Biology subjects

Newton, C.

Publications and source records attributed to Newton, C..

6 recordsLinked to original sources

bioRxiv2024

High-throughput proteomic and phosphoproteomic analysis of formalin-fixed paraffin-embedded tissue

Formalin-fixed, paraffin-embedded (FFPE) patient tissues are a valuable resource for proteomic studies with the potential to associate the derived molecular insights with clinical annotations and outcomes. Here we present an optimized, partially automated workflow for FFPE proteomics combining pathology-guided macro-dissection, Adaptive Focused Acoustics (AFA) sonication for lysis and decrosslinking, S-Trap digestion to peptides, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using Orbitrap, Astral or timsTOF HT instrumentation. The workflow enables analysis of up to 96 dissected FFPE tissue samples or 10 {micro}m scrolls, identifying 8,000-10,000 unique proteins per sample with median CVs <20%. Key optimizations include improved tissue lysis strategies, protein quantification for normalization, and peptide cleanup prior to LC-MS/MS analysis. Application to lung adenocarcinoma (LUAD) FFPE blocks confirms the platforms effectiveness in processing complex, clinically relevant samples, achieving deep proteome coverage and quantitative robustness comparable to TMT-based methods. Using the newly released Orbitrap Astral with short, 24-minute gradients, the workflow identifies up to [~]10,000 unique proteins and [~]11,000 localized phosphosites in LUAD FFPE tissue. This high-throughput, scalable workflow advances biomarker discovery and proteomic research in archival tissue samples.

systems biology↗

bioRxiv2023

Path integration selectively predicts midlife risk of Alzheimer's disease

The entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimers disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration, we predicted that path integration impairment would represent the first behavioural change in adults at-risk of AD. Using immersive virtual reality, we found that midlife path integration impairments predicted both hereditary and physiological AD risk, with no corresponding impairment on tests of episodic memory or other spatial behaviours. Impairments related to poorer angular estimation and were associated with hexadirectional grid-like fMRI signal in the posterior-medial EC. These results indicate that altered path integration may represent the transition point from at-risk state to disease onset in AD, prior to impairment in other cognitive domains.

neuroscience↗

bioRxiv2022

Comparable human spatial memory distortions in physical, desktop virtual and immersive virtual environments

Boundaries define regions of space and are integral to episodic memories. The impact of boundaries on spatial memory and neural representations of space has been extensively studied in freely-moving rodents. But less is known in humans and many prior studies have employed desktop virtual reality (VR) which lacks the body-based self-motion cues of the physical world, diminishing the potentially strong input from path integration to spatial memory. We replicated a desktop-VR study testing the impact of boundaries on spatial memory (Hartley et al., 2004) in a physical room (2.4m x 2.4m, 2m tall) by having participants (N = 27) learn the location of a circular stool and then after a short delay replace it where they thought they had found it. During the delay, the wall boundaries were either expanded or contracted. We compared performance to groups of participants undergoing the same procedure in a laser-scanned replica in both desktop VR (N = 44) and freely-walking head mounted display (HMD) VR (N = 39) environments. Performance was measured as goodness of fit between the spatial distributions of group responses and seven modelled distributions that prioritised different metrics based on boundary geometry or walking paths to estimate the stool location. The best fitting model was a weighted linear combination of all the geometric spatial models, but an individual model derived from place cell firing in Hartley et al. 2004 also fit well. High levels of disorientation in all three environments prevented detailed analysis on the contribution of path integration. We found identical model fits across the three environments, though desktop VR and HMD-VR appeared more consistent in spatial distributions of group responses than the physical environment and displayed known variations in virtual depth perception. Thus, while human spatial representation appears differentially influenced by environmental boundaries, the influence is similar across virtual and physical environments. Despite differences in body-based cue availability, desktop and HMD-VR allow a good and interchangeable approximation for examining human spatial memory in small-scale physical environments.

neuroscience↗

bioRxiv2020

Predictive Maps in Rats and Humans for Spatial Navigation

Much of our understanding of navigation comes from the study of individual species, often with specific tasks tailored to those species. Here, we provide a novel experimental and analytic framework, integrating across humans, rats and simulated reinforcement learning (RL) agents to interrogate the dynamics of behaviour during spatial navigation. We developed a novel open-field navigation task (Tartarus Maze) requiring dynamic adaptation (shortcuts and detours) to frequently changing obstructions in the path to a hidden goal. Humans and rats were remarkably similar in their trajectories. Both species showed the greatest similarity to RL agents utilising a successor representation, which creates a predictive map. Humans also displayed trajectory features similar to model-based RL agents, which implemented an optimal tree-search planning procedure. Our results help refine models seeking to explain mammalian navigation in dynamic environments, and highlight the utility of modelling the behaviour of different species to uncover the shared mechanisms that support behaviour.

animal behavior and cognition↗

bioRxiv2019

Integration of ethnobotany and population genetics uncovers the agrobiodiversity of date palms of Siwa Oasis (Egypt) and their importance to the evolutionary history of the species

Crop diversity is shaped by biological and social processes interacting at different spatiotemporal scales. Here we combined population genetics and ethnobotany to investigate date palm (Phoenix dactylifera L.) diversity in Siwa Oasis, Egypt. Based on interviews with farmers and observation of practices in the field, we collected 149 date palms from Siwa Oasis and 27 uncultivated date palms from abandoned oases in the surrounding desert. Using genotyping data from 18 nuclear and plastid microsatellite loci, we confirmed that some named types each constitute a clonal line, i.e. a true-to-type cultivar. We also found that others are collections of clonal lines, i.e. ethnovarieties, or even unrelated samples, i.e. local categories. This alters current assessments of agrobiodiversity, which are visibly underestimated, and uncovers the impact of low-intensity, but highly effective, farming practices on biodiversity. These hardly observable practices, hypothesized by ethnographic survey and confirmed by genetic analysis, are enabled by the way Isiwans conceive and classify living beings in their oasis, which do not quite match the way biologists do: a classic disparity of etic vs. emic categorizations. In addition, we established that Siwa date palms represent a unique and highly diverse genetic cluster, rather than a subset of North African and Middle Eastern palm diversity. As previously shown, North African date palms display evidence of introgression by the wild relative Phoenix theophrasti, and we found that the uncultivated date palms from the abandoned oases share even more alleles with this species than cultivated palms in this region. The study of Siwa date palms could hence be a key to the understanding of date palm diversification in North Africa. Integration of ethnography and population genetics promoted the understanding of the interplay between diversity management in the oasis (short-time scale), and the origins and dynamic of diversity through domestication and diversification (long-time scale).

evolutionary biology↗

bioRxiv2017

The Date Palm (Phoenix dactylifera L.) In Siwa Oasis (Egypt): How Ethnographic, Morphometric, And Genetic Analyses Together Explain The Local Agrobiodiversity

The agrobiodiversity of the Siwa oasis (in Egypt), located at the crossroads of ancient Trans-Saharan routes, is evaluated in this article focusing on the date palm (Phoenix dactylifera L.), the oasis \"ecosystem engineer\". This assessment confronts different ontologies: diversity as expressed and maintained by the folk categorization system of the Siwa inhabitants (through the results of an ethnographical analysis) and diversity described by genetic sciences and a morphometric tool based on the size and geometry of the seeds. This work is also an opportunity to evaluate this tool intended for archaeobotany. Beyond a simple instrumentalization of one discipline by another, this study offers a space of mutual enrichment: on the relative importance of the feral and cultivated date palms, the local relevance of the concept of \"cultivar\" and the confirmation of the existence of \"ethnovarieties\".

plant biology↗