Yoshio Suzuki’s research while affiliated with The University of Tokyo and other places

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Publications (321)


Figure Legends 492
Sub-microsecond 2D Molecular Motion Mapping of Polymer Resin Enabled by Machine Learning
  • Preprint
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May 2025

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11 Reads

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Shunya Shimomura

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We developed a time-resolved X-ray method, Transmitted X-ray Blinking (TXB), with a temporal resolution of 900 ns per frame, enabling sub-microsecond analysis of molecular dynamics. TXB was applied to two structurally distinct polymer resins—crystalline PEEK and amorphous PEI—which exhibit nearly identical X-ray transmission images. Despite this similarity, single-pixel autocorrelation function (spACF) analysis revealed statistically significant differences in their dynamic behaviour. Complementary Diffracted X-ray Blinking (DXB) measurements confirmed dynamic differences, indicating that contrast arises not only from temporal resolution but also from sensitivity to distinct molecular motions, such as rotational diffusion. Although a two-dimensional map of decay constants showed only partial separation, applying principal component analysis (PCA) followed by linear discriminant analysis (LDA) to the spACF curves enabled >90% classification accuracy. Spectral analysis further revealed that the key discriminative components involved periodic fluctuations with peaks around 300 and 400 kHz. These findings demonstrate that TXB, especially when combined with multivariate analysis, can uncover hidden dynamic features in materials with otherwise indistinguishable static contrast. While demonstrated on solid-state polymers, this approach holds promise for broader applications in soft and biological materials, where subtle dynamic signatures often play critical roles in structure–function relationships.

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Murine AI excels at cats and cheese: Structural differences between human and mouse neurons and their implementation in generative AIs

October 2024

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16 Reads

Mouse and human brains have different functions that depend on their neuronal networks. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the mouse medial prefrontal cortex and compared them with structures of the human anterior cingulate cortex. The obtained results indicated that mouse neuronal somata are smaller and neurites are thinner than those of human neurons. These structural features allow mouse neurons to be integrated in the limited space of the brain, though thin neurites should suppress distal connections according to cable theory. We implemented this mouse-mimetic constraint in convolutional layers of a generative adversarial network (GAN) and a denoising diffusion implicit model (DDIM), which were then subjected to image generation tasks using photo datasets of cat faces, cheese, human faces, and birds. The mouse-mimetic GAN outperformed a standard GAN in the image generation task using the cat faces and cheese photo datasets, but underperformed for human faces and birds. The mouse-mimetic DDIM gave similar results, suggesting that the nature of the datasets affected the results. Analyses of the four datasets indicated differences in their image entropy, which should influence the number of parameters required for image generation. The preferences of the mouse-mimetic AIs coincided with the impressions commonly associated with mice. The relationship between the neuronal network and brain function should be investigated by implementing other biological findings in artificial neural networks.


Nano-CT analysis of human brain neurons
(A) Brain tissues of Brodmann area 24 (BA24) of the anterior cingulate cortex were stained using the Golgi method and mounted on the sample stage of synchrotron radiation nano-CT. (B) A series of X-ray images of layer V neurons were taken while rotating the sample. This data collection process was repeated by shifting the sample along the sample rotation axis so as to cover the neuronal arborization. (C) Tomographic slices were reconstructed from the image series and then stacked to obtain a three-dimensional image of the neuron. (D) Three-dimensional rendering of dataset S8A of the schizophrenia S8 case (S4 Table). Voxel values 60–800 were rendered with the scatter HQ algorithm of the VG Studio Max software (Volume Graphics, Germany). (E) The three-dimensional image was traced to build a Cartesian coordinate model by using the MCTrace software [37]. Geometric parameters were calculated from the resultant three-dimensional coordinates. Structural constituents are color-coded. Nodes composing the model are depicted as circles. Scale bar: 10 μm.
Relation between neurite curvature and age
(A) Bee-swarm and violin plots of neurite curvature of control cases. Each neurite is indicated with a blue dot. Cases are labeled with their age and sex. Quartiles are indicated with bars. Curvature maximum decreases with age, resulting in a decrease in the distribution span due to aging. This age-dependent decrease in the span leads to a correlation in panel B. (B) Scatter plot of standard deviation of neurite curvature versus age. Control cases are plotted with triangles and schizophrenia cases with circles. The dashed line indicates a linear regression (Pearson’s r = -0.80, p = 0.018).
Differences in structural parameters between schizophrenia and control groups
(A) Neurite curvature (p = 7.8 × 10⁻⁴, Welch’s t-test). (B) Neurite radius (p = 0.028, Welch’s t-test).
Differences in neurite structure between schizophrenia and control cases
(A) Frequency distribution of neurite curvatures of schizophrenia cases. Relative frequency in each 0.1 μm⁻¹ bin of curvature is plotted. Cases are color-coded. The distribution shows a long tail for every schizophrenia case. (B) Frequency distribution of neurite curvature of control cases. The distribution beyond 0.8 μm⁻¹ is negligible for every control case. (C) Three-dimensional rendering of neurites of the schizophrenia S8A structure. Voxel values 100–800 were rendered with the scatter HQ algorithm of VG Studio Max. Image width: 35 μm. (D) Rendering of neurites of the control N5A structure at the same scale.
Scatter plot of neurite curvature and auditory hallucination score
Schizophrenia cases are plotted with circles and controls with triangles. The dashed line indicates a linear regression (Pearson’s r = 0.80, p = 1.8 × 10⁻⁴).
Structural aging of human neurons is opposite of the changes in schizophrenia

June 2023

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89 Reads

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1 Citation

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson’s r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 × 10⁻⁴). The neurite curvature also showed a correlation with a hallucination score (Pearson’s r = 0.80, p = 1.8 × 10⁻⁴), indicating that neurite structure is relevant to brain function. This report is based on our 3D analysis of human brain tissues over a decade and is unprecedented in terms of the number of cases. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia.



Structural aging of human neurons is the opposite of the changes in schizophrenia

November 2022

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30 Reads

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson's r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 x 10^(-4)). The neurite curvature also showed a correlation with a hallucination score (Pearson's r = 0.80, p = 1.8 x 10^(-4)), indicating that neurite structure is relevant to brain function. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia. This nano-CT paper is the result of our decade-long analysis and is unprecedented in terms of number of cases.


Figure 1. Rendering of three-dimensional image of BA22 cerebral tissue of schizophrenia case S1 and Cartesian-coordinate model of its vessel network. The pial surface is toward the top. (A) Three-dimensional image of the tissue. Linear attenuation coefficients of 8-50 cm −1 were rendered in gray scale with the maximum projection method of the VG Studio software. Scale bar: 100 μm. (B) Cartesian-coordinate model of vessel network built by tracing the three-dimensional image. The model is viewed from nearly the same direction as the rendering. The vessel models of the other 23 samples were built in the same manner (Supplementary Figures S1-S17). The model was drawn with the MCTrace software. Model constituents are color-coded. The vessels magnified in panels C-E are indicated with boxes. (C-E) Cartesian-coordinate models of capillary vessels (red) superposed on cage representations of the three-dimensional image (gray) contoured at 6 times the standard deviation of the image from its mean intensity. Blood cells were visualized in the vessel lumen as lowintensity bodies. Positions of these vessels are indicated with boxes in (B). Scale bar: 10 μm.
Figure 4. (A) Relationship between mean capillary curvature and mean neurite curvature of the BA22 or BA24 area of each case. The dashed line indicates a linear regression. Schizophrenia cases S1-S4 and controls N1-N4 are color-coded. (B) Relationship between mean capillary diameter and mean neurite thickness radius. Cases are color-coded as in (A).
Vessel diameter distribution. The frequency distribution in each 0.4-μm diameter bin is represented by the length fraction, which was calculated by dividing the vessel length per bin by the total vessel length. Insets show magnifications of capillary peaks. Schizophrenia cases S1–S4 and controls N1–N4 are color-coded. Solid lines represent BA22 distributions, and dashed lines represent BA24 distributions. (A) Diameter distribution of the schizophrenia cases. (B) Diameter distribution of the control cases.
Vessel structures in (A) tissue of schizophrenia S3-22 and (B) tissue of control N4-22B. The capillary vessels of S3-22 had curved structures, whereas those of N4-22B were rather straight. The pial surface is toward the top. The structures are drawn to the same scale using MCTrace. Nodes composing each vessel are indicated with octagons. The color coding and structural orientation are the same as in Supplementary Figures S2 and S7. Scale bar: 50 μm.
Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures

June 2021

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110 Reads

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20 Citations

Brain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels. Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7–9 μm, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases. Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.


Geometric analysis of neurons at nanometer scale
A Brain tissues of Brodmann area 22 (BA22, magenta) of the temporal lobe were stained with Golgi impregnation and subjected to synchrotron radiation nanotomography to visualize three-dimensional tissue structures in layer V. The obtained datasets along with those of the BA24 area (blue) of the anterior cingulate cortex were used for the geometric analysis. The rendering shows a three-dimensional image of the S1A dataset taken from BA22 tissue of the schizophrenia S1 case. The pial surface is toward the top. Voxel values of 160–800 were rendered with the scatter HQ algorithm using VGStudio (Volume Graphics, Germany). Scale bar: 10 μm. B The neuronal network was reconstructed in Cartesian coordinate space by tracing structures in the image. First, neurites were scanned by calculating the gradient vector flow³⁷ and then traced using a three-dimensional Sobel filter³⁸. The resultant computer-generated model was examined and edited as reported previously⁹. The obtained model of the S1A dataset was drawn using MCTrace²². Structural constituents are color-coded. The same analysis was repeated for 34 datasets of 4 schizophrenia and 4 control cases. C Three-dimensional cage representation of the observed image (gray) is superposed on the structural model of an apical dendrite (red) indicated with a small dashed box in B. The three-dimensional map is contoured at 3.0 times the standard deviation (3.0 σ) of the voxel values with a grid size of 97.6 nm. Nodes composing the structure are indicated with octagons. D Three-dimensional Cartesian coordinates of the traced structure were used to calculate geometric parameters, including average curvature and average torsion for each neurite. A volume indicated with the lower box in B is magnified and its two representative neurites are highlighted, of which the blue one is tortuous and hence has a high average curvature, while the black one is rather straight and hence has a low average curvature. Arrows indicate corresponding positions in the beeswarm plot that shows the curvature distribution of all neurites in this S1A structure.
Differences in neuron structure between brain areas and between cases
A, B Neurite curvature (A) and spine thickness radius (B) of temporal (BA22) cortex calculated from each dataset vary depending on the cases (p = 2.9 × 10⁻⁸ and F = 91.7, for neurite curvature, p = 4.5 × 10⁻⁸ and F = 74.9, for spine radius, Welch’s ANOVA with case as the main factor). Schizophrenia cases S1–S4 and age/gender-matched control cases N1–N4 are color-coded. Neurite curvature was calculated by averaging the curvature along the neurite. Spine radius was calculated by averaging the thickness radius along the dendritic spine. Circles indicate mean values of each dataset, and error bars indicate standard deviation. C, D Frequency distribution of neurite curvature (C) and spine radius (D) of temporal (BA22) and prefrontal (BA24) cortexes of each case. Schizophrenia cases S1–S4 and controls N1–N4 are indicated with labels. The equality of distributions between BA22 and BA24 was examined using Kolmogorov–Smirnov test, and their p values were corrected with the Holm–Bonferroni method. ****p < 10⁻⁸; ***p < 10⁻⁴; **p < 10⁻². Quartiles are indicated with bars. Dot size is adjusted for visibility. Differences in neuron structure between brain areas and between cases. E Mean spine length is significantly shorter in BA22 than in BA24 (*p = 0.023, F = 6.7, two-way ANOVA with group (schizophrenia/control) and brain area (BA22/BA24) as main factors). Schizophrenia cases S1–S4 and controls N1–N4 are color-coded. F Mean neurite curvature is significantly higher in the schizophrenia cases than in the controls (*p = 0.031, F = 5.9, two-way ANOVA with group (schizophrenia/control) and brain area (BA22/BA24) as main factors). G Neurites of BA22 of the schizophrenia S1 case are tortuous and thin, H while those of the age/gender-matched control N1 case are smooth and thick. Structures of S1A and N1A are drawn to the same scale using MCTrace²². The pial surface is toward the top. Structural constituents are color-coded. Nodes composing each constituent are indicated with octagons. The color coding and structural orientation are the same as in Fig. 1B and Supplementary Fig. 5B. Scale bar: 10 μm. I, J Cumulative distribution of neurite curvature of schizophrenia cases (I) and controls (J). Solid lines represent BA22 distributions, and dashed lines represent BA24 distributions. Cases are color-coded.
Common structural features of neurons
A Linear correlation between mean thickness radii of neurites and spines. Arithmetic mean of neurite radii or spine radii was calculated for BA22 or BA24 of each case. Schizophrenia cases S1–S4 and controls N1–N4 are color-coded. B Reciprocal relationship between curvature and thickness radius. Arithmetic mean of curvature or radius of neurites (orange) or spines (green) was calculated for BA22 or BA24 of each case.
Structural diverseness of neurons between brain areas and between cases

January 2021

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162 Reads

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12 Citations

Translational Psychiatry

The cerebral cortex is composed of multiple cortical areas that exert a wide variety of brain functions. Although human brain neurons are genetically and areally mosaic, the three-dimensional structural differences between neurons in different brain areas or between the neurons of different individuals have not been delineated. Here we report a nanometer-scale geometric analysis of brain tissues of the superior temporal gyrus of schizophrenia and control cases. The results of the analysis and a comparison with results for the anterior cingulate cortex indicated that (1) neuron structures are significantly dissimilar between brain areas and that (2) the dissimilarity varies from case to case. The structural diverseness was mainly observed in terms of the neurite curvature that inversely correlates with the diameters of the neurites and spines. The analysis also revealed the geometric differences between the neurons of the schizophrenia and control cases. The schizophrenia cases showed a thin and tortuous neuronal network compared with the controls, suggesting that the neuron structure is associated with the disorder. The area dependency of the neuron structure and its diverseness between individuals should represent the individuality of brain functions.


Hard x-ray phase-contrast microscopy using a Gabor hologram without a zero-order term

In order to achieve a nanometer-scale resolution in an x-ray microscopy system, a Gabor-type hologram was produced by eliminating the zero-order term of the object diffraction pattern. In this system, a Fresnel zone plate was used for strong illumination of an object, and the zero-order diffraction was physically eliminated by a center stop. An accurate phase plate of π/2\pi /{{2}} in the Zernike method was numerically created, and the phase-contrast image was realized. The theoretical resolution was 19.8 nm. We proved that a gold nanocube with a size of 50 nm can be reconstructed with the predicted resolution.


Structural diverseness of neurons between brain areas and between cases

June 2020

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44 Reads

The cerebral cortex is composed of multiple cortical areas that exert a wide variety of brain functions. Although human brain neurons are genetically and areally mosaic, the three-dimensional structural differences between neurons in different brain areas or between the neurons of different individuals have not been delineated. Here, we report a nanometer-scale geometric analysis of brain tissues of the superior temporal gyrus of 4 schizophrenia and 4 control cases by using synchrotron radiation nanotomography. The results of the analysis and a comparison with results for the anterior cingulate cortex indicated that 1) neuron structures are dissimilar between brain areas and that 2) the dissimilarity varies from case to case. The structural diverseness was mainly observed in terms of the neurite curvature that inversely correlates with the diameters of the neurites and spines. The analysis also revealed the geometric differences between the neurons of the schizophrenia and control cases, suggesting that neuron structure is associated with brain function. The area dependency of the neuron structure and its diverseness between individuals should represent the individuality of brain functions.


Recent Progress in Synchrotron Radiation 3D-4D Nano-imaging based on X-Ray Full-Field Microscopy

May 2020

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68 Reads

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29 Citations

Microscopy (Oxford

The advent of high-flux, high-brilliance synchrotron radiation (SR) has prompted the development of high-resolution X-ray imaging techniques such as full-field microscopy, holography, coherent diffraction imaging, and ptychography. These techniques have strong potential to establish non-destructive three- and four-dimensional nanoimaging when combined with computed tomography (CT), called nano-tomography (nano-CT). X-ray nano-CTs based on full-field microscopy are now routinely available and widely used. Here we discuss the current status and some applications of nano-CT using a Fresnel zone plate as an objective. Optical properties of full-field microscopy, such as spatial resolution and off-axis aberration, which determine the effective field of view, are also discussed, especially in relation to 3D tomographic imaging.


Citations (45)


... Analyses of the relationships between the neuronal network and brain function can provide clues to understanding the functional basis of the brain. We have recently reported nanometer-scale three-dimensional studies of human cerebral tissues of the anterior cingulate cortex and the superior temporal gyrus of schizophrenia and control cases (Mizutani et al., 2019(Mizutani et al., , 2023. The results indicated that the neurites of schizophrenia cases are significantly thinner and more tortuous than those of controls and that the neurite curvature in the anterior cingulate cortex showed a correlation with the auditory hallucination score (Mizutani et al., 2023). ...

Reference:

Murine AI excels at cats and cheese: Structural differences between human and mouse neurons and their implementation in generative AIs
Structural aging of human neurons is opposite of the changes in schizophrenia

... This can happen in capillaries, which are already critical for CTC extravasation due to slow blood flow velocities and thin walls, that facilitate transvascular transport of CTCs and other biological substances from blood into tissue ( Figure 1). 27 Capillaries also have small diameters that often range from 5 μm to 10 μm, [28][29][30] which are smaller than CTCs' size (TNBC's diameter 12.4 ± 2.1 μm) 31 and are characterized by their many branches. In the trapping theory, capillaries' small diameters and many branches allow CTCs to be physically trapped in the blood F I G U R E 1 Overview of metastatic cascade. ...

Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures

... At synapses they are termed synaptic adhesion molecules and contact pre-and post-synaptic cells at puncta adherentia junctions (PAJs), thus providing an extracellular skeleton holding the cells tightly together and preventing separation due to physical stress (Figure 2). Nectins also have similar functions at PAJs [19]. ...

Structural diverseness of neurons between brain areas and between cases

Translational Psychiatry

... More recently, optical clearing of whole organs was achieved; however, such methods require several months, volume-suitable high-resolution three-dimensional read-outs are lacking, staining is dependent on antibody penetration depth and extremely large datasets have to be processed 44 . In contrast, the high penetration power of X-rays, e.g. in PBI, achieves a high ratio of object thickness to spatial resolution 47 . ...

Recent Progress in Synchrotron Radiation 3D-4D Nano-imaging based on X-Ray Full-Field Microscopy
  • Citing Article
  • May 2020

Microscopy (Oxford

... Compared to attenuation-based imaging, PBI significantly improves contrastto-noise, which is especially important for differentiating structures with similar attenuation, such as different soft tissues [47,37]. PBI has been employed for ex vivo studies of human organs and tissues [34,56], as well as in vivo studies with small animals [37,18,45]. Much of this imaging has been performed at synchrotron X-ray sources, which offer high coherence, high flux, and low divergence. ...

Methods for dynamic synchrotron X-ray respiratory imaging in live animals

... Due to the ambiguity a cos(φ) = −a cos(φ ± π), the sign of a sinusoid's amplitude may generally be flipped when simultaneously accounting for a phase shift of 180°. Whenever the phase shift is explicitly constrained by suiting prior knowledge, negative amplitudes and visibilities can therefore result, as is e.g. the case in [210]. A physical interpretation of this mathematical peculiarity can be found in the relation between the complex amplitude and the observable intensity of light waves. ...

Probing Surface Morphology using X-ray Grating Interferometry

... Similarly, a high differential contrast of tissues and cell nuclei was achieved in our multimodal imaging of medaka embryos and fish retinal organoids. To avoid shrinkage of tissues due to staining procedure water-based, contrast agents like iodine 40 or ionic liquids 86 can be used for sample preparation. The most promising further development is a combination of light-sheet microscopy, instead of absorption, with phase-contrast X-ray tomography 19,31 . ...

Use of ionic liquid for X-ray micro-CT specimen preparation of imbibed seeds

Microscopy: the journal of the Quekett Microscopical Club

... deletion syndrome. 70 Besides, slight changes have been reported in patients with schizophrenia, such as abnormalities in neurites 71 and complex macromolecular structures in the synapse, 72 which standard pathological observation methods cannot observe. To understand the neurobiological aspects of incident dementia in older patients with schizophrenia, further clinicopathological studies are needed not only in the context of co-existing neurodegeneration based on the current pathological classification, but also from other perspectives, including glia-related neurotransmission and proven integration with molecular genetics in schizophrenia research. ...

Three-dimensional alteration of neurites in schizophrenia

Translational Psychiatry

... δMnO 2 , a type of ferromanganese (Fe-Mn) oxide deposited on the seafloor, oxidizes dissolved Co (Co 2+ ) in seawater and incorporates Co 3+ into its crystal structure (Hein et al., 2020). This hydrogenous Fe-Mn oxide is known to be the major source of Co in pelagic clay (Uramoto et al., 2019;Yasukawa et al., 2020). Assuming that the hydrogenous Fe-Mn oxides incorporate Co at the relatively constant ratio in the oxic pelagic ocean, which is supported by positive correlation between MnO Note. ...

Significant contribution of subseafloor microparticles to the global manganese budget

... Using the collected 2D diffraction images DXB analysis was performed for each temperature. The detailed procedure has been reported previously 27,31 , but the main points and considerations for this sample are as follows. A region of interest including all pixels along the Debye-Scherrer rings for the peaks labeled in Fig. 3ab that could be sufficiently resolved from background noise were selected for analysis. ...

Diffracted X-ray Blinking Tracks Single Protein Motions