Biology subjects

Noonan, M.

Publications and source records attributed to Noonan, M..

6 recordsLinked to original sources

bioRxiv2026

Preserved self-other integration during social decision making among individuals with elevated autistic traits

Autistic people can find social interactions difficult to navigate, traditionally attributed to difficulties in taking others perspectives. However, we have a limited understanding of how autistic people integrate self and other information efficiently during social decision-making. We conducted four highly powered experiments (total N = 1,621) to determine whether autistic traits affect two aspects of self-other integration during social decision making: self-bias and social basis function use. Using Bayesian analyses, we found strong support for the absence of a relationship between autistic traits and either aspect of social decision making, even after controlling for potential confounds (BF01 = 32.13 for self-bias, BF01 = 7.04 for social basis function use). Our results indicate that variations along autistic traits do not impact how people prioritise self-relevant information (self-bias) or utilize compressed social patterns of interaction (social basis function use) to guide their decisions about oneself and other people. These findings nuance the conceptualisation of social-cognitive processes across autistic traits while highlighting the need for large samples to validate null effects.

neuroscience↗

bioRxiv2025

Too few, too many, or just right? Optimizing sample sizes for population-level inferences in animal tracking projects

O_LISuccessful animal tracking projects depend on well-informed sampling strategies and robust methods to yield biologically meaningful inferences. Considering financial and logistical constraints, the reliability of research outputs is shaped by key decisions regarding study duration (how long should each individual be tracked?), sampling frequency (how often should new locations be collected?), and how many individuals should be tracked. To maximize their conservation value, studies must consider estimator precision and avoid biased inferences of key parameters related to movement behavior and space use, as this can lead to wasted resources and misguide management actions. C_LIO_LITo address these challenges, we propose a workflow for determining the optimal sample sizes for population-level home range area and speed estimates, explicitly addressing the trade-offs between sampling duration (T), sampling interval (reciprocal of frequency; {Delta}t), and population sample size (m). While a priori study design is considered best practice, this workflow can be applied at multiple stages, including concurrent with data collection, or as a post hoc evaluation. C_LIO_LIBy selecting robust methods that are sampling-insensitive, and by quantifying and propagating uncertainty through downstream analyses, we can determine whether our sample sizes (both at the individual- and population-level) are sufficient to yield robust population-level inferences. Furthermore, researchers can integrate additional logistical constraints such as fix success rate, location error, and potential device malfunctions, while also accounting for individual variation. We illustrate potential applications of this workflow through empirically-guided simulations. C_LIO_LITo facilitate its use and implementation, we incorporated this workflow into the user-friendly movedesign R Shiny application. This application enables researchers to easily test different sampling strategies, and as of version 0.3.3, integrates population-level analytical targets. This workflow has the potential to improve the rigor and reliability of animal tracking projects conducted under logistical and financial constraints, and thereby support more effective scientific research, wildlife management, and conservation efforts. It can also support grant or permit submissions by generating evidence-based recommendations for the number of biologgers needed or sampling effort required to achieve research objectives. C_LI

ecology↗

bioRxiv2024

Identification of Human Pathways Acting on Nuclear Non-Coding RNAs Using the Mirror Forward Genetic Approach

Despite critical roles in diseases, human pathways acting on strictly nuclear non-coding RNAs have been refractory to forward genetics. To enable their forward genetic discovery, we developed a single-cell approach that "Mirrors" activities of nuclear pathways with cytoplasmic fluorescence. Application of Mirror to two nuclear pathways targeting MALAT1s 3' end, the pathway of its maturation and the other, the degradation pathway blocked by the triple-helical Element for Nuclear Expression (ENE), identified nearly all components of three complexes: Ribonuclease P and the RNA Exosome, including nuclear DIS3, EXOSC10, and C1D, as well as the Nuclear Exosome Targeting (NEXT) complex. Additionally, Mirror identified DEAD-box helicase DDX59 associated with the genetic disorder Oral-Facial-Digital syndrome (OFD), yet lacking known substrates or roles in nuclear RNA degradation. Knockout of DDX59 exhibits stabilization of the full-length MALAT1 with a stability-compromised ENE and increases levels of 3'-extended forms of small nuclear RNAs. It also exhibits extensive retention of minor introns, including in OFD-associated genes, suggesting a mechanism for DDX59 association with OFD. Mirror efficiently identifies pathways acting on strictly nuclear non-coding RNAs, including essential and indirectly-acting components, and, as a result, uncovers unexpected links to human disease.

genetics↗

bioRxiv2022

Microplastics are present in follicular fluid and compromise gamete function in vitro: Is the Anthropocene throw-away society throwing away fertility?

The past several decades have seen alarming declines in the reproductive health of humans, animals and plants. While humans have introduced numerous pollutants that can impair reproductive systems (such as well-documented endocrine disruptors), the potential for microplastics (MPs) to be contributing to the widespread declines in fertility is particularly noteworthy. Over the same timespan that declines in fertility began to be documented, there has been a correlated shift towards a "throw-away society" that is characterised by the excessive consumption of single-use plastic products and a concomitant accumulation of MPs pollution. Studies are showing that MPs can impair fertility, but data have been limited to rodents that were force-fed hundreds of thousands of times more plastics than they would be exposed in the environment. As a first step to link in vitro health effects with in vivo environmental exposure, we quantified microplastics in the follicular fluid of women and domestic cows. We found that the concentrations of polystyrene microplastics that naturally occurred in follicular fluid were sufficient to compromise the maturation of bovine oocytes in vitro. Collectively, these findings demonstrate that microplastics may also be contributing to the widespread declines in fertility that have been occurring over recent Anthropocene decades.

developmental biology↗

bioRxiv2022

Single Cell Cortical Bone Transcriptomics Defines Novel Osteolineage Gene Sets Altered in Chronic Kidney Disease

Due to a lack of spatial-temporal resolution at the single cell level, the etiologies of the bone dysfunction caused by diseases such as normal aging, osteoporosis, and the metabolic bone disease associated with chronic kidney disease (CKD) remain largely unknown. To this end, flow cytometry and scRNAseq were performed on long bone cells from Sost-cre/Ai9+ mice, and pure osteolineage transcriptomes were identified, including novel osteocyte-specific gene sets. Clustering analysis isolated osteoblast precursors that expressed Tnc, Mmp13, and Spp1, and a mature osteoblast population defined by Smpd3, Col1a1, and Col11a1. Osteocytes were demarcated by Cd109, Ptprz1, Ramp1, Bambi, Adamts14, Spns2, Bmp2, WasI, and Phex. We validated our in vivo scRNAseq using integrative in vitro promoter occupancy via ATACseq coupled with transcriptomic analyses of a conditional, temporally differentiated MSC cell line. Further, trajectory analyses predicted osteoblast-to-osteocyte transitions via defined pathways associated with a distinct metabolic shift as determined by single-cell flux estimation analysis (scFEA). Using the adenine mouse model of CKD, at a time point prior to major skeletal alterations, we found that gene expression within all stages of the osteolineage was disturbed. In sum, distinct populations of osteoblasts/osteocytes were defined at the single cell level. Using this roadmap of gene assembly, we demonstrated unrealized molecular defects across multiple bone cell populations in a mouse model of CKD, and our collective results suggest a potentially earlier and more broad bone pathology in this disease than previously recognized.

cell biology↗

bioRxiv2019

Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques

One of the most influential accounts of central orbitofrontal cortex- that it mediates behavioral flexibility - has been challenged by the finding that discrimination reversal in macaques -the classic test of behavioral flexibility -is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.

neuroscience↗