ExonImpact: prioritizing pathogenic alternative splicing events

Alternative splicing (AS) is a closely regulated process that allows a single gene to encode multiple protein isoforms, thereby contributing to the diversity of the proteome. Dysregulation of the splicing process has been found to be associated with many inherited diseases. However, among the pathogenic AS events, there are numerous “passenger” events whose inclusion or exclusion does not lead to significant changes with respect to protein function. In this study, we evaluate the secondary and tertiary structural features of proteins associated with disease-causing and neutral AS events, and show that several structural features are strongly associated with the pathological impact of exon inclusion. We further develop a machine-learning-based computational model, ExonImpact, for prioritizing and evaluating the functional consequences of hitherto uncharacterized AS events. We evaluated our model using several strategies including cross-validation, and data from the Gene-Tissue Expression (GTEx) and ClinVar databases. ExonImpact is freely available at http://watson.compbio.iupui.edu/ExonImpact

Effects of 8-Year Nitrogen and Phosphorus Treatments on the Ecophysiological Traits of Two Key Species on Tibetan Plateau

Understanding how nitrogen (N) and/or phosphorus (P) addition affects plants carbon- and water- related ecophysiological characteristics is essential for predicting the global change impact on the alpine meadow ecosystem structure and function in carbon and water cycling. The Qinghai-Tibetan Plateau (QTP) with the largest alpine meadow in the world is regarded as the third pole in the earth and has been experiencing increased atmospheric N deposition. In this project, we focused on two key species (Elymus dahuricus and Gentiana straminea) of the alpine meadow on the Tibetan Plateau and investigated the variability of photosynthetic and stomatal responses to 8-year N and/or P treatments through field measurements and modeling. We measured photosynthesis- and gs-response curves to generate parameter estimates from individual leaves with two widely used stomatal models (the BWB model and MED model) for validation of growth and ecosystem models and to elucidate the physiological basis for observed differences in productivity and WUE. We assessed WUE by means of gas exchange measurements (WUEi) and stable carbon isotope composition (Δ13C) to get the intrinsic and integrated estimates of WUE of the two species. P and N+P treatments, but not N, improved the photosynthetic capacity (Anet and Vcmax) for both species. Stomatal functions including instaneous measurements of stomatal conductance, intrinsic water-use efficiency and stomatal slope parameters of the two widely used stomatal models were altered by the addition of P or N+P treatment, but the impact varied across years and species. The inconsistent responses across species suggest that an understanding of photosynthetic, stomatal functions and water-use should be evaluated on species separately. WUE estimated by Δ13C values had a positive relationship with Anet and gs and a negative relationship with WUEi. Our findings should be useful for understanding the underlying mechanisms of the response of alpine plants growth and alpine meadow ecosystem to global change

regSNPs-splicing: a tool for prioritizing synonymous single-nucleotide substitution

While synonymous single-nucleotide variants (sSNVs) have largely been unstudied, since they do not alter protein sequence, mounting evidence suggests that they may affect RNA conformation, splicing, and the stability of nascent-mRNAs to promote various diseases. Accurately prioritizing deleterious sSNVs from a pool of neutral ones can significantly improve our ability of selecting functional genetic variants identified from various genome-sequencing projects, and, therefore, advance our understanding of disease etiology. In this study, we develop a computational algorithm to prioritize sSNVs based on their impact on mRNA splicing and protein function. In addition to genomic features that potentially affect splicing regulation, our proposed algorithm also includes dozens structural features that characterize the functions of alternatively spliced exons on protein function. Our systematical evaluation on thousands of sSNVs suggests that several structural features, including intrinsic disorder protein scores, solvent accessible surface areas, protein secondary structures, and known and predicted protein family domains, show significant differences between disease-causing and neutral sSNVs. Our result suggests that the protein structure features offer an added dimension of information while distinguishing disease-causing and neutral synonymous variants. The inclusion of structural features increases the predictive accuracy for functional sSNV prioritization

Leaf size of woody dicots predicts ecosystem primary productivity

A key challenge in ecology is to understand the relationships between organismal traits and ecosystem processes. Here, with a novel dataset of leaf length and width for 10 480 woody dicots in China and 2374 in North America, we show that the variation in community mean leaf size is highly correlated with the variation in climate and ecosystem primary productivity, independent of plant life form. These relationships likely reflect how natural selection modifies leaf size across varying climates in conjunction with how climate influences canopy total leaf area. We find that the leaf size–primary productivity functions based on the Chinese dataset can predict productivity in North America and vice-versa. In addition to advancing understanding of the relationship between a climate-driven trait and ecosystem functioning, our findings suggest that leaf size can also be a promising tool in palaeoecology for scaling from fossil leaves to palaeo-primary productivity of woody ecosystems

Global patterns of species richness of the holarctic alpine herb Saxifraga: The role of temperature and habitat heterogeneity

Postponed access: the file will be available after 2022-08-03The effects of contemporary climate, habitat heterogeneity and long-term climate change on species richness are well studied for woody plants in forest ecosystems, but poorly understood for herbaceous plants, especially in alpine–arctic ecosystems. Here, we aim to test if the previously proposed hypothesis based on the richness–environment relationship could explain the variation in richness patterns of the typical alpine–arctic herbaceous genus Saxifraga. Using a newly compiled distribution database of 437 Saxifraga species, we estimated the species richness patterns for all species, narrow- and wide-ranged species. We used generalized linear models and simultaneous autoregressive models to evaluate the effects of contemporary climate, habitat heterogeneity and historical climate on species richness patterns. Partial regressions were used to determine the independent and shared effects of different variables. Four widely used models were tested to identify their predictive power in explaining patterns of species richness. We found that temperature was negatively correlated with the richness patterns of all and wide-ranged species, and that was the most important environmental factor, indicating a strong conservatism of its ancestral temperate niche. Habitat heterogeneity and long-term climate change were the best predictors of the spatial variation of narrow-ranged species richness. Overall, the combined model containing five predictors can explain ca. 40%–50% of the variation in species richness. We further argued that additional evolutionary and biogeographical processes might have also played an essential role in shaping the Saxifraga diversity patterns and should be considered in future studies.acceptedVersio

Suicidality and epilepsy: A systematic review and meta-analysis

BackgroundWe aimed to evaluate the association between epilepsy and suicidality, including suicidal ideation, attempts and completed suicide.MethodsWe systematically searched PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov from 1946 to June 21, 2021 and assessed the quality of the studies using the Newcastle–Ottawa Scale. We calculated the pooled OR and the crude rate for suicidal ideation, suicide attempts and completed suicide in patients with epilepsy (PWE).ResultsWe screened 2,786 studies and included 88 articles with 1,178,401 PWE and 6,900,657 participants as controls. Search terms included epilepsy and suicide. The pooled rates of suicidal ideation, suicide attempts and completed suicide in PWE were 19.73% (95% CI: 17.00–22.62%), 5.96% (95% CI: 4.82–7.20%), and 0.24% (95% CI: 0.11–0.42%), respectively. Compared to the control group, PWE were at a significantly higher risk of total suicidality (pooled OR, 2.60; 95%: 2.13–3.18), including suicidal ideation (pooled OR, 2.70; 95% CI, 2.21–3.30), suicide attempts (pooled OR, 2.74; 95% CI, 2.08–3.61) and completed suicide (pooled OR, 2.36; 95% CI, 1.45–3.83). Subgroup analyses showed significant differences in the subgroups of the measurement of suicidality.ConclusionThe rate of suicidal ideation, suicide attempts and completed suicide in PWE were about 19.73, 5.96, and 0.24%. And there was an increased risk of suicidality in PWE especially temporal lobe epilepsy and drug-resistant epilepsy. Clinicians need to be aware of this risk in PWE with early identification and prevention at the time of diagnosis.Protocol Registration: PROSPERO CRD42021278220

Mine earthquake mechanism of extremely thick strata based on focalmemchanism analysis

In the Ordos mining area of North China, the Jurassic coal seam is commonly overlain by extremely thick cretaceous sandstone strata. Based on the seismic displacement field and relative moment tensor inversion method, this paper investigates the mine earthquake mechanism and roof fracture characteristics of coal seams under extremely thick strata. In this study, by using seismic source groups as units and microseismic stations as objects, the source mechanism of mine earthquakes is inverted by constructing an inversion matrix, which greatly improves the inversion efficiency and accuracy. The focal mechanism of large-energy mine earthquakes located in solid coal section and goaf section under extremely thick strata is calculated. The characteristics of roof fracture evolution and the influence of vibration wave radiation are quantitatively analyzed. The results show that the extremely thick strata of Cretaceous goaf start to break when the panel below retreats along goaf. During this period, the surface subsidence increases rapidly, and the significant mine earthquakes with energy above 100 kJ begin to occur, and the mine earthquake distribution is more concentrative than that in the solid coal stage. Most of the large-energy mine earthquakes are located behind the goaf, which is closely related to the breakage and slide of the thick roof. Roof tension rupture accounts for more than 85% of the mine earthquakes. During mining along goaf, the seismic sources tend to expand upward, and more shear slip ruptures are presented compared with that in the solid coal mining stage. The strike of the fracture surface has a similar direction or an angle of “X” with the advancing direction. However, compared with that in the solid coal stage, the angle of “X” during mining along goaf increases from 30° to 45°. For the source rupture surface, the dip angle of between 0°−30° accounts for about 50% of the total. The failure type of roof is dominated by horizontal separation tension and roof rotation compression. The generated P waves mostly propagate to the goaf below, which causes a minor influence on the mining face. Only a small part of the P waves propagate to the surrounding working face, which may pose a great impact on the working face. The prevention and control strategy on the extremely-thick-strata type mine earthquakes can be conducted by weakening the integrity of thick strata and making thick strata break in tiers, aiming to reduce the rockburst risks to the working face induced by the breakage of the whole thick strata

Spatio-temporal patterns in the woodiness of flowering plants

Under embargo until: 2023-12-31Aim Woody and herbaceous habits represent one of the most distinct contrasts among angiosperms, and the proportion of woody species in floras (i.e., “woodiness” hereafter) represents a fundamental structural element of plant diversity. Despite its core influence on ecosystem processes, spatio-temporal patterns in woodiness remain poorly understood. Here, we aim to demonstrate the global spatio-temporal patterns in angiosperm woodiness and their relationship with environmental factors. Location Global. Time period Cenozoic, 66 Ma to present. Major taxa studied Angiosperms. Methods Using newly compiled data on the growth forms and distributions of c. 300,000 angiosperm species and an angiosperm phylogeny, we mapped the current global geographical patterns in angiosperm woodiness, reconstructed ancestral states of growth forms through the angiosperm phylogeny and demonstrated the Cenozoic evolutionary dynamics of woodiness. We evaluated the relationships between woodiness and current climate and palaeoclimate. Results We found that c. 42.7% of angiosperms are woody. Woodiness decreased spatially from the equator towards high latitudes, temporally since the early Cenozoic. Temperature was the best predictor of the spatio-temporal decline in woodiness and was positively correlated with woodiness. Despite the temporal decline in woodiness, macroevolutionary herbaceous-to-woody transitions increased through time and contributed to the evolution of woody floras in temperate drylands, whereas the opposite transitions decreased through time and contributed to herbaceous floras in tropical and subtropical drylands. Main conclusions Our study improves understanding of the spatio-temporal dynamics of angiosperm woodiness. Our findings suggest that temperature is likely to be a determinant of spatio-temporal variations in woodiness, highlighting the role of temperature in maintaining the growth form composition of ecosystems. Our study also calls for attention to growth form transitions (e.g., secondary woodiness) in temperate drylands that have been neglected before.acceptedVersio