Biology subjects

Frazier, A. E.

Publications and source records attributed to Frazier, A. E..

5 recordsLinked to original sources

bioRxiv2025

Challenges and opportunities in detecting leaf water and carotenoid content across biomes from satellite multispectral indices

Climate change is causing vegetation stress across the globe, increasing the need for reliable indicators to monitor plant health. Leaf water and carotenoid content, and the chlorophyll/carotenoid ratio, are established proxies for environmental stress that can be detected by remote sensing. Here, we evaluated the sensitivity of 11 multispectral vegetation indices (VIs) designed to monitor these three stress-related leaf traits across a broad range of environmental and vegetation conditions. For this, we combined radiative transfer modeling with cross-biome field and satellite observations from Sentinel-2, Landsat 8, and MODIS from the National Ecological Observatory Network (NEON), spanning in most major terrestrial ecosystems. Our model-based analysis showed that VIs have a low to moderate sensitivity to their target traits, ranging from water indices with 66% of their variability explained by leaf water content, to carotenoid indices with 27% variability explained by leaf carotenoid content. Surprisingly, our field-based analyses revealed minimal to no sensitivity to leaf water and carotenoid content and chlorophyll/carotenoid ratio across all VIs. In contrast, we showed that leaf area index was the dominant driver of all studied VIs, accounting for 54-74 % of their variability in the field-based analysis. Lastly, we detected that VI[s] sensitivity to atmospheric conditions and field sampling issues contribute to their low performance in validating ground truth observations. These findings show that improvements in the VIs formulation and field sampling strategies are needed to increase the reliability of vegetation stress monitoring from multispectral satellites and support a generalized use of VIs across ecosystems. Highlights: 3-5 bullet points, 85 characters[bullet] Sensitivity of water and carotenoid multispectral indices was evaluated [bullet]Analysis based on cross-biome field data and radiative transfer models [bullet]Field data showed indices had minimal sensitivity to leaf water and carotenoid [bullet]Leaf area index explained most cross-biome variation in water and carotenoid indices [bullet]We propose strategies to improve stress-related index formulation and validation

ecology↗

bioRxiv2023

Atf3 controls transitioning in female mitochondrial cardiomyopathy as identified by single-cell transcriptomics

Oxidative phosphorylation defects results in mitochondrial diseases, with cardiac involvement markedly impacting prognosis. However, the mechanisms underlying the transition from compensation to dysfunction in response to metabolic deficiency remain unclear, impeding the development of effective treatments. Here, we employed single-nucleus RNA sequencing (snRNA-seq) on hearts from mitochondrial cardiomyopathy (MCM) mice with cardiac-specific Ndufs6 knockdown (FS6KD). Pseudotime trajectory analysis of cardiomyocytes from early stage of female FS6KD hearts revealed dynamic cellular state transitioning from compensation to severe compromise, coincided with transient upregulation of a critical transcription factor, activating transcription factor 3 (Atf3). Genetic ablation or adeno-associated virus-mediated Atf3 knockdown in FS6KD mice effectively delayed cardiomyopathy progression in a female-specific manner. Notably, human MCM snRNA-seq revealed a similar transition, including the dynamic expression of ATF3. In conclusion, our findings highlight a fate-determining role of Atf3 in female MCM progression, providing a promising therapeutic candidate for the currently intractable disease.

cell biology↗

bioRxiv2021

Multi-omics reveal intricate network of mitochondrial adaptations to training in human skeletal muscle

Mitochondrial defects are implicated in multiple diseases and aging. Exercise training is an accessible and inexpensive therapeutic intervention improving mitochondrial bioenergetics and quality of life. By combining a multi-omics approach with biochemical and in silico normalization, we removed the bias arising from the training-induced increase in human skeletal muscle mitochondrial content to unearth an intricate and previously undemonstrated network of differentially prioritized mitochondrial adaptations. We show that changes in hundreds of transcripts, proteins, and lipids are not stoichiometrically linked to the increase in mitochondrial content. We demonstrate that enhancing electron flow to oxidative phosphorylation (OXPHOS) is more important to improve ATP generation than increasing the abundance of the OXPHOS machinery, and that training-induced supercomplex formation does not confer enhancements in mitochondrial bioenergetics. Our study provides a new analytical approach allowing unbiased and in-depth investigations of training-induced mitochondrial adaptations, challenging our current understanding and calling for careful reinterpretation of previous findings.

cell biology↗

bioRxiv2020

Rothmund-Thomson Syndrome-like RECQL4 truncating mutations cause a haploinsufficient low bone mass phenotype in mice

Rothmund-Thomson Syndrome (RTS) is an autosomal recessive disorder characterized by poikiloderma, sparse or absent hair, and defects in the skeletal system such as bone hypoplasia, short stature, low bone mass, and an increased incidence of osteosarcoma. RTS type 2 patients typically present with germline compound bi-allelic protein-truncating mutations of RECQL4. As existing murine models predominantly employ Recql4 null alleles, we have here attempted to more accurately model the mutational spectrum of RTS by generating mice with patient-mimicking truncating Recql4 mutations. We found that truncating mutations impaired stability and subcellular localization of RECQL4, which translated to a homozygous embryonic lethality and haploinsufficient low bone mass and reduced cortical bone thickness phenotypes. Combination of a truncating mutation with a conditional Recql4 null allele demonstrated that these defects were intrinsic to the osteoblast lineage. However, the truncating mutations did not promote tumorigenesis, even after exposure to irradiation. We also utilized murine Recql4 null cells to assess the impact of a wider range of human RECQL4 mutations using an in vitro complementation assay. We found differential effects of distinct RECQL4 mutations. While some created unstable protein products, others altered subcellular localization of the protein. Interestingly, the severity of the phenotypes correlated with the extent of protein truncation. Collectively, our results reveal that truncating RECQL4 mutations lead to the development of an osteoporosis-like phenotype through defects in early osteoblast progenitors in mice and identify RECQL4 gene dosage as a novel regulator of bone mass.

cancer biology↗

bioRxiv2019

Neuronal-specific function of hTim8a in Complex IV assembly provides insight into the molecular mechanism underlying Mohr-Tranebjaerg syndrome

Human Tim8a is a member of an intermembrane space chaperone network, known as the small TIM family, which transport hydrophobic membrane proteins through this compartment. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjaerg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells and consequently how lack of hTim8a leads to a neurodegenerative disease. We identified a novel cell-specific function of hTim8a in the assembly of Complex IV, which is mediated through a transient interaction with the copper chaperone COX17. Complex IV assembly defects in cells lacking hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c and Bax, which primes cells for cell death. Alleviation of oxidative stress using Vitamin E rescues cells from apoptotic vulnerability. We hypothesis that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.

cell biology↗