Truncating and zinc-finger variants in GLI2 are associated with hypopituitarism.

Variants in transcription factor GLI2 have been associated with hypopituitarism and structural brain abnormalities, occasionally including holoprosencephaly (HPE). Substantial phenotypic variability and nonpenetrance have been described, posing difficulties in the counseling of affected families. We present three individuals with novel likely pathogenic GLI2 variants, two with truncating and one with a de novo missense variant p.(Ser548Leu), and review the literature for comprehensive phenotypic descriptions of individuals with confirmed pathogenic (a) intragenic GLI2 variants and (b) chromosome 2q14.2 deletions encompassing only GLI2. We show that most of the 31 missense variants previously reported as pathogenic are likely benign or, at most, low-risk variants. Four Zn-finger variants: p.(Arg479Gly), p.(Arg516Pro), p.(Gly518Lys), and p.(Tyr575His) were classified as likely pathogenic, and three other variants as possibly pathogenic: p.(Pro253Ser), p.(Ala593Val), and p.(Pro1243Leu). We analyze the phenotypic descriptions of 60 individuals with pathogenic GLI2 variants and evidence a morbidity spectrum that includes hypopituitarism (58%), HPE (6%) or other brain structure abnormalities (15%), orofacial clefting (17%) and dysmorphic facial features (35%). We establish that truncating and Zn-finger variants in GLI2 are associated with a high risk of hypopituitarism, and that a solitary median maxillary central incisor is part of the GLI2-related phenotypic variability. The most prevalent phenotypic feature is post-axial polydactyly (65%) which is also the mildest phenotypic expression of the condition, reported in many parents of individuals with systemic findings. Our approach clarifies clinical risks and the important messages to discuss in counseling for a pathogenic GLI2 variant.

DecodeME: community recruitment for a large genetics study of myalgic encephalomyelitis / chronic fatigue syndrome.

BACKGROUND: Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test or effective treatment and we lack knowledge of its causes. Identification of genes and cellular processes whose disruption adds to ME/CFS risk is a necessary first step towards development of effective therapy. METHODS: Here we describe DecodeME, an ongoing study co-produced by people with lived experience of ME/CFS and scientists. Together we designed the study and obtained funding and are now recruiting up to 25,000 people in the UK with a clinical diagnosis of ME/CFS. Those eligible for the study are at least 16 years old, pass international study criteria, and lack any alternative diagnoses that can result in chronic fatigue. These will include 5,000 people whose ME/CFS diagnosis was a consequence of SARS-CoV-2 infection. Questionnaires are completed online or on paper. Participants' saliva DNA samples are acquired by post, which improves participation by more severely-affected individuals. Digital marketing and social media approaches resulted in 29,000 people with ME/CFS in the UK pre-registering their interest in participating. We will perform a genome-wide association study, comparing participants' genotypes with those from UK Biobank as controls. This should generate hypotheses regarding the genes, mechanisms and cell types contributing to ME/CFS disease aetiology. DISCUSSION: The DecodeME study has been reviewed and given a favourable opinion by the North West - Liverpool Central Research Ethics Committee (21/NW/0169). Relevant documents will be available online ( www.decodeme.org.uk ). Genetic data will be disseminated as associated variants and genomic intervals, and as summary statistics. Results will be reported on the DecodeME website and via open access publications.

Modelling field scale spatial variation in water run-off, soil moisture, N2O emissions and herbage biomass of a grazed pasture using the SPACSYS model.

In this study, we evaluated the ability of the SPACSYS model to simulate water run-off, soil moisture, N2O fluxes and grass growth using data generated from a field of the North Wyke Farm Platform. The field-scale model is adapted via a linked and grid-based approach (grid-to-grid) to account for not only temporal dynamics but also the within-field spatial variation in these key ecosystem indicators. Spatial variability in nutrient and water presence at the field-scale is a key source of uncertainty when quantifying nutrient cycling and water movement in an agricultural system. Results demonstrated that the new spatially distributed version of SPACSYS provided a worthy improvement in accuracy over the standard (single-point) version for biomass productivity. No difference in model prediction performance was observed for water run-off, reflecting the closed-system nature of this variable. Similarly, no difference in model prediction performance was found for N2O fluxes, but here the N2O predictions were noticeably poor in both cases. Further developmental work, informed by this study's findings, is proposed to improve model predictions for N2O. Soil moisture results with the spatially distributed version appeared promising but this promise could not be objectively verified.

Larger phylogenetic distances in litter mixtures: lower microbial biomass and higher C/N ratios but equal mass loss.

Phylogenetic distances of coexisting species differ greatly within plant communities, but their consequences for decomposers and decomposition remain unknown. We hypothesized that large phylogenetic distance of leaf litter mixtures increases differences of their litter traits, which may, in turn, result in increased resource complementarity or decreased resource concentration for decomposers and hence increased or decreased chemical transformation and reduction of litter. We conducted a litter mixture experiment including 12 common temperate tree species (evolutionarily separated by up to 106 Myr), and sampled after seven months, at which average mass loss was more than 50%. We found no effect of increased phylogenetic distance on litter mass loss or on abundance and diversity of invertebrate decomposers. However, phylogenetic distance decreased microbial biomass and increased carbon/nitrogen (C/N) ratios of litter mixtures. Consistently, four litter traits showed (marginally) significant phylogenetic signal and in three of these traits increasing trait difference decreased microbial biomass and increased C/N. We suggest that phylogenetic proximity of litter favours microbial decomposers and chemical transformation of litter owing to a resource concentration effect. This leads to a new hypothesis: closely related plant species occurring in the same niche should promote and profit from increased nutrient availability.

Influence of N doses and form on ¹5N natural abundance of pepper plants: considerations for using δ¹5N values as indicator of N source.

BACKGROUND: The aim of this study was to ascertain the effect of the N form (NO(3) (-) , NH(4) (+) and organic N) and N concentration on plant isotopic fractionation and on the contribution of the different N sources to the plant N budget, in order to evaluate the feasibility of using plant δ(15) N values for discriminating between conventional and organic crops. To this end, different N concentrations (applied as NO(3) (-) ), N forms (NO(3) (-) versus NH(4) (+) ), and increasing NO(3) (-) applications to an organic N-based fertilization regime were studied. RESULTS: When using NO(3) (-) as N source, intra-plant fractionation was significant and tended to increase when NO(3) (-) concentration increased in the root medium. However, negligible net isotopic fractionation was observed when comparing theoretical and measured plant δ(15) N values. On the other hand, when plants are fertilized with a mixture of NO(3) (-) and NH(4) (+) , differences in uptake patterns for both salts could result in variation in plant δ(15) N regarding to the expected value. Finally, the application of NO(3) (-) to plants was detected when it was combined with high levels of organic N sources, from 99:1 organic:inorganic N ratio. CONCLUSION: Under certain conditions and following some considerations concerning sampling, δ(15) N values can be considered to be a potential tool to guarantee the authenticity of organic products.

Root imaging showing comparisons in root distribution and ontogeny in novel Festulolium populations and closely related perennial ryegrass varieties.

The incorporation of new sophisticated phenotyping technologies within a crop improvement program allows for a plant breeding strategy that can include selections for major root traits previously inaccessible due to the challenges in their phenotype assessment. High-throughput precision phenotyping technology is employed to evaluate root ontogeny and progressive changes to root architecture of both novel amphiploid and introgression lines of Festulolium over four consecutive months of the growing season and these compared under the same time frame to that of closely related perennial ryegrass (L. perenne) varieties. Root imaging using conventional photography and assembled multiple merged images was used to compare frequencies in root number, their distribution within 0-20 and 20-40 cm depths within soil columns, and progressive changes over time. The Festulolium hybrids had more extensive root systems in comparison with L. perenne, and this was especially evident at depth. It was shown that the acquisition of extensive root systems in Festulolium hybrids was not dependent on the presence of an entire Festuca genome. On the contrary, the most pronounced effect on root development within the four Festulolium populations studied was observed in the introgression line Bx509, where a single small genome sequence from F. arundinacea had been previously transferred onto its homoeologous site on the long arm of chromosome 3 of an otherwise complete L. perenne genome. This demonstrates that a targeted introgression-breeding approach may be sufficient to confer a significant improvement in the root morphology in Lolium without a significant compromise to its genome integrity. The forage production of Bx509 was either higher (months 1-3) or equivalent to (month 4) that of its L. perenne parent control demonstrating that the enhanced root development achieved by the introgression line was without compromise to its agronomic performance.

Assessment of soil water, carbon and nitrogen cycling in reseeded grassland on the North Wyke Farm Platform using a process-based model.

The North Wyke Farm Platform (NWFP) generates large volumes of temporally-indexed data that provides a valuable test-bed for agricultural mathematical models in temperate grasslands. In our study, we used the primary datasets generated from the NWFP (https://nwfp.rothamsted.ac.uk/) to validate the SPACSYS model in terms of the dynamics of water loss and forage dry matter yield estimated through cutting. The SPACSYS model is capable of simulating soil water, carbon (C) and nitrogen (N) balance in the soil-plant-atmosphere system. The validated model was then used to simulate the responses of soil water, C and N to reseeding grass cultivars with either high sugar (Lolium perenne L. cv. AberMagic) or deep rooting (Festulolium cv. Prior) traits. Simulation results demonstrated that the SPACSYS model could predict reliably soil water, C and N cycling in reseeded grassland. Compared to AberMagic, the Prior grass could fix more C in the second year following reseeding, whereas less C was lost through soil respiration in the first transition year. In comparison to the grass cultivar of the permanent pasture that existed before reseeding, both grasses reduced N losses through runoff and contributed to reducing water loss, especially Prior in relation to the latter. The SPACSYS model could predict these differences as supported by the rich dataset from the NWFP, providing a tool for future predictions on less characterized pasture.

Modest enhancements to conventional grassland diversity improve the provision of pollination services.

Grassland for livestock production is a major form of land use throughout Europe and its intensive management threatens biodiversity and ecosystem functioning in agricultural landscapes. Modest increases to conventional grassland biodiversity could have considerable positive impacts on the provision of ecosystem services, such as pollination, to surrounding habitats.Using a field-scale experiment in which grassland seed mixes and sward management were manipulated, complemented by surveys on working farms and phytometer experiments, the impact of conventional grassland diversity and management on the functional diversity and ecosystem service provision of pollinator communities were investigated.Increasing plant richness, by the addition of both legumes and forbs, was associated with significant enhancements in the functional diversity of grassland pollinator communities. This was associated with increased temporal stability of flower-visitor interactions at the community level. Visitation networks revealed pasture species Taraxacum sp. (Wigg.) (dandelion) and Cirsium arvense (Scop.) (creeping thistle) to have the highest pollinator visitation frequency and richness. Cichorium intybus (L.) (chichory) was highlighted as an important species having both high pollinator visitation and desirable agronomic properties.Increased sward richness was associated with an increase in the pollination of two phytometer species; Fragaria × ananassa (strawberry) and Silene dioica (red campion), but not Vicia faba (broad bean). Enhanced functional diversity, richness and abundance of the pollinator communities associated with more diverse neighbouring pastures were found to be potential mechanisms for improved pollination. Synthesis and applications. A modest increase in conventional grassland plant diversity with legumes and forbs, achievable with the expertise and resources available to most grassland farmers, could enhance pollinator functional diversity, richness and abundance. Moreover, our results suggest that this could improve pollination services and consequently surrounding crop yields (e.g. strawberry) and wildflower reproduction in agro-ecosystems.