Biology subjects

Fischer, M.

Publications and source records attributed to Fischer, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Oncogene Silencing via ecDNA Micronucleation

Extrachromosomal DNA (ecDNA) contributes to cancer genome instability by enabling high-copy oncogene amplification, intratumoural heterogeneity and rapid genetic change. Micronuclei (MN) are frequently observed in chromosomally unstable cancers, yet their origins and relevance in ecDNA-driven tumours remain incompletely understood. Here, we investigate the relationship between ecDNA segregation errors and MN formation. We find that ecDNA frequently localizes to MN and represents a prominent source of MN content in ecDNA-positive cancer cells. Mitotic clustering of oncogene-bearing ecDNAs is associated with asymmetric inheritance and mis-segregation into MN. Transfer of oncogenes from ecDNA into MN is accompanied by reduced transcriptional output. Single-MN sequencing shows that individual MN are enriched for ecDNA to a degree that exceeds expectations from stochastic mis-segregation and that in MN oncogenes originating from multiple distinct ecDNAs coalesce. Using live-cell imaging, we observe that cells inheriting ecDNA-positive MN show limited proliferative capacity and an increased likelihood of cell death. In neuroblastoma patients with MYCN-amplified ecDNA, higher frequencies of ecDNA-positive MN at diagnosis are associated with improved event-free and overall survival. Together, these findings link ecDNA mis-segregation to MN formation and reduced cellular fitness, suggesting that ecDNA-positive MN may reflect a state of impaired oncogenic ecDNA function with potential relevance for clinical outcome.

cancer biology↗

bioRxiv2025

Accounting for spatial interactions in the upscaling of ecosystem services

O_LIMaps of ecosystem service (ES) supply are frequently used to guide spatial planning, policy making, and ecosystem management. However, these are typically based upon coarse land-cover proxies. This approach lacks a strong mechanistic basis, and neglects spatial biodiversity dynamics and interactions among landscape properties that can modify ES provision. C_LIO_LIWe present an analytical framework for ES upscaling that incorporates spatial interactions between landscape properties to determine ES supply. The resulting models can be viewed as a spatially informed ES production function. The approach comprises seven steps that include several elements absent from most existing approaches, notably a procedure for identifying geodata variables that represent the true mechanistic drivers, the inclusion of spatial interactions in the upscaling model, and modification following expert feedback on the selected model. C_LIO_LIWe demonstrate the approach using two example ES from German grasslands: biodiversity conservation and water supply. We show that the inclusion of spatial interactions in the upscaling model improved model predictions from 15% to 33% depending on the ES evaluated. In addition, inclusion of spatial interactions led to reduced error associated with the upscaled estimates. C_LIO_LIBy overcoming several shortcomings of existing, upscaling approaches we generate resulting maps of ES supply that can more reliably inform spatial planning Further, the underlying models allow for simulation of changes in the drivers of ES supply and estimation of respective outcomes. These advantages have the potential to better link detailed local-scale ecological understanding and land management with large-scale ES supply mapping, and thus better inform decision making and spatial planning. C_LI

ecology↗

bioRxiv2024

Future climate and land use change will equally impact global terrestrial vertebrate diversity

Aim: Terrestrial biodiversity is impacted by both climate and land use change. Yet, future biodiversity projections have rarely considered these two drivers in combination. In this study, we aim to assess the individual and combined impact of future climate and land use change on global terrestrial vertebrate diversity under a "sustainability" (SSP1-RCP2.6) and an "inequality" (SSP4-RCP6.0) scenario. Location: Global land, excluding Antarctica. Time period: 1995, 2080 Major taxa studied: Amphibians, birds, and mammals. Methods: We combined global climate-driven species distribution model (SDM) projections of 13903 vertebrates (amphibians, birds, and mammals) with future and present land use projections from the Land Use Harmonization 2 (LUH2) project. We refined the SDM outputs by the habitat requirements of each species using a land use filtering approach. We then analyzed future species richness changes globally, per region, and per land use category, and looked at taxon-specific effects. Results: Under both scenarios, decreases in future species richness dominate at low and mid-latitudes, with climate and land use change playing an equally important role. Land use change can be either an alleviating (SSP1-RCP2.6) or an exacerbating (SSP4-RCP6.0) factor of climate-induced biodiversity loss. Sub-Saharan Africa is projected to become a high-risk area for future land use-driven biodiversity loss under the SSP4-RCP6.0. Under SSP1-RCP2.6, forested and non-forested land areas increase, while SSP4-RCP6.0 leads to higher rates of deforestation and pasture expansion. Mammals experience the largest climate-driven losses, affecting 56.4% of land area under SSP4-RCP6.0, while amphibians are particularly vulnerable to land use-driven losses, especially under SSP4-RCP6.0. Main conclusions: Our results suggest that both climate and land use pressures on biodiversity will be highest in lower latitudes, which harbor the highest levels of biodiversity.

ecology↗

bioRxiv2024

CREB3 gain of function variants protect against ALS

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly evolving neurodegenerative disease that arises from the loss of glutamatergic corticospinal neurons (CSN) and cholinergic motoneurons (MN). The disease is mostly sporadic, but genetics is expected to highly contribute to disease onset and progression. Genome wide association studies identified a few genetic disease modifiers, mostly associated with a negative outcome, and demonstrated that ALS is primarily a disease of excitatory glutamatergic neurons. Here, we reasoned that at least a subpart of genetic disease modifiers may directly modulate the molecular pathways selectively activated in vulnerable neurons as the disease progresses, and concentrated on CSN for their selective vulnerability and glutamatergic identity. We implemented comparative cross-species transcriptomics using snRNAseq data from postmortem motor cortex of ALS patients and controls, and longitudinal RNAseq data from anatomically defined CSN purified from the Sod1G86R mouse model of ALS. We report that disease vulnerable neuronal populations undergo ER stress and altered mRNA translation, and identify the transcription factor CREB3 and its regulatory network as a resilience marker of neuronal dysfunction in ALS. Using genetic and epidemiologic analyses we further identify the rare variant CREB3R119G (rs11538707) as a new disease modifier in ALS. Through gain of function, CREB3R119G decreases both the risk of developing ALS and the progression rate of ALS patients. This study reveals novel genetic variants that protect against ALS and highlights the benefice of combining transcriptomics and genetics to identify new disease modifiers and therapeutic targets.

genomics↗

bioRxiv2024

Robust CRISPR/dCas13 RNA blockers specifically perturb miRNA-target interactions and rescue type 1 myotonic dystrophy pathology

While RNA-targeting strategies are powerful tools for disease therapy, challenges, including low target engagement and off-target collateral effects, currently limit their efficacy. Here, we report the engineering and optimisation of a CRISPR/dCas13 RNA steric blocker (CRISPR-Lock) that prevents mRNA translation, shields mRNAs from miRNA-mediated silencing, and blocks RNA-protein interactions. By tuning the spatial resolution and mismatch tolerance of CRISPR-Lock, we develop a high-resolution perturbation approach that employs genetically encoded CRISPR-Lock as a miRNA target protector. This system enables precise spatiotemporal control of miRNA:mRNA interactions, offering broader applicability compared to phosphorodiamidate mor-pholino (PMO) target protectors. Moreover, we demonstrate the potential therapeutic application of CRISPR-Lock for blocking pathological RNA-protein interactions in type 1 myotonic dystro-phy (DM1). Optimising CRISPR-Lock to target expanded repeat RNAs corrects approximately 85% of clinically relevant splicing biomarkers in patient-derived myotubes and significantly out-performs third-generation PMO antisense oligonucleotides. Finally, by delivering a miniaturised AAV-encoded CRISPR-Lock system into an established DM1 mouse model, we demonstrate the dose-dependent correction of intranuclear foci and splicing dysregulation, underscoring the potential therapeutic application of this technology.

bioengineering↗

bioRxiv2024

The Greenland shark (Somniosus microcephalus) genome provides insights into extremelongevity

The Greenland shark (Somniosus microcephalus) is the longest-lived vertebrate known, with an estimated lifespan of [~] 400 years. Here, we present a chromosome-level assembly of the 6.45 Gb Greenland shark, rendering it one of the largest non-tetrapod genomes sequenced so far. Expansion of the genome is mostly accounted for by a substantial expansion of transposable elements. Using public shark genomes as a comparison, we found that genes specifically duplicated in the Greenland shark form a functionally connected network enriched for DNA repair function. Furthermore, we identified a unique insertion in the conserved C-terminal region of the key tumor suppressor p53. We also provide a public browser to explore its genome.

genomics↗

bioRxiv2024

Circadian clock disruption engages the DREAM complex in suppressing cellular health.

Circadian clock disruption and lack of sleep impair organismal health, but remedies remain elusive. Here, we used multi-omics, molecular and functional assays in C. elegans, human retinal cells and mouse brain to identify the DREAM complex as a conserved mediator of sleep and clock benefits at the cellular level. We show that DREAM abundance is under circadian control with high levels seen during wakefulness. DREAM elevation confers increased chromatin compaction and shields DNA from damage while altering fundamental cellular processes such as translation, stress responses and OXPHOS. Conversely, DREAM levels are lowered during sleep enabling cellular maintenance and repair. When sleep or clock are altered, DREAM levels remain high, and repair activities remain suppressed triggering cellular and organismal deterioration that can be reversed by genetic and pharmacological inhibition of DREAM in vivo and in vitro. We thus reveal the potential of DREAM inhibitors to replicate the benefits of sleep in sleep-deprived and clock-impaired organisms.

physiology↗

bioRxiv2024

Levels of DNA accessibility in human sperm vary across individuals with differing reproductive parameters

Mammalian sperm DNA is packaged in a much denser form than in somatic cells, protecting the DNA from damage and reducing the size of the nucleus to improve passage towards the oocyte. While defective sperm DNA packaging correlates with reduced fertilization rates and impaired pre-implantation embryonic development, these defects are not currently examined in standard semen analysis. Here, we adapted NicE-view, an assay that directly labels accessible DNA, for use in human sperm and applied this method including extensive image quantification to examine spermatozoa from individuals with normal conventional semen parameters but variable reproductive outcomes. We found that two sub-populations of cells differing greatly in their DNA accessibility exist within both total and motile sperm. The frequencies of these two sub-populations vary between individuals, and selection of motile sperm by swim-up generally enriches for sperm with high DNA accessibility. Individuals with high frequencies of sperm with high DNA accessibility possess decreased sperm concentrations and increased DNA nicking levels and a subset of these individuals have a history of post-fertilization embryogenic failure. NicE-view shows much clearer separation of staining levels than alternative DNA labeling approaches, and represents a valuable tool for the assessment of human sperm.

molecular biology↗

bioRxiv2024

Automated high-throughput selection of DNA aptamers using a common optical next-generation sequencer

Aptamers are conventionally selected via Systematic Evolution of Ligands by Exponential Enrichment (SELEX). This process is, however, laborious, time-consuming, and has a relatively low efficacy. Here, we developed an automated high-throughput screening platform for the selection of DNA aptamers which consists of an optical next-generation sequencer with a modified software and hardware to automatically perform fluorescence-based binding assays on the displayed DNA sequences subsequent to sequencing. Using this platform, after only three to five SELEX rounds we selected highly affine DNA aptamers for the lectins LecA and LecB of Pseudomonas aeruginosa as well as for the Pseudomonas Exotoxin A. In comparison, twelve rounds of conventional SELEX resulted in three-fold less affine aptamers for LecA and PEA and none for LecB. Our high throughput-approach bears great potential to augment SELEX as it significantly increases time efficiency, enabling the selection of aptamers within only one week.

biochemistry↗

bioRxiv2024

PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and has traditionally been thought to begin with the uptake of the Sec carrier selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP undergoes metabolisation via selenocysteine lyase (SCLY), producing selenide, a substrate used by selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor - selenophosphate - for the biosynthesis of the selenocysteine tRNA. Here, we report the discovery of an alternative pathway mediating Sec metabolisation that is independent of SCLY and mediated by peroxiredoxin 6 (PRDX6). Mechanistically, we demonstrate that PRDX6 can readily react with selenide and interact with SEPHS2, potentially acting as a selenium delivery system. Moreover, we demonstrate the presence and functional significance of this alternative route in cancer cells where we reveal a notable association between elevated expression of PRDX6 with a highly aggressive neuroblastoma subtype. Altogether, our study sheds light on a previously unrecognized aspect of Sec metabolism and its implications in ferroptosis, offering new avenues for therapeutic exploitation.

cell biology↗

bioRxiv2024

Blind but alive - congenital loss of atoh7 disrupts the visual system of adult zebrafish.

1PurposeVision is the predominant sense in most animal species. Loss of vision can be caused by a multitude of factors resulting in anatomical as well as behavioral changes. In mice and zebrafish, atoh7 mutants are completely blind as they fail to generate retinal ganglion cells during development. In contrast to mice, raising blind zebrafish to adulthood is challenging and this important model is currently missing in the field. Here, we report the phenotype of homozygous mutant adult zebrafish atoh7 mutants that have been raised using adjusted feeding and holding conditions. MethodsThe phenotype of adult mutants was characterized using classical histology and immunohistochemistry as well as optical coherence tomography. In addition, the optokinetic response was characterized. ResultsAdult atoh7 mutants display dark body pigmentation and significantly reduced body length. They fail to form retinal ganglion cells, the resulting nerve fiber layer as well as the optic nerve, and consequently behave completely blindly. In contrast, increased amounts of other retinal neurons and Muller glia are formed. In addition, the optic tectum is anatomically reduced in size, presumably due to the missing retinal input. ConlusionsTaken together, we provide a comprehensive characterization of a completely blind adult zebrafish mutant with focus on retinal and tectal morphology, as a useful model for glaucoma and optic nerve aplasia.

neuroscience↗

bioRxiv2024

Natural history of eukaryotic DNA viruses with double jelly-roll major capsid proteins

The phylum Preplasmiviricota (kingdom Bamfordvirae, realm Varidnaviria) is a broad assemblage of diverse viruses with comparatively short double-stranded DNA genomes (<50 kbp) that produce icosahedral capsids built from double jelly-roll major capsid proteins. Preplasmiviricots infect hosts from all cellular domains, testifying to their ancient origin and, in particular, are associated with six of the seven supergroups of eukaryotes. Preplasmiviricots comprise four major groups of viruses, namely, polintons, polinton-like viruses (PLVs), virophages, and adenovirids. We employed protein structure modeling and analysis to show that protein-primed DNA polymerases (pPolBs) of polintons, virophages, and cytoplasmic linear plasmids encompass an N-terminal domain homologous to the terminal proteins (TPs) of prokaryotic PRD1-like tectivirids and eukaryotic adenovirids that are involved in protein-primed replication initiation, followed by a viral ovarian tumor-like cysteine deubiquitinylase (vOTU) domain. The vOTU domain is likely responsible for the cleavage of the TP from the large pPolB polypeptide and is inactivated in adenovirids, in which TP is a separate protein. Many PLVs and transpovirons encode a distinct derivative of polinton-like pPolB that retains the TP, vOTU and pPolB polymerization palm domains but lacks the exonuclease domain and instead contains a supefamily 1 helicase domain. Analysis of the presence/absence and inactivation of the vOTU domains, and replacement of pPolB with other DNA polymerases in eukaryotic preplasmiviricots enabled us to outline a complete scenario for their origin and evolution. SignificanceStructural modeling of protein domains using advanced artificial intelligence-based methods such as AlphaFold2 may lead to insights into evolutionary relationships among proteins that are unreachable by sequence analysis. We applied this approach to elucidate the evolutionary relationships of four major groups of eukaryotic viruses: polintons, polinton-like viruses (PLVs), virophages, and adenovirids. We identified previously uncharacterized protein domains predicted to be essential for virus genome replication. Analysis of the presence/absence and inactivation of these domains suggests a complete scenario for the origin and evolution of this major part of the eukaryotic virosphere.

microbiology↗

bioRxiv2024

One to rule them all? Assessing the performance of Forest Europe's biodiversity indicators against multitaxonomic data

Several regional initiatives and reporting efforts assess the state of forest biodiversity through broad-scale indicators based on data from national forest inventories. Although valuable, these indicators are essentially indirect and evaluate habitat quantity and quality rather than biodiversity per se. Therefore, their link to biodiversity may be weak, which decreases their usefulness for decision-making. For several decades, Forest Europe indicators assessed the state of European forests, in particular their biodiversity. However, no extensive study has been conducted to date to assess their performance - i.e. the capacity of the indicators to reflect variations in biodiversity - against multitaxonomic data. We hypothesized that no single biodiversity indicator from Forest Europe can represent overall forest biodiversity, but that several indicators would reflect habitat quality for at least some taxa in a comprehensive way. We tested the set of Forest Europes indicators against the species richness of six taxonomic and functional groups across several hundreds of sampling units over Europe. We showed that, while some indicators perform relatively well across groups (e.g. deadwood volume), no single indicator represented all biodiversity at once, and that a combination of several indicators performed better. Forest Europe indicators were chosen for their availability and ease of understanding for most people. However, we showed that gaps in the monitoring framework persist, and that surveying certain taxa along with stand structure is necessary to support policymaking and tackle forest biodiversity loss at the large scale. Adding context (e.g. forest type) may also contribute to increase the performance of biodiversity indicators. Impact statementBiodiversity indicators used to assess the state of Europes forests perform unequally; a combination of indicators is more informative

ecology↗

bioRxiv2024

Old, deciduous stands support both high biodiversity and carbon storage in German forests

Ecosystems worldwide face threats related to human-driven degradation, climate change, and biodiversity loss. Addressing these challenges requires management strategies that combine biodiversity conservation with climate change mitigation. Here, we aimed to identify local-scale management actions that promote biodiversity at multiple trophic levels while also promoting carbon storage and sequestration. We combined data on the diversity of nine taxonomic groups (plants, birds, moths, Mollusca, soil fungi, active soil bacteria, Cercozoan and Endomyxan soil protists, Oomycotan soil protists, and nematodes), with above- and belowground carbon storage in 150 temperate forest plots in three regions of Germany. These were dominated by European beech, pine, spruce and oak. We investigated the relationships between multiple forest structure and management variables, biodiversity and carbon storage and sequestration in forest plots with different management types. Carbon storage was 32% higher in uneven-aged than even-aged forests and increased with mean tree diameter, while carbon sequestration in trees was 15% higher in even-aged than uneven-aged stands. Mean tree diameter was positively related to overall biodiversity, especially bird species richness and the richness of forest specialist birds. Oak and beech-dominated stands harboured higher biodiversity than stands dominated by conifers (especially Pine). One exception to this was the richness of plant species and forest specialist plants, which were highest in spruce plantations. Surprisingly, deadwood input did not significantly affect the diversity of any taxonomic group in this study. By showing that older forests with a high proportion of uneven-aged broad-leafed trees, or oak-dominated forests, can promote both biodiversity and carbon storage, our results could help inform sustainable local-scale forest management in Central Europe that promotes both biodiversity conservation and carbon storage. These findings can form the basis of further larger-scale studies investigating such relations at larger spatial scales to inform landscape-level recommendations for sustainable multifunctional forest management.

ecology↗

bioRxiv2023

Comparison of the mechanism of antimicrobial action of the gold(I) compound auranofin in Gram-positive and Gram-negative bacteria

The antirheumatic gold(I) compound auranofin has been suggested to exhibit bactericidal activity by disrupting the thiol homeostasis through direct inhibition of bacterial thioredoxin reductase (TrxB). While highly effective at killing Gram-positive bacteria, it lacks significant activity against Gram-negative species for reasons that largely remain unclear. Here, we aimed to elucidate the molecular mechanisms underlying the low susceptibility of the Gram-negative model organism Escherichia coli to auranofin when compared to the Gram-positive model organism Bacillus subtilis. A change in the proteome of E. coli exposed to auranofin suggested that the effect of this gold compound is a combination of inactivation of thiol-containing enzymes, upregulation of proteins involved in basal metabolism, and the consequent induction of systemic oxidative stress. Susceptibility tests in E. coli mutants lacking the proteins upregulated upon auranofin treatment suggested that none of them are directly involved in E. colis high tolerance to auranofin. To elucidate factors that could make Gram-negative bacteria less susceptible to auranofin, we tested E. coli cells lacking the efflux pump component TolC. These cells were more sensitive to auranofin treatment than the wild type, but not to an extent that would fully explain the observed difference in susceptibility of Gram-positive and Gram-negative organisms. We thus tested if E. colis thioredoxin reductase (TrxB) is inherently less sensitive to auranofin than TrxB from B. subtilis, which was not the case. E. coli cells lacking components of the thioredoxin-system were also only marginally more susceptible to auranofin. However, E. coli strains lacking the low molecular weight thiol glutathione, but not glutathione reductase, showed a high susceptibility to auranofin. Bacterial cells expressing the genetically encoded redox probe roGFP2 allowed us to observe the oxidation of cellular protein thiols in situ. In line with their susceptibility, the kinetics of probe oxidation and the degree of oxidation promoted by auranofin is significantly higher in Gram-positive bacteria when compared to Gram-negative bacteria. Based on our findings, we hypothesize that auranofin leads to a global disturbance in the cellular thiol redox homeostasis in bacteria, but Gram-negative bacteria are inherently more resistant due to the presence of drug export systems and high cellular concentrations of glutathione.

biochemistry↗

bioRxiv2023

METTL3/MYCN cooperation drives m6A modification during trunk neural crest differentiation and represents a therapeutic vulnerability in MYCN-amplified neuroblastoma

Neuroblastoma (NB) is the most common extracranial childhood cancer, caused by the improper differentiation of developing trunk neural crest cells (tNCC) in the sympathetic nervous system. The N6-methyladenosine (m6A) epitranscriptomic modification controls post-transcriptional gene expression but the mechanism by which the m6A methyltransferase complex METTL3/METTL14/WTAP is recruited to specific loci remains to be fully characterized. We explored whether the m6A epitranscriptome could fine-tune gene regulation in migrating/differentiating tNCC. We demonstrate that the m6A modification regulates the expression of HOX genes in tNCC, thereby contributing to their timely differentiation into sympathetic neurons. Furthermore, we show that posterior HOX genes are m6A modified in MYCN-amplified NB with reduced expression. In addition, we provide evidence that sustained overexpression of the MYCN oncogene in tNCC drives METTL3 recruitment to a specific subset of genes including posterior HOX genes creating an undifferentiated state. Moreover, METTL3 depletion/inhibition induces DNA damage and differentiation of MYCN overexpressing cells and increases vulnerability to chemotherapeutic drugs in MYCN-amplified patient-derived xenografts (PDX) cells, suggesting METTL3 inhibition could be a potential therapeutic approach for NB.

cancer biology↗

bioRxiv2023

A fast-slow trait continuum at the level of entire communities

Across the tree of life, organismal functional strategies form a continuum from slow-to fast-growing organisms, in response to common drivers such as resource availability and disturbance. However, the synchronization of these strategies at the entire community level is untested. We combine trait data for >2800 above-and belowground taxa from 14 trophic guilds spanning a disturbance and resource availability gradient in German grasslands. Most guilds consistently respond to these drivers through both direct and trophically-mediated effects, resulting in a slow-fast axis at the level of the entire community. Fast trait communities were also associated with faster rates of whole ecosystem functioning. These findings demonstrate that slow and fast strategies can be manifested at the level of whole ecosystems, opening new avenues of ecosystem-level functional classification.

ecology↗

bioRxiv2023

Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia

Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodelling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodelling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodelling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/539799v4_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@14fa4bcorg.highwire.dtl.DTLVardef@1c86bbborg.highwire.dtl.DTLVardef@118edfcorg.highwire.dtl.DTLVardef@1b06916_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗