Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer
The members of the Nedd4-like E3 family participate in various biological processes. However, their role in clear cell renal cell carcinoma (ccRCC) is not clear. This study systematically analyzed the Nedd4-like E3 family members in ccRCC data sets from multiple publicly available databases. NEDD4L was identified as the only NEDD4 family member differentially expressed in ccRCC compared with normal samples. Bioinformatics tools were used to characterize the function of NEDD4L in ccRCC. It indicated that NEDD4L might regulate cellular energy metabolism by co-expression analysis, and subsequent gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A prognostic model developed by the LASSO Cox regression method showed a relatively good predictive value in training and testing data sets. The result revealed that NEDD4L was associated with biosynthesis and metabolism of ccRCC. Since NEDD4L is downregulated and dysregulation of metabolism is involved in tumor progression, NEDD4L might be a potential therapeutic target in ccRCC.
Zhao et al. (2021) Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer. PeerJ 9:e11880 https://doi.org/10.7717/peerj.11880
Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma
Mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in cell proliferation, survival, metabolism and immunity, was reportedly activated in various cancers. However, the clinical role of mTOR in renal cell carcinoma (RCC) is controversial. Here we detected the expression and prognosis of total mTOR and phosphorylated mTOR (p-mTOR) in clear cell RCC (ccRCC) patients, and explored the interactions between mTOR and immune infiltrates in ccRCC. The protein level of mTOR and p-mTOR was determined by western blotting (WB), and their expression was evaluated in 145 ccRCC and 13 non-tumor specimens by immunohistochemistry (IHC). The relationship to immune infiltration of mTOR was further investigated using TIMER and TISIDB databases, respectively. WB demonstrated the ratio of p-mTOR to mTOR was higher in ccRCC than adjacent specimens (n = 3), and IHC analysis elucidated that p-mTOR expression was positively correlated with tumor size, stage and metastasis status, and negatively correlated with cancer-specific survival (CSS). In univariate analysis, high grade, large tumor, advanced stage, metastasis, and high p-mTOR expression were recognized as prognostic factors of poorer CSS, and multivariate survival analysis elucidated that tumor stage, p-mTOR and metastasis were of prognostic value for CSS in ccRCC patients. Further TIMER and TISIDB analyses uncovered that mTOR gene expression was significantly associated with numerous immune cells and immunoinhibitors in patients with ccRCC. Collectively, these findings revealed p-mTOR was identified as an independent predictor of poor survival, and mTOR was associated with tumor immune infiltrates in ccRCC patients, which validated mTOR could be implicated in the initiation and progression of ccRCC.
Li et al. (2021) Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma. PeerJ 9:e11901 https://doi.org/10.7717/peerj.11901
Influence of tied-ridge-furrow with inorganic fertilizer on grain yield across semiarid regions of Asia and Africa: A meta-analysis
Background In semiarid areas, low productivity of crops has been attributed to lack of appropriate soil moisture conservation practices since droughts and soil erosion are rampant in most areas of this region. Consequently, ridge-furrow rainwater harvesting is widely used in these regions across the globe. Despite ridge-furrow being widely practiced, tied-ridge-furrow has not been extensively adopted by small-scale farmers in semi-arid regions. Consequently, the effectiveness of tied-ridge-furrow as a viable method of increasing crop yield has received less attention. Methodology For large-scale implementation, a detailed assessment of how ridge furrow, tied–ridge-furrow with fertilizer, tied-ridge-furrow with mulching and tied-ridge-furrow without mulching or fertilizer influence crop yield in different agro-environments under varying climatic conditions is needed. This study used the PRISMA guidelines to determine the impact of tied-ridge-furrow rainwater harvesting technique with mulching or fertilizer on sorghum (Sorghum bicolor) and pearl millet (Pennisetum glaucum) grain yields. Results Sorghum grain yield increased by 17% greater in tied-ridge-furrow without mulching or fertilizer in comparison to flat planting. This may be due to increase in soil organic carbon in the region (9 g kg−1). Grain yield of millet significantly increased by 20–40% in Africa from 18 study observations in tied-ridge-furrow with fertilizer application as compared to tied-ridge-furrow without mulching or fertilizer treatments. This might be due to the significant increase in total nitrogen by 13–42% in the soil at <50 mg kg−1 quantity which had an effect size of 469.14 [65.60, 872.67]. In terms of soil texture, grain yield of millet and sorghum significantly increased in heavy textured soils (clay loam, silt clay, and clay soils) with an effect size of 469.14 [65.60, 872.67] compared to light and medium-textured soils of zero effect sizes. Millet and sorghum grain yields in tied-ridge-furrow with mulching, on the other hand, were not significantly different from those in flat planting. This may be due to the mulching materials used in those tests. Conclusion In view of yields of sorghum and millet increased significantly by 32% and 17% in tied-ridge-furrow without mulching or fertilizer treatment compared to flat planting and tied-ridge-furrow with fertilizer treatment compared with tied-ridge-furrow without mulching or fertilizer treatment, respectively, this study recommend the use of fertilizers in a tied-ridge-furrow system to increase grain yield in semiarid areas compared to flat planting. Again, the study recommends more research on tied-ridge-furrow systems with other organic mulches and fertilizers in semiarid areas.
Mak-Mensah et al. (2021) Influence of tied-ridge-furrow with inorganic fertilizer on grain yield across semiarid regions of Asia and Africa: A meta-analysis. PeerJ 9:e11904 https://doi.org/10.7717/peerj.11904
Diverse methanogens, bacteria and tannase genes in the feces of the endangered volcano rabbit (Romerolagus diazi)
Background The volcano rabbit is the smallest lagomorph in Mexico, it is monotypic and endemic to the Trans-Mexican Volcanic Belt. It is classified as endangered by Mexican legislation and as critically endangered by the IUCN, in the Red List. Romerolagus diazi consumes large amounts of grasses, seedlings, shrubs, and trees. Pines and oaks contain tannins that can be toxic to the organisms which consume them. The volcano rabbit microbiota may be rich in bacteria capable of degrading fiber and phenolic compounds. Methods We obtained the fecal microbiome of three adults and one young rabbit collected in Coajomulco, Morelos, Mexico. Taxonomic assignments and gene annotation revealed the possible roles of different bacteria in the rabbit gut. We searched for sequences encoding tannase enzymes and enzymes associated with digestion of plant fibers such as cellulose and hemicellulose. Results The most representative phyla within the Bacteria domain were: Proteobacteria, Firmicutes and Actinobacteria for the young rabbit sample (S1) and adult rabbit sample (S2), which was the only sample not confirmed by sequencing to correspond to the volcano rabbit. Firmicutes, Actinobacteria and Cyanobacteria were found in adult rabbit samples S3 and S4. The most abundant phylum within the Archaea domain was Euryarchaeota. The most abundant genera of the Bacteria domain were Lachnoclostridium (Firmicutes) and Acinetobacter (Proteobacteria), while Methanosarcina predominated from the Archaea. In addition, the potential functions of metagenomic sequences were identified, which include carbohydrate and amino acid metabolism. We obtained genes encoding enzymes for plant fiber degradation such as endo 1,4 β-xylanases, arabinofuranosidases, endoglucanases and β-glucosidases. We also found 18 bacterial tannase sequences.
Montes-Carreto et al. (2021) Diverse methanogens, bacteria and tannase genes in the feces of the endangered volcano rabbit (Romerolagus diazi). PeerJ 9:e11942 https://doi.org/10.7717/peerj.11942
Non-linear genetic diversity and notable population differentiation caused by low gene flow of bermudagrass [Cynodon dactylon (L.) Pers.] along longitude gradients
Background Environmental variation related to ecological habitat is the main driver of plant adaptive divergence. Longitude plays an important role in the formation of plant population structure, indicating that environmental differentiation can significantly shape population structure. Methods Genetic diversity and population genetic structure were estimated using 105 expressed sequence tag-derived simple sequence repeat (EST-SSR) loci. A total of 249 C. dactylon (L.) Pers. (common bermudagrass) individuals were sampled from 13 geographic sites along the longitude (105°57′34″–119°27′06″E). Results There was no obvious linear trend of intra-population genetic diversity along longitude and the intra-population genetic diversity was not related to climate in this study. Low gene flow (Nm = 0.7701) meant a rich genetic differentiation among populations of C. dactylon along longitude gradients. Significantly positive Mantel correlation (r = 0.438, P = 0.001) was found between genetic distance and geographical interval while no significant partial Mantel correlation after controlling the effect of mean annual precipitation, which indicated geographic distance correlated with mean annual precipitation affect genetic distance. The genetic diversity of C. dactylon with higher ploidy level was higher than that with lower ploidy level and groups of individuals with higher ploidy level were separated further away by genetic distance from the lower ploidy levels. Understanding the different genetic bases of local adaptation comparatively between latitude and longitude is one of the core findings in the adaptive evolution of plants.
Zhang et al. (2021) Non-linear genetic diversity and notable population differentiation caused by low gene flow of bermudagrass [Cynodon dactylon (L.) Pers.] along longitude gradients. PeerJ 9:e11953 https://doi.org/10.7717/peerj.11953
A variable-rate quantitative trait evolution model using penalized-likelihood
In recent years it has become increasingly popular to use phylogenetic comparative methods to investigate heterogeneity in the rate or process of quantitative trait evolution across the branches or clades of a phylogenetic tree. Here, I present a new method for modeling variability in the rate of evolution of a continuously-valued character trait on a reconstructed phylogeny. The underlying model of evolution is stochastic diffusion (Brownian motion), but in which the instantaneous diffusion rate (σ2) also evolves by Brownian motion on a logarithmic scale. Unfortunately, it’s not possible to simultaneously estimate the rates of evolution along each edge of the tree and the rate of evolution of σ2 itself using Maximum Likelihood. As such, I propose a penalized-likelihood method in which the penalty term is equal to the log-transformed probability density of the rates under a Brownian model, multiplied by a ‘smoothing’ coefficient, λ, selected by the user. λ determines the magnitude of penalty that’s applied to rate variation between edges. Lower values of λ penalize rate variation relatively little; whereas larger λ values result in minimal rate variation among edges of the tree in the fitted model, eventually converging on a single value of σ2 for all of the branches of the tree. In addition to presenting this model here, I have also implemented it as part of my phytools R package in the function multirateBM. Using different values of the penalty coefficient, λ, I fit the model to simulated data with: Brownian rate variation among edges (the model assumption); uncorrelated rate variation; rate changes that occur in discrete places on the tree; and no rate variation at all among the branches of the phylogeny. I then compare the estimated values of σ2 to their known true values. In addition, I use the method to analyze a simple empirical dataset of body mass evolution in mammals. Finally, I discuss the relationship between the method of this article and other models from the phylogenetic comparative methods and finance literature, as well as some applications and limitations of the approach.
Revell (2021) A variable-rate quantitative trait evolution model using penalized-likelihood. PeerJ 9:e11997 https://doi.org/10.7717/peerj.11997
Virulence effector SidJ evolution in Legionella pneumophila is driven by positive selection and intragenic recombination
Effector proteins translocated by the Dot/Icm type IV secretion system determine the virulence of Legionella pneumophila (L. pneumophila). Among these effectors, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism mediated by another effector, SidJ. Host-cell calmodulin (CaM) activates SidJ to glutamylate the SidEs of ubiquitin (Ub) ligases and to make a balanced Ub ligase activity. Given the central role of SidJ in this regulatory process, studying the nature of evolution of sidJ is important to understand the virulence of L. pneumophila and the interaction between the bacteria and its hosts. By studying sidJ from a large number of L. pneumophila strains and using various molecular evolution algorithms, we demonstrated that intragenic recombination drove the evolution of sidJ and contributed to sidJ diversification. Additionally, we showed that four codons of sidJ which are located in the N-terminal (NTD) (codons 58 and 200) and C-terminal (CTD) (codons 868 and 869) domains, but not in the kinase domain (KD) had been subjected to strong positive selection pressure, and variable mutation profiles of these codons were identified. Protein structural modeling of SidJ provided possible explanations for these mutations. Codons 868 and 869 mutations might engage in regulating the interactions of SidJ with CaM through hydrogen bonds and affect the CaM docking to SidJ. Mutation in codon 58 of SidJ might affect the distribution of main-chain atoms that are associated with the interaction with CaM. In contrast, mutations in codon 200 might influence the α-helix stability in the NTD. These mutations might be important to balance Ub ligase activity for different L. pneumophila hosts. This study first reported that intragenic recombination and positive Darwinian selection both shaped the genetic plasticity of sidJ, contributing to a deeper understanding of the adaptive mechanisms of this intracellular bacterium to different hosts.
Zhan et al. (2021) Virulence effector SidJ evolution in Legionella pneumophila is driven by positive selection and intragenic recombination. PeerJ 9:e12000 https://doi.org/10.7717/peerj.12000
Estimating the impact of climate change on the potential distribution of Indo-Pacific humpback dolphins with species distribution model
As IUCN critically vulnerable species,the Indo-Pacific humpback dolphins (Sousa chinensis) have attracted great public attention in recent years. The threats of human disturbance and environmental pollution to this population have been documented extensively. However, research on the sensitivity of this species to climate change is lacking. To understand the effect of climate change on the potential distribution of Sousa chinensis, we developed a weighted ensemble model based on 82 occurrence records and six predictor variables (e.g., ocean depth, distance to shore, mean temperature, salinity, ice thickness, and current velocity). According to the true skill statistic (TSS) and the area under the receiver operating characteristic curve (AUC), our ensemble model presented higher prediction precision than most of the single-algorithm models. It also indicated that ocean depth and distance to shore were the most important predictors in shaping the distribution patterns. The projections for the 2050s and 2100s from our ensemble model indicated a severe adverse impact of climate change on the Sousa chinensis habitat. Over 75% and 80% of the suitable habitat in the present day will be lost in all representative concentration pathway emission scenarios (RCPS) in the 2050s and 2100s, respectively. With the increased numbers of records of stranding and deaths of Sousa chinensis in recent years, strict management regulations and conservation plans are urgent to safeguard the current suitable habitats. Due to habitat contraction and poleward shift in the future, adaptive management strategies, including designing new reserves and adjusting the location and range of reserves according to the geographical distribution of Sousa chinensis, should be formulated to minimize the impacts of climate change on this species.
Fu et al. (2021) Estimating the impact of climate change on the potential distribution of Indo-Pacific humpback dolphins with species distribution model. PeerJ 9:e12001 https://doi.org/10.7717/peerj.12001
On the use of sequence-quality information in OTU clustering
Background High-throughput sequencing has become an essential technology in life science research. Despite continuous improvements in technology, the produced sequences are still not entirely accurate. Consequently, the sequences are usually equipped with error probabilities. The quality information is already employed to find better solutions to a number of bioinformatics problems (e.g. read mapping). Data processing pipelines benefit in particular (especially when incorporating the quality information early), since enhanced outcomes of one step can improve all subsequent ones. Preprocessing steps, thus, quite regularly consider the sequence quality to fix errors or discard low-quality data. Other steps, however, like clustering sequences into operational taxonomic units (OTUs), a common task in the analysis of microbial communities, are typically performed without making use of the available quality information. Results In this paper, we present quality-aware clustering methods inspired by quality-weighted alignments and model-based denoising, and explore their applicability to OTU clustering. We implemented the quality-aware methods in a revised version of our de novo clustering tool GeFaST and evaluated their clustering quality and performance on mock-community data sets. Quality-weighted alignments were able to improve the clustering quality of GeFaST by up to 10%. The examination of the model-supported methods provided a more diverse picture, hinting at a narrower applicability, but they were able to attain similar improvements. Considering the quality information enlarged both runtime and memory consumption, even though the increase of the former depended heavily on the applied method and clustering threshold. Conclusions The quality-aware methods expand the iterative, de novo clustering approach by new clustering and cluster refinement methods. Our results indicate that OTU clustering constitutes yet another analysis step benefiting from the integration of quality information. Beyond the shown potential, the quality-aware methods offer a range of opportunities for fine-tuning and further extensions.
Müller et al. (2021) On the use of sequence-quality information in OTU clustering. PeerJ 9:e11717 https://doi.org/10.7717/peerj.11717
Common motor patterns of asymmetrical and symmetrical bipedal gaits
Background Synergy modules have been used to describe activation of lower limb muscles during locomotion and hence to understand how the system controls movement. Walking and running have been shown shared synergy patterns suggesting common motor control of both symmetrical gaits. Unilateral skipping, an equivalent gait to the quadrupedal gallop in humans, has been defined as the third locomotion paradigm but the use by humans is limited due to its high metabolic cost. Synergies in skipping have been little investigated. In particular, to the best of our knowledge, the joint study of both trailing and leading limbs has never been addressed before. Research question How are organized muscle activation patterns in unilateral skipping? Are they organized in the same way that in symmetrical gaits? If yes, which are the muscle activation patterns in skipping that make it a different gait to walking or running? In the present research, we investigate if there are shared control strategies for all gaits in locomotion. Addressing these questions in terms of muscle synergies could suggest possible determinants of the scarce use of unilateral skipping in humans. Methods Electromyographic data of fourteen bilateral muscles were collected from volunteers while performing walking, running and unilateral skipping on a treadmill. Also, spatiotemporal gait parameters were computed from 3D kinematics. The modular composition and activation timing extracted by non-negative matrix factorization were analyzed to detect similarities and differences among symmetrical gaits and unilateral skipping. Results Synergy modules showed high similarity throughout the different gaits and between trailing and leading limbs during unilateral skipping. The synergy associated with the propulsion force operated by calf muscles was anticipated in bouncing gaits. Temporal features of synergies in the leading leg were very similar to those observed for running. The different role of trailing and leading legs in unilateral skipping was reflected by the different timing in two modules. Activation for weight acceptance was anticipated and extended in the trailing leg, preparing the body for landing impact after the flight phase. A different behaviour was detected in the leading leg, which only deals with a pendular weight transference. Significance The evidence gathered in this work supports the hypothesis of shared modules among symmetrical and asymmetrical gaits, suggesting a common motor control despite of the infrequent use of unilateral skipping in humans. Unilateral skipping results from phase-shifted activation of similar muscular groups used in symmetrical gaits, without the need for new muscular groups. The high and anticipated muscle activation in the trailing leg for landing could be the key distinctive event of unilateral skipping.
Pequera et al. (2021) Common motor patterns of asymmetrical and symmetrical bipedal gaits. PeerJ 9:e11970 https://doi.org/10.7717/peerj.11970