EMBO/sd-character-level-ner huggingface dataset:
Figure 5(A) Microtubule triplet reconstruction from the beginning of the proximal region, displayed with a low contour threshold value to show the triplet base density (green) connected to the pinhead (purple) and the A-C linker (turquoise). (B) Two adjacent triplets from the beginning of proximal region, displayed with a higher contour threshold than in A. The A-C linker is segmented into different substructures (patterned turquoise colors) according to nomenclature (Li et al., 2019). The green dashed line indicates the putative position of the triplet base. Non-tubulin densities are colored in dark salmon and dijon. The pinhead has been hidden in this view, as its reconstruction is not correct due to the 8.5 nm initial subvolume picking that imposes this periodicity on the structure. (C) Three-dimensional side view of the A-C linker from the lumen of the centriole. (D) Three-dimensional side view of the A-C linker from outside the centriole (rotated 180o from C). (E) Top views of independent averages from the more proximal (grey) and more distal (blue) parts of the P. tetraurelia proximal region. (F) Focus on the A-C linker from the most proximal region (left, grey), the most distal proximal region (middle, blue), and the superimposition of both structures (right).
Figure 6 CPEB2-WT and -KO mice were transduced with adeno-associated virus (AAV) expressing full-length (AAV_CP2) or RNA-binding domain (AAV_RBD) of CPEB2. Immunostaining of CPEB2 and UCP1 in KO BAT transduced with AAV_CP2 for 2 weeks, with Hoechst staining of nuclei. Scale bar, 10 µm. See more images in Fig EV4D   Western blot analysis of UCP1 in BAT lysates from WT and KO male mice 2 weeks after AAV transduction (n = 6 mice per group). *p < 0.05, Student's t test  BAT temperature of WT and KO male mice after 2 weeks of AAV transduction measured during 12-h light time (n = 7 mice per group). *p < 0.05, Student's t test   BAT temperature in WT and KO male mice, and of AAV_CP2-transduced WT and KO male mice (n = 7 mice per group) before and after i.p. injection of CL316243 (CL). * p < 0.05, repeated-measures two-way ANOVA   CPEB2 activates polyadenylation-induced translation of mouse Ucp1 mRNA with long 3'-UTR via β3AR signaling for adaptive thermogenesis in BAT. Mice lacking the translational regulator CPEB2 show impaired BAT thermogenesis
Figure 3Mixed WT:DKO BM chimeras established as in Figure 2A were injected with EdU on three consecutive days. EdU incorporation was analyzed one day after the last injection. Steady-state WT and DKO mice were injected with EdU and analyzed as in A. Representative flow cytometry plots of EdU incorporation by AMs (C) and their quantification (results pooled from two independent experiments, 7 WT and 6 DKO mice were analyzed in total) (B) is shown. WT (CD45.1) and DKO (CD45.2) AMs were sorted, mixed in a 1:1 ratio, labeled with CellTrace Violet and cultured in the presence of GM-CSF. The ratio of CD45.1 and CD45.2 cells and CellTrace Violet dilution was analyzed prior to culture (day 0) and after 7 days of culture as described in Materials and Methods. RNA-seq analysis of Maf and Mafb expression in WT and DKO AMs, which were isolated by flow cytometry from mice in steady state (top) or from mixed BM chimeras (bottom).
Usp26-deficient mice produce 41, XXY offspringA Sequences of the WT and Usp26 mutant alleles in mice.Figure 2A Sequences of the WT and Usp26 mutant alleles in mice. B The USP26 protein was absent in Usp26-/Y testes. Immunoblotting of USP26 was performed in Usp26+/Y and Usp26-/Y testes. Histone 3 served as the loading control. C, D The fertility of Usp26-/Y mice was reduced with increasing age. The fertility assessment experiments were performed in 2-month-old Usp26+/Y, Usp26-/Y mice (n =5 independent experiments) and 6-month-old Usp26+/Y, Usp26-/Y mice (n=5 independent experiments) (C). The litter sizes were observed in 2-month-old Usp26+/Y, Usp26-/Y mice (n=14, 22 independent experiments for Usp26+/Y and Usp26-/Y, respectively) and 6-month-old Usp26+/Y, Usp26-/Y mice (n=10, 8 independent experiments for Usp26+/Y and Usp26-/Y, respectively) (D). Red dots indicate Usp26+/Y mice and green dots indicate Usp26-/Y mice. E Genotyping of Usp26-/Y mice offspring. The upper subpanel indicates the genotyping of Usp26-/Y mice male offspring by using Usp26 and Sry primers. The lower subpanel indicates the genotyping of Usp26-/Y, Usp26+/Y male mice and Usp26+/-, Usp26+/+ female mice by using Usp26 and Sry primers. F The wild-type (WT) and Usp26 knock out alleles in XUsp26+XUsp26-Y mice. G The proportion of 41, XXY mice among the male offspring of 2-month-old Usp26+/Y, Usp26-/Y and 6-month-old Usp26+/Y, Usp26-/Y mice (n=14, 22, 10 and 8 independent experiments for the offspring of 2-month-old Usp26+/Y, Usp26-/Y mice, 6-month-old Usp26+/Y, and Usp26-/Y mice, respectively). Red dots indicate Usp26+/Y mice and green dots indicate Usp26-/Y mice. Two pair of X chromosomes could be detected in the 2-month-old XUsp26+XUsp26-Y spermatocytes. FISH analysis of Chr X-FISH (green) and Chr Y-FISH (red) was performed in WT and XUsp26+XUsp26-YY spermatocytes (H). The arrows indicate the Y chromosome and the arrowheads indicate the X chromosome. Nuclei were stained with DAPI (blue). Immunofluorescence analysis of Chr X-FISH (green), Chr Y-FISH (red), and SYCP3 (white) was performed in WT and XUsp26+XUsp26-YY spermatocytes (I). The arrows indicate the Y chromosome and the arrowheads indicate the X chromosome. Nuclei were stained with DAPI (blue). Three sex chromosome axes could be detected in the 2-month-old XUsp26+XUsp26-Y spermatocytes. Immunofluorescence analysis of SYCP3 (red) and SYCP1 (green) in (J), ATR (red) and SYCP3 (green) in (K) was performed in 2-month-old WT and XUsp26+XUsp26-Y spermatocytes. Nuclei were stained with DAPI (blue).The arrows indicate the Y chromosome. The arrowheads indicate the X chromosome. Three sex chromosome axes could be detected in the 2-month-old XUsp26+XUsp26-Y spermatocytes. Immunofluorescence analysis of BRCA1 (red) and SYCP3 (green) in (L) was performed in 2-month-old WT and XUsp26+XUsp26-Y spermatocytes. Nuclei were stained with DAPI (blue).The arrows indicate the Y chromosome. The arrowheads indicate the X chromosome.
Figure 2(A) Representation of the zebrafish adult brain shows the lateral and dorsal view with abbreviations for the following domains: olfactory bulb [OB], telencephalon [Tel], epiphysis cerebri or pineal [E], optic tectum [TeO], cerebellum [Ce], medulla oblongata [MO], hypothalamus [H] and hypophysis [Pit]. Transcriptome sequencing was performed on cDNA from wild-type and opn4 dko eyes and brains, sampled in the light phase (ZT4-6). The brains were separated in an anterior part, which includes part of the forebrain and the pineal, and a posterior part, which includes part of the forebrain and the whole mid-hindbrain. The cut lines through the depicted brain indicate where the brain was partitioned and which parts were subjected to transcriptome sequencing. The blue (anterior brain) and grey (posterior brain) arrows connect the brain parts in A with the differentially expressed genes in B. (B) Venn diagram shows the number of differentially expressed genes in the opn4 dko anterior brain (dark blue circle), posterior brain (grey circle), and eye (light blue circle). The cutoff for differential expression was set at a significance level of α=0.05. Heat maps of all the differentially expressed genes are presented in Appendix Figure S1A-C. The number of differentially expressed genes that are shared between the data sets is indicated where the datasets overlap. (C) Fisher's exact test shows that the shared differentially expressed genes between data sets are unlikely to be the result of coincidence. P-values for the common differentially expressed genes are indicated where the datasets overlap. The large number of common differentially expressed genes between the anterior and posterior brain parts is likely due to forebrain regions that are shared between these data sets. (D) Pie chart shows the number of differentially expressed genes in the opn4 dko anterior brain that were assigned with KEGG software to phototransduction (dark blue), metabolic (orange) and other pathways. Of the metabolic pathway, 5 genes were assigned to the subcategory tryptophan metabolism (red), which encode all the enzymes that convert tryptophan into melatonin. Note that 189 genes were not assigned to a pathway. (E) Ancestor charts show the gene ontology attributes to which the differentially expressed genes in the opn4 dko anterior brain were assigned with FuncAssociate software (cutoff: α=0.05). The number of genes assigned to an attribute is indicated in the upper right corner. All retrieved biological processes and molecular functions are associated with light, consistent with knockout of a photoreceptor.
Figure 4The competition model is an extension of the monoculture model. (i.) Species have the same growth, lags, and resource consumption as in monocultures, but now compete for the same resource pool. (ii.) After saturation, population sizes are divided by the dilution factor (104 in this figure) and resource concentrations are reset to the supply concentrations. With parameters matching those used experimentally in Fig 1C, the growth-lag model predicts coexistence of Aci2 and Pa on alanine and glutamate, as observed in competition experiments. Model prediction of growth rates and population sizes over the course of one day after the 1:1 alanine:glutamate co-culture has reached steady state. Pa starts the day with a population fraction of 0.42, declines to a population fraction of 0.07 at alanine depletion, and recovers to a population fraction of 0.42 by the time glutamate is depleted. The alanine and glutamate resource depletion times vary with the (start-of-day) population fractions due to different resource preferences and initial growth rates. These variations modulate the relative fitness of the two strains and in doing so facilitate a negative-frequency dependent interaction that stabilizes coexistence. Relative Fitness of Pa is calculated as its fold growth over the course of a day divided by Aci2's fold growth and shown as a function of its population fraction at the start of the day. The model predicts the competitive outcome will depend on the resource supply fractions with exclusion occurring as the supply approaches entirely alanine or entirely glutamate.
Yip1A-knockdown prevents maturation of B.Fig 7(A) Representative electron micrographs of Brucella-infected control (left-hand panel) and Yip1A-knockdown (right-hand panel) cells at 24 hr p.i. Insets are magnifications of the boxed areas on the main image, showing the typical forms of BCVs. In control cells, BCVs can be seen in the form of ER-derived membrane-bound compartments (inset in left-hand panel, defined as 'I'). Note the presence of ribosomes on the membrane (arrowheads). In Yip1A-knockdown cells, the bacteria were not sequestered into such compartments (inset in right-hand panel, defined as 'II'). Scale bars are 2 μm. (B) Representative electron micrograph of Brucella-infected IRE1-knockdown cells at 24 hr p.i. Inset is a magnification of the boxed area in the main image, showing that the bacteria were not sequestered into ER-derived membrane. Scale bar is 2 μm. ) The percentages of the two forms of BCVs (I and II) present in control and Yip1A-knockdown cells at 24 hr p.i. The total numbers of BCVs analyzed were 67 for control cells and 37 for Yip1A-knockdown cells. (D, E) Representative confocal micrographs of control (upper panels), Yip1A-knockdown (middle panels), and IRE1-knockdown (lower panels) cells double-stained for Lamp2 (a marker for late endosomes/lysosomes; green) and B. abortus (red) at 24 hr p.i. BCVs co-localized with Lamp2 are indicated by arrowheads. The infected cells are outlined with white dashed lines. Scale bars are 10 μm. The percentage of Lamp2-positive BCVs was determined, and is shown in the line graph (E). (D, E) Representative confocal micrographs of control (upper panels), Yip1A-knockdown (middle panels), and IRE1-knockdown (lower panels) cells double-stained for Lamp2 (a marker for late endosomes/lysosomes; green) and B. abortus (red) at 24 hr p.i. BCVs co-localized with Lamp2 are indicated by arrowheads. The infected cells are outlined with white dashed lines. Scale bars are 10 μm. The percentage of Lamp2-positive BCVs was determined, and is shown in the line graph (E). . (F) Magnification of the electron micrograph of the Brucella-infected control cell in (A), showing large vacuoles studded locally with ribosomes (arrows). (G-I) Representative confocal micrographs of Brucella-infected control cells at 24 hr p.i. triple-stained for HA-Sec61α (a marker for rough ER; green), B. abortus (red), and Lamp2 (a marker for endosomes/lysosomes; blue) (G). An expression construct for HA-Sec61α was co-transfected with scramble siRNA. The infected cell is outlined with white dashed lines. Scale bars are 10 μm. Magnifications of the boxed areas 'a' and 'b' are shown in (H) and (I), respectively. Large vacuoles adjacent to replicating bacteria were stained for both Sec61α and Lamp2 (H). B. abortus was co-stained with Sec61α but not with Lamp2 (I).
Figure 2The upper schematic illustrates the stage-specific supplementation of splicing inhibitor PLB and on day 8 CD43+ HSPCs were examined by flow cytometry. The bottom bar graph showing the normalized frequency of CD43+ cells to DMSO control under distinct PLB treatment windows. P-values were calculated by one-way followed by Dunnett's test. The top panel is a representative RT-PCR electropherogram depicting the inclusion or exclusion LAS1L exon 9 in cells at day 2 as well as cells at day 5 without or with PLB treatment with indicated concentrations, respectively. The quantification of percent spliced-in (PSI) was presented in the bottom bar graph. P-values were calculated by one-way ANOVA followed by Dunnett's test. The representative FACS plots show the generation of CD31+CD34+ EPCs at day 5 of differentiation upon PLB treatment from day 2.5 to 5. The frequency of CD31+CD34+ EPCs with PLB treatment in (C) was normalized to DMSO control. P-values were calculated by one-way ANOVA followed by Dunnett's test. Cell apoptotic level assessed using Annexin V and 7-AAD at day 5 of differentiation by flow cytometry. The cells were treated with or without PLB from day 2.5 to 5. The proportion of G0/G1, S and G2/M cells at day 5 of differentiation treated with or without PLB from day 2.5 to 5. The cell cycle was determined by flow cytometry with Propidium Iodide staining. The experimental schematic (upper panel). APLNR+ cells on day 2 were FACS-purified and treated with various dosages of PLB from day 2.5 to 5 during inducing hematopoietic differentiation. On day 5, the generation of CD31+CD34+ EPCs and CD31+CD34+CD73- HEPs were assessed. The representative FACS plots showed the frequency of APLNR+ cells, CD31+CD34+ EPCs and CD31+CD34+CD73- HEPs without or with PLB treatment. The bar graphs show the percentage of CD31+CD34+ EPCs and CD31+CD34+CD73- HEPs without or with PLB treatment.
MERTK is a prognostic marker in CRC patients.Figure 6(A) Western Blot visualising MERTK expression in two negative (RKO, CC07) and two positive control cell lines (CaCo-2; HT55). (B) IHC staining of MERTK expression in RKO (negative control) and CaCo-2 (positive control) cells. (C) IHC staining of three representative TMAs from patients enrolled in the QUASAR 2 clinical trial and the corresponding quantification of the signal by pathologists. (D) Kaplan-Meier plots showing worse overall, disease-free and recurrence-free survival of patients with high cytoplasmic/membranous expression of MERTK.
LT-HSC restore protein synthesis and proliferative function upon transplantation to a non-leukemic host.Figure 5A diagram showing the scheme of repopulation experiments on non-leukemic host. KSL were purified from Molm-14-xenografted male mice (red), or control males (black) and transplanted into 150cGy sub-lethally irradiated female recipients (104 cells per mouse) CFU-C assay showing the relative number of colonies (left panel) and the colony subtypes (right panel) from KSL cells derived from Molm-14-xenografted mice (red, n=6) vs. non-engrafted control mice (black, n=5) and in vitro cultured for 7 days in methylcellulose media. Experiments were performed in technical triplicates. "G" Granulocyte, "M" Monocyte, "E" Erythrocytes. LT-HSC assessment after repopulation, recipient female mice (n=4 per group) were sacrificed after 21 days and their LT-HSC were compared using P53, pS6RP and OPP flow cytometric assays. (D-E) Evaluation of the in vivo long-term repopulation capacity. Evaluation of the in vivo long-term repopulation capacity. For secondary transplantation (n=6 per group), PB samples were collected twice weekly for 12 weeks (WK) and the donor chimerism was measured by qPCR of Sex-determining Region Y (SRY) normalized to Gapdh gatekeeper as shown in the left panel. Sixteen weeks later, mice were sacrificed and BM male chimerism percentage was assessed as shown in the right panel. Tertiary transplantation, unfractionated BM cells from the secondary recipients (n=6 per group, 106 cells per mouse) were injected into tertiary 150cGy sub-lethally irradiated female recipients and blood SRY levels were assessed for 20 weeks.
Figure 9A. Structure of the sheath/baseplate complex of the bacteriophage T4, adapted from Kostyuchenko et al. (Kostyuchenko, Leiman et al., 2003). A colour code with corresponding gp protein is provided. The proposed corresponding homolog in the T6SS is indicated with parentheses. B. The T4 bacteriophage baseplate organisation versus a putative T6SS baseplate working model. Schematic representation (adapted from (Aksyuk et al., 2009b)) of the T4 bacteriophage baseplate/tail complex (left) and a putative similar T6SS structure (right). The protein-protein interaction network of both, T4 phage and T6SS, is shown with grey lines. The interactions between T6SS proteins found in this work are shown with black lines.
Shank2-/- mice display no gross abnormalities in hormonal gene and receptor expression.Figure 4(A-G) qRT-PCR analysis of mRNA expression levels of hormonal genes and hormonal receptors normalized to house-keeping gene HMBS of 9-10 week old naive and postnatal day 1 Shank2+/+ and Shank2-/- mice: (A) Oxytocin gene expression did not differ between Shank2+/+ and Shank2-/- mice, one-way ANOVA, P=0.335. (B) Vasopressin gene expression did not differ between Shank2+/+ and Shank2-/- mice, one-way ANOVA, P=0.945. (C) Prolactin gene expression did not differ between Shank2+/+ and Shank2-/- mice, one-way ANOVA, P=0.202. Additionally, no significant difference was evident in (D) oxytocin receptor, one-way ANOVA, P=0.675, (E) prolactin receptor, one-way ANOVA, P=0.912, (F) vasopressin receptor, one-way ANOVA, P=0.418 and (G) estrogen receptor alpha expression, one-way ANOVA, P=0.890 in comparison to Shank2+/+ mice. All data are presented as mean ± SEM, NS: not significant. Pituitary gland, (n=3 pituitary glands pooled per value, n=3 hypothalamus (Oxytocin, Vasopressin, Oxytocin receptor, Vasopressin receptor, estrogen alpha) n=2-3 hypothalamus (Prolactin receptor)). HYP, hypothalamus; PIT, pituitary gland.
Figure 5A) Schematic representation of RA-BAX mutant and deletion variants analyzed for the interaction with GB-DRP1. The variants are displayed in the corresponding region of BAX secondary structure (boxes correspond to BAX helices 1-9 as indicated). B) Representative confocal microscopy images of U2OS BAX/BAK DKO cells of the interactions between RA-BAX variants and GB-DRP1, shown as green signal, 3 h after apoptosis induction. Mitochondria labeled with mito-BFP in magenta. Scale bar 10 μm. C-E) Quantification of the interaction of DRP1 with variants of BAX based on the % cells with detectable RA-BAX/GB-DRP1 fluorescence signal (interacting cells) normalized to the number of mito-BFP positive cells. Box plots represent the interquartile (box), median (line) and SD (whiskers) of n=3 independent experiments (with n=100 cells each). Levels of significance were determined by paired two-tailed Student´s t-test (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001) compared to BAX wild type (WT). F) Schematic representation of GB-DRP1 mutant variants analyzed for the interaction with RA-BAX. The variants are displayed in the domain distribution of DRP1 (amino acid positions correspond to DRP1 isoform 3). G) Representative confocal microscopy images of U2OS BAX/BAK DKO cells of the interactions between RA-BAX and GB-DRP1 variants, shown as green signal, 3 h after apoptosis induction. Mitochondria labeled with mito-BFP in magenta. Scale bar 10 μm. H) Quantification of the interaction of DRP1 variants with BAX based on the % cells with detectable RA-BAX/GB-DRP1 fluorescence signal (interacting cells) normalized to the number of mito-BFP positive cells. Box plots represent the interquartile (box), median (line) and SD (whiskers) of n=3 independent experiments (with n=100 cells each). Significance was tested using paired two-tailed Student´s t-test (n.s. p > 0.05) compared to DRP1 WT.
Figure 7Control cell line (Tgfbr2wt) (A) and two Tgfbr2-mutant cell lines (Tgfbr2mut1 and Tgfbr2mut2) (B-C) were treated with TGFβ at different time points, and cell growth (MTT) assays were performed. P value by t test is shown. NS, not significant. Subcutaneous tumors established from control cell line (D) and two Tgfbr2-mutant cell lines (E-F) in C57Bl/6 mice received rat IgG Mac48 (control) or 2G8 (each 30 mg/kg 2x/week, n = 4/group). Therapy started at day 12 post tumor cell injection; mice were on therapy for 16 days. Tumor volume was measured twice per week. P values by t test are shown. Control cell line (Tgfbr2wt; G&I) and the Tgfbr2-mutant cell line (Tgfbr2mut1; H&J) were orthotopically implanted in C57Bl/6 mice. Mice received rat IgG Mac48 or 2G8, n = 9-10/group for survival study (each 30 mg/kg 2x/week). Control cell line (Tgfbr2wt; G&I) and the Tgfbr2-mutant cell line (Tgfbr2mut1; H&J) were orthotopically implanted in C57Bl/6 mice. Mice were sacrificed when they became moribund. Tumors were harvested and weighed (K-L). Immunohistochemistry with tumor samples from (G-H) for Ki67 (M-O), P-STAT3 (P-R), ZAP70, and CD3 (S-X) was performed. ZAP70 is a common marker for NK cells and T cells and was stained with a brown chromogen, and CD3 is a specific T-cell marker and was stained with a blue chromogen. Brown signal was converted to red signal and blue signal was converted to green by ImageJ (V); therefore NK cells are highlighted as red (ZAP70+CD3-) and T cells are highlighted as yellow (ZAP70+CD3+). Scale bars outside the magnification boxes = 50 μm, scale bars inside the magnification boxes = 10 μm. n = 4/group, P values vs. control by t test are shown.