Identification of a novel association for the WWOX/HIF1A axis with gestational diabetes mellitus (GDM)
Background Although the WW-domain-containing oxidoreductase (WWOX)/Hypoxia-inducible factor 1 (HIF1) pathway is a well-known regulator of cellular glucose and energy metabolism in pathophysiological processes, its role in gestational diabetes mellitus (GDM), remains elusive. We undertook this study to determine the effect of WWOX/HIF1A signaling on the expression of glucose metabolism genes in GDM patients. Methods Leukocytes were obtained from 135 pregnant women with (n = 98) or without (n = 37) GDM and, in turn, 3 months (n = 8) and 1 year (n = 12) postpartum. Quantitative RT-PCR was performed to determine gene expression profiles of the WWOX/HIF1A-related genes, including those involved in glucose transport (SLC2A1, SLC2A4), glycolytic pathway (HK2, PKM2, PFK, LDHA), Wnt pathway (DVL2, CTNNB1), and inflammatory response (NFKB1). Results GDM patients displayed a significant downregulation of WWOX with simultaneous upregulation of HIF1A which resulted in approximately six times reduction in WWOX/HIF1A ratio. As a consequence, HIF1A induced genes (SLC2A1, HK2, PFK, PKM) were found to be overexpressed in GDM compared to normal pregnancy and negative correlate with WWOX/HIF1A ratio. The postpartum WWOX expression was higher than during GDM, but its level was comparable to that observed in normal pregnancy. Conclusions The obtained results suggest a significant contribution of the WWOX gene to glucose metabolism in patients with gestational diabetes. Decreased WWOX expression in GDM compared to normal pregnancy, and in particular reduction of WWOX/HIF1A ratio, indicate that WWOX modulates HIF1α activity in normal tissues as described in the tumor. The effect of HIF1α excessive activation is to increase the expression of genes encoding proteins directly involved in the glycolysis which may lead to pathological changes in glucose metabolism observed in gestational diabetes.
Baryla et al. (2021) Identification of a novel association for the WWOX/HIF1A axis with gestational diabetes mellitus (GDM). PeerJ 9:e10604 https://doi.org/10.7717/peerj.10604
Tumor microenvironment related novel signature predict lung adenocarcinoma survival
Background Lung adenocarcinoma (LUAD) is the most common histological type of lung cancers, which is the primary cause of cancer‐related mortality worldwide. Growing evidence has suggested that tumor microenvironment (TME) plays a pivotal role in tumorigenesis and progression. Hence, we investigate the correlation of TME related genes with LUAD prognosis. Method The information of LUAD gene expression data was obtained from The Cancer Genome Atlas (TCGA). According to their immune/stromal scores calculated by the ESTIMATE algorithm, differentially expressed genes (DEGs) were identified. Then, we performed univariate Cox regression analysis on DEGs to obtain genes that are apparently bound up with LUAD survival (SurGenes). Functional annotation and protein-protein interaction (PPI) was also conducted on SurGenes. By validating the SurGenes with data sets of lung cancer from the Gene Expression Omnibus (GEO), 106 TME related SurGenes were generated. Further, intersection analysis was executed between the 106 TME related SurGenes and hub genes from PPI network, PTPRC and CD19 were obtained. Gene Set Enrichment Analysis and CIBERSORT analysis were performed on PTPRC and CD19. Based on the TCGA LUAD dataset, we conducted factor analysis and Step-wise multivariate Cox regression analysis for 106 TME related SurGenes to construct the prognostic model for LUAD survival prediction. The LUAD dataset in GEO (GSE68465) was used as the testing dataset to confirm the prognostic model. Multivariate Cox regression analysis was used between risk score from the prognostic model and clinical parameters. Result A total of 106 TME related genes were collected in our research totally, which were markedly correlated with the overall survival (OS) of LUAD patient. Bioinformatics analysis suggest them mainly concentrated on immune response, cell adhesion, and extracellular matrix. More importantly, among 106 TME related SurGenes, PTPRC and CD19 were highly interconnected nodes among PPI network and correlated with immune activity, exhibiting significant prognostic potential. The prognostic model was a weighted linear combination of the 106 genes, by which the low-OS LUAD samples could be separated from the high-OS samples with success. This model was also able to rebustly predict the situation of survival (training set: p-value < 0.0001, area under the curve (AUC) = 0.649; testing set: p-value = 0.0009, AUC = 0.617). By combining with clinical parameters, the prognostic model was optimized. The AUC achieved 0.716 for 3 year and 0.699 for 5 year. Conclusion A series of TME-related prognostic genes were acquired in this research, which could reflect immune disorders within TME, and PTPRC and CD19 show the potential to be an indicator for LUAD prognosis and tumor microenvironment modulation. The prognostic model constructed base on those prognostic genes presented a high predictive ability, and may have clinical implications in the overall survival prediction of LUAD.
Chen et al. (2021) Tumor microenvironment related novel signature predict lung adenocarcinoma survival. PeerJ 9:e10628 https://doi.org/10.7717/peerj.10628
Comparative analysis and implications of the chloroplast genomes of three thistles (Carduus L., Asteraceae)
Background Carduus, commonly known as plumeless thistles, is a genus in the Asteraceae family that exhibits both medicinal value and invasive tendencies. However, the genomic data of Carduus (i.e., complete chloroplast genomes) have not been sequenced. Methods We sequenced and assembled the chloroplast genome (cpDNA) sequences of three Carduus species using the Illumina Miseq sequencing system and Geneious Prime. Phylogenetic relationships between Carduus and related taxa were reconstructed using Maximum Likelihood and Bayesian Inference analyses. In addition, we used a single nucleotide polymorphism (SNP) in the protein coding region of the matK gene to develop molecular markers to distinguish C. crispus from C. acanthoides and C. tenuiflorus. Results The cpDNA sequences of C. crispus, C. acanthoides, and C. tenuiflorus ranged from 152,342 bp to 152,617 bp in length. Comparative genomic analysis revealed high conservation in terms of gene content (including 80 protein-coding, 30 tRNA, and four rRNA genes) and gene order within the three focal species and members of subfamily Carduoideae. Despite their high similarity, the three species differed with respect to the number and content of repeats in the chloroplast genome. Additionally, eight hotspot regions, including psbI-trnS_GCU, trnE_UUC-rpoB, trnR_UCU-trnG_UCC, psbC-trnS_UGA, trnT_UGU-trnL_UAA, psbT-psbN, petD-rpoA, and rpl16-rps3, were identified in the study species. Phylogenetic analyses inferred from 78 protein-coding and non-coding regions indicated that Carduus is polyphyletic, suggesting the need for additional studies to reconstruct relationships between thistles and related taxa. Based on a SNP in matK, we successfully developed a molecular marker and protocol for distinguishing C. crispus from the other two focal species. Our study provides preliminary chloroplast genome data for further studies on plastid genome evolution, phylogeny, and development of species-level markers in Carduus.
Jung et al. (2021) Comparative analysis and implications of the chloroplast genomes of three thistles (Carduus L., Asteraceae). PeerJ 9:e10687 https://doi.org/10.7717/peerj.10687
Taphonomic patterns mimic biologic structures: diagenetic Liesegang rings in Mesozoic coleoids and coprolites
Because of physiology of coleoids, their fossils preserve soft-tissue-remains more often than other cephalopods. Sometimes, the phosphatized soft-tissues, particularly parts of the muscular mantle, display dark circular patterns. Here, we showcase that these patterns, here documented for fossil coleoids from the Jurassic of Germany and the Cretaceous of Lebanon, superficially resemble chromatophores (which enable living coleoids to alter their coloration). We examined and chemically analyzed the circular structures in these specimens, describe them, and discuss their genesis. Based on their structure and color, we visually differentiate between three types of circles. By comparison with similar structures, we suggest that these structures are not biogenic but Liesegang rings, which formed due to reaction-diffusion processes very soon after death.
Klug et al. (2021) Taphonomic patterns mimic biologic structures: diagenetic Liesegang rings in Mesozoic coleoids and coprolites. PeerJ 9:e10703 https://doi.org/10.7717/peerj.10703
Genome-wide miRNA expression profiling in potato (Solanum tuberosum L.) reveals TOR-dependent post-transcriptional gene regulatory networks in diverse metabolic pathway
Target of rapamycin (TOR) operates as a hub of the signal transduction that integrates nutrient and energy signaling to promote cell proliferation and growth through mediating the transcriptional and post- transcriptional regulator networks in all eukaryotic species. MicroRNAs (miRNAs) are widespread classes of small, single-stranded, non-coding endogenous RNAs and are widely found in eukaryotes, which play a vital role in regulating gene expression by degrading targeted mRNAs or translational repression at post-transcriptional level. Recent studies found that there were necessarily close connections between miRNA and TOR pathways in mammals. However, there is little information about the interplay between the miRNA and TOR in plants. Thus, the aim of this study was to identify potential TOR-miRNA-mRNA regulatory networks in TOR signaling through global mRNA and microRNA expression profiling in potato. Based on the previous high-throughput transcriptome sequencing and filtering, a total of 2,899 genes were significantly differentially expressed in potato under TOR inhibitors treatment. Pathway analysis revealed that these genes were significantly enriched in multiple metabolic processes. Similarly, in the present study, suppression of TOR resulted in 41 miRNAs up-regulated and 45 down-regulated, revealing that TOR plays a crucial role in the regulation of miRNA regulatory network. Furthermore, integrated mRNA and miRNA expression profiling uncovered that these miRNAs participated in large-scale metabolic process in the TOR signal pathway in potato, such as regulation of autophagy and ubiquitination, and biosynthesis of secondary metabolites. Overall, the results shed new insight into TOR related post-transcriptional gene regulatory networks in potato and suggesting TOR-miRNA-targeting genes relevant networks as a potential genetic resource for potato improvement.
Deng et al. (2021) Genome-wide miRNA expression profiling in potato (Solanum tuberosum L.) reveals TOR-dependent post-transcriptional gene regulatory networks in diverse metabolic pathway. PeerJ 9:e10704 https://doi.org/10.7717/peerj.10704
Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection
Although liver cirrhosis and hepatocellular carcinoma are major consequences of hepatitis C (HCV), there has been an increasing number of studies examining extrahepatic manifestations, especially those caused by systemic chronic inflammation and metabolic complications that might predispose HCV patients to atherosclerosis and ischemic cerebrovascular disease (CVD). The aim of our study was to assess E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection and to correlate them with cerebrovascular reactivity. A blood sample was taken from eighteen patients with chronic hepatitis C infection and from the same number of healthy blood donors in the control group. The aim was to analyse markers of endothelial dysfunction and to correlate them with cerebrovascular reactivity expressed as breath-holding index (BHI) determined using transcranial color Doppler. The obtained results revealed significant differences between the groups in all endothelial markers except for the E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. A significant reduction of 0.5 (95% CI 0.2, 0.8) in the mean BHI was found in the hepatitis group (mean BHI 0.64) compared to controls (mean BHI 1.10). No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group, the scatter plot of ICAM-1 vs BHI suggested that the association might be present. In conclusion, the results of this study confirm an association between a chronic HCV infection and altered cerebrovascular reactivity as well as higher levels of markers of endothelial activation (ICAM-1, VCAM-1) as possible indicators of an increased CVD risk.
Pavicic Ivelja et al. (2021) Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection. PeerJ 9:e10723 https://doi.org/10.7717/peerj.10723
Monitoring oyster culture rafts and seagrass meadows in Nagatsura-ura Lagoon, Sanriku Coast, Japan before and after the 2011 tsunami by remote sensing: their recoveries implying the sustainable development of coastal waters
Background Coastal ecosystems are blue infrastructures that support coastal resources and also aquaculture. Seagrass meadows, one of coastal ecosystems, provide substrates for epiphytic diatoms, which are food resources for cultured filter feeder organisms. Highly intensive coastal aquaculture degrades coastal environments to decrease seagrass meadows. Therefore, efficient aquaculture management and conservation of seagrass meadows are necessary for the sustainable development of coastal waters. In ria-type bays, non-feeding aquaculture of filter feeders such as oysters, scallops, and ascidians are actively practiced along the Sanriku Coast, Japan. Before the 2011 Great East Japan Earthquake, the over-deployment of oyster culture facilities polluted the bottom environment and formed an hypoxic bottom water layer due to the organic excrements from cultured oysters. The tsunami in 2011 devastated the aquaculture facilities and seagrass meadows along the Sanriku Coast. We mapped the oyster culture rafts and seagrass meadows in Nagatsura-ura Lagoon, Sanriku Coast before and after the tsunami and monitored those and environments after the tsunami by field surveys. Methods We conducted field surveys and monitored the environmental parameters in Nagatsura-ura Lagoon every month since 2014. We used high-resolution satellite remote sensing images to map oyster culture rafts and seagrass meadows at irregular time intervals from 2006 to 2019 in order to assess their distribution. In 2019, we also used an unmanned aerial vehicle to analyze the spatial variability of the position and the number of ropes suspending oyster clumps beneath the rafts. Results In 2013, the number and distribution of the oyster culture rafts had been completely restored to the pre-tsunami conditions. The mean area of culture raft increased after the tsunami, and ropes suspending oyster clumps attached to a raft in wider space. Experienced local fishermen also developed a method to attach less ropes to a raft, which was applied to half of the oyster culture rafts to improve oyster growth. The area of seagrass meadows has been expanding since 2013. Although the lagoon had experienced frequent oyster mass mortality events in summer before the tsunami, these events have not occurred since 2011. The 2011 earthquake and tsunami deepened the sill depth and widened the entrance to enhance water exchange and improve water quality in the lagoon. These changes brought the expansion of seagrass meadows and reduction of mass mortality events to allow sustainable oyster culture in the lagoon. Mapping and monitoring of seagrass meadows and aquaculture facilities via satellite remote sensing can provide clear visualization of their temporal changes. This can in turn facilitate effective aquaculture management and conservation of coastal ecosystems, which are crucial for the sustainable development of coastal waters.
Spatial and Geographic Information Science
Murata et al. (2021) Monitoring oyster culture rafts and seagrass meadows in Nagatsura-ura Lagoon, Sanriku Coast, Japan before and after the 2011 tsunami by remote sensing: their recoveries implying the sustainable development of coastal waters. PeerJ 9:e10727 https://doi.org/10.7717/peerj.10727
Geographic potential of the world’s largest hornet, Vespa mandarinia Smith (Hymenoptera: Vespidae), worldwide and particularly in North America
The Asian giant hornet (AGH, Vespa mandarinia) is the world’s largest hornet, occurring naturally in the Indomalayan region, where it is a voracious predator of pollinating insects including honey bees. In September 2019, a nest of Asian giant hornets was detected outside of Vancouver, British Columbia; multiple individuals were detected in British Columbia and Washington state in 2020; and another nest was found and eradicated in Washington state in November 2020, indicating that the AGH may have successfully wintered in North America. Because hornets tend to spread rapidly and become pests, reliable estimates of the potential invasive range of V. mandarinia in North America are needed to assess likely human and economic impacts, and to guide future eradication attempts. Here, we assess climatic suitability for AGH in North America, and suggest that, without control, this species could establish populations across the Pacific Northwest and much of eastern North America. Predicted suitable areas for AGH in North America overlap broadly with areas where honey production is highest, as well as with species-rich areas for native bumble bees and stingless bees of the genus Melipona in Mexico, highlighting the economic and environmental necessity of controlling this nascent invasion.
Nuñez-Penichet et al. (2021) Geographic potential of the world’s largest hornet, Vespa mandarinia Smith (Hymenoptera: Vespidae), worldwide and particularly in North America. PeerJ 9:e10690 https://doi.org/10.7717/peerj.10690
Antibiotic prescription practices and attitudes towards the use of antimicrobials among veterinarians in the City of Tshwane, South Africa
Background Understanding the prescription practices and attitudes of veterinarians towards antimicrobial resistance (AMR) is crucial in guiding efforts to curb AMR. This study investigated prescription practices and attitudes towards AMR among veterinarians in the City of Tshwane, South Africa. Methods Out of the 83 veterinarians invited to participate in the study, 54 signed the consent form and completed the questionnaire. Percentages and 95% confidence intervals of all categorical variables were computed. A multinomial logistic model was used to identify predictors of the veterinarians’ view towards antimicrobial use. Results The majority (88%) of respondents indicated that improper use of antimicrobials contributed to selection for AMR. Veterinarians relied on clinical signs and symptoms (88%, 48/54) to decide whether to prescribe antimicrobials or not. However, the choice of antimicrobials depended on the cost of antibiotics (77.2%), route of administration (81.5%), and risk of potential adverse reactions (79.6%; 43/54). Many (61.5%) veterinarians were of the view that often antimicrobials are appropriately prescribed and 88.7% agreed that improper use of antimicrobials contributed to selection for antimicrobial resistant organisms. Compared to females, males were significantly more likely (Relative Risk Ratio (RRR) = 9.0; P = 0.0069) to agree rather than to “neither agree nor disagree” that their colleagues over-prescribed antimicrobials. Conclusions The decisions to prescribe antimicrobials by the veterinarians depended on clinical presentation of the patient, while the choice of antimicrobial depended on cost, route of administration, and risk of potential adverse reactions. Most veterinarians were of the view that antimicrobials were prescribed judiciously.
Samuels et al. (2021) Antibiotic prescription practices and attitudes towards the use of antimicrobials among veterinarians in the City of Tshwane, South Africa. PeerJ 9:e10144 https://doi.org/10.7717/peerj.10144
Genome-wide comparison of four MRSA clinical isolates from Germany and Hungary
Staphylococcus aureus is a drug-resistant pathogen, capable of colonizing diverse ecological niches and causing a broad spectrum of infections related to a community and healthcare. In this study, we choose four methicillin-resistant S. aureus (MRSA) clinical isolates from Germany and Hungary based on our previous polyphasic characterization finding. We assumed that the selected strains have a different genetic background in terms of the presence of resistance and virulence genes, prophages, plasmids, and secondary metabolite biosynthesis genes that may play a crucial role in niche adaptation and pathogenesis. To clarify these assumptions, we performed a comparative genome analysis of these strains and observed many differences in their genomic compositions. The Hungarian isolates (SA H27 and SA H32) with ST22-SCCmec type IVa have fewer genes for multiple-drug resistance, virulence, and prophages reported in Germany isolates. Germany isolate, SA G6 acquires aminoglycoside (ant(6)-Ia and aph(3’)-III) and nucleoside (sat-4) resistance genes via phage transduction and may determine its pathogenic potential. The comparative genome study allowed the segregation of isolates of geographical origin and differentiation of the clinical isolates from the commensal isolates. This study suggested that Germany and Hungarian isolates are genetically diverse and showing variation among them due to the gain or loss of mobile genetic elements (MGEs). An interesting finding is the addition of SA G6 genome responsible for the drastic decline of the core/pan-genome ratio curve and causing the pan-genome to open wider. Functional characterizations revealed that S. aureus isolates survival are maintained by the amino acids catabolism and favor adaptation to growing in a protein-rich medium. The dispersible and singleton genes content of S. aureus genomes allows us to understand the genetic variation among the CC5 and CC22 groups. The strains with the same genetic background were clustered together, which suggests that these strains are highly alike; however, comparative genome analysis exposed that the acquisition of phage elements, and plasmids through the events of MGEs transfer contribute to differences in their phenotypic characters. This comparative genome analysis would improve the knowledge about the pathogenic S. aureus strain’s characterization, and responsible for clinically important phenotypic differences among the S. aureus strains.
Naorem et al. (2021) Genome-wide comparison of four MRSA clinical isolates from Germany and Hungary. PeerJ 9:e10185 https://doi.org/10.7717/peerj.10185