Mendelian randomization analyses reveal causal relationships between brain functional networks and risk of psychiatric disorders.

Dysfunction of brain resting-state functional networks has been widely reported in psychiatric disorders. However, the causal relationships between brain resting-state functional networks and psychiatric disorders remain largely unclear. Here we perform bidirectional two-sample Mendelian randomization (MR) analyses to investigate the causalities between 191 resting-state functional magnetic resonance imaging (rsfMRI) phenotypes (n = 34,691 individuals) and 12 psychiatric disorders (n = 14,307 to 698,672 individuals). Forward MR identified 8 rsfMRI phenotypes causally associated with the risk of psychiatric disorders. For example, the increase in the connectivity of motor, subcortical-cerebellum and limbic network was associated with lower risk of autism spectrum disorder. In adddition, increased connectivity in the default mode and central executive network was associated with lower risk of post-traumatic stress disorder and depression. Reverse MR analysis revealed significant associations between 4 psychiatric disorders and 6 rsfMRI phenotypes. For instance, the risk of attention-deficit/hyperactivity disorder increases the connectivity of the attention, salience, motor and subcortical-cerebellum network. The risk of schizophrenia mainly increases the connectivity of the default mode and central executive network and decreases the connectivity of the attention network. In summary, our findings reveal causal relationships between brain functional networks and psychiatric disorders, providing important interventional and therapeutic targets for psychiatric disorders at the brain functional network level.

Mendelian randomization reveals the causal links between microRNA and schizophrenia.

MicroRNAs have pivotal roles in gene regulation. However, microRNAs that have causal effects on schizophrenia remain largely unknown. To investigate the causal relationships between microRNAs and schizophrenia, here we conduct a Mendelian randomization (MR) study. The genome-wide association study (GWAS) of schizophrenia (67,390 cases and 94,015 controls) from PGC3 were used as the outcome. Genetic variants associated with microRNAs were used as exposure in MR analysis. We identified 6 microRNAs that showed causality on schizophrenia. These microRNAs include hsa-miR-570-3p (OR = 1.03, 95% confidence interval (CI): 1.02 to 1.05, P = 5.45 × 10-5), hsa-miR-550a-3p (OR = 1.12, 95% CI: 1.06 to 1.18, P = 5.99 × 10-5), hsa-miR-130a-3p (OR = 1.10, 95% CI: 1.05 to 1.15, P = 1.58 × 10-4), hsa-miR-210 (OR = 0.87, 95% CI: 0.82 to 0.93, P = 3.09 × 10-5), hsa-miR-337-3p (OR = 1.01, 95% CI: 1.01 to 1.02, P = 3.39 × 10-4), and hsa-miR-130b-3p (OR = 0.89, 95% CI: 0.84 to 0.94, P = 1.50 × 10-5). Differential expression analysis showed dysregulation of hsa-miR-130b-3p in schizophrenia cases compared with controls. Gene Ontology (GO) analysis showed that the targets of these causal microRNAs were significantly enriched in RNA splicing pathways. This MR study identified six microRNAs whose genetically regulated expression might have a causal role in schizophrenia, indicating the causality of these microRNAs in schizophrenia. Our findings also indicate that these microRNAs may be used as potential biomarkers for schizophrenia.

Genetic regulatory and biological implications of the 10q24.32 schizophrenia risk locus.

Genome-wide association studies have identified 10q24.32 as a robust schizophrenia risk locus. Here we identify a regulatory variant (rs10786700) that disrupts binding of transcription factors at 10q24.32. We independently confirmed the association between rs10786700 and schizophrenia in a large Chinese cohort (n = 11 547) and uncovered the biological mechanism underlying this association. We found that rs10786700 resides in a super-enhancer element that exhibits dynamic activity change during the development process and that the risk allele (C) of rs10786700 conferred significant lower enhancer activity through enhancing binding affinity to repressor element-1 silencing transcription factor (REST). CRISPR-Cas9-mediated genome editing identified SUFU as a potential target gene by which rs10786700 might exert its risk effect on schizophrenia, as deletion of rs10786700 downregulated SUFU expression. We further investigated the role of Sufu in neurodevelopment and found that Sufu knockdown inhibited proliferation of neural stem cells and neurogenesis, affected molecular pathways (including neurodevelopment-related pathways, PI3K-Akt and ECM-receptor interaction signalling pathways) associated with schizophrenia and altered the density of dendritic spines. These results reveal that the functional risk single nucleotide polymorphism rs10786700 at 10q24.32 interacts with REST synergistically to regulate expression of SUFU, a novel schizophrenia risk gene which is involved in schizophrenia pathogenesis by affecting neurodevelopment and spine morphogenesis.

Single-cell RNA Sequencing Reveals Thoracolumbar Vertebra Heterogeneity and Rib-genesis in Pigs.

Development of thoracolumbar vertebra (TLV) and rib primordium (RP) is a common evolutionary feature across vertebrates, although whole-organism analysis of the expression dynamics of TLV- and RP-related genes has been lacking. Here, we investigated the single-cell transcriptome landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene expression signatures. In-depth dissection of the gene expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and RP development. Further analysis of cell type-specific and strand-specific expression uncovered the extremely high level of HOXA10 3'-UTR sequence specific to osteoblasts of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.

Alkalibacillus aidingensis sp. nov., an Bacterium Isolated from Aiding Lake in Xinjiang Province, North-West China.

A bacterial strain, Gram staining negative, aerobic, long rod, motile bacterium with flagellum, designated strain YIM 98829T, was isolated from the Aiding Lake in Xinjiang province, North-West China. The isolate produced oval subterminal endospores in swollen sporangia. The predominant menaquinone was MK-7. The cell wall peptidoglycan contained ornithine, serine, aspartic acid, glutamic acid, and alanine, while diaminopimelic acid could not be detected. The major whole-cell sugars contained xylose, glucose, galactose, and mannose. Diphosphatidylglycerol, phosphatidylglycerol, one unknown phospholipid, and two unidentified aminophospholipids were part of the polar lipid profile. Iso-C15:0 and anteiso-C15:0 were the major fatty acids. The DNA G + C content of the type strain was 38.0 mol%. Phylogenetic analysis indicated that the isolate belongs to the genus Alkalibacillus. However, it differed from its closest relatives, A. haloalkaliphilus DSM 5271T (97.04%), A. filiformis 4AGT (96.99%), and A. silvisoli BM2T (96.95%) in some physiological characteristics. DNA-DNA hybridization result indicated low levels of relatedness between strain YIM 98829T and A. haloalkaliphilus JCM 12303T (16.9%). On the basis of physiological, phenotypic, and chemotaxonomic data, strain YIM 98829T represents a novel species of genus Alkalibacillus, for which the name Alkalibacillus aidingensis sp. nov. is proposed. The type strain is YIM 98829T (= NBRC 114103T = CGMCC 1.17260T = DSM 112470T).

Oceanobacillus salinisoli sp. nov., a bacterium isolated from saline soil of Turpan city in Xinjiang province, north-west China.

YIM B00359T, a novel bacterial strain was isolated from the saline soil of Turpan city in Xinjiang province, north-west China. The strain was Gram-stain-positive, motile, aerobic, produced oval subterminal endospores in swollen sporangia. The whole-cell hydrolysates contain meso-diaminopimelic acid as the cell-wall diamino acid, with xylose, glucose, and ribose as the major whole-cell sugars. The phospholipids are diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids, unidentified glycolipids, and one unidentified glycophospholipid. The predominant menaquinone is MK-7. The major fatty acids are anteiso-C15:0, iso-C14:0, iso-C15:0, and iso-C16:0. The DNA G + C content of the type strain is 37.5 mol%. Phylogenetic analysis indicated that the isolate belongs to the genus Oceanobacillus. However, it differed from its closest relatives, Oceanobacillus halophilus DSM 23996 T and Oceanobacillus senegalensis Marseille-P3587T in many physiological and chemotaxonomic characteristics. Based on comparative analysis of polyphasic taxonomic data, strain YIM B00359T represents a novel species of the genus Oceanobacillus, for which the name Oceanobacillus salinisoli sp. nov. is proposed. The type strain is YIM B00359T (= CGMCC 1.17509T = KCTC 43185T).

Oceanobacillus halotolerans sp. nov., a bacterium isolated from salt lake in Xinjiang province, north-west China.

A bacterial strain, designated YIM 98839T, was isolated from the hypersaline sediment of Aiding Lake in Xinjiang province, North-West China. The strain was Gram-stain-positive, motile, aerobic, produced oval subterminal or central endospores in swollen sporangia. The whole-cell hydrolysates contain meso-diaminopimelic acid as the diagnostic cell-wall diamino acid. Galactose, fucose and ribose are the major whole-cell sugars. The phospholipids are diphosphatidylglycerol, phosphatidylglycerol and one unknown phospholipid. The predominant menaquinone is MK-7. The major fatty acids are anteiso-C15:0, anteiso-C17:0 and iso-C15:0. The DNA G + C content of the type strain is 37.0 mol%. Phylogenetic analysis indicated that the isolate belongs to the genus Oceanobacillus. However, it differed from its closest relative, Oceanobacillus limi H9BT in many physiological characteristics. Moreover, the DNA-DNA relatedness values between the novel isolate and the relative type strain was 20.2%. Based on comparative analysis of polyphasic taxonomic data, strain YIM 98839T represents a novel species of the genus Oceanobacillus, for which the name Oceanobacillus halotolerans sp. nov. is proposed. The type strain is YIM 98839T (= CGMCC 1.17002T = KCTC 43140T).