Biology subjects

Moreau, E.

Publications and source records attributed to Moreau, E..

9 recordsLinked to original sources

bioRxiv2026

Thinking outside of the box: Refining rat housing to improve welfare

Standard rat housing may impede species-typical behaviors and impact rat welfare and research outcomes. This research investigated the effects of housing on behavioral and physiological outcomes of rats through the use of modified large animal cages for housing, and was conducted in two studies. Study A: 70 Sprague Dawley (SD) rats (34 males, 36 females; 5 wk old) were randomly assigned to standard polycarbonate shoebox cages (C: 733.9cm2) or modified stainless steel primate cages (T: 10,416cm2) for 18 days. In Study B: 48 SD rats (24 males, 24 females; 7.5 wk old) were held in T housing for 90 days to assess long term impacts. All rats received gentle handling for 15s 3x/week. Rats were assessed for body weight, anxiety-like behavior in an elevated plus maze, response during a voluntary human approach test, and overall home cage behavior, posture, and space usage. Data were analyzed using generalized linear mixed models, with sex and treatment as fixed effects, and cage as the random effect. The results of study A suggest that the modified large animal cages (T) had positive impacts on rat behavior and welfare. T rats were less anxious (P=0.038) and more active (P<0.0001) and explorative (P=0.0003) compared to C rats. In both groups, activity levels declined towards the end of the 18-day study period (P<0.0001). For study B, similar patterns were observed, with rats becoming more inactive (P<0.0001) over 90 days. However, rats spent significant time on elevated shelves in T housing, which increased throughout the study (P<0.0001), suggesting continued use of the resources the housing provided. In both studies, there were no differences in latency to approach humans (P>0.05), but T rats spent less time in contact with human handlers, suggesting differences in motivation to interact with humans that should be explored further.

animal behavior and cognition↗

bioRxiv2025

Cytochrome P450 inhibition impedes pyrethroid effects on insects through Nav channel regulation

Insecticides used in various formulations are inevitable in agricultural pest control and prevention of vector-borne diseases. Piperonyl butoxide (PBO) is a synergist widely used to enhance the effectiveness of insecticides, notably pyrethroids, by inhibiting the detoxifying cytochrome P450 enzymes, thus reducing the capacity of insects to metabolize and resist insecticides. Recent studies, however, reveal an unexpectedly weak restoration of pyrethroid efficacy by PBO, but the underlying mechanism is unknown. Here, we demonstrate that the PBO-induced inhibition of cytochrome P450 impedes the effect of deltamethrin by mainly affecting its interaction with the inactivated state of voltage-gated sodium channels (Nav). We describe a new octopamine-dependent regulatory mechanism involving Gs, PKA, DARPP-32, and PP1-2A, which affect the cytochrome P450 conformation, thus limiting the effect of PBO and modulating the Nav gating. As a result, deltamethrin cannot reach its final binding site in the fenestration to exert its full effect. We confirmed in vivo that under chemical stressor, the level of octopamine is elevated, which decreases the deltamethrin efficacy. Our findings reveal a novel adaptation mechanism that increases insect survival by reducing insecticide efficacy, thus emphasizing the necessity of developing more effective formulations and technologies for pest and vector control.

pharmacology and toxicology↗

bioRxiv2022

Mining impactful discoveries from the biomedical literature

MotivationLiterature-Based Discovery (LBD) aims to help researchers to identify relations between concepts which are worthy of further investigation by text-mining the biomedical literature. While the LBD literature is rich and the field is considered mature, standard practice in the evaluation of LBD methods is methodologically poor and has not progressed on par with the domain. The lack of properly designed and decent-sized benchmark dataset hinders the progress of the field and its development into applications usable by biomedical experts. ResultsThis work presents a method for mining past discoveries from the biomedical literature. It leverages the impact made by a discovery, using descriptive statistics to detect surges in the prevalence of a relation across time. This method allows the collection of a large amount of time-stamped discoveries which can be used for LBD evaluation or other applications. The validity of the method is tested against a baseline representing the state of the art "time sliced" method. AvailabilityThe source data used in this article are publicly available. The implementation and the resulting data are published under open-source license: https://github.com/erwanm/medline-discoveries (code) https://zenodo.org/record/5888572 (datasets). An online exploration tool is also provided at https://brainmend.adaptcentre.ie/. Contacterwan.moreau@adaptcentre.ie

bioinformatics↗

bioRxiv2022

Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis

Lipoarabinomannan (LAM), a component of the Mycobacterium tuberculosis (MTB) cell wall, is detectable in the urine of MTB infected patients with active tuberculosis (TB). LAM-specific antibodies (Igs) have been developed by a variety of traditional and recombinant methods for potential use in a rapid diagnostic test (RDT). We evaluated the analytical performance of the TB LAM Igs to identify pairs that offer superior performance over existing urine LAM tests. We assessed 25 new and 4 existing Igs in a matrixed format using a multiplex electrochemiluminescence-based liquid immunoassay. A total of 841 paired Ig combinations were challenged with in vitro cultured LAM (cLAM) derived from MTB strains representing diverse phylogenetic lineages, alongside urinary LAM (uLAM) from the urine of adults with active pulmonary TB. Analytical sensitivity of down-selected Ig pairs was determined using MTB Aoyama-B cLAM, while diagnostic accuracy was determined using clinical samples. When testing cLAM, the reactivity of Ig pairs was similar across MTB lineages 1-4 but lineage 5:6 had significantly more reactivity among Ig pairs. Overall, 41 Ig pairs had a strong binding affinity to cLAM, as compared to the reference pair of S4-20/A194-01, and 28 Ig pairs therein exhibited a strong affinity for both cLAM and uLAM. Retrospective testing on clinical urine specimens demonstrated varying sensitivities (12-80%) and specificities (14-100%). The five top pairs had a similar analytical limit of detection to the reference pair but in four instances, the sensitivity and specificity with clinical uLAM samples was poor. Overall, epitopes presented by uLAM are different from cLAM, which may affect antibody performance when testing uLAM in patient samples. Several new Ig pairs had similar ranges of high sensitivity to cLAM but overall, there were no new candidate Ig pairs identified in this round of screening with increased performance with uLAM as compared to an existing optimal pair.

microbiology↗

bioRxiv2021

Literature-Based Discovery beyond the ABC paradigm: a contrastive approach

Literature-Based Discovery (LBD) aims to help researchers to identify relations between concepts which are worthy of further investigation by text-mining the biomedical literature. The vast majority of the LBD research follows the ABC model: a relation (A,C) is a candidate for discovery if there is some intermediate concept B which is related to both A and C. The ABC model has been successful in applications where the search space is strongly constrained, but there is limited evidence about its usefulness when applied in a broader context. Through a case study of 8 recent discoveries related to neurodegenerative diseases (NDs), we show the limitations of the ABC model in an open-ended context. The study emphasizes the impact of the choice of source data and extraction method on the resulting knowledge base: different "views" of the biomedical literature offer different levels of accuracy and coverage. We propose a novel contrastive approach which leverages these differences between "views" in order to target relations between concepts of interest. We explore various parameters and demonstrate the relevance of our approach through quantitative evaluation on the 8 target discoveries. The source data used in this article are publicly available. The different parts of the software used to process the data are published under open-source license and provided with detailed instructions. The main code for this paper is available at https://github.com/erwanm/lbd-contrast (required dependencies are detailed in the documentation). A prototype of the system is also provided as an online exploration tool at brainmend.adaptcentre.ie.

bioinformatics↗

bioRxiv2021

Isolation and Purification of Lipoarabinomannan from Urine of Adults with Active Tuberculosis

Lipoarabinomannan (LAM) is a cell wall component of Mycobacterium tuberculosis that is excreted in the urine of persons with active tuberculosis (TB). Limited diagnostic sensitivity of LAM immunoassays has been due to selecting antibodies against LAM derived from in vitro cultured M. tuberculosis, rather than LAM purified from in vivo clinical urine specimens. Urinary LAM (uLAM) is critical to enable the development of and/or screening of novel uLAM-specific antibodies but is typically dilute and in heterogeneous mixtures with other urine components. We used physical, enzymatic, and chemical processes for the scaled isolation and purification of uLAM. The purified material may then be used to develop more sensitive uLAM diagnostic tests for active TB disease.

microbiology↗

bioRxiv2021

Nuclear HMGB1 protects from non-alcoholic fatty liver diseases through negative regulation of liver X receptor

Dysregulations of lipid metabolism in the liver may trigger steatosis progression leading to potentially severe clinical consequences such as non-alcoholic fatty liver diseases (NAFLD). Molecular mechanisms underlying liver lipogenesis are very complex and fine-tuned by chromatin dynamics and the activity of multiple key transcription factors. Here, we demonstrate that the nuclear factor HMGB1 acts as a strong repressor of liver lipogenesis during metabolic stress in NAFLD. Mice with liver-specific Hmgb1-deficiency display exacerbated liver steatosis and hepatic insulin resistance when subjected to a high-fat diet or after fasting/refeeding. Global transcriptome and functional analysis revealed that the deletion of Hmgb1 gene enhances LXR activity resulting in increased lipogenesis. HMGB1 repression is not mediated through nucleosome landscape re-organization but rather via a preferential DNA occupation in region carrying genes regulated by LXR. Together these findings suggest that hepatocellular HMGB1 protects from liver steatosis development. HMGB1 may constitute a new attractive option to therapeutically target LXR axis during NAFLD.

pathology↗

bioRxiv2020

Interaction of Amphiphilic Lipoarabinomannan with Host Carrier Lipoproteins in Tuberculosis Patients: Implications for Blood-based Diagnostics.

Lipoarabinomannan (LAM), an amphiphilic lipoglycan of the Mycobacterium tuberculosis cell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to "concentrate" LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms but no positive culture for M. tuberculosis, and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach. Further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.

microbiology↗

bioRxiv2020

Computer modeling of whole-cell voltage-clamp analyses to delineate guidelines for good practice of manual and automated patch-clamp

The patch-clamp technique has contributed to major advances in the characterization of ion channels. The recent development of high throughput patch-clamp provides a new momentum to the field. However, whole-cell voltage-clamp technique presents certain limits that need to be considered for robust data generation. One major caveat is that current amplitude profoundly impacts the precision of the analyzed characteristics of the ion current under study. For voltagegated channels, the higher the current amplitude is, the less precise the characteristics of voltagedependence are. Similarly, in ion channel pharmacology, the characteristics of dose-response curves are hindered by high current amplitudes. In addition, the recent development of high throughput patch-clamp technique is often associated with the generation of stable cell lines demonstrating high current amplitudes. It is therefore critical to set the limits for current amplitude recordings to avoid inaccuracy in the characterization of channel properties or drug actions, such limits being different from one channel to another. In the present study, we use kinetic models of a voltage-gated sodium channel and a voltage-gated potassium channel to edict simple guidelines for good practice of whole-cell voltage-clamp recordings.

biophysics↗