Biology subjects

Hu, M.

Publications and source records attributed to Hu, M..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

An Epigenomic Roadmap Primes Non-Growing Oocytes for Maturation and Early Embryogenesis

Female reproductive lifespan is defined by long-lived, non-growing oocytes (NGOs) that comprise the ovarian reserve. NGOs are assumed to acquire the epigenetic marks that will define the early embryo only after they exit the ovarian reserve and become activated for growth. Contrary to this dogma, we show that mouse NGOs possess abundant histone modifications that both underlie maintenance of the ovarian reserve and prime the epigenome of growing oocytes for early embryogenesis. As NGOs are established around birth, Polycomb Repressive Complex 1 (PRC1) mediates abundant H2AK119 ubiquitylation and reprograms the H3K27 acetylation landscape, which is essential to maintain the ovarian reserve. Importantly, the PRC1-driven epigenetic state of NGOs provides a blueprint for subsequent generation of a PRC2-catalyzed H3K27 trimethylation profile in growing oocytes that is characterized by broad domains and DNA methylation-independent imprints that are transmitted to the embryo. Thus, Polycomb complexes play pivotal roles in priming the NGO epigenome for oocyte maturation and early embryogenesis. HighlightsNon-growing oocytes have rich epigenetic landscapes to prime subsequent development Reprogramming of H3K27ac by PRC1 is required to maintain non-growing oocytes PRC1-catalyzed H2AK119ub provides a blueprint for PRC2-H3K27me3 in growing oocytes In non-growing oocytes, PRC1 primes DNA methylation-independent H3K27me3-imprinting

developmental biology↗

bioRxiv2025

A bottom-up approach to understanding ultrasound mediated blood-brain barrier opening using long and short pulses

Ultrasound-mediated blood-brain barrier (BBB) opening is promising for non-invasive, localized, and reversible drug delivery to the brain. However, the underlying mechanisms remain unclear, particularly at microscopic level in real time. Recently developed short-pulse ultrasound enhances safety by reducing side effects compared to conventional long-pulse ultrasound. Using vessel-mimicking microchannels cultured with brain endothelial monolayers, we directly observed bubble dynamics and cellular bioeffects under flow conditions. Intriguingly, cyclic jetting during stable cavitation occurs at long-pulse mode, accompanied by a few localized cell detachments and extensive sonoporation. In contrast, short-pulse ultrasound induced milder, uniform bubble dynamics, reversible sonoporation and calcium signaling, promoting safer BBB modulation. In vivo two-photon imaging and histology in mice confirmed these findings, showing that long-pulse ultrasound enabled higher drug delivery efficiency but caused localized endothelial damage, while short-pulse ultrasound facilitated uniform delivery and faster BBB recovery. The differential bubble dynamics and cellular responses correlated well between in vitro and in vivo models. This study establishes a cross-scale framework for real-time analysis of ultrasound-mediated BBB opening, revealing key biophysical factors governing safety and efficacy. The findings provide guidance for the optimization of ultrasound protocols for vascular drug delivery, with potential applications in treating brain tumors, neurodegenerative diseases, and other disorders.

biophysics↗

bioRxiv2025

Parameterization of cell-free systems with time-series data using KETCHUP

Kinetic models mechanistically link enzyme levels, metabolite concentrations, and allosteric regulation to metabolic reaction fluxes. This coupling allows for the quantitative elucidation of the dynamics of the evolution of metabolite concentrations and metabolic fluxes as a function of time. So far, most large-scale kinetic model parameterizations are carried out using mostly steady-state flux measurements supplemented with metabolomics and/or proteomics data when available. Even though the parameterized kinetic model can trace a temporal evolution of the system, lack of anchoring to temporal data reduces confidence in the dynamics predictions. Notably, the simulation of enzymatic cascade reactions requires the full description of the dynamics of the system as a steady-state is not applicable given that all measured metabolite concentrations vary with time. Here we describe how kinetic parameters fitted to the dynamics of single-enzyme assays remain accurate for the simulation of multi-enzyme cell-free systems. Herein, we demonstrate two extensions for the Kinetic Estimation Tool Capturing Heterogeneous datasets Using Pyomo (KETCHUP) software tool for parameterizing a kinetic model of the cell-free kinetics of formate dehydrogenase (FDH) and 2,3-butanediol dehydrogenase (BDH) through the use of time-course data across various initial conditions. An implemented extension of KETCHUP allowing for the reconciliation of measurement time-lag errors present in datasets was used to parameterize multiple datasets. By combining the kinetic parameters identified by the FDH and BDH assays, accurate simulation of the binary FDH-BDH system was achieved. KETCHUP can be accessed at https://github.com/maranasgroup/KETCHUP. Author SummaryMetabolic engineering of microorganisms offers a sustainable and renewable alternative for industrial scale production of commodity chemicals. Large-scale metabolic stoichiometric models enable means to elucidate an organisms physiological behavior towards both environment and genetic perturbations and predict optimal interventions to maximize production. Kinetic models extend stoichiometric models capabilities in characterizing metabolic phenotypes by mathematically linking enzyme catalyzed reactions in metabolic networks as functions of metabolite concentrations, enzyme levels, and allosteric regulations. Although these kinetic descriptions improve predictive accuracy and strain design, the lack of enzyme information, raw experimental data, and high computational cost preclude the construction and parameterization of detailed large-scale kinetic models. Here, we introduce an extension of KETCHUP, an open-source semi-automatic kinetic construction and parameterization tool that utilizes steady-state data as a pilot for the parameterization of single-enzyme cell-free time-course data. We show that this tool offers comparable performance to existing tools during parameterization of single enzymes and successful recapitulation of metabolite profiles for a two-enzyme system when simulating a kinetic model with parameters from the two single-enzymes. This study showcases a high throughput pipeline that can be integrated into our framework for larger scaled networks.

systems biology↗

bioRxiv2025

New alleles of Arabidopsis BIK1 reinforce its predominant role in pattern-triggered immunity and caution interpretations of other reported functions

The receptor-like cytoplasmic kinase BIK1 and its close homolog PBL1 have been widely recognized as central components of plant immunity. However, most genetic studies of BIK1 and PBL1 functions were carried out with single T-DNA insertional mutant alleles. Some phenotypes observed in these mutants, e.g. autoimmunity, have been difficult to reconcile with the proposed role of BIK1 and PBL1 in pattern-triggered immunity. In this study, we generated multiple new alleles of bik1 and pbl1 by CRISPR-Cas9-based gene editing and systematically analyzed these mutants alongside existing T-DNA insertional lines. These analyses reinforced the central role of BIK1 and PBL1 in pattern-triggered immunity mediated by both receptor kinases and receptor-like proteins. At the same time, however, we revealed several pleiotropic phenotypes associated with T-DNA insertions that are not necessarily linked to loss of BIK1 or PBL1 function. Further analyses of newly generated bik1 pbl1 double mutants uncovered an even greater contribution of these kinases to immune signaling and disease resistance than previously appreciated. These findings clarify longstanding ambiguities surrounding BIK1 and PBL1 functions.

plant biology↗

bioRxiv2025

Multimodal Validation of the Existence of Transitional Cerebellar Progenitors in the Human Fetal Cerebellum

The developing human cerebellum comprises a series of transient progenitor states that are essential for generating diverse neural subtypes, yet the identity and validation of intermediate cell populations bridging stem-like and lineage-committed neuronal precursors remain limited. In our previous single-cell transcriptomic study, we identified a distinct transitional cerebellar progenitor (TCP) population enriched in specific progenitor zones such as the rhombic lip during human fetal cerebellar development. To address the concerns raised in the Matters Arising regarding the existence of the TCP cells, we provide additional multimodal validations of this population. Rigorous reanalysis of our single-cell transcriptomic data, applying stringent quality control measures, validated the quality of TCP cells and their classification as a transcriptionally distinct population. Multiple orthogonal validations of TCP signature genes (SOX11 and HNRNPH1) using RNAscope in situ hybridization, Xenium-based spatial transcriptomics, and immunohistochemistry on additional fetal cerebellar samples across different stages demonstrated the consistent presence of TCPs in the rhombic lip, transitioning from PRTG+ stem-like zones in the ventricular zone at early developmental stages to the subventricular zone overlapping with EOMES+ unipolar brush cell precursors at later stages. TCP-like populations were also independently identified in two fetal cerebellar single-nucleus transcriptomic atlases, and their gene signature was enriched in a cell population associated with aggressive medulloblastomas. Collectively, these multimodal validations confirm the existence of a transitional progenitor population in the human fetal cerebellum, with implications for cerebellar lineage progression and medulloblastoma origin.

developmental biology↗

bioRxiv2025

The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR

The protein tyrosine phosphatases (PTPs) TCPTP, PTPN22, and SHP1 are critical regulators of the activating phosphotyrosine (pY) site on the initiating T cell kinase, LckY394. Still, the broader implications of these phosphatases in T cell receptor (TCR) signalling and T cell biology remain unclear. By combining CRISPR/Cas9 gene editing and mass spectrometry, we evaluate the protein- and pY-level effects of TCPTP, PTPN22, and SHP1 in the Jurkat T cell model system. We find that deletion of each phosphatase corresponds to unique changes in the proteome of T cells, with few large-scale changes to TCR signalling proteins. Notably, PTPN22 and SHP1 deletions have opposing effects on pY abundance globally, while TCPTP deletion modestly elevates pY levels. Finally, we show that TCPTP is indirectly involved in Erk1/2 positive feedback to the TCR. Overall, our work provides evidence for alternative functions of three T cell phosphatases long thought to be redundant.

systems biology↗

bioRxiv2025

Sialylated CD43 is a glyco-immune checkpoint for macrophage phagocytosis

Macrophages in the tumor microenvironment exert potent anti-tumorigenic activity through phagocytosis. Yet therapeutics that enhance macrophage phagocytosis have not improved outcomes in clinical trials for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). To systematically identify regulators of phagocytosis, we performed genome-scale CRISPR knockout screens in human leukemia cells co-cultured with human monocyte-derived macrophages. Surprisingly, we found that whereas the classic "dont eat me" signal CD47 inhibited mouse macrophages, it did not inhibit phagocytosis by human macrophages. In contrast, the O-linked glycosylation and sialylation pathways were strong negative regulators of phagocytosis. In AML, the cell surface O-linked glycoprotein CD43 was the major effector of the O-linked glycosylation and sialylation pathways. Genetic deletion or antibody blockade of CD43 enhanced macrophage phagocytosis. This work highlights the importance of using human platforms to identify immune checkpoints, and nominates CD43 as a glyco-immune regulator of human macrophage phagocytosis.

cancer biology↗

bioRxiv2025

New Insights on Bridging Integrator 1 Protein Isoforms as a Risk Increasing Gene in Alzheimer's Disease

INTRODUCTIONGenome-wide association studies (GWAS) have identified Bridging Integrator 1 (BIN1) as the second-most significant genetic risk factor for Alzheimers disease (AD). We performed GWAS by proxy (GWAX) using UKBiobank and replicated this finding. However, the mechanism by which BIN1 impacts AD risk is largely unknown. METHODSTo address this, we first measured the expression of BIN1 isoforms in a human induced pluripotent stem cells (hiPSC) model and further evaluated whether the BIN1 risk loci associated with the expression of BIN1 isoforms in a Phase 2 AD clinical trial. RESULTSOur data indicated BIN1 isoform expression patterns associated with the differentiation of hiPSC into neurons or microglia and found the variant rs35103166 impacts the expression of the BIN1 microglia-specific isoforms. DISCUSSIONGiven the strong association with susceptibility to AD, exploring the mechanisms of BIN1 genetic variants and their impacts on cell-type specific expression could serve as a valuable resource for novel drug discovery. HighlightsO_LIBIN1 variants are significantly associated with AD risk in GWAX analysis from UKBB. C_LIO_LIBIN1 isoforms show a cell-type-specific expression pattern during hiPSC differentiation into neurons or microglia. C_LIO_LIBIN1 risk alleles associate with BIN1 isoform expression in a Phase 2 AD trial (NCT02880956). C_LI

neuroscience↗

bioRxiv2025

Enhanced FLI1 accessibility mediates STAG2-mutant leukemogenesis

Chromatin architecture governs transcriptional output and cell identity; however, how its disruption promotes leukemic transformation remains incompletely understood. Here, we show that loss of the cohesin subunit STAG2 creates a hyper-accessible chromatin landscape that amplifies FLI1 activity and extends its binding to ectopic loci. Using multi-omic analyses in human AML samples, cell lines, and mouse models, we identify chromatin-dependent co-occupancy of FLI1 and Menin, accompanied by amplification of Menin occupancy at non-canonical loci beyond its HOXA/MEIS1 targets. Therapeutically, the aberrant expansion of Menin binding drives an altered response towards Revumenib and activates interferon response pathways, creating a therapeutic vulnerability to Menin inhibition. Functionally, STAG2/NPM1c co-mutation drives a stem cell-like immunophenotype and a fully penetrant leukemia in vivo. Collectively, these findings define a model in which cohesin loss rewires transcription factor occupancy to amplify oncogenic chromatin programs and expose context-specific therapeutic dependencies.

cancer biology↗

bioRxiv2025

Chemoselective Characterization of New Extracellular Matrix Deposition in Bioengineered Tumor Tissues

The extracellular matrix (ECM), present in nearly all tissues, provides extensive support to resident cells through structural, biomechanical, and biochemical means, and in return the ECM undergoes constant remodeling from interacting cells to adapt to the evolving tissue states. Bioengineered 3D tissues, commonly known as cell-ECM composites, are robust model systems to recapitulate and investigate native pathophysiology. Key to this engineered morphogenesis process are the intricate cell-ECM interactions reflected by how cells respond to and thereby modulate their surrounding microenvironments through their ongoing ECM secretome. However, investigating ECM-regulated new ECM production has been challenging due to the proteomic background from the pre-existing biomaterial ECM. To address this hindrance, here we present a chemoselective strategy to label, enrich, and characterize newly synthesized ECM (newsECM) proteins produced by resident cells, allowing distinction from the pre-existing ECM background. Applying our analytical pipeline to bioengineered tumor tissues, either built upon decellularized ECM (dECM-tumors) or as ECM-free tumor spheroids (tumoroids), we observed distinct ECM synthesis patterns that were linked to their extracellular environments. Tumor cells responded to the dECM presence with elevated ECM remodeling activities, mediated by augmented digestion of pre-existing ECM coupled with upregulated synthesis of tumor-associated ECM. Our findings highlight the sensitivity of newsECM profiling to capture remodeling events that are otherwise under-represented by bulk proteomics and underscore the significance of dECM support for enabling native-like tumor cell behaviors. We anticipate the described newsECM analytical pipeline to be broadly applicable to other tissue-engineered systems to probe ECM-regulated ECM synthesis and remodeling, both fundamental aspects of cell-ECM crosstalk in engineered tissue morphogenesis.

bioengineering↗

bioRxiv2025

TDP-43 Aggregate Seeding Impairs Autoregulation and Causes TDP-43 Dysfunction

The aggregation, cellular mislocalization and dysfunction of TDP-43 are hallmarks of multiple neurodegenerative disorders. We find that inducing TDP-43 aggregation through prion-like seeding gradually diminishes normal TDP-43 nuclear localization and function. Aggregate-affected cells show signature features of TDP-43 loss of function, such as DNA damage and dysregulated TDP-43-target expression. We also observe strong activation of TDP-43-controlled cryptic exons in cells, including human neurons treated with proteopathic seeds. Furthermore, aggregate seeding impairs TDP-43 autoregulation, an essential mechanism controlling TDP-43 homeostasis. Interestingly, proteins that normally interact with TDP-43 are not recruited to aggregates, while other factors linked to TDP-43 pathology, including Ataxin 2, specifically colocalize to inclusions and modify seeding-induced aggregation. Our findings indicate that TDP-43 aggregation, mislocalization and loss of function are strongly linked and suggest that disruption of TDP-43 autoregulation establishes a toxic feed-forward mechanism that amplifies aggregation and may be central in mediating this pathological connection.

cell biology↗

bioRxiv2025

Benchmarking, detection, and genotyping of structural variants in a population of whole-genome assemblies using the SVGAP pipeline

Comparisons of complete genome assemblies offer a direct procedure for characterizing all genetic differences among them. However, existing tools are often limited to specific aligners or optimized for specific organisms, narrowing their applicability, particularly for large and repetitive plant genomes. Here, we introduce SVGAP, a pipeline for structural variant (SV) discovery, genotyping, and annotation from high-quality genome assemblies at the population level. Through extensive benchmarks using simulated SV datasets at individual, population, and phylogenetic contexts, we demonstrate that SVGAP performs favorably relative to existing tools in SV discovery. Additionally, SVGAP is one of the few tools to address the challenge of genotyping SVs within large assembled genome samples, and it generates fully genotyped VCF files. Applying SVGAP to 26 maize genomes revealed hidden genomic diversity in centromeres, driven by abundant insertions of centromere-specific LTR-retrotransposons. The output of SVGAP is well-suited for pan-genome construction and facilitates the interpretation of previously unexplored genomic regions.

bioinformatics↗

bioRxiv2025

Somatic mutations distinguish melanocyte subpopulations in human skin

To better understand the homeostatic mechanisms governing melanocytes, we performed deep phenotyping of clonal expansions of single melanocytes from human skin. In total, we interrogated the mutational landscapes, gene expression profiles, and morphological features of 297 melanocytes from 31 donors. To our surprise, a population of melanocytes with low mutation burden was maintained in sun damaged skin. These melanocytes were more stem-like, smaller, less dendritic and displayed distinct gene expression profiles compared to their counterparts with high mutation burdens. We used single-cell spatial transcriptomics (10X Xenium) to reveal the spatial distribution of melanocytes inferred to have low and high mutation burdens (LowMut and HighMut cells), based on their gene expression profiles. LowMut melanocytes were found in hair follicles as well as in the interfollicular epidermis, whereas HighMut melanocytes resided almost exclusively in the interfollicular epidermis. We propose that melanocytes in the hair follicle occupy a privileged niche, protected from UV radiation, but periodically migrate out of the hair follicle to replenish the interfollicular epidermis after waves of photodamage. More broadly, our study illustrates the advantages of a cell atlas that includes mutational information, as cells can change their cellular states and positional coordinates over time, but mutations are like scars, providing a historical record of the homeostatic processes that were operative on each cell.

cell biology↗

bioRxiv2025

Cigarette smoke and biological age induce degenerative heterogeneity in retinalpigment epithelium

Environmental exposure such as cigarette smoke induces epigenetic changes that can induce degenerative heterogeneity and accelerate aging. In early age-related macular degeneration (AMD), the leading worldwide cause of blindness among the elderly, retinal pigment epithelial (RPE) cell heterogeneity is a key change. Since smoking is the strongest environmental risk factor for AMD, we hypothesized that cigarette smoke induces degenerative RPE heterogeneity through epigenetic changes that are distinct from aging, and that with aging, the RPE becomes vulnerable to cigarette smoke insult. We administered cigarette smoke condensate (CSC) intravitreally to young and aged mice and performed snRNA-seq and snATAC-seq on the RPE/choroid. This analysis identified separate cell clusters corresponding to healthy and abnormal, dedifferentiated RPE in both aged vehicle-treated and young CSC-treated mice. The dedifferentiated RPE were characterized by a global decrease in chromatin accessibility and decreased expression of genes in functional categories that were linked to hallmarks of aging. Notably, young, dedifferentiated RPE also exhibited a compensatory upregulation of hallmarks of aging-related genes, specifically those related to mitochondrial function and proteostasis. In contrast, aged dedifferentiated RPE did not express these compensatory changes, and did not survive CSC treatment, as experimentally verified with TUNEL labeling. These changes are relevant to early AMD because we identified through scRNA-seq, similar dedifferentiated and healthy macular RPE clusters in a donor who smoked and another with early AMD, but not from a nonsmoker. Degenerative cellular heterogeneity can include an abnormal cluster that jeopardizes cell survival and may represent an additional hallmark of ocular aging.

neuroscience↗

bioRxiv2025

Druggable genome CRISPRi screen in 3D hydrogels reveals regulators of cortactin-driven actin remodeling in invading glioblastoma cells

To identify new therapeutic targets that limit glioblastoma (GBM) invasion, we applied druggable-genome CRISPR screens to patient-derived GBM cells in micro-dissectible biomimetic 3D hydrogel platforms that permit separation and independent analysis of core vs. invasive fractions. We identified 12 targets whose suppression limited invasion, of which ACP1 (LMW-PTP) and Aurora Kinase B (AURKB) were validated in neurosphere assays. Proximity labeling analysis identified cortactin as an ACP1- AURKB link, as cortactin undergoes serine phosphorylation by AURKB and tyrosine dephosphorylation by ACP1. Suppression of ACP1 or AURKB in culture and in vivo shifted the balance of cortactin phosphorylation in GBM and reduced actin polymerization and actin-cortactin co-localization. Additional biophysical analysis implicated AURKB in GBM cell adhesion and cortical stiffness, and ACP1 in resistance to mechanical stress and shape plasticity needed for 3D migration. These findings reveal a novel targetable axis that balances kinase and phosphatase activities to regulate actin polymerization during GBM invasion.

cancer biology↗

bioRxiv2025

Single-cell digital twins identify drug targets and repurposable medicine in Alzheimers disease

Alzheimers disease (AD) is a complex and poorly understood neurodegenerative disorder without sufficiently effective treatments. Novel approaches to identify FDA-approved drugs that may hold potential for mitigating symptoms of AD hold promise for addressing this problem. One such strategy is the use of digital twins (DTs), which are virtual representations of physical entities that facilitate therapeutic target identification by accurately characterizing disease heterogeneities in real time through continuous feedback and dynamic model updates. In this study, we developed a single-cell digital twin (scDT) framework using single-nuclei RNA-seq (1,197,032 nuclei) and ATAC-seq (740,875 nuclei) data from the middle temporal gyrus of 84 donors across 4 degrees of AD neuropathological change (ADNC). We observed differential gene expression for six major cell types intensified at severe ADNC. We also constructed cell type-specific transcription factor (TF)-target gene networks by leveraging peak-to-gene linkages and motif enrichment analyses. By integrating genome-wide association study (GWAS) loci with cell type-specific cis-regulatory DNA elements (CREs), we identified 141 ADNC-associated genes. Using gene set enrichment analysis (GSEA) and network proximity analysis, we identified 13 candidate repurposable drugs that were associated with these ADNC-associated genes. In summary, we constructed a single-cell digital twin (scDT) framework cell type-specific target identification and drug repurposing in AD and other complex diseases if broadly applied.

bioinformatics↗

bioRxiv2024

Priming Epigenetic Landscape at Gene Promoters through Transcriptional Activation in Mammalian Germ Cells

In mammalian germ cells, a cycle of erasing and resetting epigenetic information is crucial for sex-specific gametogenesis and early embryogenesis. Specific chromatin states at promoters allow genes to be expressed at the appropriate time during germ cell development, however, the mechanism that establishes such characteristic chromatin states remains unclear. Here, we show that, in mouse male embryonic germ cells, promoters of developmental and housekeeping genes are selectively protected from de novo DNA methylation, coinciding with their transient upregulation and genome-wide erasure of H3K27me3. Importantly, a specific level of H3K4me3 density at the promoters serves as a potent probe that distinguishes between hypo- and hyper-DNA methylation states. Subsequent restoration of H3K27me3 contributes to establishing bivalent chromatin states that prime genes for activation at later developmental stages. These findings reveal a molecular framework shaping the epigenetic landscape at promoters with long-term effects beyond germ cell development.

genomics↗

bioRxiv2024

Mapping Pesticide-Induced Metabolic Alterations in Human Gut Bacteria

Pesticides can modulate gut microbiota (GM) composition, but their specific effects on GM remain largely elusive. Our study demonstrated that pesticides inhibit or promote growth in various GM species, even at low concentrations, and can accumulate in GM to prolong their presence in the host. Meanwhile, the pesticide induced changes in GM composition are associated with significant alterations in gut bacterial metabolism that reflected by the changes of hundreds of metabolites. We generated a pesticide-GM-metabolites (PMM) network that not only reveals pesticide-sensitive gut bacteria species but also report specific metabolic changes in 306 pesticide-GM pairs (PGPs). Using an in vivo mice model, we further demonstrated a PGPs interactions and verified the inflammation-inducing effects of pesticides on the host through dysregulated lipid metabolism of microbes. Taken together, our findings generate a PMM interactions atlas, and shed light on the molecular level of how pesticides impact host health by modulating GM metabolism. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/623895v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@17ed5f5org.highwire.dtl.DTLVardef@10d3e0org.highwire.dtl.DTLVardef@c61b43org.highwire.dtl.DTLVardef@27d035_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗