Publications by authors named "Kevin Mulder"

Article Synopsis
  • Amphibians are a diverse group of tetrapods facing significant threats, with about 41% of species at risk of extinction due to various factors like habitat loss and climate change.
  • Genomic research on amphibians is critical for understanding their biology, including unique traits like tissue regeneration and adaptation, yet it has lagged behind other vertebrates due to technical challenges.
  • The newly formed Amphibian Genomics Consortium (AGC) aims to enhance global collaboration and accelerate genomic research in amphibians, with over 282 members from 41 countries already involved.
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Article Synopsis
  • Dendritic cells (DC) are essential immune cells that connect the body's innate and adaptive immune responses, with two main types: plasmacytoid DC (pDC) and conventional DC (cDC).
  • Research using in vivo deuterium-glucose labeling revealed that a specific subset of cDC known as AXL+ Siglec6+ DC (ASDC) circulates in the bloodstream for about 2.16 days, while other cDC types have slightly shorter lifespans.
  • The study also showed that ASDC are quickly recruited to inflamed areas, highlighting their role in managing immune responses during inflammation and suggesting new insights into the behavior of different DC subsets.
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Macrophages orchestrate tissue homeostasis and immunity. In the tumor microenvironment (TME), macrophage presence is largely associated with poor prognosis because of their reprogramming into immunosuppressive cells. We investigated the effects of hypoxia, a TME-associated feature, on the functional, epigenetic, and transcriptional reprogramming of macrophages and found that hypoxia boosts their immunogenicity.

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Novel individual biomarkers are needed to guide therapeutic decisions for patients with head and neck cancer. We report for the first time, granulomas of TREM2-expressing multinucleated giant macrophages in keratin-rich tumor niches, as a biomarker of favorable prognosis and developed a deep-learning model to automate its quantification on routinely stained pathological slides.

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Tumor-associated macrophages (TAMs) are a heterogeneous population of cells whose phenotypes and functions are shaped by factors that are incompletely understood. Herein, we asked when and where TAMs arise from blood monocytes and how they evolve during tumor development. We initiated pancreatic ductal adenocarcinoma (PDAC) in inducible monocyte fate-mapping mice and combined single-cell transcriptomics and high-dimensional flow cytometry to profile the monocyte-to-TAM transition.

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Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomic resources is more urgent than ever due to the increasing threats to this group.

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Spatial omics data allow in-depth analysis of tissue architectures, opening new opportunities for biological discovery. In particular, imaging techniques offer single-cell resolutions, providing essential insights into cellular organizations and dynamics. Yet, the complexity of such data presents analytical challenges and demands substantial computing resources.

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FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors.

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Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL.

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The chytrid fungus Batrachochytrium dendrobatidis (Bd) was discovered in 1998 as the cause of chytridiomycosis, an emerging infectious disease causing mass declines in amphibian populations worldwide. The rapid population declines of the 1970s-1990s were likely caused by the spread of a highly virulent lineage belonging to the Bd-GPL clade that was introduced to naïve susceptible populations. Multiple genetically distinct and regional lineages of Bd have since been isolated and sequenced, greatly expanding the known biological diversity within this fungal pathogen.

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Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage.

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Article Synopsis
  • - Antibiotics can reduce the effectiveness of PD-1 blockade in cancer treatment, but we still don’t fully understand how they weaken immune responses.
  • - The study found that after antibiotics, certain gut bacteria lead to a decrease in MAdCAM-1, promoting regulatory T cells to leave the gut and move into tumors, which negatively impacts immune function.
  • - In cancer patients, lower levels of soluble MAdCAM-1 in the blood were associated with poorer outcomes, suggesting that targeting the MAdCAM-1-α4β7 pathway could improve cancer immunotherapy strategies.
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Brain macrophage populations include parenchymal microglia, border-associated macrophages, and recruited monocyte-derived cells; together, they control brain development and homeostasis but are also implicated in aging pathogenesis and neurodegeneration. The phenotypes, localization, and functions of each population in different contexts have yet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematically delineate brain macrophage populations.

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Article Synopsis
  • - Biomarkers are necessary to optimize the use of immune-checkpoint blockers (ICB) like pembrolizumab for patients with localized muscle-invasive bladder cancer (MIBC), as highlighted by the study on T cells and immune responses.
  • - The research identified follicular helper CD4+ T cells (TFH) and specific antibodies against E. coli as potential biomarkers that correlate with better clinical outcomes for patients receiving pembrolizumab treatment.
  • - Understanding the connections between tumor infections and immune responses can lead to improved therapeutic strategies and better patient management in the future.
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The ability to bear live offspring, viviparity, has evolved multiple times across the tree of life and is a remarkable adaptation with profound life-history and ecological implications. Within amphibians the ancestral reproductive mode is oviparity followed by a larval life stage, but viviparity has evolved independently in all three amphibian orders. Two types of viviparous reproduction can be distinguished in amphibians; larviparity and pueriparity.

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Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues.

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Until recently many historical museum specimens were largely inaccessible to genomic inquiry, but high-throughput sequencing (HTS) approaches have allowed researchers to successfully sequence genomic DNA from dried and fluid-preserved museum specimens. In addition to preserved specimens, many museums contain large series of allozyme supernatant samples, but the amenability of these samples to HTS has not yet been assessed. Here, we compared the performance of a target-capture approach using alternative sources of genomic DNA from 10 specimens of spring salamanders (Plethodontidae: Gyrinophilus porphyriticus) collected between 1985 and 1990: allozyme supernatants, allozyme homogenate pellets and formalin-fixed tissues.

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A period of isolation in allopatry typically precedes local adaptation and subsequent divergence among lineages. Alternatively, locally adapted phenotypes may arise and persist in the face of gene flow, resulting in strong correlations between ecologically-relevant phenotypic variation and corresponding environmental gradients. Quantifying genetic, ecological, and phenotypic divergence in such lineages can provide insights into the abiotic and biotic mechanisms that structure populations and drive the accumulation of phenotypic and taxonomic diversity.

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The radiation of Palearctic green toads (Bufotes) holds great potential to evaluate the role of hybridization in phylogeography at multiple stages along the speciation continuum. With fifteen species representing three ploidy levels, this model system is particularly attractive to examine the causes and consequences of allopolyploidization, a prevalent yet enigmatic pathway towards hybrid speciation. Despite substantial efforts, the evolutionary history of this species complex remains largely blurred by the lack of consistency among the corresponding literature.

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Species with narrow environmental tolerances are often distributed within fragmented patches of suitable habitat, and dispersal among these subpopulations can be difficult to directly observe. Genetic data can help quantify gene flow between localities, which is especially important for vulnerable species with a disjunct range. The Shenandoah salamander () is a federally endangered species known only from three mountaintops in Virginia, USA.

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The presence of mast cells in human atherosclerotic plaques has been associated with adverse cardiovascular events. Mast cell activation, through the classical antigen sensitized-IgE binding to their characteristic Fcε-receptor, causes the release of their cytoplasmic granules. These granules are filled with neutral proteases such as tryptase, but also with histamine and pro-inflammatory mediators.

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Effective conservation and management of pond-breeding amphibians depends on the accurate estimation of population structure, demographic parameters, and the influence of landscape features on breeding-site connectivity. Population-level studies of pond-breeding amphibians typically sample larval life stages because they are easily captured and can be sampled nondestructively. These studies often identify high levels of relatedness between individuals from the same pond, which can be exacerbated by sampling the larval stage.

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Infectious diseases are causing catastrophic losses to global biodiversity. Iridoviruses in the genus Ranavirus are among the leading causes of amphibian disease-related mortality. Polymorphisms in major histocompatibility complex (MHC) genes are significantly associated with variation in amphibian pathogen susceptibility.

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The Major Histocompatibility Complex (MHC) is a genomic region encoding immune loci that are important and frequently used markers in studies of adaptive genetic variation and disease resistance. Given the primary role of infectious diseases in contributing to global amphibian declines, we characterized the hypervariable exon 2 and flanking introns of the MHC Class IIβ chain for 17 species of frogs in the Ranidae, a speciose and cosmopolitan family facing widespread pathogen infections and declines. We find high levels of genetic variation concentrated in the Peptide Binding Region (PBR) of the exon.

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The complete mitochondrial genome of was reconstructed using bycatch sequences from an RNAseq library generated from muscle tissue. This study shows the potential of using data originally produced for transcriptome assembly to additionally generate complete mitochondrial genomes. The resulting mitogenome was circular, consisted of 16,331 bp and followed the standard vertebrate gene order.

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