Biology subjects

Durand, M.

Publications and source records attributed to Durand, M..

At least 19 recordsLinked to original sources

bioRxiv2026

NANOCUTSIGHT: A NANOPORE-SEQUENCING APPROACH AND ANALYSIS PIPELINE TO ASSESS GENOME EDITING EFFICACY IN VARIOUS CELL POPULATIONS

Genome editing has revolutionized biomedical sciences and is now an essential tool to define molecular pathways through genetic interaction and loss-of-function studies. Through its diverse variations, it allows for the generation of specific knockout cell lines or organisms, as well as the creation of endogenously edited gene regions. While high-throughput methodologies exist to map CRISPR/Cas9 genetic modifications, the validation of guide efficiencies in cell populations is often performed through analysis of the targeted gene product by western blotting or by deconvolution of Sanger sequencing chromatograms using TIDE or ICE assays. Here, we highlight a rapid nanopore sequencing pipeline, which we have named NanoCutSight, to quantify the percentage of indels at a specific genomic locus and to identify the types of modifications generated. We also benchmarked the methodology on various guide RNAs and in both cultured cell and organoid models. We believe that NanoCutSight will simplify the analysis of complex sample editing and enable the rapid screening of edited samples.

bioinformatics↗

bioRxiv2026

ALDH Activity in Monocytes is Associated with Subclinical Coronary Atherosclerosis in Treated People with HIV-1

People living with HIV-1 (PWH) receiving antiretroviral therapy (ART) exhibit an increased cardiovascular disease (CVD) risk. Coronary atherosclerotic plaque formation is linked to chronic immune activation, a process fueled in PWH by additional mechanisms likely including residual HIV-1 production and microbial translocation from the gut during ART. Our previous studies demonstrated that aldehyde dehydrogenase (ALDH), an enzyme converting vitamin A into retinoic acid (RA), is upregulated in myeloid cells upon exposure to viral/bacterial/fungal products and that RA promotes HIV-1 production. To explore the link between ALDH/RA pathway and CVD risk, we used PBMC/plasma from ART-treated PWH (PWH+ART; n=51) and people without HIV-1 (Pw/oH; n=63) from the Canadian HIV/Aging Cohort Study, with/without subclinical coronary atherosclerosis, measured by coronary computed tomography angiography. ALDH expression was analyzed by flow cytometry on monocyte subsets, dendritic cells, and CD4+ T-cells. Unsupervised t-SNE-guided FlowSOM analysis associated top ALDH activity with a monocyte phenotype. The frequency of ALDH+ monocytes and plasma levels of RA and retinol binding protein 4 were increased in PWH+ART versus Pw/oH, with the highest RA levels coinciding with detectable plasma levels of soluble HIV-1 gp120. Multivariate regression models linked ALDH activity in monocytes to subclinical coronary atherosclerosis (i.e., total plaque volume, low attenuated plaque volume, coronary artery calcification score) presence/burden in PWH+ART, independently of Framingham risk score. Finally, ALDH+ monocyte frequency and RA levels positively correlated with pericoronary fat attenuation index, an emerging CVD predictor. Thus, ALDH/RA pathway may represent a new marker of metabolic/immune dysfunction contributing to CVD risk in ART-treated PWH.

immunology↗

bioRxiv2026

Nef and Vpu protect infected cells from ADCP mediated by plasma from people with HIV-1

The HIV-1 envelope glycoprotein (Env) represents the only viral antigen at the surface of infected cells, making it an ideal target for antibody-based therapies. Most antibodies elicited in people with HIV (PWH) do not recognize Env in its native "closed" conformation but readily bind to Env when it samples the CD4-bound "open" conformation. Downregulation of CD4 at the surface of infected cells by the viral accessory proteins Nef and Vpu prevents the premature opening of Env and has been shown to protect infected cells from antibody-dependent cellular cytotoxicity (ADCC) mediated by PWH plasma. Here, we report that deletion of Nef and Vpu from primary infectious molecular clones renders infected cells vulnerable to antibody-dependent cellular phagocytosis (ADCP) mediated by PWH plasma. This is in part linked to the premature engagement of Env with CD4. In agreement with an "open" Env being vulnerable to ADCP, small CD4 mimetic compounds (CD4mc) sensitize in vitro-infected cells and ex vivo-expanded CD4 T cells to ADCP mediated by autologous monocytes in presence of PWH plasma. This effect was further improved by increasing cell surface Env through IFN-induced BST-2 upregulation. IMPORTANCEDeveloping new therapies to eliminate HIV-1-infected cells is essential to decrease the size of the HIV-1 reservoir. Fc-effector functions such as antibody dependent cellular cytotoxicity (ADCC) have shown potential in eliminating in vitro-infected cells and ex vivo-expanded infected cells from people with HIV, decreasing the size of the reservoir and delaying viral rebound in humanized mice. Here, we report that antibody dependent cellular phagocytosis (ADCP) can also be harnessed to eliminate HIV-1-infected cells. We show that infected cells harboring "open" Env conformations are susceptible to ADCP-mediated killing in the presence of plasma from people with HIV. A better understanding of the contribution of different Fc-effector functions in the elimination of infected cells could help guide the development of new therapeutic approaches toward an HIV-1 cure.

microbiology↗

bioRxiv2026

Geissoschizine scaffolding enzymes shape monoterpene indole alkaloid biosynthesis

For decades, medicinal plants have been an invaluable source of therapeutics for human health. Among plant specialized metabolites, monoterpene indole alkaloids (MIAs) display remarkable chemical diversity and potent bioactivities, including anticancer properties. While the biosynthetic pathways leading to major MIAs such as vincristine, vinblastine, and camptothecin have been extensively studied, the mechanisms regulating metabolic flux within these pathways remain poorly understood. Here, we uncover an unexpected regulatory layer in MIA biosynthesis involving medium-chain dehydrogenase/reductase (MDR) proteins. Using a combination of in vitro biochemical assays, pathway reconstitution in planta, protein-protein interaction analyses, and metabolic engineering in yeast, we show that specific MDRs do not function as classical catalysts but instead enhance both the activity and diversify the stereochemical outputs of geissoschizine synthase (GS). These proteins physically interact with GS and strictosidine {beta}-glucosidase (SGD), forming ternary complexes that likely facilitate substrate channeling of reactive intermediates. Importantly, introduction of these MDRs into engineered yeast strains leads to a dramatic increase in the production of geissoschizine, a central MIA precursor. Collectively, our findings reveal a previously unrecognized role for MDR proteins as regulators of metabolic flux and highlight their potential as powerful tools for metabolic engineering of valuable plant natural products.

plant biology↗

bioRxiv2026

Chronopharmacological targeting of mitochondrial dihydroorotate dehydrogenase prevents diet-induced obesity in male mice

Daily hepatic mitochondrial rhythms are strengthened by time-restricted feeding in diet-induced obesity in male mice, as shown by metabolomics, including an early enhancement of oscillations within the de novo pyrimidine pathway. We tested whether timed inhibition of dihydroorotate dehydrogenase (DHODH, which links pyrimidine synthesis to respiratory-chain flux), can reproduce selected TRF-associated mitochondrial and metabolic effects. Administering the short-half-life inhibitor BAY2402234 at dawn transiently decreased DHODH activity, restored daily mitochondrial oxidative dynamics (ubiquinone/ubiquinol ratio), and amplified rhythms of respiratory exchange ratio and mitochondrial dynamics-related markers upon high-fat diet. Under ZT0 dosing, mice showed reduced weight gain, reduced adiposity and hepatic triglycerides, and improved glucose tolerance without changes in food intake; while ZT12 dosing was ineffective. Hepatic Dhodh knockdown did not reproduce the anti-obesity phenotype, and uridine supplementation blunted BAY2402234 benefits, implicating de novo pyrimidine flux. Our findings reveal rhythm-aware DHODH inhibition as a chronopharmacological preclinical candidate approach against overnutrition.

physiology↗

bioRxiv2025

Tissue macrophages stem sepsis induced altered organ repair

IntroductionSepsis, the most severe manifestation of infection, remains both common and life-threatening. Beyond the acute phase, growing evidence highlights that sepsis survivors face an increased risk of chronic organ dysfunction, including kidney and heart failure. While early immune mechanisms of sepsis have been extensively studied, the biological processes underlying delayed post-sepsis organ sequelae remain poorly understood. MethodsUsing murine models of sepsis, we investigated the long-term impact of sepsis on organ immune landscapes and tissue repair. Fate-mapping experiments were conducted to trace macrophage origin and persistence. Single-cell RNA sequencing of the heart and kidney was performed to characterize macrophage subpopulations and transcriptional reprogramming following sepsis. Functional consequences of this immune remodeling were assessed by challenging post-septic animals with angiotensin II to evaluate secondary injury susceptibility and fibrotic remodeling. ResultsSepsis induced transient multiorgan failure but led to a sustained expansion of tissue macrophages. Fate-mapping demonstrated that this expansion was largely driven by the recruitment and engraftment of monocyte-derived macrophages. Single-cell transcriptomic analyses revealed that post-septic macrophages acquired a distinct proinflammatory and profibrotic signature, consistent with persistent microenvironmental activation. Functionally, this altered macrophage landscape impaired organ resilience, as evidenced by increased mortality and exacerbated cardiac and renal fibrosis upon secondary challenge. DiscussionOur findings identify macrophage reprogramming as a central mechanism linking sepsis to long-term organ vulnerability. The persistence of monocyte-derived macrophages with maladaptive transcriptional profiles promotes fibrotic remodeling and impaired tissue repair. Targeting macrophage recruitment or reprogramming may represent a promising strategy to prevent chronic organ failure among sepsis survivors. SIGNIFICANCE STATEMENTSepsis survivors often develop chronic organ dysfunction, yet the mechanisms linking acute infection to long-term damage remain unclear. We show that sepsis triggers expansion of inflammatory and profibrotic macrophages derived from bone marrow precursors in the kidney and heart. These alterations were associated with impaired organ resilience to subsequent injury, which suggest macrophage-driven maladaptive repair as a potential target to improve long-term outcomes after sepsis.

immunology↗

bioRxiv2025

Splicing Isoforms Associated to TGFb-Induced Myofibroblast Activation

Myofibroblast differentiation is a key process in developmental biology and involved in numerous physiopathology. The gene expression program orchestrating fibroblast to myofibroblast differentiation, as well as its recapitulation by TGF{beta} stimulation in vitro, is relatively well characterized. Intriguingly, it is known that the splicing isoform EDA+FN1 is a marker and driver of myofibroblast differentiation, but the alternative splicing landscape of myofibroblast is unknown. Here, we performed a high-throughput transcriptomic approach by RNA-Seq in a primary skin fibroblast line and uncover more than 250 splicing isoforms associated with TGF{beta}-induced myofibroblasts using two different bioinformatic pipelines. This splicing profile highlights a distinct layer of regulation when compared to the global gene expression profile of myofibroblasts. A 5 alternative splicing event (ASE) signature [ACTN1-19A/19B; COL5A1-64A/64B; COL6A3 exon 4; FLNA exon 30 and TPM1-6a/6b] was further validated by ddPCR and AS-PCR and retrieved in publicly available RNA-Seq datasets describing other TGF{beta}-stimulated lung and skin fibroblasts. Surprisingly, TGF{beta} does not induce an EDA+FN1 splicing shift, although it stimulates global fibronectin expression. Thus, we conclude that the 5 ASEs signature may be used as putative universal myofibroblast markers and be of functional significance to myofibroblast formation and biology.

genomics↗

bioRxiv2025

Oral OM-89 in combination with antibiotics prevents recurrent infection in a mouse model of urinary tract infection

Urinary tract infection (UTI) is a very common infection. Approximately 25% of all women will experience recurrent infection, defined by 2 UTI in 6 months or 3 UTI in a 12 month period. Recurrent infection is thought to be due in part to the development of local bacterial reservoirs in the bladder after an infection. These reservoirs are undetected by the host immune system and may re-emerge after resolution of the primary infection. Frequently, recurrent UTI require repeated antibiotic use, leading to the development of resistance, and negatively impacting the quality of life of the patient. Given the rise in multidrug resistant uropathogens, treatments that do not rely upon antibiotics are urgently needed for this patient population. We assessed the capacity of a lyophilized E. coli extract, OM-89(R), as a preventive measure to reduce the incidence of spontaneous recurrence in a mouse cystitis model. Administration of OM-89 per os after the initiation of an acute UTI significantly reduced the number of spontaneous recurrent UTI in female mice over a 1 month follow-up period only when the animals were also treated with antibiotics. Protection against recurrent UTI arose quickly and without changes in any adaptive immune response parameter measured, ruling out a role for OM-89 in augmenting adaptive immunity to protect against spontaneous recurrent UTI in the first month of use.

immunology↗

bioRxiv2025

Evolution of CYP71D as a driving force of the diversification of monoterpene indole alkaloid biosynthesis

Monoterpene indole alkaloids (MIAs) constitute a vast group of plant natural products synthesized within the Gentianales order. MIAs possess outstanding pharmacological properties that explain their wide use in the treatment of human diseases. These biological activities result from the complex structure of MIAs that originate from intricated biosynthetic pathways involving several enzyme families and notably cytochrome P450s. The early steps of MIA synthesis involve several P450s from the 71 clade, which catalyse the conversion of various reduced strictosidine aglycones into MIAs from the mavacurane, strychnane, akuammilane, sarpagane, and heteroyohimane groups. An extensive study of these P450 distribution in genomic resources reveals that they all belong to a single evolutionary lineage named GAS clade, restricted to the MIA producing Gentianales (Gelsemiaceae and Rauvolfioideae). A related but distinct P450 lineage (named sister GAS clade) was found in non-MIA producing Gentianales and species producing structurally distinct MIAs (Rubiaceae). Functional characterization of 36 members of the GAS clade revealed that these enzymes felt into four main groups of activity depending on substrate acceptance (ex: tetrahydroalstonine, geissoschizine, ajmalicine...) and the nature of the catalyzed reaction (aromatization, cyclisation). These characterizations also lead to the identification of a yohimbane aromatization activity for several of these P450s, increasing the number of MIA scaffolds associated with GAS activity to six. Lastly, the chronology of emergence of these GAS activities was assessed by using ancestral sequence reconstitution, establishing that the initial ancestor of the whole GAS clade exhibits a main alstonine synthase activity. Subsequent gene duplication events, combined with neofunctionalization, facilitated the progressive emergence of eight additional activities, variably distributed among the four GAS subgroups. This comprehensive enzyme characterization establishes the evolutionary trajectory of the GAS clade, demonstrating how its diversification has progressively shaped the chemical diversity of MIAs in Gentianales.

biochemistry↗

bioRxiv2024

A simple ex vivo bladder infection model permits study of host-pathogen interactions in UTI

Urinary tract infections (UTI) are one of the most common infections, worldwide. To understand mechanisms of UTI pathogenesis and find new treatments, researchers often use animal models, such as mice or rats. However, studying certain phenotypes in animals can be difficult. Additionally, using animals in research comes with significant administrative and ethical challenges. To address these challenges, we developed a simple, reproducible, and cost-effective model to study UTI using donated mouse bladder tissue that would otherwise be discarded. This model allows researchers of all experience levels to study interactions between the host and pathogen in a controlled environment. We tested uropathogenic E. coli colonization and invasion of isolated urothelial sheets from 30 minutes to 24 hours, finding that bacterial burden in our ex vivo model was comparable to in vivo UTI mouse models. To optimize reproducibility, we tested multiple variables, including technical parameters, such as incubator conditions, and biological factors, such as biological sex or prior pregnancy in the donor mouse. This method offers several advantages, including assessment of early host-pathogen interactions, immune cell uptake of bacteria, the impact of age and sex of donor animals in infection, and diverse bacterial strains, mutants, or treatments. In addition, in some countries, sharing material recovered from animals sacrificed for other reasons does not require additional ethical approval by the receiving laboratory, providing a resource for labs without access to animals and reducing administrative burden. Given the breadth of the model with respect to sex, age, mouse and bacterial strain, and the ability to test any parameter that can be included in a 96-well plate, we believe this model will be useful to UTI researchers, with potential application beyond infection or even beyond the bladder to other tissues.

immunology↗

bioRxiv2024

Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection in hospitalized COVID-19 patients

Genome-wide association studies performed in patients with coronavirus disease 2019 (COVID-19) have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity. However, the underlying cis-regulatory genetic factors that contribute to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we used single-cell RNA-sequencing to quantify genetic contributions to cis-regulatory variation in 361,119 peripheral blood mononuclear cells across 63 COVID-19 patients during acute infection, 39 samples collected in the convalescent phase, and 106 healthy controls. Expression quantitative trait loci (eQTL) mapping across cell types within each disease state group revealed thousands of cis-associated variants, of which hundreds were detected exclusively in immune cells derived from acute COVID-19 patients. Patient-specific genetic effects dissipated as infection resolved, suggesting that distinct gene regulatory networks are at play in the active infection state. Further, 17.2% of tested loci demonstrated significant cell state interactions with genotype, with pathways related to interferon responses and oxidative phosphorylation showing pronounced cell state-dependent variation, predominantly in CD14+ monocytes. Overall, we estimate that 25.6% of tested genes exhibit gene-environment interaction effects, highlighting the importance of environmental modifiers in the transcriptional regulation of the immune response to SARS-CoV-2. Our findings underscore the importance of expanding the study of regulatory variation to relevant cell types and disease contexts and argue for the existence of extensive gene-environment effects among patients responding to an infection.

genomics↗

bioRxiv2024

Novel Immunological Markers of Intestinal Impairment Indicative of HIV-1 Status and/or Subclinical Atherosclerosis

Antiretroviral therapy (ART) controls HIV-1 replication in people with HIV-1 (PWH), but immunological restauration is not achieved at mucosal barriers. Intestinal integrity impairment fuels microbial translocation and chronic immune activation, thus heightening the cardiovascular disease (CVD) risk. Here, we sought to identify novel immunological predictors of the HIV and CVD status in the peripheral blood of ART-treated PWH (HIV+; n=42) and uninfected participants (HIV-; n=40) of the Canadian HIV and Aging Cohort Study (CHACS), with/without subclinical coronary atherosclerotic plaques, measured by Coronary Computed Tomography Angiography as total plaque volume (TPV, mm3). PBMCs were analyzed by flow cytometry for the expression of T-cell lineage (CD45, CD3, CD4, CD8, CD8{beta}, TCR{beta}, TCR{gamma}{delta}), epithelial cell (EpCAM/CD326), activation (HLA-DR), and gut-homing/residency markers (CD69, CD196/CCR6, CD199/CCR9, CD49d/Itg4, CD103/ItgE, Itg{beta}7). CellEngine supervised clustering of the flow cytometry data revealed profound alterations in the CD3+ T-cell pool in relationship with the HIV status, with the accumulation of peculiar CD8+TCR{beta}+ and TCR{gamma}{delta}+ cells, to the detriment of CD4+TCR{beta}+ subsets. FlowJo manual gating further identified CD4+ T-cell subsets with peculiar CD326+CD69+CCR6+ItgE+ and CCR6+Itg{beta}7- phenotypes that were increased in frequency in HIV+ versus HIV- participants, together with a decreased frequency of CD8+ T-cells with an intraepithelial lymphocyte (IEL)-like CD3+CD4- TCR{beta}+TCR{gamma}{delta}-CD8+CD8{beta}- phenotype. Finally, multivariate logistic regression revealed the predictive capacity of specific T-cell subsets regarding the HIV/CVD status, and TPV values. Of particular relevance, we identified ItgE+CD8+, ItgE-CD8+, CCR6+CD4+, and CCR6+Itg{beta}7- CD4+ T-cell subsets as strong positive predictors of atherosclerotic plaque volume in crude models or upon adjustment for HIV/CVD confounding factors.

immunology↗

bioRxiv2024

Genome-based discovery of pachysiphine synthases in Tabernaemontana elegans

Plant specialized metabolism represents an inexhaustible source of active molecules, some of which have been used in human health for decades. Among these, monoterpene indole alkaloids (MIAs) include a wide range of valuable compounds with anticancer, antihypertensive, or neuroactive properties. This is particularly the case for the pachysiphine derivatives which show interesting antitumor and anti-alzheimer activities but accumulate at very low levels in several Tabernaemontana species. Unfortunately, genome data in Tabernaemontanaceae are lacking and knowledge on the biogenesis of pachysiphine-related MIAs in planta remains scarce, limiting the prospects for biotechnological supply of many pachysiphine-derived biopharmaceuticals. Here, we report a raw version of the toad tree (Tabernaemontana elegans) genome sequence. These new genomic resources led to the identification and characterization of a couple of genes encoding cytochrome P450 with pachysiphine synthase activity. Our phylogenomic and docking analyses highlights the different evolutionary processes that have been recruited to epoxidize the pachysiphine precursor tabersonine at a specific position and in a dedicated orientation, thus enriching our understanding of the diversification and speciation of the MIA metabolism in plants. These gene discoveries also allowed us to engineer the synthesis of MIAs in yeast through the combinatorial association of metabolic enzymes resulting in the tailor-made synthesis of non-natural MIAs. Overall, this work represents a step forward for the future supply of pachysiphine-derived drugs by microbial cell factories. Significance StatementWhile pachysiphine is a monoterpene indole alkaloid of high interest and the precursor of an anti-Alzheimer compound, its biosynthesis involving the epoxidation of tabersonine remains uncharacterized. By sequencing and assembling the genome of Tabernaemontana elegans, we identified two P450s exhibiting a pachysiphine synthase activity that we modelized to explore the evolutionary scenario leading to the acquisition of this expoxidase activity; and used to engineer yeast cell factories for securing pachysiphine supply and producing new-to-nature alkaloids.

plant biology↗

bioRxiv2024

Overexpressing NRT2.7 induces nitrate export from the vacuole and increases growth of Arabidopsis

Nitrogen nutrition is essential for crop yield but applying fertilizers has detrimental effects on the environment. Compartmenting nitrate into vacuoles is one of the options to develop Nitrogen-efficient crop adapted to less fertilizers. Only few proteins involved in nitrate transport on the tonoplast have been identified. CLCa is the major transporter involved in nitrate storage in Arabidopsis but it can also facilitate nitrate remobilization from the vacuole in guard cells. Several other nitrate transporters amongst NRT2.7 have been localized in this membrane. The transport mechanism of NRT2.7 has not yet been defined as this protein is present mainly in seed cells that are not easily amenable for electrophysiology analysis. Here, we investigated NRT2.7 function through its ectopic overexpression in a clca knock-out mutant. Although the growth diminution of clca on nitrogen sufficient medium was complemented, nitrate homeostasis was not restored by NRT2.7 activity. Moreover, NRT2.7 ectopic overexpression in wild-type background (WT) increased growth under limiting nitrogen supply, suggesting that NRT2.7 stimulates nitrate efflux from vacuoles. This hypothesis was demonstrated by electrophysiological nitrate flux measurements on isolated vacuoles. This discovery of NRT2.7 function and more largely the coupling of vacuolar nitrate fluxes with growth under low nitrate supply, will enable new strategies for engineering better NUE for a more sustainable agriculture. HighlightThe overexpression of the nitrate transporter NRT2.7 stimulates growth by increasing the export of nitrate from the vacuole, the main cell compartment for nitrate storage.

plant biology↗

bioRxiv2023

A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy

Cardiovascular disease (CVD) remains an important co-morbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed on the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) >5%), revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by Computed tomography angiography scan (CTAScan) as total (TPV) and low attenuated plaque volume (LAPV) in ART-treated PLWH (HIV+) versus uninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+ T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells, were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1 and triglyceride levels, lower Th17/Treg ratios, and classical monocyte expansion. Among HIV+, TPV+ versus TPV- exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhigh monocyte, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhigh monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.

immunology↗

bioRxiv2023

Corythauma ayyari (Insecta, Heteroptera, Tingidae) depends on its host plant to invade Europe

Biological invasions increase with the intensity of globalization, human activities, and climate change. Insects represent a high potential of invasive species due to their adaptability to new environment. We analysed here the invasiveness of an Asian phytophagous bug, Corythauma ayyari (Heteroptera, Tingidae), recently recorded in Europe, and that depends on Jasminum spp., an ornamental plant widespread in Europe. We modelled its current distribution, projected it into the future and tested its niche overlap between native and invaded areas. When considering the host plant as environmental variable, the analysis shows that C. ayyari shifted to a new ecological niche but its distribution is restricted by its host plant distribution. Including or excluding the host plant as environmental variable has an impact on species distribution and should be considered when dealing with phytophagous species.

ecology↗

bioRxiv2022

Subclinical Atherosclerosis is Associated with Discrepancies in BAFF and APRIL Levels and Altered Breg Potential of Precursor-like Marginal Zone B-Cells in HIV Treated Individuals

Chronic inflammation persists in people living with HIV (PLHIV) despite antiretrovial therapy (ART), and is involved in their premature development of cardiovascular diseases (CVD) such as atherosclerosis. We have previously reported that an excess of "B-cell activating factor" (BAFF), an important molecule for the selection and activation of first line Marginal Zone (MZ) B-cell populations, is associated with deregulations of precursor-like MZ (MZp), whose potent B-cell regulatory (Breg) capacities are altered in PLHIV, early on and despite 1-2 years of ART. Based on these observations, and growing evidence that MZ populations are involved in atherosclerosis control, we designed a cross sectional study to explore the associations between BAFF and its analogue "A proliferation-inducing ligand" (APRIL) with subclinical CVD in long time treated individuals of the Canadian HIV and Aging Cohort Study (CHACS) imaging sub-study group. We also characterized the Breg profile of MZp from the blood of these individuals. Results were correlated with the total volume of atherosclerotic plaques (TPV) and with CVD risk factors and biomarkers. TPV was measured using cardiac computerised tomography angiography, and presence of CVD was defined as TPV > 0. We report that blood levels of BAFF are elevated and correlate positively with CVD and its risk factors in PLHIV from the CHACS, in contrast to APRIL levels, which correlate negatively with these factors. Expression levels of Breg markers such as NR4A3, CD39, CD73 and CD83 are significantly lower in PLHIV when compared to those of HIV-uninfected controls. In vitro experiments show that APRIL upregulates the expression of Breg markers by blood MZp from HIV-uninfected individuals, while this modulation is dampened by the addition of recombinant BAFF. Altogether, our observations suggest that strategies viewed to modulate levels of BAFF and/or APRIL could eventually represent a potential treatment target for CVD in PLHIV.

immunology↗

bioRxiv2022

The Arabidopsis transcription factor NLP2 regulates early nitrate responses and integrates nitrate assimilation with energy and carbon skeleton supply

Nitrate signaling improves plant growth under limited nitrate availability and, hence, optimal resource use for crop production. Ongoing work has identified several transcriptional regulators of nitrate signaling, including the Arabidopsis thaliana transcription factor NIN-LIKE PROTEIN 7 (NLP7), but additional regulators likely remain to be identified. Here, we characterized Arabidopsis NLP2 as a master upstream transcriptional regulator of early nitrate responses that interacts with NLP7 in vivo and shares key molecular features such as nitrate-dependent nuclear localization, a DNA binding motif, and some target genes with NLP7. Additional genetic, genomic and metabolic approaches revealed a specific role for NLP2 in the nitrate-dependent regulation of carbon and energy-related processes that likely influence plant growth under distinct nitrogen environments. Our findings highlight the complementarity and specificity of NLP2 and NLP7 in orchestrating a multi-tiered nitrate regulatory network that links nitrate assimilation with carbon and energy metabolism for efficient nitrogen use and biomass production. One-sentence summaryNLP2 and NLP7 orchestrate plant responses to nitrate supply and control nitrate- dependent regulation of carbon and energy metabolism.

plant biology↗