Biology subjects

Yoo, J. H.

Publications and source records attributed to Yoo, J. H..

12 recordsLinked to original sources

bioRxiv2026

Optimizing resource allocation in Miscanthus breeding with sparse testing designs for genomic prediction

Phenotyping high-biomass perennial crops is laborious and the rate of genetic gain in perennial crop breeding programs is typically low. So, it is especially important to identify methods that produce efficiency gains in the breeding process. Miscanthus is a C4 perennial grass with favorable characteristics for producing biomass as a feedstock for biofuels and diverse biobased products. Increasing biomass yield will increase profitability and environmental benefits, so is a key target for Miscanthus breeding. In addition, the identification of well-adapted genotypes across a wide range of environmental conditions requires the establishment of multi-environment trials (METs). Sparse testing is a genomic prediction-based strategy that reduces the phenotyping costs in METs by selecting a subset of genotypes to evaluate in a subset of environments and then predicts the performance of the unobserved genotype-environment combinations. A Miscanthus sacchariflorus (MSA) population comprising 336 genotypes observed across three environments was analyzed. Three prediction models considering main effects (environments, genotypes, genomic) and interaction effects (genotype-by-environment; GxE interaction) were implemented for forecasting dry biomass yield (YDY), total culm (TCM), average internode length (AIL), and culm node number (CNN). Multiple calibration sets based on different compositions and sizes were considered to evaluate performance in terms of the predictive ability (PA) and the mean square error (MSE) for a fixed testing set size. The training set size ranged from 52 to 112 to predict a fixed set of 224 unobserved genotypes across all three environments. The results showed that the model accounting for GxE interaction presented the highest PA and the lowest MSE for CNN (PA: [~]0.77, MSE: [~]0.5) and YDY (PA: [~]0.70, MSE: [~]1.3) while for TCM and AIL these ranged from [~]0.28 to 0.41 and [~]1.3 to 4.3, respectively. Overall, varying training sets and allocation strategies did not affect PA and MSE, with 52 non-overlapping and 0 overlapping genotypes per environment as the optimal cost-effective allocation framework. This suggests that implementing sparse testing designs could significantly reduce phenotyping costs by fivefold, without compromising PA in breeding programs for perennial crops such as Miscanthus.

genomics↗

bioRxiv2026

Multi-trait Multi-environment Genomic Prediction Strategies for Miscanthus sacchariflorus Populations

Genomic selection holds the potential to serve as a strategic tool to enhance the genetic gain of complex traits in Miscanthus breeding programs. The development of improved cultivars requires their assessment for various traits across diverse environments to ensure suitable overall performance. Hence, the multi-trait multi-environment (MTME) genomic prediction (GP) models offer an opportunity to improve selection accuracy. This study aims to evaluate the potential of five GP models: (1) three MTME models including genotype-by-trait-by-environment interaction (GxExT) and (2) two single-trait multi-environment (STME) models (with and without GxE interaction). A Miscanthus sacchariflorus population comprising 336 genotypes evaluated in three environments and scored for four traits (biomass yield YDY, total culm number TCM, average internode length AIL, and culm node number CNN) was analyzed. The predictive ability of the models was evaluated considering three cross-validation schemes resembling realistic scenarios (CV1: predicting new genotypes, CVP: predicting missing traits in a given environment, and CV2: predicting partially observed genotypes). On average, in all cross-validation schemes compared to the STME the predictive ability of the MTME models was 10% to 70% higher for TCM and AIL. On the other hand, for YDY and CNN, both STME models performed similarly or slightly better (between 5 to 64%) than the MTME models in most environments. While the MTME models were not successful for all traits when compared to their STME counterparts, MTME models improved the prediction of the performance of genotypes that were untested across environments or lacked trait information in a specific environment. Overall, our study suggests that MTME GP models can be implemented in Miscanthus breeding programs to improve the predictive ability of the complex traits, shorten breeding cycles, and accelerate selection decisions.

genomics↗

bioRxiv2026

Weather Characterization for Optimizing Genomic Prediction in Miscanthus sacchariflorus

Environmental factors affect crop growth and development thus their consideration across sites and years become essential for genotypic evaluation. Genomic selection (GS) has been broadly implemented to accelerate breeding cycles by skipping field evaluations thus allowing early identification of outperforming genotypes. In this study, 7,740 phenotypic records corresponding to 516 Miscanthus sacchariflorus genotypes evaluated in five locations across three years were considered for analysis. Additionally, environmental data on six weather covariates was implemented to characterize similarities between locations. Different sets of locations of variable sizes were used for model calibration based on two cross-validations (CV00 and CV0) schemes leaving out one location at a time. Predictive ability across locations of the best model varied between 0.45 and 0.90 for both schemes. These results were compared to associate predictive ability in function of weather patterns between training and testing sets to allow models calibration optimization. We found it is feasible to optimize resource allocation by considering environmentally correlated sets. In most cases, the information from only one and, at most, two locations were enough to deliver better results than using all four locations, reducing training sets by up to 75%. The results obtained shed light on helping breeders make informed decisions considering weather data when designing evaluations.

genomics↗

bioRxiv2026

ENHANCING GENOMIC PREDICTION MODELS IN MISCANTHUS POPULATIONS BY INCORPORATING THE GENOTYPE-BY-ENVIRONMENT INTERACTION

Giant Miscanthus giganteus (Mxg) is one of the most promising perennial crops to generate biomass feedstock for bioenergy and biobased products. It is derived from the natural inter-species hybridization of Miscanthus sacchariflorus (Msa) and Miscanthus sinensis (Msi) species, thus population improvement within these species is crucial. Genomic selection (GS) is an attractive option to accelerate breeding of perennial grasses, such as Miscanthus, which requires up to three years of evaluation to produce reliable phenotypic data. Hence, genotypes are observed in multiple years and locations causing inconsistent response patterns from one year to the next, between location, and/or location-by-year combinations. These inconsistencies are known as the genotype-by-environment interaction effect (GxE). Although GS has been successfully implemented in multiple annual crops where straightforward cross-validation schemes exist to assess the levels of predictive ability that can be reached, for perennial crops new cross-validation schemes will help avoid data contamination. Here, we propose a series of cross-validation schemes to evaluate model performance for perennial crops. We perform a case study by analyzing one panel of each species (516 genotypes of Msa, 280 genotypes of Msi) scored for biomass yield at different locations around the world over several years. The results of the different cross-validation schemes provide insights about the usefulness of GS to accelerate the breeding process of Miscanthus species. In addition, leveraging the GxE effects of different types significantly increases predictive ability (up to 10% in Msa and 30% for Msi) compared to the conventional approaches based on main effects only.

genomics↗

bioRxiv2025

Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.

There has been a substantial investment in elucidating the mechanism of expansion in hopes of identifying therapeutic targets for Huntington disease (HD). Although an expanded CAG allele is the causal mutation for HD, there is evidence that somatic expansion may not be the only disease driver. We report here that double strand breaks (DSBs) drive HD toxicity by an independent mechanism from somatic expansion. The mutant HD protein inhibits non-homologous end joining (NHEJ) activity, leading to the accumulation of DSBs. DSBs promote transcriptional pathology in mice that cannot expand their CAG tracts somatically. Conversely, Inhibition of DSBs reverses neuronal toxicity in animals that undergo somatic expansion. Although they coexist in neurons, DSBs and somatic expansion are independent therapeutic targets for HD.

molecular biology↗

bioRxiv2024

Identification of a proteolysis regulator for an essential enzyme in Mycobacterium tuberculosis

In Mycobacterium tuberculosis proteins that are post-translationally modified with Pup, a prokaryotic ubiquitin-like protein, can be degraded by proteasomes. While pupylation is reversible, mechanisms regulating substrate specificity have not been identified. Here, we identify the first depupylation regulators: CoaX, a pseudokinase, and pantothenate, an essential, central metabolite. In a {Delta}coaX mutant, pantothenate synthesis enzymes were more abundant, including PanB, a substrate of the Pup-proteasome system. Media supplementation with pantothenate decreased PanB levels in a coaX and Pup-proteasome-dependent manner. In vitro, CoaX accelerated depupylation of Pup[~]PanB, while addition of pantothenate inhibited this reaction. Collectively, we propose CoaX contributes to proteasomal degradation of PanB by modulating depupylation of Pup[~]PanB in response to pantothenate levels. One Sentence SummaryA pseudo-pantothenate kinase regulates proteasomal degradation of a pantothenate synthesis enzyme in M. tuberculosis.

microbiology↗

bioRxiv2024

Characterization of a cytokinin-binding protein locus in Mycobacterium tuberculosis

Cytokinins are adenine-based hormones that have been well-characterized in plants but are also made by bacteria, including the human-exclusive pathogen Mycobacterium tuberculosis. In M. tuberculosis, cytokinins activate transcription of an operon that affects the bacterial cell envelope. In plants, cytokinins are broken down by dedicated enzymes called cytokinin oxidases into adenine and various aldehydes. In proteasome degradation-deficient M. tuberculosis, the cytokinin-producing enzyme Log accumulates, resulting in the buildup of at least one cytokinin-associated aldehyde. We therefore hypothesized that M. tuberculosis encodes one or more cytokinin oxidases. Using a homology-based search for homologs of a plant cytokinin oxidase, we identified Rv3719 and a putative cytokinin-specific binding protein, Rv3718c. Deletion of the locus encoding these proteins did not have a measurable effect on in vitro growth. Nonetheless, Rv3718c bound a cytokinin with high specificity. Our data thus support a model whereby cytokinins play one or more roles in mycobacterial physiology. IMPORTANCENumerous bacterial species encode cytokinin-producing enzymes, the functions of which are almost completely unknown. This work contributes new knowledge to the cytokinin field for bacteria, and also revealed further conservation of cytokinin-associated proteins between plants and prokaryotes.

microbiology↗

bioRxiv2022

Effects of parental verbal abuse experience on the Glutamate response to swear words in the ventromedial prefrontal cortex: A functional H1-magnetic resonance spectroscopy study

Several lines of evidence indicate verbal abuse (VA) critically impacts the developing brain; however, whether VA results in changes in brain neurochemistry has not been established in humans. Here, we hypothesized that exposure to recurrent parental VA elicits heightened glutamate (Glu) responses during the presentation of swear words, which can be measured with functional magnetic resonance spectroscopy (fMRS). During an emotional Stroop task consisting of blocks of color and swear words, metabolite concentration changes were measured in the ventromedial prefrontal cortex (vmPFC) and the left amygdalohippocampal region (AMHC) of healthy adults (14 F/27 M, 23{+/-}4 years old) using fMRS. The dynamic changes in Glu and their associations with the emotional state of the participants were finally evaluated based on 36 datasets from the vmPFC and 30 from the AMHC. A repeated-measures analysis of covariance revealed a modest effect of parental VA severity on Glu changes in the vmPFC. Furthermore, the total score on the Verbal Abuse Questionnaire by parents (pVAQ) was associated with the Glu response to swear words ({Delta}GluSw e). The interaction term of {Delta}GluSw e and baseline N-acetyl aspartate (NAA) level in the vmPFC could be used to predict state-trait anxiety level and depressive mood. We could not find any significant associations between {Delta}GluSw e in the AMHC and either pVAQ or emotional states. We conclude that parental VA exposure in individuals is associated with a greater Glu response towards VA-related stimuli in the vmPFC and that the accompanying low NAA level may be associated with anxiety level or depressive mood.

neuroscience↗

bioRxiv2022

Hippocampal protein aggregation signatures fully distinguish pathogenic and wildtype UBQLN2 in amyotrophic lateral sclerosis

Mutations in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) characterised by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus, and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial ALS or FTD cases not caused by UBQLN2 mutations, particularly C9orf72-linked cases. This makes the mechanistic role of ubiquilin 2 mutations and the value of ubiquilin 2 pathology for predicting genotype unclear. Here we examine a cohort of 41 genotypically diverse ALS cases with or without FTD, including five cases with UBQLN2 variants (resulting in p.S222G, p.P497H, p.P506S, and two cases with p.T487I). Using multiplexed (5-label) fluorescent immunohistochemistry, we mapped the co-localisation of ubiquilin 2 with phosphorylated TDP-43 (pTDP-43), dipeptide repeat aggregates, and p62, in the hippocampus of controls (n=5), or ALS with or without FTD in sporadic (n=20), unknown familial (n=3), SOD1-linked (n=1), FUS-linked (n=1), C9orf72-linked (n=5), and UBQLN2-linked (n=5) cases. We differentiate between i) ubiquilin 2 aggregation together with pTDP-43 or dipeptide repeat proteins, and ii) ubiquilin 2 self-aggregation promoted by UBQLN2 gene mutations that cause ALS/FTD. Overall, we describe a hippocampal protein aggregation signature that fully distinguishes mutant from wildtype ubiquilin 2 in ALS with or without FTD, whereby mutant ubiquilin 2 is more prone than wildtype to aggregate independently of driving factors. This neuropathological signature can be used to assess the pathogenicity of UBQLN2 gene variants and to understand the mechanisms of UBQLN2-linked disease.

neuroscience↗

bioRxiv2021

Gut bacteria regulate the pathogenesis of Huntington's disease in Drosophila

Changes in the composition of gut microbiota are implicated in the pathogenesis of several neurodegenerative disorders. Here, we investigated whether gut bacteria affect the progression of Huntingtons disease (HD) in transgenic Drosophila melanogaster (fruit fly) models expressing human full-length or N-terminal fragments of mutant huntingtin (HTT) protein, here referred to as HD flies. We find that elimination of commensal gut bacteria by antibiotics reduces the aggregation of amyloidogenic N-terminal fragments of HTT and delays the development of motor defects. Conversely, colonization of HD flies with Escherichia coli (E. coli), a known pathobiont of human gut with links to neurodegeneration, accelerates HTT aggregation, aggravates immobility and shortens lifespan. Similar to antibiotics, treatment of HD flies with small compounds such as luteolin, a flavone, or crocin a beta-carotenoid, ameliorates disease phenotypes and promotes survival. Crocin prevents colonization of E. coli in the gut and alters the abundance of commensal bacteria, which may be linked to its protective effects. The opposing effects of E. coli and crocin on HTT aggregation, motor defects and survival in transgenic Drosophila models support the involvement of gut-brain networks in the pathogenesis of HD.

neuroscience↗

bioRxiv2021

Sonicated fibrils of huntingtin exon-1 preferentially seed neurons and produce toxic assemblies

Huntingtons disease (HD) is a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) repeats in the exon-1 of huntingtin protein (HTT). The expanded polyQ enhances the amyloidogenic propensity of HTT exon 1 (HTTex1), which forms a heterogeneous mixture of assemblies with some being neurotoxic. While predominantly intracellular, monomeric and aggregated mutant HTT species are also present in the cerebrospinal fluids of HD patients, however, their biological properties are not well understood. To explore the role of extracellular mutant HTT in aggregation and toxicity, we investigated the possible uptake and amplification of recombinant HTTex1 assemblies in cell culture models. We found seeding-competent species in the sonicated HTTex1 fibrils, which preferentially entered human neurons and triggered the amplification of neurotoxic assemblies; astrocytes or epithelial cells were not permissive to the HTTex1 seeding. The aggregation of HTTex1 seeds in neurons depleted endogenous HTT protein with non-pathogenic polyQ repeat, activated apoptotic caspase-3 pathway and induced nuclear fragmentation. Using a panel of novel monoclonal antibodies and genetic mutation, we identified epitopes within the N-terminal 17 amino acids and proline-rich domain of HTTex1 mediating neural seeding. Synaptosome preparations from the brains of HD mice also contained similar neurotoxic seeding-competent mutant HTT species. Our findings suggest that amyloidogenic extracellular mutant HTT assemblies may selectively enter neurons, propagate and produce neurotoxic assemblies.

neuroscience↗

bioRxiv2020

Manage flowering time in Miscanthus and sugarcane to facilitate intra- and intergeneric crosses

Miscanthus is a close relative of Saccharum and a potentially valuable genetic resource for improving sugarcane. Differences in flowering time within and between Miscanthus and Saccharum hinders intra- and interspecific hybridizations. A series of greenhouse experiments were conducted over three years to determine how to synchronize flowering time of Saccharum and Miscanthus genotypes. We found that day length was an important factor influencing when Miscanthus and Saccharum flowered. Sugarcane could be induced to flower in a central Illinois greenhouse using supplemental lighting to reduce the rate at which days shortened during the autumn and winter to 1 min d-1, which allowed us to synchronize the flowering of some sugarcane genotypes with Miscanthus genotypes primarily from low latitudes. In a complementary growth chamber experiment, we evaluated 33 Miscanthus genotypes, including 28 M. sinensis, 2 M. floridulus, and 3 M. xgiganteus collected from 20.9{degrees} S to 44.9{degrees} N for response to three day lengths (10 h, 12.5 h, and 15 h). High latitude-adapted M. sinensis flowered mainly under 15 h days, but unexpectedly, short days resulted in short, stocky plants that did not flower; in some cases, flag leaves developed under short days but heading did not occur. In contrast, for M. sinensis and M. floridulus from low latitudes, shorter day lengths typically resulted in earlier flowering, and for some low latitude genotypes, 15 h days resulted in no flowering. However, the highest ratio of reproductive shoots to total number of culms was typically observed for 12.5 h or 15 h days. Latitude of origin was significantly associated with culm length, and the shorter the days, the stronger the relationship. Nearly all entries achieved maximal culm length under the 15 h treatment, but the nearer to the equator an accession originated, the less of a difference in culm length between the short-day treatments and the 15 h day treatment. Under short days, short culms for high-latitude accessions was achieved by different physiological mechanisms for M. sinensis genetic groups from the mainland in comparison to those from Japan; for mainland accessions, the mechanism was reduced internode length, whereas for Japanese accessions the phyllochron under short days was greater than under long days. Thus, for M. sinensis, short days typically hastened floral induction, consistent with the expectations for a facultative short-day plant. However, for high latitude accessions of M. sinensis, days less than 12.5 h also signaled that plants should prepare for winter by producing many short culms with limited elongation and development; moreover, this response was also epistatic to flowering. Thus, to flower M. sinensis that originates from high latitudes synchronously with sugarcane, the former needs day lengths >12.5 h (perhaps as high as 15 h), whereas that the latter needs day lengths <12.5 h.

plant biology↗