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La, T.

Publications and source records attributed to La, T..

14 recordsLinked to original sources

A transcriptomic atlas of grass senescence reveals divergent underground sink networks limit nitrogen recycling in annuals

Senescence enables plants to remobilize and recycle nutrients from aging organs to support growth, reproduction, and survival. In annual crops like maize, nitrogen remobilization from leaves to grain is incomplete, with 30-50% of nitrogen stranded in aboveground tissues and subject to environmental loss. Mitigating nitrogen loss in annual crops could be achieved by leveraging the physiological strategies of perennial grasses, which remobilize nitrogen and other nutrients into underground organs at the end of the growing season, thereby preventing environmental leakage. To uncover the molecular basis of perennial nitrogen recycling to underground organs, we built a transcriptomic atlas from field-grown plants, comprising 2,685 RNA-seq libraries from 14 grass species within the Panicoideae (Poaceae), utilizing maize and sorghum as annual references for comparative analyses. The atlas spans leaves, roots, stalks, and rhizomes across two seasons, from mid-growing season to senescence. Using a photosynthetic index to align the leafs transition from nitrogen sink to source across species, co-expression network analysis revealed that the subnetworks driving leaf nitrogen recycling are preserved across annuals and perennials. However, we discovered that the subnetworks associated with underground sink establishment, specifically those associated with seed-like dormancy and desiccation tolerance pathways, have diverged among annual crop accessions. Our work identifies conserved gene candidates and networks that could be used to reintroduce perennial-like nutrient recycling into annual crops to enhance long-term nutrient retention in the field.

plant biology↗

Incentive Salience, not Psychomotor Sensitization or Tolerance, Drives Escalation of Cocaine Self-Administration in Heterogeneous Stock Rats

Sensitization and tolerance are two phenomena often studied independently despite overlapping neurobiological substrates. Each has extensive research showing their influence on the development and maintenance of addiction, but the degree to which they drive escalation in cocaine self-administration is poorly understood. Using self-administration, intravenous noncontingent infusions, and pose-estimation machine vision, we find that incentive salience, not psychomotor sensitization or tolerance, drives the escalation of cocaine self-administration in heterogenous stock rats. Individual differences in psychomotor sensitization or tolerance were found to have no effect on cocaine intake. Incentive salience as measured by locomotion and active lever entrances per meter traveled occurring before the self-administration session began (pre-lever activity measures) during Short Access (2-hours) was found to predict intake during Long Access (6-hours). Both pre-lever locomotion and active lever entrances per meter were found to increase during Long Access and after two-to-three days of abstinence. Critically, rats with low pre-lever activity during Short Access escalated both their intake and pre-lever measures by the end of Long Access to levels comparable with high pre-lever activity rats who maintained their elevated responding. These findings support the notion that incentive salience during Short Access is a catalyst to escalated use and an early marker of addiction vulnerability. Moreover, they suggest that individuals initially resistant to incentive salience can, with sufficient exposure, become sensitized and escalate cocaine use to the same level as more susceptible individuals. Analysis of pre-lever activity offers a novel longitudinal behavioral marker to predict vulnerability and provides a framework for understanding individual trajectories of addiction.

neuroscience↗

Cross-species optimization of nuclei isolation in plants

Single-cell technologies are transforming plant biology, yet broadly transferable nuclei isolation remains a key bottleneck for snRNA-seq. We developed a reproducible, Percoll-based workflow that is applicable to multiple maize tissues and eight additional plant species. In maize, nuclei from root, stem, leaf, and embryo consistently concentrated at the 80% Percoll interface and exhibited high integrity, with typical recoveries > 50,000 nuclei per sample. For other species, gradient compositions were tuned according to genome size to achieve efficient enrichment and clean suspensions, and yields ranged from 20,000 to 50,000 nuclei per sample. Downstream validation showed that nuclei from special interest maize and Tripsacum generated high-quality 10x Genomics snRNA-seq libraries, as supported by cDNA quality profiles. These results demonstrate the versatility and robustness of the method across species and tissues.

plant biology↗

Grass Rhizome Proteomics Reveals Convergent Freezing-Tolerance Strategies

O_LIGrasses in the PACMAD clade independently colonized cold environments from warm-climate ancestors, but whether their molecular responses to freezing reflect shared evolutionary solutions or lineage-specific innovations remains unknown. We used comparative proteomics to test whether protein-level cold responses show stronger cross-species conservation than previously observed at the transcript level. C_LIO_LIWe quantified seasonal rhizome proteomes (winter vs summer) from five PACMAD species grown in a common garden exposed to sustained sub-zero temperatures, identified differentially abundant proteins, and compared fold-change magnitudes across species using orthogroup-based correlation analyses. We further examined LEA3 protein structure through hydropathy profiling and motif analysis. C_LIO_LIShared cold-responsive proteins showed higher cross-species fold-change correlation ({rho} = 0.80) than background proteins ({rho} = 0.45), despite greater divergence in baseline abundance. LEA3 was the only ortholog elevated across all five species. Cold-tolerant species contained more tandem 11-mer repeats than the cold-sensitive maize, and two species accumulated multiple LEA3 paralogs, increasing total LEA3 abundance. C_LIO_LIIndependent evolution of freezing tolerance in PACMAD grasses is governed by evolutionary constraints on protein-level response magnitude, reflecting the retention of an ancestral protective capacity. Structural divergence of LEA3 in maize suggests that transcriptional induction alone does not ensure freezing tolerance; functional protection likely requires intact motif architecture. C_LI

evolutionary biology↗

Extensive modulation of a conserved cis-regulatory code across 589 grass species

The growing availability of genomes from non-model organisms offers new opportunities to identify functional loci underlying trait variation through comparative genomics. While cis-regulatory regions drive much of phenotypic evolution, linking them to specific functions remains challenging. We identified 514 cis-regulatory motifs enriched in regulatory regions of five diverse grass species, with 73% consistently enriched across all, suggesting a deeply conserved regulatory code. We then quantified conservation of specific motif instances across 589 grass species, revealing widespread gain and loss over evolutionary time. Conservation declined rapidly over the first few million years of divergence, yet [~]50% of motif instances were conserved back to the origin of grasses [~]100 million years ago. Conservation patterns varied by gene class, with modestly higher conservation at transcription factor genes. To test for adaptive cis-regulatory changes, we used phylogenetic mixed models to identify motif gains and losses associated with ecological niche transitions. Our models revealed polygenic adaptation across 810 motif-orthogroup combinations, including convergent gains of HSF/GARP motifs at an Alpha-N-acetylglucosaminidase gene associated with adaptation to temperate environments. Our results support a "stable code, variable sites" model in which cis-regulatory evolution involves extensive turnover of individual binding site instances while largely preserving transcription factors binding preferences. Cis-regulatory changes at hundreds to thousands of genes appear to contribute to environmental adaptation. Our results highlight the potential of comparative genomics and phylogenetic mixed models to reveal the genetic basis of complex traits.

genomics↗

Extensive genome evolution distinguishes maize within a stable tribe of grasses

Over the last 20 million years, the Andropogoneae tribe of grasses has evolved to dominate 17% of global land area. Domestication of these grasses in the last 10,000 years has yielded our most productive crops, including maize, sugarcane, and sorghum. The majority of Andropogoneae species, including maize, show a history of polyploidy - a condition that, while offering the evolutionary advantage of multiple gene copies, poses challenges to basic cellular processes, gene expression, and epigenetic regulation. Genomic studies of polyploidy have been limited by sparse sampling of taxa in groups with multiple polyploidy events. Here, we present 33 genome assemblies from 27 species, including chromosome-scale assemblies of maize relatives Zea and Tripsacum. In maize, the after-effects of polyploidy have been widely studied, showing reduced chromosome number, biased fractionation of duplicate genes, and transposable element (TE) expansions. While we observe these patterns within the genus Zea, 12 other polyploidy events deviate significantly. Those tetraploids and hexaploids retain elevated chromosome number, maintain nearly complete complements of duplicate genes, and have only stochastic TE amplifications. These genomes reveal variable outcomes of polyploidy, challenging simple predictions and providing a foundation for understanding its evolutionary implications in an ecologically and economically important clade.

evolutionary biology↗

Contrasting Rhizosphere Nitrogen Dynamics in Andropogoneae Grasses: Implications for Sustainable Agriculture

Background: Nitrogen (N) fertilization in crop production significantly impacts ecosystems, often disrupting natural plant-microbe-soil interactions and causing environmental pollution. Our research tested the hypothesis that phylogenetically related perennial grasses might preserve rhizosphere management strategies conducive to a sustainable N economy for crops. Method: We analyzed the N cycle in the rhizospheres of 36 Andropogoneae grass species related to maize and sorghum, investigating their impacts on N availability and losses. This assay is supplemented with the collection and comparison of native habitat environment data for ecological inference as well as cross-species genomic and transcriptomic association analyses for candidate gene discovery. Result: Contrary to our hypothesis, all examined annual species, including sorghum and maize, functioned as N "Conservationists," reducing soil nitrification potential and conserving N. In contrast, some perennial species enhanced nitrification and leaching ("Leachers"). Yet a few other species exhibited similar nitrification stimulation effects but limited NO3- losses ("Nitrate Keepers"). We identified significant soil characteristics as influential factors in the eco- evolutionary dynamics of plant rhizospheres, and highlighted the crucial roles of a few transporter genes in soil N management and utilization. Conclusion: These findings serve as valuable guidelines for future breeding efforts for global sustainability.

plant biology↗

Fishing for a reelGene: evaluating gene models with evolution and machine learning

Assembled genomes and their associated annotations have transformed our study of gene function. However, each new assembly generates new gene models. Inconsistencies between annotations likely arise from biological and technical causes, including pseudogene misclassification, transposon activity, and intron retention from sequencing of unspliced transcripts. To evaluate gene model predictions, we developed reelGene, a pipeline of machine learning models focused on (1) transcription boundaries, (2) mRNA integrity, and (3) protein structure. The first two models leverage sequence characteristics and evolutionary conservation across related taxa to learn the grammar of conserved transcription boundaries and mRNA sequences, while the third uses conserved evolutionary grammar of protein sequences to predict whether a gene can produce a protein. Evaluating 1.8 million gene models in maize, reelGene found that 28% were incorrectly annotated or nonfunctional. By leveraging a large cohort of related species and through learning the conserved grammar of proteins, reelGene provides a tool for both evaluating gene model accuracy and genome biology.

genomics↗

It All Rolls Downstream: Upstream Control of Physical Activity Regulation

Physical activity is regulated by a variety of genetic molecules. However, the pathways through which those molecules work to regulate activity is largely unknown. The purpose of this study was to gather the known genetic molecules that are associated with activity regulation and define overall upstream regulator pathways through which these molecules work. We conducted a systematic review to gather all available published datasets related to physical activity regulation, standardized the data for genomic location and species, and used this data, in an unbiased manner to create a dataset that was used: (1) to physically map and visualize all identified molecules to homologous chromosome locations and (2) as the dataset for which an Upstream Regulator Analysis (URA) was conducted using Qiagen Ingenuity Pathway Analysis (IPA) software. Our search resulted in 469 genetic molecules (e.g. genomic variant, transcript, protein, micro-RNA) that were split into brain (n=366) and muscle (n=345) sub-groups, which was our attempt to separate differences in central vs peripheral pathways. The brain and muscle data sets had several potential upstream regulators, the top-rated being {beta}-estradiol as a regulator for 19.5% and 21% of the brain and muscle datasets respectively. To our knowledge, {beta}-estradiols identification as a potential regulator, is the first evidence to link the well-known effects of sex hormones on physical activity with genetic regulation of physical activity. There were a variety of potential upstream regulators for the molecules collected in this review, but interestingly, three of the top five for both brain and muscle are nuclear receptor binding ligands; estradiol (estrogen receptor), dexamethasone (glucocorticoid receptor), and tretinoin (retinoic acid receptor), indicating a potential role of nuclear receptors in the regulation of physical activity. Selective nuclear receptor modulation may be an area of interest in future mechanistic studies of the genetic regulation of physical activity.

genetics↗

Melon pan-genome and multi-parental framework for high-resolution trait dissection

Linking between genotype and phenotype is a fundamental goal in biology and requires robust data for both layers. The prominent increase in plant genome sequencing and comparisons of multiple related individuals, exposed the abundance of structural genomic variation and suggest that a single reference genome cannot represent the complete sequence diversity of a crop species, leading to the expansion of the pan-genome concept. For high-resolution forward genetics, this unprecedented access to genomic variation should be paralleled by availability and phenotypic characterization of genetic diversity, and effective integration between these layers. Here, we describe a multi-parental framework for trait dissection in melon, leveraging a novel pan-genome constructed for this crop. Melon (Cucumis melo L.) is an important crop from the Cucurbitaceae family, which display extensive phenotypic variation available for breeding. A diverse core set of 25 founder lines (MelonCore25) was sequenced using a combination of short and long-read technologies and their genomes were assembled de novo. The construction of a melon pan-genome exposed substantial variation in genome size and structure, including detection of ~300,000 structural variants and ~9 million SNPs. A half-diallel derived set of 300 F2 populations representing all possible MelonCore25 parental combinations was constructed as framework for trait dissection through integration with the pan-genome. We demonstrate the potential of this unified framework for genetic analysis of various melon traits, including rind color and mottling pattern, fruit sugar content and resistance to fungal diseases. We anticipate that utilization of this integrated resource will enhance genetic dissection of important traits and accelerate melon breeding. Significance statementPan-genomes aim to address the abundance of genome structural variation within species for improved genomic analyses. New pan-genome, constructed from de novo genome assemblies of 25 diverse melon (Cucumis melo L.) accessions is integrated with a half-diallel derived set of 300 F2 populations representing all possible parental combinations. The potential of this unified multi-parental trait dissection framework for melon genetics and breeding is presented.

genetics↗

Mitochondrial DNA metabolism is coupled with 20S proteasome function via regulation of deoxyribonucleotide homeostasis in Saccharomyces cerevisiae

The synthesis of mitochondrial DNA (mtDNA) is not coupled with cell cycle. Previous studies have shown that the size of deoxyribonucleoside triphosphate (dNTP) pools plays an important role in regulating mtDNA replication and amplification. In yeast, dNTPs are synthesized by the cytosolic ribonucleotide reductase (RNR). It is currently poorly understood as to how RNR activity is regulated in non-dividing or quiescent cells to finely tune mtDNA metabolism to cope with different metabolic states. Here, we show that defect in the 20S proteasome drastically destabilizes mtDNA. The mtDNA instability phenotype in 20S proteasome mutants is suppressed by overexpression of RNR3 or by the deletion of SML1, encoding a minor catalytic subunit and an intrinsic inhibitor of RNR respectively. We found that Sml1 is stabilized in the 20S proteasomal mutants, suggesting that 20S affects mtDNA stability by stabilizing Sml1. Interestingly, defect in the regulatory 19S proteasomal function has only subtle effect on mtDNA stability, supporting a role of the 20S proteasome in dNTP homeostasis independent of 19S. Finally, we found that when cells are transitioned from glycolytic to oxidative growth, Sml1 level is reduced in a 20S-dependent manner. In summary, our study establishes a link between cellular proteostasis and mtDNA metabolism through the regulation of dNTP homeostasis. We propose that increased degradation of Sml1 by the 20S proteasome under respiratory conditions provides a mechanism to stimulate dNTP synthesis and promote mtDNA amplification.

genetics↗

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. In consequence, PLANE promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor patient outcomes. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.

cancer biology↗

The microstructure investigation of plant architecture with X-ray microscopy

BackgroundIn recent years, the plant morphology has been well studied by multiple approaches at cellular and subcellular levels. Two-dimensional (2D) microscopy techniques offer imaging of plant structures on a wide range of magnifications for researchers. However, subcellular imaging is still challenging in plant tissues like roots and seeds.\n\nResultsHere we use a three-dimensional (3D) imaging technology based on the ZEISS X-ray microscope (XRM) Versa and analyze several plant tissues from different plant species. The XRM provides new insights into plant structures using non-destructive imaging at high-resolution and high contrast. We also developed a workflow aiming to acquire accurate and high-quality images in the context of the whole specimen. Multiple plant samples including rice, tobacco, Arabidopsis and maize were used to display the differences of phenotypes, which indicates that the XRM is a powerful tool to investigate plant microstructure.\n\nConclusionsOur work provides a novel observation method to evaluate and quantify tissue specific differences for a range of plant species. This new tool is suitable for non-destructive seed observation and screening.

plant biology↗

Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis

Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts and Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infection in mammals. While the uptake of cholesterol by Mtb is mediated by the Mce4 transporter, the route(s) of uptake of fatty acids remain unknown. Here, we demonstrate that an uncharacterized protein LucA, integrates the assimilation of both cholesterol and fatty acids in Mtb. LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters. We also demonstrate that Mce1 functions as an important fatty acid transporter in Mtb and we determine that the integration of cholesterol and fatty acid transport by LucA is required for full bacterial virulence in vivo. These data establish that fatty acid and cholesterol assimilation are inexorably linked in Mtb and reveals a key role for LucA in coordinating both transport activities.

microbiology↗