Biology subjects

Baxter, B.

Publications and source records attributed to Baxter, B..

11 recordsLinked to original sources

bioRxiv2026

Salinity is associated with habitat use and mitochondrial lineage diversity in halophilic Ephydra flies (Diptera: Ephydridae)

Brine flies of the genus Ephydra (Diptera: Ephydridae) are ubiquitous extremophile animals whose larval forms are able to thrive in high-stress environments, including hypersaline and high carbonate waters. Despite their historical and ecological importance, little is known about their evolutionary history. Here, we focus on an understudied population of Ephydra living in former industrial salt evaporation ponds of the San Francisco Bay Area (SFBA), a region which has undergone significant environmental changes in the past century. We observed and collected Ephydra specimens and took salinity measurements of waters they inhabited during a 6-month period in 2024. We found that E. millbrae and E. gracilis demonstrate strong salinity preferences. We also analyzed DNA from Ephydra spp. specimens from distant sites and a timespan of ~40 years, generating the most comprehensive gene genealogy of the group to date based on a single mitochondrial locus. Our analysis of phylogenetic signals suggests that salinity envelopes are influenced by evolutionary relationships in Ephydra. This study provides new information about the natural history of extremophile flies in the SFBA and fills in current gaps in our knowledge about the evolutionary history of the genus more broadly.

evolutionary biology↗

bioRxiv2026

Study of microbe-microbe interactions between the sexually transmitted parasite Trichomonas vaginalis with the cervicovaginal bacteria Lactobacillus iners

Trichomonas vaginalis is the leading cause of non-viral sexually transmitted infections and it is associated with comorbidities that affect female health. Lactobacillus iners is one of the most predominant bacteria in the cervicovaginal microbiome. As so, both microbes are likely to encounter one another upon T. vaginalis infection. To our knowledge, the interaction of both microbes has not been previously investigated. Here, we report that T. vaginalis and L. iners bind to one another at early time points of co-incubation. Using imaging flow cytometry and scanning electron microscopy, we capture the dynamics of this microbe-microbe association. We observed active remodeling of the T. vaginalis cell surface leading to thin-membrane protrusions that make contact with L. iners. Larger T. vaginalis membrane extensions that surround and engulf L. iners were also visible. These T. vaginalis-L. iners interactions ultimately lead to a reduction of L. iners viability while T. vaginalis viability was unaffected by exposure to L. iners. Inhibition of actin polymerization blocked T. vaginalis antibacterial activity against L. iners. Together our findings reveal novel insight about T. vaginalis-L. iners interactions and highlight a new T. vaginalis pathogenic effect.

microbiology↗

bioRxiv2026

Two Novel Genes, Stb23 and Stb24, Conferring Multi-stage Resistance to Zymoseptoria tritici: Rapid Deployment in Marker-Assisted Wheat Breeding

The fungal pathogen Zymoseptoria tritici poses a major global threat to wheat production, causing severe yield losses and necessitating intensive and costly fungicide applications. The increasing demand for durable genetic resistance has intensified interest in quantitative resistance loci, particularly those exhibiting multi-stage resistance (MSR), which suppress pathogen development continuously throughout the wheat life cycle. Many previously effective resistance genes are now showing declining efficacy, underscoring the urgent need for novel and long-lasting sources of resistance. In this study, we report the identification and genetic mapping of two quantitative resistance loci that address this need. The first locus, designated Stb23, is a major QTL on chromosome 1DS, with LOD scores exceeding 9 and explaining 6-36% of phenotypic variation at the seedling stage and 2-16% at the adult-plant stage. The second locus, designated Stb24, is a major QTL on chromosome 3DL, with LOD scores of approximately 10 and accounting for 11-30% of seedling-stage variation and 9-23% of adult-plant variation. Furthermore, two tightly linked KASP markers-snp_1D1217527 for Stb23 and snp_3D1077880 for Stb24-were developed and validated across three popular Australian bread wheat cultivars, providing practical tools for deploying these loci in breeding programs targeting improved resistance to Z. tritici. Key messageTwo significant major-effect resistance loci on chromosomes 1DS (proposed as Stb23) and 3DL (proposed as Stb24) were identified and characterized. Two tightly linked KASP markers with these loci were also discovered and validated for molecular-assisted breeding programs.

genetics↗

bioRxiv2025

Microbial community dynamics during historic drought and flood in the Great Salt Lake

Understanding human-driven environmental impacts on microbial community distribution, abundance, and function remains a central challenge in microbial ecology. In particular, the drivers of temporal succession in community membership following perturbation remain unclear. The Great Salt Lake, Utah, bears clear hallmarks of human disturbance, including a rock-filled railroad causeway that sequestered its northern arm from freshwater river influx, leading to localized hypersalination and food web collapse. Following decades of riverine water diversion, the southern arm of this terminal lake reached a historic low elevation during a time of increased climatic change, placing strong environmental pressure on the robust saline ecosystem. Here we use molecular methods to report microbial community composition during this severe drought year at sites across the lake, including where the north and south arm waters contact. At sites of hypersaline water intrusion, we observe surprising stability in north arm community composition, in contrast with strong perturbation in south arm community structure. We use hydrodynamic modeling to pinpoint physical water flow dynamics as a key driver of these community shifts. At saturated salinity north arm sites away from hyposaline water intrusion, abundance shifts were detected in predatory and parasitic taxa, a discovery that reveals surprising ecological dynamics in saturated hypersaline systems. In sum, this study demonstrates drastic hypersaline microbial community shifts during salinity and extreme weather perturbations.

ecology↗

bioRxiv2025

Quantitative Membrane Binding Assays Reveal an Inhibitory Role for the BRAF-Specific Region in CRD and Lipid Interaction

BRAF is a serine/threonine kinase and a central effector of the mitogen-activated protein kinase (MAPK) signaling pathway, frequently mutated in cancer. Its activation is tightly controlled by autoinhibitory mechanisms that regulate membrane recruitment and dimerization. The BRAF-specific region (BSR), located at the N-terminus, is known to promote isoform-preferred RAS binding and facilitate dimerization with kinase suppressor of RAS (KSR), yet its role in regulating lipid interaction has remained unexplored. Here, we identify the BSR as a previously unrecognized inhibitory module that attenuates lipid binding by the cysteine-rich domain (CRD). Using quantitative in vitro reconstitution with supported lipid bilayers and fluorescence microscopy, we demonstrate that the BRAF CRD exhibits high intrinsic affinity for phosphatidylserine-rich membranes, but the inclusion of the BSR markedly reduces the membrane binding. We further demonstrate that the inhibitory function of the BSR correlates with its global electrostatic properties rather than a single defined sequence motif. This inhibitory effect of BSR was corroborated in live cells by quantifying plasma membrane localization of BRAF constructs, including the full-length protein. When canonical autoinhibition of CRD--mediated by sequestration within the 14-3-3 dimer--is disrupted by oncogenic mutation or RAF inhibitor treatment, the BSR assumes a compensatory role in repressing CRD-lipid interaction. This additional regulatory layer provided by the BSR prevents RAS-independent membrane recruitment under both physiological and pathological conditions. Broad Impact StatementProtein-lipid interactions are a fundamental mechanism for regulating the localization and activity of signaling proteins. This study reveals that the N-terminal segment of BRAF acts as an inhibitory module that suppresses lipid engagement by CRD, particularly when canonical autoinhibition is disrupted by oncogenic mutation or inhibitor treatment. This additional layer of regulation provides new insight into BRAF membrane dynamics and may have implications in therapeutic intervention of dysregulated BRAF signaling.

biochemistry↗

bioRxiv2024

Hippocampal ripples mediate motor learning during brief rest breaks in humans

Critical aspects of motor learning and memory happen offline, during both wake and sleep. When healthy young people learn a motor sequence task, most of their performance improvement happens not while typing, but offline, during interleaved rest breaks. In contrast, the performance of patients with dense amnesia due to hippocampal damage actually gets worse over the rest breaks and improves while typing. These findings indicate that an intact hippocampus is necessary for offline motor learning during wake, but do not specify its mechanism. Here, we studied epilepsy patients (n=17) undergoing direct intracranial EEG monitoring of the hippocampus as they learned the same motor sequence task. Like healthy young people, they showed greater speed gains across rest breaks than while typing. They also showed higher hippocampal ripple rates during these rest breaks that predicted offline gains in speed. This suggests that motor learning during brief rest breaks during wake is mediated by hippocampal ripples. These results expand our understanding of the role of hippocampal ripples beyond declarative memory to include enhancing motor procedural memory. Significance StatementIn patients with epilepsy undergoing direct intracranial EEG monitoring of the hippocampus, we found a higher rate of ripples during the brief rest breaks of a motor sequence task than during task execution. These offline hippocampal ripples predicted the amount of performance improvement over the break. We conclude that the hippocampus contributes to motor learning during brief rest breaks, and propose that this offline learning is mediated by ripples.

neuroscience↗

bioRxiv2023

Human thalamic recordings reveal that epileptic spikes block sleep spindle production during non-rapid eye movement sleep

In severe epileptic encephalopathies, epileptic activity contributes to progressive cognitive dysfunction. Several epileptic encephalopathies share the trait of spike-wave activation during non-rapid eye movement sleep (EE-SWAS), a state dominated by sleep oscillations known to coordinate offline memory consolidation. How epileptic activity impacts these thalamocortical sleep oscillations has not been directly observed in humans. Using a unique dataset of simultaneous human thalamic and cortical recordings in subjects with and without EE-SWAS, we reconcile prior conflicting observations about how epileptic spikes coordinate with sleep oscillations and provide direct evidence for epileptic spike interference of sleep spindle production. We find that slow oscillations facilitate both epileptic spikes and sleep spindles during stage 2 sleep (N2) at different phases of the slow oscillation. We show that sleep activated cortical epileptic spikes propagate to the thalamus (thalamic spike rate is increased after a cortical spike, p[~]0). Thalamic spikes increase the spindle refractory period (p<1.5e-21). In patients with EE-SWAS, the abundance of thalamic spikes result in downregulation of spindles for 30 seconds after each thalamic spike (p=3.4e-11) and decreased overall spindle rate across N2 (p=2e-7). These direct human thalamocortical observations identify a novel mechanism through which epileptiform spikes could impact cognitive function, wherein sleep-activated epileptic spikes inhibit thalamic sleep spindles in epileptic encephalopathy.

neuroscience↗

bioRxiv2022

Improved breeding for Fusarium pseudograminarium (Fusarium crown rot) using qPCR measurement of infection in multi-species winter cereal experiments

Fusarium crown rot (FCR) causes significant grain yield loss in winter cereals around the world. Breeding for resistance and/or tolerance to FCR has been slow with relatively limited success. In this study, multi-species experiments were used to demonstrate an improved method to quantify FCR infection levels at plant maturity using qPCR, as well as the genotype yield retention using residual regression deviation. Using qPCR to measure FCR infection allowed a higher degree of resolution between genotypes than traditional visual stem basal browning assessments. The results were consistent across three environments with different levels of disease expression. The improved measure of FCR infection along with genotype yield retention allows for partitioning of both tolerance and partial resistance. Together these methods offer new insights to FCR partial resistance and its relative importance to tolerance in bread wheat and barley. This new approach offers a more robust, cost-effective way to select for both FCR traits within breeding programs. Key messageGenetic gain for tolerance and partial resistance against Fusarium crown rot (FCR) in winter cereals has been impeded by laborious and variable visual measures of infection severity. This paper presents results of an improved method to quantify FCR infection that are strongly correlated to yield loss and reveal previously unrecognised partial resistance in barley and wheat varieties.

pathology↗

bioRxiv2022

Multi-stage resistance to Zymoseptoria tritici revealed by GWAS in an Australian bread wheat (Triticum aestivum L.) diversity panel

Septoria tritici blotch (STB) has been ranked the third most important wheat disease in the world, threatening a large area of wheat production. Although major genes play an important role in the protection against Zymoseptoria tritici infection, the lifespan of their resistance unfortunately is very short in modern agriculture systems. Combinations of quantitative resistance with minor effects, therefore, are believed to have prolonged and more durable resistance to Z. tritici. In this study new quantitative trait loci (QTLs) were identified that are responsible for seedling-stage resistance and adult-plant stage resistance (APR). More importantly was the characterisation of a previously unidentified QTL that can provide resistance during different stages of plant growth or multi-stage resistance (MSR). At the seedling stage, we discovered a new isolate-specific QTL, QSt.wai.1A.1. At the adult-plant stage, the new QTL QStb.wai.6A.2 provided stable and consistent APR in multiple sites and years, while the QTL QStb.wai.7A.2 was highlighted to have MSR. The stacking of multiple favourable MSR alleles was found to improve resistance to Z. tritici by up to 40%. Key messageAn Australian GWAS panel discovered three new QTLs associated with seedling-stage resistance, adult-plant stage resistance, and multi-stage resistance, respectively.

genetics↗

bioRxiv2019

High accuracy DNA sequencing on a small, scalable platform via electrical detection of single base incorporations

High throughput DNA sequencing technologies have undergone tremendous development over the past decade. Although optical detection-based sequencing has constituted the majority of data output, it requires a large capital investment and aggregation of samples to achieve optimal cost per sample. We have developed a novel electronic detection-based platform capable of accurately detecting single base incorporations. The GenapSys technology with its electronic detection modality allows the system to be compact, accessible, and affordable. We demonstrate the performance of the system by sequencing several different microbial genomes with varying GC content. The platform is capable of generating up to 2 Gb of high-quality nucleic acid sequence in a single run. We routinely generate sequence data that exceeds 99% raw accuracy with read lengths of up to 175 bp. Average quality scores remain above Q30 (99.9% raw sequencing accuracy) beyond 150 bp, with more than 85% of total bases at or above Q30. The utility of the platform is highlighted by targeted sequencing of the human genome. We show high concordance of SNP detection on the human NA12878 HapMap cell line with data generated on the Illumina sequencing platform. In addition, we sequenced a targeted panel of cancer-associated genes in a well characterized reference standard. With multiple library preparation approaches on this sample, we were able to identify low frequency mutations at expected allele frequencies.

genomics↗

bioRxiv2018

Discovering novel calcineurin inhibitors through quantitative mapping of protein-peptide affinity landscapes

Transient, regulated binding of globular protein domains to Short Linear Motifs (SLiMs) in disordered regions of other proteins drives cellular signaling. Mapping the energy landscapes of these interactions is essential for deciphering and therapeutically perturbing signaling networks, but is challenging due to their weak affinities. We present a powerful technology, MRBLE-pep, that simultaneously quantifies protein binding to a library of peptides directly synthesized on beads containing unique spectral codes. Using computational modeling and MRBLE-pep, we systematically probe binding of calcineurin (CN), a conserved protein phosphatase essential for the immune response and target of immunosuppressants, to the PxIxIT SLiM. We establish that flanking residues and post- translational modifications critically contribute to PxIxIT-CN affinity, and discover CN-inhibitory peptides with unprecedented affinity and therapeutic potential. The quantitative measurements provided by this approach will improve computational modeling efforts, elucidate a broad range of weak protein-SLiM interactions, and revolutionize our understanding of signaling networks.

bioengineering↗