Biology subjects

Andrews, P.

Publications and source records attributed to Andrews, P..

11 recordsLinked to original sources

bioRxiv2025

Both conventionally and organically fertilized tomatoes maintain fruit quality through uncontrolled green peach aphid infestation, with a transcriptional shift towards catabolism

Aphids are a major pest of greenhouse-grown temperate crops, responsible for billions in crop damage yearly. As organic agriculture rapidly grows in popularity, understanding how plants grown under organic systems respond to insect pest pressure may give insights into better management practices and information about the genes of interest for crop improvement. We measured the response of tomato (Solanum lycopersicum) leaf and fruit transcriptome, as well as a few selected metabolites in the mature fruit, to an infestation of the generalist green peach aphid (Myzus persicae). The aphids were introduced approximately halfway through the lifecycle of the plants that were grown under conventional and organic fertilizer regimes. While plants provided with conventional fertilizer experienced greater aphid infestation, neither group suffered a significant loss in total yield or fruit quality. This result is likely a consequence of ample nutrient and water availability. Co-expression network analysis using WGCNA revealed that in leaf tissue, both treatment groups showed a general shift from diverse anabolic processes to catabolism, while fruit tissue experienced relatively minor changes. At the stage of infestation investigated, abscisic acid appeared to be the main phytohormone response. One coexpression network module showed a correlation with both organic fertilizer treatment and aphid infestation; its hub gene (Solyc02g078940.3) may be of interest in exploring unique responses to phloem feeding insect infestation under an organic production regime.

plant biology↗

bioRxiv2023

High-throughput single-nucleus hybrid sequencing reveals genome-transcriptome correlations in cancer

To deepen our understanding of cancer heterogeneity and uncover the dynamic interactions of tumor and host cells, we introduce hybrid BAG-seq: a high-throughput, multi-omic method that simultaneously captures DNA and RNA from tens of thousands of individual single nuclei. This method provides dual molecular layer information: DNA to distinguish tumor from stroma, identify tumor subclones, and detect mutant stromal sub-populations; and RNA to characterize distinct cell types, cell states, and signatures of aberrant expression. Additionally, we developed a suite of analysis tools to illuminate cluster phylogeny and connections between DNA identity and RNA expression. We applied this hybrid protocol to 65,499 single nuclei from samples of five uterine cancer patients, and validated the clustering using RNA-only and DNA-only protocols on 34,651 and 21,432 nuclei, respectively, from the same tissues. Multiple tumor genome or expression clusters were often present within a patient, with different tumor clones projecting into distinct or shared expression states, demonstrating nearly all possible genome-transcriptome correlations across the cohort. While tumor expression profiles were highly unique to each patient, the stromal cell types generally recurred across samples, but certain patients and tissues exhibited unique stromal sub-types characterized by aberrant expression. Moreover, we identified mutant stroma in various cell types from several patients with a significant loss of the X-chromosome. This study reveals the complex landscape of genome and transcriptome interactions at the resolution of single nuclei, providing new insights into mutant stroma and tumor heterogeneity.

genomics↗

bioRxiv2021

GABAergic neuronal IL-4R mediates T cell effect on memory

Mechanisms governing how immune cells and their derived molecules impact homeostatic brain function are still poorly understood. Here, we elucidate neuronal mechanisms underlying effects of T cells on synaptic function and episodic memory. Depletion of CD4 T cells led to memory deficits and impaired long term potentiation. Severe combined immune-deficient (SCID) mice exhibited amnesia, which was reversible by repopulation with T cells from wild-type but not from IL-4-knockout mice. This rescue was mediated via IL-4 receptors (IL-4R) expressed on neurons. Exploration of snRNAseq of neurons participating in memory processing provided insights into synaptic organization and plasticity-associated pathways and genes regulated by immune cells and molecules. IL-4R knockout in inhibitory neurons impaired contextual fear memory, suggesting participation of an IL-4-associated switch in regulating synaptic function and promoting contextual fear memory. These findings provide insights into neuroimmune interactions at the transcriptional and functional levels in neurons.

neuroscience↗

bioRxiv2020

The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure.

The Origin Recognition Complex (ORC) cooperates with CDC6, MCM2-7, and CDT1 to form pre- RC complexes at origins of DNA replication. Here we report tiling-sgRNA CRISPR screens that show that each subunit of ORC and CDC6 are essential in human cells. Using an auxin-inducible degradation system, stable cell lines were created that ablate ORC2 rapidly, revealing multiple cell division cycle phenotypes. The primary defect in the absence of ORC2 was cells encountering difficulty in initiating DNA replication or progressing through the cell division cycle due to reduced MCM2-7 loading onto chromatin in G1 phase. The nuclei of ORC2 deficient cells were also large, with decompacted heterochromatin. Some ORC2 deficient cells that completed DNA replication entered into, but never exited mitosis. ORC1 knockout cells also demonstrated extremely slow cell proliferation and abnormal cell and nuclear morphology. Thus, ORC proteins and CDC6 are indispensable for normal cellular proliferation and contribute to nuclear organization.

molecular biology↗

bioRxiv2019

A phenotypic screening platform utilising human spermatozoa identifies new compounds with contraceptive activity

There is an urgent need to develop new methods for male contraception, however a major barrier to drug discovery has been the lack of validated targets and the absence of an effective high-throughput phenotypic screening system. To address this deficit, we developed a fully-automated robotic screening platform that provided quantitative evaluation of compound activity against two key attributes of human sperm function: motility and acrosome reaction. In order to accelerate contraceptive development, we screened the comprehensive collection of 12,000 molecules that make up the ReFRAME repurposing library, comprising nearly all the small molecules that have been approved or have undergone clinical development, or have significant preclinical profiling. We identified several compounds that potently inhibit motility representing either novel drug candidates or routes to target identification. This platform will now allow for major drug discovery programmes that address the critical gap in the contraceptive portfolio as well as uncover novel human sperm biology.

developmental biology↗

bioRxiv2019

Concomitant phytonutrient and transcriptome analysis of mature fruit and leaf tissues of tomato (Solanum lycopersicum L. cv. Oregon Spring) grown using organic and conventional fertilizer

Enhanced levels of antioxidants, phenolic compounds, carotenoids and vitamin C have been reported for several crops grown under organic fertilizer, albeit with yield penalties. As organic agricultural practices continue to grow and find favor it is critical to gain an understanding of the molecular underpinnings of the factors that limit the yields in organically farmed crops. Concomitant phytochemical and transcriptomic analysis was performed on mature fruit and leaf tissues derived from Solanum lycopersicum L. Oregon Spring grown under organic and conventional fertilizer conditions to evaluate the following hypotheses. 1. Organic soil fertilizer management results in greater allocation of photosynthetically derived resources to the synthesis of secondary metabolites than to plant growth, and 2. Genes involved in changes in the accumulation of phytonutrients under organic fertilizer regime will exhibit differential expression, and that the growth under different fertilizer treatments will elicit a differential response from the tomato genome. Both these hypotheses were supported, suggesting an adjustment of the metabolic and genomic activity of the plant in response to different fertilizers. Organic fertilizer treatment showed an activation of photoinhibitory processes through differential activation of nitrogen transport and assimilation genes resulting in higher accumulation of phytonutrients. This information can be used to identify alleles for breeding crops that allow for efficient utilization of organic inputs.\n\nSignificance statementOrganic fertilizer changes the expression of the tomato genome, induces photosynthetic stress which elicits higher production of secondary metabolites.

plant biology↗

bioRxiv2019

Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties

Transplantation of Olfactory Ensheathing Cells (OECs) is a potential therapy for the regeneration of damaged neurons. While they maintain tissue homeostasis in the olfactory mucosa (OM) and olfactory bulb (OB), their regenerative properties also support the normal sense of smell by enabling continual turnover and axonal regrowth of olfactory sensory neurons (OSNs). However, the molecular physiology of OECs is not fully understood, especially that of OECs from the mucosa. Here, we carried out whole-cell patch clamp recordings from individual OECs cultured from the OM and OB of the adult rat, and from the human OM. A subset of OECs from the rat OM cultured 1-3 days in vitro (DIV) had large weakly rectifying K+ currents, which were sensitive to Ba2+ and desipramine, blockers of Kir4-family channels. Kir4.1 immunofluorescence was detectable in OM cells co-labelled for the OEC marker S100, and found adjacent to axons of OSNs. OECs cultured from rat OB had distinct properties though, displaying strongly rectifying inward currents at hyperpolarized membrane potentials and strongly rectifying outward currents at depolarized potentials. Kir4.1 immunofluorescence was not evident in OECs adjacent to axons of OSNs in the OB. A subset of human OECs cultured from the OM of adults had membrane properties comparable to those of the rat OM, i.e. dominated by Ba2+-sensitive weak inwardly rectifying currents. The membrane properties of peripheral OECs are different to those in central OECs, suggesting they may play distinct roles during olfaction.\n\nTable of Contents Image\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC=\"FIGDIR/small/640839v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (39K):\norg.highwire.dtl.DTLVardef@7bc4edorg.highwire.dtl.DTLVardef@1bdc7c1org.highwire.dtl.DTLVardef@85851corg.highwire.dtl.DTLVardef@1e620b8_HPS_FORMAT_FIGEXP M_FIG C_FIG Main pointsO_LIPeripheral and central OECs are functionally distinct\nC_LIO_LIPeripheral OECs have large weak inward rectifier currents\nC_LIO_LICentral OECs have strong inward and outward rectifier currents\nC_LI

physiology↗

bioRxiv2019

Assessing nasal obstruction with the nasal acoustic device: a pilot study on distinguishing between subjects with and without chronic rhinosinusitis

This article aims to demonstrate the concept and potential of a novel diagnostic device - the nasal acoustic device (NAD), which captures the nasal breathing sounds over the ala on both sides of the nose. Using the newly defined inspiratory nasal acoustic score (INA score), the unique characteristics of the nasal breathing sounds can be quantified and used for diagnostic purposes.\n\nIn this pilot study, the NAD was compared with the well-established nasal inspiratory peak flow meter (NIPF) to try to distinguish between subjects with and without chronic rhinosinusitis (CRS). Measurements were made before and after nasal decongestants, which were applied to eliminate the nasal cycle. Patients were divided into two groups based on the presence or absence of CRS, irrespective of other pathological conditions being present.\n\nBased on the post-decongestant measurements, the sensitivity/specificity in distinguishing subjects who have CRS (n=11) from subjects who do not (n=29; of whom 13 were controls) were 70%/66% for the NIPF and 82%/79% for the NAD. The non-CRS groups showed statistically significant changes after decongestant for both methods, but the CRS group did not. The results firstly demonstrated that the CRS subjects in this cohort tended to be less responsive to decongestant and therefore the post-decongestant NIPF measurements provided a certain degree of diagnostic value in identifying CRS subjects, but it would appear the NAD better captured the unique sounds associated with CRS, providing a superior diagnostic capability. This study also demonstrates that the NAD can measure the improvement in the nasal airway following treatment effect.

bioengineering↗

bioRxiv2019

Single chromosome gains can function as metastasis suppressors and metastasis promoters

Most human tumors display chromosome-scale copy number alterations, and high levels of aneuploidy are frequently associated with advanced disease and poor patient prognosis. To examine the relationship between aneuploidy and cancer progression, we generated and analyzed a series of congenic human cell lines that harbor single extra chromosomes. We find that different aneuploidies can have distinct effects on invasive behavior: across 13 different cell lines, 12 trisomies suppressed invasiveness or were largely neutral, while a single trisomy increased metastatic behavior by triggering a partial epithelial-mesenchymal transition. In contrast, chromosomal instability, which can lead to the development of aneuploidy, uniformly suppressed cellular invasion. By analyzing genomic copy number and survival data from 10,133 cancer patients, we demonstrate that specific aneuploidies are associated with distinct clinical outcomes, and the acquisition of certain aneuploidies is in fact linked with a favorable prognosis. Thus, aneuploidy is not a uniform driver of malignancy, and different chromosome copy number changes can uniquely influence tumor progression. At the same time, the gain of a single chromosome is capable of inducing a profound cell state transition, underscoring how genomic plasticity can engender phenotypic plasticity and lead to the acquisition of enhanced metastatic properties.

cancer biology↗

bioRxiv2018

Cross-linking/Mass Spectrometry: A Community-Wide, Comparative Study Towards Establishing Best Practice Guidelines

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has largely increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats that are generally accepted in the field and that have shown to lead to high-quality results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. From the results obtained, common protocols will be established. Our study serves as basis for establishing best practice guidelines in the field for conducting cross-linking experiments, performing data analysis, and reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results.

biochemistry↗

bioRxiv2017

De novo indels within introns contribute to ASD incidence

Copy number profiling and whole-exome sequencing has allowed us to make remarkable progress in our understanding of the genetics of autism over the past ten years, but there are major aspects of the genetics that are unresolved. Through whole-genome sequencing, additional types of genetic variants can be observed. These variants are abundant and to know which are functional is challenging. We have analyzed whole-genome sequencing data from 510 of the Simons Simplex Collections quad families and focused our attention on intronic variants. Within the introns of 546 high-quality autism target genes, we identified 63 de novo indels in the affected and only 37 in the unaffected siblings. The difference of 26 events is significantly larger than expected (p-val = 0.01) and using reasonable extrapolation shows that de novo intronic indels can contribute to at least 10% of simplex autism. The significance increases if we restrict to the half of the autism targets that are intolerant to damaging variants in the normal human population, which half we expect to be even more enriched for autism genes. For these 273 targets we observe 43 and 20 events in affected and unaffected siblings, respectively (p-value of 0.005). There was no significant signal in the number of de novo intronic indels in any of the control sets of genes analyzed. We see no signal from de novo substitutions in the introns of target genes.

genetics↗