A haplotype-like, chromosome-level assembled and annotated genome of Biomphalaria glabrata, an important intermediate host of schistosomiasis and the best studied model of schistosomiasis vector snails.

Schistosomiasis is one of the world's most devastating parasitic diseases, afflicting 251 million people globally. The Neotropical snail Biomphalaria glabrata is an important intermediate host of the human blood fluke Schistosoma mansoni and a predominant model for schistosomiasis research. To fully exploit this model snail for biomedical research, here we report a haplotype-like, chromosome-level assembled and annotated genome of the homozygous iM line of B. glabrata that we developed at the University of New Mexico. Using multiple sequencing platforms, including Illumina, PacBio, and Omni-C sequencing, 18 sequence contact matrices representing 18 haploid chromosomes (2n = 36) were generated (337x genome coverage), and 96.5% of the scaffold sequences were anchored to the 18 chromosomes. Protein-coding genes (n = 34,559), non-coding RNAs (n = 2,406), and repetitive elements (42.52% of the genome) were predicted for the whole genome, and detailed annotations for individual chromosomes were also provided. Using this genomic resource, we have investigated the genomic structure and organization of the Toll-like receptor (TLR) and fibrinogen-domain containing protein (FReD) genes, the two important immune-related gene families. Notably, TLR-like genes are scattered on 13 chromosomes. In contrast, almost all (39 of 40) fibrinogen-related genes (FREPs) (immunoglobulin superfamily (IgSF) + fibrinogen (FBG)) are clustered within a 5-million nucleotide region on chromosome 13, yielding insight into mechanisms involved in the diversification of FREPs. This is the first genome of schistosomiasis vector snails that has been assembled at the chromosome level, annotated, and analyzed. It serves as a valuable resource for a deeper understanding of the biology of vector snails, especially Biomphalaria snails.

Transcriptional profiling of Bulinus globosus provides insights into immune gene families in snails supporting the transmission of urogenital schistosomiasis.

Schistosomiasis, urogenital and intestinal, afflicts 251 million people worldwide with approximately two-thirds of the patients suffering from the urogenital form of the disease. Freshwater snails of the genus Bulinus (Gastropoda: Planorbidae) serve as obligate intermediate hosts for Schistosoma haematobium, the etiologic agent of human urogenital schistosomiasis. These snails also act as vectors for the transmission of schistosomiasis in livestock and wildlife. Despite their crucial role in human and veterinary medicine, our basic understanding at the molecular level of the entire Bulinus genus, which comprises 37 recognized species, is very limited. In this study, we employed Illumina-based RNA sequencing (RNAseq) to profile the genome-wide transcriptome of Bulinus globosus, one of the most important intermediate hosts for S. haematobium in Africa. A total of 179,221 transcripts (N50 = 1,235) were assembled and the benchmarking universal single-copy orthologs (BUSCO) was estimated to be 97.7%. The analysis revealed a substantial number of transcripts encoding evolutionarily conserved immune-related proteins, particularly C-type lectin (CLECT) domain-containing proteins (n = 316), Toll/Interleukin 1-receptor (TIR)-containing proteins (n = 75), and fibrinogen related domain-containing molecules (FReD) (n = 165). Notably, none of the FReDs are fibrinogen-related proteins (FREPs) (immunoglobulin superfamily (IgSF) + fibrinogen (FBG)). This RNAseq-based transcriptional profile provides new insights into immune capabilities of Bulinus snails, helps provide a framework to explain the complex patterns of compatibility between snails and schistosomes, and improves our overall understanding of comparative immunology.

Yolk proteins of the schistosomiasis vector snail Biomphalaria glabrata revealed by multi-omics analysis.

Vitellogenesis is the most important process in animal reproduction, in which yolk proteins play a vital role. Among multiple yolk protein precursors, vitellogenin (Vtg) is a well-known major yolk protein (MYP) in most oviparous animals. However, the nature of MYP in the freshwater gastropod snail Biomphalaria glabrata remains elusive. In the current study, we applied bioinformatics, tissue-specific transcriptomics, ovotestis-targeted proteomics, and phylogenetics to investigate the large lipid transfer protein (LLTP) superfamily and ferritin-like family in B. glabrata. Four members of LLTP superfamily (BgVtg1, BgVtg2, BgApo1, and BgApo2), one yolk ferritin (Bg yolk ferritin), and four soma ferritins (Bg ferritin 1, 2, 3, and 4) were identified in B. glabrata genome. The proteomic analysis demonstrated that, among the putative yolk proteins, BgVtg1 was the yolk protein appearing in the highest amount in the ovotestis, followed by Bg yolk ferritin. RNAseq profile showed that the leading synthesis sites of BgVtg1 and Bg yolk ferritin are in the ovotestis (presumably follicle cells) and digestive gland, respectively. Phylogenetic analysis indicated that BgVtg1 is well clustered with Vtgs of other vertebrates and invertebrates. We conclude that, vitellogenin (BgVtg1), not yolk ferritin (Bg yolk ferritin), is the major yolk protein precursor in the schistosomiasis vector snail B. glabrata.

The potential role of ribonucleic acid methylation in the pathological mechanisms of fragile X syndrome.

Fragile X syndrome (FXS) is a common inherited cause of intellectual disabilities and single-gene cause of autism spectrum disorder (ASD), resulting from the loss of functional fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein (RBP) encoded by the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Ribonucleic acid (RNA) methylation can lead to developmental diseases, including FXS, through various mechanisms mediated by 5-hydroxymethylcytosine, 5-methylcytosine, N6-methyladenosine, etc. Emerging evidence suggests that modifications of some RNA species have been linked to FXS. However, the underlying pathological mechanism has yet to be elucidated. In this review, we reviewed the implication of RNA modification in FXS and summarized its specific characteristics for facilitating the identification of new therapeutic targets.

Oxidative Stress-Involved Mitophagy of Retinal Pigment Epithelium and Retinal Degenerative Diseases.

The retinal pigment epithelium (RPE) is a highly specialized and polarized epithelial cell layer that plays an important role in sustaining the structural and functional integrity of photoreceptors. However, the death of RPE is a common pathological feature in various retinal diseases, especially in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitophagy, as a programmed self-degradation of dysfunctional mitochondria, is crucial for maintaining cellular homeostasis and cell survival under stress. RPE contains a high density of mitochondria necessary for it to meet energy demands, so severe stimuli can cause mitochondrial dysfunction and the excess generation of intracellular reactive oxygen species (ROS), which can further trigger oxidative stress-involved mitophagy. In this review, we summarize the classical pathways of oxidative stress-involved mitophagy in RPE and investigate its role in the progression of retinal diseases, aiming to provide a new therapeutic strategy for treating retinal degenerative diseases. The role of mitophagy in AMD and DR. In AMD, excessive ROS production promotes mitophagy in the RPE by activating the Nrf2/p62 pathway, while in DR, ROS may suppress mitophagy by the FOXO3-PINK1/parkin signaling pathway or the TXNIP-mitochondria-lysosome-mediated mitophagy.

Promotion of axon regeneration and protection on injured retinal ganglion cells by rCXCL2.

BACKGROUND: In addition to rescuing injured retinal ganglion cells (RGCs) by stimulating the intrinsic growth ability of damaged RGCs in various retinal/optic neuropathies, increasing evidence has shown that the external microenvironmental factors also play a crucial role in restoring the survival of RGCs by promoting the regrowth of RGC axons, especially inflammatory factors. In this study, we aimed to screen out the underlying inflammatory factor involved in the signaling of staurosporine (STS)-induced axon regeneration and verify its role in the protection of RGCs and the promotion of axon regrowth. METHODS: We performed transcriptome RNA sequencing for STS induction models in vitro and analyzed the differentially expressed genes. After targeting the key gene, we verified the role of the candidate factor in RGC protection and promotion of axon regeneration in vivo with two RGC-injured animal models (optic nerve crush, ONC; retinal N-methyl-D-aspartate, NMDA damage) by using cholera toxin subunit B anterograde axon tracing and specific immunostaining of RGCs. RESULTS: We found that a series of inflammatory genes expressed upregulated in the signaling of STS-induced axon regrowth and we targeted the candidate CXCL2 gene since the level of the chemokine CXCL2 gene elevated significantly among the top upregulated genes. We further demonstrated that intravitreal injection of rCXCL2 robustly promoted axon regeneration and significantly improved RGC survival in ONC-injured mice in vivo. However, different from its role in ONC model, the intravitreal injection of rCXCL2 was able to simply protect RGCs against NMDA-induced excitotoxicity in mouse retina and maintain the long-distance projection of RGC axons, yet failed to promote significant axon regeneration. CONCLUSIONS: We provide the first in vivo evidence that CXCL2, as an inflammatory factor, is a key regulator in the axon regeneration and neuroprotection of RGCs. Our comparative study may facilitate deciphering the exact molecular mechanisms of RGC axon regeneration and developing high-potency targeted drugs.

Succinylation-associated lncRNA signature to predict the prognosis of colon cancer based on integrative bioinformatics analysis.

Colon cancer (CC) has a poor 5-year survival rate though the treatment techniques and strategies have been improved. Succinylation and long noncoding RNAs (lncRNAs) have prognostic value for CC patients. We analyzed and obtained succinylation-related lncRNA by co-expression in CC. A novel succinylation-related lncRNA model was developed by univariate and Least absolute shrinkage and selection operator (Lasso) regression analysis and we used principal component analysis (PCA), functional enrichment annotation, tumor immune environment, drug sensitivity and nomogram to verify the model, respectively. Six succinylation-related lncRNAs in our model were finally confirmed to distinguish the survival status of CC and showed statistically significant differences in training set, testing set, and entire set. The prognosis of with this model was associated with age, gender, M0 stage, N2 stage, T3 + T4 stage and Stage III + IV. The high-risk group showed a higher mutation rate than the low-risk group. We constructed a model to predict overall survival for 1-, 3-, and 5-year with AUCs of 0.694, 0.729, and 0.802, respectively. The high-risk group was sensitive to Cisplatin and Temozolomide compounds. Our study provided novel insights into the value of the succinylation-related lncRNA signature as a predictor of prognosis, which had high clinical application value in the future.

Interleukin 35: protective role and mechanism in type 1 diabetes.

Interleukin 35 (IL-35), a cytokine secreted by regulatory T (Treg) cells from the differentiation of conventional CD4+ T cells, is a member of the IL-12 family. The IL-12 family of cytokines exhibits an anti-inflammatory property. IL-35 has recently been shown to influence the immune modulation in various diseases, including inflammatory bowel disease, Graves' disease, rheumatoid arthritis, colitis, psoriasis, and type 1 diabetes (T1D). T1D is an immune-related disease caused by destruction of pancreatic ß cells, characterized by an absolute lack of insulin. Recently, studies have suggested that protective effects of IL-35 work by improving blood glucose levels and preventing an attack of inflammatory factors on the islets. The protective mechanism may be closely related to the anti-inflammatory properties of IL-35, which include regulating macrophage phenotype, suppressing T cell proliferation, decreasing the differentiation of Th17 cells, increasing the Treg cell population, and inducing IL-35-producing regulatory T cells (iTr35). Here, we review the protective effects and mechanisms of action of IL-35 in T1D.

A genome sequence for Biomphalaria pfeifferi, the major vector snail for the human-infecting parasite Schistosoma mansoni.

BACKGROUND: Biomphalaria pfeifferi is the world's most widely distributed and commonly implicated vector snail species for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. In efforts to control S. mansoni transmission, chemotherapy alone has proven insufficient. New approaches to snail control offer a way forward, and possible genetic manipulations of snail vectors will require new tools. Towards this end, we here offer a diverse set of genomic resources for the important African schistosome vector, B. pfeifferi. METHODOLOGY/PRINCIPAL FINDINGS: Based largely on PacBio High-Fidelity long reads, we report a genome assembly size of 772 Mb for B. pfeifferi (Kenya), smaller in size than known genomes of other planorbid schistosome vectors. In a total of 505 scaffolds (N50 = 3.2Mb), 430 were assigned to 18 large linkage groups inferred to represent the 18 known chromosomes, based on whole genome comparisons with Biomphalaria glabrata. The annotated B. pfeifferi genome reveals a divergence time of 3.01 million years with B. glabrata, a South American species believed to be similar to the progenitors of B. pfeifferi which undertook a trans-Atlantic colonization < five million years ago. CONCLUSIONS/SIGNIFICANCE: The genome for this preferentially self-crossing species is less heterozygous than related species known to be preferential out-crossers; its smaller genome relative to congeners may similarly reflect its preference for selfing. Expansions of gene families with immune relevance are noted, including the FReD gene family which is far more similar in its composition to B. glabrata than to Bulinus truncatus, a vector for Schistosoma haematobium. Provision of this annotated genome will help better understand the dependencies of trematodes on snails, enable broader comparative insights regarding factors contributing to susceptibility/ resistance of snails to schistosome infections, and provide an invaluable resource with respect to identifying and manipulating snail genes as potential targets for more specific snail control programs.

Identification of Hub Genes for Colorectal Cancer with Liver Metastasis Using miRNA-mRNA Network.

Background: Liver metastasis is an important cause of death in patients with colorectal cancer (CRC). Increasing evidence indicates that microRNAs (miRNAs) are involved in the pathogenesis of colorectal cancer liver metastasis (CRLM). This study is aimed at exploring the potential miRNA-mRNA regulatory network. Methods: From the GEO database, we downloaded the microarray datasets GSE56350 and GSE73178. GEO2R was used to conduct differentially expressed miRNAs (DEMs) between CRC and CRLM using the GEO2R tool. Then, GO and KEGG pathway analysis for differentially expressed genes (DEGs) performed via DAVID. A protein-protein interaction (PPI) network was constructed by the STRING and identified by Cytoscape. Hub genes were identified by miRNA-mRNA network. Finally, the expression of the hub gene expression was assessed in the GSE81558. Results: The four DEMs (hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p) were identified as common DEMs in GSE56350 and GSE73178 datasets. The SP1 was likely to adjust the upregulated DEMs; however, the YY1 could regulate both the upregulated and downregulated DEMs. A total of 3925 genes (3447 upregulated DEM genes and 478 downregulated DEM genes) were screened. These predicted genes were mainly linked to Platinum drug resistance, Cellular senescence, and ErbB signaling pathway. Through the gene network construction, most of the hub genes were found to be modulated by hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p. Among the top 20 hub genes, the expression of CREB1, RHOA, and EGFR was significantly different in the GSE81558 dataset. Conclusion: In this study, miRNA-mRNA networks in CRLM were screened between CRC patients and CRLM patients to provide a new method to predict for the pathogenesis and development of CRC.

Early 7,8-Dihydroxyflavone Administration Ameliorates Synaptic and Behavioral Deficits in the Young FXS Animal Model by Acting on BDNF-TrkB Pathway.

Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and the most common cause of autism spectrum disorders. FXS patients exhibit severe syndromic features and behavioral alterations, including anxiety, hyperactivity, impulsivity, and aggression, in addition to cognitive impairment and seizures. At present, there are no effective treatments or cures for FXS. Previously, we have found the divergence of BDNF-TrkB signaling trajectories is associated with spine defects in early postnatal developmental stages of Fmr1 KO mice. Here, young fragile X mice were intraperitoneal injection with 7,8-Dihydroxyflavone (7,8-DHF), a high affinity tropomyosin receptor kinase B (TrkB) agonist. 7,8-DHF ameliorated morphological abnormities in dendritic spine and synaptic structure and rescued synaptic and hippocampus-dependent cognitive dysfunction. These observed improvements of 7,8-DHF involved decreased protein levels of BDNF, p-TrkBY816, p-PLCγ, and p-CaMKII in the hippocampus. In addition, 7,8-DHF intervention in primary hippocampal neurons increased p-TrkBY816 and activated the PLCγ1-CaMKII signaling pathway, leading to improvement of neuronal morphology. This study is the first to account for early life synaptic impairments, neuronal morphological, and cognitive delays in FXS in response to the abnormal BDNF-TrkB pathway. Present studies provide novel evidences about the effective early intervention in FXS mice at developmental stages and a strategy to produce powerful impacts on neural development, synaptic plasticity, and behaviors.

Prognostic significance of prognostic nutritional index and systemic immune-inflammation index in patients after curative breast cancer resection: a retrospective cohort study.

BACKGROUND: Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. METHODS: We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan-Meier method. RESULTS: Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19-0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend < 0.001). CONCLUSIONS: A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.

Compatibility between snails and schistosomes: insights from new genetic resources, comparative genomics, and genetic mapping.

The freshwater snail Biomphalaria glabrata is an important intermediate host of the parasite Schistosoma mansoni that causes human intestinal schistosomiasis. To better understand vector snail biology and help advance innovative snail control strategies, we have developed a new snail model consisting of two homozygous B. glabrata lines (iM line and iBS90) with sharply contrasting schistosome-resistance phenotypes. We produced and compared high-quality genome sequences for iM line and iBS90 which were assembled from 255 (N50 = 22.7 Mb) and 346 (N50 = 19.4 Mb) scaffolds, respectively. Using F2 offspring bred from the two lines and the newly generated iM line genome, we constructed 18 linkage groups (representing the 18 haploid chromosomes) covering 96% of the genome and identified three new QTLs (quantitative trait loci), two involved in snail resistance/susceptibility and one relating to body pigmentation. This study provides excellent genomic resources for unveiling complex vector snail biology, reveals genomic difference between resistant and susceptible lines, and offers novel insights into genetic mechanism of the compatibility between snail and schistosome.

Glyceraldehyde-3-phosphate dehydrogenase affects the growth of Schistosoma japonicum schistosomula.

This study was conducted to evaluate the effect of glyceraldehyde-3-phosphate dehydrogenase from Schistosoma japonicum (SjGAPDH) on the growth of schistosomula. Quantitative reverse transcription PCR and immunohistochemical analysis were performed to analyze the mRNA levels and immune localization of SjGAPDH. RNA interference experiments were conducted to further examine the role of SjGAPDH in the schistosomula growth of S. japonicum. The results demonstrated that SjGAPDH mRNA was expressed during all stages of S. japonicum development, with its expression gradually increasing over time. SjGAPDH was mainly distributed on the surface and in some parenchymal cells of S. japonicum. Double-stranded RNA-mediated GAPDH knockdown reduced SjGAPDH expression by approximately 59%. Light microscopic observations revealed that the size, length, width, volume, and area of schistosomula in the SjGAPDH interference group were significantly lower than those in the enhanced green fluorescent protein control group. These findings indicate that SjGAPDH may affect the growth of S. japonicum schistosomula and could be a useful target for treating schistosomiasis.

Cerebellum neuropathology and motor skill deficits in fragile X syndrome.

Fragile X syndrome (FXS) is a leading form of inherited intellectual disability and single-gene cause of autism spectrum disorder (ASD) and is characterized by core deficits in cognitive flexibility, sensory sensitivity, emotion, and social interactions. Motor deficits are a shared feature of FXS and autism. The cerebellum has emerged as one of the target brain areas affected by neurodevelopmental diseases. Alterations in the cerebellar structure, circuits, and function may be the key drivers of impaired fine and gross motor skills in FXS and fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we briefly examined recent findings in FXS and present a discussion on the literature supporting motor skill deficits in FXS. Subsequently, we focused on neuropathological alterations in the cerebellum in FXS and FXTAS. We highlight studies that have directly examined the function of fragile X mental retardation protein and related epigenetic variations in the cerebellum. Overall, we obtained considerable supporting evidence for the hypothesis that cerebellar dysfunction is evident in FXS and FXTAS; however, compared with studies on other ASD models, studies on motor skills related to fragile X disorders are particularly rare and inconclusive. Hence, future research should address FXS-related motor and behavioral trajectories and examine the underlying mechanisms at both the cell and circuit levels.

Early environmental enrichment for autism spectrum disorder Fmr1 mice models has positive behavioral and molecular effects.

Autism spectrum disorder is a complex neurodevelopmental condition with genetic and phenotypic heterogeneity characterized by hallmark impairments in social functioning and repetitive behaviors. Fragile X syndrome (FXS), the leading single-gene form of autism spectrum disorder, is the most common form of inherited intellectual disability. Environmental enrichment has been shown to improve several aspects of brain development and affect histopathological, cognitive, and behavioral outcomes. However, the optimal time window to initiate it and improve cognitive and emotional development is largely unexplored. In the current study, we determined the longitudinal trends of BDNF-TrkB expression and dendritic development in FXS mice. Additionally, FXS mice were housed in an enriched environment when they showed significantly different BDNF-TrkB pathways and the phenotype of dendritic spines on postnatal day 10 (P10) until P60. The environmental enrichment delayed and attenuated some neurological alterations in FXS mice and prevented the development of cognitive and anxiety-related abnormalities and repetitive stereotyped behaviors. The correlation between neurotrophin-related pathways and multiple autistic-like behaviors was confirmed. Transcriptional profiling indicates that environmental enrichment increases the differences in the prefrontal cortex and hippocampal gene expression associated with the neural system and behavioral development. Our results provide novel evidence on the usefulness of early intervention for neurodevelopmental disorders as a strategy to facilitate positive effects on neural development and behaviors by acting on the BDNF/TrkB-PLCγ1-CaMKII pathway.

Comparative mitogenomics of freshwater snails of the genus Bulinus, obligatory vectors of Schistosoma haematobium, causative agent of human urogenital schistosomiasis.

Among the snail genera most responsible for vectoring human-infecting schistosomes, Bulinus, Biomphalaria, and Oncomelania, the former is in many respects the most important. Bulinid snails host the most common human blood fluke, Schistosoma haematobium, responsible for approximately two-thirds of the estimated 237 million cases of schistosomiasis. They also support transmission of schistosomes to millions of domestic and wild animals. Nonetheless, our basic knowledge of the 37 Bulinus species remains incomplete, especially with respect to genome information, even including mitogenome sequences. We determined complete mitogenome sequences for Bulinus truncatus, B. nasutus, and B. ugandae, and three representatives of B. globosus from eastern, central, and western Kenya. A difference of the location of tRNA-Asp was found between mitogenomes from the three species of the Bulinus africanus group and B. truncatus. Phylogenetic analysis using partial cox1 sequences suggests that B. globosus is a complex comprised of multiple species. We also highlight the status of B. ugandae as a distinct species with unusual interactions with the S. haematobium group parasites deserving of additional investigation. We provide sequence data for potential development of genetic markers for specific or intraspecific Bulinus studies, help elucidate the relationships among Bulinus species, and suggest ways in which mitogenomes may help understand the complex interactions between Schistosoma and Bulinus snails and their relatives.

Virus-derived sequences from the transcriptomes of two snail vectors of schistosomiasis, Biomphalaria pfeifferi and Bulinus globosus from Kenya.

Schistosomiasis, which infects more than 230 million people, is vectored by freshwater snails. We identified viral sequences in the transcriptomes of Biomphalaria pfeifferi (BP) and Bulinus globosus (BuG), two of the world's most important schistosomiasis vectors in Africa. Sequences from 26 snails generated using Illumina Hi-Seq or 454 sequencing were assembled using Trinity and CAP3 and putative virus sequences were identified using a bioinformatics pipeline. Phylogenetic analyses were performed using viral RNA-dependent RNA polymerase and coat protein sequences to establish relatedness between virus sequences identified and those of known viruses. Viral sequences were identified from the entire snail holobiont, including symbionts, ingested material and organisms passively associated with the snails. Sequences derived from more than 17 different viruses were found including five near full-length genomes, most of which were small RNA viruses with positive sense RNA genomes (i.e., picorna-like viruses) and some of which are likely derived from adherent or ingested diatoms. Based on phylogenetic analysis, five of these viruses (including BPV2 and BuGV2) along with four Biomphalaria glabrata viruses reported previously, cluster with known invertebrate viruses and are putative viruses of snails. The presence of RNA sequences derived from four of these novel viruses in samples was confirmed. Identification of the genome sequences of candidate snail viruses provides a first step toward characterization of additional gastropod viruses, including from species of biomedical significance.

Involvement of the fatty acid-binding protein in the growth of Schistosoma japonicum schistosomula.

This study aimed to explore the effect and mechanism underlying the role of the Schistosoma japonicum antigen of fatty acid-binding protein (SjFABP) on the growth of the schistosomula. SjFABP levels were evaluated by quantitative real-time polymerase chain reaction of samples of mice infected with S. japonicum; SjFABP was expressed and its levels gradually increased during all stages of S. japonicum schistosomula, including on 3, 10, 14, and 21 days of the growth process. Immunohistochemistry results demonstrated that SjFABP was distributed in the parenchyma, especially in the digestive tract of the S. japonicum schistosomula. RNA interference resulted in more than 60% knockdown of SjFABP leading to a reduction in length, volume, width, and area of the schistosomula as compared to control samples, as determined by light microscopy. Terminal deoxynucleotidyl transferase dUTP nick-end labeling detection further suggested that SjFABP knockdown resulted in increased apoptosis of schistosomes. Taken together, these results suggest that SjFABP may be related to the growth and survival of S. japonicum schistosomula, thereby representing a potential target for the treatment of schistosomiasis.