Dynamical modeling predicts an inflammation-inducible CXCR7+ B cell precursor with potential implications in lymphoid blockage pathologies
Background The blockage at the early B lymphoid cell development pathway within the bone marrow is tightly associated with hematopoietic and immune diseases, where the disruption of basal regulatory networks prevents the continuous replenishment of functional B cells. Dynamic computational models may be instrumental for the comprehensive understanding of mechanisms underlying complex differentiation processes and provide novel prediction/intervention platforms to reinvigorate the system. Methods By reconstructing a three-module regulatory network including genetic transcription, intracellular transduction, and microenvironment communication, we have investigated the early B lineage cell fate decisions in normal and pathological settings. The early B cell differentiation network was simulated as a Boolean model and then transformed, using fuzzy logic, to a continuous model. We tested null and overexpression mutants to analyze the emergent behavior of the network. Due to its importance in inflammation, we investigated the effect of NFkB induction at different early B cell differentiation stages. Results While the exhaustive synchronous and asynchronous simulation of the early B cell regulatory network (eBCRN) reproduced the configurations of the hematopoietic progenitors and early B lymphoid precursors of the pathway, its simulation as a continuous model with fuzzy logics suggested a transient IL-7R+ ProB-to-Pre-B subset expressing pre-BCR and a series of dominant B-cell transcriptional factors. This conspicuous differentiating cell population up-regulated CXCR7 and reduced CXCR4 and FoxO1 expression levels. Strikingly, constant but intermediate NFkB signaling at specific B cell differentiation stages allowed stabilization of an aberrant CXCR7+ pre-B like phenotype with apparent affinity to proliferative signals, while under constitutive overactivation of NFkB, such cell phenotype was aberrantly exacerbated from the earliest stage of common lymphoid progenitors. Our mutant models revealed an abnormal delay in the BCR assembly upon NFkB activation, concomitant to sustained Flt3 signaling, down-regulation of Ebf1, Irf4 and Pax5 genes transcription, and reduced Ig recombination, pointing to a potential lineage commitment blockage. Discussion For the first time, an inducible CXCR7hi B cell precursor endowed with the potential capability of shifting central lymphoid niches, is inferred by computational modeling. Its phenotype is compatible with that of leukemia-initiating cells and might be the foundation that bridges inflammation with blockage-related malignancies and a wide range of immunological diseases. Besides the predicted differentiation impairment, inflammation-inducible phenotypes open the possibility of newly formed niches colonized by the reported precursor. Thus, emergent bone marrow ecosystems are predicted following a pro-inflammatory induction, that may lead to hematopoietic instability associated to blockage pathologies.
Enciso et al. (2020) Dynamical modeling predicts an inflammation-inducible CXCR7+ B cell precursor with potential implications in lymphoid blockage pathologies. PeerJ 8:e9902 https://doi.org/10.7717/peerj.9902
Study of marsh wetland landscape pattern evolution on the Zoigê Plateau due to natural/human dual-effects
Zoigê Plateau, China’s largest plateau marsh wetland, has experienced large-scale degradation of the marsh wetland and evolution of the wetland landscape pattern over the past 40 years due to climate warming and human activities. How exactly do the wetland landscape pattern characteristics change? How do climatic change and human activities affect the wetland evolution? These questions are yet to be systematically investigated. In order to investigate changes to the marsh wetland on the Zoigê Plateau, field investigations, spatial and statistical analysis were undertaken. Findings from our study indicate that from 1977–2016, the area of marsh wetland on the Plateau reduced by 56.54%, approximately 66,700 hm2 of marsh wetland has been lost. The centroids of both marsh and marshy meadow migrated and the landscape centroid migration behaviors were also correlated with the distribution and variation of the marsh wetland on different slopes. In addition, the number of marsh landscape patches initially increased before decreasing; the number of marshy meadow landscape patches also recorded an initial increase, followed by a decline before a final increase. As the effects of human activities weakened, the aggregation degrees of both marsh and marshy meadow increased. Overall, the fragmentation degree, diversity and fractal dimension of the marsh wetland all declined. An investigation into the driving factors affecting the Plateau area shows that the increase of annual average temperature was the natural factor while trenching and overgrazing were the main human factors resulting in wetland degradation. Results from this study provide basic data and theoretical foundation for the protection and restoration of marsh wetland in alpine regions.
Spatial and Geographic Information Science
Dong et al. (2020) Study of marsh wetland landscape pattern evolution on the Zoigê Plateau due to natural/human dual-effects. PeerJ 8:e9904 https://doi.org/10.7717/peerj.9904
A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma
Background Hepatocellular carcinoma (HCC) is one of the most universal malignant liver tumors worldwide. However, there were no systematic studies to establish glycolysis‑related gene pairs (GRGPs) signatures for the patients with HCC. Therefore, the study aimed to establish novel GRGPs signatures to better predict the prognosis of HCC. Methods Based on the data from Gene Expression Omnibus, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium databases, glycolysis-related mRNAs were used to construct GRGPs. Cox regression was applied to establish a seventeen GRGPs signature in TCGA dataset, which was verified in two validation (European and American, and Asian) datasets. Results Seventeen prognostic GRGPs (HMMR_PFKFB1, CHST1_GYS2, MERTK_GYS2, GPC1_GYS2, LDHA_GOT2, IDUA_GNPDA1, IDUA_ME2, IDUA_G6PD, IDUA_GPC1, MPI_GPC1, SDC2_LDHA, PRPS1_PLOD2, GALK1_IER3, MET_PLOD2, GUSB_IGFBP3, IL13RA1_IGFBP3 and CYB5A_IGFBP3) were identified to be significantly progressive factors for the patients with HCC in the TCGA dataset, which constituted a GRGPs signature. The patients with HCC were classified into low-risk group and high-risk group based on the GRGPs signature. The GRGPs signature was a significantly independent prognostic indicator for the patients with HCC in TCGA (log-rank P = 2.898e−14). Consistent with the TCGA dataset, the patients in low-risk group had a longer OS in two validation datasets (European and American: P = 1.143e−02, and Asian: P = 6.342e−08). Additionally, the GRGPs signature was also validated as a significantly independent prognostic indicator in two validation datasets. Conclusion The seventeen GRGPs and their signature might be molecular biomarkers and therapeutic targets for the patients with HCC.
Zhou et al. (2020) A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma. PeerJ 8:e9944 https://doi.org/10.7717/peerj.9944
Identification of hub genes and small molecule therapeutic drugs related to breast cancer with comprehensive bioinformatics analysis
Breast cancer is one of the most common malignant tumors among women worldwide and has a high morbidity and mortality. This research aimed to identify hub genes and small molecule drugs for breast cancer by integrated bioinformatics analysis. After downloading multiple gene expression datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, 283 overlapping differentially expressed genes (DEGs) significantly enriched in different cancer-related functions and pathways were obtained using LIMMA, VennDiagram and ClusterProfiler packages of R. We then analyzed the topology of protein–protein interaction (PPI) network with overlapping DEGs and further obtained six hub genes (RRM2, CDC20, CCNB2, BUB1B, CDK1, and CCNA2) from the network via STRING and Cytoscape. Subsequently, we conducted genes expression verification, genetic alterations evaluation, immune infiltration prediction, clinicopathological parameters analysis, identification of transcriptional and post-transcriptional regulatory molecules, and survival analysis for these hub genes. Meanwhile, 29 possible drug candidates (e.g., Cladribine, Gallium nitrate, Alvocidib, 1β-hydroxyalantolactone, Berberine hydrochloride, Nitidine chloride) were identified from the DGIdb database and the GSE85871 dataset. In addition, some transcription factors and miRNAs (e.g., E2F1, PTTG1, TP53, ZBTB16, hsa-miR-130a-3p, hsa-miR-204-5p) targeting hub genes were identified as key regulators in the progression of breast cancer. In conclusion, our study identified six hub genes and 29 potential drug candidates for breast cancer. These findings may advance understanding regarding the diagnosis, prognosis and treatment of breast cancer.
Hao et al. (2020) Identification of hub genes and small molecule therapeutic drugs related to breast cancer with comprehensive bioinformatics analysis. PeerJ 8:e9946 https://doi.org/10.7717/peerj.9946
Clostridioides difficile infection after cardiac surgery: Assessment of prevalence, risk factors and clinical outcomes—retrospective study
Background Clostridioides difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. There is little available data regarding risk factors of CDI for patients who undergo cardiac surgery. The study evaluated the course of CDI in patients after cardiac surgery. Methods Of 6,198 patients studied, 70 (1.1%) developed CDI. The control group consisted of 73 patients in whom CDI was excluded. Perioperative data and clinical outcomes were analyzed. Results Patients with CDI were significantly older in comparison to the control group (median age 73.0 vs 67.0, P = 0.005) and more frequently received proton pump inhibitors, statins, β-blockers and acetylsalicylic acid before surgery (P = 0.008, P = 0.012, P = 0.004, and P = 0.001, respectively). In addition, the presence of atherosclerosis, coronary disease and history of malignant neoplasms correlated positively with the development of CDI (P = 0.012, P = 0.036 and P = 0.05, respectively). There were no differences in the type or timing of surgery, aortic cross-clamp and cardiopulmonary bypass time, volume of postoperative drainage and administration of blood products between the studied groups. Relapse was more common among overweight patients with high postoperative plasma glucose or patients with higher C-reactive protein during the first episode of CDI, as well as those with a history of coronary disease or diabetes mellitus (P = 0.005, P = 0.030, P = 0.009, P = 0.049, and P = 0.025, respectively). Fifteen patients died (21.4%) from the CDI group and 7 (9.6%) from the control group (P = 0.050). Emergent procedures, prolonged stay in the intensive care unit, longer mechanical ventilation and high white blood cell count during the diarrhea were associated with higher mortality among patients with CDI (P = 0.05, P = 0.041, P = 0.004 and P = 0.007, respectively). Conclusions The study did not reveal any specific cardiac surgery-related risk factors for development of CDI.
Rzucidło-Hymczak et al. (2020) Clostridioides difficile infection after cardiac surgery: Assessment of prevalence, risk factors and clinical outcomes—retrospective study. PeerJ 8:e9972 https://doi.org/10.7717/peerj.9972
The predisposing factors of AKI for prophylactic strategies in burn care
Background Acute kidney injury (AKI) is one of the most severe complications of burn injury. AKI with severe burn injury causes high mortality. This study aims to investigate the incidence of and predisposing factors for AKI in burn patients. Methods This is a single-center, retrospective, descriptive criterion standard study conducted from June 27, 2015, to March 8, 2016. We used Kidney Disease Improving Global Outcomes criteria to define and select patients with AKI. The study was conducted by recruiting in hospital patients who suffered from the flammable cornstarch-based powder explosion and were treated under primary care procedures. A total of 49 patients who suffered from flammable dust explosion-related burn injury were enrolled and admitted on June 27, 2015. The patients with more than 20% total body surface area of burn were transferred to the intensive care unit. Patients received fluid resuscitation in the first 24 hours based on the Parkland formula. The primary measurements were the incidence of and predisposing factors for AKI in these patients. Demographic characteristics, laboratory data, and inpatient outcomes were also evaluated. The incidence of AKI in this cohort was 61.2% (n = 30). The mortality rate was 2.0% (n = 1) during a 59-day follow-up period. The multivariate analysis revealed inhalation injury (adjusted OR = 22.0; 95% CI [1.4–358.2]) and meeting ≥3 American Burn Association (ABA) sepsis criteria (adjusted OR = 13.7; 95% CI [1.7–110.5]) as independent risk factors for early advanced AKI. Conclusions The incidence rate of AKI was higher in this cohort than in previous studies, possibly due to the flammable dust explosion-related burn injury. However, the mortality was lower than that expected. In clinical practice, indicators of inflammation, including ABA sepsis criteria may help in predicting the risk of AKI in patients with burn injury.
Tsai et al. (2020) The predisposing factors of AKI for prophylactic strategies in burn care. PeerJ 8:e9984 https://doi.org/10.7717/peerj.9984
Coral reefs as a source of climate-active aerosols
We review the evidence for bio-regulation by coral reefs of local climate through stress-induced emissions of aerosol precursors, such as dimethylsulfide. This is an issue that goes to the core of the coral ecosystem’s ability to maintain homeostasis in the face of increasing climate change impacts and other anthropogenic pressures. We examine this through an analysis of data on aerosol emissions by corals of the Great Barrier Reef, Australia. We focus on the relationship with local stressors, such as surface irradiance levels and sea surface temperature, both before and after notable coral bleaching events. We conclude that coral reefs may be able to regulate their exposure to environmental stressors through modification of the optical properties of the atmosphere, however this ability may be impaired as climate change intensifies.
Jackson et al. (2020) Coral reefs as a source of climate-active aerosols. PeerJ 8:e10023 https://doi.org/10.7717/peerj.10023
The mechanism of the plant roots’ soil-reinforcement based on generalized equivalent confining pressure
Background To quantitatively evaluate the contribution of plant roots to soil shear strength, the generalized equivalent confining pressure (GECP), which is the difference in confining pressure between the reinforced and un-reinforced soil specimens at the same shear strength, was proposed and considered in terms of the function of plant roots in soil reinforcement. Methods In this paper, silt loam soil was selected as the test soil, and the roots of Indigofera amblyantha were chosen as the reinforcing material. Different drainage conditions (consolidation drained (CD), consolidation undrained (CU), and unconsolidated undrained (UU)) were used to analyse the influences of different root distribution patterns (horizontal root (HR), vertical root (VR), and complex root (CR)) and root contents (0.25%, 0.50%, and 0.75%) on the shear strength of soil-root composites. Results The cohesion (c) values of the soil-root composites varied under different drainage conditions and root contents, while the internal friction angle (φ ) values remain basically stable under different drainage conditions. Under the same root content and drainage conditions, the shear strength indexes ranked in order of lower to higher were HR, VR and CR. The GECP of the soil-root composites with a 0.75% root content was 1.5–2.0 times that with a 0.50% root content and more than 5 times that with a 0.25% root content under the CD and CU conditions. The GECP in reinforced soil followed the sequence of CD > CU > UU. The GECP of the plant roots increased as confining pressure increased under CD and CU conditions while showed a complex change to the confining pressure under the UU condition. Conclusion It was concluded that the evaluation of plant root reinforcing soil based on GECP can be used to measure effectively the influences of roots on soil under different drainage conditions and root distribution patterns.
Environmental Contamination and Remediation
Guo et al. (2020) The mechanism of the plant roots’ soil-reinforcement based on generalized equivalent confining pressure. PeerJ 8:e10064 https://doi.org/10.7717/peerj.10064
Hydrological and soil physiochemical variables determine the rhizospheric microbiota in subtropical lakeshore areas
Background Due to intensive sluice construction and other human disturbances, lakeshore vegetation has been destroyed and ecosystems greatly changed. Rhizospheric microbiota constitute a key part of a functioning rhizosphere ecosystem. Maintaining rhizosphere microbial diversity is a central, critical issue for sustaining these rhizospheric microbiota functions and associated ecosystem services. However, the community composition and abiotic factors influencing rhizospheric microbiota in lakeshore remain largely understudied. Methods The spatiotemporal composition of lakeshore rhizospheric microbiota and the factors shaping them were seasonally investigated in three subtropical floodplain lakes (Lake Chaohu, Lake Wuchang, and Lake Dahuchi) along the Yangtze River in China through 16S rRNA amplicon high-throughput sequencing. Results Our results showed that four archaeal and 21 bacterial phyla (97.04 ± 0.25% of total sequences) dominated the rhizospheric microbiota communities of three lakeshore areas. Moreover, we uncovered significant differences among rhizospheric microbiota among the lakes, seasons, and average submerged depths. The Acidobacteria, Actinobacteria, Bacteroidetes, Bathyarchaeota, Gemmatimonadetes, and Proteobacteria differed significantly among the three lakes, with more than half of these dominant phyla showing significant changes in abundance between seasons, while the DHVEG-6, Ignavibacteriae, Nitrospirae, Spirochaetes, and Zixibacteria varied considerably across the average submerged depths (n = 58 sites in total). Canonical correspondence analyses revealed that the fluctuation range of water level and pH were the most important factors influencing the microbial communities and their dominant microbiota, followed by total nitrogen, moisture, and total phosphorus in soil. These results suggest a suite of hydrological and soil physiochemical variables together governed the differential structuring of rhizospheric microbiota composition among different lakes, seasons, and sampling sites. This work thus provides valuable ecological information to better manage rhizospheric microbiota and protect the vegetation of subtropical lakeshore areas.
Zhang et al. (2020) Hydrological and soil physiochemical variables determine the rhizospheric microbiota in subtropical lakeshore areas. PeerJ 8:e10078 https://doi.org/10.7717/peerj.10078
Loss of inner kinetochore genes is associated with the transition to an unconventional point centromere in budding yeast
Background The genomic sequences of centromeres, as well as the set of proteins that recognize and interact with centromeres, are known to quickly diverge between lineages potentially contributing to post-zygotic reproductive isolation. However, the actual sequence of events and processes involved in the divergence of the kinetochore machinery is not known. The patterns of gene loss that occur during evolution concomitant with phenotypic changes have been used to understand the timing and order of molecular changes. Methods I screened the high-quality genomes of twenty budding yeast species for the presence of well-studied kinetochore genes. Based on the conserved gene order and complete genome assemblies, I identified gene loss events. Subsequently, I searched the intergenic regions to identify any un-annotated genes or gene remnants to obtain additional evidence of gene loss. Results My analysis identified the loss of four genes (NKP1, NKP2, CENPL/IML3 and CENPN/CHL4) of the inner kinetochore constitutive centromere-associated network (CCAN/also known as CTF19 complex in yeast) in both the Naumovozyma species for which genome assemblies are available. Surprisingly, this collective loss of four genes of the CCAN/CTF19 complex coincides with the emergence of unconventional centromeres in N. castellii and N. dairenensis. My study suggests a tentative link between the emergence of unconventional point centromeres and the turnover of kinetochore genes in budding yeast.
Vijay (2020) Loss of inner kinetochore genes is associated with the transition to an unconventional point centromere in budding yeast. PeerJ 8:e10085 https://doi.org/10.7717/peerj.10085