Biology subjects

Raymond, J.

Publications and source records attributed to Raymond, J..

12 recordsLinked to original sources

bioRxiv2026

Anti-inflammatory and pro-proliferative effects of fasudil in human trisomy 21 neural progenitor cells

Down syndrome (DS) results from trisomy for human chromosome 21 and is the most frequent genetic cause of intellectual disability. No effective treatments currently exist that improve neurodevelopment and cognition. Atypical brain development in individuals with DS is apparent before birth, which suggests that the optimal time to begin administration of therapies is prenatally. Human neural progenitor cell (NPC) cultures provide a tractable in vitro model system to examine the effects of trisomy 21 (T21) on neurodevelopment and to measure the effects of pharmacological interventions. Here we report the results of preclinical studies evaluating 24 candidate therapies. RNA-Seq analyses found that euploid and T21 NPCs showed different transcriptomic responses to five candidate pharmacotherapies. The Rho-associated coiled-coil kinase (ROCK) inhibitor fasudil increased proliferation of T21 NPCs, reduced expression of inflammatory pathway genes in T21 NPCs, and reduced markers of inflammation in LPS-stimulated microglia model systems. These results demonstrate that fasudil can alter multiple T21-associated abnormalities in a beneficial manner, suggesting that fasudil warrants further study as a candidate prenatal pharmacotherapy for DS.

pharmacology and toxicology↗

bioRxiv2026

Early-warning surveillance of West Nile and Usutu viruses in water and mosquito excreta using digital PCR

1.West Nile virus (WNV) and Usutu virus (USUV) are mosquito-borne pathogens maintained in bird-mosquito cycles and increasingly cause human and equine disease in temperate regions. As most infections are asymptomatic, surveillance based on clinical and veterinary reports provides delayed signals for vector control and equine vaccination strategies. We implemented, in 2024 and 2025, an operational environmental surveillance strategy combining molecular xenomonitoring of adult mosquito excreta with water sampling from wetlands and mosquito breeding sites, coupled to a standardized multiplex reverse transcription digital PCR workflow. Viral detection was performed using a multiplex digital PCR assay with characterized limits of blank, detection, and quantification, and low-level positives were confirmed by Sanger sequencing. This multi-matrix approach detected WNV RNA in southern France as early as 1 July 2024, 40 days before the first human case and 67 days before the first equine alert, and on 9 April 2025, a full 19 weeks ahead of the first human case that year. USUV RNA was similarly detected from 5 July 2024 and 22 April 2025, providing actionable early warnings to guide targeted vector control and preparedness. Across both years, WNV and USUV were detected 29 and 8 times among 396 samples in 2024, and 90 and 14 times among 815 samples in 2025, revealing previously unrecognized, cryptic virus circulation. These results demonstrate that integrating environmental surveillance provides a sensitive, proactive framework for the early detection of emerging Culex-borne arboviruses, offering precious lead time for public one-health strategies.

ecology↗

bioRxiv2025

Acoustic Coupling for Double-Blind Human Low-Intensity Focused Ultrasound Neuromodulation

ObjectiveLow-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique with the potential for precise targeting of small and deep human brain circuitry. To ensure rigorous and reproducible effects, it is necessary to implement double-blinding to mitigate potential experimental biases. This study innovates on previous ultrasound coupling methods by embedding a 3D-printed thermoplastic disc in a high-density gel-polymer matrix to create identical gel-plastic coupling devices that either transmit (verum) or block (sham) ultrasound. MethodsWe evaluated varying thicknesses (1.5 mm, 2,0 mm, 2.5 mm) and infill densities (25%, 50%, 75%, and 100%) of Acrylonitrile Butadiene Styrene (ABS) for insertion loss and effects on beam characteristics across relevant human neuromodulation frequencies from 0.2 - 1 MHz. ResultsABS at 1.5 mm thickness and 50 % infill had the lowest insertion loss at 0.50 MHz of 0.9 {+/-} 0.04 dB demonstrating acoustic transparency suitable for a verum device. For the sham device, we introduced an internal air gap that produced 31 dB insertion loss at 0.50 MHz. The verum device demonstrated minimal effects on the beam shape with a radial peak shift of 0.3 {+/-} 0.2 mm and an average axial shift of 0.5 mm. DiscussionThis novel gel-plastic coupling device can be tailored to most LIFU transducer shapes and is designed to support double-blind protocols by maintaining visual and tactile indistinguishability while controlling transmitted energy. This method provides a cost-effective and easily implementable solution for double-blinding in human LIFU studies to improve the reliability and rigor of experimental outcomes.

neuroscience↗

bioRxiv2025

EFFECT OF METHANOL STEM-BARK EXTRACT OF Erythrina senegalensis ON SERUM ALBUMIN LEVEL OF CARBON TETRACHLORIDE INDUCED LIVER DAMAGE IN WISTAR ALBINO RATS.

IntroductionPrevious investigations already established the pharmacological importance of Erythrina senegalensis. The current study was conducted to determine the effect of methanol stem-bark extract of Erythrina senegalensis (MEES) on serum albumin level of carbon tetrachloride (CCl4) induced liver damage in wistar rats. MethodThirty wister rats of either sex weighing were randomly divided into six groups of five rats each. Group 1 served as the control received standard pelleted rat feed with normal distilled water. Group 2-6 were administered 30% CCl4 1ml/kg body weight in liquid paraffin at 72hrs interval. Group 2 was untreated while group 3 was orally treated with standard drug salymarin for 14days. Group 4-6 were orally treated respectively with 100, 300 and 500mg/kg body weight of the MEES. ResultThe phytochemical analysis of the MEES indicated the presence of saponins, phenols, flavonoids, and tannins while the acute toxicity test showed no adverse reaction within the test population at a dose range of 200-2000mg/kg body weight. Unlike the control, inducement of CCL4 to Group2-6 indicated significant changes (p < 0.05) in the serum albumin level and hematological parameters. However, treatment with silymarin and increasing doses of the MEES restore the changes. The histopathological studies also reveal that increasing concentration of administered doses of the MEES significantly (p < 0.05) reduces cell necrosis around central vein. ConclusionThe findings reveal that MEES at recommended doses can serve as alternative source for the development of safe, effective, and affordable liver-supplement drug.

biochemistry↗

bioRxiv2023

How random is the review outcome? A systematic study of the impact of external factors on eLife peer review

The advance of science rests on a robust peer review process. However whether or not a paper is accepted can depend on random external factors--e.g. the timing of the submission, the matching of editors and reviewers--that are beyond the quality of the work. This article systematically investigates the impact of these random factors independent of the papers quality on peer review outcomes in a major biomedical journal, eLife. We analyzed all of the submissions to eLife between 2016 to 2018, with 23,190 total submissions. We examined the effects of random factors at each decision point in the review process, from the gatekeeping senior editors who may desk-reject papers to review editors and reviewers who recommend the final outcome. Our results suggest that the peer-review process in eLife is robust overall and that random external factors have relatively little quantifiable bias.

bioinformatics↗

bioRxiv2022

Combining historical agricultural and climate datasets sheds new light on early 20th century barley performance

Barley (Hordeum vulgare ssp. vulgare) is cultivated globally across a wide range of environments, both in highly productive agricultural systems and in subsistence agriculture and provides valuable feedstock for the animal feed and malting industries. However, as the climate changes there is an urgent need to identify adapted spring barley varieties that will consistently yield highly under increased environmental stresses. In this research we combined recently released historical weather data with published early 20th century Irish spring barley trials data for two heritage varieties: Archer and Goldthorpe, following an analysis first published by Student in 1923. Using linear mixed models, we show that interannual variation in observed spring barley yields can be partially explained by recorded weather variability. We find that whilst Archer largely yields more highly, Goldthorpe is more stable under wetter growing conditions, highlighting the importance of considering growing climate in variety selection. Furthermore, this study demonstrates the benefits of access to historical trials and climatic data and the importance of incorporating climate data in modern day breeding programmes to improve climate resilience of future varieties.

plant biology↗

bioRxiv2021

BRN2 is a non-canonical melanoma tumor-suppressor

While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, we show that BRN2 haplo-insufficiency is sufficient to promote melanoma initiation and metastasis, acting as a non-canonical tumor suppressor. Mechanistically, BRN2 directly modulates PTEN expression, and PI3K signaling, to drive tumor initiation and progression. Collectively our results reveal that somatic deletion of one BRN2 allele elicits melanoma initiation and progression. SIGNIFICANCEHere, we report frequent mono-allelic loss of the transcription factor BRN2 in human cutaneous melanoma metastases. We developed a mouse model for Brn2-deficient melanoma based on the most common alterations (BrafV600E and Pten loss) in human melanoma and established the role of Brn2 as a functional regulator of tumor initiation, tumor growth, and the formation of metastases in vivo. Mechanistically, BRN2 loss increases PI3K-signaling through PTEN repression, either via MITF induction or not. Overall, we describe a novel tumor suppressor of high prevalence in human melanoma that regulates several steps of in vivo melanomagenesis through two previously unknown molecular mechanisms.

cancer biology↗

bioRxiv2019

Brucella effector hijacks endoplasmic reticulum quality control machinery to prevent premature egress

Perturbation of endoplasmic reticulum (ER) functions can have critical consequences for cellular homeostasis. An elaborate surveillance system known as ER quality control (ERQC) ensures that only correctly assembled proteins reach their destination. Persistence of misfolded or improperly matured proteins upregulates the unfolded protein response (UPR) to cope with stress, activates ER associated degradation (ERAD) for delivery to proteasomes for degradation. We have identified a Brucella abortus type IV secretion system effector called BspL that targets Herp, a key component of ERQC and is able to augment ERAD. Modulation of ERQC by BspL results in tight control of the kinetics of autophagic Brucella-containing vacuole formation, preventing premature bacterial egress from infected cells. This study highlights how bacterial pathogens may hijack ERAD components for fine regulation of their intracellular trafficking.

microbiology↗

bioRxiv2019

CellSIUS provides sensitive and specific detection of rare cell populations from complex single cell RNA-seq data

Comprehensive benchmarking of computational methods for single-cell RNA sequencing (scRNA-seq) analysis is scarce. Using a modular workflow and a large dataset with known cell composition, we benchmarked feature selection and clustering methodologies for scRNA-seq data. Results highlighted a methodology gap for rare cell population identification for which we developed CellSIUS (Cell Subtype Identification from Upregulated gene Sets). CellSIUS outperformed existing approaches, enabled the identification of rare cell populations and, in contrast to other methods, simultaneously revealed transcriptomic signatures indicative of the rare cells function. We exemplified the use of our workflow and CellSIUS for the characterization of a human pluripotent cell 3D spheroid differentiation protocol recapitulating deep-layer corticogenesis in vitro. Results revealed lineage bifurcation between Cajal-Retzius cells and layer V/VI neurons as well as rare cell populations that differ by migratory, metabolic, or cell cycle status, including a choroid plexus neuroepithelial subgroup, revealing previously unrecognized complexity in human stem cell-derived cellular populations.

bioinformatics↗

bioRxiv2018

Gender and international diversity improves equity in peer review

The fairness of scholarly peer review has been challenged by evidence of disparities in publication outcomes based on author demographic characteristics. To assess this, we conducted an exploratory analysis of peer review outcomes of 23,876 initial submissions and 7,192 full submissions that were submitted to the biosciences journal eLife between 2012 and 2017. Women and authors from nations outside of North America and Europe were underrepresented both as gatekeepers (editors and peer reviewers) and authors. We found evidence of a homophilic relationship between the demographics of the gatekeepers and authors and the outcome of peer review; that is, there were higher rates of acceptance in the case of gender and country homophily. The acceptance rate for manuscripts with male last authors was seven percent, or 3.5 percentage points, greater than for female last authors (95% CI = [0.5, 6.4]); this gender inequity was greatest, at nine percent or about 4.8 percentage points (95% CI = [0.3, 9.1]), when the team of reviewers was all male; this difference was smaller and not significantly different for mixed-gender reviewer teams. Homogeny between countries of the gatekeeper and the corresponding author was also associated with higher acceptance rates for many countries. To test for the persistence of these effects after controlling for potentially confounding variables, we conducted a logistic regression including document and author metadata. Disparities in acceptance rates associated with gender and country of affiliation and the homophilic associations remained. We conclude with a discussion of mechanisms that could contribute to this effect, directions for future research, and policy implications. Code and anonymized data have been made available at https://github.com/murrayds/elife-analysis\n\nAuthor summaryPeer review, the primary method by which scientific work is evaluated, is ideally a fair and equitable process in which scientific work is judged solely on its own merit. However, the integrity of peer review has been called into question based on evidence that outcomes often differ between male and female authors, and for authors in different countries. We investigated such disparities at the biosciences journal eLife by analyzing the demographics of authors and gatekeepers (editors and peer reviewers), and peer review outcomes of all submissions between 2012 and 2017. Outcomes were more favorable for male authors and those affiliated with institutions in North America and Europe; these groups were also over-represented among gatekeepers. There was evidence that peer review outcomes were influenced by homophily --a preference of gatekeepers for manuscripts from authors with shared characteristics. We discuss mechanisms that could contribute to this effect, directions for future research, and policy implications.

scientific communication and education↗

bioRxiv2018

Genome-Scale CRISPR Screening Identifies Novel Human Pluripotent Gene Networks

Human pluripotent stem cells (hPSCs) generate a wide variety of disease-relevant cells that can be used to improve the translation of preclinical research. Despite the potential of hPSCs, their use for genetic screening has been limited because of technical challenges. We developed a renewable Cas9/sgRNA-hPSC library where loss-of-function mutations can be induced at will. Our inducible-mutant hPSC library can be used for an unlimited number of genome-wide screens. We screened for novel genes involved in 3 of the fundamental properties of hPSCs: Their ability to self-renew/survive, their capacity to differentiate into somatic cells, and their inability to survive as single-cell clones. We identified a plethora of novel genes with unidentified roles in hPSCs. These results are available as a resource for the community to increase the understanding of both human development and genetics. In the future, our stem cell library approach will be a powerful tool to identify disease-modifying genes.\n\nVISUAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC=\"FIGDIR/small/323436_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (48K):\norg.highwire.dtl.DTLVardef@5101e4org.highwire.dtl.DTLVardef@5321f2org.highwire.dtl.DTLVardef@1d9c94corg.highwire.dtl.DTLVardef@12ebd53_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2017

Universal Scaling in Biochemical Networks

The application of network science to biology has advanced our understanding of the metabolism of individual organisms and the organization of ecosystems but has scarcely been applied to life at a planetary scale. To characterize planetary-scale biochemistry, we constructed biochemical networks using a global database of 28,146 annotated genomes and metagenomes, and 8,658 cataloged biochemical reactions. We uncover scaling laws governing biochemical diversity and network structure shared across levels of organization from individuals to ecosystems, to the biosphere as a whole. Comparing real biochemical networks to random chemical networks reveals the observed biological scaling is not solely a product of the biochemistry shared across life on Earth. Instead, it emerges due to how the global inventory of biochemical reactions is partitioned into individuals. We show the three domains of life are topologically distinguishable, with > 80% accuracy in predicting evolutionary domain based on biochemical network size and average topology. Taken together our results point to a deeper level of organization in biochemical networks than what has been understood so far.

systems biology↗