Narrowing down the candidates of beneficial A-to-I RNA editing by comparing the recoding sites with uneditable counterparts.

Adar-mediated adenosine-to-inosine (A-to-I) RNA editing mainly occurs in nucleus and diversifies the transcriptome in a flexible manner. It has been a challenging task to identify beneficial editing sites from the sea of total editing events. The functional Ser>Gly auto-recoding site in insect Adar gene has uneditable Ser codons in ancestral nodes, indicating the selective advantage to having an editable status. Here, we extended this case study to more metazoan species, and also looked for all Drosophila recoding events with potential uneditable synonymous codons. Interestingly, in D. melanogaster, the abundant nonsynonymous editing is enriched in the codons that have uneditable counterparts, but the Adar Ser>Gly case suggests that the editable orthologous codons in other species are not necessarily edited. The use of editable versus ancestral uneditable codon is a smart way to infer the selective advantage of RNA editing, and priority might be given to these editing sites for functional studies due to the feasibility to construct an uneditable allele. Our study proposes an idea to narrow down the candidates of beneficial recoding sites. Meanwhile, we stress that the matched transcriptomes are needed to verify the conservation of editing events during evolution.

Identification and Interpretation of A-to-I RNA Editing Events in Insect Transcriptomes.

Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent RNA modification in the nervous systems of metazoans. To study the biological significance of RNA editing, we first have to accurately identify these editing events from the transcriptome. The genome-wide identification of RNA editing sites remains a challenging task. In this review, we will first introduce the occurrence, regulation, and importance of A-to-I RNA editing and then describe the established bioinformatic procedures and difficulties in the accurate identification of these sit esespecially in small sized non-model insects. In brief, (1) to obtain an accurate profile of RNA editing sites, a transcriptome coupled with the DNA resequencing of a matched sample is favorable; (2) the single-cell sequencing technique is ready to be applied to RNA editing studies, but there are a few limitations to overcome; (3) during mapping and variant calling steps, various issues, like mapping and base quality, soft-clipping, and the positions of mismatches on reads, should be carefully considered; (4) Sanger sequencing of both RNA and the matched DNA is the best verification of RNA editing sites, but other auxiliary evidence, like the nonsynonymous-to-synonymous ratio or the linkage information, is also helpful for judging the reliability of editing sites. We have systematically reviewed the understanding of the biological significance of RNA editing and summarized the methodology for identifying such editing events. We also raised several promising aspects and challenges in this field. With insightful perspectives on both scientific and technical issues, our review will benefit the researchers in the broader RNA editing community.

Phylomitogenomic Analyses Provided Further Evidence for the Resurrection of the Family Pseudoacanthocephalidae (Acanthocephala: Echinorhynchida).

The phylum Acanthocephala is an important monophyletic group of parasites, with adults parasitic in the digestive tracts of all major vertebrate groups. Acanthocephalans are of veterinary, medical, and economic importance due to their ability to cause disease in domestic animals, wildlife, and humans. However, the current genetic data for acanthocephalans are sparse, both in terms of the proportion of taxa surveyed and the number of genes sequenced. Consequently, the basic molecular phylogenetic framework for the phylum is still incomplete. In the present study, we reported the first complete mitochondrial genome from a representative of the family Pseudoacanthocephalidae Petrochenko, 1956. The mitogenome of Pseudoacanthocephalus bufonis (Shipley, 1903) is 14,056 bp in length, contains 36 genes (12 protein-coding genes (PCGs) (lacking atp8), 22 tRNA genes, and 2 rRNA genes (rrnL and rrnS)) and two non-coding regions (NCR1 and NCR2), and displayed the highest GC-skew in the order Echinorhynchida. Phylogenetic results of maximum likelihood (ML) and Bayesian inference (BI) using the amino acid sequences of 12 protein-coding genes in different models provided further evidence for the resurrection of the family Pseudoacanthocephalidae and also supported that the order Echinorhynchida is paraphyletic. A monophyletic clade comprising P. bufonis and Cavisoma magnum suggests a close affinity between Pseudoacanthocephalidae and Cavisomatidae. Our phylogenetic analyses also showed that Polymorphidae has a closer relationship with Centrorhynchidae than Plagiorhynchidae in the monophyletic order Polymorphida.

First complete mitochondrial genome of the tribe Coccini (Hemiptera, Coccomorpha, Coccidae) and its phylogenetic implications.

Soft scale insects (Hemiptera, Coccidae) are important pests of various agricultural and horticultural crops and ornamental plants. They have negative impacts on agriculture and forestry. The tribe Coccini represents one of the most ancient evolutionary lineages of soft scale insects. However, no complete Coccini mitochondrial genome (mitogenome) is available in public databases. Here, we described the complete mitogenome of Coccushesperidum L., 1758. The 15,566 bp mitogenome of C.hesperidum had a high A+T content (83.4%) and contained a typical set of 37 genes, with 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs) and two ribosomal RNA genes (rRNAs). Only seven tRNAs had the typical clover-leaf secondary structure and the remaining tRNAs lacked the DHU arm, TψC arm or both. Moreover, a comparative analysis of all reported scale insect mitogenomes from GenBank database was performed. The mitogenomes of scale insects showed high similarities in base composition and A+T content. Additionally, our phylogenetic analysis confirmed the monophyly of Coccomorpha and revealed that the archaeococcoids were the most basal lineage within Coccomorpha, while Ericeruspela and Didesmococcuskoreanus, belonging to Coccidae, were often mixed with Aclerdidae, making Coccidae a paraphyletic group. These findings expand the mitogenome database of scale insects and provide new insights on mitogenome evolution for future studies across different insect groups.

Association of Pain with Plasma C5a in Patients with Neuromyelitis Optica Spectrum Disorders During Remission.

Objective: To investigate the association of pain with plasma C5a levels and other related inflammatory cytokines in neuromyelitis optica spectrum disorders (NMOSD) patients during remission. Participants and Methods: NMOSD patients (n = 87) and healthy controls (HC; n = 44) were consecutively recruited between January 2017 and April 2018. Plasma complement 5 (C5), C5a, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1ß levels were detected. Visual Analogue Scale (VAS), ID pain scale, 24-item Hamilton Depression Scale (HAMD), Multiple Sclerosis Impact Scale (MSIS-29), and Kurtzke Expanded Disability Status Scale (EDSS) were used to evaluate the degree and types of pain, the existence of depression and anxiety, and the life quality and disability status of patients. Binary logistic regression equation was used to assess the association of pain with plasma C5a levels. Results: Among the 87 NMOSD patients, 40 complained of pain that in 67.5% (27/40) of cases had a neuropathic component (ID pain ≥2). Plasma C5a, IL-6, TNF-α, and IL-1ß levels were significantly elevated in NMOSD patients than in HC. Plasma C5 levels were negatively correlated with the time from sampling to the last relapse or disease onset. NMOSD patients with pain had higher plasma C5a levels, and they suffered from a higher disability, more anxiety, and worse life quality compared to those patients without pain. In NMOSD patients with pain, there were not significant differences between plasma levels of C5, C5a, IL-6, TNF-α, or IL-1ß, regardless of neuropathic pain or not. Binary logistic regression showed that the OR of plasma C5a level was 1.002, with gender and EDSS score were identified as independent factors associated with pain in NMOSD. Conclusion: NMOSD patients during remission had elevated C5a and related inflammatory cytokines levels in peripheral blood. Elevated C5a may have a unique role in the pathogenesis of pain in NMOSD patients.

The first mitochondrial genome of Creophilus Leach and Platydracus Thomson (Coleoptera: Staphylinidae: Staphylinini) and phylogenetic implications.

Creophilus Leach and Platydracus Thomson are two genera whose members were formerly included in a poorly defined Staphylinus. Both include large-sized rove beetles that can be frequently found in carrion, faeces, and other such rotting materials worldwide. But there are not yet mitochondrial genomes in public databases, which deters scientists from further studies that involve species of these two genera. Here we present the first complete mitochondrial genomes of two typical Palaearctic species, Creophilus maxillosus and Platydracus impotens, which are also the first for the two genera. Additionally, we included the new mitogenomic data in a phylogenetic context using maximum likelihood phylogenetic analyses. Our results confirm the results of previous studies but show that the position of Creophilus, and therefore the monophyly of Staphylinina, could be affected by dataset constitution and model selection.

Comparative description of the mitochondrial genome of Scaphidium formosanum Pic, 1915 (Coleoptera: Staphylinidae: Scaphidiinae).

Scaphidium is a rove beetle genus (Coleoptera: Staphylinidae) of remarkable and diverse colouration. Although most of Scaphidium species are easily distinguished by the colour patterns, there exist some confusing variants, which may introduce bias into rapid identification. Molecular identification using the mitochondrial genome is a reliable approach that overcomes the shortcoming of morphological recognition for those who have limited experience in species-level identification. Here we described the nearly complete mitochondrial genome of Scaphidium formosanum Pic, 1915, a species with variant colour types, and tested the reliability of identification based on mitochondrial genes by both gene-wise metrics and phylogenetic analyses. In this study, the 17,455 bp mitochondrial genome of S. formosanum is composed of 13 protein-coding genes (PCGs), 22 tRNAs, and 2 rRNAs. All PCGs start with typical ATN codons, except Nad4l which began with the TTG codon. The gene order is consistent with the typical linear arrangement of the published rove beetle mitochondrial genomes. The nucleotide composition is highly A+T biased (76.42%): A - 39.99%, T - 36.44%, C - 15.08%, and G - 8.49%. Multiple metrics support that our sample has a higher similarity to S. quadrimaculatum than to other species. Maximum likelihood trees confirm the placement of our sample as the closest related entity to S. quadrimaculatum. We conclude that the mitochondrial genome has a reliable performance in molecular identification in this case.

Nonsurgical treatment of chronic subdural hematoma with Chinese herbal medicine: A STROBE-compliant retrospective study.

The aim of the study was to observe the efficacy of nonsurgical treatment with Chinese herbal medicine (CHM) for chronic subdural hematoma (CSDH). This study includes clinical results of a STROBE-compliant retrospective study.Forty patients diagnosed with CSDH were recruited from outpatient. Different CHM prescriptions were dispensed for each patient based on syndrome differentiation until the patient had a stable neurologic condition for 2 weeks and/or CSDH completely resolved according to the computed tomography scan. Markwalder grading scale for neurologic symptoms and head computed tomography scan for hematoma volumes were performed before and after CHM treatment to evaluate efficacy.Patients received uninterrupted CHM treatment for 2.81 ±â€Š1.45 months (0.75-6 months). The hematoma volume significantly reduced from 73.49 ±â€Š35.43 mL to 14.72 ±â€Š15.94 mL (P < .001). The Markwalder grading scale scores of patients at the end of CHM treatment decreased significantly, from 1.3 ±â€Š0.69 to 0.15 ±â€Š0.36 (P < .001). Ninety percent of the patients showed >50% decrease in the hematoma volume and complete improvement in neurologic symptoms. The linear regression analysis suggested that change in hematoma was significantly related to the duration of CHM treatment (R = 0.334; P < .001; Y = 25.03 + 11.91X). Leonurus heterophyllus Sweet (Yi-Mu-Cao, 90.5%), Semen persicae (Tao-Ren, 88.8%), and Acorus tatarinowii Schott (Shi-Chang-Pu, 86.2%) were the top 3 single Chinese herbs prescribed in CHM treatment.The CHM treatment for CSDH based on syndrome differentiation with appropriate duration relieved neurologic symptoms quickly and promoted hematoma absorption effectively. It could be an effective nonsurgical therapy for CSDH.

Influences of pregnancy on neuromyelitis optica spectrum disorders and multiple sclerosis.

OBJECTIVE: To assess the influences of pregnancy on disease progression of neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS). METHODS: A total of 148 NMOSD patients and 170 MS patients were reviewed retrospectively. The changes in mean annualized relapse rate (ARR) in NMOSD and MS during and after pregnancy were compared. The influences of different pregnancy outcomes on disease courses were also analyzed. RESULTS: Sixty-two relapses had occurred during pregnancy or within 1 year after delivery/abortion in NMOSD patients and 64 in MS patients. The proportion of pregnancy-related onset and relapse in NMOSD was not significantly higher than that in MS. The ARR during 0-3 months and 7-9 months postpartum/postabortal periods in NMOSD and during 0-3 months and 10-12 months postpartum/postabortal periods in MS increased significantly. The ARR in 7-9 months postpartum/postabortal period in NMOSD patients was significantly higher than that in MS patients. Different pregnancy outcomes affected the course of disease similarly in patients irrespective of NMOSD or MS. CONCLUSIONS: Both NMOSD and MS presented increased onset and relapses after delivery/abortion. Significant differences were observed in ARRs at different stages between them. Both delivery and abortion exerted detrimental effects on disease courses in NMOSD and MS.

Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission.

BACKGROUND: A prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD) is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3) and CCL13 [monocyte chemoattractant protein (MCP)-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26) and MCPs (CCL13, CCL2, CCL8, and CCL7) in patients with NMOSD during remission. METHODS: Healthy controls (HC; n = 30) and patients with MS (n = 47) and NMOSD (n = 58) in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß levels were detected using the human cytokine multiplex assay. RESULTS: Plasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1ß, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD. CONCLUSION: The study indicates that in NMOSD, the overproduction of cytokines such as IL-1ß and TNF-α during remission stimulates eosinophilic chemoattractants such as CCL13, CCL11, and CCL26, which in turn bind to their receptor (CCR3); this could lead to eosinophil hypersensitivity. These findings suggest that the elevated secretion of CCL13, CCL11, and CCL26 may be a critical step in eosinophil recruitment during NMOSD remission.