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Li, S.

Publications and source records attributed to Li, S..

At least 181 records · Page 10Linked to original sources

Recessive POPDC1 Truncation Causes Lethal Short-QT Pattern Arrhythmogenic Cardiomyopathy with Multi-Ion Channel Remodeling and Ankyrin-G Scaffold Disruption

AimsBiallelic variants in Popeye domain containing 1 (POPDC1) classically cause limb-girdle muscular dystrophy, but their impact on cardiac system remains unclear. We investigated the functional consequence of a POPDC1 frameshift variant (c.448delT), first identified in a consanguineous family with arrhythmogenic cardiomyopathy (ACM) and sudden death. Methods and resultsComprehensive clinical and genetic evaluation was followed by mechanistic studies in an orthologous Popdc1 knock-in rat model. Functional characterization included biotelemetry and programed electrical stimulation, optical mapping, patch clamp, intracellular Ca2+ imaging, proteomics, and oxidative stress assays. Homozygous mutants (Popdc1fs/fs) exhibited a shortened QTc interval and high incidence of ventricular tachycardia compared to wild-type (Popdc1+/+). Urethane anesthesia provoked second-degree AV block in all 10 Popdc1fs/fs rats but in only 1 of 9 Popdc1+/+ littermates. Optical mapping demonstrated abbreviated action potentials, slowed conduction velocity, and inducible polymorphic VT. Patch clamp confirmed accelerated repolarization, with upregulated transient outward potassium currents (Ito) and L-type calcium currents (ICa, L), but downregulated peak sodium currents (INa). Multi-omics and ultrastructural analyses revealed a post-translational collapse of intercalated disc: POPDC1 loss destabilized Ankyrin-G and its membrane-anchored cargo, Nav1.5, coinciding with enhanced Kv4.3 and Cav1.2 protein levels. These disruptions create a convergence of delayed conduction and shortened refractoriness, forming substrate for malignant re-entry. ConclusionWe defined a recessive short-QT ACM leading to potentially fatal arrhythmias caused by biallelic POPDC1 truncation driving Ankyrin-G disruption, manifesting as a triad: (1) bradycardia/AV block, (2) accelerated repolarization as short-QT pattern/diffuse T-wave flattening or inversion, and (3) progressive cardiomyopathy and sudden death. Whats new?O_LIWe define a novel diagnostic triad for recessive short-QT arrhythmogenic cardiomyopathy (rSQT-ACM) in a loss-of-function POPDC1 truncation: (1) early-onset bradyarrhythmia (sinus bradycardia or AV block); (2) a paradoxical short-QT interval with maladaptive rate response/diffuse T-wave flattening or inversion; and (3) progressive cardiomyopathy accompanied accompanied by with SCD. C_LIO_LIMechanistically, biallelic POPDC1 truncation induces collapse of the POPDC1-AnkG hub, which triggers a unique "opposing remodeling" phenotype (severe INa reduction coupled with paradoxical upregulation of Kv4.3-mediated Ito), and established a unified "slow-conduction, short-wavelength" substrate that underpins malignant re-entry. C_LIO_LIImplications for safety and device therapy: Nav1.5 deficiency indicates that sodium channel blockers may be contraindicated, and early ICD implantation may be preferable to bradycardia pacing. C_LIO_LIMechanism-directed treatments: POPDC1s recessive inheritance and small gene size make it a strong candidate for AAV-mediated gene supplementation aimed at restoring the intercalated disc architecture and ion-channel anchoring. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/710328v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1012d79org.highwire.dtl.DTLVardef@5073dcorg.highwire.dtl.DTLVardef@1e69bc2org.highwire.dtl.DTLVardef@fc15ec_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

genetics↗

Metabolic control of drug resistance by a mycobacterial ion channel

Pyrazinamide (PZA) is a cornerstone of modern tuberculosis therapy, yet its context-dependent activity has obscured both its mode of action and resistance mechanisms. Using a host-mimicking culture system integrated with genome-wide CRISPRi profiling, metabolomics, and comparative genomics, we identify a previously unrecognized driver of PZA resistance in humans: loss of the ion channel Rv2571c. Rv2571c mediates -ketoglutarate efflux, amplifying PZA-induced cytoplasmic acidification under host-relevant acidic conditions. Loss-of-function mutations confer resistance in vitro and in vivo and are under positive selection in clinical isolates, establishing this pathway as a resistance determinant in patients. Together, these findings define a novel, ion channel-mediated resistance mechanism, establish cytoplasmic acidification as the basis of PZA killing, and inform resistance detection and treatment-shortening drug development.

microbiology↗

TFBSpedia: a comprehensive human and mouse transcription factor binding sites database

Mapping the genomic locations and patterns of transcription factor binding sites (TFBS) is essential for understanding gene regulation and advancing treatments for diseases driven by DNA modifications, including epigenetic changes and sequence variants. Although several TFBS databases exist, no study has systematically benchmarked these databases across different sequencing technologies and computational algorithms. In this study, we addressed this gap by constructing a TFBS database that integrates all available ENCODE cell line ATAC-seq and Cistrome Data Browser ChIP-seq datasets, comprising 11.3 million human and 1.87 million mouse TFBS. We also integrated previously published TFBS resources (Factorbook, Unibind, RegulomeDB, and ENCODE_footprint) and found each contains a substantial fraction of unique TFBS predictions, highlighting significant discrepancies among existing resources. To assess the accuracy of the combined TFBS regions, we assembled ten independent genomic annotation datasets for evaluation and found that TFBS regions predicted by multiple databases are more likely to represent true and biologically meaningful binding sites. For each predicted TFBS region, we define two scores: the confidence score reflects prediction reliability, while the importance score represents biological functional relevance. Finally, we introduce TFBSpedia, a lightweight and efficient search engine that enables rapid retrieval of TFBS regions and comprehensive annotation information across the integrated databases.

bioinformatics↗

DPGT: A spark based high-performance joint variant calling tool for large cohort sequencing

BackgroundJoint variant calling is a crucial step in population-scale sequencing analysis. While population-scale sequencing is a powerful tool for genetic studies, achieving fast and accurate joint variant calling on large cohorts remains computationally challenging. FindingsTo meet this challenge, we developed Distributed Population Genetics Tool (DPGT), an efficient computing framework and a robust tool for joint variant calling on large cohorts based on Apache Spark. DPGT simplifies joint calling tasks for large cohorts with a single command on a local computer or a computing cluster, eliminating the need for users to create complex parallel workflows. We evaluated the performance of DPGT using 2,504 1000 Genomes Project (1KGP), 6 Genome in a Bottle (GIAB) and 9,158 internal whole genome sequencing (WGS) samples together with existing methods. As a result, DPGT produced results comparable in accuracy to existing methods, with less time and better scalability. ConclusionsDPGT is a fast, scalable, and accurate tool for joint variant calling. The source code is available under a GPLv3 license at https://github.com/BGI-flexlab/DPGT, implemented in Java and C++.

bioinformatics↗

RankMap: Rank-based reference mapping for fast and robust cell type annotation in spatial and single-cell transcriptomics

Accurate cell type annotation is essential for the analysis of single-cell and spatial transcriptomics data. While reference-based annotation methods have been widely adopted, many existing approaches rely on full-transcriptome profiles and incur substantial computational cost, limiting their applicability to large-scale spatial datasets and platforms with partial gene panels. Here, we present RankMap (https://github.com/jinming-cheng/RankMap), an efficient and flexible R package for reference-based cell type annotation across both single-cell and spatial transcriptomics. RankMap transforms gene expression profiles into rank-based representations using the top expressed genes per cell, improving robustness to platform-specific biases and expression scale differences. A multinomial regression model trained with elastic net regularization is then used to predict cell types and associated confidence scores. We benchmarked RankMap on five spatial transcriptomics datasets, including Xenium, MERFISH, and Stereo-seq, as well as two single-cell datasets, and compared it with established methods such as SingleR, Azimuth, and RCTD. RankMap achieved competitive or superior annotation accuracy while consistently reducing runtime compared to existing methods, particularly for large spatial datasets. These results demonstrate that RankMap provides a scalable and robust solution for reference-based cell type annotation in modern single-cell and spatial transcriptomics studies.

bioinformatics↗

CD8+ T cells are primed by cDC1 and exacerbate tau-mediated neurodegeneration

There are changes in adaptive immunity in Alzheimers disease (AD) and increases in activated CD8+ T cells in brain correlate with tau pathology1-3. However, which cells mediate T cell priming in tau-mediated neurodegeneration remains unclear. In different conditions such as cancer, viral infections, and autoimmune diseases outside the CNS, conventional type-1 dendritic cells (cDC1) perform antigen cross-presentation to prime CD8+ T cells4,5. We demonstrate that tauopathy mice deficient in cDC1 are markedly protected against tau-mediated neurodegeneration and display a selective decrease in brain CD8+ T cell infiltration and glial reactivity. The remaining CD8+ T cells showed an antigen inexperienced status with less clonal expansion, indicating suboptimal T cell priming. We confirm that brain derived antigens are presented in secondary lymphoid tissues to prime CD8+ T cells. Our study identifies cDC1 cells as critical for CD8+ T cell priming outside the CNS. This priming is required for a large increase of activated CD8+ T cells in the brain which promotes tau-mediated neurodegeneration.

neuroscience↗

Targeted knockout of CYP79A1 reduces cyanogenic potential in grain sorghum

Sorghum bicolor is a climate-resilient C4 crop used for food, forage, and bioenergy, but broader adoption is constrained by accumulation of the cyanogenic glucoside dhurrin, which can release toxic hydrogen cyanide (HCN) upon tissue damage. Dhurrin levels are especially high in juvenile tissues, creating risk for grazing animals and limiting use in mixed crop-livestock systems. Here, we establish a CRISPR-Cas9 genome-editing strategy targeting CYP79A1, which catalyzes the first committed step in dhurrin biosynthesis, in the elite grain sorghum inbred RTx430, yielding transgene-free lines with stable, heritable reduction in cyanogenic potential across early vegetative development. Homozygous cyp79a1 knockouts were negligibly cyanogenic, whereas heterozygous plants exhibited approximately half the cyanogenic potential of unedited nulls. Consistent with established livestock grazing guidelines, only homozygous knockouts fell below thresholds considered hazardous for incidental grazing. This work establishes CYP79A1 as a practical and heritable genome-editing target for reducing sorghum cyanogenesis and provides a clear path for deployment of low-cyanogenic alleles in elite breeding backgrounds.

plant biology↗

Efficient derivation and transcriptional characterization of mouse extra-embryonic endoderm stem cell lines generated by somatic cell nuclear transfer

Somatic cell nuclear transfer (SCNT) holds great promise for regenerative medicine and agriculture, but its application is severely hampered by low efficiency, primarily attributable to aberrant epigenetic reprogramming. Although embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) have been successfully derived from cloned embryos, an in vitro counterpart of the primitive endoderm (PrE) lineage has remained unavailable. To address this gap, this study reports the first successful establishment of extra-embryonic endoderm stem cell lines (XENs) from mouse SCNT-derived blastocysts (NT-XENs). Under conventional culture conditions, NT-XENs were generated from hybrid B6D2F1 blastocysts at a high efficiency of 55%, comparable to that of fertilization-derived XEN lines (FD-XENs, 50%), whereas derivation from inbred C57BL/6J SCNT-derived blastocysts was markedly lower (12.5%). Immunofluorescence and NanoString multiplex gene expression profiling confirmed that NT-XENs robustly expressed specific marker genes for PrE/XENs (e.g., Gata4, Gata6, Sox17), while exhibiting negligible or absent expression of pluripotency and trophoblast markers. Based on NanoString assay data, NT-XENs and FD-XENs shared highly similar global gene expression patterns, yet also exhibited some nonnegligible differences, exemplified by the differentially expressed genes (DEGs) Pecam1, Gtl2, Thbd and Xlr3b, which may suggest that the NT-XENs resided in a more differentiated state (potentially biased toward parietal endoderm (PE)) and retained SCNT-specific epigenetic imprinting errors, including aberrant X-chromosome inactivation and dysregulation of imprinted domains. In summary, this study successfully establishes NT-XEN cell lines, providing a valuable in vitro model for investigating the reprogramming scenarios of PrE lineage in SCNT and offering novel insights into the mechanisms underlying developmental failure of cloned embryos.

developmental biology↗

Sampling Mismatch and Correction for Ptychographic Single-Particle Analysis

Ptychographic single-particle analysis (SPA) is a promising technique for high-resolution biological imaging but is still limited by sub-nanometer resolution. In this study, we identified and investigated a critical issue termed sampling mismatch in ptychography that is caused by inaccuracies in the scanning step size and the pixel size of convergent beam electron diffraction (CBED) images. This mismatch induces pixel-size deviations in the reconstructed micrographs and modulates information transfer through a mismatch-induced modulation function (MIMF), which is characterized by phase reversals at specific spatial frequencies of the micrographs. These phase reversals, which vary with the defocus, cause destructive interference when merging micrographs, fundamentally limiting the resolution of SPA. We proposed a correction strategy and demonstrated, on the T. Acidophilum 20S proteasome and apoferritin datasets, that correcting sampling parameters eliminates signal distortions and improves resolution for [~]1.5 [A]. These findings underscore the necessity for the precise control and calibration of the scanning system to achieve high-resolution ptychographic SPA.

biophysics↗

Accurate Macromolecular Complex Modeling for Cryo-EM with CryoZeta

Cryogenic electron microscopy (cryo-EM) has become a widely used technique for determining the three-dimensional structures of biological macromolecules. Despite its advantages, building accurate structural models from cryo-EM data remains challenging, particularly at non-atomic resolutions. Here, we present CryoZeta, a de novo structure modeling program that leverages a diffusion-based generative deep neural network to integrate cryo-EM map density features with a biomolecular structure prediction pipeline similar to Alphafold3. By jointly leveraging sequence information and density-based features, CryoZeta generates highly accurate structural models that are consistent with the experimental map density. Evaluated on benchmark datasets covering protein complexes, protein-nucleic acid assemblies, and nucleic acid-only systems at resolutions up to 10 [A], CryoZeta consistently outperforms existing cryo-EM modeling methods in atomic accuracy. These results highlight the benefits of directly incorporating cryo-EM density into modern structure prediction pipelines and establish the method as a robust tool for automated, high-fidelity modeling from cryo-EM maps.

bioinformatics↗

ATP8B1-TMEM30B Flippase Activity Maintains Stereocilia Lipid Asymmetry Required for Hearing

Sensory hair cells convert sound-induced vibrations into electrical signals through a process called mechano-electrical transduction (MET). While the protein components of the MET complex are well studied, increasing evidence indicates that MET channel properties are significantly modulated by the surrounding lipid bilayer. The asymmetric distribution of membrane lipids between the inner and outer membrane leaflets is well established to shape membrane mechanics. The recent discovery that the core MET components TMC1 and TMC2 also act as lipid scramblases suggests a direct role for membrane lipid asymmetry in the dynamic shaping of auditory transduction. Because scramblase activity of TMC1/2 disrupts lipid asymmetry, we hypothesized that an opposing flippase may be required to restore and maintain lipid asymmetry. Here, we identify the P4-ATPase ATP8B1 and its chaperone TMEM30B as selectively expressed in outer hair cells (OHCs), enriched in stereocilia, and upregulated following the onset of MET and hearing. Loss of either protein results in elevated auditory brainstem response (ABR) thresholds, phosphatidylserine (PS) externalization, and rapid hair-cell degeneration, demonstrating that lipid homeostasis is crucial for OHC survival. Together, these findings establish ATP8B1 and TMEM30B as key regulators of membrane lipid asymmetry in sensory hair cells and establish TMEM30B as a novel deafness gene.

cell biology↗

Artificial Recombination of Nonribosomal Peptide Synthetases Rapidly Evolves Natural Products

Efficient engineering of nonribosomal peptide synthetases (NRPSs) is a key strategy for expanding valuable peptide natural products. Current bioinformatics-guided approaches are often constrained by a set of predefined fusion sites, remaining experimentally challenging in most NRPS systems. Here we present the Recombineering Accelerated Evolution (RACE), which harnesses Red/ET recombineering mediated partially matched homologous recombination to recapitulate recombination-driven NRPS evolution on a highly accelerated timescale. Application of RACE to six known NRPS gene clusters generated 830 recombinants and yielded over 600 novel peptides including novel bis-lipopeptides. These recombinants reveal 112 previously unrecognized recombination fusion sites, providing an extensive landscape for NRPS evolution and more useful resources for guiding NRPS engineering. The RACE establishes a new paradigm for programmable NRPS evolution and enables rapid discovery of bioactive peptides.

synthetic biology↗

Artificial Intelligence of Things-Enhanced Automated Surveillance System for Global Antimicrobial Resistance in Food Supply Chain

Antimicrobial resistance (AMR) threatens food safety across the farm-to-fork continuum. Real-time surveillance is crucial to mitigate its global escalation, yet conventional antimicrobial susceptibility testing (AST) remains slow, labor-intensive, and impractical for large-scale monitoring. We developed an Artificial Intelligence of Things (AIoT)-integrated multiplex microfluidic platform enabling automated AMR surveillance of pathogens in food supply chain. Each node combines a single-board AIoT controller (Orange Pi 5B), portable incubator, colorimetric microfluidic chips, and environmental sensors, reducing costs by 98% compared with standard AST. A lightweight YOLOv5 model embedded in the controller achieved >99% accuracy in identifying bacterial growth and inhibition under antibiotic pressure, showing 96% and 95% agreement with standard results for Salmonella and Campylobacter, respectively. Data are synchronized to a cloud server for real-time aggregation and early resistance warning. This fully automated and low-cost system minimizes human error and workload, providing a scalable sample-to-answer solution for AMR surveillance in global agri-food system.

microbiology↗

Glucose hypometabolism and hyperphosphorylated Tau synergistically drive neuronal necroptosis

The combination of brain glucose hypometabolism and hyperphosphorylated Tau (p-Tau) pathology is the strongest known clinical predictor of imminent cognitive decline, yet how these factors cooperate to drive dementia remains unknown. Here, we show that glucose hypometabolism synergizes with p-Tau to trigger neuronal loss through necroptosis. Under low-glucose conditions, accumulated p-Tau forms a molecular scaffold that directly recruits the necroptotic kinase RIPK1, while concomitant loss of the necroptosis checkpoint protein A20 removes a critical brake on this death pathway. This dual mechanism thereby precipitates neuronal necroptosis independent of classical TNF/TNFR1 signaling paradigm. Restoring A20 expression with acetyl-L-carnitine as a dietary supplement or preventing the p-Tau - RIPK1 interaction using a RIPK1 derived competitive peptide alleviates neuronal necroptosis and brain atrophy in a Tau transgenic mouse model. Collectively, our findings uncover a previously unrecognized metabolism-driven necroptotic signaling cascade initiated by a p-Tau-RIPK1 hub, providing mechanical insight into how glucose hypometabolism synergizes with p-Tau to drive neurodegeneration.

neuroscience↗

Functional Annotation of the Major Histocompatibility Complex Locus

The human major histocompatibility complex (MHC) locus has the greatest density of disease-associations in the human genome, including links to over 100 polygenic disorders. Its complex haplotype structure, rich gene density, and high degree of linkage disequilibrium combine to make deciphering the gene regulatory logic of the MHC locus extremely challenging. Employing complementary high-throughput CRISPR interference (CRISPRi) and activation (CRISPRa) epigenetic screens coupled with single-cell transcriptome profiling across three distinct human cell types, we identified hundreds of new connections between cis-regulatory elements (CREs) and their target genes in this locus. These CRE-gene links are largely cell type-specific and act as enhancers. Additionally, some CREs have complex features, including harboring both active and repressive histone marks, lacking chromatin accessibility, targeting multiple genes, or acting as silencers. Computational methods fail to predict a majority of these CRE-gene connections. These findings emphasize the potential for functional perturbation experiments to dissect complex loci and reveal shared and cell type-specific regulatory mechanisms relevant to genomics of complex diseases. Collectively, this study provides a unique resource for understanding the complex regulatory landscape within the MHC locus and supports the need for creating new models that encompass CRE-gene interactions, cell type-specific gene expression, and disease genetics in the noncoding genome.

genomics↗

Physics-Informed Neural Network for Mapping Vascular and Tissue Dynamics Using Laser Speckle Contrast Imaging

SignificanceQuantitatively mapping both cerebral blood flow and tissue dynamics from laser speckle contrast imaging (LSCI) is powerful for studying cerebral blood flow and neurovascular coupling, particularly in the context of stroke. Conventional multi-exposure fitting is slow and difficult to scale. Efficient, physically grounded methods are needed to extract both vascular and tissue dynamic biomarkers from LSCI data. AimTo develop and validate a physics-informed neural network (PINN) that quantitatively estimates fast (vascular) and slow (tissue-related) speckle decorrelation parameters directly from LSCI measurements without requiring ground-truth labels. ApproachWe developed a physics-informed neural network (PINN) to estimate fast (vascular) and slow (tissue-related) speckle decorrelation parameters directly from multi-exposure LSCI data without requiring ground-truth labels. The analytical LSCI model is embedded in the network loss function, enforcing consistency with speckle physics during training. The model operates in a self-supervised manner and performs pixel-wise inference across full-field images. The framework was evaluated using in vivo mouse stroke LSCI datasets. ResultsThe PINN accurately recovered fast decorrelation rates associated with cerebral blood flow and slower dynamics linked to tissue and cellular motion. The parameter maps closely match those from traditional nonlinear fitting, but at orders-of-magnitude higher speed, reducing analysis to under one second per image. It also generalizes to unseen subjects and remains robust under noise. ConclusionsOur approach establishes physics-informed learning as a practical framework for near real-time extraction of vascular and cellular biomarkers from LSCI, enabling longitudinal monitoring of stroke progression and potentially facilitating clinical translation.

bioengineering↗

Genetic analysis and mapping of adult plant stripe rust resistance loci in CIMMYT wheat 'Kijil under Mexican and Chinese field environments

Stripe rust, caused by Puccinia striiformis f. sp. tritici, can cause severe yield losses in wheat (Triticum aestivum L.) during epidemics. Breeding resistant wheat varieties remains the most cost-effective approach to manage this disease; and the identification of new resistance loci is essential for maintaining genetic diversity. The CIMMYT-derived wheat line Kijil was highly resistant to stripe rust in both Mexican and Chinese environments. A population of 153 F recombinant inbred lines (RILs) was derived from a cross between Kijil and the susceptible parent Apav#1. The population was phenotyped for stripe rust resistance across seven environments in two countries and genotyped using a genotyping-by-sequencing (GBS) platform. Inclusive composite interval mapping (ICIM) was uesd to construct a genetic map and identify significant resistance quantitative trait loci (QTLs) using 5,468 polymorphic markers. Mapping revealed the known resistance loci Yr29, Yr30 and QYr.hzau-3AS, along with two novel loci, QYr.hzau-2BS and QYr.hzau-5DL, across both Chinese and Mexican rust environments. Among these, QYr.hzau-2BS accounted for 11.75% to 19.19% of the phenotypic variance. A corresponding KASP marker, KASP_2BS, was developed to facilitate maker-assisted selection. Based on the mapping interval, four candidate genes underlying this locus were predicted. Further analysis revealed that Yr29 showed significant additive effects with other stripe rust resistance genes/loci, and the combination of Yr29, Yr30, and QYr.hzau-2BS reduced disease severity by up to 67.8%. Our findings suggest that Kijil and RILs carrying Yr29, Yr30, and QYr.hzau-2BS can serve as valuable donors for breeding wheat varieties with improved stripe rust resistance. Author summaryStripe rust is an important disease that seriously threatens the yield and quality of wheat. It is crucial to explore new resistant resources and cultivate durable resistant varieties in the current breeding programme. In this study, we analysed the genetic basis of resistance to stripe rust in the wheat line "Kijil", which has broad-spectrum resistance to stripe rust. Through genetic mapping, we identified five quantitative trait loci for stripe rust, including two new resistance loci. A closely linked KASP marker, KASP_2BS, was developed for the QYr.hzau-2BS, which can be used for rapid and accurate screening of resistant plants in early breeding populations. Meanwhile, within this QTL region, we screened four candidate genes based on expression analysis. In addition, it was found that polymerization of QYr.hzau-2BS with known resistance genes, Yr29 and Yr30, significantly enhanced resistance and reduced disease severity to low levels and near immunity. In conclusion, this study provides new genetic resources, practical molecular markers and effective gene polymerization strategies for breeding wheat for stripe rust resistance. Kijil and the lines containing resistance loci have important breeding utilization value.

plant biology↗

Measuring the potential for community rescue under environmental stress

The widely used half maximal inhibitory concentration and related indices, e.g., minimum inhibitory concentration and mutant prevention concentration, are in vitro measures of response of biological or biochemical processes to inhibitor substances. We propose to adapt the above concepts for developing standard measures of functional resistance and rescue of ecological communities under environmental pollution. First, a "half inhibitory concentration" index (IC50) is defined as the concentration at which a pollutant reduces a community-level function to 50% of the baseline state immediately after exposure; note that this is different from the "half maximal effective concentration" (EC50) index commonly used for estimating drug safety. Second, a "half community rescue prevention concentration" index (CRPC50) is the concentration at which a pollutant can prevent community-level ecological function from recovering to 50% of the baseline state after a prolonged period of recovery. CRPC50 is supposedly higher than IC50. We performed two experiments with natural aquatic microbial communities and considered respiration rate as a surrogate of whole-community function. The IC50 and CRPC50 of the herbicide glyphosate and the heavy metallic salt copper sulfate were estimated by dose-response curves. One specific finding is that CRPC50 values of glyphosate were typically higher than IC50 by > 2.4 folds, while for copper sulfate the CRPC50 values did not significantly differ from IC50. This suggested that our studied microbial communities showed little adaptive response to the latter pollutant agent. Standardized measures of functional resistance and community rescue potential such as those proposed in the present study would be comparable across environmental stress agents and study systems, and improve our study of short- and long-term consequences of environmental pollutants for microbial community functioning.

ecology↗