Cryptosporidium spp. and Giardia duodenalis emissions from humans and animals in the Three Gorges Reservoir in Chongqing, China
Cryptosporidium spp. and Giardia duodenalis are two waterborne protozoan parasites that can cause diarrhea. Human and animal feces in surface water are a major source of these pathogens. This paper presents a GloWPa-TGR-Crypto model that estimates Cryptosporidium and G. duodenalis emissions from human and animal feces in the Three Gorges Reservoir (TGR), and uses scenario analysis to predict the effects of sanitation, urbanization, and population growth on oocyst and cyst emissions for 2050. Our model estimated annual emissions of 1.6 × 1015 oocysts and 2.1 × 1015 cysts from human and animal feces, respectively. Humans were the largest contributors of oocysts and cysts, followed by pigs and poultry. Cities were hot-spots for human emissions, while districts with high livestock populations accounted for the highest animal emissions. Our model was the most sensitive to oocyst excretion rates. The results indicated that 74% and 87% of total emissions came from urban areas and humans, respectively, and 86% of total human emissions were produced by the urban population. The scenario analysis showed a potential decrease in oocyst and cyst emissions with improvements in urbanization, sanitation, wastewater treatment, and manure management, regardless of population increase. Our model can further contribute to the understanding of environmental pathways, the risk assessment of Cryptosporidium and Giardia pollution, and effective prevention and control strategies that can reduce the outbreak of waterborne diseases in the TGR and other similar watersheds.
Environmental Contamination and Remediation
Huang et al. (2020) Cryptosporidium spp. and Giardia duodenalis emissions from humans and animals in the Three Gorges Reservoir in Chongqing, China. PeerJ 8:e9985 https://doi.org/10.7717/peerj.9985
Exosomal cargoes in OSCC: current findings and potential functions
Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in head and neck cancer, with high recurrence and mortality. Early diagnosis and efficient therapeutic strategies are vital for the treatment of OSCC patients. Exosomes can be isolated from a broad range of different cell types, implicating them as important factors in the regulation of human physiological and pathological processes. Due to their abundant cargo including proteins, lipids, and nucleic acids, exosomes have played a valuable diagnostic and therapeutic role across multiple diseases, including cancer. In this review, we summarize recent findings concerning the content within and participation of exosomes relating to OSCC and their roles in tumorigenesis, proliferation, migration, invasion, metastasis, and chemoresistance. We conclude this review by looking ahead to their potential utility in providing new methods for treating OSCC to inspire further research in this field.
Zhao et al. (2020) Exosomal cargoes in OSCC: current findings and potential functions. PeerJ 8:e10062 https://doi.org/10.7717/peerj.10062
Serum uric acid level is correlated with the clinical, pathological progression and prognosis of IgA nephropathy: an observational retrospective pilot-study
Objectives This study was aimed to assess the relationship between serum uric acid (SUA) level and the clinical, pathological phenotype of IgA nephropathy (IgAN), and to determine the role of SUA level in the progression and prognosis of IgAN. Methods A total of 208 patients with IgAN were included in this study, and were classified into the normo-uricemia group and hyperuricemia group according to the SUA level. The clinical data at baseline, IgAN Oxford classification scores (MEST-C scoring system), and other pathological features were collected and further analyzed. All patients were followed up and the prognosis was assessed using Kaplan-Meier survival curves. GraphPad Prism 7.0 and SPSS 23.0 were used for statistical analyses. Results In clinical indicators, patients with hyperuricemia had the significantly higher proportion of males to females, mean arterial pressure, the levels of total cholesterol, triglyceride, Scr, BUN, 24 hour-urine protein, C3, and C4, the lower levels of high-density lipoprotein cholesterol and eGFR than those without (p < 0.05). In terms of pathological characteristics, the tubular atrophy/interstitial fibrosis scores, vascular injury scores, and glomerular sclerosis percentage were significantly higher in patients with hyperuricemia compared with those without (p < 0.01). There was no significant difference in the scores of mesangial hypercellularity, endocapillary hypercellularity, focal segmental glomerulosclerosis, as well as crescents between the two groups (p > 0.05). As for the depositions of immune complexes deposition in IgAN, the hyperuricemia group had less deposition of immunoglobulin G and FRA than the normo-uricemia group (p < 0.05), while the deposition of immunoglobulin A, immunoglobulin M, and complement C3 in the two groups showed no statistical difference. The survival curve suggested that patients in the hyperuricemia group have significantly poorer renal outcome than those in the normo-uricemia group (p = 0.0147). Results also revealed that the SUA level is a valuable predictor of renal outcome in patients with IgAN. The optimal cutoff value was 361.1 µmol/L (AUC = 0.76 ± 0.08167) and 614 µmol/L (AUC = 0.5728 ± 0.2029) for female and male, respectively. Conclusions The level of SUA is associated with renal function level and pathological severity of IgAN, and maybe a prognostic indicator of IgAN.
Lu et al. (2020) Serum uric acid level is correlated with the clinical, pathological progression and prognosis of IgA nephropathy: an observational retrospective pilot-study. PeerJ 8:e10130 https://doi.org/10.7717/peerj.10130
In silico structural homology modeling and characterization of multiple N-terminal domains of selected bacterial Tcps
Several bacterial pathogens produce Toll/interleukin-1 receptor (TIR) domain-containing protein homologs that are important for subverting the Toll-like receptor (TLR) signaling cascades in hosts. Consequently, promoting the persistence and survival of the bacterial pathogens. However, the exact molecular mechanisms elucidating the functional characteristics of these bacterial proteins are not clear. Physicochemical and homology modeling characterization studies have been conducted to predict the conditions suitable for the stability and purification of these proteins and to predict their structural properties. The outcomes of these studies have provided important preliminary data for the drug discovery pipeline projects. Here, using in silico physicochemical and homology modeling tools, we have reported the primary, secondary and tertiary structural characteristics of multiple N-terminal domains of selected bacterial TIR domain-containing proteins (Tcps). The results show variations between the primary amino acid sequences, secondary structural components and three-dimensional models of the proteins, suggesting the role of different molecular mechanisms in the functioning of these proteins in subverting the host immune system. This study could form the basis of future experimental studies advancing our understanding of the molecular basis of the inhibition of the host immune response by the bacterial Tcps.
Alaidarous (2020) In silico structural homology modeling and characterization of multiple N-terminal domains of selected bacterial Tcps. PeerJ 8:e10143 https://doi.org/10.7717/peerj.10143
A 22-amino-acid peptide regulates tight junctions through occludin and cell apoptosis
Occludin is a structural protein of tight junctions (TJ) in the blood–testis barrier (BTB). A 22-amino-acid peptide (22AA) in the second extracellular loop can reversibly regulate TJ, but its regulatory mechanism is unknown. In this study, a 22AA-induced TJ destruction animal model was constructed to investigate the effect of 22AA on Sertoli cells (SCs) and spermatid counts and cell apoptosis at different time points using a multiplex immunofluorescence technique. The effect of 22AA on the location and distribution of occludin was analyzed via dual confocal fluorescence microscope. Western blotting was used to analyze dynamic changes in occludin expression. Real-time RT-PCR was used to analyze miR-122-5p expression changes. Sperm density counts and mating methods were used to analyze the effect of 22AA on fertility in mice. The results showed that 22AA promoted SC and spermatid apoptosis, downregulated occludin, upregulated miR-122-5p, and decreased sperm density and litter size before 27 days (27D). After 27D, the expression of occludin increased again, miR-122-5p expression decreased again, both sperm density and litter size returned to normal, apoptosis stopped, and spermatogenesis began to recover. Therefore, it can be concluded that 22AA can destroy TJ by downregulating occludin and inducing cell apoptosis. After 27D, TJ and spermatogenesis functions return to normal.
Zhu et al. (2020) A 22-amino-acid peptide regulates tight junctions through occludin and cell apoptosis. PeerJ 8:e10147 https://doi.org/10.7717/peerj.10147
Habitat preference, movements and growth of giant mottled eels, Anguilla marmorata, in a small subtropical Amami-Oshima Island river
Although anguillid eel populations have decreased remarkably in recent decades, few detailed ecological studies have been conducted on tropical eels such as the giant mottled eel whose range extends across the whole Indo-Pacific. This species was studied throughout the entire 0.5 km mainstem reaches of Oganeku River on the subtropical Amami-Oshima Island of Japan over a two-year period using four sampling periods to understand its habitat preference, early life-stage dispersal process, movements, and annual growth using a mark-recapture experiment conducted with quantitative electrofishing. A total of 396 juvenile growth-phase A. marmorata eels were caught and tagged, with 48 individuals being recaptured at least once. Their density irrespective of size of eels was most strongly determined by distance from the river mouth, followed by riverbank type according to random forest models. Eel density decreased with increasing distance from the freshwater tidal limit located about 100–150 m from the river mouth. Eels preferred vegetated riverbanks, while they avoided those of concrete and sand. The density of small eels (total length: TL < 240 mm) was also associated with depth and velocity, with small eels tending to prefer riffle or run habitats. In contrast, large eels (TL ≥ 240 mm) were found in habitats of any depth and velocity. The TL of eels had a minimum peak at around the tidal limit, and it increased with increasing distance from the tidal limit. The observed density and size gradients of eels in relation to the distance from the river mouth suggested that A. marmorata initially recruited to freshwater tidal limit areas and then dispersed in both downstream and upstream directions. The growth rate of eels varied greatly among individuals that were at large for various periods of time and ranged from 0 to 163.2 mm/year (mean ± SD of 31.8 ± 31.0 mm/year). Of the recaptured eels, 52.1% were recaptured in a section that was different from the original capture section, and their mean ± SD distance travelled was 46.5 ± 72.5 m (median = 20 m). 47.9% of the eels were recaptured from the original section of capture (i.e., <10 m distances travelled), suggesting that they had strong fidelity to specific habitats with limited movements. The distance travelled of eels that had moved was greater for small eels (range = 10–380 m; mean ± SD = 84.4 ± 121.9 m) than large individuals (range = 10–120 m; mean ± SD = 30.9 ± 31.0 m), which indicates that the mobility of the eels declines as they grow. This is the first clear detailed documentation of the spatial distribution, growth, and movements of tropical eels in a small river system in relation to environmental conditions that provides an example of how future studies can be conducted in other areas to understand how conservation efforts can be most efficiently targeted for maximum success.
Itakura et al. (2020) Habitat preference, movements and growth of giant mottled eels, Anguilla marmorata, in a small subtropical Amami-Oshima Island river. PeerJ 8:e10187 https://doi.org/10.7717/peerj.10187
A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases
Households are known to be high-risk locations for the transmission of communicable diseases. Numerous modelling studies have demonstrated the important role of households in sustaining both communicable diseases outbreaks and endemic transmission, and as the focus for control efforts. However, these studies typically assume that households are associated with a single dwelling and have static membership. This assumption does not appropriately reflect households in some populations, such as those in remote Australian Aboriginal and Torres Strait Islander communities, which can be distributed across more than one physical dwelling, leading to the occupancy of individual dwellings changing rapidly over time. In this study, we developed an individual-based model of an infectious disease outbreak in communities with demographic and household structure reflective of a remote Australian Aboriginal community. We used the model to compare the dynamics of unmitigated outbreaks, and outbreaks constrained by a household-focused prophylaxis intervention, in communities exhibiting fluid vs. stable dwelling occupancy. We found that fluid dwelling occupancy can lead to larger and faster outbreaks in modelled scenarios, and may interfere with the effectiveness of household-focused interventions. Our findings suggest that while short-term restrictions on movement between dwellings may be beneficial during outbreaks, in the longer-term, strategies focused on reducing household crowding may be a more effective way to reduce the risk of severe outbreaks occurring in populations with fluid dwelling occupancy.
Chisholm et al. (2020) A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases. PeerJ 8:e10203 https://doi.org/10.7717/peerj.10203
Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study
Objective The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known. Methods Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday–Wednesday–Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational period. The assessment of neurocognitive function was conducted using the MATRICS Consensus Cognitive Battery at baseline, 13 and 26 days. Tasks were designed to test speed of processing, working memory, visual learning and verbal learning. Results A significant improvement was found only in scores of speed of processing (F = 9.9, p = 0.001) after a 2-week observational period, which was accounted for by the improvement of depression symptoms. There were no significant changes over time in terms of working memory, visual learning and verbal learning. Pearson correlation analysis showed that the improvement of depression symptoms through six ketamine infusions was greater among TRBD patients with lower working memory at baseline (r = 0.54, p = 0.03). In multiple regression analysis, the significant correlation was still maintained (beta = 0.67, t = 2.2, p = 0.04). Conclusion This preliminary study indicated that six ketamine infusions were not harmful but were slightly beneficial for speed of processing in TRBD. However, this change was mainly accounted for the improvement of depression symptoms over time. Lower baseline working memory appears to be associated with greater antidepressant response after completion of six ketamine infusions in patients with TRBD.
Zheng et al. (2020) Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study. PeerJ 8:e10208 https://doi.org/10.7717/peerj.10208
Antimicrobial resistant gene prevalence in soils due to animal manure deposition and long-term pasture management
The persistence of antimicrobial resistant (AMR) genes in the soil-environment is a concern, yet practices that mitigate AMR are poorly understood, especially in grasslands. Animal manures are widely deposited on grasslands, which are the largest agricultural land-use in the United States. These nutrient-rich manures may contain AMR genes. The aim of this study was to enumerate AMR genes in grassland soils following 14-years of poultry litter and cattle manure deposition and evaluate if best management practices (rotationally grazed with a riparian (RBR) area and a fenced riparian buffer strip (RBS), which excluded cattle grazing and poultry litter applications) relative to standard pasture management (continuously grazed (CG) and hayed (H)) minimize the presence and amount of AMR genes. Quantitative PCR (Q-PCR) was performed to enumerate four AMR genes (ermB, sulI, intlI, and blactx-m-32) in soil, cattle manure, and poultry litter environments. Six soil samples were additionally subjected to metagenomic sequencing and resistance genes were identified from assembled sequences. Following 14-years of continuous management, ermB, sulI, and intlI genes in soil were greatest (P < 0.05) in samples collected under long-term continuous grazing (relative to conservation best management practices), under suggesting overgrazing and continuous cattle manure deposition may increase AMR gene presence. In general, AMR gene prevalence increased downslope, suggesting potential lateral movement and accumulation based on landscape position. Poultry litter had lower abundance of AMR genes (ermB, sulI, and intlI) relative to cattle manure. Long-term applications of poultry litter increased the abundance of sulI and intlI genes in soil (P < 0.05). Similarly, metagenomic shotgun sequencing revealed a greater total number of AMR genes under long-term CG, while fewer AMR genes were found in H (no cattle manure) and RBS (no animal manure or poultry litter). Results indicate long-term conservation pasture management practices (e.g., RBS and RBR) and select animal manure (poultry litter inputs) may minimize the presence and abundance of AMR genes in grassland soils.
Yang et al. (2020) Antimicrobial resistant gene prevalence in soils due to animal manure deposition and long-term pasture management. PeerJ 8:e10258 https://doi.org/10.7717/peerj.10258
Increased expression of POLR3G predicts poor prognosis in transitional cell carcinoma
Background Previous studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC. Methods The RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC. Results Transcriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT. Conclusions POLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.
Liu et al. (2020) Increased expression of POLR3G predicts poor prognosis in transitional cell carcinoma. PeerJ 8:e10281 https://doi.org/10.7717/peerj.10281