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Biology subjects

Ash, J. D.

Publications and source records attributed to Ash, J. D..

3 recordsLinked to original sources

Functional traits fail to predict long-term responses to climate change

AimEnvironmental conditions strongly affect the distribution and abundance of species via complex forces. Shifts in environmental conditions and differences in the speed and scale of these effects complicate our efforts to infer how species will respond to future environmental change. We test how 18 functional traits affect plant species responses to gradients in environmental conditions and 50-year shifts in climate. LocationWe analyzed 50-year shifts in the distribution and abundance of 153 plant species distributed across 284 sites in Wisconsin, USA. Time period1950s to 2000s. Major taxa studiedVascular plants (much of the flora of NE North America). MethodsWe used random forest and integrated hierarchical mixed models to test how plant abundances (and 50-year changes in abundance) track gradients in overstory, soil, and climatic conditions. ResultsWithin study periods, plant abundances reflect gradients in environmental conditions. Leaf traits affected local abundance (both directly and via trait-environment interactions) in the 1950s and 2000s. Strong soil and temperature effects in the 1950s have weakened while precipitation effects have strengthened. Although we expected these models to also predict how plants would respond to shifts in climate, they did not. Main conclusionsLags in species responses, increases in the stochastic forces affecting community assembly, and other forces limit the ability of models fitted to static data (e.g., space-for-time substitutions) to predict how plant species will respond to long-term shifts in environmental conditions. We must therefore be cautious about applying trait-based species distribution models to predict how climate change will affect species distributions and community structure.

ecology↗

AMP-activated-kinase (AMPK) is essential sensor and metabolic regulator of retinal neurons and their integrated metabolism with RPE.

The retina has one of the highest energy demands in the human body, and proper regulation of metabolism among the cell types of the retina is required for functional vision. Recent studies have reported that retinal metabolism is disrupted during retinal degeneration and aging, while therapies designed to enhance metabolism can slow or prevent degeneration. Here, we show that multiple metabolic pathways, including those regulated by a key ATP sensor and regulator of metabolism, AMP-activated-kinase (AMPK), were dysregulated in a model of inherited retinal degeneration. In order to assess the direct role of AMPK in regulating retinal metabolism, we used mice with retina-specific knockout of AMPK activity. Conditional loss of AMPK resulted in impaired visual function at an early age, with slow photoreceptor loss observed in older mice. Moreover, we found that loss of AMPK resulted in decreased metabolic flux from glucose, decreased mitochondrial DNA copy number, decreased mitochondrial-related gene expression, and alterations in mitochondrial morphology in the photoreceptors, all of which preceded degeneration. Surprisingly, metabolic changes from the loss of AMPK in retinal neurons also resulted in secondary degeneration of retinal pigment epithelial (RPE) cells. Together, these data show that AMPK signaling is important for maintaining metabolic homeostasis of the retina and support the hypothesis that photoreceptors and RPE have a shared metabolic ecosystem that is controlled, in part, by AMPK.

neuroscience↗

A drug-tunable gene therapy for broad-spectrum protection against retinal degeneration

Retinal degenerations are a large cluster of diseases characterized by the irreversible loss of light-sensitive photoreceptors that impairs the vision of 9.1 million people in the US. An attractive treatment option is to use gene therapy to deliver broad-spectrum neuroprotective factors. However, this approach has had limited clinical translation because of the inability to control transgene expression. To address this problem, we generated an adeno-associated virus vector named RPF2 that was engineered to express domains of leukemia inhibitory factor fused to the destabilization domain of bacterial dihydrofolate reductase. Fusion proteins containing the destabilization domain are degraded in mammalian cells but can be stabilized with the binding of the drug trimethoprim. Our data show that expression levels of RPF2 are tightly regulated by the dose of trimethoprim, and can be reversed by trimethoprim withdrawal. We further show that stabilized RPF2 can protect photoreceptors and prevent blindness in treated mice.

bioengineering↗