Biology subjects

Richardson, A. D.

Publications and source records attributed to Richardson, A. D..

9 recordsLinked to original sources

bioRxiv2026

Dynamic engagement of dual-role regulators by the Sin3 complex

Gene expression is governed by dynamic switches between repressive and activating transcriptional states1,2. Among the molecules mediating these transitions, chromatin readers and transcription factors play pivotal roles3,4. However, how they assemble with regulatory machineries to enable crosstalk between gene repression and activation remains unknown. Here, we use an integrative structural dynamics approach - combining cryo-EM, crosslinking mass spectrometry, fragment-resolved protein interactome mapping and crystallography - to show how the dual-role chromatin reader Cti6 and transcription factors Ash1 and Ume6 engage the Sin3 deacetylase complex, a major regulatory hub in eukaryotes5. We find that Cti6 competes with Ash1 to drive its dynamic recruitment to a shared peripheral module, while Ume6 engages the Sin3 scaffold through a defined, minimal interface. Using high-throughput mutational scanning, we reveal deleterious and gain-of-function mutations in Sin3, identifying evolutionarily conserved residues essential for anchoring transcription factors. Together, these results provide structural and functional insights into how dual-role regulators engage the central Sin3 complex, revealing subtle assembly principles that may facilitate crosstalk between gene repression and activation. They also establish an integrative multidisciplinary framework to dissect the dynamics of macromolecular assemblies across biological systems.

molecular biology↗

bioRxiv2026

MassID provides near complete annotation of metabolomics data with identification probabilities

Liquid chromatography coupled to mass spectrometry (LC/MS) is a powerful tool in metabolomics research, generating tens-of-thousands of signals from a single biological sample. However, current software solutions for unbiased assessment of metabolomics data analysis are limited by complex sources of noise and non-quantitative metabolite identifications that make results difficult to interpret. Here, we present MassID, a cloud-based untargeted metabolomics pipeline that aims to overcome the innate challenges of unbiased metabolite analysis and perform end-to-end data processing, transforming raw spectra to normalized and identified metabolite profiles. MassID incorporates a suite of software functionalities, including deep learning-based peak detection and comprehensive noise filtering. In addition, with MassID we introduce a novel software module: DecoID2 that enables probabilistic metabolite identification for false discovery rate (FDR)-controlled metabolomics. When applied to a human plasma dataset, MassID results in near-complete signal annotation, identification of >4,000 metabolites (including >1,200 compounds at an FDR <5%) across four complementary LC/MS runs, and enables integrated downstream analyses to understand biochemical dysregulation at both the molecular and pathway level. When compared to the Metabolomics Standards Initiative (MSI) confidence levels, identification probability generally correlated with MSI levels. However, only 356/418 of MSI Level 1 compounds were identified with <5% FDR and the remaining 884 FDR < 5% compounds were identified from MSI L2-L3 compounds, highlighting the enhanced specificity and discovery potential achieved by MassID.

bioinformatics↗

bioRxiv2025

Asymmetric Spring and Autumn Phenology Control Growing Season Length in Temperate Deciduous Forests

Forest phenological responses to climatic variation among species and populations across broad spatial scales remain poorly understood. Here, we quantify four decades of phenological dynamics for 10 major deciduous tree species by compiling a unique dataset that integrates high spatial resolution remote sensing with extensive field inventory data across the Northeastern and Midwestern United States. We found that spring and autumn phenology impose asymmetric controls on growing season length, with spring regulating interannual variation and autumn driving long-term trends. Spring phenology across all species was primarily controlled by temperature, while autumn phenology was influenced by spring phenology and an interacting suite of species-specific environmental factors. Our study demonstrates the promise of combining high resolution remote sensing with forest inventory data to investigate phenological dynamics over large regions. More importantly, our results provide new insights into how species-specific sensitivities to environmental drivers regulate growing season length in temperate forests.

ecology↗

bioRxiv2024

Implications of carbon source-sink feedbacks for plant growth responses to environmental factors

Current global models of vegetation dynamics are largely carbon (C) source-driven, with behaviour primarily determined by the environmental responses of photosynthesis. However, real plants operate as integrated wholes, with feedbacks between sources, such as photosynthesis, and sinks, such as growth, resulting in homeostatic concentrations of metabolites such as sugars. A parsimonious approach to implementing this homeostatic coupling of C sources and sinks in a tree growth model is presented, and its implications for the responses of net photosynthesis and growth to environmental factors and tree size assessed. Hill functions describe inhibition of C sources (net photosynthesis) and activation of sinks (structural growth) as sucrose concentration increases. The model is parameterised for a typical tree growing at a site in the Amazonian rainforest and its qualitative behaviour is found to be consistent with observations. A key outcome is that sinks and sources strongly regulate each other. Hence environmental factors that affect potential net photosynthesis, such as atmospheric CO2, have greatly reduced effects on growth when homeostatic feedbacks from sucrose concentrations are considered. For example, compared with a C-source-only-driven approach (as in most current global models), the response of tree biomass for a tree currently 300 yr old, to increasing atmospheric CO2 projected to the end of this century under a high scenario, is reduced by ca.77%, from +122% to +29%, with net photosynthesis and growth rate responses reduced by a similar amount. Furthermore, in this coupled approach, any direct controls on growth (either environmental or through phenological controls on xylogensis) will influence source activity through the sucrose feedback. For example, a reduction in potential growth through temperature constraints on cell-wall construction increases sucrose concentrations, resulting in a compensating reduction in net photosynthesis. While net photosynthesis controls growth, growth controls net photosynthesis. In addition, we find a strong effect of changing tree allometry on C source-sink relations as the tree grows. Larger trees are less source-limited due to a higher ratio of sapwood area (and hence potential C assimilation rate) to potential growth rate, consistent with the observed decline in growth response to atmospheric CO2 as trees age. We suggest that the implications of including C source-sink coupling in models of vegetation dynamics, such as dynamic global vegetation models, are likely to be profound.

plant biology↗

bioRxiv2023

Phenology across scales: an intercontinental analysis of leaf-out dates in temperate deciduous tree communities

AimTo quantify the intra-community variability of leaf-out (ICVLo) among dominant trees in temperate deciduous forests, assess its links with specific and phylogenetic diversity, identify its environmental drivers, and deduce its ecological consequences with regard to radiation received and exposure to late frost. LocationEastern North America (ENA) and Europe (EUR). Time period2009-2022 Major taxa studiedTemperate deciduous forest trees. MethodsWe developed an approach to quantify ICVLo through the analysis of RGB images taken from phenological cameras. We related ICVLo to species richness, phylogenetic diversity and environmental conditions. We quantified the intra-community variability of the amount of radiation received and of exposure to late frost. ResultsLeaf-out occurred over a longer time interval in ENA than in EUR. The sensitivity of leaf-out to temperature was identical in both regions (-3.4 days per {degrees}C). The distributions of ICVLo were similar in EUR and ENA forests, despite the latter being more species-rich and phylogenetically diverse. In both regions, cooler conditions and an earlier occurrence of leaf-out resulted in higher ICVLo. ICVLo resulted in a ca. 8% difference of radiation absorption over spring among individual trees. Forest communities in ENA had shorter safety margins as regards the exposure to late frosts, and were actually more frequently exposed to late frosts. Main conclusionsWe conducted the first intercontinental analysis of the variability of leaf-out at the scale of tree communities. North American and European forests showed similar ICVLo, in spite of their differences in terms of species richness and phylogenetic diversity, highlighting the relevance of environmental controls on ICVLo. We quantified two ecological implications of ICVLo (difference in terms of radiation absorption and exposure to late frost), which should be explored in the context of ongoing climate change, which affects trees differently according to their phenological niche.

ecology↗

bioRxiv2022

Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV-animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures.

microbiology↗

bioRxiv2020

The Wood Image Analysis and Dataset (WIAD): open-access visual analysis tools to advance the ecological data revolution

O_LIEcological data is collected and shared at an increasingly rapid pace, but it is often shared in inconsistent and untraceable processed forms. Images of wood contain a wealth of information such as colours and textures but are most commonly reduced to ring-width measurements before they can be shared in various common file formats. Archiving digital images of wood samples in libraries, that have been developed for ecological analysis and are publicly available, remains the exception. C_LIO_LIWe developed the Wood Image Analysis and Dataset (WIAD) an open-source application including a web-interface to integrate basic visual analysis of wood samples, such as increment cores, thin sections or x-ray films, basic data processing, and archiving of the images and derived data to facilitate transparency and reproducibility in studies using visual characteristics of wood. C_LIO_LIWIAD provides user-friendly tools to manipulate images of wood samples, mark and measure wood characteristics such as growth increments, density fluctuations, early- and latewood widths, and fire scars, and to visualise, process, and archive images, metadata, and the derived data. C_LIO_LIWIAD constitutes a step towards the reproducible automation of tree-ring analysis, while establishing an open-source foundation to create improved community developed repositories which would enable novel ecological studies harnessing the wealth of existing visual data. C_LI

plant biology↗

bioRxiv2020

Wood formation in an evergreen conifer is controlled by phloem transport of labile carbon, but nonstructural carbon concentrations are not

Wood formation is a crucial process for carbon sequestration, yet how variations in carbon supply affect wood formation and carbon dynamics in trees more generally remains poorly understood. To better understand the role of carbon supply in wood formation, we restricted phloem transport using girdling and compression around the stem of mature white pines and monitored the effects on local wood formation and stem CO2 efflux, as well as nonstructural carbon concentrations in needles, stems, and roots. Growth and stem CO2 efflux varied with location relative to treatment (i.e., above or below on the stem). We observed up to a two-fold difference in the number of tracheids formed above versus below the manipulations over the remaining growing season. In contrast, the treatments did not affect mean cell size noticeably and mean cell-wall area decreased only slightly below them. Surprisingly, nonstructural carbon pools and concentrations in the xylem, needles, and roots remained largely unchanged, although starch reserves declined and increased marginally below and above the girdle, respectively. Our results suggest that phloem transport strongly affects cell proliferation and respiration in the cambial zone of mature white pine, but has little impact on nonstructural carbon concentrations. These findings contribute to our understanding of how wood formation is controlled. HighlightRestrictions in phloem transport designed to affect carbon supply, lead to changes in wood formation and stem respiration of mature white pines without substantially changing local nonstructural carbon concentrations.

plant biology↗

bioRxiv2019

A reference map of the human protein interactome

Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here we present the first human \"all-by-all\" binary reference interactome map, or \"HuRI\". With ~53,000 high-quality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.

systems biology↗