Transcriptome profiling of avian pathogenic Escherichia coli and the mouse microvascular endothelial cell line bEnd.3 during interaction
Background Avian pathogenic Escherichia coli (APEC), an important extraintestinal pathogenic E. coli, causes colibacillosis, an acute and mostly systemic disease involving multiple organ lesions such as meningitis. Meningitis-causing APEC can invade the host central nervous system by crossing the blood–brain barrier (BBB), which is a critical step in the development of meningitis. However, the bacteria-host interaction mechanism in this process remains unclear. Methods In this study, we examined E. coli and bEnd.3 cells transcriptomes during infection and mock infection to investigate the global transcriptional changes in both organisms using RNA sequencing approach. Results When APEC infected the bEnd.3 cells, several significant changes in the expression of genes related to cell junctional complexes, extracellular matrix degradation, actin cytoskeleton rearrangement, immune activation and the inflammatory response in bEnd.3 cells were observed as compared to the mock infection group. Thus, the immune activation of bEnd.3 cells indicated that APEC infection activated host defenses. Furthermore, APEC may exploit cell junction degradation to invade the BBB. In addition, amino acid metabolism and energy metabolism related genes were downregulated and the protein export pathway related genes were upregulated in APEC cultured with bEnd.3 cells, compared to that in control. Thus, APEC may encounter starvation and express virulence factors during incubation with bEnd.3 cells. Conclusion This study provides a comprehensive overview of transcriptomic changes that occur during APEC infection of bEnd.3 cells, and offers insights into the bacterial invasion strategies and the subsequent host defense mechanism.
Wang et al. (2020) Transcriptome profiling of avian pathogenic Escherichia coli and the mouse microvascular endothelial cell line bEnd.3 during interaction. PeerJ 8:e9172 https://doi.org/10.7717/peerj.9172
Development and validation of a prognostic nomogram to predict overall survival and cancer-specific survival for patients with anaplastic thyroid carcinoma
Background Anaplastic thyroid carcinoma (ATC) is a rare malignant tumor with a poor prognosis. However, there is no useful clinical prognostic predictive tool for ATC so far. Our study identified risk factors for survival of ATC and created a reliable nomogram to predict overall survival (OS) and cancer-specific survival (CSS) of patients with ATC. Methods A total of 1,404 cases of ATC diagnosed between 1983 and 2013 were extracted from on the Surveillance, Epidemiology and End Results database based on our inclusion criteria. OS and CSS were compared among patients between each variable by Kaplan–Meier methods. The Cox proportional hazards model was used to evaluate multiple prognostic factors and obtain independent predictors. All independent risk factors were included to build nomograms, whose accuracy and practicability were tested by concordance index (C-index), calibration curves, ROC curves, DCA, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results Historic stage, tumor size, surgery and radiotherapy were independent risk factors associated with ATC according to multivariate Cox regression analysis of OS. However, gender was also an important prognostic predictor in CSS besides the factors mentioned above. These characteristics were included in the nomograms predicting OS and CSS of patients with ATC. The nomograms predicting OS and CSS performed well with a C-index of 0.765 and 0.773. ROC curves, DCA, NRI and IDI suggested that the nomogram was superior to TNM staging and age. Conclusion The proposed nomogram is a reliable tool based on the prediction of OS and CSS for patients with ATC. Such a predictive tool can help to predict the survival of the patients.
Gui et al. (2020) Development and validation of a prognostic nomogram to predict overall survival and cancer-specific survival for patients with anaplastic thyroid carcinoma. PeerJ 8:e9173 https://doi.org/10.7717/peerj.9173
Extensive protein expression changes induced by pamidronate in RAW 264.7 cells as determined by IP-HPLC
Background Bisphosphonate therapy has become a popular treatment for osteoporosis, Paget’s disease, multiple myeloma, osteogenesis imperfecta, myocardial infarction, and cancer despite its serious side effects. Bisphosphonate-induced molecular signaling changes in cells are still not clearly elucidated. Methods As bisphosphonates are primarily engulfed by macrophages, we treated RAW 264.7 cells (a murine macrophage cell line) with pamidronate and investigated global protein expressional changes in cells by immunoprecipitation high performance liquid chromatography (IP-HPLC) using 218 antisera. Results Pamidronate upregulated proliferation-activating proteins associated with p53/Rb/E2F and Wnt/β-catenin pathways, but downregulated the downstream of RAS signaling, pAKT1/2/3, ERK-1, and p-ERK-1, and subsequently suppressed cMyc/MAX/MAD network. However, in situ proliferation index of pamidronate-treated RAW264.7 cells was slightly increased by 3.2% vs. non-treated controls. Pamidronate-treated cells showed increase in the expressions of histone- and DNA methylation-related proteins but decrease of protein translation-related proteins. NFkB signaling was also suppressed as indicated by the down-regulations of p38 and p-p38 and the up-regulation of mTOR, while the protein expressions related to cellular protection, HSP-70, NRF2, JNK-1, and LC3 were upregulated. Consequently, pamidronate downregulated the protein expressions related to immediate inflammation,cellular differentiation, survival, angiogenesis, and osteoclastogenesis, but upregulated PARP-1 and FAS-mediated apoptosis proteins. These observations suggest pamidronate affects global protein expressions in RAW 264.7 cells by stimulating cellular proliferation, protection, and apoptosis but suppressing immediate inflammation, differentiation, osteoclastogenesis, and angiogenesis. Accordingly, pamidronate appears to affect macrophages in several ways eliciting not only its therapeutic effects but also atypical epigenetic modification, protein translation, RAS and NFkB signalings. Therefore, our observations suggest pamidronate-induced protein expressions are dynamic, and the affected proteins should be monitored by IP-HPLC to achieve the therapeutic goals during treatment.
Lee et al. (2020) Extensive protein expression changes induced by pamidronate in RAW 264.7 cells as determined by IP-HPLC. PeerJ 8:e9202 https://doi.org/10.7717/peerj.9202
Comparison between radiofrequency ablation and sublobar resections for the therapy of stage I non-small cell lung cancer: a meta-analysis
Background Sublobar resection (SLR) and radiofrequency ablation (RFA) are the two minimally invasive procedures performed for treating stage I non-small cell lung cancer (NSCLC). This study aimed to compare SLR and RFA for the treatment of stage I NSCLC using the meta-analytical method. Methods We searched PubMed and Embase for articles published till December 2019 to evaluate the comparative studies and assess the survival and progression-free survival rates and postoperative complications (PROSPERO registration number: CRD42018087587). A meta-analysis was performed by combining the outcomes of the reported incidences of short-term morbidity and long-term mortality. The fixed or random effects model was utilized to calculate the pooled odds ratios (OR) and the 95% confidence intervals. Results Four retrospective studies were considered in the course of this study. The studies included a total of 309 participants; 154 were assigned to the SLR group, and 155 were assigned to the RFA group. Moreover, there were statistically significant differences between the one- and three-year survival rates and one- and three-year progression-free survival rates for the two groups, which were in favor of the SLR group. Among the post-surgical complications, pneumothorax and pleural effusion were more common for the SLR group, while cardiac abnormalities were prevalent in the RFA group. There was no difference in prevalence of hemoptysis between SLR and RFA groups, which might be attributed to the limited study sample size. Conclusion Considering the higher survival rates and disease control in the evaluated cases, surgical resection is the preferred treatment method for stage I NSCLC. RFA can be considered a valid alternative in patients not eligible for surgery and in high-risk patients as it is less invasive and requires shorter hospital stay.
Chen et al. (2020) Comparison between radiofrequency ablation and sublobar resections for the therapy of stage I non-small cell lung cancer: a meta-analysis. PeerJ 8:e9228 https://doi.org/10.7717/peerj.9228
Evaluation of the effective dose of amygdalin for the improvement of antioxidant gene expression and suppression of oxidative damage in mice
Background Little is known regarding the toxic and therapeutic doses of amygdalin. Treatment regimens and schedules can vary between humans and animal models, and there have been reports of cyanide toxicity due to amygdalin use. Objective The aim of this study was to evaluate the effect of different doses of amygdalin on antioxidant gene expression and suppression of oxidative damage in mice. Methods Forty adult male mice were divided randomly into four groups (n = 10) as follows and treated orally for two weeks: a control group treated with saline solution, a group treated with amygdalin at 200 mg/kg body weight, a group treated with amygdalin at 100 mg/kg body weight, and a group treated with amygdalin at 50 mg/kg body weight. Liver and testis samples were collected for gene expression, biochemical and histopathological analyses. Results The mice treated with medium-dose amygdalin (100 mg/kg) showed upregulated mRNA expression of glutathione peroxidase (P < 0.01) and superoxide dismutase (P < 0.05) and significantly decreased lipid peroxidation (P < 0.05) in hepatic and testicular tissues compared to those in the untreated groups (controls), with mild histopathological effects. The mice treated with high-dose of amygdalin (200 mg/kg) showed downregulated mRNA expression of glutathione peroxidase and superoxide dismutase (P < 0.01) and significantly increased lipid peroxidation (P < 0.05) in both hepatic and testicular tissues compared to those in the untreated groups (controls), with an apparent effect at the histopathological level. No effects were observed in the mice treated with low-dose amygdalin (50 mg/kg) at the gene, protein and histopathological level. Conclusion Low-and medium-dose amygdalin did not induce toxicity in the hepatic and testicular tissues of male mice, unlike high-dose amygdalin, which had a negative effect on oxidative balance in mice. Therefore, amygdalin at a moderate dose may improve oxidative balance in mice.
Albogami et al. (2020) Evaluation of the effective dose of amygdalin for the improvement of antioxidant gene expression and suppression of oxidative damage in mice. PeerJ 8:e9232 https://doi.org/10.7717/peerj.9232
Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions
Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.
Farkas et al. (2020) Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions. PeerJ 8:e9255 https://doi.org/10.7717/peerj.9255
High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment
Glioma is one of the most fatal tumors in central nervous system. Previous studies gradually revealed the association between tumor microenvironment and the prognosis of gliomas patients. However, the correlation between tumor-infiltrating immune cell and stromal signatures are unknown. In our study, we obtained gliomas samples from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). The landscape of tumor infiltrating immune cell subtypes in gliomas was calculated by CIBERSORT. As a result, we found high infiltration of macrophages was correlated with poor outcome (P < 0.05). Then functional enrichment analysis of high/low macrophage-infiltrating groups was performed by GSEA. The results showed three gene sets includes 102 core genes about angiogenesis were detected in high macrophage-infiltrating group. Next, we constructed PPI network and analyzed prognostic value of 102 core genes. We found that five stromal signatures indicated poor prognosis which including HSPG2, FOXF1, KDR, COL3A1, SRPX2 (P < 0.05). Five stromal signatures were adopted to construct a classifier. The classifier showed powerful predictive ability (AUC = 0.748). Patients with a high risk score showed poor survival. Finally, we validated this classifier in TCGA and the result was consistent with CGGA. Our investigation of tumor microenvironment in gliomas may stimulate the new strategy in immunotherapy. Five stromal signature correlated with poor prognosis also provide a strong predator of gliomas patient outcome.
Tian et al. (2020) High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment. PeerJ 8:e9038 https://doi.org/10.7717/peerj.9038
Distribution of the acoustic occurrence of dolphins during the summers 2011 to 2015 in the Upper Gulf of California, Mexico
Baseline knowledge of spatial and temporal distribution patterns is essential for cetacean management and conservation. Such knowledge is particularly important in areas where gillnet fishing occurs, as the Upper Gulf of California, which increases the probability of bycatch of cetaceans. In this area, the vaquita porpoise (Phocoena sinus) has been widely studied, but the knowledge of other cetaceans is scarce and based on traditional visual survey methods. We used data collected by an array of acoustic click detectors (C-PODs) during the summers 2011 to 2015 to analyze the distribution of dolphins in the Vaquita Refuge in the Upper Gulf of California. We recorded 120,038 echolocation click trains of dolphins during 12,371 days of recording effort at 46 sampling sites. Based on simultaneous visual and acoustic data, we estimated a false positive acoustic detection rate of 19.4%. Dolphin acoustic activity varied among sites, with higher activity in the east of the Vaquita Refuge. Acoustic activity was higher at night than during the day. We used negative binomial generalized linear models to study the count of clicks of dolphins in relation to spatial, temporal, physical, biological and anthropogenic explanatory variables. The best model selected for the response variable included sampling site, day-night condition, and vertical component of tide speed. Patterns in the spatial distribution of predicted acoustic activity of dolphins were similar to the acoustic activity observed per sampling season. Higher acoustic activity was predicted at night, but the tide speed variable was not relevant under this condition. Acoustic activity patterns could be related to the availability of prey resources since echolocation click trains are associated with foraging activities of dolphins. This is the first study of the distribution of dolphins in Mexico using medium-term systematic passive acoustic monitoring, and the results can contribute to better management to the natural protected area located in the Upper Gulf of California.
Cárdenas Hinojosa et al. (2020) Distribution of the acoustic occurrence of dolphins during the summers 2011 to 2015 in the Upper Gulf of California, Mexico. PeerJ 8:e9121 https://doi.org/10.7717/peerj.9121
Impact of cost distance and habitat fragmentation on the daily path length of Rhinopithecus bieti
An understanding of primate movement patterns in response to natural and anthropogenically induced changes in habitat heterogeneity, food availability, and plant species distribution is essential for developing effective management and conservation programs. Therefore, from July 2013 to June 2014, we examined the effects of landscape configuration on the ranging behavior (daily path length, DPL) of the Endangered Yunnan snub-nosed monkey (Rhinopithecus bieti) in the Baimaxueshan National Nature Reserve (27°34′N, 99°17′E) in Gehuaqing, China. Given the extreme difficulties in following the study group across high altitude mountainous terrain across an elevation of 2,500–4,000 m, we were only able to collect DPL using 3-4 GPS points per day on 21 individual days. We found that R. bieti traveled the shortest DPL in winter (1,141.31 m), followed by spring (2,034.06 m) and autumn (2,131.19 m). The cost distance, a statistical tool designed to estimate the difficulty of a species moving across its distributional range, was lowest in autumn (205.47), followed by spring (225.93) and winter (432.59) (one-way ANOVA: F = 3.852, P = 0.026, df = 2). The habitat fragmentation index (HFI), which measures the density of forest patches, indicated areas visited in the winter were more fragmented (HFI = 2.16) compared to spring (HFI = 1.83) or autumn (HFI = 1.3). Although our results should be considered preliminary, they suggest that both the availability of suitable travel routes and habitat fragmentation, driven by high-intensity human disturbance, constrain the movement of R. bieti. We found that undisturbed areas of the bands’ range contained a high density of lichens, which represent a nutritious and abundant and year-round food source for Yunnan snub-nosed monkeys. In order to protect this Endangered species, we recommend that researchers construct detailed maps of landscape heterogeneity, particularly habitat connectivity, forest fragmentation, and seasonal variation in the location of major food patches in order to better understand and mitigate the effects of seasonal habitat change on patterns of R. bieti habitat utilization and population viability.
Li et al. (2020) Impact of cost distance and habitat fragmentation on the daily path length of Rhinopithecus bieti. PeerJ 8:e9165 https://doi.org/10.7717/peerj.9165
The effect of landscape on functional connectivity and shell shape in the land snail Humboldtiana durangoensis
The populations of Humboldtiana durangoensis have experienced a drastic reduction in the effective population size; in addition, the species is threatened by anthropogenic activities. For the aforementioned, landscape genetics will serve as a tool to define the potential evolutionarily significant units (ESU) for this species. To complete our objective, we evaluated the effect of cover vegetation and climate on the functional connectivity of the species from the last glacial maximum (LGM) to the present as well as the effect of climate on shell shape. Partial Mantel tests, distance-based redundance analysis and a Bayesian framework were used to evaluate connectivity. On the other hand, geometric morphometrics, phylogenetic principal component analysis and redundancy analysis were used for the analysis of shell shape. Our results suggest that the suitable areas have been decreasing since the LGM; also, vegetation cover rather than climate has influenced the genetic connectivity among land snail populations, although temperature had a high influence on shell shape in this species. In conclusion, vegetation cover was the main factor that determined the functional connectivity for the land snail; however, local selective pressures led to different phenotypes in shell shape that allowed us to postulate that each one of the previously defined genetic groups must be considered as a different ESU.
López et al. (2020) The effect of landscape on functional connectivity and shell shape in the land snail Humboldtiana durangoensis. PeerJ 8:e9177 https://doi.org/10.7717/peerj.9177