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Perrin, C.

Publications and source records attributed to Perrin, C..

7 recordsLinked to original sources

Quantification of anatomical changes in young grapevine wood over time and in response to Neofusicoccum parvum with image processing

Grapevine Trunk diseases (GTDs) represent a major threat for the wine industry. Despite several break-through, their etiology remains unclear and no curative treatment is currently available. Wood anatomy and water transport contribute to the symptoms of young plant decline. This study investigates wood anatomical alterations in two Alsatian grapevine cultivars presenting different susceptibility to GTDs, focusing on wood structure over six months of vegetative growth and in response to infection. Using a validated FasGa staining protocol, wood sections from transverse, tangential, and radial directions were stained to differentiate lignified and cellulosic tissues. Microscopic analysis was performed at x4, x10, and x40 magnifications, yielding a dataset of 4771 images. To support this high-throughput quantitative analysis of microscopy images, a computational model was developed, enabling reliable and efficient assessment of anatomical traits. Pre-established woody tissues presented higher xylem vessels diameter in Gewurztraminer than Riesling, with a dorsoventral arrangement whereas the number of vessels remained the same all over the cross section. No significant anatomical changes were observed in established woody tissues, whereas newly formed xylem anatomy showed a possible rearrangement during infection, especially in Gewurztraminer cultivar. Furthermore, colorimetric analysis quantified the lignification of woody tissues in response to wounding damage compared to un-treated plants. While definitive conclusions remain limited due to the experimental timeframe and sample variability, the findings highlight the need for longer-term studies and broader cultivar evaluation. Code and microscopy images have been made publicly available, providing a scalable digital tool for future research in plant vascular systems.

plant biology↗

Transcutaneous auricular vagus nerve stimulation during movement modulates motor neural circuitry without widespread cortical or autonomic activation

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising neuromodulatory approach for treating neurological disorders, with growing interest in its potential to support motor rehabilitation. Yet, its mechanisms of action, potentially influenced by behavioral context, remain elusive. This sham-controlled study investigated transient taVNS interactions with movement in healthy adults, focusing on autonomic, neuromodulatory, and motor circuits. During a finger-tapping paradigm, heart rate (HR), galvanic skin response (GSR), pupil diameter, and electroencephalography (EEG) were recorded to probe movement-dependent stimulation effects. This study first identified a novel physiological dissociation: all measures responded to movement, but taVNS did not significantly alter HR, GSR, or general EEG spectral slope; taVNS increased pupil diameter in both conditions, but enhanced sensorimotor EEG spectral slope solely during movement. This context-specific effect on motor systems was further supported by a transcranial magnetic stimulation (TMS) experiment demonstrating increased corticospinal excitability during taVNS. These findings provide mechanistic insights into how taVNS may selectively enhance motor system responsiveness during active states, supporting future exploration of behaviorally paired stimulation protocols for neurorehabilitation.

neuroscience↗

Preclinical Study of Cannflavins A and B Action Against Glioblastoma Cells

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSFlavonoids represent a large group of naturally occurring polyphenolic compounds, many of which have been found to produce valuable biological outcomes, including action against cancer cells. Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is associated with a poor prognosis and has limited treatment options. Previous findings suggest that cannflavins can produce promising effects for pancreatic and bladder cancers, but the efficacy of these phytochemicals in attacking brain tumour cells remains unknown. Our study evaluates the potential of cannflavin A and cannflavin B against GBM cells using a range of in vitro approaches. ResultsWe conducted experiments using A-172 and U-87 GBM lines to assess the impact of cannflavins A and B on cell viability, cycle, migration, and invasion capacity. Our results revealed a consistent dose-dependent decrease in cell viability in both lines after the addition of cannflavin B to the culture media. Interestingly, we found that chrysoeriol (the non-prenylated synthesis precursor of cannflavins in the Cannabis sativa plant) only has a limited adverse effect on survival using the same approach, while techtochrysin (an O-methylated flavone) has none. Using time-lapse live-cell imaging and a scratch assay, we also show that cannflavins can inhibit tumor cell migration at concentrations below those that produce significant cell death. Finally, we found that cannflavin B exhibits anti-migratory and anti-invasive properties in transwell and tumorsphere assays, underscoring its multifaceted therapeutic potential. ConclusionThese findings suggest that cannflavin B holds promise as a therapeutic agent in the treatment of GBM. HO_SCPLOWIGHLIGHTSC_SCPLOWO_LICannflavin B but not cannflavin A limits the viability of A-172 and U-87 GBM cells in a concentration- and time-dependent manner. C_LIO_LIUsing time-lapse live-cell imaging and a scratch assay, we provide evidence that cannflavins A and B can inhibit GBM cell migration at concentrations below those that result in a significant reduction in cell viability. C_LIO_LICannflavin B exhibits robust anti-migratory and anti-invasive properties in transwell and tumorsphere assays, underscoring its multifaceted therapeutic potential. C_LIO_LIAlthough previous work had reported the capacity of cannflavins A and B to interfere with TrkB and downstream the MAPK/AKT signaling pathways in mouse primary neurons, the effect of those molecules is limited in GBMs, suggesting that other targets are engaged to produce the cellular effects. C_LI

pharmacology and toxicology↗

Interference of Neuronal TrkB Signaling by the Cannabis-Derived Flavonoids Cannflavins A and B

Cannflavins A and B are flavonoids that accumulate in the Cannabis sativa plant. These specialized metabolites are uniquely prenylated and highly lipophilic, which, a priori, may permit their interaction with membrane-bound enzymes and receptors. Although previous studies found that cannflavins can produce anti-inflammatory responses by inhibiting the biosynthesis of pro- inflammatory mediators, the full extent of their cellular influence remains to be understood. Here, we studied these flavonoids in relation to the Tropomyosin receptor kinase B (TrkB), a receptor tyrosine kinase that is activated by the growth factor brain-derived neurotrophic factor (BDNF). Using mouse primary cortical neurons, we first collected evidence that cannflavins prevent the accumulation of Activity-regulated cytoskeleton-associated (Arc, also known as Arg3.1) protein upon TrkB stimulation by exogenous BDNF in these cells. Consistent with this effect, we also observed a reduced activation of TrkB and downstream signaling effectors that mediate Arc mRNA transcription when BDNF was co-applied with the cannflavins. Of note, we also performed a high-throughput screen that demonstrated a lack of agonist action of cannflavins towards 320 different G protein-coupled receptors, a result that specifically limit the possibility of a TrkB transinactivation scenario via G protein signaling to explain our results with dissociated neurons. Finally, we used Neuro2a cells overexpressing TrkB to show that cannflavins can block the growth of neurites and increased survival rate produced by the higher abundance of the receptor in this model. Taken together, our study offers a new path to understand the reported effects of cannflavins and other closely related compounds in different cellular contexts.

pharmacology and toxicology↗

Cytolysin-positive Enterococcus faecalis is elevated in patients with chronic alcoholic pancreatitis

IntroductionPatients with alcoholic hepatitis have an increase in cytolysin-producing Enterococcus faecalis that correlates with disease severity and mortality. AimTo determine whether patients with chronic alcoholic pancreatitis have an elevated abundance of cytolysin-producing E. faecalis. MethodsQuantification by qPCR of cytolysin-producing E. faecalis in controls and patients with alcoholic hepatitis or pancreatitis. ResultsPatients with alcoholic pancreatitis had a higher proportion of intestinal cytolysin-positive E. faecalis than healthy controls and patients with alcoholic hepatitis. ConclusionCytolytic E. faecalis may also be involved in this other alcohol-related complication and benefit from targeted microbiota editing strategies.

physiology↗

Disentangling heterogeneity of Malignant Pleural Mesothelioma through deep integrative omics analyses

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Using the largest series of whole-genome sequencing data integrated with transcriptomic and epigenomic data using multi-omic factor analysis, we demonstrate that MPM heterogeneity arises from four sources of variation: tumor cell morphology, ploidy, adaptive immune response, and CpG island methylator phenotype. Previous genomic studies focused on describing only the tumor cell morphology factor, although we robustly find the three other sources in all publicly available cohorts. We prove how these sources of variation explain the biological functions performed by the cancer cells, and how genomic events shape MPM molecular profiles. We show how these new sources of variation help understand the heterogeneity of the clinical behavior of MPM and drug responses measured in cell lines. These findings unearth the interplay between MPM functional biology and its genomic history, and ultimately, inform classification, prognostication and treatment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/461908v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@b6c43corg.highwire.dtl.DTLVardef@10d45a9org.highwire.dtl.DTLVardef@58746eorg.highwire.dtl.DTLVardef@143f880_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

Countries are out of step with international recommendations for tuberculosis testing, treatment, and care: Findings from a 29-country survey of policy adoption and implementation

BackgroundTuberculosis (TB) poses a global health crisis requiring robust international and country-level action. Adopting and implementing TB policies from the World Health Organization (WHO) is essential to meeting global targets for reducing TB burden. However, many high TB burden countries lag in implementing WHO recommendations. Assessing the progress of implementation at national level can identify key gaps that must be addressed to expand and improve TB care. MethodsIn 2016/2017, Medecins Sans Frontieres and the Stop TB Partnership conducted a survey on adoption and implementation of 47 WHO TB policies in the national TB programs of 29 countries. Here we analyze a subset of 23 key policies in diagnosis, models of care, treatment, prevention, and drug regulation to provide a snapshot of national TB policy adoption and implementation. We examine progress since an analogous 2015 survey of 23 of the same countries. ResultsAt the time of the survey, many countries had not yet aligned their national guidelines with all WHO recommendations, although some progress was seen since 2015. For diagnosis, about half of surveyed countries had adopted the WHO-recommended initial rapid test (Xpert MTB/RIF). A majority of countries had adopted decentralized models of care, although one-third of them still required hospitalization for drug-resistant (DR-)TB. Recommended use of the newer drugs bedaquiline (registered in only 6 high-burden TB countries) and delamanid (not registered in any high-burden country) was adopted by 23 and 18 countries, respectively, but short-course (9-month) and newer pediatric regimens by only 13 and 14 countries, respectively. Guidelines in all countries included preventive treatment of latent TB infection for child TB contacts and people living with HIV/AIDS, but only four extended this to adult contacts. ConclusionTo reach global TB targets, greater political will is needed to rapidly adopt and implement internationally recognized care guidelines. KEY MESSAGESO_ST_ABSWhat is already known?C_ST_ABSO_LICountries may be slow to adopt and implement updated World Health Organization (WHO) Tuberculosis (TB) testing, treatment, and prevention recommendations. C_LIO_LIImplementing updated TB guidelines from WHO is a fundamental first step to honoring international commitments, made through the United Nations (UN) Sustainable Development Goals (SDGs) and UN High-Level Meeting on TB Political Declaration, to end TB by 2030. C_LI What are the new findings?O_LIOf 29 mostly high TB burden countries, none had fully aligned their national guidelines with WHO recommendations, although some progress has been made since 2015. C_LIO_LIA lack of alignment with WHO recommendations was found across all policy areas surveyed, including prevention, diagnosis, treatment, models of care and drug regulation, particularly regarding uptake of newer, faster, more effective approaches. C_LI What do the new findings imply?O_LITo reach global TB targets, greater political will is needed to adopt and implement internationally recognized care guidelines more rapidly, and specifically, to keep up with the latest recommendations. C_LIO_LIPeriodic surveys of progress at the national level are a valuable way to identify specific areas where countries or regions have fallen behind and that require specific policy and/or programmatic attention. C_LI

epidemiology↗