Biology subjects

Davis, J. A.

Publications and source records attributed to Davis, J. A..

8 recordsLinked to original sources

bioRxiv2026

Microbial diversity and insights into feeding behavior of the two-spot cotton leaf hopper (Amrasca biguttula)

The recent invasion of the two-spot cotton leaf hopper (TSCL) (Amrasca biguttula) into the U.S. now threatens row and vegetable crops as well as ornamentals. TSCL ecology and biology, including microbial diversity, are understudied. Insect-specific microbes could influence host biology and ecology including insect-plant interactions. Here, microbiota (bacteria and viruses) within TSCL along with its feeding behavior were characterized using high throughput sequencing, microscopy, and Electrical penetration graph (EPG). Results revealed low diversity of bacteria dominated by Wolbachia and confirm the absence of obligate (primary) symbionts. Two distinct and differentially abundant Wolbachia strains (B-supergroup) were found co-infecting midgut tissues of 60% of TSCL tested, and the remaining 40% were free of symbionts. Virome analysis uncovered a diverse complex of at least eight dsDNA genomes (12-17 kb) of Adintoviruses (Eupolintoviridae), but no RNA viruses commonly found in other leafhoppers were identified in TSCL. The mesophyll feeding nature of TSCL was identified by observing chlorophyll derived autofluorescence in midguts and higher abundance of chloroplast transcripts (photosystem I, II, Rubisco, cytochrome b6 and ATP synthase complex) in TSCL (whole insects) compared with thrips and aphids. EPG recordings show a cell-rupture style of feeding with differences between adults and nymphs. Lastly, consistent with its cell-rupturing feeding style, no evidence for the presence of plant-pathogenic bacteria or viruses that could induce hopperburn was found. These results overall provide insights into the microbial diversity and feeding pattern of TSCL and lay a foundation for future research. Key messageThis work characterizes the TSCL microbiome and its mesophyll feeding pattern. Symbionts within insects often complement the nutritional deficiencies of its host and can aid insect spread by boosting immunity. The findings of this study lay the foundation for future research on the biology, ecology, and management of this invasive pest.

microbiology↗

bioRxiv2026

Polytraumatic SCI worsens maladaptive plasticity in spinal motor systems

Spinal cord injury (SCI) results in dysfunction of both motor and sensory systems, which can be characterized by neuropathic pain, hypersensitivity, muscular spasticity and rigidity. Most SCIs result from incidents such as vehicle accidents or falls, resulting in polytraumatic SCI that includes peripheral injuries in addition to direct CNS damage. Recent findings suggest that spinal cord synaptic plasticity plays a crucial role in neuropathic pain pathophysiology, specifically in association with spinal sensitization and the consequent onset of AMPA-related maladaptive plasticity. Further findings have demonstrated that nociceptive peripheral stimulation in the acute phase of SCI results in maladaptive spinal synaptic plasticity by overdriving GluA2-lacking calcium-permeable AMPARs (CP-AMPARs). Here, we investigated the effect of a spared nerve injury (SNI) in conjunction with SCI to determine the effect of polytraumatic SCI on maladaptive plasticity in the spinal cord. Near-IR quantitative Western blot analysis demonstrated that SCI+SNI increases spinal GluA1 expression, but not GluA2. Patch-clamp confirmed that AMPAR currents in spinal motorneurons increase after SCI with SNI, and decrease after the administration of NASPM, a CP-AMPAR antagonist. Data-driven analysis using non-linear principal components analysis (NL-PCA) also demonstrated that SCI with SNI produces a multivariate signature of AMPAR plasticity that is observed in other forms of nociceptive peripheral input, indicating a general mechanism for maladaptive plasticity in spinal motor systems in response to polytraumatic SCI.

neuroscience↗

bioRxiv2023

Quality Control for Single Cell Analysis of High-plex Tissue Profiles using CyLinter

Tumors are complex assemblies of cellular and acellular structures patterned on spatial scales from microns to centimeters. Study of these assemblies has advanced dramatically with the introduction of high-plex spatial profiling. Image-based profiling methods reveal the intensities and spatial distributions of 20-100 proteins at subcellular resolution in 103-107 cells per specimen. Despite extensive work on methods for extracting single-cell data from these images, all tissue images contain artefacts such as folds, debris, antibody aggregates, optical aberrations and image processing errors that arise from imperfections in specimen preparation, data acquisition, image assembly, and feature extraction. We show that these artefacts dramatically impact single-cell data analysis, obscuring meaningful biological interpretation. We describe an interactive quality control software tool, CyLinter, that identifies and removes data associated with imaging artefacts. CyLinter greatly improves single-cell analysis, especially for archival specimens sectioned many years prior to data collection, such as those from clinical trials.

pathology↗

bioRxiv2023

BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or Menin inhibitor

BRG1 (SMARCA4) and BRM (SMARCA2) are the core ATPases of chromatin remodeling BAF (BRG1/BRM-associated factor) complexes, which enable transcription factors/co-factors to modulate gene-expressions, mediating growth, differentiation-arrest and survival of AML cells. In AML with MLL1r (MLL1 rearrangement) or mutant (mt) NPM1, although monotherapy with Menin inhibitor (MI) induces clinical remissions, most patients either fail to respond or relapse. FHD-286 is a selective BRG1/BRM inhibitor, undergoing clinical development in AML. Here, FHD-286 induced differentiation and lethality in AML cells with MLL1r or mtNPM1, reducing chromatin accessibility and repressing c-Myc, PU.1 and CDK4/6. Whereas FHD-286 monotherapy reduced AML burden, leukemia-initiating potential and improved survival, FHD-286 combinations with MI, BET inhibitor, decitabine or venetoclax was significantly more effective in reducing AML burden and improved survival, without significant toxicity, in xenograft models of AML with MLL1r or mtNPM1. These findings highlight promising FHD-286-based combinations for therapy of AML with MLL1r or mtNPM1. Statement of SignificanceInhibition of BRG1/BRM ATPases by FHD-286 reduced chromatin accessibility, repressed c-Myc, PU.1 and CDK4/6, inducing differentiation, leukemia-initiating potential and lethality in AML stem-progenitor cells. FHD-286-based combinations with Menin or BET inhibitor or decitabine reduced AML burden and improved survival in xenograft models of AML with MLL rearrangement or mutant NPM1.

cancer biology↗

bioRxiv2023

Improving rigor and reproducibility in western blot experiments with the blotRig analysis software

Western blot is a popular biomolecular analysis method for measuring the relative quantities of independent proteins in complex biological samples. However, variability in quantitative western blot data analysis poses a challenge in designing reproducible experiments. The lack of rigorous quantitative approaches in current western blot statistical methodology may result in irreproducible inferences. Here we describe best practices for the design and analysis of western blot experiments, with examples and demonstrations of how different analytical approaches can lead to widely varying outcomes. To facilitate best practices, we have developed the blotRig tool for designing and analyzing western blot experiments to improve their rigor and reproducibility. The blotRig application includes functions for counterbalancing experimental design by lane position, batch management across gels, and analytics with covariates and random effects.

neuroscience↗

bioRxiv2022

Proteomic Analysis Defines the Interactome of Telomerase in the Protozoan Parasite, Trypanosoma brucei

Telomerase is a ribonucleoprotein enzyme responsible for maintaining the telomeric end of the chromosome. The telomerase enzyme requires two main components to function: the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR), which provides the template for telomeric DNA synthesis. TR is a long noncoding RNA, which forms the basis of a large structural scaffold upon which many accessory proteins can bind and form the complete telomerase holoenzyme. These accessory protein interactions are required for telomerase activity and regulation inside cells. The interacting partners of TERT have been well studied in yeast, human, and Tetrahymena models, but not in lower eukaryotes, including clinically relevant human parasites. Here, using the protozoan parasite, Trypanosoma brucei (T. brucei) as a model, we have identified the interactome of T. brucei TERT (TbTERT) using a mass spectrometry-based approach. We identified previously known and unknown interacting factors of TbTERT, highlighting unique features of T. brucei telomerase biology. These unique interactions with TbTERT, suggest mechanistic differences in telomere maintenance between T. brucei and other eukaryotes.

molecular biology↗

bioRxiv2021

Increasing seed thiamin content impacts stored carbon partitioning and subsequent seedling stress tolerance

Thiamin and thiamin pyrophosphate (TPP) are essential components for the function of enzymes involved in the metabolism of carbohydrates and amino acids in living organisms. In addition to its role as a cofactor, thiamin plays a key role in resistance against biotic and abiotic stresses in plants. Most of the studies used exogenous thiamin to enhance stress tolerance in plants. In this study, we achieved this objective by genetically engineering Arabidopsis thaliana and Camelina sativa for the seed-specific co-overexpression of the Arabidopsis thiamin biosynthetic genes Thi4, ThiC, and ThiE. Elevated thiamin content in the seeds of transgenic plants was accompanied by the enhanced expression levels of transcripts encoding thiamin cofactor-dependent enzymes. Furthermore, seed germination and root growth in thiamin over-producing lines were more tolerant to oxidative stress caused by salt and paraquat treatments. The transgenic seeds also accumulated more oil (up to16.4% in Arabidopsis and17.9% in C. sativa) and carbohydrate but less protein than the control seeds. The same results were also observed in TPP over-producing Arabidopsis plants generated by the seed-specific overexpression of TPK1. Together, our findings suggest that thiamin and TPP over-production in transgenic lines confer a boosted abiotic stress tolerance and alter the seed carbon partitioning as well.

bioengineering↗

bioRxiv2021

Impaired clock gene expression and abnormal diurnal regulation of hippocampal inhibitory transmission and spatial memory in a mouse model of Alzheimers disease

Patients with Alzheimers disease (AD) often have fragmentation of sleep/wake cycles and disrupted 24-h (circadian) activity. Despite this, little work has investigated the potential underlying day/night disruptions in cognition and neuronal physiology in the hippocampus. The molecular clock, an intrinsic transcription-translation feedback loop that regulates circadian behavior, may also regulate hippocampal neurophysiological activity. We hypothesized that disrupted diurnal variation in clock gene expression in the hippocampus corresponds with loss of normal day/night differences in membrane excitability, synaptic physiology, and cognition. We previously reported that the Tg-SwDI mouse model of AD has disrupted circadian locomotor rhythms and neurophysiological output of the suprachiasmatic nucleus (the primary circadian clock). Here, we report that Tg-SwDI mice failed to show day-night differences in a spatial working memory task, unlike wild-type controls that exhibited enhanced spatial working memory at night. Moreover, Tg-SwDI mice had lower levels of Per2, one of the core components of the molecular clock, at both mRNA and protein levels when compared to age-matched controls. Interestingly, we discovered neurophysiological impairments in area CA1 of the Tg-SwDI hippocampus. In controls, spontaneous inhibitory post-synaptic currents (sIPSCs) in pyramidal cells showed greater amplitude and lower inter-event interval during the day than the night. However, the normal day/night differences in sIPSCs were absent (amplitude) or reversed (inter-event interval) in pyramidal cells from Tg-SwDI mice. In control mice, current injection into CA1 pyramidal cells produced more firing during the night than during the day, but no day/night difference in excitability was observed in Tg-SwDI mice. The normal day/night difference in excitability in controls was blocked by GABA receptor inhibition. Together, these results demonstrate that the normal diurnal regulation of inhibitory transmission in the hippocampus is diminished in a mouse model of AD, leading to decreased daytime inhibition onto hippocampal CA1 pyramidal cells. Uncovering disrupted day/night differences in circadian gene regulation, hippocampal physiology, and memory in AD mouse models may provide insight into possible chronotherapeutic strategies to ameliorate Alzheimers disease symptoms or delay pathological onset.

neuroscience↗