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1.
PLoS Genet ; 19(9): e1010938, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37721956

RESUMEN

mTORC1 (mechanistic target of rapamycin complex 1) is a metabolic sensor that promotes growth when nutrients are abundant. Ubiquitous inhibition of mTORC1 extends lifespan in multiple organisms but also disrupts several anabolic processes resulting in stunted growth, slowed development, reduced fertility, and disrupted metabolism. However, it is unclear if these pleiotropic effects of mTORC1 inhibition can be uncoupled from longevity. Here, we utilize the auxin-inducible degradation (AID) system to restrict mTORC1 inhibition to C. elegans neurons. We find that neuron-specific degradation of RAGA-1, an upstream activator of mTORC1, or LET-363, the ortholog of mammalian mTOR, is sufficient to extend lifespan in C. elegans. Unlike raga-1 loss of function genetic mutations or somatic AID of RAGA-1, neuronal AID of RAGA-1 robustly extends lifespan without impairing body size, developmental rate, brood size, or neuronal function. Moreover, while degradation of RAGA-1 in all somatic tissues alters the expression of thousands of genes, demonstrating the widespread effects of mTORC1 inhibition, degradation of RAGA-1 in neurons only results in around 200 differentially expressed genes with a specific enrichment in metabolism and stress response. Notably, our work demonstrates that targeting mTORC1 specifically in the nervous system in C. elegans uncouples longevity from growth and reproductive impairments, and that many canonical effects of low mTORC1 activity are not required to promote healthy aging. These data challenge previously held ideas about the mechanisms of mTORC1 lifespan extension and underscore the potential of promoting longevity by neuron-specific mTORC1 modulation.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Caenorhabditis elegans/metabolismo , Longevidad/genética , Complejos Multiproteicos/genética , Reproducción/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Mamíferos/metabolismo
2.
Ecol Appl ; 33(2): e2763, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36264047

RESUMEN

Mature forests provide important wildlife habitat and support critical ecosystem functions globally. Within the dry conifer forests of the western United States, past management and fire exclusion have contributed to forest conditions that are susceptible to increasingly severe wildfire and drought. We evaluated declines in conifer forest cover in the southern Sierra Nevada of California during a decade of record disturbance by using spatially comprehensive forest structure estimates, wildfire perimeter data, and the eDaRT forest disturbance tracking algorithm. Primarily due to the combination of wildfires, drought, and drought-associated beetle epidemics, 30% of the region's conifer forest extent transitioned to nonforest vegetation during 2011-2020. In total, 50% of mature forest habitat and 85% of high density mature forests either transitioned to lower density forest or nonforest vegetation types. California spotted owl protected activity centers (PAC) experienced greater canopy cover decline (49% of 2011 cover) than non-PAC areas (42% decline). Areas with high initial canopy cover and without tall trees were most vulnerable to canopy cover declines, likely explaining the disproportionate declines of mature forest habitat and within PACs. Drought and beetle attack caused greater cumulative declines than areas where drought and wildfire mortality overlapped, and both types of natural disturbance far outpaced declines attributable to mechanical activities. Drought mortality that disproportionately affects large conifers is particularly problematic to mature forest specialist species reliant on large trees. However, patches of degraded forests within wildfire perimeters were larger with greater core area than those outside burned areas, and remnant forest habitats were more fragmented within burned perimeters than those affected by drought and beetle mortality alone. The percentage of mature forest that survived and potentially benefited from lower severity wildfire increased over time as the total extent of mature forest declined. These areas provide some opportunity for improved resilience to future disturbances, but strategic management interventions are likely also necessary to mitigate worsening mega-disturbances. Remaining dry mature forest habitat in California may be susceptible to complete loss in the coming decades without a rapid transition from a conservation paradigm that attempts to maintain static conditions to one that manages for sustainable disturbance dynamics.


Asunto(s)
Incendios , Tracheophyta , Incendios Forestales , Ecosistema , Bosques , Árboles
3.
Cell Rep Methods ; 3(3): 100433, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-37056370

RESUMEN

Here, we introduce a single-copy knockin translating ribosome immunoprecipitation (SKI TRIP) toolkit, a collection of Caenorhabditis elegans strains engineered by CRISPR in which tissue-specific expression of FLAG-tagged ribosomal subunit protein RPL-22 is driven by cassettes present in single copy from defined sites in the genome. Through in-depth characterization of the effects of the FLAG tag in animals in which endogenous RPL-22 has been tagged, we show that it incorporates into actively translating ribosomes and efficiently and cleanly pulls down cell-type-specific transcripts. Importantly, the presence of the tag does not impact overall mRNA translation, create bias in transcript use, or cause changes to fitness of the animal. We propose SKI TRIP use for the study of tissue-specific differences in translation and for investigating processes that are acutely sensitive to changes in translation like development or aging.


Asunto(s)
Caenorhabditis elegans , Biosíntesis de Proteínas , Animales , Caenorhabditis elegans/genética , ARN Mensajero/genética , Biosíntesis de Proteínas/genética , Ribosomas/genética , Proteínas Ribosómicas/genética , Inmunoprecipitación
4.
Data Brief ; 51: 109807, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38075613

RESUMEN

Contemporary reference sites in California's Sierra Nevada represent areas where a frequent, low-intensity fire regime - an integral ecological process in temperate dry forests - has been reintroduced after several decades of fire suppression. Produced by an intact fire regime, forest structural patterns in these sites are likely more resilient to future disturbances and climate, and thus can provide reference conditions to guide management and ecological research. In this paper, we present a set of 119 delineated contemporary reference sites in the Sierra Nevada yellow pine and mixed-conifer zone along with a suite of key remote sensing-derived forest structure metrics representing conditions within these sites. We also provide a set of summary figures for individual reference sites and sites grouped by dominant climate class. We identified restored frequent-fire landscapes using a combination of fire history, burn severity, management history, and forest type datasets and we delineated individual polygons using catchment basins, fire perimeters, and imagery. Reference sites ranged in size from 101-966 ha with a mean size of 240 ha. Where available (for 59 sites), we used airborne lidar datasets to characterize a suite of key forest structure metrics within reference sites. Across all 119 sites, we provide a set of forest structure metrics produced by the California Forest Observatory. Reference sites were categorized based on their dominant climate class to assist users in identifying the most climatically relevant reference conditions for their project or study area. We encourage the use of the reference sites and associated forest structure datasets for guiding ecologically focused forest management and research in the Sierra Nevada.

5.
Science ; 370(6515): 417, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33093103
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