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Biology subjects

Liu, M.

Publications and source records attributed to Liu, M..

At least 109 records · Page 6Linked to original sources

Marginal zone B cells are antigenically activated, infiltrate the kidneys, and exacerbate angiotensin II-dependent hypertension in mice

AimsB cells contribute to the development of hypertension, yet, the specific B cell subsets involved, the mechanism underlying their activation, and the relevance of these responses to human disease remain poorly defined. Methods and resultsWe used single-cell RNA sequencing, single-cell B cell receptor (BCR) VDJ sequencing, and high dimensional flow cytometry to characterise B cell responses in murine angiotensin II-induced hypertension. Chronic angiotensin II infusion in male and female mice increased systolic blood pressure and selectively expanded marginal zone B (MZB) cells, with evidence of antigen-dependent activation, including clonal BCR expansion, enrichment of IGHV1 B cell receptor variants, and increased expression of activation markers (CD69 and Nur77). Intercellular communication analyses revealed enhanced antigen-presentation signalling between MZB and CD8+ T cells in hypertensive mice. Activated MZB-like memory B cells also accumulated in the kidneys of hypertensive mice. Consistent with these findings, multiomic analysis of kidneys from patients with hypertensive chronic kidney disease (CKD) demonstrated an increase in memory B cells with a MZB phenotype and enrichment of antigen-presentation-linked communication with CD8+ T cells. Importantly, hypertensive responses to angiotensin II infusion were significantly blunted in mice lacking MZB cells (BAFF-R-/-). ConclusionOur findings identify MZB cells as a selectively activated, antigen-responsive B cell subset that amplified pathogenic immune responses in murine and human hypertension. By linking subset-specific BCR activation to immune cross-talk and disease causality, this study identifies MZB cells - and the (auto)antigens that activate them - as promising targets for precision immunomodulatory strategies in hypertension.

physiology↗

Splicing of HPV16 E6 promotes aggressive invasion in oropharyngeal cancer via endocytosis of E-cadherin

Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) has become the most common HPV-associated cancer in developed countries, yet a significant subset of patients develops recurrence despite favorable treatment responses. Biomarkers that identify aggressive tumors at diagnosis are therefore needed. In HPV+ cancers, the viral E6 transcript can be expressed as two main variants, the full-length isoform (E6FL) and the spliced E6*I isoform. Here, we investigated the functional and clinical impact of E6FL and E6*I in HPV+OPSCC. Across multiple preclinical models, E6*I promoted migration and aggressive invasion relative to E6FL and was associated with redistribution of E-cadherin away from the cell membrane. In multi-institutional patient cohorts, a previously developed E6FL:E6ALL influence score, which captures E6 splicing-associated host transcriptional biology, was associated with clinical outcomes. Lower scores, reflecting greater E6*I impact, were associated with worse overall survival and recurrence-free survival. Multiplexed immunofluorescence of 75 primary pretreatment biopsies further showed that a lower influence score was linked to reduced membrane and increased cytoplasmic localization of E-cadherin, while a tissue-based E-cadherin localization score was associated with recurrence. Mechanistically, E6*I overexpression promotes E-cadherin internalization, likely through the Rab11-associated trafficking pathway. Splice-switching oligonucleotides that shifted endogenous E6 splicing toward E6FL reduced invasion in two HPV+ OPSCC models. Together, these findings position HPV E6 splicing as a regulatory axis underlying aggressive HPV+ OPSCC biology and support E6 splicing and membrane-to-cytoplasmic ECAD localization as candidate risk-stratification biomarkers.

cancer biology↗

Automatic Change Detection of Human Attractiveness: Comparing Visual and Auditory Perception

Change detection of social cues across individuals plays an important role in human interaction. Here we investigated the automatic change detection of facial and vocal attractiveness in 19 female participants by recording ERPs. We adopted a deviant-standard-reverse oddball paradigm where high- or low-attractive items were embedded as deviants in a sequence of opposite attractive standard stimuli. Both high- and low-attractive faces and voices elicited mismatch negativities (MMNs). Furthermore, low-attractive versus high-attractive items induced larger mismatch negativities in the voice condition but larger P3 amplitudes in the face condition. These data indicate that attractiveness can be automatically detected but that differences exist between facial and vocal attractiveness processing. Generally, change detection seems to work better for unattractive than attractive information possibly in line with a negativity bias.

neuroscience↗

Belief updating in uncertain environments are differentially sensitive to reward and punishment learning: Evidence from ERP

Learning from rewards and punishments is crucial for adaptive decision-making, but it is still unclear how individuals integrate prediction errors to update beliefs in uncertain environments, particularly the distinctions between reward and punishment learning. We employed a probabilistic classification task and situated electroencephalography (EEG) signals within a hierarchical Bayesian framework, investigating distinctions between reward and punishment learning. Our findings indicate that participants exhibited superior learning performance in reward context compared to punishment context. Fitting the hierarchical Bayesian model revealed that punishment drives faster Bayesian belief updates, although these did not translate into improved behavioral outcomes. At the neural level, higher-level precision-weighted prediction error (pwPE2) was significantly positively correlated with FRN amplitude in the punishment context but not in the reward context, and the positive effect of pwPE2 on P300 amplitude was stronger in the punishment than the reward condition. These results provide electrophysiological signatures of punish context driving faster belief updates in uncertain environments. Our results provide novel evidence for a dual-process framework in reinforcement learning, underscoring distinct neural mechanisms underlying reward and punishment learning.

neuroscience↗

CNS-penetrant NLRP3 inhibitor achieves durable weight loss and reverses hypothalamic inflammation in diet-induced obesity

The NLRP3 inflammasome is a key mediator of innate immunity that integrates inflammatory and metabolic stress signals. Increased and/or chronic activation of this critical pathway has been implicated in obesity, with hypothalamic neuroinflammation linked to dysregulation of energy balance. TN-783 is an investigational, CNS-penetrant, small-molecule NLRP3 inhibitor that potently suppressed inflammasome activation across multiple in vitro assays. In diet-induced obese (DIO) mice, only TN-783, and not the peripherally restricted NLRP3 inhibitor TN-101, produced progressive and sustained weight loss, underscoring the requirement for central target engagement. Weight loss was driven by a persistent reduction in food intake across both acute and chronic phases, without altering energy expenditure. This effect was further characterized by selective reduction of fat mass, with minimal impact on lean tissues. Mechanistically, NLRP3 inhibition attenuated DIO-induced hypothalamic neuroinflammation and partially reversed obesity-associated molecular changes based on transcriptomic and proteomic profiling of the hypothalamus. Beyond monotherapy, TN-783 enhanced the effects of the GLP-1 receptor agonist semaglutide by amplifying weight loss, reinitiating weight loss after semaglutide effect had plateaued, and maintaining the weight loss benefit after semaglutide withdrawal. Discontinuation of TN-783 resulted in reversal of both weight and feeding effects, indicating that its therapeutic activity requires ongoing target engagement rather than permanent remodeling of metabolic pathways. Collectively, these observations support central NLRP3 inhibition as a distinct and promising approach for obesity treatment, offering robust induction and sustained maintenance of weight loss while preserving reversibility.

neuroscience↗

Humidity-driven shape morphing enhances fog harvesting in porous cactus spines

Cacti develop spines instead of conventional leaves, which often serve as mechanical defence against herbivores and protection from excess sunlight. However, some cactus species grow porous and flexible spines, suggesting fundamentally different functions. Here we demonstrate that the porous spines of Turbinicarpus alonsoi, a cactus native to central Mexico, function as hygro-morphing fog harvesters. We discovered that the spines are highly hygroscopic and straighten when exposed to fog, leading to increased fog water collection rates. Experiments and numerical simulations confirm that straightening is driven by swelling-induced pressure in the cell walls of the spine tissue. Swelling results from capillary imbibition of fog water and predominantly generates expansion in the transverse plane, which causes the pre-curved spines to straighten. Despite their porosity and hygroscopicity, the spines prevent direct absorption of fog water into the living cortex due to the presence of a suberin-rich tissue layer at the spine base that instead promotes surface runoff towards the roots. Our work suggests that hygro-morphing emerges from distinct structural, biochemical and geometric adaptations of cactus spines, and enables a fine modulation of the flow dynamics on the surface of spines. The increasing plant water supply from fog by shape morphing provides a potential advantage for survival in a hot, semi-arid region with frequent fog formation. Significance statementIn many arid regions of the world, fog is a critical source of fresh water. Plants display striking ways to harvest this fog water. For cacti with porous spines, it has long been assumed that they collect fog water directly by capillary imbibition. However, we demonstrate that, in Turbinicarpus alonsoi, water-impermeable tissue at the spine base prevents direct transport of water into the living cortex. Instead, a dual process increases fog water collection: the curved spines initially imbibe fog water, which causes them to swell and straighten, and a thin liquid film then forms on the spine and runs off along the plant surface down to the roots. Hygro-morphing spines therefore enhance the capacity of cacti to collect fog water.

plant biology↗

Development of a High-Throughput Screening Method for Anti-NNV Drugs

Nervous necrosis virus (NNV) is an infectious pathogen, characterized by rapid infection and high mortality, commonly encountered in the aquaculture industry. Therefore, there is an urgent need to develop effective antiviral drugs against NNV, which is crucial for targeted treatment strategies, pathogen control, and loss reduction. Screening of effective antiviral active compounds, namely drug precursors, is key to developing highly efficient drugs against NNV. Reverse transcription-quantitative real-time PCR (RT-qPCR) is widely applied to screen and evaluate various substances to prevent and control virus infection. However, RT-qPCR is a cumbersome procedure and not suitable for high-throughput rapid screening. The aptamer TNA1c, which specifically binds to NNV-infected cells, was used to construct a target-driven activatable aptamer probe (TAA). Then, the TAA probe was applied to establish a high-throughput screening (TAA-HTS) method for efficient evaluation of substances against NNV infection. TAA-HTS technology achieved rapid, sensitive, and specific screening of bioactive substances with significant anti-NNV effects. As compared to commonly used analytical methods, such as RT-qPCR, TAA-HTS has the advantages of easy operation and high sensitivity and specificity. The findings of this study provide data support and a theoretical basis for the development of effective antivirus preparations. IMPORTANCEIn this study, a target-driven activatable aptamer probe was employed to establish a high-throughput screening method for anti-NNV drugs. This method enables rapid, sensitive, and specific screening of anti-NNV compounds while reducing background interference. Although RT-qPCR is currently the most widely used technique for antiviral drug screening and validation, the screening approach developed in this study significantly shortens screening time while achieving results consistent with those of RT-qPCR. This demonstrates that the screening method presented here has the potential to become a universal strategy for future drug screening against viral diseases. Moreover, this study not only provides a novel technical solution for NNV control but also demonstrates the potential of aptamer-based probes in high-throughput antiviral screening, serving as a model for combating viral pathogens in aquaculture and other fields.

pathology↗

A microfluidic rheometer for tumor mechanics and invasion studies

Clinically, the feel, touch, and shape of a solid tumor are important diagnostic methods for determining the malignant state of the disease. However, there are limited tools for quantifying the mechanics and the malignancy of the tumor in a physiologically realistic setting. Here, we developed a microfluidic rheometer - termed the microrheometer - that enables simultaneous measurements of tumor spheroid mechanics and their invasiveness into a 3D extracellular matrix (ECM). The microrheometer consists of a pneumatic pressure control unit for applying controlled static or cyclic compression to tumor spheroids, and a sample chamber for containing spheroid embedded ECM. The innovation here lies in the integration of a polyacrylamide membrane force sensor within the sample chamber, enabling a direct force measurement in a physiologically relevant setting. We found that both tumor stiffness and the viscoelastic properties of the tumor are closely correlated with tumor invasiveness. The microrheometer allowed us to measure tumor mechanics in a short time (less than a minute) and has the potential to be used clinically in the future. We note that the microrheometer here can be easily extended to studies of mechanics of single cell, nucleus, as well as other cell/tissue types.

bioengineering↗

Metachronal wave coordination encodes multimodal swimming in ciliated unicellular predators

Motile cilia are slender cellular appendages, conserved across eukaryotes ranging from unicellular protists to humans, that beat to generate fluid flow. In most organisms, cilia form dense arrays of thousands of filaments that coordinate their motion into persistent, temporally synchronized patterns known as metachronal waves. Despite their ubiquity, the dynamics of these patterns and their role in tuning propulsion remain poorly understood. Here, we investigate how metachronal coordination shapes the navigation of Didinium nasutum, a highly agile unicellular predator with two circumferential ciliary bands. Using high-speed imaging of freely swimming cells, we capture and quantify the dynamics of metachronal wave coordination and track their evolution across different swimming states and transitions. Combining these measurements with a hydrodynamic model, we uncover how dynamic changes in coordination directly regulate propulsion and maneuverability. We show that stable metachronal waves support persistent directed swimming, local inhomogeneities in coordination give rise to curved trajectories, and global wave reversals accommodate rapid evasion-like reorientations. Our findings reveal that transitions between coordination modes allow Didinium to access a diverse swimming repertoire, highlighting dynamic ciliary patterning as a key mechanism to encode complex microscale navigation strategies. More broadly, they provide mechanistic insights into how metachronal coordination shapes fluid flows generated by dense ciliary arrays found in unicellular protists and airway epithelia alike, ultimately influencing swimming and transport in biological systems.

biophysics↗

In Vivo Non-Invasive Observation of Dynamic Changes in Hair Shaft, Melanin, and Collagen During the C57BL/6 Follicle Cycle

This study systematically monitored hair shaft, melanin, and collagen dynamics in vivo using non-invasive methods, enabling continuous observation over multiple hair follicle cycles. The hair shafts of C57BL/6 mice were observed in vivo using dermoscopy, photography, and electron microscopy. Second harmonic generation (SHG) and photography were employed for in vivo observation and quantification of melanin dynamics throughout the hair follicle cycle--specifically during the anagen phase, catagen phase, and telogen phase stages. Accuracy was validated via hematoxylin and eosin (H&E) staining. Additionally, SHG was used for in vivo observation and quantification of collagen changes across the same hair cycle phases, with validation performed using a liquid crystal polarizing imaging system and Sirius Red staining. This project provides non-invasive and in vivo methods for evaluating hair shafts, melanin, and collagen fibers across different growth cycles, thereby supporting non-invasive research in the development of active agents for hair loss treatment.

animal behavior and cognition↗

Discovery of A Small Molecule non-IMiD Degrader of ZBTB7A for the Treatment of β-hemoglobinopathies

Sickle cell disease and {beta}-thalassemia, two major {beta}-hemoglobinopathies, pose significant clinical challenges globally. Current treatments often face limitations in efficacy and tolerability. The transcription factor ZBTB7A has emerged as a promising therapeutic target for reactivating fetal hemoglobin expression. Here, we report the discovery and characterization of SH6, a small molecule non-IMiD degrader of ZBTB7A. SH6 induces fetal hemoglobin in erythroid cell lines in a CRBN and ZBTB7A-dependent manner, and it is capable of inducing fetal hemoglobin expression in healthy donor, SCD and {beta}-thalassemia patient CD34+ cell derived erythroid cells. The efficacy of SH6 is confirmed in a xenotransplantation humanized mouse model. SH6 outperforms currently available therapeutic agents in vitro, and shows synergy with hypomethylating agents. SH6 exhibits a favorable in vivo toxicity profile. Our findings establish SH6 as a promising therapeutic lead candidate for further optimization towards clinical development for treatment of sickle cell disease and {beta}-thalassemia.

cell biology↗

Eco-genomic analysis uncovers precision-conservation targets for the western Pacific's southernmost salmonid

Understanding how isolated small populations persist and adapt in adverse environments is instrumental to evolutionary and conservation biology. We combine a chromosome-level genome assembly, population resequencing and forward-time simulations to reconstruct the history and viability of the Formosan landlocked salmon (Oncorhynchus formosanus), now restricted to a handful of high-mountain headwaters in Taiwan. We estimate that this lineage has diverged from Japanese masu salmon over one million years ago and has no detectable gene flow for [~]50,000 years. It has accumulated extensive chromosome fusions and expansions of cold-adaptation gene families, qualifying it as a new species rather than a subspecies of Japanese masu salmon. Whole-stream sampling reveals an overlooked Hehuan-Creek population that retains high heterozygosity and has gained unique alleles. Life-table simulations show that the Hehuan population has a notably lower extinction risk and can persist or even grow under low-to-moderate typhoon frequency, whereas Qijiawan-Creek population would decline precipitously under the same or higher frequency . These findings contradict the notion that peripheral populations are likely genetically depleted and support stream-specific "precision conservation" in place of broad, untargeted translocations that could erode local adaptation potential. Thus, our genomic-ecological analysis has uncovered hidden strong resilience in a critically endangered, climate-threatened salmonid lineage.

genomics↗

RetINaBox: A hands-on learning tool for experimental neuroscience

An exciting aspect of neuroscience is developing and testing hypotheses via experimentation. However, due to logistical and financial hurdles, the experiment and discovery component of neuroscience is generally lacking in classroom and outreach settings. To address this issue, here we introduce RetINaBox: a low-cost open-source electronic visual system simulator that provides users with a hands-on tool to discover how the visual system builds feature detectors. RetINaBox features an LED array for generating visual stimuli and a photodiode array that acts as a mosaic of model photoreceptors. Custom software on a Raspberry Pi computer reads out responses from model photoreceptors and allows users to control the polarity and delay of the signal transfer from model photoreceptors to model retinal ganglion cells. Interactive lesson plans are provided, guiding users to discover different types of visual feature detectors--including ON/OFF, center-surround, orientation selective, and direction selective receptive fields--as well as their underlying circuit computations.

neuroscience↗

EHMT2 Controls Neural Crest-Derived Craniofacial Development but is Dispensable in Limb Development

Post-translational modifications of histones, such as methylation of histone H3 at lysine 9 (H3K9), play critical roles in regulating chromatin structure and gene expression. EHMT2 (also called G9A), a histone methyltransferase, mediates H3K9 mono- and dimethylation and has been implicated in both transcriptional repression and context-specific gene activation. Although global knockout of the mouse Ehmt2 gene results in early embryonic lethality, tissue-specific knockouts have uncovered diverse roles in organ development. However, how EHMT2 contributes to skeletal development in a lineage-specific manner remains to be fully elucidated. Here, we investigated the role of EHMT2 in skeletal development by conditionally inactivating Ehmt2 in neural crest-derived and mesoderm-derived progenitors using Wnt1-Cre and Prx1-Cre mouse lines, respectively. Loss of Ehmt2 function in neural crest cells led to postnatal growth failure and craniofacial defects, including delayed intramembranous ossification and malformations of the jaw and cranial base. Transcriptomic analysis of neural crest cells revealed disrupted chromatin regulatory networks, reduced expression of proliferation-associated genes, and upregulation of inflammatory pathways. In contrast, inactivation of Ehmt2 in Prx1-expressing mesodermal progenitors had minimal impact on limb and cranial bone development, with no significant alterations in bone mass or osteoblast function. Together, these results reveal a lineage-specific requirement for EHMT2 in neural crest-derived skeletal tissues, suggesting that distinct progenitor populations exhibit differential dependency for bone development.

cell biology↗

The prokaryotic origins of the COMMD protein family involved in eukaryotic membrane trafficking

The ten eukaryotic COMMD proteins are core components of the Commander complex, with central roles in endosomal membrane trafficking and signalling. Each protein has an -helical N-terminal (HN) domain with a C-terminal copper metabolism gene MURR1 (COMM) domain. These ten family members assemble into a heterodecameric ring composed of five specific heterodimers. In this work we have combined structural homology searches with genome-wide predicted structures to identify ancestral COMMD-like proteins that exist as single genes in Bacteria and Archaea. Although there is limited sequence similarity to the eukaryotic proteins the bacterial and archaeal COMMD-like proteins are predicted to form homomeric ring-shaped assemblies like their eukaryotic counterparts. Our biophysical studies, crystal and cryo-EM structures confirm COMMD-like proteins readily form homooligomeric rings composed of eight or ten subunits assembled from core dimeric building blocks and inter-dimer interactions that are analogous to the heterodecameric core structure of the eukaryotic Commander complex. Phylogenetic analyses using amino acid sequences and FoldSeek structural alphabet (3Di) infer that the closest identified relatives to the eukaryotic COMMD proteins are found in Myxococcota bacteria. These findings indicate that COMMD genes emerged early in eukaryotic evolution through multiple rounds of duplication from a single ancestral gene likely acquired from bacteria.

biochemistry↗

Gabija restricts phages that antagonize a conserved host DNA repair complex

Anti-bacteriophage systems like restriction-modification and CRISPR-Cas have DNA substrate specificity mechanisms that enable identification of invaders. How Gabija, a highly prevalent nuclease-helicase anti-phage system, executes self-vs. non-self-discrimination remains unknown. Here, we propose that phage-encoded DNA end-binding proteins that antagonize host RecBCD sensitize phages to Gabija. When targeting a temperate Lambda-like phage in Pseudomonas aeruginosa, Gabija protects the cell by preventing phage genome circularization and subsequent replication. Phage and plasmid sensitivity to Gabija is licensed by DNA end-binding complexes such as a phage exonuclease together with a ssDNA-annealing protein or GamMu dimers, which prevent loading of host repair complex RecBCD. Escape phages lacking these end-binding proteins become protected from Gabija by RecBCD translocation activities. RecBCD activity on the bacterial genome also prevents Gabija from targeting self-DNA. Therefore, we propose that Gabija antagonizes circularization of linear DNA devoid of RecBCD as a mechanism to identify foreign invaders.

microbiology↗

Dyslipidemic SPTLC3 Integrates Bile Acid-FXR Signaling with Sphingolipid Remodeling in MASLD

Molecular mechanisms driving metabolic disease pathogenesis remain poorly understood. Genetic and functional studies implicate SPTLC3 with dyslipidemia. SPTLC3 synthesizes atypical long-chain bases (LCB) precursors for sphingolipid production. We demonstrate significant SPTLC3 expression in human liver. ORMDL1-3 regulate SPTLC3 post-translationally in hepatic and non-hepatic cells. Independently, farnesoid X receptor (FXR) represses hepatic SPTLC3 transcription via a negative promoter element. In mice, high-fat diet (HFD) induced whereas bile acids normalized hepatic SPTLC3 transcription. SPTLC3 derived LCBs in plasma originate from the liver and are elevated in HFD-fed mice and in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Cross-species comparison revealed marked differences in LCB composition between mice and humans. Notably, omega-3-methylsphingosine (meC18SO) was significantly associated with MASLD in humans but undetectable in mice. In Huh7 cells, meC18SO enhanced complex II and IV activity, oxygen consumption, and mitochondrial ROS content. FXR-SPTLC3 axis and presented findings have potential implications for future translational research.

biochemistry↗

Clarifying the priming requirement and activator specificity for the NLRP3 inflammasome in human keratinocytes in vitro

While NLRP3 has been extensively studied in myeloid cells, its existence and regulation in epithelial cells, including keratinocytes, are unclear. In fact, whether human keratinocytes express a functional NLRP3 inflammasome at all remains a matter of debate in the inflammasome field. Here, we provide additional evidence that NLRP3 is repressed in human keratinocytes cultured under non-inflammatory conditions but can be sharply induced by interferon-{gamma} (IFN{gamma})--but not lipopolysaccharide (LPS). In this IFN{gamma}-primed state, not all established NLRP3 activators are specific to NLRP3. We report that nigericin-driven keratinocyte pyroptosis occurs via both NLRP1 and NLRP3, whereas Staphylococcus aureus -hemolysin (Hla) exclusively and nonredundantly activates NLRP3, even though both require K+ efflux. Furthermore, in the presence of T cells, certain virulent S. aureus strains can cause NLRP3-dependent pyroptotic death in keratinocytes in vitro through the cooperative actions of superantigens (SAgs) and Hla. In summary, our findings establish the strict inducibility and functional relevance of the NLRP3 inflammasome in non-myeloid, epithelial cells in vitro. These results resolve conflicting reports and position keratinocytes as a context-specific, non-hematopoietic cellular model for studying NLRP3 activation in host-microbe interactions at barrier tissues. KEY FINDINGSO_LIAdditional evidence that NLRP3 is absent in resting, nonstimulated human keratinocytes in vitro C_LIO_LIIFN{gamma}, but not LPS, is a potent priming signal for NLRP3 in human keratinocytes in vitro C_LIO_LIIn IFN{gamma}-primed keratinocytes, S. aureus -hemolysin (Hla) selectively activates NLRP3, whereas nigericin activates both NLRP1 and NLRP3 in vitro C_LIO_LISAg and Hla kill keratinocytes via NLRP3-driven pyroptosis in the presence of T cells in vitro C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/669639v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@4996f4org.highwire.dtl.DTLVardef@155a2a9org.highwire.dtl.DTLVardef@12a21a0org.highwire.dtl.DTLVardef@105bc15_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗