Biology subjects

Gerard, C.

Publications and source records attributed to Gerard, C..

11 recordsLinked to original sources

bioRxiv2025

CP12 controls ribulose 1,5 bisphosphate recycling and carbon acquisition in Chlamydomonas reinhardtii

The small chloroplastic protein CP12 has multiple functions, including the regulation of enzymes in the Calvin-Benson-Bassham cycle. Here, we investigated its role in the acclimation of Chlamydomonas reinhardtii to varying CO2 availability. This alga has a CO2 concentrating mechanism that increases the supply of CO2 to ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and involves hallmarks such as HCO3- transporters and carbonic anhydrases as well as the condensation of RuBisCO within the pyrenoid via its interaction with a scaffold protein named Essential Pyrenoid Component 1 (EPYC1). We showed that compared to the wild type, at high CO2, C. reinhardtii CP12 deletion mutants, or partially complemented mutants, have less phosphoribulokinase and ribulose-1,5-bisphosphate (RuBP) indicating that the regeneration of RuBP is regulated by CP12. In the absence of CP12, the expected relocation of RuBisCO towards the pyrenoid was not observed upon transition from high to very low CO2, contrary to WT cells. The CP12 deletion mutants are a unique example where the induction of CO2 concentrating mechanism hallmarks at very low CO2 was not accompanied by RuBisCO relocation. Altogether, these results suggest that CP12 contributes to the coordination between RuBP regeneration, RuBisCO location and CO2 acquisition. HighlightCP12 regulates phosphoribulokinase amount and its product RuBP. The CP12 deletion mutants are unique example where the RuBisCO location was not correlated with the induction of CO2 concentration mechanism. This reveals a novel link between Calvin-Benson-Bassham cycle regulation and CO2 concentrating mechanisms in Chlamydomonas reinhardtii. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/659560v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1cdadb2org.highwire.dtl.DTLVardef@46ae27org.highwire.dtl.DTLVardef@538295org.highwire.dtl.DTLVardef@a214c7_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

How does urbanization shape shell phenotype, behaviour and parasite prevalence in the snail Cornu aspersum?

Urbanization is a complex and multivariate environmental change, leading to e.g. habitat fragmentation and loss, changes in local climate, soil imperviousness, pollution, etc. This is likely to exert pressures simultaneously on various dimensions of organisms multivariate phenotypes, leading to trait shifts with potential ecological consequences. However, responses to urbanization are often studied one (type of) trait at a time. In this context, we studied how, in the brown garden snail Cornu aspersum, shell phenotype (shell size and colour/reflectance), behaviour (food intake, mobility) and metazoan parasite prevalence respond to urbanization. Within an urbanization gradient spanning the French city of Rennes, we found that snails from more urbanized sites closer to the urban centre were smaller, whereas urbanization had no detectable effect on shell reflectance, parasite prevalence or behaviour. Larger snails and snails with paler shells were more likely to be infected by trematode metacercariae and sexually-transmitted nematodes (Nemhelix bakeri), respectively. Snails harbouring trematode sporocysts ate typically less, while those infected by N. bakeri moved more slowly. We discuss the decrease of snail size along the urbanization gradient in relation with the Urban Heat Island effect and the potential decrease of resource quality and availability in urban sites. The absence of detectable effects of urbanization on shell reflectance, mobility and parasite prevalence may be due to scale mismatches between how urbanization is measured and how snails experience microhabitats. We propose further experimental and field studies to decipher interactions between urbanization effects, shell phenotype, life-history traits and parasitism.

ecology↗

bioRxiv2023

Surface temperatures are influenced by handling stress independently of glucocorticoid levels in wild king penguins

Assessing the physiological stress responses of wild animals opens a window for understanding how organisms cope with environmental challenges. Since stress response is associated with changes in body temperature, the use of body surface temperature through thermal imaging could help to measure acute and chronic stress responses non-invasively. We used thermal imaging, acute handling-stress protocol and an experimental manipulation of corticosterone (the main glucocorticoid hormone in birds) levels in breeding king penguins (Aptenodytes patagonicus), to assess: 1. the potential contribution of the Hypothalamo-Pituitary-Adrenal (HPA) axis in mediating chronic and acute stress-induced changes in adult surface temperature, 2. the influence of HPA axis manipulation on parental investment through thermal imaging of eggs and brooded chicks, and 3. the impact of parental treatment on offspring thermals response to acute handling. Maximum eye temperature (Teye) increased and minimum beak temperature (Tbeak) decreased in response to handling stress in adults, but neither basal nor stress-induced surface temperatures were significantly affected by corticosterone implant. While egg temperature was not significantly influenced by parental treatment, we found a surprising pattern for chicks: chicks brooded by the (non-implanted) partner of corticosterone-implanted individuals exhibited higher surface temperature (both Teye and Tbeak) than those brooded by glucocorticoid-implanted or control parents. Chicks response to handling in terms of surface temperature was characterized by a drop in both Teye and Tbeak independently of parental treatment. We conclude that the HPA axis seems unlikely to play a major role in determining chronic or acute changes in surface temperature in king penguins. Changes in surface temperature may primarily be mediated by the Sympathetic-Adrenal-Medullary (SAM) axis in response to stressful situations. Our experiment did not reveal a direct impact of parental HPA axis manipulation on parental investment (egg or chick temperature), but a potential influence on the partners brooding behaviour. HighlightsO_LIExperimental increase in corticosterone does not affect king penguins surface temperature C_LIO_LIAcute handling stress increases eye but decreases beak surface temperature in adults C_LIO_LIAcute handling decreases both eye and beak surface temperatures in young chicks C_LIO_LIParental corticosterone treatment does not affect egg surface temperature during incubation C_LIO_LIChicks brooded by non-implanted partners of corticosterone parents are warmer than chicks brooded by others adults. C_LI

zoology↗

bioRxiv2022

Morph-dependent effect of nematode infection on host movement in the land snail Cepaea nemoralis (Mollusca, Gastropoda)

Host behaviour can be influenced by parasitic risk and infection through a variety of direct and indirect mechanisms. We can expect individuals expressing different phenotypes to also differ in the ways their behaviour is altered by parasites. We used the land snail Cepaea nemoralis, a species with various shell colour morphs differing in behaviour and physiology, as a model to study the link between parasite response and individual behaviour variation. We analysed metazoan parasite abundance and its relation to behaviour (movement and food intake) in snails from three shell morphs (from light unbanded to darker five-banded) and from two neighbouring populations from contrasted environments. Snails were parasitized by mites, trematodes and nematodes, from rarest to most frequent. We confirm that terrestrial gastropods can defend against infection by trapping parasitic nematodes in their shell. We show that nematode encapsulated in shells can uncover past infections even when a snail population is currently nematode-free, possibly due to parasite seasonality. We present new observations suggesting that not only nematodes but also mites might be encapsulated in shells. Infection levels varied between morphs, with darker snails harbouring fewer nematodes. Behaviour (movement and food intake) was linked to nematode, but not trematode infection. Individuals with higher nematode load ate less, irrespective of morph and population. The most-infected morph (unbanded snails) showed reduced activity in the nematode-infected population compared to the one that was nematode-free at sampling time. As a result, parasites may cancel previously described behavioural differences between morphs. We discuss the possible mechanisms explaining morph-dependent responses to parasites, and how parasite risk may be an unseen force shaping C. nemoralis morph variation in space and time. We conclude on the possible ecological consequences of the link, mediated by shell colour, between thermal and immune responses.

ecology↗

bioRxiv2020

Unacylated ghrelin and AZP531 suppress the 3D growth of breast cancers

Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, it remains the second leading cause of cancer-related death in the US. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. One major area of research relates to its reported effects to increase insulin sensitivity in diabetics, this being the basis for the development of unacylated ghrelin analog, AZP531 or livoletide, now in clinical trials for the treatment of Prader-Willi Syndrome. The mechanism of action of unacylated ghrelin is largely uncharacterized, in any system, because it does not bind to or activate the cognate ghrelin receptor, GHSR1a. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP531. We report potent effects of unacylated ghrelin, at picomolar doses, on the growth of breast cancer cells, dependent on 3D culture and activation of Gi. Suppression of MAPK signaling by unacylated ghrelin leads to cell cycle arrest and apoptosis. AZP531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

cancer biology↗

bioRxiv2019

A novel mouse model designed for studying cholangiocarcinoma tumorigenesis uncovers a role for a SOX17-Tensin 4 pathway

Background & AimsAlthough earlier diagnosis and treatment of intrahepatic cholangiocarcinoma (iCCA) is necessary to improve therapy, there is still limited information available about initiation and evolution of iCCA precursor lesions. Therefore, there is a need to identify mechanisms driving formation of precancerous lesions and their progression towards invasive tumor using experimental models that faithfully recapitulate human tumorigenesis. MethodsWe generated a new mouse model which combines cholangiocyte-specific expression of KrasG12D with 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-induced inflammation to mimic iCCA development in patients with cholangitis. Histological and transcriptomic analyses of the mouse precursor lesions and iCCA were performed and compared with human analyses. The function of genes overexpressed during tumorigenesis was investigated in human cell lines. ResultsMice expressing KrasG12D in cholangiocytes and fed a DDC diet developed cholangitis, ductular proliferations, intraductal papillary neoplasms of bile ducts (IPNBs) and eventually iCCAs. The histology of mouse and human IPNBs were highly similar, and mouse iCCAs displayed histological characteristics of human mucin-producing large duct type iCCA. Signaling pathways activated in human iCCA were activated in mice. The identification of transition zones between IPNB and iCCA on tissue sections, combined with RNA-sequencing analyses of the lesions supported that iCCAs derive from IPNBs. We provide evidence that a gene cascade which comprises KRASG12D, SRY-related HMG box transcription factor 17 (SOX17) and Tensin 4 (TNS4), and which is activated by epidermal growth factor, promotes tumor progression. ConclusionsWe developed a novel mouse model that faithfully recapitulates human iCCA tumorigenesis and identified a gene cascade promoting tumor progression.

cancer biology↗

bioRxiv2019

Modeling the dynamics of Let-7-coupled gene regulatory networks linking cell proliferation to malignant transformation

The microRNA Let-7 controls the expression of proteins that belong to two distinct gene regulatory networks, namely a cyclin-dependent kinases (Cdks) network driving the cell cycle and a cell transformation network which can undergo an epigenetic switch between a non-transformed and a malignant transformed cell state.\n\nUsing mathematical modeling and transcriptomic data analysis, we here investigate how Let-7 controls the cdk-dependent cell cycle network, and how it couples the latter with the transformation network. We also determine whether the two networks can be combined into a larger entity that impacts on cancer progression.\n\nOur analysis shows that the switch from a quiescent to a cycling state depends on the relative levels of Let-7 and several cell cycle activators. Numerical simulations further indicate that the Let-7-coupled cell cycle and transformation networks control each other, and our model identifies key players for this mutual control. Transcriptomic data analysis from the The Cancer Genome Atlas (TCGA) suggest that the two networks are activated in cancer, in particular in gastrointestinal cancers, and that the activation levels vary significantly among patients affected with a same cancer type. Our mathematical model, when applied to a heterogeneous cell population, suggests that heterogeneity among tumors results from stochastic switches between a non-transformed cell state with low proliferative capability and a transformed cell state with high proliferative property. The model further predicts that Let-7 may reduce tumor heterogeneity by decreasing the occurrence of stochastic switches towards a transformed, proliferative cell state.\n\nIn conclusion, we identified the key components responsible for the qualitative dynamics of two GRNs interconnected by Let-7. The two GRNs are heterogeneously involved in several cancers, thereby stressing the need to consider patients specific GRN characteristics to optimize therapeutic strategies.

systems biology↗

bioRxiv2018

Changes in rumen microbiota of cows in response to dietary supplementation with nitrate, linseed and saponin alone or in combination.

Dietary supplementation with linseed, saponins and nitrate is a promising methane mitigation strategy in ruminant production. The main objective of this work was to assess the effects of these additives on the rumen microbiota in order to understand underlying microbial mechanisms of methane abatement. Two 2 x 2 factorial design studies were conducted simultaneously, which also allowed us to make a broad-based assessment of microbial responses. Eight non-lactating cows were fed diets supplemented with linseed or saponin in order to decrease hydrogen production and nitrate to deviate hydrogen consumption; also, combinations of linseed plus nitrate or saponin plus nitrate were used to explore the interaction between dietary treatments. Amplicon sequencing of 18S and 16S rRNA genes was employed to characterise rumen microbes. Nitrate fed alone or in combination in both studies dramatically affected the composition and structure of rumen microbiota, though impacts were more evident in one of the studies. Linseed moderately modified bacterial community structure with no effect on rumen methanogens and protozoa. Indicator OTU analysis revealed that both linseed and nitrate reduced the relative abundance of hydrogen-producing Ruminococcaceae. Linseed increased the proportion of bacteria known to reduce succinate to propionate, whereas nitrate supplementation increased nitrate-reducing bacteria and decreased the metabolic activity of rumen methanogens. Saponins had no effect on the microbiota. Inconsistency found between the two studies, when nitrate was fed to the cows could be explained by changes in microbial ecosystem functioning rather than changes in microbial community structure.\n\nImportanceThis study aimed at identifying the microbial mechanisms of enteric methane mitigation when linseed, nitrate and saponins were fed to non-lactating cows alone or in a combination. Hydrogen is a limiting factor in rumen methanogenesis. We hypothesised that linseed and saponins would affect hydrogen producers and nitrate would deviate hydrogen consumption thus leading to reduced methane production in the rumen. Contrary to what was foreseen, both linseed and nitrate had a deleterious effect on hydrogen producers; linseed also redirected hydrogen consumption towards propionate production, whereas nitrate stimulated the growth of nitrate reducing and hence hydrogen-consuming bacterial taxa. Fundamental knowledge of microbial mechanism involved in rumen methanogenesis, provides novel insights for the development of new or the optimisation of existing methane mitigation strategies.

molecular biology↗

bioRxiv2018

Dynamics and predicted drug response of a gene network linking dedifferentiation with beta-catenin dysfunction in hepatocellular carcinoma

Alterations of individual genes variably affect development of hepatocellular carcinoma (HCC), prompting the need to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRN). Here, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of CTNNB1 ({beta}-CATENIN). LIN28B and CTNNB1 form a functional GRN with SMARCA4 (BRG1), Let-7b, SOX9, TP53 and MYC. GRN activity is detected in HCC and gastrointestinal cancers; it negatively correlates with HCC prognosis and contributes to a transcriptomic profile typical of the proliferative class of HCC. Using data from The Cancer Genome Atlas and from transcriptomic, transfection and mouse transgenic experiments, we generated and validated a quantitative mathematical model of the GRN. The model predicts how the expression of GRN components changes when the expression of another GRN member varies or is inhibited by a pharmacological drug. The dynamics of GRN component expression reveal distinct cell states that can switch reversibly in normal condition, and irreversibly in HCC. We conclude that identification and modelling of the GRN provides insight into prognosis, mechanisms of tumor-promoting genes and response to pharmacological agents in HCC.

cancer biology↗

bioRxiv2018

Microbiome inhibition of IRAK-4 by trimethylamine mediates metabolic and immune benefits in high-fat-diet-induced insulin resistance

The global type 2 diabetes epidemic is a major health crisis and there is a critical need for innovative strategies to fight it. Although the microbiome plays important roles in the onset of insulin resistance (IR) and low-grade inflammation, the microbial compounds regulating these phenomena remain to be discovered. Here, we reveal that the microbiome inhibits a central kinase, eliciting immune and metabolic benefits. Through a series of in vivo experiments based on choline supplementation, blocking trimethylamine (TMA) production then administering TMA, we demonstrate that TMA decouples inflammation and IR from obesity in the context of high-fat diet (HFD) feeding. Through in vitro kinome screens, we reveal TMA specifically inhibits Interleukin-1 Receptor-associated Kinase 4 (IRAK4), a central kinase integrating signals from various toll-like receptors and cytokine receptors. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells, and improves mouse survival after a lipopolysaccharide-induced septic shock. Consistent with this, genetic deletion and chemical inhibition of IRAK4 result in similar metabolic and immune improvements in HFD. In summary, TMA appears to be a key microbial compound inhibiting IRAK4 and mediating metabolic and immune effects with benefits upon HFD. Thereby we highlight the critical contribution of the microbial signalling metabolome in homeostatic regulation of host disease and the emerging role of the kinome in microbial-mammalian chemical crosstalk.

systems biology↗

bioRxiv2017

Bottled aqua incognita: Microbiota assembly and dissolved organic matter diversity in natural mineral waters

BackgroundNon-carbonated natural mineral waters contain microorganisms that regularly grow after bottling despite low concentrations of dissolved organic matter (DOM). Yet, the compositions of bottled water microbiota and organic substrates that fuel microbial activity, and how both change after bottling, are still largely unknown.\n\nResultsWe performed a multifaceted analysis of microbiota and DOM diversity in twelve natural mineral waters from six European countries. 16S rRNA gene-based analyses showed that less than ten species-level operational taxonomic units (OTUs) dominated the bacterial communities in the water phase and associated with the bottle wall after a short phase of post-bottling growth. Members of the betaproteobacterial genera Curvibacter, Aquabacterium, and Polaromonas (Comamonadaceae) grew in most waters and represent ubiquitous, mesophilic, heterotrophic aerobes in bottled waters. Ultrahigh-resolution mass spectrometry of DOM in bottled waters and their corresponding source waters identified thousands of molecular formulae characteristic of mostly refractory, soil-derived DOM.\n\nConclusionsThe bottle environment, including source water physicochemistry, selected for growth of a similar low-diversity microbiota across various bottled waters. Relative abundance changes of hundreds of multi-carbon molecules were related to growth of less than ten abundant OTUs. We thus speculate that individual bacteria cope with oligotrophic conditions by simultaneously consuming diverse DOM molecules.

microbiology↗