Amounts of the neonicotinoids excreted in urine during a 24 h period before (day 0) and after a single 2 μg dose was ingested (circles) and the model curves (red lines).

<p>The green bars are the means and the lower and upper blue whiskers are the standard deviations.</p

Amounts of the labeled compounds found to be excreted in the urine (μg d⁻¹) in a 24 h period after a single dose was ingested (circles) and the model curves (red lines).

<p>The green bars are the means and the lower and upper blue whiskers are the standard deviations.</p

Deuterium-labeled neonicotinoids used in the dosing study.

<p>Deuterium-labeled neonicotinoids used in the dosing study.</p

Distribution of neonicotinoid excretion rates in healthy adults (μg/d).

<p>The horizontal bars show the frequencies (the <i>x</i>-axis is the number of individual samples in each class). The black line boxes at the center of each graph show the first, second, and third quartiles. The lower whisker indicates the lowest value within the −1.5 interquartile range of the first quartile. The upper whisker indicates the highest value within the +1.5 interquartile range of the third quartile. Outlying values are shown as dots. The blue bars on the right-hand sides of the graphs are the means and standard deviations.</p

Imaging data of II-2 in Family 1.

<p>(A) MRA image. TOF-3D MRA verifies typical steno-occlusive changes of the circle of Willis. Distal T segments of both internal carotid arteries are occluded and basal moyamoya vessels are clearly seen (anteroposterior view, left panel). Typical “puff-of-smoke” look of moyamoya vessels. Internal carotid arteries are relatively hypoplastic compared with the vertebrobasilar system (lateral view, right panel). (B) Digital subtraction angiography. Catheterization angiography of left vertebral artery (left panel), left carotid artery (middle panel), and right carotid artery (right panel). (C) Transcranial color-coded sonography. Severely dampened flow in the M1 segment of the left middle cerebral artery.</p

Migration assay using HUVECs transfected with <i>RNF213</i> D4013N, R4019C and V4146A.

<p>Representative images are shown in upper panel. The re-endothelialized areas were quantified by imaging analysis (lower panel). “Vector” represents backbone vector, not including <i>RNF213</i>. Data with bars represent mean ± SD (<i>n</i> = 3 or 4). *<i>P</i> < 0.05 compared with vector, #<i>P</i> < 0.05 compared with WT according to Student’s <i>t</i>-test.</p

MAF in database and prediction of functional change of identified RNF213 variants.

<p>MAF in database and prediction of functional change of identified RNF213 variants.</p

Homology of identified RNF213 variants.

<p>Homology of identified RNF213 variants.</p

Identification of <i>RNF213</i> rare variants in three families.

<p>(A) Pedigree chart and genotypes of <i>RNF213</i> rare variants and microsatellite markers of the three families. Filled and unfilled symbols indicate affected and unaffected individuals, respectively. Squares and circles represent males and females, respectively. Arrows indicate index case. (B) Sequence chromatography of the identified <i>RNF213</i> rare variants. (C) Haplotype for p.R4019C and p.E4042K determined by cloning in II-1 in Family 2.</p

Schematic diagram of <i>RNF213</i> rare variants identified in MMD patients.

<p>Variants in Asian and white patients are shown above and below the protein, respectively. The five variants identified in MMD patients from this study are shown in bold characters. AA, amino acid; AAA+, ATPase associated with diverse cellular activities domain; RING, RING-finger domain. This figure was modified from the original version described in Reference 6.</p