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0.455161 | f536451a185a4f27952d9fe06a11b692 | Testing Cas9-CtBP range of action on a luciferase reporter gene in S2 cells.S2 cells were transfected with actin-GAL4, the Mpp6-luciferase reporter, one of the dCas9 effectors, and a single gRNA. A) Schematic of luciferase reporter that was designed to be regulated by the Mpp6 promoter, with gRNA positions indicated below. B) dCas9-CtBP(S) has position-specific effects. Position 2 led to the most severe repression. Position 5 caused the same level of repression as dCas9 alone, suggesting steric hindrance. C) dCas9-CtBP(L) has position-specific effects, which are similar to those of CtBP(S). D) The dCas9 control did not lead to significant repression, aside from position 5. The dCas9 results are the same control experiments as presented in Raicu et al. In prep. | PMC10245716 | nihpp-2023.05.19.541472v1-f0004.jpg |
0.4584 | 89ff8a82a3194afdb6241ca808fdc5cb | Literature search and screening process. | PMC10247142 | gr1.jpg |
0.45789 | f3be2cbfc52442dbada5c2b2d575ff5f | Association between IL and 6 receptor antagonists vs usual care or placebo and outcome of 28-Day all-cause mortality. | PMC10247142 | gr2.jpg |
0.466548 | b49b7f4ba2754899a886e863780427ca | Association between IL and 6 receptor antagonists vs usual care or placebo and outcome of hospital mortality. | PMC10247142 | gr3.jpg |
0.396102 | dc5de971da1f469688a23930f1321f0c | Association between IL and 6 receptor antagonists vs usual care or placebo and outcome in the length of hospital stay. | PMC10247142 | gr4.jpg |
0.457865 | 6c02564428774c4ca320c86060edcd2a | Association between IL and 6 receptor antagonists vs usual care or placebo and outcome in the length of ICU stay. | PMC10247142 | gr5.jpg |
0.495337 | 1ba595868a6140f1a08850cbd4c79289 | The effect of β-arr 2 transfection on the CL2: 6 cells viability. The cells were grown
six-well plates at 80% confluency and then transfected with β-arr 2 plasmid. Viability was evaluated by Prestoblue assay and 24h, 48h and 72h. Results are the mean between three independent experiments±SD, *p<0.05 vs. untransfected control cells.
| PMC10248488 | CHSJ-48-04-407-fig1.jpg |
0.489822 | 8d892a0b80404453abd9294f2677cfb7 | The influence of TMZ treatment on the CL2: 6 HGG cells versus β-arr 2 transfection at 24h. Cells were seeded in 96-well plates and treated with 200µM, 250µM and 300µM TMZ.
The viability was evaluated by Prestoblue assay and 24h. Results are the mean between three independent experiments±SD, *p<0.05 vs. untransfected control cells.
| PMC10248488 | CHSJ-48-04-407-fig2.jpg |
0.522321 | 323eb668f5f1413e9a12580d49ae15a3 | The influence of TMZ treatment on the CL2: 6 HGG cells versus β-arr 2 transfection at 48h. Cells were seeded in 96-well plates and treated with 200µM, 250µM and 300µM TMZ.
The viability was evaluated by Prestoblue assay and 48h. Results are the mean between three independent experiments±SD, *p <0.05 vs. untransfected control cells.
| PMC10248488 | CHSJ-48-04-407-fig3.jpg |
0.562072 | 9e026f23500c4352b2a57911c489d717 | The influence of TMZ treatment on the CL2: 6 HGG cells versus β-arr 2 transfection at 72h. Cells were seeded in 96-well plates and treated with 200µM, 250µM and 300µM TMZ.
The viability was evaluated by Prestoblue assay and 48h. Results are the mean between three independent experiments±SD, *p<0.05 vs. untransfected control cells.
| PMC10248488 | CHSJ-48-04-407-fig4.jpg |
0.430016 | 3e9c7faa1d504561b96f708561315192 | Aligned alpha helices of ß‐amyloid (green) and aquaporin4 (blue). Arrow indicates isoleucine 77 of ß‐amyloid overlying valine 162 in exon 3 of aquaporin 4. | PMC10249176 | CDT3-9-177-g001.jpg |
0.455657 | 58c6199586db49bcb6760496e33b8176 | Pymol performed five cycles of calculations on 29 aligned atoms of aquaporin‐4 and ß‐amyloid proteins, with a final root mean square deviation of atomic positions (RMSD) of 0.300 Å for 21 atoms. | PMC10249176 | CDT3-9-177-g002.jpg |
0.454872 | 237f27c8972a4e62beed0dd5acb72f53 | Amyloid precursor protein (APP) RNA expression. Like AQP4, APP is strongly expressed throughout the brain. Human Protein Atlas https://www.proteinatlas.org/ENSG00000142192-APP/brain. | PMC10249176 | CDT3-9-177-g003.jpg |
0.413382 | 02ed9e185c8f441799c59ca86f322e53 | AQP4 RNA human brain expression, data normalized. A_23_P107565 probe. AQP4 RNA is strongly and broadly expressed in a variety of brain areas, including the hippocampal and parahippocampal regions, where Alzheimer's disease (AD) originates. Data from Allen Brain Atlas. | PMC10249176 | CDT3-9-177-g004.jpg |
0.478343 | 0d5d3989630e4c3789a35732ce72baf3 | AQP4 RNA expression. AQP4 RNA is strongly and broadly expressed in a variety of brain areas in both the human and mouse (not shown). The donor was a 24‐year‐old Male Black or African American. Allen Brain Atlas http://human.brain-map.org/microarray/gene/show/358. | PMC10249176 | CDT3-9-177-g005.jpg |
0.418156 | 805925b7307c408d8c11f11971cbbe0b | The prevalence of cams used by the patients. CAM: complementary and alternative medicine. *Respondents may report more than one answer. | PMC10249343 | gr1_lrg.jpg |
0.460115 | 5e0c7ef90c7a4b4d845d9f5141a416f4 | Fifty sampling sites in the Overberg region of South Africa.Freshwater bodies (coloured by wetland type: Temporary vlei purple, River edge green, Large dam brown, Small dam blue and Fynbos pool red) are constructed (diamonds) or natural (circles) (inset shows extreme southwest of southern Africa). For details of the selected sites see Table S1. | PMC10249618 | peerj-11-15516-g001.jpg |
0.438837 | 34f3e1ea601d46b8b882aa99b2660058 | The relationship between 50 sites sampled and their amphibian communities in the Overberg region of South Africa from a reduced redundancy analysis (reduced RDA).The position and influence of environmental variables are shown with arrow lengths, when variables are factors separate arrows are shown for each factor. Species names are abbreviated to the first letters of genus and specific name (see Table 1). | PMC10249618 | peerj-11-15516-g002.jpg |
0.386841 | a1f9d4f86bc44450b5bb768b4f3cb0ac | The relationship between 36 permanent water sites sampled and their amphibian communities in the Overberg region of South Africa using a non-metric multidimensional scaling (NMDS) analysis.Points and ellipses are coloured by whether fish are present (red) or absent (blue). The position and influence of species are shown with arrow lengths. Species names are abbreviated to the first letters of genus and specific name (see Table 1). | PMC10249618 | peerj-11-15516-g003.jpg |
0.439518 | b89570fa0c2146efa213f7e2537f12a4 | Grades for daily behaviors in 2020 and 2022. | PMC10250634 | fpubh-11-1172168-g001.jpg |
0.380511 | 0024383f5162412180f85efd02fecbb6 | Percent of indicators with no results, for each equity-deserving group. | PMC10250634 | fpubh-11-1172168-g002.jpg |
0.522716 | 7d876755ae2744b89f70bdc9c2f7dc8d | Grade comparisons beyond daily behaviors in 2020 and 2022. | PMC10250634 | fpubh-11-1172168-g003.jpg |
0.452047 | b0cf877894a74590ad989e60b6113caf | Thyroid hormones bind to membrane protein extracts from Strongylocentrotus purpuratus gastrulae and can be displaced by integrin ligands. (A–G) In fluorescence anisotropy competitive binding assays, T4, T3, T2, Tetrac, and RGD peptide bind to membrane protein extract. Normalized mP: Millipolarization normalized on a scale of 0-100. We were not able to detect binding of rT3. Out of the tested ligands, T4 showed the highest affinity for membrane proteins, with a calculated Ki of approximately 1.1 x 10-9 M. (H) In a saturation binding assay, thyroxine labeled with rhodamine (RHT4) binds to membrane protein extract with a Kd of approximately 9.5 x 10-8 M, roughly two orders of magnitude lower in affinity when compared to unlabeled T4. | PMC10250714 | fendo-14-1195733-g001.jpg |
0.389271 | 734c6f1c0fef427599a21200b2a56a82 | Thyroid hormone exposure accelerates skeletogenesis in Strongylocentrotus purpuratus larvae. (A) Representative images of TH exposure effects on skeletogenesis in the gastrula and late-stage larvae. In gastrulae, TH exposure accelerates initiation of skeletogenesis with initial spicules for larval skeleton appearing several hours earlier compared to the control (no TH). In the rudiment, THs accelerate development of skeletal features, including tube feet, spines, and test. ls: Larval skeleton, r: Rudiment, s: Skeleton, sp: Juvenile spines. (B) THs accelerate skeletogenesis in Gastrula in a MAPK-dependent manner. Data reproduced from 13. All THs and RGD peptide are shown at a concentration of 10-7M, PD98059 at 5 x 10-6M. * indicates a rate of skeletogenesis statistically different from the control (Binary logistic regression with Bonferroni corrected p-values). THs, including T4, T3, and T2, accelerate skeletogenesis.†: While we have displayed here all THs at 10-7M, a higher concentration of T4 is able to outcompete the inhibitory effect of RGD peptide, as discussed in 13. (C) THs accelerate skeletogenesis in late-stage larvae in a partially MAPK-dependent manner, including T3 and T4 (One-way ANOVA with Bonferroni-corrected t tests; F(10,121) = [20.88], p = 4.96e-22). The effect of T2 was not significant after correcting for multiple comparisons (adjusted p = 0.063). Unlike in gastrulae, inhibiting MAPK with PD98059 is insufficient to fully prevent the effect of T4 on skeletogenesis. * indicates a rate of skeletogenesis statistically different from the control (Bonferroni-corrected t-test, p<0.05). | PMC10250714 | fendo-14-1195733-g002.jpg |
0.411887 | 2072d37a1e974ad3a8cdb6a00ae542f2 | Summary of transcriptome data structure. Gene expression clusters by age and hormone treatment T4-exposed samples are dissimilar from control and T3-exposed samples within each age group. (A) UMAP analysis of individual replicates reveals clustering primarily by age, with highly divergent gene expression patterns between the gastrulae and older larvae groups. Control and T3-exposed groups cluster more tightly together than with T4-exposed groups. (B) Heatmap of gene expression with genes separated into 4 clusters by k-means using the ComplexHeatmap R package. Gene counts are normalized to z-scores. The heatmap reveals that genes are differentially regulated in gastrulae and older larvae (9613 DEGs between 27-day old and gastrulae control groups), as well as in T4-exposed groups relative to control and T3-exposed groups in older larvae (1730 DEGs in T4 27d relative to control). | PMC10250714 | fendo-14-1195733-g003.jpg |
0.451151 | c8be1bb44ed047f7a4cc88f0f4da0232 | Summary of top ten significantly enriched GO slim categories of upregulated and downregulated genes. Gene ontology (GO) enrichment was determined by Fisher’s exact test in T3 and T4-exposed gastrulae (G), 23-day old larvae (23d), and 27-day old larvae (27d). More GO categories were enriched in the upregulated subset of DEGs. The most differentially enriched groups between (A) upregulated and (B) downregulated DEGs in each major GO category were cytoskeleton, and plasma membrane (CC), signaling, vesicle-mediated transport, and microtubule-based movement (BP), and cytoskeletal protein binding and cytoskeletal motor activity (MF). Cells are coloured and GO slim categories are sorted by number of DEGs assigned to each GO slim category. Every displayed GO slim category was significantly enriched in at least one sample. Fisher’s exact test was used to determine significantly enriched GO categories relative to control groups. The top ten groups sorted by lowest p values (<0.05) are displayed for each major GO category (Cellular Component, Biological Process, and Molecular Function). GO annotations were sourced from Ensembl Metazoa and mapped to GO slim annotations. | PMC10250714 | fendo-14-1195733-g004.jpg |
0.424688 | 3bd39dbecdab41fabd358c67229c6ee6 | Summary of upregulated and downregulated genes by manually annotated functional group. DEGs were determined using DESeq2 comparisons between TH-exposed groups and the control group of the same age. T4 resulted in regulation of more genes than T3, with dramatically more DEGs in older larvae compared to gastrulae. More DEGs are upregulated than downregulated. Individual categories are explored in more detail in
Figures 6
–
12
. | PMC10250714 | fendo-14-1195733-g005.jpg |
0.404499 | 8ca248c3c43a4d84bcc63d958e5f3e38 | T4 regulates gene expression of skeletogenesis-related genes in older larvae. (A) Heatmap of top 30 skeletogenesis-related genes, sorted by p-value (low to high, determined by DESeq2) and clustered by expression pattern. Colours are scaled to log2(foldchange) and capped at 2-fold, while numbered cells display foldchange. Spicule proteome was updated from 46. PMC-expressed genes were obtained from 47. The Skeletogenic GRN list was compiled from the Davidson Lab Gene Regulatory Network model hosted on BioTapestry. (B) Volcano plots of all skeletogenesis related genes. | PMC10250714 | fendo-14-1195733-g006.jpg |
0.376167 | d8850844f71849129da749b19242151f | T4 regulates gene expression of thyroid hormone-related genes in older larvae. Deiodinases and some putative TH transporters are strongly upregulated. Tg-like cholinesterases (>40% identity to Tg with >4% tyrosine content) and sulfotransferases are generally downregulated in 27-day-old post-rudiment development larvae (27d). (A) Heatmap of top 30 TH-related genes, sorted by p-value (low to high, determined by DESeq2) and clustered by expression pattern. Colours are scaled to log2(foldchange) and capped at 2-fold, while numbered cells display foldchange. Genes were compiled from annotations in the S. purpuratus 5.0 genome release and verified with manual BLAST searches against chordate genomes. (B) Volcano plots of all TH-related genes. | PMC10250714 | fendo-14-1195733-g007.jpg |
0.375277 | cc90a38381474fb881e94475f181f357 | T4 regulates gene expression of nuclear hormone receptors in older larvae. Notably, all the upregulated nuclear receptors excepting NR5A2 are in the NR1 family. The putative nuclear TH receptor is among those genes found to be upregulated in larvae with rudiments (27d), but not in younger larvae without rudiments (23d). (A) Heatmap of top 30 nuclear hormone receptor genes, sorted by p-value (low to high, determined by DESeq2) and clustered by expression pattern. Colours are scaled to log2(foldchange) and capped at 2-fold, while numbered cells display foldchange. Genes were compiled from annotations in the S. purpuratus 5.0 genome release and verified with manual BLAST searches against chordate genomes. (B) Volcano plots of all nuclear hormone receptor genes. | PMC10250714 | fendo-14-1195733-g008.jpg |
0.405802 | 2f7f53248bb7477d9e1839bdca443d4e | T4 regulates gene expression of apoptosis-related genes in older larvae. The most highly upregulated and downregulated genes are putative orthologs of cytochrome C (Cyt C), an inhibitor of apoptosis. (A) Heatmap of top 30 apoptosis-related genes, sorted by p-value (low to high, determined by DESeq2) and clustered by expression pattern. Colours are scaled to log2(foldchange) and capped at 2-fold, while numbered cells display foldchange. Apoptosis-related genes were compiled from the Reactome pathway database and matched to S. purpuratus via annotations available on Echinobase or by best BLAST match to the S.p. 5.0 genome. (B) Volcano plots of all apoptosis related genes. | PMC10250714 | fendo-14-1195733-g009.jpg |
0.396982 | 115a3b704ccd41f3b75c7c93ac92b31b | T4 regulates gene expression of adhesome-related genes in older larvae, however not to the extent of other categories we examine. Integrin alpha-8-like is dramatically downregulated, while integrin alpha-PS1 and several cadherins are moderately upregulated, along with elements of the Cadhesome and Adhesome. Transglutaminases are also notably downregulated in older larvae. (A) Heatmap of top 30 adhesome-related genes, sorted by p-value (low to high, determined by DESeq2) and clustered by expression pattern. Colours are scaled to log2(foldchange) and capped at 2-fold, while numbered cells display foldchange. Genes were compiled from annotations in the S. purpuratus 5.0 genome release and verified with manual BLAST searches against chordate genomes. (B) Volcano plots of all adhesome related genes. | PMC10250714 | fendo-14-1195733-g010.jpg |
0.376059 | 8a06a680d0424062b34de3e9560d40d4 | T4 regulates gene expression of neuronal genes in older larvae. Aromatic L-amino acid decarboxylase (AADC), a key component of dopamine and serotonin synthesis, is dramatically upregulated by T4 in older larvae. As well, histamine receptors and several acetylcholine receptors are also upregulated. Several serotonin and acetylcholine receptors are downregulated. (A) Heatmap of top 30 neuronal genes, sorted by p-value (low to high, determined by DESeq2) and clustered by expression pattern. Colours are scaled to log2(foldchange) and capped at 2-fold, while numbered cells display foldchange. Genes were compiled from annotations in the S. purpuratus 5.0 genome release and verified with manual BLAST searches against chordate genomes. (B) Volcano plots of all neuronal genes. | PMC10250714 | fendo-14-1195733-g011.jpg |
0.414833 | 4d4e736aca2f4396b593eff9d2541851 | Some immune genes are strongly upregulated in our T4-exposed groups (5.7% of total annotated genes), including a variety of SRCR-domain containing proteins. Several clotting and coagulation-related genes were strongly downregulated by T4. (A) Heatmap of top 30 immune genes, sorted by p-value and clustered by expression pattern. Colours are scaled to log2(foldchange) and capped at 2-fold, while numbered cells display foldchange. Immune gene list was compiled and updated from 57. (B) Volcano plots of all immune genes. | PMC10250714 | fendo-14-1195733-g012.jpg |
0.407284 | 0d7957db16bb4fada390d5eeb75039d8 | Genes with thyroid hormone response elements (TREs) <500 bp upstream are more likely to be regulated by THs. (A) Genes with >10 nearby TRE halfsites were regulated an average of 2.6-fold and 2.0-fold more strongly by T4 and T3 respectively when compared with genes that have no nearby TRE halfsites. Similarly, genes with nearby DR4 (B) and DR0-6 (C) sites were more heavily regulated by THs than genes with no nearby TRE sites. Nearby TRE sites were the strongest predictor of regulation in 27-day-old larvae, compared to younger larvae and gastrulae. * represents p<0.05 by two tailed T test comparison to sites with no nearby TRE. | PMC10250714 | fendo-14-1195733-g013.jpg |
0.410756 | 520e47a0de764c42889a67dffe312416 |
(A) Average enrichment of predicted TRE sites within <500 bp upstream of >2-fold DEG transcription initiation sites, relative to unregulated genes. Genes which are at least 2-fold upregulated by THs are more likely to have nearby (<500bp) TRE sites. In 23 and 27-day old larvae, T3 requires more nearby TRE sites to regulate genes than T4. In particular, genes sensitive to T3 regulation in 27-day old larvae had over 2-fold enrichment of nearby TRE halfsites, DR4 and DR0-6 predicted sites. * represents p<0.05 by two tailed T test comparison to unregulated genes. (B) Proportion of DEGs with nearby predicted TRE sites. Significantly more TRE halfsites and DR4 sites were present in genes regulated by T4 in Gastrulae, and T3 in 27-day-old larvae, with a trend of increased TRE sites near DEGs in 23-day-old larvae as well. * represents p<0.05 by two-tailed T test comparison to unregulated genes. | PMC10250714 | fendo-14-1195733-g014.jpg |
0.443052 | fccac3c7364d4671bc863a6b5c54c2e0 | BA.1-LAV and BA.5-LAV as boosters.a Genome organization of BA.1-LAV and BA.5-LAV. Leader sequence (red), transcriptional regulatory sequence within the leader sequence and within the body are highlighted as green bars. The polybasic insert “HRRA” was removed from the spike protein proteins and ORF6-8 were removed from the WA1/2020 backbone. Locations of K164A/H165A are highlighted in the figure. b Pseudovirus (PsV) bearing BA.5 spike but not WA1/2020 spike infected 293-mACE2 cell line. Infected cells are shown in green. Blue, DAPI strained nuclei. Scale bars in the lower right corner indicate 50 µm. c Overall study design to test BA.1-LAV and BA.5-LAV as boosters. 10-week-old male BALB/c mice were employed in this study. d Neutralizing antibody titers were measured from pre- and post-boost sera in BA.1 and BA.5 boosted mice (n = 5 in each group). Each solid circle represents one animal. Numbers above each group and average bars indicate the geometric means of neutralizing antibody titers with error bars signifying standard deviations. Values were compared using Student’s unpaired t test in GraphPad Prism 9.4.0. | PMC10250859 | 41467_2023_39090_Fig10_HTML.jpg |
0.399491 | 55d4db5efa09432ba003956f66e9e3c2 | Intranasal immunization with 100 PFU Nsp1-K164A/H165A induces IgG and IgA.a Genome organization of the attenuated SARS-CoV-2-ΔPRRA-ΔORF6-8-Nsp1K164A/H165A (abbreviated as Nsp1-K164A/H165A). The polybasic insert “PRRA” together with ORF6-8(green) were removed from the WA1/2020 genome. Locations of K164A/H165A within Nsp1 are indicated at the bottom left of the panel. b–h Hamster sera or nasal wash samples were collected at 14- and 30-days post-intranasal inoculation of 100 PFU Nsp1-K164A/H165A or WA1/2020 and then tested for binding to WA1-2020 receptor binding domain (RBD) by ELISA (b) and for neutralization against WA1/2020 (c). Samples from naïve hamsters were included as negative controls. d Secretory IgA levels in nasal wash samples (NW IgA) collected 30 DPI were measured by ELISA. *p = 0.0302. e–h Hamster sera of 30 DPI were measured for anti-Delta RBD IgG (e) and neutralization (f), for anti-Omicron BA.1 RBD IgG (g), and neutralization (h). Biologically independent samples for WA1/2020 (n = 13), Nsp1-K164A/H165A (n = 14), and naïve hamsters (n = 16) were used in a single independent experiment. Bar graphs indicate mean titers with standard deviations shown as error bars. Each solid circle indicates individual hamsters from a single experiment. Statistical differences were calculated using ordinary one-way analysis of variance (ANOVA) in GraphPad Prism 9.4.0 with Tukey’s multiple comparisons tests. For statistical significance, *p < 0.05 and ****p < 0.0001. DPI days post-infection. | PMC10250859 | 41467_2023_39090_Fig1_HTML.jpg |
0.519104 | 2308d2f1b6bb40a3a6d06986ab0b0976 | Intranasal immunization with Nsp1-K164A/H165A induces mucosal and systemic humoral immunity and cellular immunity.Male (4-month-old, n = 8) Syrian hamsters were intranasally vaccinated with 104 PFU Nsp1-K164A/H165A. Animals were bled at 14 and 28 DPI to collect sera and n = 4 animals were euthanized at each time point to collect broncho-alveolar lavage fluid (BALF). Anti-RBD IgG titers against WA1/2020 (blue) or BA.1 (red) in serum (a) and BALF (b) were measured by ELISA. Anti-RBD IgA (***p = 0.0002) was likewise quantified in serum (c) and BALF (***p = 0.0003) (d). e Serum nAb titers at 28 DPI were measured against WA1/2020 (WA1), Delta (B.1.617.2), as well as Omicron subvariants (BA.1, BA.2.12.1, BA.4, BA.5) using a 50% focus reduction neutralization (FRNT50) assay. f Splenocytes were isolated from naive and vaccinated hamsters at 14 DPI and pulsed with 10 μM WA1/2020 Spike (S) and Nucleocapsid (N) antigen pools for 48 h. IFNγ-secreting splenocytes were enumerated by ELISPOT. Bar graphs represent mean values with standard deviation for samples collected at two time points from the same animals in a single experiment with dots representing individual animals. *p = 0.0246, **p = 0.0026. ELISPOT data were compared using two-way ANOVA with Sidak’s multiple comparison test. Unless otherwise indicated, statistical differences were calculated using ordinary one-way analysis of variance (ANOVA) in GraphPad Prism 9.4.0 with Tukey’s multiple comparisons tests. For statistical significance, *p < 0.05, **p < 0.01, and ****p < 0.0001. DPI days post-infection. | PMC10250859 | 41467_2023_39090_Fig2_HTML.jpg |
0.422602 | d179d4049b5342698d6e79888d4b0ac5 | Intranasal immunization of Syrian hamsters with 100 PFU Nsp1-K164A/H165A significantly reduces viral loads in both upper and lower respiratory tract following challenge with Delta and Omicron variants.a Syrian hamsters were vaccinated with 100 PFU Nsp1-K164A/H165A or infected with 100 PFU WA1/2020 35 days prior to challenge with 104 PFU Delta (n = 6) or BA.1 Omicron (n = 7) isolates on day 0. b–c From 1–5 DPC, infectious virus from nasal wash samples was quantified by focus-forming assays in vaccinated, convalescent, or unvaccinated hamsters (n = 8 for Delta, b; n = 7 for Omicron BA.1, c). Graphs for b and c indicate mean values from a single experiment with standard deviations shown as error bars. ***p = 0.001. d Viral sgRNA levels in lung, trachea, and nasal turbinate samples from 4 DPC (n = 4 each, except WA1/2020-Delta at n = 3) were measured by qRT-PCR. **p = 0.0041, ***p = 0.0008. e Infectious virus titers of lung homogenates at 4 DPC were determined by focus-forming assays. f Viral sgRNA levels in lungs and trachea at 7 DPC with Delta and BA.1 Omicron were measured by qRT-PCR. Infectious and qRT-PCR based titrations of Nsp1-K164A/H165A (n = 3), WA1/2020 (n =n = 3) vaccinated, or unvaccinated (n = 4) biological replicates in one independent challenge experiment each for Delta and Omicron BA.1. ***p = 0.0052. Dot plots represent samples collected from individual animals in a single experiment. Statistical differences were calculated using ordinary one-way analysis of variance (ANOVA) in GraphPad Prism 9.4.0 with Tukey’s multiple comparisons tests. For statistical significance, ****p < 0.0001. Δ delta variant challenge, Ο omicron BA.1 challenge, DPC days post-challenge. | PMC10250859 | 41467_2023_39090_Fig3_HTML.jpg |
0.42825 | 0e3767cdc726479d8df2702ce6ffccde | Nsp1-K164A/H165A vaccination blocks virus propagation and MX1 induction in hamster lungs.Syrian hamsters were vaccinated with a low (100 PFU) dose of Nsp1-K164A/H165A or WA1/2020 35 days prior to challenge with Delta or BA.1 isolate on day 0. Serial lung sections from non-infected non-vaccinated hamsters (mock) or hamster at 4 DPC were stained by a H&E or double-immunostained for b SARS-CoV-2 nucleocapsid protein (NP) and MX1 (interferon-induced antiviral protein). In a, images are shown at one level of magnification (×0.7) while corresponding serial immunostained images in b are shown at two levels of magnification (×0.7 and ×5) with white boxes delimiting the regions of magnification. c Semiquantitative analysis of viral NP staining in hamster lungs at 4 DPC. The plotted values represent the percent NP positive area as a function of the total lung area for each section (n = 3–4 animals per group). d High magnification immunofluorescence/differential interference contrast images of NP and MX1 in representative bronchioles of lung sections from mock hamsters or Delta-infected non-vaccinated or Nsp1-K164A/H165A-vaccinated hamsters at 4 DPC. Prominent cytoplasmic and nuclear localization of MX1 was detected in NP-positive bronchiolar epithelium in Delta-infected unvaccinated hamsters compared to low cytoplasmic expression of MX1 in mock and vaccinated hamsters. Nuclei were counterstained with Hoechst 33342 dye (blue). Scale bars: 5 mm (×0.7), 500 μm (×5), 20 μm (×60). Δ delta variant challenge, Ο omicron BA.1 challenge, DPC days post-challenge. | PMC10250859 | 41467_2023_39090_Fig4_HTML.jpg |
0.436255 | a59b2371e08c45be90bc2c87b85b08d8 | Intranasal immunization of Syrian hamsters with Nsp1-K164A/H165A protects against Delta and Omicron challenge.a Weight change was recorded for hamsters (described in Fig. 3a) after challenge by Delta and Omicron BA.1 variants for 7 days with points representing mean values with standard deviations indicated by error bars. Percentage of consolidation (*p = 0.0352 left, 0.0386 right) (b) and pathology score (***p = 0.0002) (c) in fixed lung tissues were compared between WA1/2020 convalescent (n = 7), Nsp1-K164A/H165A vaccinated (n = 8), and unvaccinated control (n = 8) lungs at 4 DPC. Individual pathologies were graded by severity and presented in a heat map (d). Percentage of consolidation (e) and pathology score (f) were also compared at 7 DPC between WA1/2020 convalescent (n = 6), Nsp1-K164A/H165A vaccinated (n = 6), and unvaccinated control (n = 8) lungs (*p = 0.0195). g Heat-map presentation of individual pathologies at 7 DPC. Dot plots represent samples collected from individual animals in a single experiment with bars and error bars indicating mean values with standard deviations. Statistical differences were calculated using ordinary one-way analysis of variance (ANOVA) in GraphPad Prism 9.4.0 with Tukey’s multiple comparisons tests. For statistical significance, *p < 0.05, ***p < 0.001, and ****p < 0.0001. Δ delta variant challenge, Ο omicron BA.1 challenge, DPC days post-challenge. | PMC10250859 | 41467_2023_39090_Fig5_HTML.jpg |
0.419829 | 65c06d7f91e04c95a74bd4a16a2ec983 | Nsp1-K164A/H165A vaccination protects against lung pathology post-challenge with Delta and Omicron isolates.Syrian hamsters were vaccinated with a low (100 PFU) dose of Nsp1-K164A/H165A or WA1/2020 35 days prior to challenge with Delta or BA.1 Omicron isolates on day 0. Serial lung sections from non-infected non-vaccinated hamsters (mock) or 7 DPC-infected hamsters were stained by a H&E or double-immunostained for either b Iba1 (macrophage marker) and Prosurfactant protein C (ProSPC, AT2 marker) or c E-cadherin (ECAD, epithelial junctional marker) and RAGE (AT1 marker). Delta-infected unvaccinated lungs (n = 4) show extensive areas of tissue consolidation (a) that correspond with regions showing abundant Iba1-labeled macrophage accumulation and loss of ProSPC-labeled AT2 cells (b) as well as loss of alveolar wall RAGE-expressing AT1 epithelium surrounding affected ECAD-stained bronchioles and aberrant reepithelization (c). Similar though less extensive pathology was observed in two of four BA.1-challenged unvaccinated hamsters. Nsp1-K164A/H165A or WA1/2020 inoculation completely prevented or suppressed Delta or BA.1-induced lung pathology. In a, images are shown at one level of magnification (×0.7) while corresponding serial immunostained images in b and c are shown at three levels of magnification (×0.7, ×10, and ×40) with white boxes delimiting the regions of magnification. Nuclei were counterstained with Hoechst 33342 dye (blue). Scale bars: 5 mm (×0.7), 250 μm (×10), 100 μm (×40). | PMC10250859 | 41467_2023_39090_Fig6_HTML.jpg |
0.422101 | b1299c7068914a6f9155fde37f54aa3e | Airborne transmission of Nsp1-K164A/H165A in Syrian hamsters.a Donor Syrian hamsters (male, 5-month-old) were first inoculated with 100 PFU Nsp1-K164A/H165A (n = 14) or WA1/2020 (n = 14). One day after inoculation, donor hamsters were paired with recipient hamsters (sentinel, n = 7/group) in the specially designed cages with metal dividers for monitoring airborne transmission. During pairing, nasal swabs were collected daily from sentinel hamsters for 4 days. b Weight loss profile of donor hamsters (n = 14) after virus inoculation. c Infectious virus titers of nasal wash samples collected from donor hamsters were measured by a TCID50 assay for up to 5 days post-inoculation and were compared using two-way ANOVA with Sidak’s multiple comparison test. *p = 0.0264, ***p = 0.0003. Symbols indicate individual hamsters from a single experiment (n = 14 per group). Statistical differences were calculated by Student’s unpaired t-test in GraphPad Prism 9.4.0. d Infectious virus titers of nasal wash samples collected from sentinel hamsters were measured by a TCID50 assay for up to 4 days post-exposure (DPE; n = 7 per group). ***p = 0.0004. e Weight loss profile of sentinel hamsters (n = 7 per group) up to 14 days post-exposure to donor hamsters. f Seroconversion of sentinel hamsters was confirmed by ELISA measuring anti-WA1/2020 RBD IgG in Nsp1-K164A/H165A (n = 7) and WA1/2020 (n = 7) hamsters in seven independent pairs each. Note, one hamster (indicated by a green diamond) after exposure to Nsp1-K164A/H165A did not seroconvert. Serum nAB titers against WA1/2020 (**p = 0.0026) (g) and BA.2.12.1 (h) in sentinel hamsters (n = 6 for sentinels exposed to Nsp1-K164A/H165A and n = 7 for those exposed to WA/2020) after four and half months post-exposure (MPE) were measured by focus forming reduction neutralization assays (**p = 0.0026). Symbols in b, e indicate mean percent weight change data of groups of hamsters relative to initial individual animal weights on day 0 with standard deviation indicated by error bars. Bar graphs indicate mean values with error bars signifying standard deviations. Statistical differences were calculated in GraphPad Prism 9.4.0 using a two-way analysis of variance (ANOVA) with Sidak’s multiple comparisons test or Student’s unpaired t test (g). | PMC10250859 | 41467_2023_39090_Fig7_HTML.jpg |
0.417081 | e498394cda77485ba8323d862f5c12d4 | Chlorophyll content of barley plants with or without plant growth promoting rhizobacteria (PGPR), biochar (BC) and PGPR together with BC under drought stress. (A) Chlorophyll-a, (B) Chlorophyll-b, (C) total chlorophyll. The bars represent the standard deviation with 3 replicates. A single asterisk represents significant differences at p< 0.05, while two asterisks represent significant differences at p< 0.01 compared to the control (using student t test). | PMC10285313 | fpls-14-1175097-g004.jpg |
0.450711 | 1a09f4f9d3814375a9d3cdbfc83535b4 | Antioxidant enzyme activity of barley plants in the control (well-watered), drought (alone), plant growth promoting rhizobacteria (PGPR with drought), biochar (BC with drought) and with PGPR and BC combined (with drought). (A) Peroxidase activity, (B) catalase activity, (C) superoxide dismutase activity. The bars represent the standard deviation with 3 replicates. A single asterisk represents significant differences at p< 0.05, while two asterisks represent significant differences at p< 0.01 compared to the control (using student t test). | PMC10285313 | fpls-14-1175097-g005.jpg |
0.515282 | 459f56d255564813b57c4ebc461aa6ad | Nutrient uptake activity of barley plants in the control (well-watered no PGPR and BC), drought (alone), plant growth promoting rhizobacteria (PGPR with drought), biochar (BC with drought) and PGPR with BC (with drought). (A) Total nitrogen content, (B) total phosphorus content, and (C) Total potassium content. The bars represent the standard deviation with 3 replicates. A single asterisk represents significant differences among treatments at p< 0.05, while two asterisks represent significant differences at p< 0.01 compared to the control (using student t tests). | PMC10285313 | fpls-14-1175097-g006.jpg |
0.450091 | 547df751399846529fd28cb402c7333f | Correlations between molecular structures and rumen degradations of CNCPS fractions of alfalfa. CNCPS = Cornell Net Carbohydrate and Protein System. Color scales: blue means positive correlation while red means negative correlation; colorless cells contain correlation coefficients that are not significant at P < 0.05. Values are correlation coefficients, and the deeper the color, the higher the absolute coefficient value. CNCPS fractions: CA4, water-soluble carbohydrate, sugar; CB1, starch; CB2, soluble fiber; CB3, digestible fiber; CC, indigestible fiber; PA2, soluble true protein; PB1, insoluble true protein; PA2, fiber bound protein; PC, indigestible protein; CHO, carbohydrate, CP, crude protein; RD, rumen degradable fractions; RU, rumen undegradable fractions. Structural parameters: TC1 to TC4, 4 major peaks in TC region at ca. 1,026 (TC1) 1,074 (TC2), 1,104 (TC3) and 1,149 (TC4) cm−1, respectively; TCA, TC peak area (ca. 1,178 to 941 cm−1); CEC, cellulosic compounds (ca. 1,237 cm−1); CECA, CEC peak area (ca. 1,283 to 1,178 cm−1); STC1-STC4, 4 major peaks at ca. 1,317 (STC1), 1,370 (STC2), 1,397 (STC3) and 1,453 (STC4) cm−1, respectively; STCA, STC peak area (ca. 1,484 to 1,178 cm−1); alpha/beta, ratio of alpha helix to beta sheet; AA, whole amide peak area (ca. 1,710 to 1,484 cm−1); AIA, amide I peak area (ca. 1,710 to 1,575 cm−1); AIIA, amide II peak area (ca. 1,575 to 1,484 cm−1); CCO, carbonyl C=O (centers at ca. 1,733 cm−1); CCOA, peak area of CCO region (baseline ca. 1,781 to 1,710 cm−1); SyCH2, symmetric CH2 (ca. 2,850 cm−1); SyCH3, symmetric CH3 (ca. 2,872 cm−1); AsCH2, asymmetric CH2 (ca. 2,920 cm−1); AsCH3, asymmetric CH3 (ca. 2,955 cm−1); ASCCA, peak area of (a)symmetric CH2 and CH3 (ASCC, ca. 3,000 to 2,761 cm−1). | PMC10285546 | gr1.jpg |
0.402535 | 8f4580fcac3446c099209602fc814d87 | Correlations between energetic profiles and structural parameters of alfalfa. Color scales: blue means positive correlation while red means negative correlation; colorless cells contain correlation coefficients that are not significant at P < 0.05. Values are correlation coefficients. The deeper the color, the higher the absolute coefficient value. Energetic values: tdNFC, truly digestible non fiber carbohydrate; tdCP, truly digestible crude protein; tdFA, truly digestible fatty acids; tdNDF, truly digestible neutral detergent fiber; TDN1x, total digestible nutrients at one time of maintenance; TDN3x, total digestible nutrients at 3 times of maintenance; DE3x, digestible energy at 3 times of maintenance; ME3x, metabolizable energy at 3 times of maintenance; NEL3x, net energy for lactation at 3 times of maintenance; NEm, net energy for maintenance; NEg, net energy for growth. Structural parameters: TC1 to TC4, 4 major peaks in TC region at ca. 1,026 (TC1) 1,074 (TC2), 1,104 (TC3) and 1,149 (TC4) cm−1, respectively; TCA, TC peak area (ca. 1,178 to 941 cm−1); CEC, cellulosic compounds (ca. 1,237 cm−1); CECA, CEC peak area (ca. 1,283 to 1,178 cm−1); STC1 to STC4, 4 major peaks at ca. 1,317 (STC1), 1,370 (STC2), 1397 (STC3) and 1,453 (STC4) cm−1, respectively; STCA, STC peak area (ca. 1,484 to 1,178 cm−1); alpha/beta, ratio of alpha helix to beta sheet; AA, whole amide peak area (ca. 1710 to 1,484 cm−1); AIA, amide I peak area (ca. 1,710 to 1,575 cm−1); AIIA, amide II peak area (ca. 1,575 to 1,484 cm−1); CCO, carbonyl C=O (centers at ca. 1,733 cm−1); CCOA, peak area of CCO region (baseline ca. 1,781 to 1,710 cm−1); SyCH2, symmetric CH2 (ca. 2,850 cm−1); SyCH3, symmetric CH3 (ca. 2,872 cm−1); AsCH2, asymmetric CH2 (ca. 2,920 cm−1); AsCH3, asymmetric CH3 (ca. 2,955 cm−1); ASCCA, peak area of (a)symmetric CH2 and CH3 (ASCC, ca. 3,000 to 2,761 cm−1). | PMC10285546 | gr2.jpg |
0.453153 | d0ab4f95919349faba00ef35bfb92ea2 | Correlations between cell wall residue, lignin, phenolics and ammonia production during in vitro fermentation and structural parameters of alfalfa. Color scales: blue means positive correlation while red means negative correlation; colorless cells contain correlation coefficients that are not significant at P < 0.05. Values are correlation coefficients. The deeper the color, the higher the absolute coefficient value Nutritional profiles: CWR, cell wall residue; numbers at the end of each ammonia item means the time point (h) of in vitro fermentation. Structural parameters: TC1 to TC4, 4 major peaks in TC region at ca. 1,026 (TC1) 1,074 (TC2), 1,104 (TC3) and 1,149 (TC4) cm−1, respectively; TCA, TC peak area (ca. 1,178 to 941 cm−1); CEC, cellulosic compounds (ca. 1,237 cm−1); CECA, CEC peak area (ca. 1,283 to 1,178 cm−1); STC1 to STC4, 4 major peaks at ca. 1,317 (STC1), 1,370 (STC2), 1,397 (STC3) and 1,453 (STC4) cm−1, respectively; STCA, STC peak area (ca. 1,484 to 1,178 cm−1); Alpha/Beta, ratio of alpha helix to beta sheet; AA, whole amide peak area (ca. 1,710 to 1,484 cm−1); AIA, amide I peak area (ca. 1,710 to 1,575 cm−1); AIIA, amide II peak area (ca. 1,575 to 1,484 cm−1); CCO, carbonyl C=O (centers at ca. 1,733 cm−1); CCOA, peak area of CCO region (baseline ca. 1,781 to1,710 cm−1); SyCH2, symmetric CH2 (ca. 2,850 cm−1); SyCH3, symmetric CH3 (ca. 2,872 cm−1); AsCH2, asymmetric CH2 (ca. 2,920 cm−1); AsCH3, asymmetric CH3 (ca. 2,955 cm−1); ASCCA, peak area of (a)symmetric CH2 and CH3 (ASCC, ca. 3,000 to 2,761 cm−1). | PMC10285546 | gr3.jpg |
0.423843 | 519d87d4f1cb4a85b88dd7bc1ab0494d | Forest plot of changes in youth general anxiety symptoms comparing before and during COVID-19 pandemic. SE, standard error; SMD, standardized mean differences; RoB, risk of bias; 95%-CI, 95%-confidence interval | PMC10286360 | 13034_2023_612_Fig1_HTML.jpg |
0.42285 | 10ad58b128e548ee9c1e3e5c1f4dc23e | Forest plot of changes in youth general anxiety symptoms comparing Oxford Stringency Index. SE, standard error; SMD, standardized mean differences; SI, stringency index; 95%-CI, 95%-confidence interval | PMC10286360 | 13034_2023_612_Fig2_HTML.jpg |
0.406603 | c4831532319e4e8f8b7254c3516fe9b9 | Forest plot of changes in youth general anxiety symptoms comparing School Closure Index. SE, standard error; SMD, standardized mean differences; SL, School Closure Index; 95%-CI, 95%-confidence interval | PMC10286360 | 13034_2023_612_Fig3_HTML.jpg |
0.380151 | 8926dd5889a74772849dcb37fc66ec10 | Forest plot of changes in youth clinically relevant anxiety symptoms comparing before and during COVID-19 pandemic. OR, Odds Ratio; RoB, risk of bias; 95%-CI, 95%-confidence interval | PMC10286360 | 13034_2023_612_Fig4_HTML.jpg |
0.465545 | cdd5b3e9dd9a41f5ac104a0df4cdb9a1 | Flowchart outlining the paper selection process of the systematic review (based on PRISMA guidelines) | PMC10286448 | 40463_2023_644_Fig1_HTML.jpg |
0.452135 | 6dfec42a36db4ddaa0ba672b6b1cb950 | Risk of bias assessment | PMC10286448 | 40463_2023_644_Fig2_HTML.jpg |
0.486493 | 3b1c4fddbf7240bda2259f3e22e4b53b | Mean pre-treatment and post-treatment differences in NOSE score at three months | PMC10286448 | 40463_2023_644_Fig3_HTML.jpg |
0.436983 | 46fe9c5069824646ad4b9a5afe436065 | Age-related change in gene expression heterogeneity during development and aging. The procedures are similar to those in Fig. 1, except, age-related heterogeneity changes (ρ values) were used instead of expression changes (β values). (a) Spearman correlations among age-related heterogeneity changes (ρ values) across datasets. (b) Principal component analysis (PCA) of heterogeneity change with age. (c) The number of genes showing significant heterogeneity change in aging and development. | PMC10287630 | 41598_2023_37105_Fig2_HTML.jpg |
0.470304 | 34994579547545288165edee22cba898 | Dys-regulated maternal translatome by Ribo-seq analysis in Nat10-ZcKO MII oocytes.a Scatter plot comparing transcript RPF values calculated via average TPM between WT and Nat10-ZcKO oocytes at the MII stage. RPFs decreased or increased more than 2-fold in Nat10-ZcKO oocytes samples were highlighted in blue and red color, respectively. b Scatter plot comparing the gene transcript overlapping between the mRNA changes and the RPF changes in Nat10-ZcKO MII oocytes. c Pie chart displaying the translatome-wide distribution of maternal transcripts with up-regulated (Red), down-regulated genes (Blue) and the others (Yellow) in Nat10-ZcKO MII oocytes. d Gene Ontology (GO) enrichment analysis of transcript RPFs up-regulated in Nat10-ZcKO MII oocytes. e Heatmap of representative genes from three major functional GO categories showing up-regulated RPFs in Nat10-ZcKO MII oocytes. f The UCSC browser tracks of representative genes from three major functional GO categories showing up-regulated RPF in Nat10-ZcKO MII oocytes. g–i Bar plots showing the relative mRNA expression levels in g, RPF in h and TE in i for a panel of up-regulated gene transcripts. j Box plots showing the relative TE values at the GV and MII stages as indicated. The box indicates the upper and lower quantiles, the thick line in the box indicates the median and the whiskers indicate 2.5th and 97.5th percentiles. Data are presented as mean ± SEM, n = 3. ****p < 0.0001 by two-tailed Student’s t-test. k Bar plots showing the numbers of high-TE genes (TE > 3) and low-TE genes (TE < 0.33) in GV and MII. Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig10_HTML.jpg |
0.394527 | 8e98cd0a5d9049a9a6105c185950a977 | Expression and Localization of Nat10 enriched in the nucleolus of oocytes in mice.a Western blot showing the relative expression levels of NAT10 protein among multiple organs in adult WT mice. GAPDH served as a loading control. n = 3 biologically independent samples were included in each group. b Dynamic mRNA expression levels of Nat10 from RNA-seq analyses in oocytes and preimplantation embryos in mice (GSE71434). ICM, Inner cell mass. c Quantitative RT-PCR results showing the relative expression levels of mouse Nat10 mRNA in oocytes, and preimplantation embryos. Data were presented as mean ± SEM, n = 3. GO, growing oocytes collected from postnatal 14-day-old (P14) female mice. d Immunofluorescence (IF) staining of NAT10 in growing (GO), GV, MI, and MII oocytes as indicated. Dashed circle indicates cellular membrane of oocytes. DNA was counterstained with 4′,6-diamidino-2-phenylindole (DAPI). Scale bar, 20 μm. e IF images of 21-day-old WT ovarian cryosections stained with anti-NAT10 antibody (Red) and DAPI (Blue) for follicles at various stages (primordial, primary, secondary, early antral, and antral stages) as indicated. Scale bar, 20 μm. n = 3 biologically independent samples were included in each group. Boxed inset area is a magnified view of the oocyte in the respective follicles. Arrows point to NAT10-positive nucleus of the oocyte in mouse-developing follicles. f IF images of 21-day-old WT ovarian sections co-stained with NAT10 antibody (Red), Nucleophosmin (NPM, Green), and DAPI (Blue) in the follicles as indicated. Scale bar, 20 μm. n = 3 biologically independent samples were included in each group. Bottom panel is a magnified view of the oocyte in the respective follicles. Arrows point to the co-localization of NAT10 and NPM in the oocyte nucleolus at varied stages of follicles. n = 3 biologically independent samples were included in each group (a–c). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig1_HTML.jpg |
0.434089 | 3bf61f867f5c4b21a7e514a079678ff7 | Pre-meiotic deletion of Nat10 caused follicular developmental arrest and premature ovarian failure (POF).a Schematic diagram showing the landmark timeline of oocyte development from embryonic meiotic cell-cycle progression to postnatal oocyte growth and maturation. Stra8-GFPcre is activated prior to Embryonic day 13.5 (E13.5); Zp3-cre is active starting from P5 in the primary follicles. b A breeding scheme by crossing Nat10lox/lox with Stra8-GFPCre to generate Nat10lox/-; Stra8-GFPCre (Nat10-ScKO) offspring. c Western blot analyses of the NAT10 protein levels in adult WT and Nat10-ScKO ovary. α-TUBULIN was used as a loading control. d Quantitative RT–PCR (qPCR) assay showing the relative expression levels of Nat10 mRNA in adult WT and Nat10-ScKO mouse ovary. Data are presented as mean ± SEM, n = 3. ****p < 0.0001 by two-tailed Student’s t-test. e Fertility test showing the cumulative average numbers of pups from breeding of WT and Nat10-ScKO females with WT males. Data are presented as the mean ± SEM, n = 5, ****p < 0.0001 by two-tailed Student’s t-test. f The gross morphology of ovaries derived from WT and Nat10-ScKO mice at 1 M. Scale bar, 200 μm. n = 3 biologically independent samples were included in each group. g H&E staining of paraffin-embedded ovarian sections showing the histology of WT and Nat10-ScKO ovaries at postnatal days as indicated. Scale bar, 200 μm. A high-resolution view of the boxed area is shown in parallel. Scale bar, 20 μm. n = 3 biologically independent samples were included in each group. Arrows point to follicles at stages as indicated. PrF primordial follicle, PF primary follicle, SF secondary follicle; EAF early antral follicle, AF antral follicle, LAF late antral follicle. h qPCR analyses of the relative expression levels for a cohort of genes showing specific or characteristic expression in ovarian granulosa cells (Left) or testicular Sertoli/Leydig cells (Right) in 1-month-old WT and Nat10-ScKO ovaries. Data are presented as the mean ± SEM, n = 3. n.s., not significant; **p < 0.01; ****p < 0.0001 by two-tailed Student’s t-test. Cldn5, p = 0.3326; Sox9, p = 0.0059. n = 3 biologically independent samples were included in each group (c, f, g). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig2_HTML.jpg |
0.383364 | cce42f99e26840079aab1a0c07d4271e | Embryonic Nat10 loss caused oocyte meiotic prophase I arrest at pachytene stage owing to deficient DSB repair.a Immunofluorescence staining of oocyte nuclear chromosome spreads by SYCP3 and SYCP1 markers in WT and Nat10-ScKO mouse ovaries at birth. Scale bar, 10 μm. Arrows point to the asynapsed structure of the lateral and central axes. b The statistical counts showing the percentage of oocytes at various stages as indicated. Data are presented as the mean ± SEM, n = 3, *p < 0.05 by two-tailed Student’s t-test. Pac, p = 0.0209; Pach-like, p = 0.0387; Dip, p = 0.0315. c IF staining by SYCP3 and γH2AX on surface-spread oocytes at pachytene and diplotene stages from WT and Nat10-ScKO mouse oocytes at birth. Scale bar, 10 μm. d The statistic counts showing the relative γH2AX signal intensity calculated by ImageJ in pachytene and diplotene oocytes. The box indicates the upper and lower quantiles, the thick line in the box indicates the median and whiskers indicate 2.5th and 97.5th percentiles. Data are presented as mean ± SEM, n = 3; ****p < 0.0001; n.s., not significant by two-tailed Student’s t-test. Dip, p = 0.9182. e IF staining on surface-spread oocytes by SYCP3 and RPA2 in WT and Nat10-ScKO mouse oocytes at birth. Scale bar, 10 μm. f Quantification of the numbers of RPA2 foci (representative of the unrepaired DSBs) in WT and Nat10-ScKO mouse oocytes at birth. Zyg zygotene, Pac pachytene, Pac-like pachytene-like, Dip diplotene. The box indicates the upper and lower quantiles, the thick line in the box indicates the median and whiskers indicate 2.5th and 97.5th percentiles. Data are presented as the mean ± SEM, n = 3; ***p < 0.001 by two-tailed Student’s t-test. Pac, p = 0.0001; Dip, p = 0.0002. n = 3 biologically independent samples were included in each group (a, c, e). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig3_HTML.jpg |
0.388303 | a8a56603d6944493917b4a0794c51146 | Postnatal Nat10 depletion caused ovarian developmental arrest at secondary follicles.a A breeding scheme for Nat10 KO in growing oocytes of primary follicles by crossing Nat10lox/lox with Zp3-Cre deleter to attain Nat10lox/-; Zp3-Cre (Nat10-ZcKO) female offspring. b, c Immunofluorescence staining by NAT10 (Red), NPM (Green), and Hoechst 33342(Blue) in the secondary follicles in b and GV oocytes in c from WT and Nat10-ZcKO ovaries. Scale bar, 20 μm. d Fertility test showing the cumulative numbers of pups from breedings of WT and Nat10-ZcKO females with WT males during a half-year caging. Data are presented as the mean ± SEM, n = 5; ****p < 0.0001 by two-tailed Student’s t-test. e The gross morphology of ovaries derived from WT and Nat10-ZcKO mice at the age of 1 month (M) (Left) and 2 months (Right). Scale bar, 200 μm. f H&E staining showing ovarian histology from WT and Nat10-ZcKO mice at 1M (Top) and 2 M (Bottom). Scale bar, 50 μm. Follicles are indicated by arrows. g Comparison of the average numbers of follicles at indicated stages in the ovaries of WT and Nat10-ZcKO mice at 1M (Top) and 2M (Bottom). Follicles were counted on serial ovarian sections after H&E staining. Data are presented as the mean ± SEM, n = 3; ***p < 0.001; ****p < 0.0001 by two-tailed Student’s t-test. 2 M SF, p = 0.0003. PO, Preovulatory Follicle. n = 3 biologically independent samples were included in each group (b, c, e, f). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig4_HTML.jpg |
0.40083 | a531216f18ae41f2bd78ee6a17eaf022 | Postnatal Nat10 deficiency impedes oocyte chromatin NSN–SN configuration transition.a The gross morphology of oocytes at Germinal vesicle (GV) stage collected from PMSG-primed WT and Nat10-ZcKO females at P21. Scale bar, 100 μm. b Quantification of collected average numbers of GV oocytes. Data are presented as the mean ± SEM, n = 4. n.s., non-significant by two-tailed Student’s t-test. c Hoechst 33342 (Blue) staining of the GV oocytes with non-surrounded nucleolus (NSN) and surrounded nucleolus (SN) chromatin configurations in WT and Nat10-ZcKO oocytes. Scale bar, 20 μm. d The percentage of NSN-type and SN-type oocytes isolated from WT and Nat10-ZcKO mice at P21. Data are presented as the mean ± SEM, n = 3. **p < 0.01 by two-tailed Student’s t-test. NSN, p = 0.003; SN, p = 0.003. e, f Immunofluorescence staining by H3K4me3 in NSN-type (Left) and SN-type (Right) oocytes from PMSG-primed WT and Nat10-ZcKO mice in e, and quantification of H3K4me3 intensity in (f). Scale bar, 10 µm. The box indicates the upper and lower quantiles, the thick line in the box indicates the median and whiskers indicate 2.5th and 97.5th percentiles. Data are presented as the mean ± SEM, n = 3; ***p < 0.001 by two-tailed Student’s t-test. NSN, p = 0.0006; SN, p = 0.0003. g, h Immunofluorescence staining by H3K9me3 in NSN-type (Left) and SN-type (Right) oocytes from PMSG-primed WT and Nat10-ZcKO mice in (g), and quantification of H3K9me3 intensity in (h). Scale bar, 10 µm. The box indicates the upper and lower quantiles, the thick line in the box indicates the median and whiskers indicate 2.5th and 97.5th percentiles. Data are presented as the mean ± SEM, n = 3; *p < 0.05 by two-tailed Student’s t-test. NSN, p = 0.0318; SN, p = 0.0270. n = 3 biologically independent samples were included in each group (a, c, e, g). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig5_HTML.jpg |
0.418469 | c43351441a874ba786e2786663abb09f | Postnatal Nat10 ablation led to defective oocyte meiotic maturation.a The gross morphology of oocytes collected at the time points as indicated for GV (0 h), and cultured in vitro for MI (6 h) and MII (16 h) from PMSG-primed WT and Nat10-ZcKO females. Scale bar, 100 μm. b, c Percentage of oocytes at GVBD in b and MII in c after the release of GV oocytes cultured in IBMX-containing medium from PMSG-primed WT and Nat10-ZcKO females. Data are presented as mean ± SEM, n = 3. **p < 0.01, ***p < 0.001 by two-tailed Student’s t-test. d Average numbers of superovulated oocytes at MII from WT (30.57 ± 0.92) and Nat10-ZcKO (3.8 ± 1.15) mice following PMSG and hCG injection in vivo. Data are presented as the mean ± SEM, n = 5. ***p < 0.001 by two-tailed Student’s t-test. e and f Immunofluorescence staining images of superovulated oocytes collected at 16 h after hCG injection by α-TUBULIN staining. Oocytes with MI arrest, Anaphase-to-telophase arrest in prophase I (AI-TI), and aberrant spindles were observed e and counted f in Nat10-ZcKO mice. Scale bar, 40 μm. Data are presented as the mean ± SEM, n = 3. ***p < 0.001 by two-tailed Student’s t-test. g, h Representative gross morphology of preimplantation embryos at various stages as indicated derived from superovulated WT and Nat10-ZcKO oocytes (after hCG priming) fertilized with WT sperm in (g). Arrows point to the blastocysts; a quantitative comparison of the average numbers of preimplantation embryos at varied stages was shown in (h). Scale bar, 100 μm. Data are presented as the mean ± SEM, n = 5. ****p < 0.0001 by two-tailed Student’s t-test. n = 3 biologically independent samples were included in each group (a, e, g). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig6_HTML.jpg |
0.429866 | c07028b2296340f6bb2a1c58417b49d3 | Mini-bulk SMART-seq2 analyses identified the dysregulated maternal transcriptome in Nat10-ZcKO oocytes.a A diagram showing mouse oocyte sample collection for mini-bulk SMART-seq2. b Bar graph showing the numbers of transcripts detected in WT and Nat10-ZcKO oocytes at GV and MII stages (TPM ≥ 1). The box indicates the upper and lower quantiles, the thick line in the box indicates the median, and the whiskers indicate the 2.5th and 97.5th percentiles. Data are presented as mean ± SEM, n = 3 biologically independent samples. n.s., non-significant by two-tailed Student’s t-test. c Scatter plot of mini-bulk SMART-seq2 data showing differentially expressed genes (DEGs) in Nat10-ZcKO MII oocytes. Red color: Up-regulated; Blue color: Down-regulated; Cutoff: fold change (FC) ≥ 2, adjusted p < 0.05. d Gene Ontology (GO) enrichment analysis of up-regulated genes in Nat10-ZcKO MII oocytes (Cutoff: FC ≥ 2, adjusted p < 0.05). e Heatmap of representative genes from four major functional GO categories showing up-regulated expression in Nat10-ScKO MII oocytes. f Bar plots showing the qPCR analyses of relative mRNA expression levels for a panel of up-regulated genes identified by mini-bulk SMART-seq2. Data are presented as the mean ± SEM, n = 3 biologically independent samples, and analyzed by two-tailed Student’s t-test. g and h Box plots showing the relative expression levels of the transcripts at the GV and MII stages as indicated in (g). The box indicates the upper and lower quantiles, the thick line in the box indicates the median, and the whiskers indicate the 2.5th and 97.5th percentiles. Data are presented as the mean ± SEM, n = 3. ****p < 0.0001 by two-tailed Student’s t-test.; and the relative fold changes of mRNA levels in (h). The box indicates the upper and lower quantiles, the thick line in the box indicates the median and the whiskers indicate 2.5th and 97.5th percentiles. Data are presented as the mean ± SEM, n = 3. ****p < 0.0001 by two-tailed Student’s t-test. i Box plot showing gene expression levels at the GV and MII stages with genes divided into 5 bins according to their relative expression abundance in the WT MII oocytes. Data are presented as the mean ± SEM, n = 3 biologically independent samples. ****p < 0.0001, n.s., non-significant by two-tailed Student’s t-test. j Sankey diagram showing the overlapping of the DEGs (1196 up-regulated vs. 555 down-regulated) with genes exhibiting up- [FC(MII/GV) ≥ 2, p < 0.05], down- [FC(MII/GV) ≤ −2, p < 0.05], or stable expression patterns in WT MII relative to GV stage oocytes (TPM ≥ 1). k Venn diagram showing the overlapping of down-regulated transcripts between WT MII oocytes relative to GV oocytes (2011, Cutoff: TPM ≥ 1, FC[GV/MII] ≥ 5), and Nat10-ZcKO MII oocytes relative to GV oocytes (1206, Cutoff: TPM ≥ 1, FC[GV/MII] ≥ 5). The total 595 overlapping transcripts represent those that were concurrently down-regulated in both WT MII and Nat10-ZcKO MII oocytes. In other words, they were degraded regardless of Nat10 presence (Nat10-unrelated). l Degradation trend patterns of maternal transcripts during the GV-MII transition in WT and Nat10-ZcKO oocytes. Each light-yellow line represents the expression levels of one gene, and the blue and red lines represent the median expression levels in WT and Nat10-ZcKO, respectively. Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig7_HTML.jpg |
0.417894 | dcd25f1d6cbe41e79b7b09fc27c622b8 | Hairpin Adaptor-Poly(A) Tail length (HA-PAT) assay validated the deficient maternal mRNA decay in Nat10-ZcKO MII oocytes.a Venn diagram showing the overlapping of transcripts that were stabilized during GV-to-MII transition in Cnot6l−/− and Nat10-ZcKO MII oocytes (FC = [WT MII/Nat10-ZcKO MII]≥2, p < 0.05). b Fold change of relative expression levels of transcripts encoding ribosomal protein subunits in Nat10-ZcKO relative to WT oocytes at the MII stage. The values of log2(FC[Nat10-ZcKO/WT]) are listed in the right column. c qPCR results showing the relative levels of indicated transcripts (Cnot6l, Cnot7 and Btg4) in WT and Nat10-ZcKO oocytes at MII stage. Data are presented as the mean ± SEM, n = 3. n.s., non-significant, **p < 0.01 by two-tailed Student’s t-test. Cnot6l, p = 0.0906; Cnot7 p = 0.0020; Btg4 p = 0.0031. d Western blot displaying the NAT10, CNOT6L, CNOT7 and BTG4 protein levels in MII oocytes of WT and Nat10-ZcKO mice. α-TUBULIN was used as a loading control. n = 3 biologically independent samples were included in each group. e A schematic illustration depicting the design strategy and the key steps for Hairpin Adaptor-Poly(A) Tail length (HA-PAT) assay. The 1st strand of cDNA was synthesized with the hairpin adaptor (HA) primer in conjunction with a P5TSO primer containing three “G”, via a mechanism of “template-switching”. GSP, Gene-specific primer; A0, the PCR product resulting from the amplification with a gene-specific pair of GSPxF and GSPxR primers; GSPxR primer was designed against an mRNA’s 3′ terminals preceding the poly(A) sequence; poly(A)-containing PCR products were amplified with GSPxF and fixed HAPrimerR primers. The full sequence for hairpin adaptor (HA) is listed at the bottom. W indicates degenerate nucleotides (A or T); * The asterisk indicates the phosphorothioate modification. f, g HA-PAT assay results showing changes in poly(A)-tail lengths of indicated transcripts in WT and Nat10-ZcKO oocytes at GV and MII stages. Experiments were performed in triplicates; a representative image is shown in the 2% agarose gel in f and the length distribution is shown in the densitometric curves in (g). n = 3 biologically independent samples were included in each group (d, f). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig8_HTML.jpg |
0.419052 | 815086fc9d464fe8a1f223c5d6450ab3 | Nat10 is translationally required for cell cycle progression.a Schematic illustration showing the procedures for the generation of two stable, TMX-inducible MEF cell lines (Nat10+/Cre, lox/lox) from the Ubc-cre; Nat10lox/lox embryos following a 3T3 protocol (see the “Methods” section). Inducible Nat10 KO was achieved by 2 µM OHT treatment for three consecutive days. Rescue of Nat10 was attained by overexpression (OE) of WT Nat10 ORF plasmid. b Western blot displaying the NAT10 and PCNA protein levels in WT and OHT (Ubc-cre; Nat10lox/lox) MEF line. α-TUBULIN was used as a loading control. c Quantitative RT–PCR results showing the relative expression levels of Nat10 in WT and OHT MEF line. Data are presented as mean ± SEM, n = 3. ****p < 0.0001 by two-tailed Student’s t-test. d Cell cycle analysis by flow cytometry between WT and OHT MEF cells. G1, p = 0.0083; S, p = 0.0017; G2/M, p < 0.0001; p-value are analyzed by two-tailed Student’s t-test. e Annexin V apoptosis detection of WT and OHT MEF cells. Q4, Viable cells, p = 0.2983; Q3, Early apoptosis, p = 0.2147; Q2, Late apoptosis, p = 0.3122; Q1, Necrotic cells, p = 0.7863. p-value are analyzed by two-tailed Student’s t-test. f CCK8 assay showing the cell proliferation rates among WT, OHT treatment and OHT plus Nat10 overexpression (OE) groups. Data are presented as the mean ± SEM, n = 3 biologically independent samples and analyzed by two-tailed Student’s t-test. g, h Comparison of cell proliferation as visualized by Ki67 labeling in g and quantification in h among WT (empty vector), OHT treatment and Nat10 overexpression groups. Scale bar, 50 μm. Data are presented as mean ± SEM, n = 3. *p < 0.05, **p < 0.01 by two-tailed Student’s t-test. Vector-OHT, p = 0.0026; OHT-Nat10, p = 0.0340. i, j The polysome profiling displaying the translational efficiency and ribosome assembly in MEF cells analyzed by sucrose density gradient centrifugation. The graphic curves showed the polysome profiles of MEF cells treated by mock (Blue) or OHT (Red) in i. Comparison of the ratios of 60S to 40S (Left) and of 80S to 40S (Right) in MEF cells with mock treatment (Blue) or OHT (Red) in (j). Data are presented as mean ± SEM, n = 3. ***p < 0.001 by two-tailed Student’s t-test. 60S/40S, p = 0.0008; 80S/40S, p = 0.0003. n = 3 biologically independent samples were included in each group (b, d, e, g, i). Source data are provided as a source data file. | PMC10287700 | 41467_2023_39256_Fig9_HTML.jpg |
0.41204 | 951df9b68d1c4128884e27258d209258 | Experimental procedure and tasks. (A) Sequential order of the tasks. First, participants performed the reachability-judgment task. Second, the actor performed the stimuli-selection task, while the observer observed his/her confederate’s performance. Third, participants realised the reachability-judgment task for a second time. Finally, participants performed again the stimuli-selection task, but switching their roles: the observer realised the stimuli-selection task, while the actor observed. (B) Distribution of the reward-yielding stimuli as function of the group. In the Control group, the probability to select a reward-yielding stimulus was 50% both in the space near the actor (rows 1, 2, 3 of the grid) and in the space near the observer (rows 4, 5, 6). In the Towards Actor group, the probability to select a reward-yielding stimulus was 75% in the space near the actor and 25% in the space near the observer. On the contrary, in the Towards Observer group, it was 75% in the space near the observer and 25% in the space near the actor. It is important to note that when the observers performed the stimuli-selection task, the probability to select a reward-yielding stimulus was 50% both in the near and far spaces (as in the Control Group) for all the three groups, regardless of the group assigned during the observation phase. In this way, we expected observers to base their selection strategy on the observation of actors’ performances, rather than on the detection of a biased distribution of reward-yielding stimuli. | PMC10287734 | 41598_2023_37189_Fig1_HTML.jpg |
0.546597 | 61c5f99caa234658b10ab0030f866a99 | Posttest–pretest difference in reachability threshold as function of the group (Control, Towards Actor, Towards Observer) and the role (Actor, Observer). (A) Actor’s posttest–pretest differences in reachability threshold. Only the Towards Observer group showed a significant change in reachability threshold, which increased in the posttest compared to the pretest (posttest–pretest > 0). No significant change was observed for the other two groups. (B) Observer’s posttest–pretest differences in reachability threshold. The Towards Actor Group showed a significant change in reachability threshold, which increased in the posttest compared to the pretest (posttest–pretest difference > 0). The Control group showed also a significant change in reachability threshold, which decreased in the posttest compared to the pretest (posttest–pretest difference < 0). No significant change was observed for the Towards Observer group. Histograms represent the mean posttest–pretest difference in reachability threshold. Dots represent individual posttest–pretest differences. Error bars represent 95% confidence intervals. *p < 0.050, **p < 0.010. | PMC10287734 | 41598_2023_37189_Fig2_HTML.jpg |
0.438805 | 4bea7c3142a541fb9f400894ff5aed30 | Density maps illustrating the frequency at which each location of the touch-screen table was chosen when it contained a stimulus. The rectangles represent the distribution grid composed of 42 cells (6 rows × 7 columns). The colour bar ranges from blue (rare selection) to red (frequent selection). The human silhouette above or below each density map represents participants’ position during the task. (A) Actors’ performance during the stimuli-selection task. The Control group tended to explore the whole surface. The Towards Actor group explored mainly the space near themselves, while the Towards Observer group explored the whole surface tending slightly towards the space near the observer. (B) Observers’ performance during the stimuli-selection task (first 3 blocks only). The three groups did not show any particular trend in their early selection strategy. (C) Mean number of reward-yielding stimuli obtained by the actor. Histograms represent the mean number of reward-yielding stimuli obtained by the actor in the distal space (i.e., near the observer). Dots represent individual data and error bars 95% confidence intervals. Percentage values represent the proportion of reward-yielding stimuli obtained in the distal space with respect to the total amount of stimuli selected. ***p < 0.001. | PMC10287734 | 41598_2023_37189_Fig3_HTML.jpg |
0.477648 | 74de5ce2e40c489189d1f0aead1189d8 | Mean percentage of stimuli selected in the space near the observer (for the actor) or near the actor (for the observer), as function of the group (Control, Towards Actor, Towards Observer) and the role (Actor, Observer). (A) Mean percentage of stimuli selected by the actor in the space near the observer across the 17 blocks, as function of the group. As shown by linear regressions, only the Towards Observer group changed its selection strategy during the task: they selected progressively more stimuli in the space near the observer, which was associated, for this group, to a higher probability of obtaining a reward-yielding stimulus. (B) Results of the permutation-based multiple comparisons tests for the actor (*p < 0.050). The Towards Actor and Control groups showed different selection strategies from the 1st block on, and throughout all the task. By contrast, the Towards Observer group showed a different strategy from the Control group from the 14th block on. (C) Mean percentage of stimuli selected by the observer in the space near the actor across the 17 blocks, as function of the group. As shown by linear regressions, the selection strategy adopted by the three groups did not change across the task. (D) Results of the permutation-based multiple comparisons for the observer. Any difference did not emerge between the three groups. *p < 0.050. | PMC10287734 | 41598_2023_37189_Fig4_HTML.jpg |
0.508907 | 3fcfd567aeca4663b00656dffff92492 | (A) Schematic representation of the experimental setting. During the reachability-judgment task, the video-projector projected an image on the mirror, through a translucent screen (which improved the sharpness of the image). This generated an optical projection effect, increasing the depth of the visual field and making the stimuli appear at the level of the touch-screen table. (B) Participants’ posture during the reachability-judgment task. The mirror hid participants’ hands and the keyboards used to provide the answers. During the task, the touch-screen table was covered by a black sheet, in order to avoid any interference from external luminous sources. Once the reachability-judgment task was completed, the mirror and the keyboards were displaced on the side, and the black sheet covering the touch-screen table removed. | PMC10287734 | 41598_2023_37189_Fig5_HTML.jpg |
0.428148 | 6c68c24d7b174e16873fdcae12b82fe4 | Development of practical catalysts for asymmetric hydrogenation of ketones affording high-value chemicals.A The state-of-the-art neutral Noyori-type catalysts for asymmetric hydrogenation of ketones. B Our conceptually advanced ultra-efficient anionic Ir-catalyst for asymmetric hydrogenation of (nitrogen-containing) ketones. ee: enantiomeric excess. | PMC10287737 | 41467_2023_39375_Fig1_HTML.jpg |
0.491458 | 88598ca615e44735a53d4dc3a0cd5f73 | Asymmetric hydrogenation of ketones using Ir/phamidol catalyst.A Laboratory scale asymmetric hydrogenation of representative benchmark acetophenone and nitrogen-containing aromatic ketones. B Laboratory scale-up asymmetric hydrogenation of nitrogen-containing ketone as a key step in a novel selective route to chiral nicotine. | PMC10287737 | 41467_2023_39375_Fig2_HTML.jpg |
0.450737 | d71c687185f946eb92fa24c3fe099843 | A selective industrial route to chiral nicotine.A Batch process data of the key asymmetric hydrogenation of S4; B Schematic of our developed process for manufacture of chiral nicotine. | PMC10287737 | 41467_2023_39375_Fig3_HTML.jpg |
0.448644 | 60029f8bc41a41099037477d662feec4 | Characterization of Ir-complexes.Formation of anionic Ir-catalyst (NH-bind cis and CO-bind cis, in solid box) from Ir-precatalyst (C and D, in dash box) through complex A as evidenced by HRMS, NMR, IR, Raman, XRD, DFT, and catalysis data. Calculated relative Gibbs free energies at 298.15 K are given in brackets. | PMC10287737 | 41467_2023_39375_Fig4_HTML.jpg |
0.488958 | 95ee826bba1048bc85ee9da56f06186a | Performance of modular modified ligands in comparison with f-phamidol.Enantioselectivities and turnover numbers are given under the ligands. | PMC10287737 | 41467_2023_39375_Fig5_HTML.jpg |
0.455025 | ea7bd60eefd1465e8bc9df5ef8f828ef | DFT calculations on the mechanism.Predicted Gibbs free energy profile for the asymmetric hydrogenation of acetophenone via the active anionic Ir-catalyst D through ONa/MH bifunctional (in red) and NNa/MH bifunctional (in blue) paths. | PMC10287737 | 41467_2023_39375_Fig6_HTML.jpg |
0.427181 | 08a06d5812ab450e977247791a8402ce | Theoretical origin of the significantly enhanced activity.Schematic three-center-four-electron (3c-4e) orbital interactions between Ir and the hydride atoms. | PMC10287737 | 41467_2023_39375_Fig7_HTML.jpg |
0.501153 | 085c6d5f93df49869051ad9c7293bba5 | Inhibition of transcriptional CDKs causes widespread intron retention. (A) Venn diagram showing the overlap between genes regulated at the gene expression (GE) and alternative splicing (AS) level by THZ1 (6 h, 100 nM). Statistical analyses were performed by Fisher's exact test. (B) Pie chart showing percentages of the indicated splicing patterns affected by THZ1. (C) Bar graph showing percentages of events annotated in FAST-DB (white columns) and of those regulated by THZ1 treatment (grey columns) within each AS pattern. Statistical analyses of comparisons between THZ1-regulated events and their expected representation in the reference database were performed by modified Fisher's test. (D) Pie charts showing percentages of intronic or exonic events in unannotated events. (E) Pie charts showing percentages of intronic or exonic events in total events. (F) Pie charts showing percentages of up- and down-regulated introns in THZ1-treated cells. (G and H) Gene Ontology of up- and down-regulated IR events performed by the g-profiler tool. | PMC10287901 | gkad258fig1.jpg |
0.462104 | e28946b382ca41899a68c4ddcb8188fc | THZ1 treatment leads to widespread retention of proximal introns. (A) Metagene representation of IR location within the gene body. (B) Bar graph showing GE fold change between the first and second introns and all other introns. Statistical analysis was performed by Student's test. (C) Bar graph showing percentages of IR genes that were regulated at the GE level or not between the first and second up-regulated introns and all other introns (left panel) and between the first and second up-regulated and down-regulated introns (right panel). Statistical analyses were performed by Fisher's exact test. (D) Graphic representation of POLH and SOGA1 genes showing the IR event in the first intron and the reduction in read coverage in downstream portions of the transcript after THZ1 treatment. (E–H) Visualization of the RNA-seq reads profile of the intron-retaining region and PCR primer strategy used in POLH (E) and SOGA1 (G) genes. Bar graphs showing the results of qPCR analyses for the expression of the retained first intron (ex1-int1) and the reduction in downstream portions of the transcript (ex5-ex6) in POLH (F) and SOGA1 (H) genes relative to FKBP9. Data represent the mean of at least three independent experiments with relative standard devation (SD). Statistical analyses were performed by Student's test *P <0.05; **P <0.01; ***P <0.001. | PMC10287901 | gkad258fig2.jpg |
0.430024 | 17068958c6034d5ebfa54ee0cb2da30e | CDK12/13 kinase activity is required for optimal splicing of THZ1-regulated proximal introns. (A) Schematic representation of the substrates inhibited by THZ1 (CDK7, CDK12 and CDK13), SY-1365 (CDK7) and THZ531 (CDK12/13). (B) Proliferation assays of MiaPaCa-2 cells after 72 h of THZ1, THZ531 and SY-1365 treatment at the indicated doses. Data represent the mean of at least three independent experiments with relative SD. (C and D) Bar graphs showing the results of qPCR analyses for the expression of the retained first intron (ex1-int1) in POLH and SOGA1 genes relative to FKBP9 in cells treated for 6 h with THZ531 (100 nM) or SY-1365 (33 nM) (C) or knocked down for CDK12/13 (shCDK12/13) or CDK7 (shCDK7) or transfected with empty vector (shCTRL) (D). Data represent the mean of at least three independent experiments with relative SD. Statistical analyses were performed by one-way analysis of variance (ANOVA), *P <0.05; **P <0.01, ns = not significant. (E and F) Correlation of the expression of CDK12 (E) or CDK13 (F) with that of POLH and SOGA1 in patients from the pancreatic adenocarcinoma project (TCGA, Firehose Legacy). Statistical analyses were performed by Pearson's correlation coefficient (E and F). | PMC10287901 | gkad258fig3.jpg |
0.456478 | c1dc85b07e7b40d08340b41061d75150 | CDK12/13 inhibition causes a splicing defect of proximal introns in target genes. (A) Schematic representation for the isolation of nascent RNAs labelled with 4sU. Transcription of cells was blocked by treatment with 100 μM DRB for 6 h. In the last hour, 200 nM THZ531 or DMSO was added; then DRB was removed by washing the cells with PBS. In the last 30 min, nascent RNAs were labelled with 4sU in the presence or not of THZ531. (B and C) Bar graphs showing the results of qRT–PCR analysis of POLH (B) and SOGA1 (C) to evaluate the level of IR in nascent RNA (4sU labelled) using primers spanning the 5′ (ex1-i1 5′) and 3′ (i1/2 3′-ex2/3) splice site regions of the regulated intron with respect to the spliced mRNA (ex1-ex2/3) and primers spanning the 5′ splice site region of a non-regulated intron (ex5-i5 5′) with respect to the spliced mRNA (ex5-ex6). A graphical representation of the genomic regions analysed and of the PCR primer strategy used is illustrated. Data represent the mean of at least three independent experiments with relative SD. Statistical analyses were performed by Student's test *P <0.05; **P <0.01, ns = not significant. | PMC10287901 | gkad258fig4.jpg |
0.416146 | 3ccb9250036c43268c1bdc5032304cfc | Proximal introns regulated by CDK12/13 activity are characterized by weak 3′ splice sites. (A) Box plots representing comparison of the 5′ and 3′ splice site strength (MaxEnt score) between proximal introns (first and second) up- and down-regulated by THZ1 treatment, reference IR events not affected by THZ1 treatment (Ref. IR), constitutively spliced introns (Ref. const.) and introns from genes regulated by THZ1 only at the GE level (Ref. GE-reg). (B and C) Boxplots showing comparison between the groups described in (A) for distance (B) and percentage of pyrimidine (C) between the branchpoint (BP) and the 3′ splice site. Statistical analyses were performed by Student's test *P <0.05; **P <0.01; ***P <0.001, ns = not significant. | PMC10287901 | gkad258fig5.jpg |
0.408962 | 5869b93a47724f14961a5331abe8acc8 | CDK12/13 inhibition impairs the physical interaction of SF3B1 with RNAPII. (A) Representative western blot analysis of the co-immunoprecipitation between RNAPII and SF3B1 from MiaPaCa-2 nuclear extracts treated or not with RNase A. Rabbit non-immune IgGs were used as negative control. To assess degradation, RNA was isolated from both RNase A-untreated and -treated cell lysates and run on a 1% agarose gel to determine the integrity of the 28S:18S rRNA. The bar graph represents densitometric analysis of the co-immunoprecipitated SF3B1 with respect to the levels of immunoprecipitated RNAPII (mean of three independent experiments with relative SD). Statistical analyses were performed by Student's test, ns = not significant. (B) Representative western blot and densitometric analyses of RNAPII phosphorylated on Ser2, Ser5 or total RNAPII that co-immunoprecipitates with SF3B1 from MiaPaCa-2 nuclear extracts (mean of three independent experiments with relative SD). Statistical analyses were performed by one-way ANOVA, ***P <0.001. (C) Representative western blot and densitometric analyses of phospho-Ser2, phospho-Ser5 and total RNAPII in MiaPaCa2 cells treated or not with 200 nM THZ531 for 3 h. HSP90 was used as loading control (mean of three independent experiments with relative SD). Statistical analyses were performed by Student's test, **P <0.01, ns = not significant. (D) Representative western blot and densitometric analyses of SF3B1 and U1A co-immunoprecipitated with RNAPII in MiaPaCa-2 cells treated or not with 200 nM THZ531 for 3 h (mean of at least three independent experiments with relative SD). Statistical analyses were performed by Student's test, **P <0.01. (E) Representative western blot of SF3B1, RNAPII, PRP6 and PRP8 in cytosol, nucleoplasm and chromatin fractions of MiaPaCa-2 cells treated for 3 h with 200 nM THZ531. TUBULIN, U1-70K and H3 expression were evaluated as loading controls of the indicated fractions. For densitometric analyses, SF3B1 levels were normalized to U170K for the nucleoplasm fraction, and SF3B1 levels were normalized to H3 for the chromatin fraction. Data represent the mean of at least three independent experiments with relative SD. Statistical analyses were performed by Student's test, *P <0.05, ns = not significant. (F and G) qPCR analyses of RIP (F) and CLIP (G) assays of the binding of SF3B1 to the 3′ splice site of POLH intron 1 and SOGA1 intron 2 from cells treated for 3 h with DMSO or THZ531 (200 nM). Non-immune IgGs were used as control of the assays (mean of three independent experiments with relative SD). Statistical analyses were performed by one-way ANOVA, *P <0.05, **P <0.01, ***P <0.001. | PMC10287901 | gkad258fig6.jpg |
0.425899 | f64f602503ca4167b57dbeaa3bc8a523 | THZ531 synergizes with spliceosome inhibition in IR regulation and suppression of cell proliferation. (A) Results of qPCR analyses for the expression of the retained first intron in POLH and SOGA1 genes relative to FKBP9 in MiaPaCa-2 cells treated with suboptimal doses of THZ531 (50 nM) and PdB (3.3 nM) either alone or in combination for 6 h (mean of at least three independent experiments with relative SD). Statistical analyses were performed by one-way ANOVA, ***P <0.001. (B) Cell proliferation analysis of MiaPaCa-2 cells treated with suboptimal doses of THZ531 (25 nM) and PdB (1 nM) either alone or in combination (mean of at least three independent experiments with relative SD). Statistical analyses are reported in light blue when referring to 25 nM THZ531 treatment, in green when referring to 1 nM PdB treatment and in grey when referring to DMSO. Statistical analyses were performed by two-way ANOVA *P <0.05; **P <0.01; ***P <0.001. (C) Representative images and bar graph of MiaPaCa-2 cells labelled with cytotoxic green and NIR dyes for live cells after 96 h of treatment with suboptimal doses of THZ531 and PdB either alone or in combination analysed by the IncuCyte SX5 technology to evaluate the percentage of dead cells in each sample (mean of three independent experiments with relative SD). Statistical analyses were performed by one-way ANOVA, ***P <0.001. Scale bar 150 μm. (D) Representative western blot analysis of PARP1, γH2AX, H3 and HSP90 in MiaPaCa-2 cells treated for 48 h as indicated. (E–H) Fluorescence-activated cell sorting (FACS) analyses showing DNA content (7-AAD) to evaluate the cell cycle state of MiaPaCa2 cells after 24 h at optimal (E) or suboptimal doses (G) of the indicated drugs. Bar graphs (F and H) show the percentage of cells in G1, S and G2 phase. Data represent the mean of four independent experiments with relative SD. Statistical analyses were performed by one-way ANOVA, *P <0.05; **P <0.01; ***P <0.001. | PMC10287901 | gkad258fig7.jpg |
0.500251 | b96cc44319d345a6b69dc4a9308f4fd9 | CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1. | PMC10287901 | gkad258figgra1.jpg |
0.385554 | e8ed5ab794604144a2d25bbccf1b36a5 | Schedule of exposure in the experiment of UC developing (a) and UC self-healing (b). The operation in white grids was carried out through drinking and the operation in gray grids was carried out through gavage. CT, control group; NPs, 300 mg/kg/d TiO2 NPs treated group; DSS, 2.5% DSS treated group; DSS + 30/100/300 NPs, 2.5% DSS + 30/100/300 mg/kg/d TiO2 NPs treated group | PMC10288682 | 12989_2023_535_Fig1_HTML.jpg |
0.4471 | 025e9cac761b477d9de1b4386b4f06d7 | Change of mice colitis activity after treatment with TiO2 NPs. Change of body weight of mice in the experiment of UC developing (a) and UC self-healing (b), and change of the DAI score in the experiment of UC developing (c) and UC self-healing (d) (n = 10, \documentclass[12pt]{minimal}
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0.405114 | 16a60f6355b645538557a64876c274ad | Histopathological changes in colon of mice in the experiment of UC developing and UC self-healing. Red circles indicate areas of goblet cells loss; black arrows indicate inflammatory cell infiltration; blue arrows indicate loss of crypt | PMC10288682 | 12989_2023_535_Fig3_HTML.jpg |
0.416308 | 259e2492c7e241ac8bd4a4c1de7f547e | Inflammatory response level in colitis mice. Colon MPO activity (a) and cytokines level of colon (b, c) and serum (d, e) in the experiment of UC developing and UC self-healing (n = 6, \documentclass[12pt]{minimal}
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0.507012 | 9e48ebc43c5048199d180b76c4c45734 | Oxidative stress in colitis mice. Antioxidase activity level of colon and serum in the experiment of UC developing and UC self-healing (n = 6, \documentclass[12pt]{minimal}
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0.436549 | e615ea82439449fba2e604d9e73c4418 | Possible mechanisms of the effect of TiO2 NPs on UC via ROS-TXNIP-NLRP3 inflammasome pathway | PMC10288682 | 12989_2023_535_Fig6_HTML.jpg |
0.44366 | 8bf898a08a6e4cdd8e4a6fc00ac8e247 | TXNIP, caspase-1, IL-1β mRNA expression of colon in the experiment of UC developing and UC self-healing (n = 6, \documentclass[12pt]{minimal}
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0.449961 | 5b066041b9974ee8a37d9eb43c6bce42 | Characterization of TiO2 NPs. The shape, size (a) and particles size distribution (b) of TiO2 NPs based on TEM. The zeta potential and hydrodynamic diameter of 3, 10 and 30 mg/ml TiO2 NPs in ultrapure water (c) tested at 0 h post sonication. The red, green and blue line represents three parallel detections | PMC10288682 | 12989_2023_535_Fig8_HTML.jpg |
0.475287 | f62bbd7be2e64cb78db36f214a4f4e83 | Cohen’s d values for group comparisons of the dependent variables studied. The order of tests in the figure follows the sequence of their administration. | PMC10288889 | medscimonit-29-e940409-g001.jpg |
0.424606 | 1a8453ba5c504319a1581355f96be10a | Map indicting the location of El Gigante rockshelter in western Honduras and planview map of the rockshelter showing the locations of test excavations and looters’ pits.All elements of the map come from Natural Earth (http://www.naturalearthdata.com/) and are compatible with the CC-BY 4.0 license. | PMC10289419 | pone.0287195.g001.jpg |
0.41714 | 30e21dd3eb2245c6bfbba3a559d0d21c | An example stratigraphic profile and associated distribution of radiocarbon dates.A. Intact stratigraphy at El Gigante, Units 1, 3 and 7 (south profiles; 2001 excavations). B. Stratigraphic distribution of 14C-dated materials, with excavated mean stratum thickness and superpositioning of main cultural components (data in S4 Table in S1 File). | PMC10289419 | pone.0287195.g002.jpg |
0.428412 | 9cd78997a2014f89aa7675b1cec18a39 | The distribution of all 369 14C dates from El Gigante rockshelter.A. Calibrated dates are grouped according to their inclusion or exclusion in the chronological model and categorized by model phase. The relative depositional intensity of these habitational episodes is generated using kernel density estimation (KDE; light gray) of calibrated 14C dates with a 50-year bandwidth. This record compares favorably with additional proxy records: the depositional rate of paleobotanical specimens (green with light green shading showing 4x exaggeration so earlier trends are visible) and the rate of sedimentation across all units (light orange). B. Sequenced radiocarbon chronology displaying modeled occupational phases shown relative to the regional cultural chronology. Probability distributions for all 14C dates and the modeled phase boundaries are provided in S1 Fig OxCal model, graphical output. Given the extensive nature of the sampled materials, gaps present in the 14C record are likely indicative of gaps in the site’s occupational sequence. The raw data, model output and model code can be found in S1–S3 Tables in S1 File. | PMC10289419 | pone.0287195.g003.jpg |
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