Biology subjects

Just, J.

Publications and source records attributed to Just, J..

14 recordsLinked to original sources

bioRxiv2026

Host specificity, seasonality, and urbanicity shape the gut microbiome of a synanthropic insect

The soapberry bug Jadera haematoloma is a classic model of rapid adaptive evolution, with a well-documented host shift from native herbaceous sapinds to the introduced goldenrain tree (Koelreuteria spp.). This host shift has facilitated the insect's spread into novel anthropogenic urban habitats. Microbial associations are often critical to insect environmental adaptation. Here, we characterize the gut microbiota of J. haematoloma across native and introduced host plants, seasonal transitions, and a gradient of urbanicity. Our findings indicate that the soapberry bug gut microbiome is highly specialized, with a small number of core bacterial amplicon sequence variants (ASVs) primarily from the families Rhizobiaceae, Streptococcaceae, Enterobacteriaceae, and Lactobacillaceae. While traits such as sex and wing morph do not correlate with microbiome structure, the host plant acts as the primary determinant of community composition. Bugs feeding on the ancestral host plant maintain a more diverse and even microbial community featuring Enterobacteriaceae, whereas the gut environment of bugs on the introduced host is overwhelmingly dominated by a single unclassified Rhizobiaceae ASV. Furthermore, seasonal transitions drive significant turnover among accessory microbial taxa. Finally, we demonstrate that urbanization introduces a distinct ecological effect on the insect's microbiome. While the degree of local green space does not systematically alter within-host taxonomic richness, it is associated with modest change in mean community composition and significantly disrupts microbial community variance. Increased urbanization correlates with significantly higher beta dispersion, indicating that anthropogenic environments lead to more stochastic microbiomes, which may be an indicator of environmental stress. Together, these results illustrate how rapid dietary host shifts and the ecological pressures of urbanization interact to shape the microbiome of a synanthropic insect.

ecology↗

bioRxiv2026

Sex shapes capillary flows and oxygen extraction in the middle-aged mouse brain

Sex differences in brain aging are well documented, but their origin within the cerebrovascular hierarchy remains unclear. Here we show that cortical blood flow is higher in female than male mice at 15 months of age, at a point when an earlier sex difference in pulsatility and resistance indices has already converged, pial vessel diameter shows no difference between sexes, and estrogen levels are similar between sexes. Using an indicator-dilution and intravascular oxygen measurements using two-photon microscopy, we found that capillary transit-time heterogeneity (CTH) scales more steeply with mean transit time in females, consistent with a passively regulated capillary network, and that this is accompanied by reduced oxygen extraction fraction (OEF) without deficit in arterial oxygen delivery. Spatial transcriptomics reveals that sex differences are organized into distinct regional programs, most prominently in white matter, where a male-associated myelin and axonogenesis signature accompanies reduced white matter volume in females. These molecular and structural differences coincide with elevated hippocampal microglial reactivity and an altered spatial search strategy in females, without any detectable differences in circulating markers of stress, blood-brain barrier integrity, or immunity. Together, these findings indicate that sex differences in the aging brain are expressed at the level of capillary flow regulation and regional tissue programs rather than through bulk cerebral blood flow alone, and that elevated blood flow in females can mask, rather than reflect, adequate tissue oxygenation.

neuroscience↗

bioRxiv2026

Fibro-adipogenic Progenitor and Macrophage Remodeling of the Aging Skeletal Muscle Niche During Exercise-Induced Hypertrophy

Fibro-adipogenic progenitors (FAPs) have emerged as central regulators of the skeletal muscle homeostasis and the muscle microenvironment. However, the role of FAPs in the context of exercise-induced muscle hypertrophy remains largely unexplored. Here, we utilized six weeks of blood flow restricted resistance exercise (BFRRE) to study cellular adaptations within the muscle microenvironment accompanying muscle hypertrophy in healthy older individuals. Using flow cytometry, we characterized global changes of key cell populations within the skeletal muscle microenvironment, including FAPs, muscle stem cells (MuSCs), and immune cells. BFRRE induced significant enlargement of both FAPs and MuSCs, consistent with cellular adaptation to exercise. Notably, exercise shifted the FAP pool toward an increased predominance of the CD90high FAP phenotype, without altering total FAP abundance. In addition to matrix and collagen-related genes, transcriptional analysis of genes associated with secretory proteins revealed enrichment of promyogenic factors in CD90high versus CD90low FAPs. Conditioned media experiments of freshly isolated FAPs demonstrated that CD90high FAPs promote myotube growth in vitro compared to CD90low counterparts, suggesting that this phenotypic shift may facilitate muscle hypertrophy. In parallel, BFRRE increased the proportion of pro-inflammatory (CD11c+) macrophages within the skeletal muscle niche, highlighting a dynamic immune response during adaptation. Finally, we show identified possible link between pro-inflammatory macrophages and FAPs, as TNF markedly reduced the proliferation of human primary FAPs ex vivo, suggesting that macrophage-derived signals may attenuate excessive FAP expansion during tissue remodelling. Together, these findings provide new insight into how the remodelling of the cellular niche may support muscle hypertrophy in response to exercise. The coordinated expansion and phenotypic remodeling of FAP and immune cell populations may represent an important mechanism through which exercise supports hypertrophy in older individuals.

cell biology↗

bioRxiv2025

Interplay between petal identity and cell layer identity in petunia flowers

In flowering plants, floral organ identity is specified by the combinatorial action of homeotic genes. While the role of these genes in the early specification of organ identity is well established, their late function throughout floral organ development and in specific cell types is much less characterized. In particular, since plant organs are structured in clonally-independent cell layers, whether and how homeotic identity interacts with cell layer identity is unknown. We have previously identified cell layer-specific mutants for the petal identity gene PhDEF in petunia flowers, resulting in drastically different petal phenotypes whether PhDEF is expressed in the petal epidermis or in the mesophyll. In this study, using a combination of single-cell RNA-Seq and chromatin immunoprecipitation on phdef cell layer-specific mutants, we find that PhDEF regulates a different set of target genes in the petal epidermis and mesophyll, with a major regulatory action in the epidermis. We uncover a high diversity of binding profiles in PhDEF target genes, with a complex combination of layer-specific or non-specific binding sites, and a much more prominent binding of PhDEF in the epidermis than in the mesophyll. Our study highlights that floral homeotic genes like PhDEF can have different regulatory actions in different cell contexts, here different cell layers, demonstrating that cell layer identity indeed influences the regulatory processes underlying homeotic identity.

developmental biology↗

bioRxiv2025

Common and distinct roles of AMPKγ isoforms in small-molecule activator-stimulated glucose uptake in mouse skeletal muscle

ObjectiveSmall-molecule activators targeting the allosteric drug and metabolite (ADaM) site of AMPK enhance insulin-independent glucose uptake in skeletal muscle and lower glucose in preclinical models of hyperglycemia. The regulatory AMPK{gamma} subunit plays a central role in energy sensing. While the skeletal muscle-selective {gamma}3 isoform is essential for AMP/ZMP-induced glucose uptake, it is dispensable for ADaM site-binding activators. We hypothesized that the predominant {gamma}1 isoform is required for ADaM site activator-stimulated glucose uptake in skeletal muscle. MethodsSingle-nucleus RNA sequencing (snRNA-seq) was performed on mouse and human skeletal muscle mapping AMPK subunit isoform distribution across resident cell types. To determine {gamma} isoform-specific requirements for activator-stimulated glucose uptake, skeletal muscle-specific inducible AMPK{gamma}1/{gamma}3 double knockout (im{gamma}1-/-/{gamma}3-/-) and single knockout (im{gamma}1-/- and im{gamma}3-/-) mice were generated. Ex vivo glucose uptake was measured following treatment with AICAR (AMP-mimetic) or MK-8722 (ADaM site activator), and in vivo MK-8722-induced blood glucose lowering was assessed. ResultssnRNA-seq revealed distinct AMPK isoform distribution: {gamma}1 was ubiquitously expressed, whereas {gamma}3 was enriched in glycolytic myofibers in both mouse and human skeletal muscle. Ex vivo, glucose uptake stimulated by either AICAR or MK-8722 was abolished in im{gamma}1-/-/{gamma}3-/- muscle, and MK-8722-induced blood glucose lowering was significantly blunted in vivo. AICAR but not MK-8722-stimulated muscle glucose uptake was abolished in im{gamma}3-/-, whereas both activators fully retained effects on glucose uptake and glucose lowering in im{gamma}1-/- mice. ConclusionsWhile {gamma}1 predominates in stabilizing the AMPK2{beta}2{gamma}1 complex, it is dispensable for AMPK activator-stimulated glucose uptake in skeletal muscle, whether mediated via the nucleotide-binding or ADaM site.

biochemistry↗

bioRxiv2024

Complementing Muscle Regeneration: Fibro-Adipogenic Progenitor and Macrophage-Mediated Repair of Elderly Human Skeletal Muscle

The capacity to regenerate skeletal muscle function after injury requires a complex and well-coordinated cellular response. Here, we unravel the intricate dynamics of human skeletal muscle regeneration by combining spatial, temporal, and single cell transcriptomics. Using spatial RNA sequencing, we profiled the expression of human protein-coding genes in elderly human skeletal muscle biopsies before as well as 2-, 8-, and 30-days post injury. Single Cell-Spatial deconvolution analysis highlights monocytes/macrophages and fibro-adipogenic progenitors (FAPs) as pivotal players in human muscle regeneration. By utilizing flow cytometry and cell sorting we confirmed increased cellular content and activity during regeneration. Spatial correlation analysis unveils FAPs and monocytes/macrophages co-localization and intercellular communication, mediated by complement factor C3. Immunostaining confirms C3 expression in FAPs and FAP secretion of C3, suggesting a role in phagocytosis. Functional assays demonstrate C3s impact on monocyte metabolism, survival and phagocytosis, unveiling its involvement in skeletal muscle regeneration. These insights elucidate FAP-macrophage interplay with perspectives for future therapeutic interventions.

physiology↗

bioRxiv2024

HSP60 chaperone deficiency disrupts the mitochondrial matrix proteome and dysregulates cholesterol synthesis

Mitochondrial proteostasis is critical for cellular function and survival. HSP60 is a molecular chaperone that interacts with more than 260 mitochondrial matrix proteins to assist in their folding and few genetic variants of HSP60 are compatible with life. The few reported human patients with HSP60 variants show phenotypes of neurodevelopmental delay associated with brain hypomyelination. It is currently unknown how deficiency of the HSP60 links to hypomyelination. Here, we studied the onset and progression of HSP60 deficiency in: (1) a HSP60 mutation-inducible cell system, (2) skin fibroblasts from patients with disease-associated HSP60 variants, and (3) zebrafish HSP60 knockout larvae. Collectively, we show how HSP60 deficiency leads to pervasive dysfunctions: (1) downregulated mitochondrial matrix proteome, (2) transcriptional activation of cytosolic stress responses, (3) and lipid accumulation with dysregulated cholesterol biosynthesis. In zebrafish larvae HSP60 deficiency induced early developmental abnormalities. Our comprehensive data identifies HSP60 as a master regulator of mitochondrial proteostasis and suggests a pivotal effect of HSP60 dysfunction on myelination through dysregulation of cholesterol biosynthesis. HighlightsO_LIHSP60 deficiency disrupts mitochondrial matrix proteins activating stress responses C_LIO_LIDisrupted matrix proteome impairs catabolism causing acetyl-CoA shortage C_LIO_LIHSP60 deficiency dysregulates cytosolic cholesterol synthesis C_LIO_LIHsp60 deficiency causes developmental abnormalities in zebrafish larvae C_LIO_LIDysregulated cholesterol synthesis links HSP60 deficiency to hypomyelination C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/578131v1_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@891066org.highwire.dtl.DTLVardef@93ae5borg.highwire.dtl.DTLVardef@19bded0org.highwire.dtl.DTLVardef@414428_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Seasonally increasing parasite load is associated with microbiome dysbiosis in wild bumblebees

The microbiome is increasingly recognized for its complex relationship with host fitness. Bumblebees are host to a characteristic gut microbiome community that is derived and reinforced through social contact between individuals. The bumblebee microbiome is species-poor, and primarily composed from a small number of core taxa that are associated with the greater tribe of corbiculate bees. Experimental findings support a role for the core bumblebee microbiome in resistance to severe infections by a common trypanosomal parasite, Crithidia bombi. However, most studies have been small in scale, often considering just one or two bumblebee species, or making use of commercially-reared bees. To better understand the microbiome diversity of wild populations, we have deeply sampled field populations of ten sympatric species found throughout central and down east Maine in a three-year microbiome field survey. We have used 16S amplicon sequencing to produce microbiome community profiles, and qPCR to screen samples for infections by Crithidia bombi. The breadth of our dataset has enabled us to test for seasonal and interspecific trends in the microbiome community. Controlling for these external sources of variation, we have identified microbial factors associated with infection and parasite load that support the role of the core microbiome in resistance to severe infection.

microbiology↗

bioRxiv2023

T-cell derived extracellular vesicles prime macrophages for improved STING based cancer immunotherapy

A key phenomenon in cancer is the establishment of a highly immunosuppressive tumor microenvironment (TME). Despite advances in immunotherapy, where the purpose is to induce tumor recognition and hence hereof tumor eradication, the majority of patients applicable for such treatment still fail to respond. It has been suggested that high immunological activity in the tumor is essential for achieving effective response to immunotherapy, which therefore have led to exploration of strategies that triggers inflammatory pathways. Here activation of the stimulator of interferon genes (STING) signaling pathway has been considered an attractive target, as it is a potent trigger of pro-inflammatory cytokines and type I and III interferons. However, immunotherapy combined with targeted STING agonists has not yielded sustained clinical remission in humans. This suggest a need for exploring novel adjuvants to improve the innate immunological efficacy. Here, we demonstrate that extracellular vesicles (EVs), derived from activated CD4+ T cells (T-EVs), sensitizes macrophages to elevate STING activation, mediated by IFN{gamma} carried on the T-EVs. Our work support that T-EVs can disrupt the immune suppressive environment in the tumor by reprogramming macrophages to a pro-inflammatory phenotype, and priming them for a robust immune response towards STING activation.

immunology↗

bioRxiv2021

Distinct developmental mechanisms influence sexual dimorphisms in the milkweed bug Oncopeltus fasciatus

Sexual dimorphism is common in animals. The most complete model of sex determination comes from Drosophila melanogaster, where the relative dosage of autosomes and X chromosomes leads indirectly to sex-specific transcripts of doublesex. Female Dsx interacts with a mediator complex protein encoded by intersex to activate female development. In males the transcription factor encoded by fruitless promotes male-specific behavior. The genetics of sex determination have been examined in a small number of other insects, yet several questions remain about the pleisomorphic state. Is doublesex required for female and male development? Is fruitless conserved in male behavior or morphology? Are other components such as intersex functionally conserved? To address these questions, we report expression and functional tests of doublesex, intersex and fruitless in the hemipteran Oncopeltus fasciatus, characterizing three sexual dimorphisms. doublesex prevents intersex phenotypes in all sexes and dimorphic traits in the milkweed bug. intersex and fruitless are expressed across the body, in females and males. fruitless and intersex also affect the genitalia of both sexes, but have effects limited to different dimorphic structures in different sexes. These results reveal roles for intersex and fruitless distinct from other insects, and demonstrate distinct development mechanisms in different sexually dimorphic structures.

developmental biology↗

bioRxiv2021

Cell layer-specific expression of the B-class MADS-box gene PhDEF drives petal tube or limb development in petunia flowers

Floral homeotic MADS-box transcription factors ensure the correct morphogenesis of floral organs, which are organized in different cell layers deriving from the meristematic L1, L2 and L3 layers. How cells from these distinct layers acquire their respective identity and coordinate their growth to ensure normal floral organ morphogenesis is unresolved. Here, we study petunia petals that form a limb and tube through congenital fusion, a complex morphology that coevolved with pollinators. We have identified petunia mutants expressing the B-class MADS-box gene PhDEF in the epidermis or in the mesophyll of the petal only, called wico and star respectively. Strikingly, wico flowers form a strongly reduced tube while their limbs are almost normal, while star flowers form a normal tube but very reduced and unpigmented limbs, showing that petunia petal morphogenesis is highly modular. Comparative transcriptome analysis of star, wico and wild-type petals revealed a strong down-regulation of the anthocyanin production pathway in star petals including its major regulator ANTHOCYANIN2 (AN2). We found that PhDEF directly binds to AN2 regulatory sequence in vitro by gel shift assay, and in vivo by chromatin immunoprecipitation, suggesting that PhDEF directly activates the petal pigmentation pathway by activating AN2. Altogether, we show that cell-layer specific homeotic activity in petunia petals differently impacts tube and limb development, revealing the relative importance of the different cell layers in the modular architecture of petunia petals.

plant biology↗

bioRxiv2020

Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetes patients

Aging and type 2 diabetes mellitus (T2DM) are associated with impaired skeletal muscle function and degeneration of the skeletal muscle microenvironment. However, the origin and mechanisms underlying the degeneration are not well described in human skeletal muscle. Here we show that skeletal muscles of T2DM patients exhibit pathological degenerative remodeling of the extracellular matrix that was associated with a selective increase of a subpopulation of fibro-adipogenic progenitors (FAPs) marked by expression of THY1 (CD90) - the FAPCD90+. We identified Platelet-derived growth factor (PDGF) signaling as key regulator of human FAP biology, as it promotes proliferation and collagen production at the expense of adipogenesis, an effect accompanied with a metabolic shift towards glycolytic lactate fermentation. FAPsCD90+ showed a PDGF-mimetic phenotype, with high proliferative activity and clonogenicity, increased production of extracellular matrix production and enhanced glycolysis. Importantly, the pathogenic phenotype of T2DM FAPCD90+ was reduced by treatment with the anti-diabetic drug Metformin. These data identify PDGF-driven conversion of a sub-population of FAPs as a key event in the pathogenic accumulation of extracellular matrix in T2DM muscles.

cell biology↗

bioRxiv2019

Transcriptomics at maize embryo/endosperm interfaces identify a novel transcriptionally distinct endosperm sub-domain adjacent to the embryo scutellum (EAS)

Seeds are complex biological systems comprising three genetically distinct tissues nested one inside another (embryo, endosperm and maternal tissues). However, the complexity of the kernel makes it difficult to understand inter compartment interactions without access to spatially accurate information. Here we took advantage of the large size of the maize kernel to characterize genome-wide expression profiles of tissues at embryo/endosperm interfaces. Our analysis identifies specific transcriptomic signatures in two interface tissues compared to whole seed compartments: The scutellar aleurone layer (SAL), and the newly named endosperm adjacent to scutellum (EAS). The EAS, which appears around 9 days after pollination and persists for around 11 days, is confined to one to three endosperm cell layers adjacent to the embryonic scutellum. Its transcriptome is enriched in genes encoding transporters. The absence of the embryo in an embryo specific (emb) mutant can alter the expression pattern of EAS marker genes. The detection of cell death in some EAS cells together with an accumulation of crushed cell walls suggests that the EAS is a dynamic zone from which cell layers in contact with the embryo are regularly eliminated, and to which additional endosperm cells are recruited as the embryo grows.

plant biology↗

bioRxiv2018

The molecular signatures of compatible and incompatible pollination

Fertilization in flowering plants depends on the early contact and recognition of pollen grains by the receptive papilla cells of the stigma. To identify the associated molecular pathways, we developed a transcriptomic analysis based on single nucleotide polymorphisms (SNPs) present in two Arabidopsis thaliana accessions, one used as female and the other as male. We succeeded in distinguishing 80 % of transcripts according to their parental origins and drew up a catalog of genes whose expression is modified after pollen-stigma interaction. Global analysis of our data reveals that pattern-triggered immunity (PTI)-associated transcripts are upregulated after compatible pollination. From our analysis, we predicted the activation of the Mitogen-activated Protein Kinase 3 on the female side after compatible pollination, which we confirmed through expression and mutant analysis. Our work defines the molecular signatures of compatible and incompatible pollination, highlights the active status of incompatible stigmas, and unravels a new MPK3-dependent cell wall feature associated with stigma-pollen interaction.

plant biology↗