Biology subjects

Newby, J.

Publications and source records attributed to Newby, J..

7 recordsLinked to original sources

bioRxiv2024

Decision support for managing an invasive pathogen through efficient clean seed systems: Cassava mosaic disease in Southeast Asia

CONTEXTEffective seed systems must both distribute high-performing varieties efficiently and slow or stop the spread of pathogens and pests. Epidemics increasingly threaten crops around the world, endangering the incomes and livelihoods of smallholder farmers. Responding to these food and economic security challenges requires stakeholders to act quickly and decisively during the early stages of invasions, typically with very limited resources. The recent introduction of cassava mosaic virus into southeast Asia threatens cassava production in the region. OBJECTIVESOur goal in this study is to provide a decision-support framework for efficient management of healthy seed systems, applied to cassava mosaic disease. The specific objectives are to (1) evaluate disease risk in disease-free parts of Cambodia, Lao PDR, Thailand, and Vietnam by integrating disease occurrence, climate, topology, and land use, using machine learning; (2) incorporate this predicted environmental risk with seed exchange survey data and whitefly spread in the landscape to model epidemic spread in a network meta-population model; and (3) use scenario analysis to identify candidate regions to be prioritized in seed system management. RESULTS AND CONCLUSIONSThe analyses allow stakeholders to evaluate strategy options for allocating their resources in the field, guiding the implementation of seed system programs and responses. Fixed rather than adaptive deployment of clean seed produced more favorable outcomes in this model, as did prioritization of a higher number of districts through the deployment of smaller volumes of clean seed. SIGNIFICANCEThe decision-support framework presented here can be applied widely to seed systems challenged by the dual goals of distributing seed efficiently and reducing disease risk. Data-driven approaches support evidence-based identification of optimized surveillance and mitigation areas in an iterative fashion, providing guidance early in an epidemic, and revising them as data accrue over time.

ecology↗

bioRxiv2023

Cooperative Motility, Force Generation and Mechanosensing in a Foraging Non-Photosynthetic Diatom

Diatoms are ancestrally photosynthetic microalgae. However, some underwent a major evolutionary transition, losing photosynthesis to become obligate heterotrophs. The molecular and physiological basis for this transition is unclear. Here, we isolate and characterize new strains of non-photosynthetic diatoms from the coastal waters of Singapore. These diatoms occupy diverse ecological niches and display glucose-mediated catabolite repression, a classical feature of bacterial and fungal heterotrophs. Live-cell imaging reveals deposition of secreted extracellular polymeric substance (EPS). Diatoms moving on pre-existing EPS trails (runners) move faster than those laying new trails (blazers). This leads to cell-to-cell coupling where runners can push blazers to make them move faster. Calibrated micropipettes measure substantial single cell pushing forces, which are consistent with high-order myosin motor cooperativity. Collisions that impede forward motion induce reversal, revealing navigation-related force sensing. Together, these data identify aspects of metabolism and motility that are likely to promote and underpin diatom heterotrophy.

cell biology↗

bioRxiv2021

Personalized Virus Load Curves of SARS-CoV-2 Infection

This manuscript has been withdrawn due to submission errors. Therefore, the authors do not wish this work to be cited as a reference. Please see and cite for reference the manuscript posted on medRxiv https://doi.org/10.1101/2021.01.21.21250268 If you have any questions, please contact the corresponding author.

physiology↗

bioRxiv2020

TDP-43 and HSP70 phase separate into anisotropic, intranuclear liquid spherical annuli

The RNA binding protein TDP-43 naturally phase separates within cell nuclei and forms cytoplasmic aggregates in age-related neurodegenerative diseases. Here we show that acetylation-mediated inhibition of TDP-43 binding to RNA produces co-de-mixing of acetylated and unmodified TDP-43 into symmetrical, intranuclear spherical annuli whose shells and cores have liquid properties. Shells are anisotropic, like liquid crystals. Consistent with our modelling predictions that annulus formation is driven by components with strong self-interactions but weak interaction with TDP-43, the major components of annuli cores are identified to be HSP70 family proteins, whose chaperone activity is required to maintain liquidity of the core. Proteasome inhibition, mimicking reduction in proteasome activity during aging, induces TDP-43-containing annuli in neurons in rodents. Thus, we identify that TDP-43 phase separation is regulated by acetylation, proteolysis, and ATPase-dependent chaperone activity of HSP70. One Sentence SummaryAcetylation of TDP-43 drives its phase separation into spherical annuli that form a liquid-inside-a-liquid-inside-a-liquid.

cell biology↗

bioRxiv2019

Short-term effects of GPS collars on the activity, behavior, and adrenal response of scimitar-horned oryx (Oryx dammah)

GPS collars have revolutionized the field of animal ecology, providing detailed information on animal movement and the habitats necessary for species survival. GPS collars also have the potential to cause adverse effects ranging from mild irritation to severe tissue damage, reduced fitness, and death. The impact of GPS collars on the behavior, stress, or activity, however, have rarely been tested on study species prior to release. The objective of our study was to provide a comprehensive assessment of the short-term effects of GPS collars fitted on scimitar-horned oryx (Oryx dammah), an extinct-in-the-wild antelope once widely distributed across Sahelian grasslands in North Africa. We conducted behavioral observations, assessed fecal glucocorticoid metabolites (FGM), and evaluated high-resolution data from tri-axial accelerometers. Using a series of non-standard regression models, we illustrate clear but short-term effects to animals fitted with GPS collars. Behavioral observations highlighted a significant increase in the amount of headshaking from pre-treatment levels, returning below baseline levels during the post-treatment period (>3 days post-collaring). Similarly, FGM concentrations (i.e., stress hormones) increased after GPS collars were fitted on animals but returned to pre-collaring levels within 5 days of collaring. Lastly, tri-axial accelerometers, collecting data at eight positions per second, indicated a > 480 percent increase in the amount of hourly headshaking immediately after collaring. This post-collaring increase in headshaking was estimated to decline in magnitude within 4 hours after GPS collar fitting. These effects constitute a handling and/or habituation response (model dependent), with animals showing short-term responses in activity, behavior, and stress that dissipated within several hours to several days of being fitted with GPS collars. Importantly, none of our analyses indicated any long-term effects that would have more pressing animal welfare concerns.

ecology↗

bioRxiv2018

Hydrodynamics of transient cell-cell contact: The role of membrane permeability and active protrusion length

In many biological settings, two or more cells come into physical contact to form a cell-cell interface. In some cases, the cell-cell contact must be transient, forming on timescales of seconds. One example is offered by the T cell, an immune cell which must attach to the surface of other cells in order to decipher information about disease. The aspect ratio of these interfaces (tens of nanometers thick and tens of micrometers in diameter) puts them into the thin-layer limit, or \"lubrication limit\", of fluid dynamics. A key question is how the receptors and ligands on opposing cells come into contact. What are the relative roles of thermal undulations of the plasma membrane and deterministic forces from active filopodia? We use a computational fluid dynamics algorithm capable of simulating 10-nanometer-scale fluid-structure interactions with thermal fluctuations up to seconds-and microns-scales. We use this to simulate two opposing membranes, variously including thermal fluctuations, active forces, and membrane permeability. In some regimes dominated by thermal fluctuations, proximity is a rare event, which we capture by computing mean first-passage times using a Weighted Ensemble rare-event computational method. Our results demonstrate that the time-to-contact increases for smaller cell-cell distances (where the thin-layer effect is strongest), leading to an optimal initial cell-cell separation for fastest receptor-ligand binding. We reproduce a previous experimental observation that fluctuation spatial scales are largely unaffected, but timescales are dramatically slowed, by the thin-layer effect. We also find that membrane permeability would need to be above physiological levels to abrogate the thin-layer effect.\n\nAuthor summaryThe elastohydrodynamics of water in and around cells is playing an increasingly recognized role in biology. In this work, we investigate the flow of extracellular fluid in between cells during the formation of a cell-cell contact, to determine whether its necessary evacuation as the cells approach is a rate-limiting step before molecules on either cell can interact. To overcome the computational challenges associated with simulating fluid in this mechanically soft, stochastic and high-aspect-ratio environment, we extend a computational framework where the cell plasma membranes are treated as immersed boundaries in the fluid, and combine this with computational methods for simulating stochastic rare events in which an ensemble of simulations are given weights according to their probability. We find that the internal dynamics of the membranes has speeds in approximately microseconds, but that as the cells approach, a new slow timescale of approximately milliseconds is introduced. Thermal undulations nor typical amounts of membrane permeability can overcome the timescale, but active forces, e.g., from the cytoskeleton, can. Our results suggest an explanation for differences in molecular interactions in live cells compared to in vitro reconstitution experiments.

biophysics↗

bioRxiv2017

Control of septin filament flexibility and bundling

Septins self-assemble into heteromeric rods and filaments to act as scaffolds and modulate membrane properties. How cells tune the biophysical properties of septin filaments to control filament flexibility and length, and in turn the size, shape, and position of higher-order septin structures is not well understood. We examined how rod composition and nucleotide availability influence physical properties of septins such as annealing, fragmentation, bundling and bending. We found that septin complexes have symmetric termini, even when both Shs1 and Cdc11 are coexpressed. The relative proportion of Cdc11/Shs1 septin complexes controls the biophysical properties of filaments and influences the rate of annealing, fragmentation, and filament flexibility. Additionally, the presence and exchange of guanine nucleotide also alters filament length and bundling. An Shs1 mutant that is predicted to alter nucleotide hydrolysis has altered filament length and dynamics in cells and impacts cell morphogenesis. These data show that modulating filament properties through rod composition and nucleotide binding can control formation of septin assemblies that have distinct physical properties and functions.

cell biology↗