Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics
Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles can transport bioactive molecules containing mRNAs, proteins, DNA fragments, and non-coding RNAs from a donor cell to recipient cells, and cause the alteration in genetic and epigenetic factors and reprogramming of the target cells. Many diverse cell types such as mesenchymal cells, immune cells, and cancer cells can induce the release of exosomes. Increasing evidence illustrated that the exosomes derived from tumor cells might trigger the tumor initiation, tumor cell growth and progression, metastasis, and drug resistance. The secreted nanovesicles of exosomes can play significant roles in cells communicate via shuttling the nucleic acid molecules and proteins to target cells and tissues. In this review, we discussed multiple mechanisms related to biogenesis, load, and shuttle of the exosomes. Also, we illustrated the diverse roles of exosomes in several types of human cancer development, tumor immunology, angiogenesis, and metastasis. The exosomes may act as the promising biomarkers for the prognosis of various types of cancers which suggested a new pathway for anti-tumor therapeutic of these nanovesicles and promoted exosome-based cancer for clinical diagnostic and remedial procedures.
Abak et al. (2018) Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics. PeerJ 6:e4763 https://doi.org/10.7717/peerj.4763
DACCOR–Detection, characterization, and reconstruction of repetitive regions in bacterial genomes
The reconstruction of genomes using mapping-based approaches with short reads experiences difficulties when resolving repetitive regions. These repetitive regions in genomes result in low mapping qualities of the respective reads, which in turn lead to many unresolved bases. Currently, the reconstruction of these regions is often based on modified references in which the repetitive regions are masked. However, for many references, such masked genomes are not available or are based on repetitive regions of other genomes. Our idea is to identify repetitive regions in the reference genome de novo. These regions can then be used to reconstruct them separately using short read sequencing data. Afterward, the reconstructed repetitive sequence can be inserted into the reconstructed genome. We present the program detection, characterization, and reconstruction of repetitive regions, which performs these steps automatically. Our results show an increased base pair resolution of the repetitive regions in the reconstruction of Treponema pallidum samples, resulting in fewer unresolved bases.
Seitz et al. (2018) DACCOR–Detection, characterization, and reconstruction of repetitive regions in bacterial genomes. PeerJ 6:e4742 https://doi.org/10.7717/peerj.4742
Non-biological synthetic spike-in controls and the AMPtk software pipeline improve mycobiome data
High-throughput amplicon sequencing (HTAS) of conserved DNA regions is a powerful technique to characterize microbial communities. Recently, spike-in mock communities have been used to measure accuracy of sequencing platforms and data analysis pipelines. To assess the ability of sequencing platforms and data processing pipelines using fungal internal transcribed spacer (ITS) amplicons, we created two ITS spike-in control mock communities composed of cloned DNA in plasmids: a biological mock community, consisting of ITS sequences from fungal taxa, and a synthetic mock community (SynMock), consisting of non-biological ITS-like sequences. Using these spike-in controls we show that: (1) a non-biological synthetic control (e.g., SynMock) is the best solution for parameterizing bioinformatics pipelines, (2) pre-clustering steps for variable length amplicons are critically important, (3) a major source of bias is attributed to the initial polymerase chain reaction (PCR) and thus HTAS read abundances are typically not representative of starting values. We developed AMPtk, a versatile software solution equipped to deal with variable length amplicons and quality filter HTAS data based on spike-in controls. While we describe herein a non-biological SynMock community for ITS sequences, the concept and AMPtk software can be widely applied to any HTAS dataset to improve data quality.
Palmer et al. (2018) Non-biological synthetic spike-in controls and the AMPtk software pipeline improve mycobiome data. PeerJ 6:e4925 https://doi.org/10.7717/peerj.4925
The relationship between body mass index and pain, disease activity, depression and anxiety in women with fibromyalgia
Background Obesity is a possible factor which affects severity of symptoms and disease activity in fibromyalgia syndrome (FMS). The aim of our study was to determine the association between body mass index (BMI) and pain, tender point count (TPC), disease activity, anxiety and depression in patients with FMS. Methods This was a descriptive study. A total of 124 female FMS patients between 18 and 55 years of age were enrolled. FMS patients were evaluated with visual analog scale (VAS), fibromyalgia impact questionnaire (FIQ), Hamilton anxiety scale (HAM-A) and Hamilton depression scale (HAM-D). Patients were divided into three groups according to BMI levels: normal weight, overweight and obese. Normal weight was defined as BMI 18.5–24.9, overweight as BMI 25.0–29.9 and obesity as BMI ≥ 30. We assessed the BMI status and its association with symptom severity in patients with FMS. Results Significant differences were detected in VAS, TPC, FIQ and HAM-D among the groups (p < 0.05). There were no significant differences between the groups in HAM-A (p = 0.328). The highest scores were found in the obese group. Significant positive correlations were determined between BMI levels and VAS, TPC, FIQ and HAM-D (r = 0.277, p = 0.002; r = 0.384, p < 0.001; r = 0.292, p = 0.001; r = 0.357, p < 0.001). Discussion Obese female FMS patients had higher levels of pain, TPC, disease activity and depression. BMI was significantly and positively correlated with clinical manifestations of FMS. Therefore, FMS treatment programs should include weight loss strategies.
Koçyiğit et al. (2018) The relationship between body mass index and pain, disease activity, depression and anxiety in women with fibromyalgia. PeerJ 6:e4917 https://doi.org/10.7717/peerj.4917
Change of niche in guanaco (Lama guanicoe): the effects of climate change on habitat suitability and lineage conservatism in Chile
Background The main goal of this contribution was to define the ecological niche of the guanaco (Lama guanicoe), to describe potential distributional changes, and to assess the relative importance of niche conservatism and divergence processes between the two lineages described for the species (L.g. cacsilensis and L.g. guanicoe). Methods We used maximum entropy to model lineage’s climate niche from 3,321 locations throughout continental Chile, and developed future niche models under climate change for two extreme greenhouse gas emission scenarios (RCP2.6 and RCP8.5). We evaluated changes of the environmental niche and future distribution of the largest mammal in the Southern Cone of South America. Evaluation of niche conservatism and divergence were based on identity and background similarity tests. Results We show that: (a) the current geographic distribution of lineages is associated with different climatic requirements that are related to the geographic areas where these lineages are located; (b) future distribution models predict a decrease in the distribution surface under both scenarios; (c) a 3% decrease of areal protection is expected if the current distribution of protected areas is maintained, and this is expected to occur at the expense of a large reduction of high quality habitats under the best scenario; (d) current and future distribution ranges of guanaco mostly adhere to phylogenetic niche divergence hypotheses between lineages. Discussion Associating environmental variables with species ecological niche seems to be an important aspect of unveiling the particularities of, both evolutionary patterns and ecological features that species face in a changing environment. We report specific descriptions of how these patterns may play out under the most extreme climate change predictions and provide a grim outlook of the future potential distribution of guanaco in Chile. From an ecological perspective, while a slightly smaller distribution area is expected, this may come with an important reduction of available quality habitats. From the evolutionary perspective, we describe the limitations of this taxon as it experiences forces imposed by climate change dynamics.
Castillo et al. (2018) Change of niche in guanaco (Lama guanicoe): the effects of climate change on habitat suitability and lineage conservatism in Chile. PeerJ 6:e4907 https://doi.org/10.7717/peerj.4907
Transcranial direct current stimulation over the right DLPFC selectively modulates subprocesses in working memory
Background Working memory, as a complex system, consists of two independent components: manipulation and maintenance process, which are defined as executive control and storage process. Previous studies mainly focused on the overall effect of transcranial direct current stimulation (tDCS) on working memory. However, little has been known about the segregative effects of tDCS on the sub-processes within working memory. Method Transcranial direct current stimulation, as one of the non-invasive brain stimulation techniques, is being widely used to modulate the cortical activation of local brain areas. This study modified a spatial n-back experiment with anodal and cathodal tDCS exertion on the right dorsolateral prefrontal cortex (DLPFC), aiming to investigate the effects of tDCS on the two sub-processes of working memory: manipulation (updating) and maintenance. Meanwhile, considering the separability of tDCS effects, we further reconfirmed the causal relationship between the right DLPFC and the sub-processes of working memory with different tDCS conditions. Results The present study showed that cathodal tDCS on the right DLPFC selectively improved the performance of the modified 2-back task in the difficult condition, whereas anodal tDCS significantly reduced the performance of subjects and showed an speeding-up tendency of response time. More precisely, the results of discriminability index and criterion showed that only cathodal tDCS enhanced the performance of maintenance in the difficult condition. Neither of the two tDCS conditions affected the performance of manipulation (updating). Conclusion These findings provide evidence that cathodal tDCS of the right DLPFC selectively affects maintenance capacity. Besides, cathodal tDCS also serves as an interference suppressor to reduce the irrelevant interference, thereby indirectly improving the working memory capacity. Moreover, the right DLPFC is not the unique brain regions for working memory manipulation (updating).
Wang et al. (2018) Transcranial direct current stimulation over the right DLPFC selectively modulates subprocesses in working memory. PeerJ 6:e4906 https://doi.org/10.7717/peerj.4906
Proteomics of Nasonia vitripennis and the effects of native Wolbachia infection on N. vitripennis
Background Nasonia vitripennis, a parasitic wasp, is a good model organism to study developmental and evolutionary genetics and to evaluate the interactions between insect hosts and their symbionts. Wolbachia may be the most prevalent endosymbiont among insect species due to their special ability to improve the fitness of the infected hosts. Transinfection of bacteria or fungi could substantially alter the expression of host immune system components. However, few studies have focused on the effects of native Wolbachia infection. Accordingly, in this study, we evaluated the proteomics of N. vitripennis following Wolbachia infection. Methods We studied the proteomics of N. vitripennis following native Wolbachia infection and in antibiotic-treated Wolbachia-free samples using isobaric tags for relative and absolute quantification-liquid chromatography tandem mass spectrometry, accompanying with some ecological experiments. Results In total, 3,096 proteins were found to be associated with a wide range of biological processes, molecular functions, and cellular components. Interestingly, there were few significant changes in immune or reproductive proteins between samples with and without Wolbachia infection. Differentially expressed proteins were involved in the binding process, catalytic activity, and the metabolic process, as confirmed by quantitative reverse transcription polymerase chain reaction. Discussion Invasion of any pathogen or bacterium within a short time can cause an immunoreaction in the host. Our results implied that during the long process of coexistence, the immune system of the host was not as sensitive as when the symbiont initially infected the host, implying that the organisms had gradually adjusted to cohabitation.
Li et al. (2018) Proteomics of Nasonia vitripennis and the effects of native Wolbachia infection on N. vitripennis. PeerJ 6:e4905 https://doi.org/10.7717/peerj.4905
Clinicopathologic characteristics, laboratory parameters, treatment protocols, and outcomes of pancreatic cancer: a retrospective cohort study of 1433 patients in China
Objectives The prognosis of people with pancreatic cancer is extremely unfavorable. However, the prognostic factors remain largely undefined. We aimed to perform comprehensive analyses of clinicopathologic characteristics, laboratory parameters, and treatment protocols for exploring their role as prognostic factors of pancreatic cancer. Methods Patients diagnosed with pancreatic cancer and hospitalized at the China National Cancer Center between April 2006 and May 2016 were enrolled in this retrospective cohort study. Clinicopathologic characteristics, laboratory parameters, and treatment protocols were compared among patients at different stages of the disease. The association between these factors and overall survival (OS) was analyzed using the Kaplan–Meier method and Cox proportional hazards model. Results The present study included 1,433 consecutive patients with pancreatic cancer. Median OS was 10.6 months (95% confidence interval [CI] 9.8–11.3 months), with 1-, 3-, and 5-year survival rates of 43.7%, 14.8%, and 8.8%, respectively. Cox multivariate analysis findings identified the following factors as independent predictors of OS: gender (female vs male, hazard ratio 0.72, 95% CI [0.54–0.95]); elevated total bilirubin (TBil; 1.82, 1.34–2.47); elevated carbohydrate antigen 19-9 (CA19-9; 1.72, 1.17–2.54); tumor being located in pancreatic body and tail (1.52, 1.10–2.10); advanced T stage (T3-4 vs T1-2, 1.62, 1.15–2.27); lymph node metastasis (1.57, 1.20–2.07); distant metastasis (1.59, 1.12–2.27); the presence of surgical resection (0.53, 0.34–0.81); and the presence of systemic chemotherapy (0.62, 0.45–0.82). Conclusions Being male, elevated TBil and carcinoembryonic antigen, tumor being located in pancreatic body and tail, advanced T stage, lymph node and distant metastasis, the absence of surgical resection, and the absence of systematic chemotherapy were associated with worse OS in patients with pancreatic cancer.
Zhang et al. (2018) Clinicopathologic characteristics, laboratory parameters, treatment protocols, and outcomes of pancreatic cancer: a retrospective cohort study of 1433 patients in China. PeerJ 6:e4893 https://doi.org/10.7717/peerj.4893
BLAST-based validation of metagenomic sequence assignments
When performing bioforensic casework, it is important to be able to reliably detect the presence of a particular organism in a metagenomic sample, even if the organism is only present in a trace amount. For this task, it is common to use a sequence classification program that determines the taxonomic affiliation of individual sequence reads by comparing them to reference database sequences. As metagenomic data sets often consist of millions or billions of reads that need to be compared to reference databases containing millions of sequences, such sequence classification programs typically use search heuristics and databases with reduced sequence diversity to speed up the analysis, which can lead to incorrect assignments. Thus, in a bioforensic setting where correct assignments are paramount, assignments of interest made by “first-pass” classifiers should be confirmed using the most precise methods and comprehensive databases available. In this study we present a BLAST-based method for validating the assignments made by less precise sequence classification programs, with optimal parameters for filtering of BLAST results determined via simulation of sequence reads from genomes of interest, and we apply the method to the detection of four pathogenic organisms. The software implementing the method is open source and freely available.
Bazinet et al. (2018) BLAST-based validation of metagenomic sequence assignments. PeerJ 6:e4892 https://doi.org/10.7717/peerj.4892
Predicting New Zealand riverine fish reference assemblages
Biomonitoring is a common method to monitor environmental change in river ecosystems, a key advantage of biomonitoring over snap-shot physicochemical monitoring is that it provides a more stable, long-term insight into change that is also effects-based. In New Zealand, the main biomonitoring method is a macroinvertebrate sensitivity scoring index, with little established methods available for biomonitoring of fish. This study models the contemporary distribution of common freshwater fish and then uses those models to predict freshwater fish assemblages for each river reach under reference conditions. Comparison of current fish assemblages with those predicted in reference conditions (as observed/expected (O/E) ratios) may provide a suitable option for freshwater fish biomonitoring. Most of the fish communities throughout the central North Island and lower reaches show substantial deviation from the modelled reference community. Most of this deviation is explained by nutrient enrichment, followed by downstream barriers (i.e. dams) and loss of riparian vegetation. The presence of modelled introduced species had relatively little impact on the presence of the modelled native fish. The maps of O/E fish assemblage may provide a rapid way to identify potential restoration sites.
Canning (2018) Predicting New Zealand riverine fish reference assemblages. PeerJ 6:e4890 https://doi.org/10.7717/peerj.4890