Atypical spatial frequency dependence of visual metacognition among schizophrenia patients

Although altered early stages of visual processing have been reported among schizophrenia patients, how such atypical visual processing may affect higher-level cognition remains largely unknown. Here we tested the hypothesis that metacognitive performance may be atypically modulated by spatial frequency (SF) of visual stimuli among individuals with schizophrenia, given their altered magnocellular function. To study the effect of SF on metacognitive performance, we asked patients and controls to perform a visual detection task on gratings with different SFs and report confidence, and analyzed the data using the signal detection theoretic measure meta-d′. Control subjects showed better metacognitive performance after yes- (stimulus presence) than after no- (stimulus absence) responses (‘yes-response advantage’) for high SF (HSF) stimuli but not for low SF (LSF) stimuli. The patients, to the contrary, showed a ‘yes-response advantage’ not only for HSF but also for LSF stimuli, indicating atypical SF dependency of metacognition. An fMRI experiment using the same task revealed that the dorsolateral prefrontal cortex (DLPFC), known to be crucial for metacognition, shows activity mirroring the behavioral results: decoding accuracy of perceptual confidence in DLPFC was significantly higher for HSF than for LSF stimuli in controls, whereas this decoding accuracy was independent of SF in patients. Additionally, the functional connectivity of DLPFC with parietal and visual areas was modulated by SF and response type (yes/no) in a different manner between controls and patients. While individuals without schizophrenia may flexibly adapt metacognitive computations across SF ranges, patients may employ a different mechanism that is independent of SF. Because visual stimuli of low SF have been linked to predictive top-down processing, this may reflect atypical functioning in these processes in schizophrenia

Increased abundance of Ruminococcus gnavus in gut microbiota is associated with moyamoya disease and non-moyamoya intracranial large artery disease

Moyamoya disease (MMD) is a rare cerebrovascular disease endemic in East Asia. The p.R4810K mutation in RNF213 gene confers a risk of MMD, but other factors remain largely unknown. We tested the association of gut microbiota with MMD. Fecal samples were collected from 27 patients with MMD, 7 patients with non-moyamoya intracranial large artery disease (ICAD) and 15 control individuals with other disorders, and 16S rRNA were sequenced. Although there was no difference in alpha diversity or beta diversity between patients with MMD and controls, the cladogram showed Streptococcaceae was enriched in patient samples. The relative abundance analysis demonstrated that 23 species were differentially abundant between patients with MMD and controls. Among them, increased abundance of Ruminococcus gnavus > 0.003 and decreased abundance of Roseburia inulinivorans < 0.002 were associated with higher risks of MMD (odds ratio 9.6, P = 0.0024; odds ratio 11.1, P = 0.0051). Also, Ruminococcus gnavus was more abundant and Roseburia inulinivorans was less abundant in patients with ICAD than controls (P = 0.046, P = 0.012). The relative abundance of Ruminococcus gnavus or Roseburia inulinivorans was not different between the p.R4810K mutant and wildtype. Our data demonstrated that gut microbiota was associated with both MMD and ICAD

Effect of trinucleotide repeat expansion on the expression of TCF4 mRNA in Fuchs' endothelial corneal dystrophy

Purpose: CTG trinucleotide repeat (TNR) expansion is frequently found in transcription factor 4 (TCF4) in Fuchs' endothelial corneal dystrophy (FECD), though the effect of TNR expansion on FECD pathophysiology remains unclear. The purpose of this study was to evaluate the effect of TNR expansion on TCF4 expression in corneal endothelium of patients with FECD. Methods: Peripheral blood DNA and Descemet membrane with corneal endothelium were obtained from 203 German patients with FECD. The CTG TNR repeat length in TCF4 was determined by short tandem repeat (STR) assays and Southern blotting using genomic DNA. Genotyping of rs613872 in TCF4 was performed by PCR. TCF4 mRNA levels in corneal endothelium were evaluated by quantitative PCR using three different probes. Control corneal endothelial samples were obtained from 35 non-FECD subjects. Results: The STR assay and Southern blotting showed that 162 of the 203 patients with FECD (80%) harbored CTG trinucleotide repeat lengths larger than 50. Quantitative PCR using all three probes demonstrated that TCF4 mRNA is significantly upregulated in the corneal endothelium of patients with FECD, regardless of the presence of TNR expansion. However, the length of the TNR tended to show a positive correlation with TCF4 expression level. No correlation was shown between the genotype of TCF4 SNP, rs613872, and the level of TCF4 expression. Conclusions: Our findings showed that TCF4 mRNA is upregulated in the corneal endothelium of patients with FECD. Further studies on the effects of TCF4 upregulation on corneal endothelial cell function will aid in understanding the pathophysiology of FECD

Myogenic Differentiation from MYOGENIN-Mutated Human iPS Cells by CRISPR/Cas9

It is well known that myogenic regulatory factors encoded by the Myod1 family of genes have pivotal roles in myogenesis, with partially overlapping functions, as demonstrated for the mouse embryo. Myogenin-mutant mice, however, exhibit severe myogenic defects without compensation by other myogenic factors. MYOGENIN might be expected to have an analogous function in human myogenic cells. To verify this hypothesis, we generated MYOGENIN-mutated human iPS cells by using CRISPR/Cas9 genome-editing technology. Our results suggest that MYOD1-independent or MYOD1-dependent mechanisms can compensate for the loss of MYOGENIN and that these mechanisms are likely to be crucial for regulating skeletal muscle differentiation and formation