Locating ligand binding sites in G-protein coupled receptors using combined information from docking and sequence conservation
GPCRs (G-protein coupled receptors) are the largest family of drug targets and share a conserved structure. Binding sites are unknown for many important GPCR ligands due to the difficulties of GPCR recombinant expression, biochemistry, and crystallography. We describe our approach, ConDockSite, for predicting ligand binding sites in class A GPCRs using combined information from surface conservation and docking, starting from crystal structures or homology models. We demonstrate the effectiveness of ConDockSite on crystallized class A GPCRs such as the beta2 adrenergic and A2A adenosine receptors. We also demonstrate that ConDockSite successfully predicts ligand binding sites from high-quality homology models. Finally, we apply ConDockSite to predict the ligand binding sites on a structurally uncharacterized GPCR, GPER, the G-protein coupled estrogen receptor. Most of the sites predicted by ConDockSite match those found in other independent modeling studies. ConDockSite predicts that four ligands bind to a common location on GPER at a site deep in the receptor cleft. Incorporating sequence conservation information in ConDockSite overcomes errors introduced from physics-based scoring functions and homology modeling.
Vidad et al. (2021) Locating ligand binding sites in G-protein coupled receptors using combined information from docking and sequence conservation. PeerJ 9:e12219 https://doi.org/10.7717/peerj.12219
Vitamin D serum levels and non-melanoma skin cancer risk
Background Skin cancer is one of the common malignancies. There is sufficient evidence that sunlight (ultraviolet radiation) contributes to the development of skin cancer, but there is also evidence that relates adequate serum levels of vitamin D produced on the skin by the action of ultraviolet radiation with the decreased risk of various types of cancers, including skin cancer. The aim of this study was to investigate the association of vitamin D serum levels among patients with non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) and controls. Methods A prospective observational case-control study was conducted in a sample of 84 subjects in Extremadura (Spain). Forty-one patients with histologically diagnosed basal cell carcinomas and squamous cell carcinomas and 43 healthy controls were randomly chosen to assess whether vitamin D (25(OH)D3) serum level, age and sex were related to non-melanoma skin cancer and to determine the possible risk of this type of skin cancer for these variables. Results When analysing serum vitamin D levels, we ensured that all our subjects, both cases and controls, had normal or low serum vitamin D levels, even though the samples were taken during months with the highest solar irradiance in our region. It is striking in our results that there was a higher percentage of subjects with deficits of vitamin D who did not have skin cancer (66%) than patients with deficits with these types of skin cancers (34%). When adjusting the model for age and sex, vitamin D values above 18 ng/ml increased the risk of suffering from non-melanoma skin cancer by nearly 7-fold (aOR: 6.94, 95% CI [1.55–31.11], p = 0.01). Conclusions Despite the controversial data obtained in the literature, our results suggest that lower levels of vitamin D may be related to a reduced incidence of non-melanoma skin cancer.
Morgado-Águila et al. (2021) Vitamin D serum levels and non-melanoma skin cancer risk. PeerJ 9:e12234 https://doi.org/10.7717/peerj.12234
Pristimantis achupalla sp. n., a new minute species of direct-developing frog (Amphibia, Anura, Strabomantidae) inhabiting bromeliads of the montane forest of the Amazonian Andes of Puno, Peru
We describe a new species of bromeliad-dwelling Pristimantis from primary montane forest (2,225 m a.s.l.) in southern Peru. The type locality is near Thiuni, in the Department of Puno (province of Carabaya) in the upper watershed of a tributary of the Inambari River. Pristimantis achupalla sp. n. is characterized by a snout-vent length of 10.0–12.8 mm in adult males (n = 4), unknown in adult females, and is compared morphologically and genetically with species in the Pristimantis lacrimosus group, and with other similar species of Pristimantis. The new species is characterized by having skin on dorsum and flanks rugose, green brownish color, distinctive scapular folds, subacuminate or acuminate snout profile, upper eyelid bearing two or three subconical tubercles and some rounded tubercles, rostral papilla, flanks light brown to brown, with irregular dark brown marks.
Ttito et al. (2021) Pristimantis achupalla sp. n., a new minute species of direct-developing frog (Amphibia, Anura, Strabomantidae) inhabiting bromeliads of the montane forest of the Amazonian Andes of Puno, Peru. PeerJ 9:e11878 https://doi.org/10.7717/peerj.11878
A predictive model for the ichnological suitability of the Jezero crater, Mars: searching for fossilized traces of life-substrate interactions in the 2020 Rover Mission Landing Site
Ichnofossils, the fossilized products of life-substrate interactions, are among the most abundant biosignatures on Earth and therefore they may provide scientific evidence of potential life that may have existed on Mars. Ichnofossils offer unique advantages in the search for extraterrestrial life, including the fact that they are resilient to processes that obliterate other evidence for past life, such as body fossils, as well as chemical and isotopic biosignatures. The goal of this paper is evaluating the suitability of the Mars 2020 Landing Site for ichnofossils. To this goal, we apply palaeontological predictive modelling, a technique used to forecast the location of fossil sites in uninvestigated areas on Earth. Accordingly, a geographic information system (GIS) of the landing site is developed. Each layer of the GIS maps the suitability for one or more ichnofossil types (bioturbation, bioerosion, biostratification structures) based on an assessment of a single attribute (suitability factor) of the Martian environment. Suitability criteria have been selected among the environmental attributes that control ichnofossil abundance and preservation in 18 reference sites on Earth. The goal of this research is delivered through three predictive maps showing which areas of the Mars 2020 Landing Site are more likely to preserve potential ichnofossils. On the basis of these maps, an ichnological strategy for the Perseverance rover is identified, indicating (1) 10 sites on Mars with high suitability for bioturbation, bioerosion and biostratification ichnofossils, (2) the ichnofossil types, if any, that are more likely to be present at each site, (3) the most efficient observation strategy for detecting eventual ichnofossils. The predictive maps and the ichnological strategy can be easily integrated in the existing plans for the exploration of the Jezero crater, realizing benefits in life-search efficiency and cost-reduction.
Spatial and Geographic Information Science
Baucon et al. (2021) A predictive model for the ichnological suitability of the Jezero crater, Mars: searching for fossilized traces of life-substrate interactions in the 2020 Rover Mission Landing Site. PeerJ 9:e11784 https://doi.org/10.7717/peerj.11784
Dietary effects on fitness in captive-reared Hawaiian tree snails
The native terrestrial snail fauna of the Hawaiian Islands faces numerous threats that have led to severe range reductions, population declines, and extinction of species. With the continued declines of many wild populations, a crucial component of preserving Hawaiian terrestrial snail biodiversity is through captive rearing programs, like that implemented by the Hawai‘i Department of Land and Natural Resources Snail Extinction Prevention Program. Rare and endangered tree snails in the family Achatinellidae, which feed on epiphytic microbial communities, are maintained in captivity with a diet that includes native vegetation brought in from nearby forests, as well as a cultured fungus originally isolated from native host trees. Recent mortality events in lab populations have been attributed to wild-gathered vegetation. These events have increased interest in developing a completely manufactured or cultured diet that would eliminate the need for exposure to wild-gathered plants. This study compared survival and egg production in Auriculella diaphana provided with lab-cultured fungus, and those provided with wild vegetation. We compared the number of eggs laid and number of deaths among three treatments: (1) wild collected vegetation only; (2) wild vegetation supplemented with laboratory-cultured fungus; and (3) laboratory cultured fungus only. Mortality did not significantly differ among treatments, but the number of eggs laid was significantly higher in snails provided wild vegetation and cultured fungus (F = 24.998; P < 0.001), compared with those provided with only wild vegetation (t = 1.88, P = 0.032) or only cultured fungus (t = 4.530, P = 0.004). Our results suggest: (1) the existing strain of cultured fungus alone is not sufficient to maintain captive-reared snail populations; (2) the additional energy or calcium provided by the cultured fungus appears to enhance egg reproduction in captive-reared populations; (3) the presence or absence of live vegetation influences snail behavior, including aestivation and egg laying. These results highlight the importance of ongoing research to culture additional species of fungi at a rate that could support captive-reared populations, as the diversity of fungi present in wild epiphytic microbial communities may be important for snail reproductive health.
Strouse et al. (2021) Dietary effects on fitness in captive-reared Hawaiian tree snails. PeerJ 9:e11789 https://doi.org/10.7717/peerj.11789
A four-gene prognostic signature for predicting the overall survival of patients with lung adenocarcinoma
Background The prognosis of patients for lung adenocarcinoma (LUAD) is known to vary widely; the 5-year overall survival rate is just 63% even for the pathological IA stage. Thus, in order to identify high-risk patients and facilitate clinical decision making, it is vital that we identify new prognostic markers that can be used alongside TNM staging to facilitate risk stratification. Methods We used mRNA expression from The Cancer Genome Atlas (TCGA) cohort to identify a prognostic gene signature and combined this with clinical data to develop a predictive model for the prognosis of patients for lung adenocarcinoma. Kaplan-Meier curves, Lasso regression, and Cox regression, were used to identify specific prognostic genes. The model was assessed via the area under the receiver operating characteristic curve (AUC-ROC) and validated in an independent dataset (GSE50081) from the Gene Expression Omnibus (GEO). Results Our analyses identified a four-gene prognostic signature (CENPH, MYLIP, PITX3, and TRAF3IP3) that was associated with the overall survival of patients with T1-4N0-2M0 in the TCGA dataset. Multivariate regression suggested that the total risk score for the four genes represented an independent prognostic factor for the TCGA and GEO cohorts; the hazard ratio (HR) (high risk group vs low risk group) were 2.34 (p < 0.001) and 2.10 (p = 0.017). Immune infiltration estimations, as determined by an online tool (TIMER2.0) showed that CD4+ T cells were in relative abundance in the high risk group compared to the low risk group in both of the two cohorts (both p < 0.001). We established a composite prognostic model for predicting OS, combined with risk-grouping and clinical factors. The AUCs for 1-, 3-, 5- year OS in the training set were 0.750, 0.737, and 0.719; and were 0.645, 0.766, and 0.725 in the validation set. The calibration curves showed a good match between the predicted probabilities and the actual probabilities. Conclusions We identified a four-gene predictive signature which represents an independent prognostic factor and can be used to identify high-risk patients from different TNM stages of LUAD. A new prognostic model that combines a prognostic gene signature with clinical features exhibited better discriminatory ability for OS than traditional TNM staging.
Liu et al. (2021) A four-gene prognostic signature for predicting the overall survival of patients with lung adenocarcinoma. PeerJ 9:e11911 https://doi.org/10.7717/peerj.11911
Organic farming practices change the soil bacteria community, improving soil quality and maize crop yields
Background The importance of organic farming has increased through the years to promote food security allied with minimal harm to the ecosystem. Besides the environmental benefits, a recurring problem associated with organic management is the unsatisfactory yield. A possible solution may rely on the soil microbiome, which presents a crucial role in the soil system. Here, we aimed to evaluate the soil bacterial community structure and composition under organic and conventional farming, considering the tropical climate and tropical soil. Methodology Our organic management treatments were composed by composted poultry manure and green manure with Bokashi. Both organic treatments were based on low nitrogen inputs. We evaluated the soil bacterial community composition by high-throughput sequencing of 16S rRNA genes, soil fertility, and soil enzyme activity in two organic farming systems, one conventional and the last transitional from conventional to organic. Results We observed that both organic systems evaluated in this study, have higher yield than the conventional treatment, even in a year with drought conditions. These yield results are highly correlated with changes in soil chemical properties and enzymatic activity. The attributes pH, Ca, P, alkaline phosphatase, and β- glucosidase activity are positively correlated with organic systems, while K and Al are correlated with conventional treatment. Also, our results show in the organic systems the changes in the soil bacteria community, being phyla Acidobacteria, Firmicutes, Nitrospirae, and Rokubacteria the most abundant. These phyla were correlated with soil biochemical changes in the organic systems, helping to increase crop yields. Conclusion Different organic management systems, (the so-called natural and organic management systems, which use distinct organic sources), shift the soil bacterial community composition, implying changes in their functionalities. Also, our results contributed to the identification of target bacterial groups and changes in soil chemical properties and enzymatic activity in a trophic organic farming system, which may contribute to higher crop yields.
Durrer et al. (2021) Organic farming practices change the soil bacteria community, improving soil quality and maize crop yields. PeerJ 9:e11985 https://doi.org/10.7717/peerj.11985
Near-natural transformation of Pinus tabuliformis better improve soil nutrients and soil microbial community
Pinus tabulaeformis plantations have been established around northern China to restore degraded land and provide timber or fuelwood. In recent years, widely distributed monoculture P. tabulaeformis forests have been transformed into mixed forests due to various ecological problems. However, the current research on the influence of near-natural transformation of P. tabulaeformis on soil microbial diversity and community composition remains limited. Therefore, we examined the effect of forest conversion from monoculture Pinus tabuliformis (PT) to P. tabuliformis-Armeniaca vulgaris (PTAU), P. tabuliformis - Robinia pseudoacacia (PTRP), P. tabuliformis - Vitex negundo L. var. heterophylla (PTVN) forests on soil microbial community diversity and composition. The results indicated that compared to PT, PTAU, PTVN, and PTRP could enhance the soil pH, TC, TN, AN, and AK in different degrees, the most obvious in PTAU. Near-natural transformation of P. tabuliformis could improve soil bacterial Pielou_e index, and Simpson index, as well as soil fungal Chao1 index. Proteobacteria and Ascomycota were the dominant soil microbial community at the phylum level. What’s more, both soil bacterial and fungal community among PT, PTAU, PTRP and PTVN showed clear different, and PTAU obviously altered the soil microbial community structure. Proteobacteria was the predominant group in PT, while, Gemmatimonadetes enriched in PTVN. Ascomycota was the predominant group in PTAU, while, Basidiomycota was the predominant group in PTRP. Near-natural transformation of P. tabuliformis could change soil microbial community via altering soil characteristics. In brief, our research results revealed the influence of tree composition and soil nutrient availability on soil microbial diversity and composition, and provided management guidance for introduction soil microbial community in forest protection and management.
Yin et al. (2021) Near-natural transformation of Pinus tabuliformis better improve soil nutrients and soil microbial community. PeerJ 9:e12098 https://doi.org/10.7717/peerj.12098
Evaluation of exotic oat (Avena sativa L.) varieties for forage and grain yield in response to different levels of nitrogen and phosphorous
A field experiment was conducted during the Rabi season 2017–2018 (October–March) at the University of Agriculture, Peshawar research farm to examine the influence of different nitrogen (N) and phosphorus (P) levels on two different oat varieties: Australian and Ukrainian. The treatments included control and three levels of nitrogen and phosphorus at 30, 60, and 90 kg ha−1. The treatments were arranged in randomized complete block design (RCBD) and replicated three times. The findings showed that the oat varieties were significantly different from one another in yield and yield parameters. The Australian variety recorded higher emergence (49 plants m−2), days to emergence (15 days), days to flowering (122 days), days to maturity (145 days), plant height (142.7 cm), number of leaves (6.03 leaves plant−1), number of tillers (92.2 tillers m−1), biological yield (8,179.2 kg ha−1), and grain yield (3,725.6 kg ha−1) than the Ukrainian variety. Similarly, different N and P levels, the maximum days to emergence, days to flowering, and days to maturity were recorded in a control plot. The application of 105 kg N + 90 kg P ha−1 was statistically similar to the application of 105 kg N + 60 kg P ha−1. Maximum emergence (60 plants m−2), number of leaves (7.0 leaves plant−1), plant height (118.6 cm), number of tillers m−1 (102.6), biological yield (9,687.5 kg ha−1), and grain yield (4,416.7 kg ha−1) were determined in Australian variety. Based on the findings of this study, the Australian variety performed better in terms of yield and yield components and the application of N and P fertilizers at the rate of 105 kg N + 60 kg P ha−1 produced the best results in both oat varieties.
Bibi et al. (2021) Evaluation of exotic oat (Avena sativa L.) varieties for forage and grain yield in response to different levels of nitrogen and phosphorous. PeerJ 9:e12112 https://doi.org/10.7717/peerj.12112
Land use changes in Zhangjiakou from 2005 to 2025 and the importance of ecosystem services
Changes in local land use affect regional ecological services, development planning, and optimal use of space. We analyzed the effects of changes in land use from 2000 to 2025 on the spatial distribution of ecosystem services using CLUS-S modeling to evaluate ecosystem functions in Zhangjiakou, China. We found that the urban ecosystem area in Zhangjiakou increased and farmland decreased between 2000–2025. Water conservation was relatively high and was concentrated in the nature reserves of southern Zhangjiakou. Soil conservation was mainly distributed in eastern and southern counties. The results of the CLUE-S model showed that the relative operating characteristics of the six land use types were > 0.70, and the logistic regression equation was able to successfully explain the distribution pattern of the different types of land use.
Xu et al. (2021) Land use changes in Zhangjiakou from 2005 to 2025 and the importance of ecosystem services. PeerJ 9:e12122 https://doi.org/10.7717/peerj.12122