Winters, T. | bioRxiv Science

bioRxiv2024

Spatiotemporal dynamic models of Amblyomma americanum questing activity in the Central Great Plains

Ticks represent important vectors of a number of bacterial and viral disease agents, owing to their hematophagous nature and their questing behavior (the process in which they seek new hosts). Questing activity is notably seasonal with spatiotemporal dynamics that needs to be understood in detail as part of mediating and mitigating tick-borne disease risk. Models of the geography of tick questing activity developed to date, however, have ignored the temporal dimensions of that behavior; more fundamentally, they have often not considered the sampling underlying available occurrence data. Here, we have addressed these shortfalls for Amblyomma americanum, the most commonly encountered tick in the central Great Plains, via (1) detailed, longitudinal sampling to characterize the spatiotemporal dimensions of tick questing activity; (2) randomization tests to establish in which environmental dimensions a species is manifesting selective use; and (3) modeling methods that include both presence data and absence data, taking fullest advantage of the information available in the data resource. The outcome was a detailed picture of geographic and temporal variation in suitability for the species through the two-year course of this study. Such models that take full advantage of available information will be crucial in understanding the risk of tick-borne disease into the future.

ecology↗

bioRxiv2021

NSun2 deficiency promotes tau hyperphosphorylation and neurodegeneration through epitranscriptomic regulation of miR-125b

Overproduction or suppression of certain microRNAs (miRNAs) in Alzheimers disease (AD) brains promote alterations in tau proteostasis and neurodegeneration. However, the mechanisms governing how specific miRNAs are dysregulated in AD brains are still under investigation. Epitranscriptomic regulation adds a layer of post-transcriptional control to brain function during development and adulthood. NOP2/Sun RNA methyltransferase 2 (NSun2) is one of the few known brain-enriched methyltransferases able to modify mammalian non-coding RNAs and loss of function autosomal-recessive mutations in NSUN2 have been associated with neurological abnormalities in humans. Here, we provide evidence that NSun2 is expressed in adult human neurons in the hippocampal formation and prefrontal cortex. When we evaluated NSun2 protein expression in post-mortem brain tissue from AD patients we find is dysregulated which was also found in mice and human cellular AD models. To probe these observed alterations were unique to AD we further evaluated brain tissue from other tauopathies, observing NSun2 protein levels were similar between cases and controls. In a well-established Drosophila melanogaster model of tau-induced toxicity we investigated the pathological role of NSun2 observing that reduction of NSun2 protein levels exacerbated tau toxicity, while overexpression of NSun2 partially abrogated the toxic effects. We further show using human induced pluripotent stem cell (iPSC) derived neuronal cultures that NSun2 deficiency results in tau hyperphosphorylation and we found in primary hippocampal neuronal cultures NSun2 levels decrease in response to amyloid-beta oligomers (A{beta}O). Furthermore, in mice, we observed that NSun2 deficiency promotes aberrant levels of m6A methylated miR-125b and tau hyperphosphorylation. Altogether, our study supports that neuronal NSun2 deficiency in AD promotes neurodegeneration by altering tau phosphorylation and tau toxicity through an epitranscriptomic regulatory mechanism and highlights a novel avenue for therapeutic targeting.

neuroscience↗