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Predicting phenotypes from a combination of genetic and environmental factors is a grand challenge of modern biology. Slight improvements in this area have the potential to save lives, improve food and fuel security, permit better care of the planet, and create other positive outcomes. In 2022 and 2023 the first open-to-the-public Genomes to Fields (G2F) initiative Genotype by Environment (GxE) prediction competition was held using a large dataset including genomic variation, phenotype and weather measurements and field management notes, gathered by the project over nine years. The competition attracted registrants from around the world with representation from academic, government, industry, and non-profit institutions as well as unaffiliated. These participants came from diverse disciplines include plant science, animal science, breeding, statistics, computational biology and others. Some participants had no formal genetics or plant-related training, and some were just beginning their graduate education. The teams applied varied methods and strategies, providing a wealth of modeling knowledge based on a common dataset. The winner's strategy involved two models combining machine learning and traditional breeding tools: one model emphasized environment using features extracted by Random Forest, Ridge Regression and Least-squares, and one focused on genetics. Other high-performing teams' methods included quantitative genetics, machine learning/deep learning, mechanistic models, and model ensembles. The dataset factors used, such as genetics; weather; and management data, were also diverse, demonstrating that no single model or strategy is far superior to all others within the context of this competition., (Published by Oxford University Press on behalf of The Genetics Society of America 2024.)

Small RNAs (sRNAs) are involved in gene silencing in multiple ways, including through cross-kingdom transfers from parasites to their hosts. Little is known about the evolutionary mechanisms enabling eukaryotic microbes to evolve functional mimics of host small regulatory RNAs. Here, we describe the identification and functional characterization of SINE_sRNA1 , an sRNA family derived from highly abundant short interspersed nuclear element (SINE) retrotransposons in the genome of the wheat powdery mildew pathogen. SINE_sRNA1 is encoded by a sequence motif that is conserved in multiple SINE families and corresponds to a functional plant microRNA (miRNA) mimic targeting Tae_AP1 , a wheat gene encoding an aspartic protease only found in monocots. Tae_AP1 has a novel function enhancing both pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), thereby contributing to the cross activation of plant defenses. We conclude that SINE_sRNA1 and Tae_AP1 are functional innovations, suggesting the contribution of transposons to the evolutionary arms race between a parasite and its host. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license., Competing Interests: The author(s) declare no conflict of interest.

Cell-surface receptors play pivotal roles in many biological processes, including immunity, development, and reproduction, across diverse organisms. How cell-surface receptors evolve to become specialised in different biological processes remains elusive. To shed light on the immune-specificity of cell-surface receptors, we analyzed more than 200,000 genes encoding cell-surface receptors from 350 genomes and traced the evolutionary origin of immune-specific leucine-rich repeat receptor-like proteins (LRR-RLPs) in plants. Surprisingly, we discovered that the motifs crucial for co-receptor interaction in LRR-RLPs are closely related to those of the LRR-receptor-like kinase (RLK) subgroup Xb, which perceives phytohormones and primarily governs growth and development. Functional characterisation further reveals that LRR-RLPs initiate immune responses through their juxtamembrane and transmembrane regions, while LRR-RLK-Xb members regulate development through their cytosolic kinase domains. Our data suggest that the cell-surface receptors involved in immunity and development share a common origin. After diversification, their ectodomains, juxtamembrane, transmembrane, and cytosolic regions have either diversified or stabilised to recognise diverse ligands and activate differential downstream responses. Our work reveals a mechanism by which plants evolve to perceive diverse signals to activate the appropriate responses in a rapidly changing environment., (© 2024. The Author(s).)

As sessile, photoautotrophic organisms, plants are subjected to fluctuating sunlight that includes potentially detrimental ultraviolet-B (UV-B) radiation. Experiments under controlled conditions have shown that the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) controls acclimation and tolerance to UV-B in Arabidopsis thaliana; however, its long-term impact on plant fitness under naturally fluctuating environments remain poorly understood. Here, we quantified the survival and reproduction of different Arabidopsis mutant genotypes under diverse field and laboratory conditions. We found that uvr8 mutants produced more fruits than wild type when grown in growth chambers under artificial low-UV-B conditions but not under natural field conditions, indicating a fitness cost in the absence of UV-B stress. Importantly, independent double mutants of UVR8 and the blue light photoreceptor gene CRYPTOCHROME 1 (CRY1) in two genetic backgrounds showed a drastic reduction in fitness in the field. Experiments with UV-B attenuation in the field and with supplemental UV-B in growth chambers demonstrated that UV-B caused the cry1 uvr8 conditional lethal phenotype. Using RNA-seq data of field-grown single and double mutants, we explicitly identified genes showing significant statistical interaction of UVR8 and CRY1 mutations in the presence of UV-B in the field. They were enriched in Gene Ontology categories related to oxidative stress, photoprotection and DNA damage repair in addition to UV-B response. Our study demonstrates the functional importance of the UVR8-mediated response across life stages in natura, which is partially redundant with that of cry1. Moreover, these data provide an integral picture of gene expression associated with plant responses under field conditions., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)

Background: The diagnostic value of allergen-specific immunoglobulin E (IgE) in horses with asthma is uncertain. A recently developed protein microarray detected abnormally high latex-specific IgE concentrations in the serum of horses with severe asthma., Objectives: The main objective was to characterize the IgE profiles of asthmatic horses in Switzerland using a protein microarray platform in serum and bronchoalveolar lavage fluid (BALF). The secondary objective was to determine whether serological and BALF allergen-specific IgE concentrations correlated., Animals: Forty-four asthmatic and 39 control horses ≥5 years of age., Methods: This prospective cross-sectional study investigated the sensitization profiles of horses with asthma compared with environmentally matched healthy controls. Both serum and BALF were analyzed using the protein microarray. Partial least square-discriminant analysis (PLS-DA) was used to identify and rank the importance of the allergens for class detection (ie, asthma vs control), with a variable influence on the projection (VIP) >1 considered significant., Results: The allergens that best discriminated (VIP >1) asthmatic horses from controls were proteins derived from fungi (Aspergillus fumigatus), insects (Culicoides spp.), and latex (Hevea brasiliensis). The serological model predictive ability was markedly inferior (area under the curve [AUC] 0.585, 95% confidence interval [CI]: 0.454-0.747) to that of the BALF (AUC 0.751, 95% CI: 0.582-0.866). The two models shared nine allergens, of which eight showed significant weak to moderate correlations., Conclusion and Clinical Importance: The concentrations of several allergen-specific IgE were higher in asthmatic horses. The protein microarray performed better on BALF than serum for detection of asthma. Serological IgE concentrations do not closely correlate with BALF concentrations and should be interpreted with caution., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Endurance athletes attribute performance not only to physiological factors, but also refer to psychological factors such as motivation. The goal of this study was to quantify the proportion of the variance in endurance performance that is explained by psychological factors in addition to the physiological factor VO 2 max. Twenty-five athletes of the U17 Swiss Cycling national team (7f, 18 m, 15.3 ± 0.5 years) were examined in a cross-sectional study with psychological factors and VO 2 max as independent variables and endurance performance in road cycling as dependent variable. Questionnaires were used to assess psychological factors (i.e. use of mental techniques, self-compassion, mental toughness, achievement motivation, and action vs. state orientation). VO 2 max was measured by a step incremental cycle ergometer test of exhaustion. Endurance performance was measured in a cycling mountain time trial (1,320 m long, incline of 546 meters). A multiple regression model was created by using forward selection of regression model predictors. Results showed that higher VO 2 max values (β = .48), being male (β = .26), and higher achievement motivation (i.e. perseverance, β = .11) were associated with a better endurance performance. A more frequent use of one particular mental technique (i.e. relaxation techniques, β = .03) was associated with a worse endurance performance. Our study shows that a physiological factor like VO 2 max explains endurance performance to a large extent but psychological factors account for additional variance. In particular, one aspect of achievement motivation, namely perseverance, was associated with a better endurance performance. HIGHLIGHTSEndurance performance is explained by physiological (e.g. VO 2 max) and psychological (e.g. perseverance) factorsVO 2 max explains young cyclists' endurance performance to a large extentPerseverance explained performance beyond the influence of VO 2 max.

N-terminal pro-b-type natriuretic peptide (NTproBNP) is a cardiac biomarker used to detect myocardial wall stress. Physical activity and cardiac disease can affect serum NTproBNP concentrations. In people, different types of physical activity have different effects on NTproBNP. Our hypothesis was that physical activity and training have an effect on NTproBNP concentrations depending on the type of exercise and the intensity. Seven German Shepherd dogs (GSD) under military training performing short bursts of fast-paced interval exercise and seven Eurohounds (EHs) training for racing competition with endurance exercise were included in the study. Blood samples were taken at enrollment (T 0 ) and after a two-month (T 2mth ) training period; on both occasions, the samples were acquired before and after physical exercise. An echocardiographic evaluation was performed at T 0 . Echocardiographic heart size was larger in the EHs compared to the GSDs. The NTproBNP concentration was higher in the EHs than in the GSDs before and after exercise at T 0 and T 2mth . Echocardiographic parameters of heart size and wall thickness correlated with NTproBNP at T 0 before and after exercise. Exercise induced an elevation of NTproBNP in the EHs at T 0 and T 2mth , while in the GSDs this was observed only at T 0 . In the EHs, post exercise was associated with higher NTproBNP at T 2mth compared to T 0 , while in the GSDs the opposite pattern was noticed. From our study, the serum NTproBNP concentration differs between breeds. Intense physical activity causes an increase in NTproBNP. A two-month training period does not affect the NTproBNP concentration at rest. Intense physical activity may increase NTproBNP above the reference range in individual dogs.

Recent reports suggest that cell-surface and intracellular immune receptors function synergistically to activate robust defence against pathogens, but whether they co-evolve is unclear. Here we determined the numbers of cell-surface and intracellular immune receptors in 350 species. Surprisingly, the number of receptor genes that are predicted to encode cell-surface and intracellular immune receptors is strongly correlated. We suggest this is consistent with mutual potentiation of immunity initiated by cell-surface and intracellular receptors being reflected in the concerted co-evolution of the size of their repertoires across plant species., (© 2022. The Author(s).)

Introgressions of chromosomal segments from related species into wheat are important sources of resistance against fungal diseases. The durability and effectiveness of introgressed resistance genes upon agricultural deployment is highly variable-a phenomenon that remains poorly understood, as the corresponding fungal avirulence genes are largely unknown. Until its breakdown, the Pm17 resistance gene introgressed from rye to wheat provided broad resistance against powdery mildew ( Blumeria graminis ). Here, we used quantitative trait locus (QTL) mapping to identify the corresponding wheat mildew avirulence effector AvrPm17 . It is encoded by two paralogous genes that exhibit signatures of reoccurring gene conversion events and are members of a mildew sublineage specific effector cluster. Extensive haplovariant mining in wheat mildew and related sublineages identified several ancient virulent AvrPm17 variants that were present as standing genetic variation in wheat powdery mildew prior to the Pm17 introgression, thereby paving the way for the rapid breakdown of the Pm17 resistance. QTL mapping in mildew identified a second genetic component likely corresponding to an additional resistance gene present on the 1AL.1RS translocation carrying Pm17. This gene remained previously undetected due to suppressed recombination within the introgressed rye chromosomal segment. We conclude that the initial effectiveness of 1AL.1RS was based on simultaneous introgression of two genetically linked resistance genes. Our results demonstrate the relevance of pathogen-based genetic approaches to disentangling complex resistance loci in wheat. We propose that identification and monitoring of avirulence gene diversity in pathogen populations become an integral part of introgression breeding to ensure effective and durable resistance in wheat.

Plant genomes encode hundreds of secreted peptides; however, relatively few have been characterised. We report here an uncharacterised, stress-induced family of plant signalling peptides, which we call CTNIPs. Based on the role of the common co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) in CTNIP-induced responses, we identified in Arabidopsis thaliana the orphan receptor kinase HAESA-LIKE 3 (HSL3) as the CTNIP receptor via a proteomics approach. CTNIP-binding, ligand-triggered complex formation with BAK1, and induced downstream responses all involve HSL3. Notably, the HSL3-CTNIP signalling module is evolutionarily conserved amongst most extant angiosperms. The identification of this novel signalling module will further shed light on the diverse functions played by plant signalling peptides and will provide insights into receptor-ligand co-evolution., Competing Interests: JR, AR, MB, BB, PD, MW, MS, FM, JS, CZ No competing interests declared, (© 2022, Rhodes et al.)

Wild plant populations show extensive genetic subdivision and are far from the ideal of panmixia which permeates population genetic theory. Understanding the spatial and temporal scale of population structure is therefore fundamental for empirical population genetics - and of interest in itself, as it yields insights into the history and biology of a species. In this study we extend the genomic resources for the wild Mediterranean grass Brachypodium distachyon to investigate the scale of population structure and its underlying history at whole-genome resolution. A total of 86 accessions were sampled at local and regional scales in Italy and France, which closes a conspicuous gap in the collection for this model organism. The analysis of 196 accessions, spanning the Mediterranean from Spain to Iraq, suggests that the interplay of high selfing and seed dispersal rates has shaped genetic structure in B. distachyon. At the continental scale, the evolution in B. distachyon is characterized by the independent expansion of three lineages during the Upper Pleistocene. Today, these lineages may occur on the same meadow yet do not interbreed. At the regional scale, dispersal and selfing interact and maintain high genotypic diversity, thus challenging the textbook notion that selfing in finite populations implies reduced diversity. Our study extends the population genomic resources for B. distachyon and suggests that an important use of this wild plant model is to investigate how selfing and dispersal, two processes typically studied separately, interact in colonizing plant species., (© 2021 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Transposable elements (TEs) constitute a large fraction of plant genomes and are mostly present in a transcriptionally silent state through repressive epigenetic modifications, such as DNA methylation. TE silencing is believed to influence the regulation of adjacent genes, possibly as DNA methylation spreads away from the TE. Whether this is a general principle or a context-dependent phenomenon is still under debate, pressing for studying the relationship between TEs, DNA methylation, and nearby gene expression in additional plant species. Here, we used the grass Brachypodium distachyon as a model and produced DNA methylation and transcriptome profiles for 11 natural accessions. In contrast to what is observed in Arabidopsis thaliana, we found that TEs have a limited impact on methylation spreading and that only few TE families are associated with a low expression of their adjacent genes. Interestingly, we found that a subset of TE insertion polymorphisms is associated with differential gene expression across accessions. Thus, although not having a global impact on gene expression, distinct TE insertions may contribute to specific gene expression patterns in B. distachyon., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Brachypodium distachyon (Brachypodium) is a non-domesticated model grass species that can be used to test if variation in genetic sequence or methylation are linked to environmental differences. To assess this, we collected seeds from 12 sites within five climatically distinct regions of Turkey. Seeds from each region were grown under standardized growth conditions in the UK to preserve methylated sequence variation. At six weeks following germination, leaves were sampled and assessed for genomic and DNA methylation variation. In a follow-up experiment, phenomic approaches were used to describe plant growth and drought responses. Genome sequencing and population structure analysis suggested three ancestral clusters across the Mediterranean, two of which were geographically separated in Turkey into coastal and central subpopulations. Phenotypic analyses showed that the coastal subpopulation tended to exhibit relatively delayed flowering and the central, increased drought tolerance as indicated by reduced yellowing. Genome-wide methylation analyses in GpC, CHG and CHH contexts also showed variation which aligned with the separation into coastal and central subpopulations. The climate niche modelling of both subpopulations showed a significant influence from the "Precipitation in the Driest Quarter" on the central subpopulation and "Temperature of the Coldest Month" on the coastal subpopulation. Our work demonstrates genetic diversity and variation in DNA methylation in Turkish accessions of Brachypodium that may be associated with climate variables and the molecular basis of which will feature in ongoing analyses.

Transposable elements (TEs) are the main reason for the high plasticity of plant genomes, where they occur as communities of diverse evolutionary lineages. Because research has typically focused on single abundant families or summarized TEs at a coarse taxonomic level, our knowledge about how these lineages differ in their effects on genome evolution is still rudimentary. Here we investigate the community composition and dynamics of 32 long terminal repeat retrotransposon (LTR-RT) families in the 272-Mb genome of the Mediterranean grass Brachypodium distachyon. We find that much of the recent transpositional activity in the B. distachyon genome is due to centromeric Gypsy families and Copia elements belonging to the Angela lineage. With a half-life as low as 66 kyr, the latter are the most dynamic part of the genome and an important source of within-species polymorphisms. Second, GC-rich Gypsy elements of the Retand lineage are the most abundant TEs in the genome. Their presence explains > 20% of the genome-wide variation in GC content and is associated with higher methylation levels. Our study shows how individual TE lineages change the genetic and epigenetic constitution of the host beyond simple changes in genome size., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

Strains of Pseudomonas that produce antimicrobial metabolites and control soilborne plant diseases have often been isolated from soils defined as disease-suppressive, i.e., soils, in which specific plant pathogens are present, but plants show no or reduced disease symptoms. Moreover, it is assumed that pseudomonads producing antimicrobial compounds such as 2,4-diacetylphloroglucinol (DAPG) or phenazines (PHZ) contribute to the specific disease resistance of suppressive soils. However, pseudomonads producing antimicrobial metabolites are also present in soils that are conducive to disease. Currently, it is still unknown whether and to which extent the abundance of antimicrobials-producing pseudomonads is related to the general disease resistance of common agricultural soils. Moreover, virtually nothing is known about the conditions under which pseudomonads express antimicrobial genes in agricultural field soils. We present here results of the first side-by-side comparison of 10 representative Swiss agricultural soils with a cereal-oriented cropping history for (i) the resistance against two soilborne pathogens, (ii) the abundance of Pseudomonas bacteria harboring genes involved in the biosynthesis of the antimicrobials DAPG, PHZ, and pyrrolnitrin on roots of wheat, and (iii) the ability to support the expression of these genes on the roots. Our study revealed that the level of soil disease resistance strongly depends on the type of pathogen, e.g., soils that are highly resistant to Gaeumannomyces tritici often are highly susceptible to Pythium ultimum and vice versa. There was no significant correlation between the disease resistance of the soils, the abundance of Pseudomonas bacteria carrying DAPG, PHZ, and pyrrolnitrin biosynthetic genes, and the ability of the soils to support the expression of the antimicrobial genes. Correlation analyses indicated that certain soil factors such as silt, clay, and some macro- and micronutrients influence both the abundance and the expression of the antimicrobial genes. Taken together, the results of this study suggests that pseudomonads producing DAPG, PHZ, or pyrrolnitrin are present and abundant in Swiss agricultural soils and that the soils support the expression of the respective biosynthetic genes in these bacteria to various degrees. The precise role that these pseudomonads play in the general disease resistance of the investigated agricultural soils remains elusive.

Despite major advances in our understanding of many aspects of human papillomavirus (HPV) biology, HPV entry is poorly understood. To identify cellular genes required for HPV entry, we conducted a genome-wide screen for siRNAs that inhibited infection of HeLa cells by HPV16 pseudovirus. Many retrograde transport factors were required for efficient infection, including multiple subunits of the retromer, which initiates retrograde transport from the endosome to the trans-Golgi network (TGN). The retromer has not been previously implicated in virus entry. Furthermore, HPV16 capsid proteins arrive in the TGN/Golgi in a retromer-dependent fashion during entry, and incoming HPV proteins form a stable complex with retromer subunits. We propose that HPV16 directly engages the retromer at the early or late endosome and traffics to the TGN/Golgi via the retrograde pathway during cell entry. These results provide important insights into HPV entry, identify numerous potential antiviral targets, and suggest that the role of the retromer in infection by other viruses should be assessed.

An IKKbeta inhibitor reported to block NF-kappaB transcriptional activities in Jurkat T cells, was found to enhance NF-kappaB translocation in HUVEC cells. These studies suggested a noncanonical NF-kappaB signaling pathway independent of IKKbeta in HUVEC cells.

Nuclear factor kappa B (NF-kappaB) is an important transcription factor. Aberrant regulation of the NF-kappaB pathway is frequently observed in a number of major ailments such as cancer and inflammatory diseases. Hence NF-kappaB modulators have been intensely pursued for their potential therapeutic applications. Numerous reviews have described recent progress in the development of these agents. More recently, a variety of structurally and functionally novel small molecules, identified through high-throughput screens conducted within the Molecular Libraries Screening Center Network (MLSCN) of the NIH Roadmap for Medical Research, have been added to the current list of NF-kappaB regulators. This review will discuss the inhibitors and activators newly discovered by Columbia's Molecular Libraries Screening Center (MLSC) using a well-designed and stable cellular assay.

We describe here a series of N-(quinolin-8-yl)benzenesulfonamides capable of suppressing the NFkappaB pathway identified from two high-throughput screens run at two centers of the NIH Molecular Libraries Initiative. These small molecules were confirmed in both primary and secondary assays of NFkappaB activation and expanded upon through analogue synthesis. The series exhibited potencies in the cell-based assays at as low as 0.6 microM, and several indications suggest that the targeted activity lies within a common region of the NFkappaB pathway.