Identification and validation of prognostic signature for breast cancer based on genes potentially involved in autophagy
We aimed to identify prognostic signature based on autophagy-related genes (ARGs) for breast cancer patients. The datasets of breast cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to construct multiple-ARG risk signature. In total, 32 ARGs were identified as differentially expressed between tumors and adjacent normal tissues based on TCGA. Six ARGs (IFNG, TP63, PPP1R15A, PTK6, EIF4EBP1 and NKX2-3) with non-zero coefficient were selected from the 32 ARGs using LASSO regression. The 6-ARG signature divided patients into high-and low-risk group. Survival analysis indicated that low-risk group had longer survival time than high-risk group. We further validated the 6-ARG signature using dataset from GEO and found similar results. We analyzed the associations between ARGs and breast cancer survival in TCGA and nine GEO datasets, and obtained 170 ARGs with significant associations. EIF4EBP1, FOS and FAS were the top three ARGs with highest numbers of significant associations. EIF4EBP1 may be a key ARG which had a higher expression level in patients with more malignant molecular subtypes and higher grade breast cancer. In conclusion, our 6-ARG signature was of significance in predicting of overall survival of patients with breast cancer. EIF4EBP1 may be a key ARG associated with breast cancer survival.
Zhong et al. (2020) Identification and validation of prognostic signature for breast cancer based on genes potentially involved in autophagy. PeerJ 8:e9621 https://doi.org/10.7717/peerj.9621
Auditory processing in the zebra finch midbrain: single unit responses and effect of rearing experience
In birds the auditory system plays a key role in providing the sensory input used to discriminate between conspecific and heterospecific vocal signals. In those species that are known to learn their vocalizations, for example, songbirds, it is generally considered that this ability arises and is manifest in the forebrain, although there is no a priori reason why brainstem components of the auditory system could not also play an important part. To test this assumption, we used groups of normal reared and cross-fostered zebra finches that had previously been shown in behavioural experiments to reduce their preference for conspecific songs subsequent to cross fostering experience with Bengalese finches, a related species with a distinctly different song. The question we asked, therefore, is whether this experiential change also changes the bias in favour of conspecific song displayed by auditory midbrain units of normally raised zebra finches. By recording the responses of single units in MLd to a variety of zebra finch and Bengalese finch songs in both normally reared and cross-fostered zebra finches, we provide a positive answer to this question. That is, the difference in response to conspecific and heterospecific songs seen in normal reared zebra finches is reduced following cross-fostering. In birds the virtual absence of mammalian-like cortical projections upon auditory brainstem nuclei argues against the interpretation that MLd units change, as observed in the present experiments, as a result of top-down influences on sensory processing. Instead, it appears that MLd units can be influenced significantly by sensory inputs arising directly from a change in auditory experience during development.
Logerot et al. (2020) Auditory processing in the zebra finch midbrain: single unit responses and effect of rearing experience. PeerJ 8:e9363 https://doi.org/10.7717/peerj.9363
The effects of humic substances on DNA isolation from soils
Background Humic substances (HS) are compounds with a complicated structure, present in the humus soil layer, water, lake sediments, peat, brown coal and shales. Due to their similar physicochemical properties to DNA, they may have an adverse effect on the subsequent use of the isolated material. The main aim of this research was to examine the effect of HS on DNA isolation depending on the soil type and land use, taking into account the spectroscopic full characteristics of HS fractions. Methods The research was conducted on eight types of soil sample. Soils represented the most important Soil Reference Groups for temperate climates: Fluvisols, Regosols, Cambisols, Arenosols, Histosols and Luvisols. Soil samples were also collected from areas diversified in terms of use: arable land, grassland and forest. The extraction of HS fractions was performed using the procedure recommended by the International HS Society. The fractional composition of HS was characterized by UV–Vis and fluorescence methods. Soil DNA is extracted by direct cell lysis in the using a CTAB-based method with a commonly-used commercial soil DNA isolation kit. The basis for assessing the quantity and quality of extracted DNA was the Polymerase chain reaction (PCR) reaction since the analysis of soil DNA often relies on the use of PCR to study soil microorganisms. Results Based on the results, it can be concluded that in the presence of a high concentration of HS, the isolated DNA was low quality and the additional purification procedure was necessary. Despite the differentiation of the internal structure of HS fractions, the decisive factor in the efficiency of DNA isolation from soil samples was the total carbon content in HS. Reduced DNA yields can significantly constrain PCR detection limits to levels inadequate for metagenomic analysis, especially from humus-rich soils.
Wnuk et al. (2020) The effects of humic substances on DNA isolation from soils. PeerJ 8:e9378 https://doi.org/10.7717/peerj.9378
Effectiveness of non-lethal predator deterrents to reduce livestock losses to leopard attacks within a multiple-use landscape of the Himalayan region
Lethal measures are widely adopted by local communities and governments to manage human-wildlife conflicts. Such measures lead to large scale decline of carnivore populations globally with trophic cascades on ecosystems and questionable impacts on human-wildlife conflicts. Mitigating human-carnivore conflicts through non-lethal measures will protect endangered predators and secure livelihoods. However, information on the effectiveness of such measures are extremely limited and hence cannot be applied in developing scientific evidence. Further to develop human-carnivore coexistence models, it is important for local community members, biologists and wildlife managers to actively participate in conservation programs. We evaluated the response of a non-lethal visual deterrent (i.e. fox lights) to deter leopard attacks on livestock within a multiple-use landscape of western Himalaya through community engagement. We monitored 16 experimental sites and 17 control sites within 27 villages and recorded data on livestock depredation by leopards between April 2018 to April 2019. A multivariate analysis was conducted to determine the influence of landscape predictors and animal husbandry practices on livestock depredation by leopards within the vicinity of human settlements. We found that visual deterrents discouraged common leopards to predate on livestock (cows and goats). We also demonstrated that community based conservation initiatives are successful in mitigating human-carnivore conflicts within large semi-natural landscapes. We suggest developing site specific coexistence strategies and adopting non-lethal measures to safeguard carnivores, livestock and humans within shared landscapes.
Naha et al. (2020) Effectiveness of non-lethal predator deterrents to reduce livestock losses to leopard attacks within a multiple-use landscape of the Himalayan region. PeerJ 8:e9544 https://doi.org/10.7717/peerj.9544
A cross-sectional assessment of the relationship between sedative medication and anticholinergic medication use and the movement behaviour of older adults living in residential aged care
Objectives Medications with anticholinergic or sedative effects are frequently used by older people but can increase risk of falls and adverse events; however, less is known about their effect on movement behaviour. Here we examine the cross-sectional association between medication use and movement behaviour in older adults living in residential aged care. Materials and Methods Twenty-eight older adults living in residential aged care in metropolitan Australia participated. Medication data were collected from participants’ medical charts and sedative load and anticholinergic burden were determined. Seven-day movement behaviour was objectively assessed by a wrist-worn triaxial accelerometer. Raw accelerations were converted to sleep, sedentary time, and time in light, moderate, and moderate-to-vigorous physical activity. To explore the relationship between medication and movement behaviour, Spearman’s Rho correlations were conducted, as the data were not normally distributed. Results Analyses indicated that while anticholinergic burden was not associated with movement behaviour, sedative load was negatively correlated with a number of variables, accounting for 14% variance in moderate-to-vigorous physical activity (MVPA), and 17% in the bout length of MVPA (p < .02). Conclusion The findings of this study showed a negative association between sedative load, due to medicines, and an individual’s movement behaviour. The impact of this could be a reduction in the ability of this population to maintain or improve their functional mobility, which may overshadow any benefits of the medicine in some circumstances.
Parfitt et al. (2020) A cross-sectional assessment of the relationship between sedative medication and anticholinergic medication use and the movement behaviour of older adults living in residential aged care. PeerJ 8:e9605 https://doi.org/10.7717/peerj.9605
Disentangling biological variability and taphonomy: shape analysis of the limb long bones of the sauropodomorph dinosaur Plateosaurus
Sauropodomorph dinosaurs constitute a well-studied clade of dinosaurs, notably because of the acquisition of gigantism within this group. The genus Plateosaurus is one of the best-known sauropodomorphs, with numerous remains from various localities. Its tumultuous taxonomic history suggests the relevance of addressing its intrageneric shape variability, mixed with taphonomic modifications of the original bone shape. Here we investigate quantitatively the morphological variation of Plateosaurus occurring at the genus level by studying the shape variation of a sample of limb long bones. By means of 3D geometric morphometrics, the analysis of the uncorrelated variation permits separation of the variation estimated as obviously taphonomically influenced from the more biologically plausible variation. Beyond the dominant taphonomic signal, our approach permits interpretation of the most biologically plausible features, even on anatomical parts influenced by taphonomic deformations. Those features are thus found on a quantitative basis from the variation of samples containing fossil specimens, by taking the impact of taphonomy into account, which is paramount in order to avoid making biologically ambiguous interpretations.
Lefebvre et al. (2020) Disentangling biological variability and taphonomy: shape analysis of the limb long bones of the sauropodomorph dinosaur Plateosaurus. PeerJ 8:e9359 https://doi.org/10.7717/peerj.9359
Morphological changes in the lower Lancang River due to extensive human activities
Background Morphological changes in river beds determine the risk for soil erosion within floodplain areas. At present, little is known about river morphological changes in high-altitude mountainous area influenced by extensive human activities. The study has important reference value for clarifying the morphological changes of mountainous rivers due to extensive human activities. Methods Based on the long-term multi-source remote sensing image data, we analyzed morphological changes in the lower Lancang River (LCR) in Southwest China at regional and local scales, and determined their influencing factors. Visual interpretation is used to extract the information and unify the interpretation standards of various localities, mainly including water bodies, sandbars, shorelines and beaches. Based on high-resolution remote sensing images, we analyzed the planforms, erosion and accretion conditions in Jinghongba (JHB) reach and Ganlanba (GLB) reach. Results Our results showed that: (1) during 1993–2016, the planforms of Jinghongba and Ganlanba in the wide valley of the lower LCR changed significantly, (2) In the interval 1993 to 2016, the JHB reach exhibited extensive erosion, with the right bank more eroded seriously than the left bank, and an erosion area of 0.36 km2. The erosion area of the GLB reach was 0.33 km2, with accretion area of 0.61 km2. The right bank was dominated by erosion, while the left bank by sedimentation; (3) Morphological changes in JHB and GLB reches were the result of the combined effects of cascade hydropower development, river regulation, and sand-mining in the river. The results improved the understanding of riverbed evolution, and could help guide sediment management in mountainous areas influenced by extensive human activities.
Spatial and Geographic Information Science
Wang et al. (2020) Morphological changes in the lower Lancang River due to extensive human activities. PeerJ 8:e9471 https://doi.org/10.7717/peerj.9471
The rule-based insensitivity effect: a systematic review
Background Adherence to inaccurate rules has been viewed as a characteristic of human rule-following (i.e., the rule-based insensitivity effect; RBIE) and has been thought to be exacerbated in individuals suffering from clinical conditions. This review intended to systematically examine these claims in adult populations. Methodology We screened 1464 records which resulted in 21 studies that were deemed eligible for inclusion. Each of these studies was examined to determine: (1) if there is evidence for the RBIE in adults and (2) if this effect is larger in those suffering from psychological problems compared to their non-suffering counterparts. In addition, we investigated how (3) different operationalizations of the RBIE, and (4) the external validity and risks of bias of the experimental work investigating this effect, might influence the conclusions that can be drawn from the current systematic review. Results (1) Out of the 20 studies that were relevant for examining if evidence exists for the RBIE in adults, only 11 were eligible for vote counting. Results showed that after the contingency change, the rule groups were more inclined to demonstrate behavior that was reinforced before the change, compared to their non-instructed counterparts. Critically, however, none of these studies examined if their no-instructions group was an adequate comparison group. As a result, this made it difficult to determine whether the effects that were observed in the rule groups could be attributed to the rules or instructions that were manipulated in those experiments. (2) The single study that was relevant for examining if adults suffering from psychological problems demonstrated larger levels of the RBIE, compared to their non-clinical counterparts, was not eligible for vote counting. As a result, no conclusions could be drawn about the extent to which psychological problems moderated the RBIE in that study. (3) Similar procedures and tasks have been used to examine the RBIE, but their precise parameters differ across studies; and (4) most studies report insufficient information to evaluate all relevant aspects affecting their external validity and risks of bias. Conclusions Despite the widespread appeal that the RBIE has enjoyed, this systematic review indicates that, at present, only preliminary evidence exists for the idea that adults demonstrate the RBIE and no evidence is available to assume that psychological problems exacerbate the RBIE in adults. The systematic review was registered in PROSPERO (CRD42018088210).
Kissi et al. (2020) The rule-based insensitivity effect: a systematic review. PeerJ 8:e9496 https://doi.org/10.7717/peerj.9496
Analysis of prognostic genes in the tumor microenvironment of lung adenocarcinoma
Background Prognostic genes in the tumor microenvironment play an important role in immune biological processes and the response of cancer to immunotherapy. Thus, we aimed to assess new biomarkers that are associated with immune/stromal cells in lung adenocarcinomas (LUAD) using the ESTIMATE algorithm, which also significantly affects the prognosis of cancer. Methods The RNA sequencing (RNA-Seq) and clinical data of LUAD were downloaded from the the Cancer Genome Atlas (TCGA ). The immune and stromal scores were calculated for each sample using the ESTIMATE algorithm. The LUAD gene chip expression profile data and the clinical data (GSE37745, GSE11969, and GSE50081) were downloaded from the Gene Expression Omnibus (GEO) for subsequent validation analysis. Differentially expressed genes were calculated between high and low score groups. Univariate Cox regression analysis was performed on differentially expressed genes (DEGs) between the two groups to obtain initial prognosis genes. These were verified by three independent LUAD cohorts from the GEO database. Multivariate Cox regression was used to identify overall survival-related DEGs. UALCAN and the Human Protein Atlas were used to analyze the mRNA /protein expression levels of the target genes. Immune cell infiltration was evaluated using the Tumor Immune Estimation Resource (TIMER) and CIBERSORT methods, and stromal cell infiltration was assessed using xCell. Results In this study, immune scores and stromal scores are significantly associated with the clinical characteristics of LUAD, including T stage, M stage, pathological stage, and overall survival time. 530 DEGs (18 upregulated and 512 downregulated) were found to coexist in the difference analysis with the immune scores and stromal scores subgroup. Univariate Cox regression analysis showed that 286 of the 530 DEGs were survival-related genes (p < 0.05). Of the 286 genes initially identified, nine prognosis-related genes (CSF2RB, ITK, FLT3, CD79A, CCR4, CCR6, DOK2, AMPD1, and IGJ) were validated from three separate LUAD cohorts. In addition, functional analysis of DEGs also showed that various immunoregulatory molecular pathways, including regulation of immune response and the chemokine signaling pathways, were involved. Five genes (CCR6, ITK, CCR4, DOK2, and AMPD1) were identified as independent prognostic indicators of LUAD in specific data sets. The relationship between the expression levels of these genes and immune genes was assessed. We found that CCR6 mRNA and protein expression levels of LUAD were greater than in normal tissues. We evaluated the infiltration of immune cells and stromal cells in groups with high and low levels of expression of CCR6 in the TCGA LUAD cohort. In summary, we found a series of prognosis-related genes that were associated with the LUAD tumor microenvironment.
Xu et al. (2020) Analysis of prognostic genes in the tumor microenvironment of lung adenocarcinoma. PeerJ 8:e9530 https://doi.org/10.7717/peerj.9530
Plastid genomics of Nicotiana (Solanaceae): insights into molecular evolution, positive selection and the origin of the maternal genome of Aztec tobacco (Nicotiana rustica)
Species of the genus Nicotiana (Solanaceae), commonly referred to as tobacco plants, are often cultivated as non-food crops and garden ornamentals. In addition to the worldwide production of tobacco leaves, they are also used as evolutionary model systems due to their complex development history tangled by polyploidy and hybridization. Here, we assembled the plastid genomes of five tobacco species: N. knightiana, N. rustica, N. paniculata, N. obtusifolia and N. glauca. De novo assembled tobacco plastid genomes had the typical quadripartite structure, consisting of a pair of inverted repeat (IR) regions (25,323–25,369 bp each) separated by a large single-copy (LSC) region (86,510–86,716 bp) and a small single-copy (SSC) region (18,441–18,555 bp). Comparative analyses of Nicotiana plastid genomes with currently available Solanaceae genome sequences showed similar GC and gene content, codon usage, simple sequence and oligonucleotide repeats, RNA editing sites, and substitutions. We identified 20 highly polymorphic regions, mostly belonging to intergenic spacer regions (IGS), which could be suitable for the development of robust and cost-effective markers for inferring the phylogeny of the genus Nicotiana and family Solanaceae. Our comparative plastid genome analysis revealed that the maternal parent of the tetraploid N. rustica was the common ancestor of N. paniculata and N. knightiana, and the later species is more closely related to N. rustica. Relaxed molecular clock analyses estimated the speciation event between N. rustica and N. knightiana appeared 0.56 Ma (HPD 0.65–0.46). Biogeographical analysis supported a south-to-north range expansion and diversification for N. rustica and related species, where N. undulata and N. paniculata evolved in North/Central Peru, while N. rustica developed in Southern Peru and separated from N. knightiana, which adapted to the Southern coastal climatic regimes. We further inspected selective pressure on protein-coding genes among tobacco species to determine if this adaptation process affected the evolution of plastid genes. These analyses indicate that four genes involved in different plastid functions, including DNA replication (rpoA) and photosynthesis (atpB, ndhD and ndhF), came under positive selective pressure as a result of specific environmental conditions. Genetic mutations in these genes might have contributed to better survival and superior adaptations during the evolutionary history of tobacco species.
Mehmood et al. (2020) Plastid genomics of Nicotiana (Solanaceae): insights into molecular evolution, positive selection and the origin of the maternal genome of Aztec tobacco (Nicotiana rustica). PeerJ 8:e9552 https://doi.org/10.7717/peerj.9552