Hydrogenated Borophene Shows Catalytic Activity as Solid Acid

Hydrogen boride (HB) or hydrogenated borophene sheets are recently realized two-dimensional materials that are composed of only two light elements, boron and hydrogen. However, their catalytic activity has not been experimentally analyzed. Herein, we report the catalytic activity of HB sheets in ethanol reforming. HB sheets catalyze the conversion of ethanol to ethylene and water above 493 K with high selectivity, independent of the contact time, and with an apparent activation energy of 102.8 ± 5.5 kJ/mol. Hence, we identify that HB sheets act as solid-acid catalysts

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Semantic Memory Organization in Japanese Patients With Schizophrenia Examined With Category Fluency

BackgroundDisorganization of semantic memory in patients with schizophrenia has been studied by referring to their category fluency performance. Recently, data-mining techniques such as singular value decomposition (SVD) analysis have been reported to be effective in elucidating the latent semantic memory structure in patients with schizophrenia. The aim of this study is to investigate semantic memory organization in patients with schizophrenia using a novel method based on data-mining approach.MethodCategory fluency data were collected from 181 patients with schizophrenia and 335 healthy controls at the Department of Psychiatry, Osaka University. The 20 most frequently reported animals were chosen for SVD analysis. In the two-dimensional (2D) solution, item vectors (i.e., animal names) were plotted in the 2D space of each group. In the six-dimensional (6D) solution, inter-item similarities (i.e., cosines) were calculated among items. Cosine charts were also created for the six most frequent items to show the similarities to other animal items.ResultsIn the 2D spatial representation, the six most frequent items were grouped in the same clusters (i.e., dog, cat as pet cluster, lion, tiger as wild/carnivorous cluster, and elephant, giraffe as wild/herbivorous cluster) for patients and healthy adults. As for 6D spatial cosines, the correlations (Pearson’s r) between 17 items commonly generated in the two groups were moderately high. However, cosine charts created for the three pairs from the six most frequent animals (dog–cat, lion–tiger, elephant–giraffe) showed that pair-wise similarities between other animals were less salient in patients with schizophrenia.DiscussionSemantic memory organization in patients with schizophrenia, revealed by SVD analysis, did not appear to be seriously impaired in the 2D space representation, maintaining a clustering structure similar to that in healthy controls for common animals. However, the coherence of those animals was less salient in 6D space, lacking pair-wise similarities to other members of the animal category. These results suggests subtle but structural differences between the two groups. A data-mining approach by means of SVD analysis seems to be effective in evaluating semantic memory in patients with schizophrenia, providing both a visual representation and an objective measure of the structural alterations

A Brief Assessment of Intelligence Decline in Schizophrenia As Represented by the Difference between Current and Premorbid Intellectual Quotient

Patients with schizophrenia elicit several clinical features, such as psychotic symptoms, cognitive impairment, and subtle decline of intelligence. The latter two features become evident around the onset of the illness, although they may exist even before the disease onset in a substantial proportion of cases. Here, we review the literature concerning intelligence decline (ID) during the progression of schizophrenia. ID can be estimated by comparing premorbid and current intellectual quotient (IQ) by means of the Adult Reading Test and Wechsler Adult Intelligence Scale (WAIS), respectively. For the purpose of brief assessment, we have recently developed the WAIS-Short Form, which consists of Similarities and Symbol Search and well reflects functional outcomes. According to the degree of ID, patients were classified into three distinct subgroups; deteriorated, preserved, and compromised groups. Patients who show deteriorated IQ (deteriorated group) elicit ID from a premorbid level (≥10-point difference between current and premorbid IQ), while patients who show preserved or compromised IQ do not show such decline (<10-point difference). Furthermore, the latter patients were divided into patients with preserved and compromised IQ based on an estimated premorbid IQ score >90 or below 90, respectively. We have recently shown the distribution of ID in a large cohort of schizophrenia patients. Consistent with previous studies, approximately 30% of schizophrenia patients had a decline of less than 10 points, i.e., normal intellectual performance. In contrast, approximately 70% of patients showed deterioration of IQ. These results indicate that there is a subgroup of schizophrenia patients who have mild or minimal intellectual deficits, following the onset of the disorder. Therefore, a careful assessment of ID is important in identifying appropriate interventions, including medications, cognitive remediation, and social/community services

Genetic Overlap between General Cognitive Function and Schizophrenia: A Review of Cognitive GWASs

General cognitive (intelligence) function is substantially heritable, and is a major determinant of economic and health-related life outcomes. Cognitive impairments and intelligence decline are core features of schizophrenia which are evident before the onset of the illness. Genetic overlaps between cognitive impairments and the vulnerability for the illness have been suggested. Here, we review the literature on recent large-scale genome-wide association studies (GWASs) of general cognitive function and correlations between cognitive function and genetic susceptibility to schizophrenia. In the last decade, large-scale GWASs (n > 30,000) of general cognitive function and schizophrenia have demonstrated that substantial proportions of the heritability of the cognitive function and schizophrenia are explained by a polygenic component consisting of many common genetic variants with small effects. To date, GWASs have identified more than 100 loci linked to general cognitive function and 108 loci linked to schizophrenia. These genetic variants are mostly intronic or intergenic. Genes identified around these genetic variants are densely expressed in brain tissues. Schizophrenia-related genetic risks are consistently correlated with lower general cognitive function (rg = −0.20) and higher educational attainment (rg = 0.08). Cognitive functions are associated with many of the socioeconomic and health-related outcomes. Current treatment strategies largely fail to improve cognitive impairments of schizophrenia. Therefore, further study is needed to understand the molecular mechanisms underlying both cognition and schizophrenia

Predicting employment status and subjective quality of life in patients with schizophrenia

Although impaired social functioning, particularly poor employment status, is a cardinal feature of patients with schizophrenia and leads to decreased quality of life (QOL), few studies have addressed the relationship between these two clinical issues. The aim of this study was to determine whether employment status predicts subjective QOL and to evaluate a model in which functional capacity mediates the relationship between general cognitive performance and employment status. Ninety-three patients with schizophrenia were administered a comprehensive battery of cognitive tests, the UCSD Performance-based Skills Assessment-Brief version (UPSA-B), the Social Functioning Scale (SFS), and the Subjective Quality of Life Scale (SQLS). First, we evaluated a model for predicting the employment/occupation subscale score of the SFS using path analysis, and the model fitted well (χ2 (4) = 3.6, p = 0.46; CFI = 1.0; RMSEA < 0.001, with 90% CIs: 0–0.152). Employment status was predicted by negative symptoms and functional capacity, which was in turn predicted by general cognitive performance. Second, we added subjective QOL to this model. In a final path model, QOL was predicted by negative symptoms and employment status. This model also satisfied good fit criteria (χ2 (7) = 10.3, p = 0.17; CFI = 0.987; RMSEA = 0.072, with 90% CIs: 0–0.159). The UPSA-B and SFS scores were moderately correlated with most measures of cognitive performance. These results support the notion that better employment status enhances subjective QOL in patients with schizophrenia