Apoptosis Governs the Elimination of Schistosoma japonicum from the Non-Permissive Host Microtus fortis

The reed vole, Microtus fortis, is the only known mammalian host in which schistosomes of Schistosoma japonicum are unable to mature and cause significant pathogenesis. However, little is known about how Schistosoma japonicum maturation (and, therefore, the development of schistosomiasis) is prevented in M. fortis. In the present study, the ultrastructure of 10 days post infection schistosomula from BALB/c mice and M. fortis were first compared using scanning electron microscopy and transmission electron microscopy. Electron microscopic investigations showed growth retardation and ultrastructural differences in the tegument and sub-tegumental tissues as well as in the parenchymal cells of schistosomula from M. fortis compared with those in BALB/c mice. Then, microarray analysis revealed significant differential expression between the schistosomula from the two rodents, with 3,293 down-regulated (by ≥2-fold) and 71 up-regulated (≥2 fold) genes in schistosomula from the former. The up-regulated genes included a proliferation-related gene encoding granulin (Grn) and tropomyosin. Genes that were down-regulated in schistosomula from M. fortis included apoptosis-inhibited genes encoding a baculoviral IAP repeat-containing protein (SjIAP) and cytokine-induced apoptosis inhibitor (SjCIAP), genes encoding molecules involved in insulin metabolism, long-chain fatty acid metabolism, signal transduction, the transforming growth factor (TGF) pathway, the Wnt pathway and in development. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and PI/Annexin V-FITC assays, caspase 3/7 activity analysis, and flow cytometry revealed that the percentages of early apoptotic and late apoptotic and/or necrotic cells, as well as the level of caspase activity, in schistosomula from M. fortis were all significantly higher than in those from BALB/c mice

A geospatial model of nature-based recreation for urban planning: Case study of Paris, France

International audienceIncorporating nature-based recreation into urban planning analyses requires understanding the accessibility, quality, and demand for urban greenspace (UGS) across a city. Here, we present a novel tool that lowers the barriers to such information by (i) providing a spatially-explicit assessment of recreational UGS supply and demand; (ii) differentiating results by population group or UGS type; and (iii) using an accessible open-source software platform that facilitates scenario comparison and communication. In a case study in Paris, France, we demonstrate how the tool helps address important urban planning questions. We show that between 42% and 55% of the population is currently below the UGS target of 10 m2 per person, depending on the accessibility criteria used. Using revealed preference data, we demonstrate that older adults are disproportionately affected by the UGS deficit. Our assessment of future scenarios reveals that UGS targets set by public policies are largely insufficient (500–2800 ha are planned by 2030, while more than 4000 ha are needed to meet the policy target). By combining the strengths of established geospatial methods, the tool helps researchers and practitioners produce a more nuanced analysis of the recreation benefits of UGS implementation

Seasonal Variation of Midgut Bacterial Diversity in Culex quinquefasciatus Populations in Haikou City, Hainan Province, China

Culex quinquefasciatus, one of the most significant mosquito vectors in the world, is widespread in most parts of southern China. A variety of diseases including Bancroft’s filariasis, West Nile disease, and St. Louis encephalitis could be transmitted by the vector. Mosquitoes have been shown to host diverse bacterial communities that vary depending on environmental factors such as temperature and rainfall. In this work, 16S rDNA sequencing was used to analyze the seasonal variation of midgut bacterial diversity of Cx. Quinquefasciatus in Haikou City, Hainan Province, China. Proteobacteria was the dominant phylum, accounting for 79.7% (autumn), 73% (winter), 80.4% (spring), and 84.5% (summer). The abundance of Bacteroidetes in autumn and winter was higher than in others. Interestingly, Epsilonbacteraeota, which only exists in autumn and winter, was discovered accidentally in the midgut. We speculated that this might participate in the nutritional supply of adult mosquitoes when temperatures drop. Wolbachia is the most abundant in autumn, accounting for 31.6% of bacteria. The content of Pantoea was highest in the summer group, which might be related to the enhancement of the ability of mosquitoes as temperatures increased. Pseudomonas is carried out as the highest level in winter. On the contrary, in spring and summer, the genus in highest abundance is Enterobacter. Acinetobacter enriches in the spring when it turns from cold to hot. By studying the diversity of midgut bacteria of Cx. quinquefasciatus, we can further understand the co-evolution of mosquitoes and their symbiotic microbes. This is necessary to discuss the seasonal variation of microorganisms and ultimately provide a new perspective for the control of Cx. quinquefasciatus to reduce the spread of the diseases which have notably vital practical significance for the effective prevention of Cx. quinquefasciatus

Apoptosis phenomenon in the schistosomulum and adult worm life cycle stages of Schistosoma japonicum

Apoptosis is an important aspect of a number of biological processes, from embryogenesis to the stress-injury response. It plays a central role in balancing cell proliferation and tissue remodeling activity in many organisms. In the present study, apoptosis in 14. days post infection schistosomula was evaluated using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assays and DAPI staining. Additionally, flow cytometry using the Annexin V-FITC/propidium iodide (PI) (Annexin V/PI) assay confirmed the percentage of early apoptotic, late apoptotic, and necrotic cells in 14 and 23. days post infection worms. Conserved Domain Database (CDD) BLAST analysis and alignment analysis of known schistosome proteins demonstrated the feasibility of detecting the activity of caspase-3 and -7 using the caspase-3/7 Glo analysis assay. Analysis of caspase-3 and -7 activities in schistosome demonstrated that both caspases were active in each developmental stage of Schistosoma japonicum, but was highest in the 14. days post infection schistosomula. Additionally, the caspase peptide inhibitor (Z-VAD-FMK) inhibited the caspase-3/7 activity at all developmental stages examined. Therefore, we hypothesized that two main signaling pathways are involved in apoptosis in S. japonicum, the caspase cascade and the mitochondrial-initiated pathway. We have constructed a model of these two pathways, including how they may interact and their biological outcomes. qRT-PCR analyses of the gene expression profiles of apoptosis-related genes supported our hypothesis of the relationship between the apoptotic pathway and parasite development. The data presented here demonstrates that apoptosis is an important biological process for the survival and development of the schistosome, and identifies potential novel therapeutic targets

Brain Functional Differences in Drug-Naive Major Depression with Anxiety Patients of Different Traditional Chinese Medicine Syndrome Patterns: A Resting-State fMRI Study

Major depressive disorder (MDD), especially combined with anxiety, has a high incidence and low detection rate in China. Literature has shown that patients under major depression with anxiety (MDA) are more likely to nominate a somatic, rather than psychological, symptom as their presenting complaint. In the theory of Traditional Chinese Medicine (TCM), clinical symptoms of MDD patients are mainly categorized into two different syndrome patterns: Deficiency and Excess. We intend to use resting-state functional magnetic resonance imaging (rs-fMRI) to investigate their brain functional differences and hopefully to find their brain function mechanism. For our research, 42 drug-naive MDA patients were divided into two groups (21 for Deficiency and 21 for Excess), with an additional 19 unaffected participants in the normal control (NC) group. We took Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), and brain fMRI scan for each group and analyzed the data. We first used Degree Centrality (DC) to map the functional differences in brain regions, utilized these regions as seed points, and used a seed-based functional connectivity (FC) analysis to identify the specific functional connection between groups. The Deficiency group was found to have higher HAMD scores, HAMA scores, and HAMD somatic factor than the Excess group. In the DC analysis, significant decreases were found in the right precuneus of both the Deficiency and Excess groups compared to the NC group. In the FC analysis, the right precuneus showed significant decreased network connectivity with the bilateral cuneus, as well as the right lingual gyrus in the Deficiency group when compared to the NC group and the Excess group. Through our research, it was found that precuneus dysfunction may have a relationship with MDA and Deficiency patients have more severe physical and emotional symptoms, and we realized that a larger sample size and multiple brain mode observations were needed in further research.</p

Differential Expression of microRNAs in the Non-Permissive Schistosome Host <i>Microtus fortis</i> under Schistosome Infection

<div><p>The reed vole <i>Microtus fortis</i> is the only mammal known in China in which the growth, development and maturation of schistosomes (<i>Schistosoma japonicum</i>) is prevented. It might be that the anti-schistosomiasis mechanisms of <i>M. fortis</i> associate with microRNA-mediated gene expression, given that the latter has been found to be involved in gene regulation in eukaryotes. In the present study, the difference between pathological changes in tissues of <i>M. fortis</i> and of mice (<i>Mus musculus</i>) post-schistosome infection were observed by using hematoxylin-eosin staining. In addition, microarray technique was applied to identify differentially expressed miRNAs in the same tissues before and post-infection to analyze the potential roles of miRNAs in schistosome infection in these two different types of host. Histological analyses showed that <i>S. japonicum</i> infection in <i>M. fortis</i> resulted in a more intensive inflammatory response and pathological change than in mice. The microarray analysis revealed that 162 miRNAs were expressed in both species, with 12 in liver, 32 in spleen and 34 in lung being differentially expressed in <i>M. fortis</i>. The functions of the differentially expressed miRNAs were mainly revolved in nutrient metabolism, immune regulation, etc. Further analysis revealed that important signaling pathways were triggered after infection by <i>S. japonicum</i> in <i>M. fortis</i> but not in the mice. These results provide new insights into the general mechanisms of regulation in the non-permissive schistosome host <i>M. fortis</i> that exploits potential miRNA regulatory networks. Such information will help improve current understanding of schistosome development and host–parasite interactions.</p> </div

Pie charts showing the distribution of GOs for predicted target genes of differentially expressed miRNAs in <i>M. fortis</i> compared with mice following <i>S. japonicum</i> infection.

<p>A represents the category of the GOs for predicted target genes of miRNAs up-regulated in liver, spleen and lung of <i>M. fortis</i>; B represents the category of the GOs for predicted target genes of miRNAs down-regulated in liver, spleen and lung of <i>M. fortis</i>. A full list of GO analysis for predicted target genes of differentially expressed miRNAs in <i>M. fortis</i> compared with mice infected with <i>S. japonicum</i> is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085080#pone.0085080.s004" target="_blank">Table S4</a>.</p