Biology subjects

Lee, T. M.

Publications and source records attributed to Lee, T. M..

5 recordsLinked to original sources

bioRxiv2025

Exploring the connections between digestion and detoxification in microevolution of insecticide resistance of the tea tortrix moth, Adoxophyes honmai

While the evolution of insecticide resistance is often assumed to come with a fitness cost, there are instances where insect populations that acquired resistance fail to show an evolutionary cost to maintaining the trait in the absence of insecticide. In comparing two populations of tea tortrix moth, Adoxophyes honmai, we found the absence of a cost of resistance but also noted differences in digestive enzyme gene expression. This raised the possibility that insecticide resistance coevolved with enhanced digestive capabilities, potentially offsetting putative costs of resistance. This study explored gene transcript patterns that may influence how traits manifest spatially and temporally, evaluating potential connections between digestion and the costs of resistance. We found that our resistant larvae had constitutively greater transcript levels of multiple putative digestive genes as well as a marker of resistance, CYP9A170. The putative digestive genes were expressed mostly in the digestive tract, whereas the tissue-specific pattern of CYP9A170 expression was strain-dependent. For most genes, the difference in expression between susceptible and resistant larvae remained consistent throughout development. Interestingly, the expression of an ABC transporter was upregulated in response to tebufenozide exposure, but only in the resistant larvae. A comparison of A. honmai transcriptomes suggests that the majority of differentially expressed genes between populations may not be directly contributing to resistance, but rather microevolutionary variations specific to individual populations. Future studies on fitness costs of resistance should consider other physiological systems and their interactions with direct mechanisms of resistance.

physiology↗

bioRxiv2025

Recessive but damaging alleles of muscle-specific ribosomal protein gene RPL3L drive neonatal dilated cardiomyopathy

The heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role1-3. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by severe dilated cardiomyopathy when both copies of the gene RPL3L are mutated4-9. RPL3L is a muscle-specific paralog1-3 of the ubiquitous ribosomal protein L3 (RPL3), which makes the closest contact of any protein to the ribosomes RNA-based catalytic center10. RPL3L-linked heart failure represents the only known human disease associated with tissue-specific ribosomes, yet the underlying pathogenetic mechanisms remain poorly understood. Intriguingly, disease is linked to a large number of mostly missense variants in RPL3L, and RPL3L-knockout resulted in no severe heart defect in either human or mice3, 11-13, challenging the prevailing view that autosomal recessive diseases are caused by loss-of-function mutations. Here, we report three new cases of RPL3L-linked severe neonatal heart failure and present a unifying pathogenetic mechanism by which a large number of variants in the muscle-specific ribosome led to disease. Specifically, affected families often carry one of two recurrent toxic gain-of-function variants alongside a family-specific putative loss-of-function variant. While the non-recurrent variants often trigger partial compensation of RPL3 similar to Rpl3l-knockout mice, both recurrent variants exhibit increased affinity for the RPL3/RPL3L chaperone GRWD114-16 and 60S biogenesis factors, sequester 28S rRNA in the nucleus, disrupt ribosome biogenesis, and trigger severe cellular toxicity that extends beyond the loss of ribosomes. These findings provide critical insights for genetic screening and therapeutic development of neonatal heart failure. Our results suggest that gain-of-toxicity mechanisms may be more prevalent in autosomal recessive diseases, and a combination of gain-of-toxicity and loss-of-function mechanisms could underlie many diseases involving genes with paralogs.

molecular biology↗

bioRxiv2024

Cost-benefit analysis across smallholder rice farmers reveals that existing fertilization practices severely compromise their income

Modernizing agricultural practices of smallholder farmers can increase considerably global food produce. Smallholder farmers are, nevertheless, often unwilling to adopt practices unfamiliar to them. Increases in the cost of fertilizers, can nonetheless render existing practices unsustainable, raising concerns of food injustice. We addressed here the potential to which we can increase yield through popularizing existing best practice agricultural approaches. We worked over a network of 40 smallholder farmers in the Danxia Mountain region, Guangdong province, China. We divided them into two crop-rotation treatments and gave them the freedom to implement agricultural management practices the way they usually do. We subsequently clustered them into three groups based on the management history. Over the final growth season, on which the clustering was based, there was an over 30% increase in crop yield between the most and the least efficient clusters. More importantly we show that the use of fertilizers not only did not promote rice production but it also had adverse effects. We finally present a cost-benefit analysis. Through familiarizing of the smallholder farmers existing management practices, policy makers could make integrating new farming guidelines easier to adopt than purely dishing out modern farming practice recommendations. We thus propose that any attempts to transition agricultural practices should involve the extensive monitoring of existing practices at the very beginning. This should effectively close existing yield gaps in relation to industrial farmers.

ecology↗

bioRxiv2023

Mutational analysis of the nitrogenase carbon monoxide protective protein CowN reveals that a conserved C-terminal glutamic acid residue is necessary for its activity

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near CowNs C-terminus is necessary for its function. Mutation of the glutamic acid residue abolishes both CowNs protection against CO inhibition and CowNs ability to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection. Overall, this work uncovers structural features in CowN that are required for its function and provides new insights into its nitrogenase binding and CO protection mechanism.

biochemistry↗

bioRxiv2023

Item-specific memory reactivation supports overnight memory consolidation

Memory consolidation stabilizes newly acquired information. Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Via unobtrusively re-playing auditory memory cues to sleeping human participants, we identified the reactivation of individual memories during slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found functionally segregated item-specific representations: the early post-cue EEG activity (0-2 seconds) contained comparable representations for memory cues and for non-memory control cues, thus reflecting sensory processing. Critically, the later EEG activity (2.5-3 s) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, demonstrating the reactivation and consolidation of individual memories. Moreover, spindles preferentially supported item-specific memory reactivation for items that were not tested before sleep. These findings delineated how cue-triggered item-specific memory reactivation, subserved by spindles during SWS, contributed to memory consolidation. These results will benefit future research aiming to perturb specific memory episodes during sleep.

neuroscience↗