Supplementary Figure 1 from Ready to detect a reversal of time's arrow: a psychophysical study using short video clips in daily scenes

Fitting of three models to the distributions of reaction time. The data (histograms) are the same as those shown in Figs. 6a-d. Three curves show the fitting of the Rayleigh model (broken line), a diffusion model with a single threshold (cyan), and a normal distribution model (green). Two parameters of each model were estimated using maximum likelihood estimation. Numbers in the legend show the negative log likelihood (the smaller the better). Note that the Rayleigh model yielded the smallest negative log likelihood in three of four distributions

Bone mineral density and bone metabolism marker levels in all study patients.

<p>Bone mineral density and bone metabolism marker levels in all study patients.</p

Bone mineral density and bone metabolism marker levels according to the period of bed confinement in all study patients.

<p>Because all patients had been bedridden from birth, the period of bed confinement was equal to their age. A) Correlation between the bone mineral density of lumbar spine vertebrae 2–4 in the anteroposterior projection and the period of bed confinement. Correlation between the bone metabolism marker levels, including the serum osteocalcin levels (B), urine N-terminal telopeptide levels (C), serum 25 (OH) vitamin D levels (D), serum intact parathyroid hormone levels (E), serum calcium levels (F), serum phosphorus levels (G), and serum alkaline phosphatase levels (H), and period of bed confinement. Red lines indicate the cutoff value for osteoporosis (bone mineral density) and those for predicting bone fracture (osteocalcin and N-terminal telopeptide), as proposed by the guidelines for the prevention and treatment of osteoporosis [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156991#pone.0156991.ref017" target="_blank">17</a>].</p

Changes in bone metabolism markers during long bedridden periods.

<p>Changes in bone metabolism markers during long bedridden periods.</p

Association between the bone metabolism marker levels at baseline with the bone mineral density during a follow-up of 12 years in patients whose baseline age was <30 years.

<p>Association between the bone metabolism marker levels at baseline with the bone mineral density during a follow-up of 12 years in patients whose baseline age was <30 years.</p

Comparisons of clinical characteristics by underlying diseases.

<p>Comparisons of clinical characteristics by underlying diseases.</p

Clinical characteristics in all study participants (n = 36).

<p>Clinical characteristics in all study participants (n = 36).</p

Baseline characteristics in 17 patients <30 years followed for 12 years.

<p>Baseline characteristics in 17 patients <30 years followed for 12 years.</p

Changes in the bone mineral density and bone metabolism marker levels during a 12-year follow-up period in patients whose baseline age was <30 years.

<p>Red lines indicate the cutoff value for osteoporosis (bone mineral density) and those for predicting bone fracture (osteocalcin and N-terminal telopeptide), as proposed by the guidelines for the prevention and treatment of osteoporosis [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156991#pone.0156991.ref017" target="_blank">17</a>].</p

A 5-bp Insertion in <em>Mip</em> Causes Recessive Congenital Cataract in KFRS4/Kyo Rats

<div><p>We discovered a new cataract mutation, <em>kfrs4</em>, in the Kyoto Fancy Rat Stock (KFRS) background. Within 1 month of birth, all <em>kfrs4/kfrs4</em> homozygotes developed cataracts, with severe opacity in the nuclei of the lens. In contrast, no opacity was observed in the <em>kfrs4/</em>+ heterozygotes. We continued to observe these rats until they reached 1 year of age and found that cataractogenesis did not occur in <em>kfrs4/</em>+ rats. To define the histological defects in the lenses of <em>kfrs4</em> rats, sections of the eyes of these rats were prepared. Although the lenses of <em>kfrs4/kfrs4</em> homozygotes showed severely disorganised fibres and vacuolation, the lenses of <em>kfrs4/</em>+ heterozygotes appeared normal and similar to those of wild-type rats. We used positional cloning to identify the <em>kfrs4</em> mutation. The mutation was mapped to an approximately 9.7-Mb region on chromosome 7, which contains the <em>Mip</em> gene. This gene is responsible for a dominant form of cataract in humans and mice. Sequence analysis of the mutant-derived <em>Mip</em> gene identified a 5-bp insertion. This insertion is predicted to inactivate the MIP protein, as it produces a frameshift that results in the synthesis of 6 novel amino acid residues and a truncated protein that lacks 136 amino acids in the C-terminal region, and no MIP immunoreactivity was observed in the lens fibre cells of <em>kfrs4/kfrs4</em> homozygous rats using an antibody that recognises the C- and N-terminus of MIP. In addition, the <em>kfrs4/</em>+ heterozygotes showed reduced expression of <em>Mip</em> mRNA and MIP protein and the <em>kfrs4/kfrs4</em> homozygotes showed no expression in the lens. These results indicate that the <em>kfrs4</em> mutation conveys a loss-of-function, which leads to functional inactivation though the degradation of <em>Mip</em> mRNA by an mRNA decay mechanism. Therefore, the <em>kfrs4</em> rat represents the first characterised rat model with a recessive mutation in the <em>Mip</em> gene.</p> </div