Summary The sustained proliferation of microglia is a key hallmark of Alzheimer’s disease (AD), accelerating its progression. Here, we aim to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesizing that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We show that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterized by increased βgal activity, a senescence-associated transcriptional signature, and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. The prevention of early microglial proliferation hinders the development of senescence and DAM, impairing the accumulation of Aβ, as well as associated neuritic and synaptic damage. Overall, our results indicate that excessive microglial proliferation leads to the generation of senescent DAM, which contributes to early Aβ pathology in AD.

Fungal symbioses with plants are ubiquitous, ancient, and vital to both ecosystem function and plant health. However, benefits to fungal symbionts are not well explored, especially in non‐mycorrhizal fungi. The Foraging Ascomycete hypothesis proposes that some wood‐decomposing fungi may shift life‐history strategies to endophytism to bridge gaps in time and space between suitable substrates. To test this hypothesis we examine spatial relationships of Xylaria endophytic fungi in the forest canopy with Xylaria decomposer fungi on the forest floor. We sampled for fungi of the genus Xylaria using a spatially explicit sampling scheme in a remote Ecuadorian cloud forest, and concurrently carried out an extensive culture‐based sampling of fungal foliar endophytes. We found 36 species of Xylaria in our 0.5 ha plot, 31 of which were found to only occur as fruiting bodies. All five species of Xylaria found as endophytes were also found as fruiting bodies. We also tested the relationships of both stages of these fungi to environmental variables. Decomposer fungi were differentiated by species‐specific habitat preferences, with three species being found closer to water than expected by chance. In contrast, endophytes displayed no sensitivity to environmental conditions, such as host, moisture, or canopy cover. We found evidence of spatial linkage between life stages in two species. We also demonstrate that direct transmission of endophytes from leaves to woody substrates is possible. These results indicate that endophytism may represent one way for decomposer fungi to escape moisture limitation, and that endophytic fungi may act as sources of dispersal for decomposer fungi consistent with predictions of the Foraging Ascomycete hypothesis.

The sustained proliferation of microglia is a key hallmark of Alzheimer's disease (AD), accelerating its progression. Here, we sought to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesising that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We found that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterised by increased bgal activity, a senescence-associated transcriptional signature and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. Prevention of early microglial proliferation hindered the development of senescence and DAM, impairing the accumulation of Ab and associated neuritic damage. Overall, our results support that excessive microglial proliferation leads to the generation of senescent DAM, which contribute to early Ab pathology in AD.

Much of the visual diversity of angiosperms is due to the frequent evolution of novel pigmentation patterns in flowers. The gene network responsible for anthocyanin pigmentation, in particular, has become a model for investigating how genetic changes give rise to phenotypic innovation. In the monkeyflower genus Mimulus, an evolutionarily recent gain of petal lobe anthocyanin pigmentation in M. luteus var. variegatus was previously mapped to genomic region pla2. Here, we use sequence and expression analysis, followed by transgenic manipulation of gene expression, to identify MYB5a - orthologous to the NEGAN transcriptional activator from M. lewisii - as the gene responsible for the transition to anthocyanin-pigmented petals in M. l. variegatus. In other monkeyflower taxa, MYB5a/NEGAN is part of a reaction-diffusion network that produces semi-repeating spotting patterns, such as the array of spots in the nectar guides of both M. lewisii and M. guttatus. Its co-option for the evolution of an apparently non-patterned trait - the solid petal lobe pigmentation of M. l. variegatus - illustrates how reaction-diffusion can contribute to evolutionary novelty in non-obvious ways. Transcriptome sequencing of a MYB5a RNAi line of M. l. variegatus reveals that this genetically simple change, which we hypothesize to be a regulatory mutation in cis to MYB5a, has cascading effects on gene expression, not only on the enzyme-encoding genes traditionally thought of as the targets of MYB5a but also on all of its known partners in the anthocyanin regulatory network.

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Plant-fungal interactions are of paramount importance. Building useful ecological models of plant-fungal interactions is challenging, due to the complexity of habitat, varying definitions of biological basic units of interest, various spatial scales of dispersal, and non-linear, emergent properties of plant-fungal systems. Here we show that the bottom-up approach of agent-based models is useful for exploring the ecology of fungi. We constructed an agent-based model of the Foraging Ascomycete hypothesis, which proposes that some fungi maintain an endophytic life stage to enhance dispersal and bridge gaps in substrate in space and time. We characterized the general conditions in which dispersal through leaves may be worth the metabolic and fitness costs of endophytism. We also modeled possible effects of deforestation on leaf endophytes, highlighting how agent-based models can be useful for asking questions about changing ecosystems.

Most trees host hundreds of species of fungi asymptomatically in their internal tissues, known collectively as fungal endophytes. The Foraging Ascomycete (FA) hypothesis proposes that some fungal endophytes inhabit the internal leaf tissue of forest trees in order to enhance dispersal to substrates on the forest floor, by using leaves as vectors and as refugia during periods of environmental stress. This dispersal strategy has been termed viaphytism. Following the FA hypothesis, many fungi may therefore be in continuous and cyclical flux between life stages as endophytes in the forest canopy and as wood-decomposing fungi on the forest floor. This cycle may represent a very common and previously-ignored process in the ecology of forests, with implications for forest health. The ecological consequences of the FA hypothesis are complex, so we constructed an agent-based model of the FA hypothesis. Our model is intended to serve as both an explicit conceptual explanation of the FA hypothesis, and as an exploration of the conditions in which a strategy of endophytism accompanied by leaf dispersal may be advantageous for fungi. In a scenario of a viaphytic fungal species on a model forest landscape, without fungal competitors, viaphytism is predicted to be a plausible alternative to dispersal to substrates by spores alone, allowing the fungus to persist reliably on the landscape. In a scenario that allows competition from aggressively dispersed non-viaphytic fungi, the model predicts some competitive benefits to fungal dispersal via leaves. However, these benefits are conditional, requiring sufficient retention through time of endophyte infections by host trees, and sufficient host trees on the landscape. In the model, loss of these fungal populations can result from increased local disturbances of forest canopy, and deforestation.

In 2008, Ecuador recognized the Constitutional Rights of Nature in a global first. This recognition implies a major shift in the human-nature relationship, from one between a subject with agency (humans) and an exploitable object (Nature), to a more equilibrated relationship of respect. However, the lack of a standard legal framework has left room for subjective interpretations and variable implementation. The recent widespread concessioning of pristine ecosystems to mining industries in Ecuador has set up an unprecedented conflict and test of these rights. Currently, a landmark case involving Los Cedros Protected Forest and mining companies has reached the Constitutional Court of Ecuador. If Ecuador’s highest Court rules in favor of Los Cedros and the Rights of Nature, it would set a legal precedent with enormous impact on biological conservation in Ecuador and, potentially, the world. Such a policy shift offers a novel conservation strategy, through citizen oversight and action.