Biology subjects

Russell, B.

Publications and source records attributed to Russell, B..

14 recordsLinked to original sources

bioRxiv2026

High ammonium suppresses nitrate transporter expression and constrains thermal plasticity in the green macroalga Codium cylindricum

Nitrogen source and availability can modulate thermal stress responses in marine macroalgae, yet the transcriptional mechanisms underpinning these effects in green seaweeds remain poorly understood. We tested how three N sources (ammonium, nitrate, urea) at low (5 M) and high (100 M) concentrations influence the thermal physiology and gene expression of Codium cylindricum. Thermal performance curves were constructed for growth, photosynthesis, and pigment content across a 5-29 {degrees}C gradient, coupled with transcriptomic analysis at three key temperatures. At high concentrations, ammonium reduced maximum growth rate by 25% and lowered the thermal optimum relative to nitrate and urea, while nitrate supported the broadest thermal performance. Urea constrained thermal breadth regardless of concentration. These responses were linked to differential expression of Nitrogen assimilation genes. Ammonium suppressed nitrate transporter genes (NRT) and nitrite transporter (FNT), and drove pigment accumulation with rising temperature despite reduced growth, suggesting resource reallocation from growth to photoprotection. In contrast, nitrate upregulated photosystem and phosphorylation-related genes. Our findings demonstrate that Nitrogen source and concentration jointly determine the thermal threshold of C. cylindricum, with high ammonium reducing both maximum growth and the temperature at which it is achieved. This highlights how shifting coastal nutrient regimes may alter macroalgal resilience under ocean warming.

ecology↗

bioRxiv2026

A chromosome-scale Plasmodium cynomolgi Berok genome reveals a distinct subtelomeric architecture and a highly diverged primate malaria lineage

Plasmodium cynomolgi is the closest relative of P. vivax and the primary experimental model for relapsing malaria, hypnozoite biology, and blood-stage drug susceptibility. Yet existing reference genomes remain fragmented, leaving structurally complex, AT-rich regions largely unresolved. We generated a chromosome-scale genome assembly for the K4-A7 cloned line of P. cynomolgi Berok by combining Hi-C chromosome conformation capture, Oxford Nanopore long reads, PacBio, and Illumina sequencing. The assembly spans 14 chromosomes plus mitochondrial and apicoplast genomes, with only seven unplaced minor contigs, the fewest for any non-P. falciparum Plasmodium genome, and an N50 of 3.06 Mb. Critically, this hybrid strategy resolved approximately 8 Mb of extremely AT-rich (~20% GC) sequence onto chromosomes 4, 8, and 13, anchoring what were previously unplaced or absent contigs into a continuous chromosomal framework. These subtelomere-like expansions (SLEs) constitute ~26.5% of the chromosomal genome and are enriched for PIR/VIR, STP1, variable surface antigen, and methyltransferase pseudogene families. Despite low gene density, SLE-encoded genes are transcriptionally active and show stage-specific expression across the erythrocytic cycle. Integrated lifecycle transcriptomics across 7,006 genes revealed a ~54-hour erythrocytic cycle with a "just-in-time" transcriptional cascade closely resembling that of P. vivax. Phylogenomic analyses and pairwise amino acid comparisons across more than 2,600 single-copy orthologs show that Berok forms a deeply diverged P. cynomolgi lineage, suggesting a distinct subspecies. This assembly establishes a high-resolution genomic foundation for comparative malaria biology, drug discovery, and the study of subtelomeric architecture, host adaptation, and lineage boundaries in primate Plasmodium.

microbiology↗

bioRxiv2026

Mapping the global distribution and spread of the Plasmodium vivax-associated virus MaRNAV-1

Matryoshka RNA virus 1 is a bi-segmented and single-stranded RNA virus associated with Plasmodium vivax, a cause of human malaria. Little has been uncovered about the epidemiology and ecology of this virus since its discovery in 2019. To address this, we used a combination of primary and publicly available metatranscriptomic data to map the geographic distribution and host associations of MaRNAV-1. We detected this virus throughout Southeast Asia, in parts of South America, and, for the first time, in Oceania. Despite its broad distribution, MaRNAV-1 was found exclusively in metatranscriptomes containing P. vivax, suggesting that there is a specific virus-host relationship that has shaped the evolutionary history of this virus. We were unable to estimate the emergence date of the MaRNAV-1 lineage; however, phylogeographic mapping analysis suggested that MaRNAV-1 may have radiated from Southeast Asia. Our findings have both evolutionary and public health implications and can serve as the basis for future investigations in these fields.

evolutionary biology↗

bioRxiv2025

Desensitization of opsin responses during all-optical interrogation depends on imaging parameters

SignificanceThe combination of two-photon calcium imaging and two-photon optogenetic stimulation, termed all-optical interrogation, provides spatial and temporal precision when recording and manipulating neural circuit activity in vivo. All-optical experiments often use red-shifted opsins in combination with green fluorescent reporters of neuronal activity. However, their excitation spectra still partially overlap, meaning that the imaging laser can excite the opsin. Though some care has been taken in the past to understand the effects of this spectral overlap, further work is required to understand its impact on the findings of all-optical studies. AimWe aimed to investigate whether two-photon imaging of the green fluorescent calcium reporter GCaMP6s at 920 nm increases the rate of desensitization in neurons expressing the red-shifted opsin C1V1. ApproachWe systematically varied either the inter-stimulus interval or the duration of two-photon calcium imaging during two-photon optogenetic stimulation of mouse layer 2/3 barrel cortex or visual cortex neurons. ResultsWe found that two-photon imaging at 920 nm increases the desensitization of photostimulation responses across trials in C1V1-expressing neurons - an effect that is exacerbated at shorter inter-stimulus intervals. Reduced photostimulation responses are not limited to targeted cells, and are found across the entire field of view. Such network effects are less pronounced at shorter imaging doses. ConclusionsOur results provide methodological optimizations that enable opsin desensitization to be mitigated in all-optical experiments. This will reduce an external source of trial-by-trial variability in future all-optical experiments.

neuroscience↗

bioRxiv2025

Deep three-photon functional imaging in the mouse cortex with adaptive optics

Three-photon (3P) microscopy enables functional non-invasive single-cell resolution imaging at greater depths than any other technique. A key challenge of deep imaging is tissue-induced optical aberration, which reduces the excitation confinement. Adaptive optics use deformable mirrors to compensate for optical distortions, hence correcting these aberrations. Here, we present a practical adaptive optics-assisted 3P imaging system for functional imaging in the mouse brain during behavior. We introduce hierarchical corrections that sequentially target aberrations caused by the microscope system, the cranial window, and tissue depth. We demonstrate the utility of this strategy in the prelimbic cortex, where large vasculature near the midline causes aberrations, and in the lateral somatosensory cortex, where side access leads to distinct wavefront distortions. In both regions, adaptive optics significantly improved imaging performance, restoring cellular visibility near vasculature and enhancing signal-to-noise ratio. Our work provides a practical framework for utilizing adaptive optics to improve 3P imaging during behavior.

neuroscience↗

bioRxiv2024

First endangered black-footed ferrets, Mustela nigripes, cloned for genetic rescue

An endangered black-footed ferret female that died in 1988 with no living descendants in the current population was successfully cloned from cryopreserved cells using cross-species somatic cell nuclear transfer, producing three healthy kits. Incorporating progeny from these clones would provide an 8th founder to the breeding program and increase genetic variation to the species limited gene-pool. This marks the first time a native U.S. endangered species has been cloned.

zoology↗

bioRxiv2023

Endangered Przewalski's horse, Equus pzrewalskii, cloned from historically cryopreserved cells

Two endangered Przewalskis horse stallions were cloned from fibroblast cells cultured and cryopreserved in 1980. These stallions are clones of a male that lived from 1975-1998 that pedigree analyses identified as a genetically valuable male for present-day conservation breeding. This is the first time that multiple healthy clones have been produced for an endangered species.

zoology↗

bioRxiv2022

ASXL1 mutations that cause Bohring Opitz Syndrome (BOS) or acute myeloid leukemia share epigenomic and transcriptomic signatures

De novo, truncating variants of ASXL1 cause two distinct disorders: Bohring-Opitz Syndrome (BOS, OMIM #605039) a rare pediatric disorder characterized by multiorgan anomalies that disrupt normal brain, heart, and bone development causing severe intellectual disability or are somatic driver mutations causing acute myeloid leukemia(AML). Despite their distinct clinical presentations, we propose that ASXL1 mutations drive common epigenetic and transcriptomic dysregulation in BOS and AML. We analyzed DNA methylation (DNAm) and RNA-seq data from BOS patients (n=13) and controls (n=38) and publicly available DNAm of AML cases with (n=3) and without (n=3) ASXL1 mutations from The Cancer Genome Atlas (TCGA), and RNA-seq data from AML cases (n=27) from the Beat AML cohort. Using a DNA-methylation based episignature that we previously developed for BOS, we clustered AML, BOS and normal controls together. We showed that AML samples with ASXL1 mutations clustered closest to individuals with BOS, whereas individuals with AML without ASXL1 mutations clustered separately. We also observe common dysregulation of the transcriptome between BOS and AML with ASXL1 mutations compared to controls. Our transcriptomic analysis identified 821 significantly differentially expressed genes that were shared between both data sets and 74.9% showed differential expression in the same direction. BOS patients are rare and have some reports of tumors but no clear guidelines on cancer screening protocols. This represents the first direct comparison between distinct diseases that show common epigenetic and transcriptomic effects, and potentially common drug targets for patients harboring ASXL1 mutations on the epigenome and transcriptome. KEY POINTSO_LIAcute myeloid leukemias harboring somatic ASXL1 driver mutations and Bohring-Opitz syndrome caused by germline ASXL1 mutations share common epigenomic and transcriptomic dysregulation C_LIO_LIA gene-centric approach can inform molecular mechanisms across distinct disease types and point towards shared targetable pathways. C_LI

cancer biology↗

bioRxiv2022

Biomechanical Investigation of Ancient Maya Warfare at Mayapan, Yucatan, Mexico

Despite significant advancements in the reconstruction of activity patterns from skeletal remains and growing scholarly interest in ancient warfare, few biomechanical studies have investigated weaponry use. We adopt a biomechanical approach to investigate who participated in ancient Maya warfare and the types of weaponry used at the Late Postclassic (ca. 1200-1450 A.D.) regional political capital of Mayapan located in northwestern Yucatan, Mexico. This has implications for the nature and scale of Maya warfare and the size of territories that could be controlled by Maya polities. Comparative Finite Element Analysis is a powerful, non-destructive method that can be applied to skeletal remains to model strain, stress and deformation of structures in response to a defined loading regime. Here, biomechanical data extracted using cross-sectional geometry were combined with Finite Element Analysis models of three ancient Maya humeri from Mayapan: one elite male, one elite female, and one commoner female. Models were created with loading conditions of archery and spear use to assess evidence for skeletal adaptation to habitual weapon use. Following suggestions by some Mayanists that elite status males were the principal participants in warfare, we hypothesized that the elite male humerus would exhibit lower strains than the two female humeri in all the loading conditions. This was supported by the Finite Element model results, with the exception of spear throwing. The elite female humerus showed similar trends to the elite male humerus, suggesting the possibility of elite female participation in warfare.

paleontology↗

bioRxiv2022

MoveApps - a serverless no-code analysis platform for animal tracking data

BackgroundBio-logging and animal tracking datasets continuously grow in volume and complexity, documenting animal behaviour and ecology in unprecedented extent and detail, but greatly increasing the challenge of extracting knowledge from the data obtained. A large variety of analysis methods are being developed, many of which in effect are inaccessible to potential users, because they remain unpublished, depend on proprietary software or require significant coding skills. ResultsWe developed MoveApps, an open analysis platform for animal tracking data, to make sophisticated analytical tools accessible to a global community of movement ecologists and wildlife managers. As part of the Movebank ecosystem, MoveApps allows users to design and share workflows composed of analysis modules (Apps) that access and analyse tracking data. Users browse Apps, build workflows, customise parameters, execute analyses and access results through an intuitive web-based interface. Apps, coded in R or other programming languages, have been developed by the MoveApps team and can be contributed by anyone developing analysis code. They become available to all user of the platform. To allow long-term and cross-system reproducibility, Apps have public source code and are compiled and run in Docker containers that form the basis of a serverless cloud computing system. To support reproducible science and help contributors document and benefit from their efforts, workflows of Apps can be shared, published and archived with DOIs in the Movebank Data Repository. The platform was beta launched in spring 2021 and currently contains 44 Apps that are used by 156 registered users. We illustrate its use through two workflows that (1) provide a daily report on active tag deployments and (2) segment and map migratory movements. ConclusionsThe MoveApps platform is meant to empower the community to supply, exchange and use analysis code in an intuitive environment that allows fast and traceable results and feedback. By bringing together analytical experts developing movement analysis methods and code with those in need of tools to explore, answer questions and inform decisions based on data they collect, we intend to increase the pace of knowledge generation and integration to match the huge growth rate in bio-logging data acquisition.

ecology↗

bioRxiv2021

CRISPR-mediated insertion of a chimeric antigen receptor produces nonviral T cell products capable of inducing solid tumor regression

BackgroundChimeric antigen receptor (CAR) T cells traditionally harbor viral vector-based sequences that encode the CAR transgene in the genome. These T cell products have yet to show consistent anti-tumor activity in patients with solid tumors. Further, viral vector manufacturing is resource intensive, suffers from batch-to-batch variability, and includes several animal components, adding regulatory and supply chain pressures. MethodsAnti-GD2 CAR T cells were generated using CRISPR/Cas9 within nine days using recombinant Cas9 protein and nucleic acids, without any viral vectors or animal components. The CAR was specifically targeted to the T Cell Receptor Alpha Constant gene (TRAC). T cell products were characterized at the level of the genome, transcriptome, proteome, and secretome using CHANGE-seq, scRNA-seq, spectral cytometry, and ELISA assays. Functionality was evaluated in vivo in an NSG xenograft neuroblastoma model. ResultsIn comparison to traditional retroviral CAR T cells, virus-free CRISPR CAR (VFC-CAR) T cells exhibit TRAC-targeted genomic integration of the CAR transgene, elevation of transcriptional and protein characteristics associated with a memory phenotype, and low tonic signaling prior to infusion arising in part from the the knockout of the TCR. Upon exposure to the GD2 target antigen, anti-GD2 VFC-CAR T cells exhibited specific cytotoxicity against GD2+ cells in vitro and induced solid tumor regression in vivo, with robust homing, persistence, and low exhaustion against a human neuroblastoma xenograft model. ConclusionsThis proof-of-principle study leveraging virus-free genome editing technology could enable flexible manufacturing of clinically relevant, high-quality CAR T cells to treat cancers, including solid tumors.

bioengineering↗

bioRxiv2021

The heterogeneity of the DNA damage response landscape determines patient outcomes in ovarian cancer

Defective DNA damage response (DDR) pathways allow cancer cells to accrue genomic aberrations and evade normal cellular growth checkpoints. Defective DDR also determines response to chemotherapy. However, the interaction and overlap between the two double strand repair pathways and the three single strand repair pathways is complex, and has remained poorly understood. Here we show that, in ovarian cancer, a disease hallmarked by chromosomal instability, explant cultures show a range of DDR abrogation patterns. Defective homologous recombination (HR) and non-homologous end joining (NHEJ) are near mutually exclusive with HR deficient (HRD) cells showing increased abrogation of the single strand repair pathways compared to NHEJ defective cells. When combined with global markers of DNA damage, including mitochondrial membrane functionality and reactive oxygen species burden, the pattern of DDR abrogation allows the construction of DDR signatures which are predictive of both ex vivo cytotoxicity, and more importantly, patient outcome. SignificanceHolistic assessment of the DDR is possible, shows improved ability to predict response to chemotherapy over single pathway assessment, and is applicable to a variety of ovarian cancer types. Such an assessment has clinical utility in settings of therapeutic dilemma such as retreatment for relapse.

cell biology↗

bioRxiv2020

Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity

Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision-making. Drug-associated cues have long been known to facilitate habitual drug-seeking, and the salient audiovisual cues embedded within modern gambling products may like-wise encourage problem gambling. The dopamine neurons of the ventral tegmental area (VTA) are exquisitely sensitive to drugs of abuse, uncertain rewards, and reward-paired cues, and may therefore be the common neural substrate mediating synergistic features of both disorders. To test this hypothesis, we first gained specific inhibitory control over VTA dopamine neurons by transducing a floxed inhibitory DREADD (AAV5-hSyn-DIO-hM4D(Gi)-mCherry) in rats expressing Cre recombinase in tyrosine hydroxylase neurons. We then trained rats in our cued rat gambling task (crGT), inhibiting dopamine neurons throughout task acquisition and performance, before allowing them to self-administer cocaine in the same diurnal period as crGT sessions. The trajectories of addiction differ in women and men, and the dopamine system may differ functionally across the sexes, therefore we used male and female rats here. We found that inhibition of VTA dopamine neurons decreased cue-induced risky choice and reduced motor impulsivity in males, but surprisingly, enhanced risky decision making in females. Inhibiting VTA dopamine neurons also prevented cocaine-induced deficits in decision making in both sexes, but nevertheless drove all animals to consume more cocaine. These findings show that chronic dampening of dopamine signalling can have both protective and deleterious effects on addiction-relevant behaviours, depending on biological sex and dependent variable of interest.

animal behavior and cognition↗

bioRxiv2020

Antimicrobial silver inhibits bacterial movement and stalls flagellar motor

Silver (Ag) has been gaining broad attention due to their antimicrobial activities and the increasing resistance of bacteria to commonly prescribed antibiotics. However, various aspects of the antimicrobial mechanism of Ag have not been understood, including how silver affects the motility of bacteria, a factor that is intimately related to bacterial virulence. Here we report our study on the antibiotic effects of Ag+ ions on the motility of E. coli bacteria using swimming and tethering assays. We observed that the bacteria slowed down dramatically when subjected to Ag+ ions, providing direct evidence showing that Ag inhibits the motility of bacteria. In addition, through tethering assays, we monitored the rotation of flagellar motors and observed that the tumbling frequency of bacteria increased significantly in the presence of Ag+ ions. Furthermore, the rotation of bacteria in the tethering assays were analyzed using hidden Markov model (HMM); and we found that Ag+-treatment led to a significant decrease in the tumbling-to-running transition rate of the bacteria, suggesting that the rotation of bacterial flagellar motors was stalled by Ag+ ions. This work provided a new quantitative understanding on the mechanism of Ag-based antimicrobial agents in bacterial motility.

biophysics↗