Biology subjects

French, K.

Publications and source records attributed to French, K..

4 recordsLinked to original sources

bioRxiv2024

Concerted neuron-astrocyte gene expression declines in aging and schizophrenia

Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a striking relationship between peoples cortical neurons and cortical astrocytes. We used single-nucleus RNA-seq to analyze the prefrontal cortex of 191 human donors ages 22-97 years, including healthy individuals and persons with schizophrenia. Latent-factor analysis of these data revealed that in persons whose cortical neurons more strongly expressed genes for synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the Synaptic Neuron- and-Astrocyte Program (SNAP). In schizophrenia and aging - two conditions that involve declines in cognitive flexibility and plasticity 1,2 - cells had divested from SNAP: astrocytes, glutamatergic (excitatory) neurons, and GABAergic (inhibitory) neurons all reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy persons of similar age, may underlie many aspects of normal human interindividual differences and be an important point of convergence for multiple kinds of pathophysiology.

neuroscience↗

bioRxiv2023

Drivers of thermal tolerance breadth of plants across contrasting biomes: do mean or seasonality in climate indices matter more?

O_LIThe climate variability hypothesis (CVH) predicts that species from environments with more variable temperatures should have wider thermal tolerance breadth. This hypothesis has not yet been tested thoroughly across diverse plants. Here, we asked how local climate predictors (including precipitation, mean and extreme temperatures and thermal variability) are associated with species physiological thermal limits. C_LIO_LIMeasures of lower (Tcrit-cold) and upper (Tcrit-hot) photosystem II thermal tolerance thresholds were used to determine thermal tolerance breadth (TTB), along with ice nucleation temperature (Tnucleation, freezing tolerance) of 69 plant species sampled from the field across three contrasting biomes: alpine, desert and coastal temperate rainforest. C_LIO_LIAll measured thermal tolerance metrics (Tcrit-cold, Tnucleation, Tcrit-hot and TTB) differed among biomes. Notably, desert species had the most cold and heat tolerant leaves, and therefore the widest TTB, whereas species in alpine and temperate biomes had similar TTB. For plants in all biomes, TTB exceeded the thermal range of their local climate. C_LIO_LIOverall, two Principal Component axes of local climate drivers explained substantial variation in all tolerance metrics. Extreme hot, dry climates improved freezing and heat tolerance. High thermal variability and low minimum temperatures also improved freezing tolerance but were unrelated to heat tolerance or TTB. Species explained a significant amount of variation among all metrics, but this was not due to phylogenetic relatedness. We discuss how the remaining variation could be due to microclimate-driven plasticity, leaf traits or thermoregulatory mechanisms. C_LIO_LISynthesis. Our results provide partial support for the climate variability hypothesis in plants: photosystem thermal tolerance breadth was greatest in more thermally variable biomes. This relationship was largely driven by cold tolerance, with variation in heat tolerance explained better by mean and extreme temperatures. Therefore, we conclude that the CVH alone is not sufficient to explain variation in plant thermal tolerance, with many other aspects of climate, environment and biology being potentially important drivers. C_LI

ecology↗

bioRxiv2018

Assessing the bioenergy potential of grassland biomass from conservation areas in England

Bioenergy may be one of the ecosystem services of the future for grasslands managed for conservation as the concept of bio-based economies is embraced worldwide. Although the idea of producing biogas and bioethanol from lignocellulosic material is not new, there are currently few regional-level comparisons of the bioenergy potential of high-diversity grasslands that would establish whether this could be a competitive bioenergy feedstock for farmers. Comparing the chemical composition and biogas yields of biomass samples from 13 grasslands in England and 73 other bioenergy feedstocks reveals that the lignin content of biomass from grasslands managed for conservation was up to 50% less than other bioenergy crops. Grasslands managed for conservation yielded up to 160% more biogas per ton dry matter than cereals or crop waste and only slightly less than Miscanthus. GIS modeling of the estimated biogas yields of grasslands managed for conservation and fields currently sown with Miscanthus show that grasslands are larger (20.57 ha) than Miscanthus fields (5.95 ha) and are projected to produce up to 117% more biogas per average field. Future incorporation of high-diversity grasslands into local and nation-wide energy plans may help reduce global fossil-fuel use in the 21st century.

ecology↗

bioRxiv2018

Live imaging of the Foreign Body Reaction (FBR) to suture implantation in zebrafish reveals how dampening inflammation can reduce fibrosis.

Implanting biomaterials such as surgical sutures leads to wound inflammation and a Foreign Body Response (FBR), which can result in scarring and ultimately biomaterial rejection. To investigate the cell and signalling events that underlie FBR, we use live imaging of zebrafish reporter lines to observe how inflammation and angiogenesis differ between a healthy acute wound versus suture implantation. We observe inflammation extending from the suture margins and correlates with subsequent avascular and fibrotic encapsulation zones: sutures that induce more inflammation result in increased zones of avascularity and fibrosis. Moreover, we capture macrophages as they fuse to become multinucleate foreign body giant cells (FBGCs) adjacent to the most pro-inflammatory sutures. Both genetic and pharmacological dampening of the inflammatory response minimises the FBR (including FBGC generation) and normalises the status of the tissue surrounding these sutures. This new model of FBR in adult zebrafish allows us, for the first time, to live image the process and to modulate it in ways that may lead us towards new strategies to ameliorate and circumvent FBR in humans.

cell biology↗