Epitranscriptomic m6A regulation following spinal cord injury.

RNA methylation is involved in multiple physiological and pathological processes. However, the role of RNA methylation in spinal cord regeneration has not been reported. In this study, we find an altered m6A (N6-methyladenosine) RNA methylation profiling following zebrafish spinal cord injury (SCI), in line with an altered transcription level of the m6A methylase Mettl3. Interestingly, many of the differential m6A-tagged genes associated with neural regeneration are hypomethylated, but their transcription levels are upregulated in SCI. Moreover, we find that METTL3 may be important for spinal cord regeneration. We also show a conserved feature of METTL3 changes in mouse SCI model, in which the expression of METTL3 is increased in both astrocytes and neural stem cells. Together, our results indicate that m6A RNA methylation is dynamic and conserved following SCI and may contribute to spinal cord regeneration.

Ultrasonographic characteristics of Killian-Jamieson diverticula.

PURPOSE: A Killian-Jamieson diverticulum (KJD) may be mistaken for a thyroid nodule on ultrasound (US). The purpose of this retrospective study was to search for specific US features that would help differentiate between KJD and thyroid nodules. METHODS: A total of 12 patients with KJD who had undergone an US examination of the neck were identified. The size, shape, boundary, echopattern, location, color flow signals on color Doppler US of KJD and the relationship between the lesion and esophageal wall were analyzed. The change of size, shape and internal echotexture were also observed when the lesion was compressed with the probe and when the patient was asked to drink water. RESULTS: All KJD were confirmed by barium esophagography. All KJD were posterior to the left thyroid lobe on US, and were associated with a semicircular hypoechoic anterior wall. The internal echotexture was heterogeneous. In eight cases, the connection to the esophageal wall was seen. When compressing with the US probe or when the patients swallowed water, the size, shape or internal echotexture of the lesion changed. CONCLUSION: The specific criteria for US diagnosis of KJD included the connection to the esophageal wall and the fact that the internal echotexture, shape and size of KJD changed in real-time when the patient swallowed water or when the lesion was compressed with the transducer.

Integrative systems and functional analyses reveal a role of dopaminergic signaling in myelin pathogenesis.

BACKGROUND: Myelin sheaths surrounding axons are critical for electrical signal transmission in the central nervous system (CNS). Diseases with myelin defects such as multiple sclerosis (MS) are devastating neurological conditions for which few effective treatments are available. Dysfunction of the dopaminergic system has been observed in multiple neurological disorders. Its role in myelin pathogenesis, however, is unclear. METHODS: This work used a combination of literature curation, bioinformatics, pharmacological and genetic manipulation, as well as confocal imaging techniques. Literature search was used to establish a complete set of genes which is associated with MS in humans. Bioinformatics analyses include pathway enrichment and crosstalk analyses with human genetic association studies as well as gene set enrichment and causal relationship analyses with transcriptome data. Pharmacological and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genetic manipulation were applied to inhibit the dopaminergic signaling in zebrafish. Imaging techniques were used to visualize myelin formation in vivo. RESULTS: Systematic analysis of human genetic association studies revealed that the dopaminergic synapse signaling pathway is enriched in candidate gene sets. Transcriptome analysis confirmed that expression of multiple dopaminergic gene sets was significantly altered in patients with MS. Pathway crosstalk analysis and gene set causal relationship analysis reveal that the dopaminergic synapse signaling pathway interacts with or is associated with other critical pathways involved in MS. We also found that disruption of the dopaminergic system leads to myelin deficiency in zebrafish. CONCLUSIONS: Dopaminergic signaling may be involved in myelin pathogenesis. This study may offer a novel molecular mechanism of demyelination in the nervous system.

Identification of genes associated with sudden cardiac death: a network- and pathway-based approach.

BACKGROUND: Sudden cardiac death (SCD) accounts for a large proportion of the total deaths across different age groups. Although numerous candidate genes related to SCD have been identified by genetic association studies and genome wide association studies (GWAS), the molecular mechanisms underlying SCD are still unclear, and the biological functions and interactions of these genes remain obscure. To clarify this issue, we performed a comprehensive and systematic analysis of SCD-related genes by a network and pathway-based approach. METHODS: By screening the publications deposited in the PubMed and Gene-Cloud Biotechnology Information (GCBI) databases, we collected the genes genetically associated with SCD, which were referred to as the SCD-related gene set (SCDgset). To analyze the biological processes and biochemical pathways of the SCD-related genes, functional analysis was performed. To explore interlinks and interactions of the enriched pathways, pathway crosstalk analysis was implemented. To construct SCD-specific molecular networks, Markov cluster algorithm and Steiner minimal tree algorithm were employed. RESULTS: We collected 257 genes that were reported to be associated with SCD and summarized them in the SCDgset. Most of the biological processes and biochemical pathways were related to heart diseases, while some of the biological functions may be noncardiac causes of SCD. The enriched pathways could be roughly grouped into two modules. One module was related to calcium signaling pathway and the other was related to MAPK pathway. Moreover, two different SCD-specific molecular networks were inferred, and 23 novel genes potentially associated with SCD were also identified. CONCLUSIONS: In summary, by means of a network and pathway-based methodology, we explored the pathogenetic mechanism underlying SCD. Our results provide valuable information in understanding the pathogenesis of SCD and include novel biomarkers for diagnosing potential patients with heart diseases; these may help in reducing the corresponding risks and even aid in preventing SCD.

The neurodevelopmental role of dopaminergic signaling in neurological disorders.

Dopamine (DA), a critical neurotransmitter of both the central and peripheral nerve system, plays important roles in a series of biological processes. Dysfunction of dopaminergic signalling may lead to a series of developmental disorders, including attention deficit/hyperactivity disorder, autism and schizophrenia. However, the exact roles of dopaminergic signalling in these diseases are far from fully understood. We analyse the roles of dopaminergic signalling in multiple physiological and pathological processes, focusing on brain development and related disorders. By summarizing current research in this area, we provide guidance for future studies. This review seeks to deepen our understanding of dopaminergic signalling in developmental disorders, which may offer clues for developing more effective therapeutic drugs.