Biology subjects

Sanders, T.

Publications and source records attributed to Sanders, T..

9 recordsLinked to original sources

bioRxiv2026

Soil nitrogen dynamics in riparian zones of two Arctic rivers

Riparian zones act as protective buffers, filtering land-to-river nutrient inputs through retention and nitrogen (N) gas losses. While rapid Arctic warming and permafrost thaw may enhance terrestrial nutrient inputs to aquatic systems, comprehensive assessments of N cycling in Arctic riparian soils are lacking. Conventionally, these zones are considered inactive due to N limitation of Arctic soils and low temperatures, leaving their N cycling unexplored. To address this, we investigated N pools and turnover processes in riparian zones of two Arctic rivers in Finland and Greenland. We combined measurements of the extractable N pool and in-situ nitrous oxide (N2O) flux with 15N-labeling techniques to quantify gross mineralization, nitrification, potential denitrification, and potential dissimilatory nitrate reduction to ammonium (DNRA). Our findings reveal that mineral N cycling in high-latitude riparian zones is more active than previously assumed. Despite low temperatures and low to intermediate soil organic carbon content, we found high gross N mineralization rates, alongside detectable rates of gross nitrification and potential DNRA. We attribute the unexpectedly high N activity in C-poor soils to low C/N ratios, which create a stoichiometric imbalance, thereby enhancing N mineralization. The presence or absence of vegetation largely determined the dominance and magnitude of these pathways. While dense vascular plant cover was associated with higher extractable N pools and gross mineralization rate, low nitrification rates and elevated DNRA potential indicated a tight N cycle. Conversely, sparsely vegetated patches with cryptogamic biocrusts acted as N2O hotspots. In bare sandy soils adjacent to the river, we found high gross nitrification rate and detectable N2O losses, possibly driven by riverine organic N inputs. Taken together, this research shows that Arctic riparian zones may play an important role in reducing terrestrial N inputs to the rivers, which should be considered when studying the fate of N in the rapidly changing Arctic.

ecology↗

bioRxiv2024

The molecular arsenal of the key coastal bioturbator Hediste diversicolor faced with changing oceans

The importance of infaunal bioturbators for the functioning of marine ecosystems cannot be overstated. Inhabitants of estuarine and coastal habitats are expected to show resilience to fluctuations in seawater temperature and pH, which adds complexity to our understanding of the effects of global change drivers. Further, stress responses may be propagated through chemical cues within and across species, which may amplify the costs of life and alter species interactions. Research into the molecular mechanisms underlying this resilience has been limited by a lack of annotated genomes and associated molecular tools. In this study, we present the first chromosome-level, annotated draft genome of the marine ragworm Hediste diversicolor, specifically mapping genes important for chemical communication, sensing and pH homeostasis. Using these resources, we then evaluate the transcriptomic and behavioural responses of two distinct populations -- one field-sampled from Portugal (Ria Formosa) and one laboratory-acclimated and -bred from the United Kingdom (Humber) -- to changes in seawater pH, temperature, and odour cues from a low pH-stressed predator. Both populations displayed adaptive responses to future oceanic conditions, with targeted acid-base regulation in the Ria Formosa population experiment, and broader changes in metabolism and growth genes in the Humber population experiment. Chemical cues from stressed fish predators induced genes related to Schreckstoff biosynthesis in ragworms. Additionally, under future ocean conditions including increased temperature, the Humber population exhibited signs of cellular stress and damage. Our findings using the new annotated genome offer novel insights into the molecular arsenal of acid-base regulation which aids in predicting the impacts of an increasingly acidified and unstable ocean, and to transfer this knowledge to investigate these mechanisms in species with less tolerance.

genomics↗

bioRxiv2024

Metapipeline-DNA: A Comprehensive Germline & Somatic Genomics Nextflow Pipeline

SummaryThe price, quality and throughout of DNA sequencing continue to improve. Algorithmic innovations have allowed inference of a growing range of features from DNA sequencing data, quantifying nuclear, mitochondrial and evolutionary aspects of both germline and somatic genomes. To automate analyses of the full range of genomic characteristics, we created an extensible Nextflow meta-pipeline called metapipeline-DNA. Metapipeline-DNA analyzes targeted and whole-genome sequencing data from raw reads through pre-processing, feature detection by multiple algorithms, quality-control and data- visualization. Each step can be run independently and is supported robust software engineering including automated failure-recovery, robust testing and consistent verifications of inputs, outputs and parameters. Metapipeline-DNA is cloud-compatible and highly configurable, with options to subset and optimize each analysis. Metapipeline-DNA facilitates high-scale, comprehensive analysis of DNA sequencing data. AvailabilityMetapipeline-DNA is an open-source Nextflow pipeline under the GPLv2 license and is available at https://github.com/uclahs-cds/metapipeline-DNA.

bioinformatics↗

bioRxiv2024

Engineering fluorescent reporters in human pluripotent cells and strategies for live imaging human neurogenesis

Investigation of cell behaviour and cell biological processes underlying human development is facilitated by creation of fluorescent reporters in human pluripotent stem cells, which can be differentiated into cell types of choice. Here we report use of a piggyBac transposon-mediated stable integration strategy to engineer human pluripotent stem cell reporter lines. These express a plasma membrane localised protein tagged with the fluorescent proteins eGFP or mKate2, the photoconvertible nuclear marker H2B-mEos3.2, or the cytoskeletal protein F-tractin tagged with mKate2. Focussing on neural development these lines were used to live image and quantify cell behaviours, including cell cycle progression and cell division orientation in spinal cord rosettes. Further, lipofection-mediated introduction of piggyBac constructs into human neural progenitors labelled single cells and small cell groups within rosettes, allowing individual cell behaviours including neuronal delamination to be monitored. Finally, using the F-tractin-mKate2 hiPSC line, novel actin dynamics were captured during proliferation in cortical neural rosettes. This study presents and validates new tools and techniques with which to interrogate human cell behaviour and cell biology using live imaging approaches.

developmental biology↗

bioRxiv2024

Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging

IntroductionClinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells. MethodsHuman-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours then the excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled vs. unlabeled NK-92 cells was assessed after 4 hours of co- incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17) using bioluminescent or GFP counts. Labeled NK-92 cells at two different doses (0.5 or 1 x 106) were administered to excised mouse brains (cerebellum), tibias, and lungs then imaged by 3D preclinical MPI (MOMENTUM imager) and localized relative to fiducial markers. NK-92 cells were imaged by clinical-scale MPI under development at Magnetic Insight Inc. ResultsNK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measured effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of VivoTrax-labeled NK-92 cells, with preclinical limit of detection of 3.1 x 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, tibias, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection of a clinically relevant dose of 4 x 107 labeled NK-92 cells was demonstrated on clinical-scale MPI. ConclusionMPI can provide sensitive, quantitative, and accurate spatial information on NK cell delivery, showing its potential to resolve a significant unmet clinical need to track NK cell treatments in patients.

biophysics↗

bioRxiv2024

Fish Blood Response to Ash-Induced Environmental Alkalinization, and their Implications to Wildfire-Scarred Watersheds

Changes in land use, warming climate and increased drought have amplified wildfire frequency and magnitude globally. Ash mixing into aquatic systems after wildfires rapidly increases water pH, creating an additional threat to wildlife, especially species that are already threatened, endangered and/or migratory. Here, Chinook salmon (Oncorhynchus tshawytscha) yearlings acclimated to 15 or 20{degrees}C were exposed to an environmentally relevant concentration of ash (0.25% w/v) which caused water pH to rapidly rise from [~]8.1 to [~]9.2. Mortalities occurred within the first 12 hours, and was higher at the higher temperature (33 versus 20 %). The greatest differences in blood chemistry between the two temperatures were dramatically greater ([~]7.5-fold) and very rapid (within 1 hour) spikes in both plasma total ammonia (to [~]1200 {micro}M) and lactate (to [~]6 mM) in warm-acclimated salmon, whereas cold-acclimated salmon experienced a much smaller and gradual rise in plasma total ammonia. Salmon at both temperatures experienced extracellular and intracellular alkalosis within 1 hour that recovered within 24 hours, but the alkalosis was smaller in magnitude in fish at warmer temperature. Impacts on plasma ion concentrations were relatively mild and plasma glucose increased by 2- to 4-fold at both temperatures. Notably, the increase in plasma total ammonia in fish at the warmer temperature was far faster and much greater than those reported in previous studies exposing fish despite higher water pH (9.4-10.5) induced without using ash. This suggests that ash has physiological impacts that cannot be explained by high water pH alone which may relate to the complex mixture of metals and organic compounds also released from ash. This demonstrates post-wildfire ash input can induce lethal yet previously unexplored physiological disturbances in fish and highlights the complex interaction with warmer temperatures typical of wildfire-scarred landscapes.

physiology↗

bioRxiv2021

Plasticity in gustatory and nociceptive neurons controls decision making in C. elegans salt navigation

A conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C. elegans between attraction to NaCl in naive animals and avoidance of NaCl in preconditioned animals, called gustatory plasticity. Ca2+ imaging in ASE and ASH NaCl sensing neurons reveals multiple cell-autonomous and distributed circuit adaptation mechanisms. A computational model quantitatively accounts for observed behaviors and reveals roles for sensory neurons in the control and modulation of motor behaviors, decision making and navigational strategy. Sensory adaptation dynamically alters the encoding of the environment. Rather than encoding the stimulus directly, therefore, we propose that these C. elegans sensors dynamically encode a context-dependent value of the stimulus. Our results demonstrate how adaptive sensory computation can directly control an animals behavioral state.

neuroscience↗

bioRxiv2020

Domain Binding and Isotype Dictate the Activity of Anti-human OX40 Antibodies

Previous data suggests that anti-OX40 mAb can elicit anti-tumour effects in mice through deletion of Tregs. However, OX40 also has powerful costimulatory effects on T cells which could evoke therapeutic responses. The contributions of these different effector mechanisms has not previously been systematically evaluated, particularly for mAb directed to human OX40. Therefore, we generated a novel human OX40 knock-in (KI) mouse to evaluate a panel of anti-hOX40 mAb and show that their activities relate directly to two key properties: 1) isotype – with mIgG1 mAb evoking receptor agonism and CD8+ T cell expansion and mIgG2a mAb evoking deletion of Treg and; 2) epitope - with membrane-proximal mAb delivering more powerful agonism. Intriguingly, both isotypes acted therapeutically in tumour models by engaging these different mechanisms. These findings highlight the significant impact of isotype and epitope on the modulation of anti-hOX40 mAb therapy, and indicate that CD8+ T cell expansion or Treg depletion might be preferable according to the composition of different tumours.Summary Human trials with anti-OX40 antibodies have been disappointing indicating that optimal reagents have not yet been developed. Here, using a new panel of antibodies, we show that isotype and epitope combine to determine agonistic and therapeutic activity.Competing Interest StatementMSC is a retained consultant for BioInvent International and has performed educational and advisory roles for Baxalta and Boehringer Ingleheim. He has received research funding from Roche, Gilead, Bioinvent International and GSK. BF, IT, LM and MS are employees of Bioinvent International.View Full Text

immunology↗

bioRxiv2018

Plasticity and environmental heterogeneity predict geographic resilience patterns of foundation species to future change

Although geographic patterns of species sensitivity to global environmental changes are defined by interacting multiple stressors, little is known about the biological mechanisms shaping regional differences in organismal vulnerability. Here, we examine large-scale spatial variations in biomineralisation under heterogeneous environmental gradients of temperature, salinity and food availability across a 30{degrees} latitudinal range (3,334 km), to test whether plasticity in calcareous shell production and composition, from juveniles to large adults, mediates geographic patterns of resilience to climate change in critical foundation species, the mussels Mytilus edulis and M. trossulus. We find mussels produced thinner shells with a higher organic content in polar than temperature regions, indicating decreasing shell calcification towards high latitudes. Salinity was the major driver of regional differences in mussel shell deposition, and in shell mineral and organic composition. In low-salinity environments, the production of calcite and organic shell layers was increased, providing higher resistance against dissolution in more corrosive waters. Conversely, under higher-salinity regimes, increased aragonite deposition suggests enhanced mechanical protection from predators. Interacting strong effects of decreasing salinity and increasing food availability on the compositional shell plasticity in polar and subpolar mussels during growth predict the deposition of a thicker external organic layer (periostracum) under forecasted future environmental conditions. This marked response potential of Mytilus species suggests a capacity for increased protection of high-latitude mussel populations from ocean acidification. Our work illustrates that mechanisms driving plastic responses to the spatial structure of multiple stressors can define geographic patterns of unforeseen species resilience to global environmental change.

ecology↗