Biology subjects

Au, C.

Publications and source records attributed to Au, C..

6 recordsLinked to original sources

bioRxiv2026

The spruce bark beetle Ips typographus transmits mutualistic fungi in mandibular mycetangia

Insects associated with mutualistic microbes often possess structures specialized for microbial transport that ensure the maintenance of these symbioses. Called mycetangia, these structures have evolved in numerous bark beetle species facilitating fungal transport to new host trees. The Eurasian spruce bark beetle Ips typographus is associated with several filamentous ascomycetes that may provide beetles with nutrition or help overcome tree defenses. I. typographus has been believed to vector its fungal symbionts mostly on the exoskeleton, but exact mechanisms of fungal transmission are unknown. Here, we report the discovery of a mandibular mycetangium in I. typographus that enables the transmission of symbiotic fungi. Extensive fungal isolation from I. typographus heads suggested the presence of a mycetangium while micro-computed tomography and histological analyses revealed a mycetangium close to the mandibles. Strikingly, we identified these fungus-carrying structures in both sexes of I. typographus and in the congeneric species I. acuminatus, and I. duplicatus, although mandibular mycetangia have been thought to be rare in Ips bark beetles. Moreover, mycetangia in male beetles in general were hardly reported in bark beetles before. The occurrence of mycetangia in Ips species highlights the important role mutualistic fungi play in the natural history of these bark beetles.

ecology↗

bioRxiv2024

Machine learning predicts lifespan and underlying causes of death in aging C. elegans

Senescence (aging) leads to senescent pathology that causes death, and genes control aging by determining such pathology. Here we investigate how senescent pathology mediates the effect of genotype on lifespan in C. elegans by means of a data-driven approach, using machine learning (ML). To achieve this we gathered extensive data on how diverse determinants of lifespan (sex, nutrition, genotype) affect patterns of age-related pathology. Our findings show that different life-extending treatments result in distinct patterns of suppression of senescent pathology. By analysing the differential effects on pathology and lifespan, our ML models were able to predict >70% of lifespan variation. Extent of pathology in the pharynx and intestine were the most important predictors of lifespan, arguing that elderly C. elegans die in part due to late-life disease in these organs. Notably, the mid-life pathogenetic burst characteristic of hermaphrodite senescence is absent from males.

genetics↗

bioRxiv2021

Epigenetic Programming during thymic development sets the stage for optimal function in effector T cells via DNA demethylation

The repressive effect of DNA methylation at promoters is well-known. However, its role within conserved sequences in intragenic and intergenic regions is less clear. Using Cd4 as a model gene, here we show that DNA methylation regulates the function of stimulus-responsive regulatory elements in effector T cells. Two cis-elements orchestrate intra-and intergenic DNA demethylation of the Cd4 gene during thymic development, which in turn licenses a stimulus-responsive element, E4a, for its later function in effector cells. Deficiency in DNA demethylation leads to impaired E4a function, reduced H3K4me3 promoter levels and an inability to repel de novo DNA methylation during replication, ultimately leading to gene silencing. This physiological reduction in CD4 expression leads to a defect in Th1 polarization during cutaneous Leishmaniasis. Similar patterns of regulation were observed in a broad number of genes, highlighting an essential role for DNA demethylation during thymic development in modulating the function of stimulus-responsive elements.

immunology↗

bioRxiv2019

Selective metabolic redundancy of Gpi1 allows for specific inhibition of inflammatory Th17 cells

SummaryTargeting glycolysis has been considered therapeutically intractable owing to its essential housekeeping role. However, the context-dependent requirement for individual glycolytic steps has not been fully explored. We show that CRISPR-mediated targeting of glycolysis in T cells in mice results in global loss of Th17 cells, whereas deficiency of the glycolytic enzyme glucose phosphate isomerase (Gpi1) selectively eliminates inflammatory encephalitogenic and colitogenic Th17 cells, without substantially affecting homeostatic microbiota-specific Th17 cells. In homeostatic Th17 cells, partial blockade of glycolysis upon Gpi1 inactivation was compensated by pentose phosphate pathway flux and increased mitochondrial respiration. In contrast, inflammatory Th17 cells experience a hypoxic microenvironment known to limit mitochondrial respiration, which is incompatible with loss of Gpi1. Our study suggests that inhibiting glycolysis by targeting Gpi1 could be an effective therapeutic strategy with minimum toxicity for Th17-mediated autoimmune diseases, and, more generally, that metabolic redundancies can be exploited for selective targeting of disease processes.

immunology↗

bioRxiv2017

Autophagy-dependent gut-to-yolk biomass conversion generates visceral polymorbidity in aging C. elegans

Aging (senescence) is characterized by the development of numerous pathologies, some of which limit lifespan. Key to understanding aging is discovery of the mechanisms (etiologies) that cause senescent pathology. In Caenorhabditis elegans a major senescent pathology of unknown etiology is atrophy of its principal metabolic organ, the intestine. Here we identify a cause of not only this pathology, but also of yolky lipid accumulation and redistribution (a form of senescent obesity): autophagy-mediated conversion of intestinal biomass into yolk. Inhibiting intestinal autophagy or vitellogenesis rescues both visceral pathologies, and can also extend lifespan. This defines a disease syndrome leading to polymorbidity and contributing to late-life mortality. Activation of gut-to-yolk biomass conversion by insulin/IGF-1 signaling (IIS) promotes reproduction and senescence. This illustrates how major, IIS-promoted senescent pathologies in C. elegans can originate not from damage accumulation, but from continued action of a wild-type function (vitellogenesis), consistent with the recently proposed hyperfunction theory of aging.

physiology↗

bioRxiv2017

c-Maf-dependent regulatory T cells mediate immunological tolerance to intestinal microbiota

Both microbial and host genetic factors contribute to the pathogenesis of autoimmune disease1-4. Accumulating evidence suggests that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease (IBD), often also colonize healthy individuals. These microbes, including the Helicobacter species, have the propensity to induce autoreactive T cells and are collectively referred to as pathobionts4-8. However, an understanding of how such T cells are constrained in healthy individuals is lacking. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus (H. hepaticus), is mediated by induction of ROR{gamma}t+Foxp3+ regulatory T cells (iTreg) that selectively restrain pro-inflammatory TH17 cells and whose function is dependent on the transcription factor c-Maf. Whereas H. hepaticus colonization of wild-type mice promoted differentiation of ROR{gamma}t-expressing microbe-specific iTreg in the large intestine, in disease-susceptible IL-10-deficient animals there was instead expansion of colitogenic TH17 cells. Inactivation of c-Maf in the Treg compartment likewise impaired differentiation of bacteria-specific iTreg, resulting in accumulation of H. hepaticus-specific inflammatory TH17 cells and spontaneous colitis. In contrast, ROR{gamma}t inactivation in Treg only had a minor effect on bacterial-specific Treg-TH17 balance, and did not result in inflammation. Our results suggest that pathobiont-dependent IBD is a consequence of microbiota-reactive T cells that have escaped this c-Maf-dependent mechanism of iTreg-TH17 homeostasis.

immunology↗