dedup-isc-ft-v107-score
float64 0.3
1
| uid
stringlengths 32
32
| text
stringlengths 1
17.9k
| paper_id
stringlengths 8
11
| original_image_filename
stringlengths 7
69
|
|---|---|---|---|---|
0.455243 | 87a63f2ed31144a2af57590adc4acf2c | (a)
SEM and optical images of a graphene aerogel and (b) schematics
of the chemical changes caused by high-temperature annealing, which
leads to a removal of oxygen functional groups and structural defects
and covalent cross-linking. (c) Electrical conductivity of graphene
aerogels as a function of annealing temperature using a four-probe
method. (d) Raman spectra of GA annealed at different temperatures.
(e) ID/IG ratio
and crystallite size analysis as a function of annealing temperature.
(f) Density of defects and FWHM of the G peak as a function of annealing
temperature. | PMC10258840 | jp3c01534_0004.jpg |
0.447188 | 4b5d868b7f27486cb771eef24b94251d | XPS
analysis of a reduced graphene oxide aerogel as a function
of annealing temperature. (a) C 1s and (b) O 1s spectra of GA annealed
at different temperatures. Concentrations of (c) sp2 and
sp3 carbon and (d) different oxygen species in the annealed
GA samples. The sp3 carbon includes both structural and
functional groups. | PMC10258840 | jp3c01534_0005.jpg |
0.418531 | c178c7aed789410190cdbbe7d3f877aa | PRISMA flowchart of the study selection process | PMC10260226 | jba-12-026-g001.jpg |
0.359299 | bacbf25b10104a19938c73cd62a98c41 | Percentage of teachers plotted against scores on BMIS scale and subscale. Low score, Moderate score, and High score | PMC10263089 | IJPsy-65-424-g001.jpg |
0.423617 | a14b27e8acf94a25886cf52233966506 | Example membrane potential recordings and cortical depth distributions of cell classes.(A) Membrane potential (Vm) recording from an excitatory neuron recorded at 375 μm below the pial surface. From top to bottom: right C2 whisker angular position (green); Vm (black, APs are truncated); active contacts between the C2 whisker and the object (grey). (B) Same as A, but for a PV-expressing GABAergic neuron recorded at 185 μm below the pial surface (Vm, red). (C) Same as A, but for a VIP-expressing GABAergic neuron recorded at 227 μm below the pial surface (Vm, blue). (D) Same as A, but for an SST-expressing GABAergic neuron recorded at 207 μm below the pial surface (Vm, orange). (E) Distribution of the estimated cell body depths for each recorded neuron according to cell class. Dashed lines indicate depth boundaries used to define cortical layers. (F) Anatomical reconstruction of the cell body locations of GABAergic neurons within the C2 barrel column (top) in three example brains from which we did not record, with the C2 barrel in layer 4 colored green. The distributions of PV-expressing (n = 4 mice), VIP-expressing (n = 3 mice) and SST-expressing (n = 3 mice) neurons are quantified across mice along the depth of the cortical column (below) with the histogram indicating mean ± SD. | PMC10263341 | pone.0287174.g001.jpg |
0.447709 | c7f34532192a4f59bd4ae1d50f7926f4 | Supra- and sub-threshold membrane potential fluctuations during quiet wakefulness.(A) Example Vm recordings from excitatory (EXC), PV-expressing, VIP-expressing and SST-expressing neurons, during 1 s of quiet wakefulness. Averaged action potentials (APs) are shown above on an expanded timescale. (B) Mean AP duration for the four cell classes. Open circles show individual neuron values. Filled circles with error bars show mean ± SD. Statistical differences between cell classes were computed using a Kruskal-Wallis test (p = 3.2x10-32) followed by a Tukey-Kramer multiple comparison test. (C) Same as B, but for the mean firing rate during (Kruskal-Wallis test, p = 3.3x10-29). (D) Same as B, but for the mean subthreshold Vm (Kruskal-Wallis test, p = 8.1x10-15). (E) Same as B, but for the mean standard deviation (SD) of the subthreshold Vm (Kruskal-Wallis test, p = 1.9x10-16). (F) Grand-average FFTs computed from the subthreshold Vm for each cell class. (G) Same as B, but for the mean 1–10 Hz FFT amplitude of the subthreshold Vm (Kruskal-Wallis test, p = 1.7x10-16). | PMC10263341 | pone.0287174.g002.jpg |
0.455479 | cbd5ed448a68445e864d83b504faaecb | Supra- and sub-threshold membrane potential changes at the onset of whisking without object contact.(A) Example Vm recordings from excitatory (EXC), PV-expressing, VIP-expressing and SST-expressing neurons during the transition from quiet wakefulness to active whisking without object contacts. The angular whisker position (green) is shown above and the Vm below (APs truncated). (B) From top to bottom: grand-average whisker angle, Vm and firing rate aligned to whisking onset at time = 0 s computed for each cell class. (C) Mean change in Vm at whisking onset (0–200 ms) for the four cell classes. Open circles show individual neuron values. Filled circles with error bars show mean ± SD. Statistical differences for the change in membrane potential comparing quiet and whisking were computed using a Wilcoxon signed rank test for each cell class (shown below the data points). Statistical differences between cell classes were computed using Kruskal-Wallis test (p = 1.1x10-9) followed by a Tukey-Kramer multiple comparison test (shown above the graph). (D) Same as C, but for the change in firing rate (Kruskal-Wallis test, p = 1.9x10-4). (E) Vm change at whisking onset in SST-expressing neurons vs cell depth showed a significant positive correlation (Spearman test: Rho = 0.66 with p = 3.5x10-8) (above). Open circles represent individual neurons. Grand-average Vm at whisking onset for SST-expressing neurons recorded between 0–250 μm (L2), 250–400 μm (L3) and 400–600 μm (L4) below the pial surface (below). | PMC10263341 | pone.0287174.g003.jpg |
0.425545 | d114a05c04eb46ea95a8ba7ef6da3f46 | Membrane potential dynamics across quiet and whisking states.(A) Mean subthreshold Vm computed for 2 s epochs of quiet wakefulness and whisking for the same neurons. Grey lines show individual neurons. Filled circles with error bars show mean ± SD. P values indicate statistical differences (Wilcoxon signed-rank test). (B) Same as A, but for the mean standard deviation (SD) of subthreshold Vm. (C) Same as A, but for the mean firing rate. (D) Grand-average FFTs of the subthreshold Vm computed for 2-s epochs of quiet wakefulness and whisking for each cell class. (E) Ratio between the mean change in FFT amplitude during whisking relative to quiet wakefulness, (FFTwhisking—FFTquiet) / FFTquiet, computed for each cell (open circles) in the 1–10 Hz and 30–90 Hz frequency bands. P values indicate statistical differences (Wilcoxon signed-rank test). | PMC10263341 | pone.0287174.g004.jpg |
0.450637 | 6fc8d1da62f84e0ea28f35da66e9c9a0 | Fast membrane potential fluctuations phase-locked with the whisking cycle.(A) Example averaged reconstructed angular whisker position (green) and averaged Vm aligned to the phase of the whisking cycle for excitatory (EXC), PV-expressing, VIP-expressing and SST-expressing neurons. (B) Mean whisker phase-locked Vm modulation amplitude for the four cell classes. Open circles show individual neuron values. Filled circles with error bars show mean ± SD. Statistical differences between cell classes were computed using a Kruskal-Wallis test (p = 7.8x10-8) followed by a Tukey-Kramer multiple comparison test. (C) Polar plots showing the mean amplitude of Vm whisking phase-locked modulation vs phase of peak Vm for the four cell classes. Open circles show individual cells. | PMC10263341 | pone.0287174.g005.jpg |
0.486576 | 159d0898eca64ee8937d310f0575fec8 | Active touch-evoked changes in membrane potential.(A) Example angular whisker position (green) and Vm averages at touch onset from excitatory (EXC), PV-expressing, VIP-expressing and SST-expressing neurons. (B) Grand-average whisker angle, change in Vm and change in firing rate at touch onset for each cell class. (C) Superimposed grand-average change in Vm (above) and in firing rate (below) for the four cell classes. The change in Vm was quantified for an early (5–20 ms) and a late (30–100 ms) time-window in panels E and F; the change in firing rate was quantified for a single (0–100 ms) time-window in panel D. (D) Mean change in firing rate after touch onset for the four cell classes (0–100 ms time-window). Open circles show individual neuron values. Filled circles with error bars show mean ± SD. Statistical significance for each cell class was tested using a Wilcoxon signed-rank test (p values are shown below); statistical differences between cell classes were computed using a Kruskal-Wallis test (p = 6.5x10-14) followed by a Tukey-Kramer multiple comparison test (p values are shown above). (E) Same as D, but for the change in Vm in the early (5–20 ms) time-window (Kruskal-Wallis test, p = 4.5x10-7). (F) Same as E, but for the late (30–100 ms) time-window (Kruskal-Wallis test, p = 0.13; no multiple comparison test). | PMC10263341 | pone.0287174.g006.jpg |
0.418322 | 9aa67cf9d9124e9ea6d771106ce92281 | Frequency-dependent active touch membrane potential signals.(A) Example Vm averages at touch onset for short (< 80 ms, light traces) and long (> 100 ms, dark traces) intercontact intervals from excitatory (EXC), PV-expressing, VIP-expressing and SST-expressing neurons. (B) Grand-average Vm and firing rate at touch onset for short and long intercontact-intervals for each cell class. (C) Mean difference of PSP amplitude between short and long intercontact intervals for the four cell classes. Open circles show individual neuron values. Filled circles with error bars show mean ± SD. Statistical significance for each cell class was tested using a Wilcoxon signed-rank test (p values are shown below); statistical differences between cell classes were computed using a Kruskal-Wallis test (p = 0.0015) followed by a Tukey-Kramer multiple comparison test (p values are shown above). (D) Same as C, but for the mean difference in peak Vm after touch onset (Kruskal-Wallis test, p = 4.9x10-4). (E) Same as C, but for the mean difference in firing rate after touch onset (Kruskal-Wallis test, p = 8.9x10-5). | PMC10263341 | pone.0287174.g007.jpg |
0.485941 | dd0672eb0c9640a2a7110c51e03036a8 | Stimulation of postinspiratory complex (PiCo) in mice that lack ChR2 or in a region outside of PiCo does not result in activation of PiCo neurons.(A) Representative traces of PiCo stimulation in Ai32+/+ mice, not crossed with any genetic cre lines, demonstrates no motor response and no effect on respiratory cycle. (B) Representative trace of PiCo stimulation in ChATcre:Vglut2FlpO mice injected with the pAAV-hSyn Con/Fon hChR2(H134R)-EYFP vector, but did not transfect ChR2 in any neurons, shows no response to PiCo stimulation. (C) Schematic of the in vivo preparation including all nerves and muscles recorded from and ventral optrode placement. Bipolar EMGs were placed in the (1) submental complex, located underneath the chin, recording from the geniohyoid, mylohyoid, and digastric muscles; (2) the laryngeal complex, consisting of the posterior cricoarytenoid; lateral, transverse, and oblique arytenoid, cricothyroid, and thyroarytenoid muscles; and (3) the costal diaphragm. Monopolar suction electrodes were attached to the hypoglossal (XII) and vagus (X) nerves. The blue circles on the surface of the ventral brainstem represents laser location of PiCo activation, corresponding to the representative trace on the right (blue) that triggers a swallow. Moving the lasers medial and slightly caudal (red triangles) does not active PiCo neurons and therefore results in no motor response depicted in the representative trace on the right with the red vertical bar. | PMC10264072 | elife-86103-fig1-figsupp1.jpg |
0.364321 | a1647d26211649b0b23212a4a608710a | Prolonged stimulation of postinspiratory complex (PiCo) does not trigger sequential swallow.10 s stimulation of ChATcre:Vglut2FlpO:ChR2 neurons reveals PiCo does not trigger multiple swallows but only a single swallow at the beginning. The blue bar indicates laser stimulation. | PMC10264072 | elife-86103-fig1-figsupp2.jpg |
0.468131 | 81d26415427b402ab1ee165a82539db8 | Optogenetic stimulation of postinspiratory complex (PiCo) neurons regulates swallow and laryngeal activation in a phase-specific manner.(A) Scatter plot of the probability of triggering a swallow (orange) or laryngeal activation (blue) across the respiratory phase (0 start of inspiration, 1 start of next inspiration) in ChATcre:Ai32 mice. * indicates significant increase in the difference between probability of evoking a swallow or laryngeal activation within the first 10% (p=0.02), 70% (p=0.04), and **90% (p=0.005) of the respiratory cycle. (Bi) Scatter plot of the probability of triggering a swallow shows no difference between Vglut2cre:Ai32 (purple), ChATcre:Ai32 (green), and ChATcre:Vglut2FlpO:ChR2 (gold) mice. (Bii) There is no change in the probability of stimulating laryngeal activation between ChATcre:Ai32 and ChATcre:Vglut2FlpO:ChR2 mice. However, there is a significant difference in the probability between Vglut2cre:Ai32 (purple) and ChATcre:Vglut2FlpO:ChR2 (gold) mice at **70% (p=0.01) and **90% (p=0.003) of the respiratory cycle and Vglut2cre:Ai32 and ChATcre:Ai32 (green) mice at ##90% (p=0.006) of the respiratory cycle. (C) Representative traces of PiCo-triggered swallow on the left showing the rostrocaudal swallow motor sequence starting with the peak activation of the submental complex and then the laryngeal complex (red arrows), plus swallow-related diaphragm activation known as Schluckatmung. Characterization of laryngeal activation on the right showing only the laryngeal complex is activated in response to the laser in blue. | PMC10264072 | elife-86103-fig1.jpg |
0.431982 | bee0475bfb374a2bb60bb8fe8fd96028 | Individual responses in ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 separated by laser pulse duration.Respiratory phase shifts plots were divided into two groups: swallow, postinspiratory complex (PiCo) laser activation that triggered a swallow, or non-swallow, PiCo activation that resulted in laryngeal activation or no motor response. Laser pulse duration does not affect respiratory rhythm reset in either swallow or non-swallow responses. This allowed to group all laser pulse durations together seen in Figure 2. | PMC10264072 | elife-86103-fig2-figsupp1.jpg |
0.484352 | a7ade7f726dd441fbc23af045cec5236 | Postinspiratory complex (PiCo)-triggered swallows reset the respiratory rhythm, while non-swallows have minimal effect.Respiratory phase shifts plots were divided into two groups: swallow, PiCo activation that triggered a swallow, or non-swallow, PiCo activation that resulted in laryngeal activation or no motor response. (A) Individual responses in ChATcre:Vglut2FlpO:ChR2 (gold), ChATcre:Ai32 (green), and Vglut2cre:Ai32 (purple) and (B) line of best fit from the above graphs. (C) Representative traces of two examples of swallow (orange star) response on respiratory cycle. On the left, PiCo-triggered swallow inhibits inspiration, resulting in an earlier onset of the next inspiratory breath, and on the right a delay in the next inspiration. | PMC10264072 | elife-86103-fig2.jpg |
0.435458 | dacd59642a754273809bfe2b93a818dd | Effect of postinspiratory complex (PiCo) stimulation duration on swallow behavior and laryngeal activity.(A) Scatter plot of behavior duration versus laser pulse duration for swallow (orange) and laryngeal activation (blue) only in ChATcre:Vglut2FlpO:ChR2 mice. Each dot represents the average duration per mouse. Data for the laryngeal activation analysis, for all genetic mouse lines, is located in Supplementary file 1A. (B) Representative traces of swallow duration shown by submental complex EMG triggered by 40 ms pulse in orange on the left and 200 ms pulse on the right. Below: representative traces of laryngeal activation, laryngeal complex EMG, duration stimulated by 40 ms pulse in blue on the left, and increases in duration when triggered by 200 ms pulse on the right. | PMC10264072 | elife-86103-fig3.jpg |
0.420983 | 3338934fc9a641cb9c4f3d8a24d1ff3c | Postinspiratory complex (PiCo)-triggered swallows have a decrease in duration and amplitude compared to water-triggered swallows.(A) Comparison of durations and (B) amplitude in swallow-related characteristics for swallows triggered by water (Water stim) and swallows triggered by stimulation of PiCo (PiCo stim) in ChATcre:Ai32 (green, N = 10), Vglut2creAi32 (purple, N = 11), and ChATcre:Vglut2FlpO:ChR2 (gold, N = 6). X, vagus nerve; XII, hypoglossal nerve; LC, laryngeal complex. | PMC10264072 | elife-86103-fig4-figsupp1.jpg |
0.493695 | f6eb8a0d78584f45bd3891682b51340e | Swallow-related characteristics in water-triggered swallows and postinspiratory complex (PiCo)-triggered swallows.(A) Representative trace of a swallow triggered by injection of water into the mouth (blue arrow) on the left and PiCo stimulation (orange) on the right. (B) Histogram of swallows in relation to the onset of inspiration for water swallows (blue, n = 105), ChATcre:Ai32 (green, n = 214), Vglut2cre:Ai32 (purple, n = 369), and ChATcre:Vglut2FlpO:ChR2 (gold, n = 291). There are more swallows in Vglut2cre:Ai32 mice due to a larger N number and a higher probability of triggering a swallow over any other behavior (Figure 1B). (C) Dot plot of each swallow in relation to the inspiratory peak. Swallows triggered by water (blue) or PiCo activation occurred at the same time in relation to inspiratory peak. Data for (B) and (C) are located in Supplementary file 2. | PMC10264072 | elife-86103-fig4.jpg |
0.398731 | 8d8857c9240a4e99b8b4f78a43a5d599 | Anatomical characterization of postinspiratory complex (PiCo) region.(A) Coronal views (Bregma level –6.6 to –7.3 mm) of the ventromedial medulla showing the location of the ChAT neurons (magenta) in PiCo region. (B) Heat map showing the density of ChAT immunoreactive neurons from (B1) coronal and (B2) ventral view of four animals. (B3) Rostrocaudal distribution of the total number of ChAT immunoreactive counted 1:2 series of 25 µm sections into PiCo. Histological analysis of (A, B) was done in C57B6 mice. (C) Coronal views (Bregma level –6.6 to –7.3 mm) of the ventromedial medulla showing the location of the double-conditioned ChATcre:Vglut2FlpO:Ai65 neurons (red) in PiCo region. (D) Heat map showing the density of ChATcre:Vglut2FlpO:Ai65 neurons from (D1) coronal and (D2) ventral view of four animals. (D3) Rostrocaudal distribution of the total number of ChATcre:Vglut2FlpO:Ai65 neurons counted 1:2 series of 25 µm sections into PiCo. Histological analysis of (C, D) was done in ChATcre:Vglut2FlpO:Ai65 mice. X-axis is the transitioning point of compact and semi-compact NAmb. cAmb, nucleus ambiguus pars compacta; scAmb, nucleus ambiguus pars semi-compacta; Amb, nucleus ambiguus pars non-compacta; VII, facial motor nucleus; IO, inferior olive; py, pyramidal tract; Sp5, spinal trigeminal nucleus. | PMC10264072 | elife-86103-fig5-figsupp1.jpg |
0.409358 | d6f4969bb8624dfca6c43c4ebbfebbb0 | Selective transfection of cholinergic/glutamatergic neurons in postinspiratory complex (PiCo) in ChATcre:Vglut2FlpO:ChR2 mice.(A) Transverse hemisection through Bregma level (–6.9 mm) of the transfected neurons into PiCo bilaterally, left (A1) and right (A2), with the pAAV-hSyn Con/Fon hChR2(H134R)-EYFP vector. (A1a) magnification of the yellow square in (A1) and (A2a) magnification of the yellow square in (A2). (B) Heat map showing the density of neurons transfected by the pAAV-hSyn Con/Fon hChR2(H134R)-EYFP vector from (1) coronal and (2) ventral view of the seven animals used in the functional experiments. X-axis is the transitioning point of compact and semi-compact NAmb. (B3) Rostrocaudal distribution of the total number of transfected neurons counted 1:2 series of 25 µm sections into PiCo. cAmb, nucleus ambiguous pars compacta; scAmb, nucleus ambiguus pars semi-compacta; IO, inferior olive; icp, inferior cerebellar peduncle; Sp5, spinal trigeminal nucleus; VII, facial motor nucleus. | PMC10264072 | elife-86103-fig5.jpg |
0.471705 | f4006083913a4bdf990961bffa5d2186 | Missed or low transfection of postinspiratory complex (PiCo) neurons stimulates upper airway responses that cannot unambiguously be characterized as either swallows or laryngeal activation as defined before.(A) Representative trace of 80 ms activation of ChATcre:Vglut2FlpO:ChR2 neurons at PiCo, resulting in an unknown upper airway activation. The red arrows show the laryngeal complex peak activation occurs before the submental complex peak activation; a reverse order from a typical swallow shown in Figure 1C. (B) Scatter plot of behavior duration versus laser pulse duration for upper airway motor activation. The behavior duration increases as the laser pulse duration increases. Data for this plot is located in Supplementary file 1B. (C) Heat map showing the density of neurons transfected by the pAAV-hSyn Con/Fon hChR2(H134R)-EYFP vector from coronal view of the four ChATcre:Vglut2FlpO:ChR2 mice. Though bilateral transfection, ipsilateral represents the side of the brainstem with the greatest amount of transfection (69 ± 8 neurons and contralateral 34 ± 4 neurons, N = 4). Amb, nucleus ambiguus; IO, inferior olive; py, pyramidal tract; Sp5, spinal trigeminal nucleus. | PMC10264072 | elife-86103-fig6.jpg |
0.422316 | 86133de4600248c09b8a4e127cdb44e1 | Schematic 3—phase model of the heart rate performance curve (HRPC) during incremental cycle ergometer exercise with regular downward deflection and non-regular linear or inverse course (solid black lines) as well as plasma adrenaline and noradrenaline concentrations (dashed and dash-dotted black and grey lines, respectively) (modified from Hofmann et al., 1997; Pokan et al., 1995). | PMC10264846 | fphys-14-1178913-g001.jpg |
0.455042 | b09286afa2d64bc08bedf46f966048a1 | Heart rate (HR) at the second ventilatory threshold (VT2) as percentage of maximum heart rate (%HRmax) in participants with a regular or non-regular deflection of the heart rate performance curve in maximal incremental treadmill exercise tests. Data are presented as box plot showing the median, upper and lower quartile as well as minimum and maximum values. | PMC10264846 | fphys-14-1178913-g002.jpg |
0.54155 | 264494d0f9f04ae29fc608ce73139028 | Deflection of the heart rate performance curve (HRPC) depending on age-groups in participants with low- and high- (50% percentile) performance levels. Significant effects of age and performance (vmax) were shown in binary logistic regression [η2 (3, N = 1,104) = 50.637, p < 0.001, Nagelkerke´s R2 = 0.101]. | PMC10264846 | fphys-14-1178913-g003.jpg |
0.50142 | c25aa15a74894423aeb51dd82789df95 | Pathophysiology of Endobiliary Radiofrequency Ablation (ERFA) (modified from 25). | PMC10266199 | fonc-13-1077794-g001.jpg |
0.447957 | 1795e666b2e640f7a601444ac0dedeae | Proposed algorithm for Endobiliary Radiofrequency Ablation (ERFA) in the management of jaundiced patients with locally advanced unresectable cholangiocarcinoma (NR-CCA), Bismuth type I-III (modified from 8 and 23). | PMC10266199 | fonc-13-1077794-g002.jpg |
0.513326 | ef6ce785b89b4a1a97f54ab97671dbcf | Mucoid EPS molecular models of acetylated poly-β-D-mannuronate fraction (1-PolyM; top) and acetylated copolymeric β-D-mannuronate-α-L-guluronate (1-PolyMG; bottom) at a 1-chain scale.Carbon atoms are shown in black, oxygen in red, hydrogen in pink. The native calcium ions are shown in blue and bonds to the calcium ions are also shown in blue. Uronate nomenclature is also given. | PMC10266685 | pone.0287191.g001.jpg |
0.59587 | 1bd46f6f023e4a1f86fa06423f66c40f | Optimised gallium 1-chain EPS complexes, along-side their formation energies (eV), for the 1-PolyM EPS scaffold.Carbon atoms are shown in black, oxygen in red, hydrogen in pink, gallium in green and sodium in yellow. Bonds to the gallium and sodium ions are shown as green and orange dashed lines respectively. The cation coordination numbers (CN) are also displayed. For reference the Ca Poly-M Ef is -3.04 eV (Fig 1). | PMC10266685 | pone.0287191.g002.jpg |
0.580716 | 14e9bdacad1245f6b47f7191182e9050 | Optimised gallium 1-chain EPS complexes, along-side their formation energies (eV), for the 1-PolyMG EPS scaffold.Carbon atoms are shown in black, oxygen in red, hydrogen in pink, gallium in green and sodium in yellow. Bonds to the gallium and sodium ions are shown as green and orange dashed lines respectively. The cation coordination numbers (CN) are also displayed. For reference the Ca Poly-MG Ef is -5.73 eV (Fig 1). | PMC10266685 | pone.0287191.g003.jpg |
0.434869 | e78def59c08f435781be9fdc1b927ab7 | Optimised gallium 2-chain EPS complexes, along-side their formation energies (eV), for the 2-PolyM EPS scaffold.(a) substitution 1, (b) substitution 2, (c) substitution 3. Carbon atoms are shown in black, oxygen in red, hydrogen in pink, gallium in green and sodium in yellow. Bonds to the gallium and sodium ions are shown as green and orange dashed lines respectively. The gallium ions are labelled and the native calcium ions are shown in blue with bonds to these calcium ions also shown in blue. For reference the Ca-saturated 2-Poly-M Ef is -9.53 eV [13]. | PMC10266685 | pone.0287191.g004.jpg |
0.449727 | 9cbd1e4531024568b3814fd33099f59f | Optimised gallium 2-chain EPS complexes, along-side their formation energies (eV), for the 2-PolyMG EPS scaffold.(a) substitution 1, (b) substitution 2, (c) substitution 3. Carbon atoms are shown in black, oxygen in red, hydrogen in pink, gallium in green and sodium in yellow. Bonds to the gallium and sodium ions are shown as green and orange dashed lines respectively. The gallium ions are labelled and the native calcium ions are shown in blue with bonds to these calcium ions also shown in blue. For reference the Ca-saturated 2-Poly-M Ef is -10.01 eV [13]. | PMC10266685 | pone.0287191.g005.jpg |
0.546255 | 5578f3e776664645a99c3f84535451a3 | Less energetically favoured twisted-boat configuration adopted by the mannuronate residue (M2 top chain) within the 2-PolyM co-substitution gallium complex.Carbon atoms are shown in black, oxygen in red, hydrogen in pink and gallium in green. Bonds to gallium are shown in green. The twisted-boat uronate residue backbone is shown as dark green for clarity. For comparison, the 4C1 chair conformation is also given. | PMC10266685 | pone.0287191.g006.jpg |
0.422868 | 25250cbc51724e36a2b7d380636e5eb5 | Overview of model training.We trained a self-supervised three-dimensional convolutional neural network (CNN) to learn internal representations of protein structures by predicting wild-type amino acid labels from protein structures. The representation model is trained to predict amino acid type based on the local atomic environment parameterized using a 3D sphere around the wild-type residue. Using the representations from the convolutional neural network as input, a second downstream and supervised fully connected neural network (FCNN) was trained to predict Rosetta ΔΔG values. | PMC10266766 | elife-82593-fig1.jpg |
0.4776 | f9ad82ea82d8400c94adffff91a2d064 | Learning curve for the self-supervised 3D convolutional neural network.The model obtained at epoch 15 achieves a classification accuracy of 63% on the validation set. | PMC10266766 | elife-82593-fig2-figsupp1.jpg |
0.517682 | ec10e58ec80743a89e415d0b4a46af96 | Mean absolute prediction error for RaSP on the validation set, split by amino acid type of the wild-type and variant residue.Substitutions from glycine and cysteine as well as to proline generally have higher errors. | PMC10266766 | elife-82593-fig2-figsupp2.jpg |
0.445473 | b12ee1c2d40343da8ea4f74d68bb4c66 | RaSP versus Rosetta ΔΔG values for a full saturation mutagenesis of 10 test proteins separated into either exposed (A) or buried (B) residues.We speculate, that the RaSP prediction task is harder in the case of buried residues because Rosetta ΔΔG values generally have higher variance in those regions. Pearson correlation coefficients and mean absolute errors (MAE) were for this figure computed using only variants with Rosetta ΔΔG values in the range [–1;7] kcal/mol. Buried and exposed residue were classified based a relative surface accessible surface area (SASA) cut-off of 0.2. | PMC10266766 | elife-82593-fig2-figsupp3.jpg |
0.43436 | a21a92d3e7f24e56b31b808a1050d508 | Overview of RaSP downstream model training and testing.(A) Learning curve for training of the RaSP downstream model, with Pearson correlation coefficients (ρ) and mean absolute error (MAEF) of RaSP predictions. During training we transformed the target ΔΔG data using a switching (Fermi) function, and MAEF refers to this transformed data (see Methods for further details). Error bars represent the standard deviation of 10 independently trained models, that were subsequently used in ensemble averaging. Val: validation set; Train: training set. (B) After training, we applied the RaSP model to an independent test set to predict ΔΔG values for a full saturation mutagenesis of 10 proteins. Pearson correlation coefficients and mean absolute errors (MAE) were for this figure computed using only variants with Rosetta ΔΔG values in the range [–1;7] kcal/mol. | PMC10266766 | elife-82593-fig2.jpg |
0.404574 | b46b2746c65e4a06a74bda83beb37a29 | Comparing RaSP and Rosetta predictions to experimental stability measurements.Stability predictions obtained using (A–E) RaSP and (F–J) Rosetta are compared to experimental data for the five test proteins; myoglobin (1BVC), lysozyme (1LZ1), chymotrypsin inhibitor (2CI2), RNAse H (2RN2) and Protein G (1PGA) (Kumar, 2006; Ó Ó Conchúir et al., 2015; Nisthal et al., 2019). In the experimental study of Protein G, 105 variants were assigned a ΔΔG value of at least 4 kcal/mol due to low stability, presence of a folding intermediate, or lack expression (Nisthal et al., 2019). | PMC10266766 | elife-82593-fig3-figsupp1.jpg |
0.445657 | 1940bc9c509a43b18558ee0ba106182c | RaSP performance on three recently published data sets (Pancotti et al., 2022): (A) The S669 data set, (B) The Ssym+ direct data set, (C) The Ssym+ reverse data set. | PMC10266766 | elife-82593-fig3-figsupp2.jpg |
0.455832 | e53c54cac5d34fc69d9373dfb424be9a | RaSP performance on the recently published mega-scale experiments (Tsuboyama et al., 2022).The experimental data has been filtered to include only well-defined experimental ΔΔG values from single substitution mutations in natural protein domains (Tsuboyama et al., 2022). This filtered data set contains a total of 164,524 variants across 164 protein domain structures. | PMC10266766 | elife-82593-fig3-figsupp3.jpg |
0.457134 | 55428d7a785a4800af50c11da8ab7a33 | Benchmarking RaSP and Rosetta using VAMP-seq data.We compare stability predictions with VAMP-seq scores for three test proteins (A) TPMT (PDB: 2H11) (Matreyek et al., 2018), (B) PTEN (PDB: 1D5R) (Matreyek et al., 2018) and (C) NUDT15 (PDB: 5BON) (Suiter et al., 2020). | PMC10266766 | elife-82593-fig3-figsupp4.jpg |
0.466301 | 36ba8327931242a5be54a670f049603e | Comparing RaSP and Rosetta predictions to experimental stability measurements.Predictions of changes in stability obtained using (A) RaSP and (B) Rosetta are compared to experimental data on five test proteins; myoglobin (1BVC), lysozyme (1LZ1), chymotrypsin inhibitor (2CI2), RNAse H (2RN2) and Protein G (1PGA) (Kumar, 2006; Ó Conchúir et al., 2015; Nisthal et al., 2019). Metrics used are Pearson correlation coefficient (ρ), mean absolute error (MAE) and mean error (ME). In the experimental study of Protein G, 105 variants were assigned a ΔΔG value of at least 4 kcal/mol due to low stability, presence of a folding intermediate, or lack expression (Nisthal et al., 2019). | PMC10266766 | elife-82593-fig3.jpg |
0.469096 | 4249a76b8da3406684c5f19a519506a8 | Stability predictions from structures created by template-based modelling.Pearson correlation coefficients (ρ) between experimental stability measurements and predictions using protein homology models with decreasing sequence identity to the target sequence. Pearson correlation coefficients were computed in the range of [–1;7] kcal/mol. | PMC10266766 | elife-82593-fig4.jpg |
0.404848 | 6ab4738ee19f44438e49d605f4ee0ca4 | Histogram of ΔΔG values from saturation mutagenesis using RaSP on 1,366 PDB structures corresponding to ∼8.8 million predicted ΔΔG values. | PMC10266766 | elife-82593-fig5-figsupp1.jpg |
0.502122 | 68a8331af3ea4d119ad7cfe00026e967 | Large-scale analysis of disease-causing variants and variants observed in the population using the RaSP model.The grey distribution shown in the background of all plots represents the distribution of ΔΔG for all single amino acid changes in the 1366 proteins that we analysed. Each plot is also labelled with the median ΔΔG of the subset analysed as well as a range of ΔΔG values that cover 95% of the data in that subset (box plot shows median, quartiles and outliers). (A) Distribution of RaSP ΔΔG values for benign (blue) and pathogenic (tan) variants extracted from the ClinVar database (Landrum et al., 2018). We observe that the median RaSP ΔΔG value is higher for pathogenic variants compared to benign variants. (B) Distribution of RaSP ΔΔG values for variants with different allele frequencies (AF) extracted from the gnomAD database Karczewski et al., 2020 in the ranges (i) AF > 10-2 (green), (ii) 10-2 > AF > 10-4 (orange), (iii) AF < 10-4 (purple). We observe a gradual shift in the median RaSP ΔΔG going from common variants (AF> 10-2) towards rarer ones (AF< 10-4). | PMC10266766 | elife-82593-fig5-figsupp2.jpg |
0.497813 | 5f95ffa69b8e42759cccf0059aa02ca3 | Histogram of ΔΔG values from saturation mutagenesis using RaSP on predicted structures of the entire human proteome corresponding to ∼300 million predicted ΔΔG values predicted from 23,391 protein structures. | PMC10266766 | elife-82593-fig5-figsupp3.jpg |
0.427729 | 0119f2b2b6c6404593c7e939e0d27948 | Large-scale analysis of disease-causing variants and variants observed in the population.The grey distribution shown in the background of all plots represents the distribution of ΔΔG values calculated using RaSP for all single amino acid changes in the 1,366 proteins that we analysed (15 of the 1381 proteins that we calculated ΔΔG for did not have variants in ClinVar or gnomAD and were therefore not included in this analysis). Each plot is also labelled with the median ΔΔG of the subset analysed as well as a range of ΔΔG values that cover 95% of the data in that subset (box plot shows median, quartiles and outliers). The plots only show values between –1 and 7 kcal/mol (for the full range see Figure 5—figure supplement 2). (A) Distribution of RaSP ΔΔG values for benign (blue) and pathogenic (tan) variants extracted from the ClinVar database (Landrum et al., 2018). We observe that the median RaSP ΔΔG value is significantly higher for pathogenic variants compared to benign variants using bootstrapping. (B) Distribution of RaSP ΔΔG values for variants with different allele frequencies (AF) extracted from the gnomAD database Karczewski et al., 2020 in the ranges (i) AF>10-2 (green), (ii) 10-2 > AF>10-4 (orange), and (iii) AF<10-4 (purple). We observe a gradual shift in the median RaSP ΔΔG going from common variants (AF>10-2) towards rarer ones (AF<10-4). | PMC10266766 | elife-82593-fig5.jpg |
0.404265 | c9703cb5a6f54135a505fe862ba86391 | Lineage tracing of the LPM into paired fins and the PAFF.a–g, Permanently labelled LPM cells can be seen within pectoral and pelvic fins and pre-anal fin fold (arrowheads). Confocal images of the pectoral fin at 4.5 dpf (a), adult pelvic fin (b–d) and pre-anal fin fold at 5 dpf (e–g) of Tg(drl:creERT2); Tg(hsp70l:Switch) transgenics following Hydroxytamoxifen treatment and heat-shock prior to imaging. Pelvic fins and PAFF are shown as transverse sections (b–g) and were fluorescently immunostained for eGFP (b,e), Zns5 (c) or Transgelin (f). Merged images are shown in (d,g). LPM-derived mesenchyme cells of the pectoral and pre-anal fin folds are indicated by white and yellow arrowheads respectively (a, e–g). LPM-derived Zns5-positive osteoblasts of the pelvic fins are indicated by white arrowheads (b–d). Scale Bars: 20 µm (d,g), 50 µm (a). | PMC10266977 | 41586_2023_6100_Fig10_ESM.jpg |
0.403294 | 45421c8a9160414d8aab623227626ef3 | Pre-anal fin fold mesenchyme originates from posterior-most drl-positive cells.a–d, Lateral (a) and ventral (b–d) views of 8ss (a–b) or 10ss (c–d) drl:H2B-Dendra2 transgenic line either prior to (a–b) or following (c–d) photoconversion of posterior-most LPM (region outlined by dotted line) using UV laser illumination. e–p, Lateral confocal images of the PAFF region at 40 hpf (e–g, k–m) and 48 hpf (h–j, n–p) of a photoconverted embryo (e–j) and an unconverted control (k–p). Panels show Dendra2-red (f,i,l,o), Dendra2-green (g,j,m,p) and merged (e,h,k,n) channels. PAFFs are indicated by yellow arrowheads, and are visible in green channel in both converted and controls, but only converted embryos show red labelled PAFFs (f,i; n = 4 photoconverted fish). Magnified views of panels (f,g,i,j,l,m,o,p) are given in panels (q–x) respectively. Scale Bars: 200 µm (b), 50 µm (d,x), 100 µm (k). | PMC10266977 | 41586_2023_6100_Fig11_ESM.jpg |
0.427941 | c2b9b15e382c489aa2ed0de7e2b857d9 | LPM origin of PAFF mesenchyme is conserved in medaka, paddlefish and Xenopus.a–c, In situ hybridisation of medaka hand2 at Stage 39 (a) and Stage 40 (b–c) showing exclusive expression in pre-anal fin mesenchyme (yellow arrowhead, b), but not in the caudal fin mesenchyme (cyan outline). Ventral caudal fin imaged in (a). d–e, Lateral confocal images of PAFF of Stage 36 transgenic Tg(-6.35drl:EGFP) medaka embryo. Fluorescent confocal images of eGFP (d) are overlayed on Nomarski image (e). Faint eGFP perdurance is seen in nascent PAFF mesenchymal cells (yellow arrowheads and inset). f–i, Ventral (f,h) and lateral (g,i) confocal images of medaka embryo injected with DiI in the posterior LPM at Stage 20 (f,h) and traced to PAFF at Stage 40 (g,i). DiI within the mesenchyme indicated by yellow arrowheads, with higher magnification example shown in inset (g,i). DiI signal (f,g) is overlayed with Nomarski (h,i). Location of paraxial mesoderm (PM), Kupffer’s vesicle (KV) and region of posterior LPM are indicated in green, red, and white respectively in (h). j–l, In situ hybridisation of hand2 in Stage 38 (j) and Stage 39 (k–l) paddlefish embryos imaged laterally (j,k) or in transverse section (l). hand2-positive PAFF fin mesenchyme indicated by yellow arrowheads is located distally. Expression of hand2 is also seen in the nascent pelvic fins at Stage 39 (green arrowheads k,l). m–o, Confocal images of a region of Xenopus laevis PAFF at NF Stage 42 injected with -6.35drl:EGFP. Lateral x-y view (n) is shown with orthogonal sections in the x-z plane (m) and y-z plane (o). Transient mosaic expression in the interstitial mesenchyme is highlighted with yellow arrowheads (m–n). Scale Bars: 20 µm (a,d), 100 µm (b,i), 50 µm (b – inset, l,o), 200 µm (h,j,k). | PMC10266977 | 41586_2023_6100_Fig12_ESM.jpg |
0.400184 | 3fa06e24300d4a5fb800de80d7b2a587 | Reduced Chordin leads to paired duplication of PAFF.a–b, Low (a) and high (b) power Nomarski images of duplicated PAFFs (yellow arrowheads) in 5 dpf larvae injected with chrd morpholino. c–j, Confocal images of PAFFs from 8 dpf Tg(hand2:EGFP) either uninjected (c,e) or injected with chrd morpholino (d,f,g–j). Confocal projections (c,d,i,j) and total surface renderings (e,f,g,h) highlight duplicated PAFFs (blue and yellow, f) compared to single PAFF in uninjected larvae (grey, e). Imaging of left (g) and right (h) duplicated PAFFs of chrd morphants indicated eGFP positive mesenchymal cells populated both fin folds (yellow arrowheads, i,j). k– l, Lateral (k) and ventral (l) Nomarski images of the duplicated PAFFs of the Ranchu goldfish strain at 6 dpf. Duplicated PAFFs and ventral caudal fin folds indicated by yellow and cyan arrowheads, respectively. m–n, Lateral (m) and transverse (n) views of 7 dpf Ranchu larvae stained by in situ hybridisation for hand2. Expression in individual mesenchymal cells of the PAFF indicated by yellow arrowheads (m). Occurrence of three PAFFs with core hand2 expression indicated by yellow arrowheads (n). Scale Bars: 100 µm (a,e,g), 50 µm (b), 500 µm (k), 200 µm (l), 20 µm (m,n). | PMC10266977 | 41586_2023_6100_Fig13_ESM.jpg |
0.471589 | ff77afc29c86446ca27b19800a3fc8f5 | Variable presence of a pre-anal fin in sharks.a–i, The Epaulette shark does not possess a PAFF. Whole mount (a,d,g) and virtual cross sections from microCT scans (b–c, e–f, h–i) of the Epaulette shark Hemiscyllium ocellatum, at the developmental stages of 25 (a–c), 27 (d–f), and 30 (g–i). Virtual cross sections for each stage show the region either anterior (Pre-anal; b,e,h), or posterior (Post-anal; c,f,i) to the developing cloaca (white arrow, a,d,g). The dashed lines (a,d,g) indicate approximate pre-anal (magenta) and post-anal (cyan) microCT section locations (separate specimens). The developing pelvic and median fin folds are indicated by green and cyan arrowheads respectively (b–c, e–f, h–i). j–m: The tropeic folds found in a pre-anal position of the adult frilled shark, Chlamydoselachus anguineus, shown in lateral (j) and ventral (k) views (yellow arrowheads) (adult male specimen, ZRC 54430 - LKC Natural History Museum, Singapore). l–m, Ventral view of another adult frilled shark exhibits partially paired tropeic folds (yellow arrowheads) in anterior half (l), which then merges to become singular (yellow arrowhead) in posterior half (m) (anterior: left, CSIRO H 7115-01, adult male 1310 mm TL, Tasmania, Australia). Scale Bars: 1 mm (a,d,g), 5 cm (k). | PMC10266977 | 41586_2023_6100_Fig14_ESM.jpg |
0.446565 | ed2012702e8a446f94f953f5b687f9ba | A non-PM-derived median fin fold.a, Larval 4 dpf zebrafish possess a median PAFF (yellow arrowhead) in addition to the caudal median fin fold (cyan arrowhead). b, Confocal image of a 3 dpf Tg(tbx16l:GAL4-VP16); Tg(UAS:Kaede) embryo with PM labelled by Kaede showing PM-derived mesenchyme in the caudal median fin fold (cyan outline) but not the PAFF (yellow outline). c–e, Confocal images of pre-anal (c), ventral caudal (d) and pectoral (e) fins of the ET37 Enhancer Trap transgenic line indicating that PAFF contains morphologically comparable mesenchyme (indicated by arrowheads) to other larval fin folds. f, In situ hybridization of the fin mesenchyme marker fbln1 in both PAFF (yellow arrowhead) and caudal fin fold (cyan arrowhead) at 3 dpf. g,h, DsRed expression in mesenchyme of both pre-anal (g) and caudal (h) fin folds of the 5 dpf Tg(-5.2lyve1b:DsRed) transgenic line. i,j, Immunostaining for collagen II in 8 dpf frf mutants (j) shows loss of fibril organization compared with WT (i). Scale bars, 200 µm (a); 100 µm (b); 20 µm (c,e); 50 µm (f,g,j). | PMC10266977 | 41586_2023_6100_Fig1_HTML.jpg |
0.426992 | 489133b8127146c1a09c8069916f0bcc | The PAFF is an LPM-derived median fin fold.a,b, Confocal images of Tg(hand2:EGFP) embryos at 2 dpf (a) and 3 dpf (b) showing eGFP labelling of the mesenchyme of the pectoral (green outline and arrowheads) and PAFFs (yellow outline and arrowheads, and magnified in inset) but not the caudal fin fold (cyan outline). c,d, In situ hybridization of hand2 at 3 dpf shows fin expression of hand2 only in the PAFF (yellow arrowheads (c), and higher magnification with Nomarski optics indicates expression in the mesenchyme (d). e, Schematic of the LPM lineage tracing transgenes. f, Lineage tracing of LPM using transgenics depicted in (e) following 4-OHT treatment and heat shock before imaging shows that PAFF mesenchyme is derived from the LPM (yellow arrowhead and magnified in inset). g,h, Ventral (g) and lateral (h) confocal images of the drl:H2B-Dendra2 transgenic line at the 10-somite stage (10 ss) (g) and 48 hpf (h) following ultra-violet laser photoconversion in the region of the LPM outlined in (g). h, Photoconverted PAFF mesenchyme is indicated by yellow arrowheads. Scale bars, 100 µm (a,c,f); 50 µm (a (inset),f (inset),g,h); 200 µm (b); 20 µm (d). | PMC10266977 | 41586_2023_6100_Fig2_HTML.jpg |
0.411522 | 4bd988a091ba49b7a13538e6834a4467 | PAFF mesenchyme expression of hand2 is conserved across vertebrates.a,b, Nomarski images of 9 dpf medaka showing PAFF (a) with dispersed mesenchymal cells (yellow arrowheads) (b). c, In situ hybridization of medaka at stage 39 showing hand2 expression in pre-anal fin mesenchyme (yellow arrowheads). d,e, In situ hybridization of hand2 in stage 36 paddlefish embryos shown laterally (d) or in transverse section (e). hand2-positive PAFF fin mesenchyme is indicated by yellow arrowheads. f,g, HandA in situ hybridization of stage E29 lamprey (P. marinus) embryos shown laterally (f) or in transverse section (g). Lamprey show strong expression of HandA in a fin anterior to the anus (yellow arrowhead in f) corresponding to cells in the interior of the fin (g). The section location of (g) is indicated by the dashed line in (f). h–j, Chromogenic (h) or fluorescent (i,j) in situ hybridization of hand2 in stage 42 X. tropicalis embryos shown laterally (h) or in transverse section (i,j). Fluorescent image (j) is overlayed on the Nomarski image (i). The small PAFF in Xenopus contains sparse hand2-positive fin mesenchyme (yellow arrowheads). St., stage. Scale bars, 100 µm (a,d,h); 10 µm (b); 20 µm (c); 50 µm (e–g,i). | PMC10266977 | 41586_2023_6100_Fig3_HTML.jpg |
0.427947 | 1f0ce936f7504510924bd89d3b30f397 | Duplication of the PAFF into paired fin folds.a,b, Lateral (a) and ventral (b) Nomarski images of PAFFs of 5 dpf (a) and 4 dpf (b) embryos injected with MO targeting chordin, resulting in duplication of PAFF (yellow arrowheads). c,d, Confocal micrographs, imaged ventrally, of PAFFs in 4 dpf ET37 transgenic larvae uninjected (c) or injected with a chrd MO (d). PAFFs are indicated with yellow lines. d, Note the duplicated anal openings following chrd MO injection. e, Ventral confocal image of chrd MO duplicated PAFFs of the transgenic line shown above. Hydroxytamoxifen treatment at the 12-somite stage and heat shock before imaging show that mesenchyme of duplicated PAFFs is derived from the LPM (yellow arrowheads). f–i, Light-sheet (f) and confocal (g–i) images of Tg(hand2:EGFP) larvae at 8 dpf (f) and 6 dpf (g–i). Orthogonal display through the x–z plane (f,g) shows that multiple PAFFs can form and that duplicated PAFFs contain eGFP-positive mesenchyme (g–i). Lateral views of left (h) and right (i) duplicated PAFFs of sample in g are given. j,k, Lateral low- (j) and high-power (k) Nomarski images of the PAFF of the Ranchu goldfish at 6 dpf. The multiple PAFFs (j) and individual mesenchyme cells (k) are indicated by yellow arrowheads. Duplicated caudal fin folds are indicated by cyan arrowheads (j). l–n, Lateral (l,m) and transverse (n) views of pre-anal (l,n) and caudal (m) fin folds of 7 dpf Ranchu larvae stained by in situ hybridization for hand2, where hand2-positive PAFF mesenchyme is indicated by yellow arrowheads. Absence of hand2 in the caudal fin fold is indicated by the cyan arrowhead (m). Scale bars, 100 µm (a,e,m); 20 µm (b,f–h,n); 50 µm (d,k); 200 µm (j). | PMC10266977 | 41586_2023_6100_Fig4_HTML.jpg |
0.520315 | 6bd77a3daf124b059da753d984690820 | Hypothesis of the elaboration of the PAFF to paired fins.Simplified evolutionary scenario of vertebrates showing the presence of a PAFF and subsequent modifications leading to paired fins. Dashed lines and dagger symbols indicate extinct lineages, and solid lines indicate extant lineages. PM-derived fins and fin folds are in cyan, while LPM-derived fins are in pink. Larval PAFF is hatched. Black arrows indicate the position of the anus. | PMC10266977 | 41586_2023_6100_Fig5_HTML.jpg |
0.413014 | 4cf0c1039dc84e6cb398bc076a6cf3e6 | A non-paraxial mesoderm derived median fin fold.a, Confocal image of 3 dpf Tg(tbx16l:GAL4-VP16); Tg(UAS:Kaede) embryo with paraxial mesoderm labelled by photoconverted Kaede (magenta). Unlabelled PAFF underscored by yellow bracket. c-d, Expression of Kaede in the dorsal caudal fin fold of 3 dpf Tg(tbx16l:GAL4-VP16); Tg(UAS:Kaede) is not due to localised de novo expression from the tbx16l promoter. Confocal images of 24 hpf trunks of both prior to (b) and after (c) UV photoconversion. Unconverted Kaede is in the green channel overlaid with converted Kaede in magenta. Region of paraxial mesoderm conversion and Nomarski image given in (b). At 3 dpf, converted cells can be seen in the adjacent fin fold dorsally indicating Kaede is reporting lineage (d). e, Nomarski image of PAFF at 3 dpf showing presence of mesenchymal cells. f–h, Confocal images of the pre-anal fin fold (f), dorsal (g) and caudal (h) regions of the caudal fin fold of the ET37 Enhancer Trap transgenic line at 3 dpf, indicating PAFF contains numerous mesenchymal cells which are morphologically comparable to mesenchyme of other larval fin folds. i–j, In situ hybridisation of fin mesenchyme markers itgb3b (i; 3 dpf) and bmp1a (j; 5 dpf) in both PAFFs (yellow) and caudal fin folds (cyan arrowhead). Scale Bars: 100 µm (a,f,i), 50 µm (c,d,e,j), 20 µm (g,h). | PMC10266977 | 41586_2023_6100_Fig6_ESM.jpg |
0.41819 | b1705a354a6d4db0abeb9af8f061769a | Expression of hand2 in the pre-anal fin fold.a–b, High (a) and low (b) magnification confocal images of Tg(hand2:EGFP) zebrafish embryos at 3 dpf (a) and 8 dpf (b) showing eGFP labelling of mesenchyme of the PAFF (yellow outline, a,b), but not the caudal fin fold (cyan outline, b). c–d, In situ hybridisation of hand2 at 5 dpf showing expression of hand2 only in the PAFF (c). Higher magnification with Nomarski optics indicates expression in mesenchyme (d). Scale Bars: 100 µm (b,c), 50 µm (d), 20 µm (a). | PMC10266977 | 41586_2023_6100_Fig7_ESM.jpg |
0.470067 | 4c259e8d39c444ec8eb9ecfaa62dfd41 | Loss of Hand2 leads to reduction of pre-anal fin folds but not caudal fin folds.a–l, Lateral Nomarski images of uninjected WT (a,c,e,g), hans6 mutants (b,h) and hand2 morphants (d,f) at 3 dpf (a–d) or 5 dpf (e–h). i–l, Confocal images of 3 dpf (i,j) and 5 dpf (k,l) ET37 Enhancer Trap transgenic larvae, uninjected (i,k) or injected with a hand2 morpholino (j,l). m,n Quantification of 3 dpf fin height of PAFFs (yellow) and caudal fin folds (cyan) in uninjected WT, hand2 mutants (hans6; m) and hand2 morphants (n). Loss of Hand2 leads to significant reduction of PAFFs but not caudal fin folds. n = 8 (WT), n = 15 (hans6), n = 5 (hand2 MO). Location of measurements of PAFF and caudal fin shown in (a) and (b) by yellow and cyan lines respectively. ***: p = 0.000008; **: p = 0.008; ns: p = 0.12 (m); ns: p > 0.9999 (n). o, Quantification of mesenchymal cell numbers in pre-anal (yellow bars) and ventral caudal (cyan bars) fin folds at 3 dpf. There is a significant reduction of PAFF mesenchyme in hand2 morphants compared to WT, but ventral caudal fin mesenchymal cell numbers are unaffected. n = 5 (WT), n = 12 (hand2 MO). ***: p = 0.000323; ns: p = 0.06. m–o: Data are presented as mean values with error bars representing standard deviations. In all cases n refers to biologically independent embryos. Two-sided Mann-Whitney test. Scale Bars: 100 µm (d,f,j,l), 200 µm (b,h).
Source data
| PMC10266977 | 41586_2023_6100_Fig8_ESM.jpg |
0.406224 | 4878a66a31364fb886887d96ef4b6bb3 | Hand2 acts cell autonomously in PAFF mesenchyme.a–d, Lateral confocal images of PAFF of 3 dpf embryos. Cells were transplanted into WT hosts from ET37 embryos that were injected with H2B-mCherry mRNA (a,b) or co-injected with H2B-mCherry mRNA and 500 µM hand2 MO (c,d). Fluorescent confocal images of mCherry (magenta) and eGFP (green) (a,c) are overlayed on Nomarski image (b,d). Arrowheads indicate transplanted cells from hand2 MO injected donors (c). Scale Bar: 20 µm (d). | PMC10266977 | 41586_2023_6100_Fig9_ESM.jpg |
0.460077 | f958c8879bfe451b9a1695e14b4be4fa | Brain sites with increased regional mean diffusivity (MD) values in patients with type 2 diabetes compared to control subjects. Brain regions showed increased MD values in the bilateral insula (a, b), bilateral anterior (c, h), and posterior (d, i) cingulate, left superior parietal cortices (e), bilateral cerebellum (f, g), right inferior frontal cortices (j), right prefrontal cortices (k), left para-hippocampal gyrus (l), and bilateral lingual gyrus (m, n). | PMC10267112 | 41598_2023_35522_Fig1_HTML.jpg |
0.48368 | 75e495da1bc74129a8f2a6d8344f929f | Brain regions with reduced regional MD values in type 2 diabetes compared to control subjects. These sites with reduced MD values included the bilateral thalamus (a, b), right putamen (c), right pallidum (d), and pons (e). | PMC10267112 | 41598_2023_35522_Fig2_HTML.jpg |
0.432735 | 4fe5e940d89d44cd955d106d38913f31 | Flow chart of the study design. SLE, systemic lupus erythematosus; OPD, Outpatient department. | PMC10267408 | fphar-14-1185809-g001.jpg |
0.414681 | cb0f0db363524d60ac00d56e0c58f22e | Conditional logistic regression of risk of pneumonia by follow-up duration stratification (60 days). †Adjusted for hypertension, hyperlipidemia, chronic liver disease, chronic kidney disease, rheumatoid arthritis, corticosteroids, NSAIDs, and hydroxychloroquine. | PMC10267408 | fphar-14-1185809-g002.jpg |
0.48237 | e0c8ece4e84c4007b7f4eb86131c99c8 | Conditional logistic regression of risk of pneumonia by antibiotics use, severity of pneumonia and days of hospitalization. ER, emergency room. †Adjusted for all variables. | PMC10267408 | fphar-14-1185809-g003.jpg |
0.385871 | 064a41f2f828468784611585b8b9d3ec | Conditional logistic regression of risk of pneumonia by different formulae of TCM. † Adjusted for hypertension, hyperlipidemia, chronic liver disease, chronic kidney disease, diabetes, chronic obstructive pulmonary disease, rheumatoid arthritis, ankylosing spondylitis, corticosteroids, NSAIDs, hydroxychloroquine, and methotrexate. KF: Chinese formulae tonifying the kidney; BF: Chinese formulae activating blood circulation. | PMC10267408 | fphar-14-1185809-g004.jpg |
0.45644 | a2364bc43e9e4430980cfa959c23e794 | Left panel depicting BMI × Intrasexual competitiveness interaction. Right panel depicting floodlight analysis for determining range of significance for the interaction. ns., the range whereby the interaction effect in statistically non-significant, sig., the point whereby the interaction becomes statistically significant (indicated by the dashed line). LLCI and ULCI, the 95% lowerbound and upperbound confidence intervals, respectively. | PMC10267438 | fpsyg-14-1167115-g001.jpg |
0.383981 | dec655a304c14e69998d7c2240b2c90d | Moderated mediation model 1. Left panel reflecting the model paths, whereby b, unstandardized regression coefficient, t, standardized t-value, ***value of p < 0.001, **value of p < 0.01. Right panel reflecting the depression × intrasexual competition interaction effect. | PMC10267438 | fpsyg-14-1167115-g002.jpg |
0.401342 | b2e33490cebf40c3897351c30e99cbe7 | Moderated mediation model 2. Left panel reflecting the model paths, whereby b, unstandardized regression coefficient, t, standardized t-value, ***value of p < 0.001, **value of p < 0.01. Right panel reflecting the BMI × intrasexual competition interaction effect. | PMC10267438 | fpsyg-14-1167115-g003.jpg |
0.444498 | 69fc4cfe26864b0392dc177cb174ba7f | Overview of RNAseqChef (RNA-seq data controller highlighting gene expression feature).A, RNAseqChef is a web-based platform of systematic transcriptome analysis and can automatically detect, integrate, and visualize the DEGs and their biological functions, by uploading the raw count files of interest. The “DEG Analysis Unit” consists of “Pair-wise DEG”, “3 conditions DEG”, and “Multi DEG”. The “Integrative Analysis Unit” then consists of “Venn diagram,” “Normalized count analysis,” and “Enrichment viewer.” The result files obtained from the DEG Analysis Unit can be used as input files for the Integrative Analysis Unit, which makes it easy to perform the bioinformatic studies on demand. B, analysis of the common and cell/tissue-specific effects of SFN on transcriptome using RNAseqChef. DEG, differentially expressed gene; SFN, Sulforaphane. | PMC10267603 | gr1.jpg |
0.423939 | d25f18497b93461aa8b38e306d0bcec4 | Cellular response to SFN is different among cell types.A, schematic representation of the RNAseqChef analysis designed to highlight SFN-induced transcriptomic features and their cell-type dependency. Raw count data were obtained from public RNA-seq datasets of epithelial cells (Epi; GSE141740) and HaCaT keratinocytes (Ker; GSE185320), under control (Ctrl; DMSO-treated) and 10 μM SFN-treated conditions (each n = 2). Along with the workflow in Figure 1, A and B, it takes approximately 5 min to complete all analyzing steps. B, transcriptome-based PCA of Ctrl and SFN-treated cells. C, Venn diagram of genes significantly upregulated by SFN treatment (using DESeq2 (FDR < 0.01)). D, heatmap of commonly upregulated genes shown in (C). E and F, top-ranked functional pathways (E) and transcription factors (TFs) (F) were enriched in gene sets upregulated by SFN treatment, including 499 common genes (green), 1146 Epi unique genes (red), and 1212 Ker unique genes (blue), as shown in (C). Enrichment analysis was performed based on MSigDB hallmark (E) and DoRothEA regulon gene set (F). FDR <0.05. G, normalized expression values of the representatives for common, Epi unique, and Ker unique genes upregulated by SFN. ∗∗p < 0.01; ∗∗∗p < 0.001. FDR, false discovery rate; PCA, Principal component analysis; SFN, Sulforaphane. | PMC10267603 | gr2.jpg |
0.427935 | 83aa9338ae6b467bb091d4c713b8a466 | SFN induces the unfolded protein response in an NRF2-independent manner.A, schematic representation of the RNAseqChef analysis designed to identify the NRF2-dependent or independent actions of SFN in epithelial cells. Gene extraction of the common genes from the normalized count data (control WT, SFN-treated WT and NRF2 KO, each n = 2) was performed in the “Normalized count analysis” section. Subsequent k-means clustering was done using the tab panel named “k-means clustering” in the same section. Enrichment analysis was performed by uploading the result file obtained from k-means clustering in the “Enrichment viewer” section. B, the k-means clustering approach separated 499 commonly upregulated genes (shown in Fig. 2C) into two groups based on NRF2 dependency. The magenta and green box indicate 281 NRF-independent and 194 NRF2-dependent upregulated genes, respectively. The 24 genes (in the bottom cluster of the heatmap) were not separated into the above groups because their expression patterns were not obvious. C and D, top-ranked functional pathways (C) and TFs (D) were enriched in gene sets upregulated by SFN treatment, including 475 ALL genes (sum of the following genes), 194 NRF2-dependent genes, and 281 NRF2-independent genes. Enrichment analysis was performed based on MSigDB hallmark (C) and DoRothEA regulon gene set (D). FDR <0.05. E, TPM expression values of the representative NRF2-dependent and NRF2-independent genes that were upregulated by SFN. ∗∗∗p < 0.001. FDR, false discovery rate; NRF2, nucleus factor-E2-related factor 2; SFN, Sulforaphane; TPM, Transcripts per million; WT, wild type. | PMC10267603 | gr3.jpg |
0.455957 | 37fd992929954634b6269352087a80d4 | SFN treatment induces tissue-specific transcriptomic changes in obese mice.A, transcriptome-based UMAP of five metabolic tissues such as BAT, eWAT, iWAT, liver, and skeletal muscle in high fat diet-fed obese mice. Data set is GSE181477 (untreated Ctrl (−) and SNF-treated (+); each n = 5, except for eWAT (n = 4)). B, Venn diagram of genes significantly upregulated by SFN treatment (FDR < 0.05). C and D, top-ranked functional pathways (C) and TFs (D) were enriched in gene sets upregulated by SFN treatment, including 157 BAT unique genes (red), 299 eWAT unique genes (yellow), 1252 liver unique genes (blue) and 65 muscle unique genes (green), as shown in (B). Enrichment analysis was performed based on MSigDB hallmark (C) and DoRothEA regulon gene set (D). FDR <0.05. E, volcano plot obtained from pair-wise DEG analysis (Ctrl versus SFN) of the liver in HFD-fed obese mice. As indicated with green dots, ATF6-targeted UPR genes were significantly upregulated by SFN treatment (FDR < 0.05). F, TPM expression values of the representative skeletal muscle-unique genes upregulated by SFN. ∗p < 0.05; ∗∗p < 0.01. BAT, brown adipose tissue; eWAT, epididymal white adipose tissue; FDR, false discovery rate; HFD, high-fat diet; iWAT, inguinal WAT; SFN, Sulforaphane; TPM, Transcripts per million; UPR, unfolded protein response; WT, wild type. | PMC10267603 | gr4.jpg |
0.415055 | 5efdb66c6adc4560922b4a936be4341c | SFN treatment downregulates collagen genes and BMAL1/CLOCK target genes in obese mice.A, Venn diagram of genes significantly downregulated by SFN treatment (FDR < 0.05). B, TPM expression values of genes commonly downregulated by SFN in five metabolic tissues of HFD-fed obese mice. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. C, heatmap of the hallmark gene set “Epithelial mesenchymal transition,” which was downregulated in the tissues of SFN-treated obese mice, as shown in Fig. S9. Fibrosis-associated genes are highlighted in red. D, TPM expression values of Bmal1 and BMAL1/CLOCK target genes downregulated in multiple tissues of SFN-treated HFD-fed obese mice. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. FDR, false discovery rate; HFD, high-fat diet; SFN, Sulforaphane; TPM, Transcripts per million. | PMC10267603 | gr5.jpg |
0.40271 | 0f95c1e692914dc69f62a8f5ec6d013f | Componential model of emotion. In this framework, emotions are conceived as resulting from the concomitant (or sequential) engagement of distinct processes, responsible for the evaluation as well as the behavioral and bodily responses to particular events. According to the CPM proposed by Scherer and colleagues, from which emotion features were defined in our study, 5 distinct functional components are postulated, which can reciprocally interact to constitute an emotional experience, including appraisal mechanisms that process contextual information about the event, motivational mechanisms that promote goal-oriented behaviors and cognitions, motor expressions and physiological changes that instantiate bodily responses, and subjective feelings that may reflect an emerging component encoding conscious emotion awareness. | PMC10267645 | bhad093f1.jpg |
0.452632 | ecb685326f584ce1a8e7a146ee275d43 | PLSC method. Participants watch emotional clips during 4 daily fMRI sessions. Matrix X summarizes the brain activity patterns during emotional events and matrix Y summarized the assessment of 32 emotion features collected during a separate behavioral session and 2 physiology features for each event. PLSC is then applied to find the commonalities between neural activity and behavioral measures. This is achieved in 3 steps, first by computing the relationship (R) between brain activities (X) and behaviors (Y). Then decomposing the relationship matrix R using singular value decomposition (SVD). And, finally, using permutation tests and bootstrapping to assess the statistical significance and saliency of latent factors. | PMC10267645 | bhad093f2.jpg |
0.410971 | 15b745b6d5294699987c78287188eace | Histogram and hierarchical clustering of discrete emotions. a) Histogram of categorical emotions based on their frequency in the ratings of 119 emotional event by 20 participants (data from 2 participants were not complete). The red dashed line shows the ideal frequency if samples were distributed uniformly. b) Hierarchical clustering of the discrete emotion profiles in the GRID space using Ward algorithm. The higher-level clusters distinguish between positive and negative emotions. The lower-level clusters reflect a segregation of feelings in terms of pleasantness (green), surprise (black), distress (blue), and annoyance or frustration (red). | PMC10267645 | bhad093f3.jpg |
0.426473 | f35cce9837c34270940b9146f637f7e4 | Histogram of GRID items. Histogram of ratings for all the 32 GRID items based on the number of times a specific rating (1–7) was selected across all assessments (119 assessments per participant) and all 20 participants (the data from 2 participants were not complete). The abbreviation “s.b.” stands for somebody. | PMC10267645 | bhad093f4.jpg |
0.40052 | 5db002efa5b841a784a19f397be6fae0 | Discrete emotion profiles in GRID space. Average profile of each discrete emotion on the 32 GRID features and 2 peripheral physiology measures (HR, RR) after within-subject normalization. For each discrete emotion, all assessments from all 20 participants with that discrete emotion label were used. Each bubble corresponds to a z-score using an exponential scaling. The smallest bubble represents a z-score = −1.27, corresponding to “not at all,” and the biggest bubble represents a z-score = +1.23 corresponding to “felt strongly.” Colors represent the different emotion components to which GRID items belong to. | PMC10267645 | bhad093f5.jpg |
0.455105 | e06a67e014204126921a83797a9121a0 | Loadings of PLSC. Loadings of PLSC for GRID items (behavioral) and peripheral measures corresponding to the 6 significant LV (1–6), respectively, interpreted as: valence, novelty, hedonic impact, goal monitoring, goal relevance, and avoidance. Each loading vector corresponds to 1 brain activity map that is shown in Fig. 7. The blue error bars indicate the standard deviation for each value that reflects the reliability of the loading when apply bootstrapping; however, because of very small variation, they are not very visible. | PMC10267645 | bhad093f6.jpg |
0.370269 | 8920e9e0406847dba272bc83ed400304 | Brain saliency maps. Brain activity maps of relative saliencies corresponding to each of the 6 significant FCP, a.k.a. LV, obtained by the PLS analysis of GRID ratings. The red spectrum accounts for positive saliencies above +2.5 and blue spectrum corresponds to negative saliencies below −2.5. | PMC10267645 | bhad093f7.jpg |
0.543142 | 8da8798fc4694e6896536567738e44a3 | Isomerization
of itaconic acid, mesaconic acid, and citraconic
acid. | PMC10268020 | ao3c00166_0002.jpg |
0.497197 | 1630fe0f7764404b8c0f193875ae628c | Aza-Michael
addition mechanism. | PMC10268020 | ao3c00166_0003.jpg |
0.484122 | ec2e2dc3adee476ebb1ad6f4968fcd11 | Functional groups in the poly(glycerol citraconate) structure
and
its characteristics. | PMC10268020 | ao3c00166_0004.jpg |
0.474315 | d157cadf6ce04b3692dc2a6e28197e4e | Reaction of citraconic anhydride with
glycerol (R = H or PGCitrn
chain). | PMC10268020 | ao3c00166_0005.jpg |
0.508473 | 4c92540c4d344b6aa90399dfe8a1da97 | FTIR spectrum of poly(glycerol citraconate)
(green), glycerol (blue),
and citraconic anhydride (red). | PMC10268020 | ao3c00166_0006.jpg |
0.455988 | e5ca77f98aab423d86b1e5384996ae68 | 1H NMR spectrum of poly(glycerol citraconate)
–
double bond area. | PMC10268020 | ao3c00166_0007.jpg |
0.507949 | 483642441f1e4aaaa822c65ccff24f28 | 13C NMR spectrum of poly(glycerol
citraconate) –
carboxyl group area. | PMC10268020 | ao3c00166_0008.jpg |
0.426854 | 5ca8ada22e944e57ac3c5587bb5cb1ae | Dependence of the esterification degree on the OH/COOH ratio and
temperature (x3 = 1). | PMC10268020 | ao3c00166_0009.jpg |
0.449818 | 18e07820c38645ccbb304b4ea087c704 | Dependence of the esterification degree on the temperature
and
OH/COOH ratio (x3 = 1). | PMC10268020 | ao3c00166_0010.jpg |
0.435918 | 04fc91339fcf477ab06d579085a59e80 | Dependence of the esterification degree on the OH/COOH
ratio and
time (x2 = −1). | PMC10268020 | ao3c00166_0011.jpg |
0.483487 | 1ac6dac6921846b091869056b25d043c | Risk of bias summary | PMC10268338 | 12890_2023_2472_Fig1_HTML.jpg |
0.422124 | 5802847d8fa0468eaab35cc974557245 | Flow chart of study selection | PMC10268338 | 12890_2023_2472_Fig2_HTML.jpg |
0.470133 | 7dfa06402076427b982b157ad327200d | Median PFS in total population | PMC10268338 | 12890_2023_2472_Fig3_HTML.jpg |
0.371333 | 8f777845c3864e78a90ed96275382e32 | Median PFS of the population with 19Del mutation and 21L858R mutation | PMC10268338 | 12890_2023_2472_Fig4_HTML.jpg |
0.533517 | daba7cb6e44d47e8a9ec97693080233a | PFS of subgroups | PMC10268338 | 12890_2023_2472_Fig5_HTML.jpg |
0.493186 | e66693f8a66c447eb0b9b8a3742c75e7 | Overall survival (OS) in total population | PMC10268338 | 12890_2023_2472_Fig6_HTML.jpg |
0.481937 | 1ef7382fa8cc4bc3ae71f1b47bf18e5e | Objective response rate (ORR) in total population | PMC10268338 | 12890_2023_2472_Fig7_HTML.jpg |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.