating tumor; a indicating adjacent tissues of tumor. Scale bar: 50 μm.
Read distributions of U1A-FUS-tRIP (left) and U1C-FUS-tRIP (right) around APA sites repressed [the first quadrant in (A)] or activated [the third quadrant in (A)] by both FUS and U1 snRNP. The p-values for the differences between repressed and activated APA sites are indicated by circles. Arrowheads indicate noticeable peaks of U1A/U1C-FUS upstream to the repressed APA sites.
(G) Representative immunoblots for Sar1, Sec23, Sec24D, and GAPDH, and relative protein levels of Sar1, Sec23, and Sec24D in control (solid bars) and IRE1-knockdown (open bars) cells at 24 hr p.i. GAPDH was used for normalization. The intensity of the bands was quantified using the MultiGauge software, and the results are shown in the bar graphs. The protein levels in control cells were assigned the value 1. Data are means ± SD from three independent experiments. *: p<0.05; **: p<0.01.
(A) Guide RNAs used to target the 5' end of exon 1 of the SLD5 gene in mouse ES cells. Each of the targeted sites contains 20 nt homology to the corresponding gRNA, followed by a 3 nt 'Protospacer Adjacent Motif' of PAM that has the form 'NGG' and is also required for cleavage by Cas9. Note that the predicted PAM site of gRNA1 has a polymorphism in E14TG2a ES cells, which prevents cleavage by Cas9 (B) The TAP or GFP tag was inserted after the initiator methionine of SLD5. The donor DNA also contained silent mutations in the first few residues of SLD5 (indicated in red), to prevent the modified locus being cut by Cas9.
B) Subcellular distribution of H3K9 MTs in the HP1-cTKO cells was examined by immunoblotting. α-Tubulin, Ezh2, and histone H3 were used as representative markers for each fraction. Stacked bar plots show the abundance ratios of H3K9 MTs among the three fractions (right).
Hepatoma HepG2 cells were treated with 30 µM 3,4-DC for the indicated time points (C,D). Then, cells were processed to measure LC3 and p62 protein levels by SDS-PAGE and immunoblot GAPDH was measured as a loading control. Band intensities of p62, GAPDH, LC3-I and LC3-II were measured and ratios of p62 or LC3-II versus GAPDH (LC3-II/GAPDH, p62/GAPDH) and LC3-II versus LC3-I (LC3-II/LC3-I) were calculated in D). Data are means ± SEM of at least three independent experiments (LC3-II/GAPDH: * = p < 0.05, ** = p < 0.01; p62/GAPDH: # = p < 0.05, ### = p < 0.001; LC3-II/LC3-I: $=p<0.05).
Immunoprecipitation of Protein C‐tagged LXRα from stable RAW 264.7macrophagenuclear extracts stimulated with 1 μM T0901317 or vehicle control for 18 h, followed by immunoblotting for endogenous NCOA5 or over‐expressed LXRα. Protein immunoblots of nuclear extracts are shown below.
(E) representative immunoblots analyzed using antibodies against the Fc-tag (for Nrxn1β-Fc) the 3G10 epitope (for the HS stub) and V5 (CA10-V5), as indicated. CA10 in input samples is shown for demonstration of equal expression. (F, Quantification of the 3G10 epitope signal normalized to Fc (for Nrxn1β-Fc) signals, Data shown are mean ±SEM of 3 biological replicates. *, p< 0.05; ***, p<0.001 by 2-way ANOVA and Holm-Sidak tests.
C Immunoblot analysis was performed during PRP8a immunoprecipitation (IP). The same volume of input, unbound fraction was loaded as well as 20 % of the eluted IP fraction. α-PRP8a and α-IgG : IP performed with anti-PRP8a or control rabbit IgG antibody, respectively.
(G) GST-pulldown of PLK1 from total cellular extracts using Cyclin B/CDK1 phosphorylated GST-EBNA2 region 342-422.
H: mRNA expression of SASP components in kidneys from young and aged mice. n = 6 for young and old mice, respectively. Data information: Data are means ± SEM. Statistical analysis: t-student test: young versus old mice.
(D,E) Metabolic 13C enrichments in BAT of male mice are shown as m+3 glycolytic intermediates (D), m+2 TCA cycle intermediates (E).
D) HEK293A cells stably expressing GFP-DFCP1 were treated as in (B), fixed and analysed by confocal microscopy. Scale bars = 20 μm. For quantification of (B), (C) and (D), 10 fields of view containing transfected cells were imaged for each of three experiments, and the number of GFP-LC3B, WIPI2 or GFP-DFCP1 puncta per cell enumerated using Imaris software (Bitplane).
H-I. Cells where treated as in (A) and where indicated 10μM H89 was added. Quantitative analysis of P-AMPK Ser485-491 phosphorylation (H) and of LC3-II/LC3-I ratio (I) during AICD are shown.
Colocalization of Stx represented by antibody staining with EB1-Gal4. Scale bar: 10um.
Flow cytometry analysis was carried out in microglia for (I) p-AKT T308. Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+ LY) was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.
(D) Quantification of the time a KT pair takes from the first contact with MTs until stable biorientation for neuroblasts (n≥12 KTs from at least 8 neuroblasts for each condition, n≥5 independent experiments). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: *, <0.05; **, <0.01; ***, <0.001; ****, <0.0001. Data are shown as mean ± SD.
A: mEPSC and mIPSC sample traces of recordings from deep CA1 pyramidal cells. B - E: Bar graphs of mEPSC and mIPSC frequencies and amplitudes in deep CA1 pyramidal cells. mEPSC frequency was not different in deep CA1 pyramidal neurons of adult (4 months) NexCre cTKO versus littermate controls (B, p = 0.6415). mEPSC amplitude was increased in deep CA1 pyramidal cells of NexCre cTKO compared to LM control cells (C, *p = 0.0363). mIPSC frequency was not different in deep CA1 pyramidal neurons of adult (4 months) NexCre cTKO versus littermate controls (D, p = 0.0564) and mIPSC amplitude was increased in deep CA1 pyramidal cells of NexCre cTKO compared to LM (E, *p = 0.0356). F: mEPSC and mIPSC sample traces of recordings from superficial CA1 pyramidal cells. G
Representative confocal microscope pictures of macrophages from SC-naïve (top) and COVID-19 patients (bottom). Nuclei are stained with DAPI (blue) and ASC speck are labeled by immunofluorescence staining (green). Macrophages were stimulated with LPS (left) and S-Protein (right) for 4h followed by stimulation with nigericin in both cases. Pictures were taken with a 60x objective using the same microscope settings.
Relative uc.291 quantification after RNA isolation from cytosolic and nuclear cellular compartments. snRNA U6 quantification was used as nuclear fraction positive control, while ACTB as cytosolic fraction positive control. Data shown are mean ± s.d.; n=3 technical on 1 of the 4 human donors used in panel (B); *p<0.05, **p<0.01, Student's t-test.
D Wet brain weight measurement of WT or Tau mice with (+TFEB) or without TFEB injection. n = 14 mice/group. ***P < 0.001 (2 way ANOVA with Bonferroni post hoc). Each bar represents average ± s.e.m.
Separase is sumoylated in response to DSBs. Hek293T cells transfected to express His6-separase (A were treated with DRB or carrier solvent (− DRB) and then subjected to denaturing IMAC followed by immunoblotting of input samples and eluates using the indicated antibodies
B) Average DNase I profiles of the 1217 iDHSs in TN (+/- PMA/I) and TB (+/-PMA/I) (left), and in TM (+/-PMA/I) (right).
(A) Exomer components localize to different extent to the TGN and to the cytoplasm. Fluorescence images of cells expressing GFP-tagged exomer components and TGN marker Sec7-DsRed. The brightness and contrast were adjusted differently in the GFP and merge images. Bar, 5 µm.(B) Quantification of the relative TGN to cytoplasm concentration of the GFP-tagged ChAPs in the cell. The mean fluorescence at the TGN and cytoplasm was determined using the Icy imaging software. 20-30 individual cells were analysed. For statistical significance testing the Student's T test was used.
D. Cell survival upon DSB induction. Average ± SD (n=4) is shown for each genotype.
Primary preadipocyes isolated from mice BAT were induced to differentiation in DMEM media with or without 1mM asparagine. Left: UCP1 and PPARγ protein levels were analyzed on day 6. Right: quantification of protein levels. n=3 biological replicates. Data information: Data represent means±SEM. *P<0.05; **P<0.01; unpaired two-tailed Student's t test.
(E and F) RAW264.7 cells were transiently transfected with control or miR-155 mimic for 24 h, and then incubated with a specific fluorescent dye MDC (50 µM). The MDC-labeled autophagic vacuoles were detected by confocal microscopy (E) and cells with MDC-positive autophagic vacuoles were quantified (F). Cells treated with rapamycin were used as a positive control. Arrows indicate the GFP-LC3 puncta or autophagic vacuoles labeled with MDC; scale bar = 5 µm. Data are shown as the mean ± SEM of three independent experiments (n = 300 cells). **, p<0.01; ***, p<0.001.
B. Small intestine and colon length from wild-type (n=4) and Angptl2-/- (n=5) mice 5 days after 12 Gy irradiation.
(C) Confocal pictures of whole‐mount retinae of a ftfd clone aged 7 days and expressing GFP∷Atg8a ubiquitously with Tub-Gal4. Red is phalloidin marking rhabdomeres, green is GFP and the clone is marked by the absence of β‐gal staining (blue). Small GFP∷Atg8a dots accumulate specifically inside ft mutant cells (arrow).
Chaining indices of the indicated genotypes. Statistical significance was compared with control. ; n = 9, 6, 7 (E) groups (10 flies per group). Courtship indices for one target (Canton-S) male and one tester male of the indicated genotypes. Changes were determined by comparing the data with control. ; n = 9, 8, 9 (F) flies. Sexual preference of single male of indicated genotypes toward a decapitated virgin female and a decapitated naïve male. Statistical significance was compared with the other gender. ; n = 10, 10, 10 (F) flies.
FRET histogram of all binding events from the construct containing a single PAM next to the partial target. Y axis represents total number of counts.
D, E | Absolute numbers of B cells in bone marrow (D) and spleens (E) from mice of the respective genotypes, determined by B220/CD19 surface expression. Mean ±SD, symbols indicate the numbers of B cells in individual mice (n). Statistical significance was calculated by using the Kruskal-Wallis test (see also Tables S2-3), n. s. = not significant; * p ≤ 0.05; *** p ≤ 0.001; **** p ≤ 0.0001.
(B) Western blot for CLU, Cdc25C, Cdc25C-T48, Cdk1, Cdk1-Y15 and Wee1 in IGRCaP-1 and PC3 parental (WT) or cabazitaxel-resistant (R-caba) cells as well as for PC3-R-caba cells transfected with siSCR or siCLU. Vinculin was used as loading control.
cell lines were transduced with either control (sgNon-targeting) or sgSLC1A3. Aspartate uptake levels were determined and compared between control and SLC1A3 KO in these cell lines. Leucine uptake level was used for normalization. The numbers above the control column denote the basal aspartate uptake capacity. Data information: Results were calculated based on three replicates (except for SUM159 and BT549 in B, n=2) and presented as mean ± SD. The p-value was calculated by two-tailed unpaired t test in Prism7. **p<0.01, ***p<0.001. a.u. indicates arbitrary unit.
D S. cerevisiae hsp42Δ btn2Δ cells expressing either GFP or LuciDM‐GFP and Htb1‐mCherry were grown at 30°C and heat‐shocked to 37°C for 30 min. Line intensity plots of luciferase‐DM‐GFP and Htb1‐mCherry before and after heat shock are given. The ratio of nuclear and cytosolic luciferase‐DM‐GFP fluorescence intensity was determined at 30°C and 37°C (n > 25). Scale bars, 2 μm.
(D) Quantitative analysis of normalized average intensity of DCLK1 in regions of interest of DIV10 neurons transfected with DCLK1 sh#1 (n = 16 neurons), DCLK1 sh#2 (n=16) and DCLK1 sh#3 (n=18). Non-transfected cells were taken as a control (n = 48). N=2. Error bars indicate SEM; *** - p < 0.001 (1-way ANOVA followed by a Tukey's Multiple Comparison Test).
E Overabundance of MIAA in LAM patients not treated with rapamycin relative to rapamycin-treated (number (n) of samples are indicated). The asterisk indicates significant difference based on two-sided Mann-Whitney test (P = 0.043). Average values are indicated with lilac-colored lines.
C-E. M-MOPS (C), primary mouse microglia (D) and hIPSC (E) (blue: P522 and red: R522) were loaded with Fluo-8 Ca2+ indicator and examined for peak changes in fluoresce after exposure to DOPS-liposomes (25 μg/ml). Data information: Data shown as the mean±SD of 3 independent experiments. The data were analysed by two-way ANOVA with Sidak's post-tests (*=p<0.05, **=p<0.01, ***=p<0.001).
F. The existence of LncBMP4 was confirmed by Northern blot, the results showed that LncBMP4 was significantly expressed in PGCs, but weakly expressed in CEF and ESCs.H2O was used as a negative control (n = 3 independent experiments).
C. Quantification of KCl-evoked FM 1-43 uptake with different stimulation times.
(A) ACE2-Fc blocked the entry of Spike-expressing pseudotyped lentivirus into HEK293T-ACE2 and H1975-ACE2 cells. The relative luciferase activities, normalized to the only virus group, represent the efficiency of virus entry. MOI: Multiplicity of infection.
(g) Normalized results of four independent experiments (n = 4) identical to e. Error bars represent s.e.m. Uncropped images of blots are shown in Supplementary Fig. S3.
A, relative expression of CD14+ and CD16+ in CD14+CD16+ sub-communities, depicted as boxplots of the mean expression levels for all samples (n = 42 patients × 2 timepoints = 84 samples), indicates that sub-community 1 has a CD14+CD16++ (aka "non-classical") phenotype, while sub-community 2 has a CD14++CD16+ (aka "intermediate") phenotype. Differences shown here are significant at FDR < 0.05 (moderated paired t-test, mixed effects model); for a view of all differences significant at this threshold
Quantification of long-lived protein degradation assay in TCHP knock-down and control cells by flow cytometry (one-way ANOVA; **p=0.0018 vs control, ##p<0.0001 vs shTCHP).
A Experimental workflow for MPRA: oligonucleotide library is cloned into an empty vector and a reporter gene and promoter are inserted using restriction sites within the oligonucleotide. The assembled plasmid is transfected into primary CD4 T cells and RNA is extracted after 24 hours. RNA barcode counts are normalised to their respective counts in the input plasmid library (DNA), which is sequenced separately.
(A) ELISA of supernatant IL-1β for unprimed THP-1 cells (UT) or LPS-primed (500 ng/ml, 3 hrs) THP-1 cells then infected with ZIKV (MOI=1) for 36 hrs. Uninfected cells serves as mock control.
(C) Cells were fixed and permeabilized then stained with antibody to LC3B (green) and Hoechst 33342 (blue). Scale bars indicate 10 µm. Left, representative fluorescence microscopy images. When puncta are not present, LC3B staining gives rise to a diffuse cytoplasmic pattern. Right, percentage of cells with LC3B puncta. Bar charts are presented as the means ± s.e.m., n = 6.
D. Weights of tissues related to energy metabolism normalized to their body weights in WT and TRPV2KO mice (n = 15).
A) Relative expression of α-tubulin and β1-tubulin in platelets from P1 and P3 (homozygous p.P160L), P4 (heterozygous p.Y106X), and P6 and P7 (heterozygous c.35delG) was quantified by Western blotting using specific antibodies against α-tubulin or β1-tubulin. With both mutations, α-tubulin expression was normal but β1-tubulin expression was significantly decreased. The β1-tubulin antibody recognizes C-terminal domain
A, Immunoblot of the indicated proteins of BNGE from female scaf1+/+ and scaf1-/- whole zebrafish mitochondria for the indicated diet (representative of n=2).
Day 7 midgut oocyst counts from mosquitoes infected with parasites, including 17XNL, Δap2-o3, Δmap2, or Δnek4 strain alone as well as mixtures of Δmap2/Δnek4, Δap2-o3/Δmap2, and Δap2-o3/Δnek4. Δnek4 and Δmap2 are female and male gamete-defect parasites, respectively. n is the number of mosquitoes dissected, Mann-Whitney test applied, two experiments repeated.
B) H3K9me3 ChIP-qPCR in the ABCB1 promoter region. Bar graph show primer pairs amplifying the sgRNA#6 break and spanning this region (+/- base pairs) for each Taxol-resistant clone compared to the parental. Bar plots show the mean of H3K9me3 relative enrichment. Each dot represents a technical replicate (n=3).
(H) Surface plasmon resonance binding kinetics of increasing concentrations of 4D9 antibody to mouse TREM2 ectodomain evaluated by BIAcore, Kon = 5.9 x 105 M-1s-1, Koff = 4.0 x 10-5 s-1, KD = 68 pM. 4D9 binding to human TREM2 or mouse TREM1 was undetectable.
(B) HeLa cells were incubated for 1 hr at 37°C or 18°C to reach the correct temperature, loaded with transferrin Alexa-555 for 1 hr, fixed, and labeled with anti-ATG9 and anti-TGN46 (marker for Trans Golgi Network). Histogram shows Pearson's coefficient between ATG9 and transferrin (Tf) or TGN46. Error bar, SEM. ∗∗∗p < 0.001. Inserts show merge at higher magnification.
C. The in vivo aminoacylation level of hTrmt13 substrate tRNAs assayed by Northern blot. The samples were also deacylated (DA) by incubating with alkaline buffer (pH 9.0) to obtain fully uncharged tRNA control.
(b-o) All panels show retinal flat mounts except for i and l. Green signal indicates PNA expression and red signal indicates red/green or blue opsin. The wild-type retina is shown at P35 in b-d. Red/green opsin (b) and PNA (c, d) expression were detected both dorsally and ventrally, whereas blue opsin (c,d) was detected only ventrally.
D HT-29 control cells and RIPK3 KO cells re-expressing PAM-mutated Dox-inducible RIPK3 WT were incubated overnight with 1 µg/ml Dox. Cells were pre-treated with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 2 h, as indicated. Strep-RIPK3 was immunoprecipitated using anti‑Strep-beads and the indicated co-immunoprecipitated proteins were analyzed by Western blotting. β-Actin served as a loading control.
(a) Representative co-immunoprecipitation results showing the effect of thioperamide on the interaction of H3R with CLIC4 during OGD/R. Full-size blots are shown in Supplementary Fig. 14.
C. Characterization of the indicated thymic T cell populations in the bone marrow of 4 wildtype and 4 Shld2−/− littermate controls.
(A) Schematic diagram outlining the generation of CRISPR/Cas9-mediated Pogz+/∆ mouse model. A region spanning critical exons 9 and 10 of the murine Pogz gene on chromosome 3 was deleted using dual sgRNA CRISPR.
(E) IRF2BP1, IRF2BP2, IRF2BP1+IRF2BP2 were knocked-down in HeLa cells for 72 hours and gene expression data were recorded by microarray analysis; non-targeting siRNAs were used as a control. IRF2BP1 and IRF2BP2 have distinct and overlapping functions. Experiments were done in triplicates.
C-E BR signaling is enhanced in the 35S:BZR1-MYC/35S:BIC1-YFP plants. Seedlings were grown for 6 days on medium supplemented with 1 μM brassinazole (BRZ) plus a gradient of concentrations of epibrassinolide (eBL) under long-day conditions. Images of the representative seedlings when grown with 500 nM eBL (+eBL) or not (-eBL) are shown in (C), and the hypocotyl lengths of the indicated genotypes were measured and are shown in (D) and (E). Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.
D. Hippocampal neurons (DIV16) co-expressing HA-VAPB with GFP-SCRN1-Y40A, GFP-SCRN1-F144A, GFP-SCRN1-F153A or GFP-SCRN1-F402A. Scale bars: 10 µm (full size) and 5 µm (zoom).
Representative images showing the effect of LATS2 on the morphology and β-galactosidase activities in cultured primary hOSE cells at the 9th passage.
(A) Quantification of cystine levels (nmol/mg protein) in control (CTNSWT) (n = 4), CRISPR-generated cystinotic cells (CTNS-/-)(n = 6), and patient-derived cystinotic cells (CTNSPatient) (n = 4).
D IF microscopy was performed as in (A) to quantify the percentage of late G2/prophase cells containing GMGs (mean ± SD, n = 3 independent experiments, 40 cells were analyzed per experiment and condition). Data information statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.
ISX transcriptionally activates luciferase activity driven by TWIST1 (c) promoter regions in A549 cells. Data are presented as mean ± SD in bar graph (p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate.
(E) (Top) 2D slice through STA transverse view of T. agilis microtubule triplet, with insets showing position of pinhead (dashed green box) and A-C linker (dashed red box). (Bottom) Longitudinal 2D slice of STA centered on the pinhead (left) or A-C linker (right). (F) Transverse view of T. agilis microtubule triplet STA. Microtubule protofilament numbers are indicated, as are the pinhead and A-C linker (only the C-link is visible; the A-link lies on the edge of the volume and is thus less well resolved in this STA -for better view see STA centered on A-C linker in (H)). Prominent microtubule inner densities (MIPs) within the A-microtubule are highlighted (empty arrowhead next to A9), as are additional external densities at the A-B and B-C inner junctions (black arrowheads). Double arrowheads point to viewing direction in indicated panels. (G) Longitudinal view of T. agilis STA centered on the pinhead from the viewing point indicated in (F). The pinfeet (PinF1 and PinF2) and pinbody (PinB) are indicated, as are microtubule protofilaments A3/A4. The average distance between pinfeet elements is 8.4 ± 0 nm in each case (both N=3). Corresponding transverse views are shown below, illustrating the connection of PinF2 with protofilament A3. (H) Longitudinal view of T. agilis STA centered on the A-C linker from the viewing point indicated in (F). Microtubule protofilaments A8/9 and C9/C10 of two adjacent triplets are indicated, as are the connected A- and C-links. The average distance between A- and C-links is 8.4 ± 0.3 nm and 8.4 ± 0.9 nm (N=6 and N=5, respectively). Corresponding transverse views are shown below, chevrons point to connection; the connection of the A-link with A9 is only partially visible in the transverse view at this height, as indicated by the dashed chevron.
(a-d) Rotenone (Rot) increased the number of GFP-LC3 puncta and the level of co-localization with mitochondria (arrows) in SH-SY5Y cells (a-c; 1 μM) and primary cortical neurons (d; 250 nM), quantified in Fig. 3f and Supplementary Fig. S1b,c. Veh, vehicle.
PLS regression analysis of codon usage of HTE (n=100) versus LTE (n=100) proteins a H) TP 46 H) Visualized by X, Y correlation loadings. Outer and inner ellipses indicate 100% and 50% explained variance respectively. Percentages of observed variances explained by the PC-1 and PC-2 are indicated in parentheses along their respective axes
Double transgenic showing endothelial membrane (red) and endothelial cytoplasm (green). The cytoplasmic reporter was visible in the parent vessel but not in the kugel (unfilled arrowhead).
(B) Face (up) and profile (down) photographs for patients II.4 (a: 8 yo, b: 16 yo), II.2 (c: 6 yo, d: 14 yo) and II.7 (e: 1 yo, f: 7 yo) over time. One can observe prominent supraciliay arches, synophris, sunken cheeks, short philtrum and retrusion in the malar region.