Biology subjects

Whitworth, A.

Publications and source records attributed to Whitworth, A..

5 recordsLinked to original sources

bioRxiv2025

Experimental assessment of large mammal population estimates from airborne thermal videography

Wildlife resource management requires reliable, fast, and affordable methods of surveying wildlife populations to develop and adaptively adjust policies. Many methods are used to survey populations of large mammals, and thermal video from drones can yield high rates of detection over large extents with relative speed and safety. In wild populations it can be difficult to estimate detection rates and the accuracy of resulting abundance estimates, especially because many factors of study design and natural systems can influence counts from thermal surveillance. We surveyed a captive white-tailed deer (Odocoileus virginianus) population of known size at the 174-ha Auburn Deer Facility in Auburn, AL, USA, and used a designed experiment to investigate the effects of observers, time-of-day, and day-to-day variation on the accuracy of abundance estimates from trial flights using drone-based airborne thermal videography. The experiment consisted of 20 full-census trials, occurring over 4 days, at times-of-day before sunset, after sunset, near midnight, before sunrise, and after sunrise, with each trial video counted by three trained observers. Counts across all trials and observers yielded a mean point estimate of 77 (95% CI 71-83) deer representing 81-97% of the known population range. Flights near sunset yielded estimates of the highest accuracy, within or close to the true range of the population. Variability in estimates was primarily influenced by daily climatic conditions and time-of-day, with only minor observer effects. Results highlight the importance of day-to-day variability in environmental conditions and diel processes, such as nocturnal cooling of the environment and crepuscular peaks in deer activity. The estimates from our experiment and resulting model illustrate that censuses conducted at optimal times-of-day and averaged across multiple days were able to achieve accurate estimates within the known range without correction, and that by averaging across flights, even including suboptimal conditions, thermal videography returned estimates within 4% of the known range with substantial overlap of the estimate. Conversely, single estimates chosen at random from any time-of-day varied widely around the known value, highlighting the need to plan flights with respect to diurnal activity patterns and landscape thermal properties, or, in the absence of information, average multiple surveys across times and days.

ecology↗

bioRxiv2022

Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster

Respiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. Drosophila melanogaster is a candidate model organism for complex I due to its high evolutionary conservation with the mammalian enzyme, well-developed genetic toolkit, and complex physiology for studies in specific cell types and tissues. Here, we isolate complex I from Drosophila and determine its structure, revealing a 43-subunit assembly with high structural homology to its 45-subunit mammalian counterpart, including a hitherto unknown homologue to subunit NDUFA3. The major conformational state of the Drosophila enzyme is the mammalian-type ready-to-go active resting state, with a fully ordered and enclosed ubiquinone-binding site, but a subtly altered global conformation related to changes in subunit ND6. The mammalian-type deactive pronounced resting state is not observed: in two minor states the ubiquinone-binding site is unchanged, but a deactive-type{pi} -bulge is present in ND6-TMH3. Our detailed structural knowledge of Drosophila complex I provides a foundation for new approaches to disentangle mechanisms of complex I catalysis and regulation in bioenergetics and physiology.

biochemistry↗

bioRxiv2020

Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson's disease at Chr16q11.2 and on the MAPT H1 allele.

Parkinsons disease (PD) is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies (GWAS) has considerably advanced our understanding of the PD genetic risk. Understanding the functional significance of the risk loci is now a critical step towards translating these genetic advances into an enhanced biological understanding of the disease. Impaired mitophagy is a key causative pathway in familial PD, but its relevance to idiopathic PD is unclear. We used a mitophagy screening assay to evaluate the functional significance of risk genes identified through GWAS. We identified two new regulators of PINK1-mitophagy, KAT8 and KANSL1, previously shown to modulate lysine acetylation. We show that KAT8 and KANSL1 modulate PINK1 gene expression and subsequent PINK1-mitophagy. These findings suggest PINK1-mitophagy is a contributing factor to idiopathic PD. KANSL1 is located on chromosome 17q21 where the risk associated gene has long been considered to be MAPT. While our data does not exclude a possible association between the MAPT gene and PD, it provides strong evidence that KANSL1 plays a crucial role in the disease. Finally, these results enrich our understanding of physiological events regulating mitophagy and establish a novel pathway for drug targeting in neurodegeneration.

neuroscience↗

bioRxiv2019

The STING pathway does not contribute to Pink1/parkin phenotypes in Drosophila

Mutations in PINK1 and Parkin/PRKN cause the degeneration of dopaminergic neurons in familial forms of Parkinsons disease but the precise pathogenic mechanisms are unknown. The PINK1/Parkin pathway has been described to play a central role in mitochondrial homeostasis by signaling the targeted destruction of damaged mitochondria, however, how disrupting this process leads to neuronal death until recently was unclear. An elegant study in mice revealed that the loss of Pink1 or Prkn coupled with an additional mitochondrial stress resulted in the aberrant activation of the innate immune signaling, mediated via the cGAS/STING pathway, causing degeneration of dopaminergic neurons and motor impairment. Genetic knockout of Sting was sufficient to completely prevent neurodegeneration and accompanying motor deficits. To determine whether Sting plays a conserved role in Pink1/parkin related pathology, we tested for genetic interactions between Sting and Pink1/parkin in Drosophila. Surprisingly, we found that loss of Sting, or its downstream effector Relish, was insufficient to suppress the behavioral deficits or mitochondria disruption in the Pink1/parkin mutants. Thus, we conclude that phenotypes associated with loss of Pink1/parkin are not universally due to aberrant activation of the STING pathway.

genetics↗

bioRxiv2018

A comprehensive genetic characterisation of the mitochondrial Ca2+ uniporter in Drosophila

Mitochondrial Ca2+ uptake is an important mediator of metabolism and cell death. Identification of components of the highly conserved mitochondrial Ca2+ uniporter has opened it up to genetic analysis in model organisms. Here we report a comprehensive genetic characterisation of the known uniporter components conserved in Drosophila. While loss of MCU or EMRE abolishes fast mitochondrial Ca2+ uptake, this results in surprisingly mild phenotypes. In contrast, loss of the regulatory gatekeeper component MICU1 has a much more severe phenotype, being developmental lethal, consistent with unregulated Ca2+ uptake. Mutants for MICU3 are viable with mild neurological phenotypes. Genetic interaction studies reveal that MICU1 and MICU3 are not functionally interchangeable. More surprisingly, loss of MCU or EMRE does not suppress MICU1 mutant lethality, suggesting that the lethality results from MCU-independent functions. This study helps shed light on the physiological requirements of the mitochondrial Ca2+ uniporter, and provides a suite of tools to interrogate their interplay in homeostasis and disease conditions.

cell biology↗