Nicolas Galanos

Emilie Gillon

Anne Imberty

Susan E Matthews

Sébastien Vidal

Pillar[5]arene-based glycoclusters: Synthesis and multivalent binding to pathogenic bacterial lectins

Anti-adhesive glycoclusters offer potential as therapeutic alternatives to classical antibiotics in treating infections. Pillar[5]arenes functionalised with either five galactose or five fucose residues were readily prepared using CuAAC reactions and evaluated for their binding to three therapeutically relevant bacterial lectins: LecA and Lec B from Pseudomonas aeuruginosa and BambL from Burkholderia ambifaria. Steric interactions were demonstrated to be a key factor in achieving good binding to LecA with more flexible galactose glycoclusters showing enhanced activity. In contrast binding to the fucose-selective lectins confirmed the importance of topology of the glycoclusters for activity with the pillar[5]arene ligand proving a selective ligand for BambL.

Introduction

Pillararenes, [1][2][3][4][5] the newest members of the calixarene family, have, since their introduction in 2008, 6 been rapidly developed for a wide range of applications including sensors, rotaxane wheels and supramolecular polymers. [1][2][3][4][5] In contrast to calix [4]arene and resorcin [4]arene, pillar [5]arene offers a highly rigid and symmetrical structure with two identical faces for functionalisation, and thus higher valency on a small platform, and is inherently chiral. Synthetic procedures have been developed for the preparation of both fully and partially functionalised pillar [5]arenes. In particular, use of nonsymmetrically functionalised alkoxybenzene derivatives in the condensation reaction provides platforms featuring five regularly distributed points of functionalisation 7 whereas further selective functionalisation can be achieved using statistical mixtures 8,9 in the condensation and through post cyclisation approaches.

The biological property of multivalency has attracted significant attention for the development of cluster molecules capable of high-affinity binding, based on a wide range of topologically different scaffolds. [10][11][12] One particular area of interest that has recently come to the fore is the development of anti-adhesive molecules against pathogen infections.

Glycoclusters capable of disrupting bacterial-to-human cell interactions and formation of bacteria biofilms through interaction with bacterial lectins have been designed. [13][14][15][16][17][18][19][20][21][22] We have previously developed a topologically diverse series of such glycoclusters based on calix[4]- 23,24 and calix [6]arenes, 25 resorcin [4]arenes, 26 fullerenes, 27,28 and porphyrins. 25,[29][30][31][32] The calix [4]arene-based glycoclusters have been demonstrated to alter the lectin-mediated infectivity of Pseudomonas aeruginosa in lungs. 23 P. aeruginosa is an opportunistic pathogen, with emerging drug resistance, responsible for severe lung infections in immunecompromised patients. 33 Two major soluble lectins involved in infectivity have been identified; the galactose specific LecA 34 and LecB, 35,36 which binds to fucose and fucose-containing oligosaccharides, particularly Lewis a trisaccharide. Whilst LecA 50 has been implicated in damage to the alveolae and uptake of the bacteria into cells, 37,38 LecB has been demonstrated to be involved in cell adhesion 15 making both lectins ideal targets for therapeutic intervention.

In contrast to the tetrameric LecB, the fucose selective lectin 55 BambL 39 from Burkholderia ambifaria self assembles into a trimeric β-propeller fold presenting six binding sites. B. ambifaria, a gram negative organism, is a component of the Burkholderia cepacia complex (BCC) which is responsible for both acute and chronic respiratory disease and, in some cases, 60 cepacia syndrome particularly in patients with cystic fibrosis. 40 Although, the role of BambL in infection has not been fully characterised, it has been shown to bind to blood group associated oligosacacharides 39 and structurally similar lectins 41 have been implicated in inflammation in epithelial cells making it 65 an interesting target for multivalent glycoclusters. Additionally, comparison of binding to tetrameric LecB versus hexameric BambL provides fundamental insights into the role of topology of glycoclusters in achieving selective lectin binding. The potential of pillar [5]arene scaffolds for the development of 70 antimicrobial glycoclusters was first shown using a decamannose functionalised pillar [5]arene which was able to inhibit adhesion of Escherichia coli to red blood cells through interaction with the FimH adhesin. 42 Similarly, pillar [5]arenebased glycoclusters, featuring five galactose moieties, facilitated 75 agglutination of E. coli, although the specific lectin interactions were not identified. 43 The potential to use pillar [5]arene based rotaxanes to simultaneously provide inhibition of both LecA and LecB has also been described. [2]Rotaxanes featuring bisfucosylated stoppers combined with deca-galactosylated wheels 44 through an aggregative interaction and LecA, through clustering.

More recently, we have reported the development of decavalent pillar [5]arenes, featuring either galactose or fucose epitopes, and evaluated binding against LecA, LecB and BambL. 45 In this series, increased valency resulted in higher affinity as did increasing flexibility of the sugar linkers. The present study describes the synthesis and characterisation of pentavalent pillar [5]arenes functionalised with either galactose or fucose and investigates their binding to LecA, LecB and BambL. The use of a combination of biophysical techniques, including 10 hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), isothermal titration microcalorimetry (ITC) and surface plasmon resonance (SPR) to determine the binding interactions is also reported.

Results and Discussion

Synthesis of glycoclusters

Building on our previous experience 24-28, 46, 47 in the development of glycoclusters using Cu(I)-assisted azide-alkyne cycloaddition (CuAAC), 48 the synthetic route focused on the preparation of pillar [5]arenes bearing either five azido or five alkynyl 20 substituents for subsequent reaction with the corresponding alkynyl or azido carbohydrate derivatives.

In both cases functionalisation was introduced prior to cyclisation by using non-symmetrical alkoxybenzenes. The penta-azido pillar [5]arene 3 was accessed through the preparation of the penta-bromo derivative 2. BF3•OEt2 mediated macrocyclization of the bromo-precursor 1 with paraformaldehyde gave pillar [5]arene 2 (Scheme 1). Subsequent azidation readily provided 3 suitable for CuAAC conjugation with the previously reported 45 propargyl galactoside and fucoside 30 affording the desired acetylated glycoclusters 4a-b. Solvolysis of the acetates provided the water soluble glycoclusters 5a-b for binding assays. It is important to note that the chirality induced by the 55 pillar [5]arene ring system 50 results in the formation of diastereoisomers upon conjugation with carbohydrates. 42 It has previously been reported 51 that separation of non-symmetrical pillar [5]arenes can be achieved, but only when there are substantial differences between the two substituents. Separation 60 of 7 has not proved possible 52 although the diastereoisomers of a specific click conjugate have been isolated. Not surprisingly, the separation of the individual diastereoisomers of 5 and 9, bearing a methyl group, was not successful even after careful column chromatography. Although these isomeric mixtures could affect 65 the interpretation of the binding studies towards lectins, the spatial arrangements of the carbohydrate epitopes for pentavalent scaffolds will not alter greatly the general presentation of the binding partners to the lectins.

O O O O O OMe MeO OMe OMe Br Br Br Br Br OMe O O O O O OMe MeO OMe OMe N N N N N OMe N N N N N N N N N N R R R R R OMe O Br a b c 1 2 3 O O O O O OMe MeO OMe OMe N 3 N 3 N 3 N 3 N 3
In addition to the two enantiomers generated during the 70 macrocyclization process, several conformers can also arise from the rotation of each arene ring (Figure 1). 7 The formation of the pillar [5]arene macrocycle provides a mixture of 4 possible constitutional isomers A1-4 (Figure 1

CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 A 1
OMe groups and several other conformers... Other chains

B 1 C 1 D 1 E 1 F 1 CH2 CH2 CH2 CH2 CH2 A 1 CH2 CH2 CH2 CH2 CH2 A 2 CH2 CH2 CH2 CH2 CH2 A 3 CH2 CH2 CH2 CH2 CH2 A 4
Figure 1. Schematic diagram of the potential isomers that can be formed during the macrocyclization.

This conformational isomerism could be easily observed in both

Binding studies

The binding properties of glycoclusters 5a and 9 with LecA were evaluated using four complementary techniques; hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), isothermal titration microcalorimetry (ITC) and LecA Binding studies Two galactosylated glycoclusters (5a and 9) were evaluated for their ability to bind to LecA (Table 1) and compared with the The stoichiometry (N) for the complex generated between the lectin and the glycocluster also varied depending on the linker. SPR experiments using LecA attached on the chip were also undertaken and affinity was evaluated using a thermodynamic approach. Typical curves were observed as the glycoclusters 5a and 9 were circulated. The SPR and ITC affinities were in the chip surface did not modify the binding to multivalent ligands. As with the other techniques, enhancement of binding was again seen for the more flexible 9 over 5a in SPR studies reinforcing the importance of flexibility to LecA binding.

O O O O O O O O O O R R R R R R R R R R N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N R =
It is interesting to compare the results seen here with those of our previously reported decavalent pillar [5]arenes. 45 Whilst it might be expected that increasing the valency would enhance binding further, in the case of glycocluster 9 in comparison to its analogous deca-functionalized pillar [5]arene 45 a Minimum inhibitory concentration (MIC) required to inhibit the agglutination of erythrocytes. b Calculated using methyl β-D-galactopyranoside (β-GalOMe) as monovalent reference. c Stoichiometry of binding defined as the number of glycoclusters per monomer of LecA. d Data from previous report. 47 e n.m. = Not measured. f RU shift was too weak due to the low molecular weight of β-GalOMe. g Data from previous report. 45

LecB and BambL Binding studies

The fucosylated glycocluster 5b was evaluated for its potential as a LecB and BambL ligand by ITC (Table 2) and showed considerable selectivity between the two topologically different fucose binding lectins, with high affinity only towards BambL. The millimolar Kd value for LecB was disappointing compared to the monosaccharide ligand and to our previously reported calix [4]arene derivatives with no enhancement achieved through presentation on a multivalent scaffold. 11 The stoichiometry (N) of the lectin-glycocluster complex indicated three LecB monomers bound to the pentavalent ligand 5b (N = 0.29) but clearly the orientation of the carbohydrate epitopes is not favorable and resulted in a loss of affinity at each site. The importance of ligand orientation is further demonstrated through comparison with 35 PillaFuc10 which is able to interact with additional binding sites and shows enhanced binding and a positive multivalent effect.

In contrast, 5b proved to be an excellent ligand for BambL (Table 2) surpassing previously reported glycoclusters based on mannose and phosphodiester cores 53 and the higher valency 40 pillar [5]arene derivatives including PillarFuc10. 45 Interestingly the β value of 45 for the pentavalent ligand 5b with a stoichiometry (N = 0.71) indicated that only a fraction of the five carbohydrate epitopes were used in the binding and that one or two lectin monomers are bound. 45 Table 2. ITC measurements for binding of pillar [5]

Conclusions

The potential of multivalent anti-adhesive drugs as therapeutics for drug-resistant bacterial infections in immune-compromised patients is an area of considerable interest. Here we have shown that the pillar [5]arene scaffold, when non-symmetrically functionalised to present five glycosides, acts as an excellent platform for interaction with bacterial lectins. Pillar [5]arenes were prepared bearing either five alkynyl or azido functional groups and glycoclusters featuring either galactose or fucose moieties were readily produced using CuAAC. Binding of galactose functionalised pillar [5]arenes to LecA from P. in stoichiometry, with the best ligand demonstrating the ability to interact simultaneously with five separate LecA tetramers. Considerable variation in binding of the fucosylated glycoclusters to the two fucose specific lectins LecB from P. aeruginosa and BambL from B. ambifaria was observed. This glycocluster proved to be an excellent ligand for BambL with low nanomolar affinity whereas no improvement in binding compared to a monovalent ligand was observed for LecB. This result demonstrates the importance of lectin topology in analysing binding selectivity.

An interesting aspect of these glycoclusters is their stereochemistry as each was obtained as a 1:1 diastereoisomer mixture due to the cyclisation of non-symmetric arenes. Some selectivity in binding may be observed between the diastereoisomers and thus the data presented here can be considered to be an average result. Our further studies will focus on the preparation of pillar [5]arene derivatives which can be chromatographically separated in order to determine whether the chirality of the glycocluster affects binding strength and selectivity.

11-LABX-003). Dr F. Albrieux, C. Duchamp and N. Henriques are gratefully acknowledged for mass spectrometry analyses. N.G. thanks the Région Rhône-Alpes (Cluster de Recherche Chimie) for additional funding and the Royal Society for funding work undertaken in S.E.M.'s laboratory (JP090449). Prof J.-F.

Nierengarten (Université de Strasbourg and CNRS) is gratefully acknowledged for helpful and critical discussions of the chirality of pillar [5]arenes.

Notes and references

Scheme 1 .Scheme 2 .

 12 Scheme 1. Synthesis of pentavalent pillar[5]arene-based glycoclusters35

  , top). These four isomers can rotate each of their arene moieties to provide a series of eight 75 rotational isomers (e.g. A1 to F1, Figure1, bottom). The conformer A1 can have one aromatic ring rotated by 180° to generate the conformer B1. Further rotations of aromatic moieties toward the right hand side provide a series of rotational conformers C1, D1, E1 and finally F1. When considering 80 conformers A1 and F1, they are mirror images of each other and therefore enantiomers, similarly for B1 and E1 and also C1 and D1. These rotations are possible due to the small size of the methoxy substituents in an in-cavity rotation. Several other conformations can also be adopted but are not depicted. These 85 occur from rotation at non-contiguous aromatic moieties and the conformers presented in Figure1illustrate the most simple and step-by-step process. Hence, variable temperature NMR experiments can provide an insight on such isomeric mixtures. This journal is © The Royal Society of Chemistry [year] Journal Name, [year], [vol], 00-00 | 3

5 1 H

 1 and 13 C NMR (Figures 2, S1 and S2). Several peaks appeared as collections of singlets showing the conformer population in solution indicating that interconversion was slower than the NMR timescale. A slight dependence on temperature was observed since heating from 20 to 100°C accelerated the equilibrium and 10 the NMR spectra displayed sharper peaks both in the 1 H and 13 C NMR data (Figures 2, S1 and S2).

Figure 2 .

 2 Figure 2. Partial 1 H NMR data (400 MHz, DMSO-d6) measured for the brominated pillar[5]arene 2.

Figure 3 .

 3 Figure 3. Structures of the galactosylated (PillarGal10) and fucosylated (PillarFuc10) decavalent pillar[5]arene-based 30

35 previously

 35 described PillarGal10. The initial HIA study highlighted efficient binding of these multivalent ligands to LecA which was confirmed in ELLA studies. Both new ligands showed moderate improvement (5a β = 23, 9 β = 73) in binding based on their multivalency. The significantly enhanced activity of 9 could 40 be ascribed to the longer triethyleneglycol linker arms in this conjugate providing greater flexibility for binding of the galactose moieties to the lectin. ITC was used to gain an insight into the thermodynamic parameters governing the binding to LecA and also the 45 stoichiometry of binding. The same enhancement in binding was observed for the more flexible glycocluster 9 over 5a although both ligands gave Kd values in the sub-micromolar range.

50

  Thus compound 5a interacted with two or three LecA monomers (N = 0.40), while, in contrast, 9 bound to five LecA monomers (N = 0.17) indicating that all the carbohydrate epitopes are engaged. This variation is probably a consequence of the longer triethyleneglycol linker arm allowing reduced steric hindrance in 55 the binding of multiple LecA monomers.

  60 same range demonstrating that the immobilization of LecA on the 4 | Journal Name, [year], [vol], 00-00 This journal is © The Royal Society of Chemistry [year]

60

  aeruginosa was shown to be heavily dependent on linker length between the core and carbohydrate and that this also plays a role This journal is © The Royal Society of Chemistry [year] Journal Name, [year], [vol], 00-00 | 5

Table 1 .

 1 (PillarGal10) this is not the case in both HIA and ELLA studies and only a 10 moderate improvement is seen in ITC. . The stoichiometry observed in ITC may provide a rationale for this as despite ten groups being available for binding, only five LecA tetramers interact with the glycoclusters and thus no advantage of the further five available carbohydrate epitopes is seen. HIA, ELLA ITC and SPR measurements for binding of pillar[5]arene-based glycoclusters to LecA

		HIA	ELLA				ITC			SPR
	Compound	MIC a (µM)	IC50 (µM)	β b	N c	-ΔH (kJ.mol -1 )	-TΔS (kJ.mol -1 )	Kd (nM)	β b	Kd th (nM)
	β-GalOMe d	6250	658	1	0.8	39	15	70 000	1	n.m. e,f
	5a	10	29	23	0.40±0.02	82±3	47.4	931±30	75	508
	9	2	9	73	0.17±0.01	174±9	138	586±38	119	337
	PillarGal10 g	5	218	3	0.20±0.01	115±2	78	366±129	191	47

15

  arene-based glycoclusters to LecB and BambL Calculated using monovalent methyl α-L-fucopyranoside (α-FucOMe) as reference. b Stoichiometry of binding defined as the number of glycoclusters per monomer of LecB. c Data from previous report.54 d Data from previous report.45 e Data from previous report.39

	Compound	Lectin	N b	-ΔH (kJ.mol -1 )	-TΔS (kJ.mol -1 )	Kd (nM)	β a
	α-FucOMe c	LecB	0.77±0.03 c	41±1	5 c	430±10	1
	5b	LecB	0.29±0.01	106±19	73	1402±45	0.3
	PillarFuc10 d	LecB	0.13±0.01	250±2	213	280±33	1.5
	α-FucOMe e	BambL	2.02	48±2	14	960±30	1
	5b	BambL	0.71±0.01	79±3	35	21±7	45
	PillarFuc10 d	BambL	0.35±0.02	201±5	160	57±16	17

a

  Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, 35 CO2-Glyco, UMR 5246, CNRS, Université Claude Bernard Lyon 1, Université de Lyon, 43 Boulevard du 11 Novembre 1918, F-6922 Villeurbanne, France. b CERMAV, UPR5301, CNRS and Université Grenoble Alpes, 601 rue de la Chimie, BP 53, 38041, Grenoble, France. 40 c School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, United Kingdom. † Electronic Supplementary Information (ESI) available: Synthesis and characterization of compounds, SPR and ITC data. See

a

MeOH, Et3N, H2O, r.t., 16 h, >95% (5a and 5b).More conveniently, the penta-alkynyl pillar[5]arene scaffold 7 was obtained directly from its precursor 6 and paraformaldehyde (Scheme 2).49 Conjugation with the azido-functionalized triethyleneglycol galactoside afforded the desired acetylated 45 glycocluster 8. Unmasking of the protecting groups provided the desired galactose glycocluster 9.

surface plasmon resonance (SPR). In contrast ITC was chosen as the single technique for evaluation of the dependence of binding of glycocluster 5b to LecB and BambL, giving access to the stoichiometry of the binding partners for each multimeric complex formed. In addition, two decavalent pillar[5]arene-based 25 glycoclusters PillarGal10 and PillarFuc10 were also included in the study for comparison (Figure3).

Acknowledgments

The authors thank the Université Claude Bernard Lyon 1 and the CNRS for financial support. This project was also supported by COST Action CM-1102 MultiGlycoNano. A.I. acknowledges support from GDR Pseudomonas and Labex ARCANE (ANR-


Thibaut Bagni
email: thibaut.bagni@sorbonne-universite.fr

David Siaussat

Annick Maria

Annabelle Fuentes

Philippe Couzi

Manuel Massot

Fitness under high temperatures is overestimated when daily thermal fluctuation is ignored

Keywords: fluctuating temperature, Jensen's inequality, metabolic cost, CTmax, insects

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

INTRODUCTION

Most organisms face temperature variations during their lifetime because temperature varies hourly, daily, monthly, seasonally, and yearly in most environments. The importance to consider effects of thermal fluctuation on species is well documented [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Sinclair | Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures?[END_REF][START_REF] Vasseur | Increased temperature variation poses a greater risk to species than climate warming[END_REF]. Thermal variation can be particularly high throughout the day compared to other temporal scales [START_REF] Sheldon | Beyond the mean: Biological impacts of cryptic temperature change[END_REF].

Notwithstanding this well-known reality, most laboratory studies are carried out with daily constant temperatures. It is therefore crucial to check the assumption of the studies that results do not differ between constant and daily fluctuating temperatures (e.g., [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Ma | Daily temperature extremes play an important role in predicting thermal effects[END_REF][START_REF] Sinclair | Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures?[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF] and to investigate the causes that might falsify this assumption. Our study focused on fitness traits. We tested the assumption of no difference between constant and daily fluctuating temperatures on multiple fitness traits of the moth Spodoptera littoralis and performed a literature review in insects (Appendix A).

In ectotherms such as insects, the response to temperature of most traits is nonlinear and asymmetric, and declines quickly at temperatures above the optimum [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Martin | Why "suboptimal" is optimal: Jensen's inequality and ectotherm thermal preferences[END_REF][START_REF] Paaijmans | Temperature variation makes ectotherms more sensitive to climate change[END_REF][START_REF] Sinclair | Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures?[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF].

The thermal performance curve (TPC) of a fitness trait can be characterised by three tipping points: the optimal temperature (Topt) where the value of a fitness trait is maximal and two critical temperatures where the value of a fitness trait is nil (minimal and maximal temperatures, respectively CTmin and CTmax), as illustrated in Fig. 1. Diverse definitions of critical values can be found in literature, notably a recent approach to define the upper thermal limit of overall fitness in ectotherms [START_REF] Jørgensen | Extreme escalation of heat failure rates in ectotherms with global warming[END_REF][START_REF] Ørsted | Finding the right thermal limit: a framework to reconcile ecological, physiological and methodological aspects of CTmax in ectotherms[END_REF]. Here, we simply consider the case for a given fitness component (e.g., [START_REF] Huey | Integrating thermal physiology and ecology of ectotherms[END_REF][START_REF] Sheldon | Beyond the mean: Biological impacts of cryptic temperature change[END_REF]. The fitness difference between constant and daily fluctuating temperatures should depend on the mean temperature studied (e.g., close to Topt, CTmin or CTmax) [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF] as well as on the breadth of variation in fluctuating temperatures [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF]. The combination of the mean temperature and breadth of variation can be summarised by the range of fluctuating temperatures investigated. In our study on S. littoralis, we focused on ranges around Topt and CTmax by comparing constant and daily fluctuating temperatures at relatively high temperatures (mean temperatures of 25, 29 and 33°C, with a daily variation of 5°C around each mean temperature). Indeed, insects will be more frequently challenged by high temperatures with climate warming [START_REF] Kearney | The potential for behavioral thermoregulation to buffer "coldblooded" animals against climate warming[END_REF]. Moreover, the responses of traits are predicted to be particularly sensitive to high temperatures because Topt and CTmax are close in typical TPCs of ectotherms [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Martin | Why "suboptimal" is optimal: Jensen's inequality and ectotherm thermal preferences[END_REF][START_REF] Paaijmans | Temperature variation makes ectotherms more sensitive to climate change[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF]. Previous studies showed that Topt and CTmax are close in S. littoralis studied under constant temperatures (Bagni et al., 2022;[START_REF] Massot | Combined influences of transgenerational effects, temperature and insecticide on the moth Spodoptera littoralis[END_REF].

Fig. 1 illustrates our predictions for the responses of fitness traits under thermal ranges close to Topt (Fig. 1A) and CTmax (Fig. 1B). Under these thermal ranges, the fitness difference between constant and fluctuating temperatures can have different causes. As a first cause, nonlinear TPCs lead to unbalanced effects between temperatures that fluctuate below and above a mean temperature [START_REF] Ruel | Jensen's inequality predicts effects of environmental variation[END_REF]. The overall response of a trait can be predicted from the mathematical property of the form of nonlinear functions known as Jensen's inequality [START_REF] Ruel | Jensen's inequality predicts effects of environmental variation[END_REF]. By definition, the function around Topt (where fitness is maximal) is a decelerating function (the convex part of the TPC in Fig. 1). The prediction for a decelerating function is that the response of traits will be worse under fluctuating temperatures than constant temperatures [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Ruel | Jensen's inequality predicts effects of environmental variation[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF]. A second cause of the differential response between fluctuating and constant temperatures is related to metabolism. The energetic cost of metabolism in ectotherms is important in the thermal range of high temperatures because the metabolic rate tends to increase exponentially as temperature increases [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Ruel | Jensen's inequality predicts effects of environmental variation[END_REF]. This accelerating function between metabolism and temperature leads to another effect of Jensen's inequality, with a metabolic cost higher under fluctuating than constant temperatures. We discuss the effect of metabolic cost independently of Jensen's inequality because metabolism is not a fitness trait but may influence fitness traits. A third cause of the differential response between fluctuating and constant temperatures involves the influence of the critical temperature CTmax [START_REF] Ma | Daily temperature extremes play an important role in predicting thermal effects[END_REF]. Temperatures close to CTmax are known to result in detrimental effects related to heat stress. Although heat stress induces the synthesis of heat shock proteins (HSPs) that allow organisms to cope with stronger and longer heat stress, even the production of HSPs has negative effects [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Feder | Heat-shock proteins, molecular chaperones and the stress response: Evolutionary and Ecological Physiology[END_REF]. These negative effects can be associated with energetic cost, consumption of nutrients, toxicity at high HSPs concentrations, and detrimental interactions with cellular processes [START_REF] Feder | Heat-shock proteins, molecular chaperones and the stress response: Evolutionary and Ecological Physiology[END_REF]. More generally, fluctuating temperatures around CTmax result in shifts between permissive temperatures and stressful higher temperatures. Because stressful temperatures beyond CTmax cause injuries, fluctuating temperatures around CTmax should accumulate injuries or costs to repair injuries [START_REF] Jørgensen | Extreme escalation of heat failure rates in ectotherms with global warming[END_REF].

We expect additive effects of the three causes of difference between constant and fluctuating temperatures (Jensen's inequality, metabolic cost, CTmax closeness) because they involve different processes that are not mutually exclusive, and Fig. 1 synthesizes our predictions. We predict lower fitness values under fluctuating than constant temperatures, both for thermal ranges close to Topt and CTmax (respectively, the Topt and Thigh scenarios in Fig. 1). However, a larger difference in the Thigh scenario is expected because of a higher metabolic cost and CTmax closeness. The difference in metabolic cost between fluctuating and constant temperatures should be higher under the Thigh than Topt scenario because metabolism usually increases exponentially as temperature increases [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Ruel | Jensen's inequality predicts effects of environmental variation[END_REF]. In summary, we expect lower fitness values in the fluctuating thermal regime than in the constant regime at optimal and high temperatures but with a clearer difference at higher temperatures. Our experimental study that tested this pattern is supplemented with a literature review on fitness traits in insects to synthetize findings on differences of fitness traits between constant and fluctuating temperatures.

MATERIALS AND METHODS

Study species

The moth S. littoralis is a widespread Mediterranean and African pest (CABI, 2020). This species is well-known, easy to rear in laboratory, with facilities to estimate fitness traits, and several studies have provided key knowledges on its thermal biology. Under constant temperatures, the thermal optimum of the population multiplication rate of S. littoralis was estimated at 29 °C in our previous studies (Bagni et al., 2022;[START_REF] Massot | Combined influences of transgenerational effects, temperature and insecticide on the moth Spodoptera littoralis[END_REF]. However, the response of this species to temperature differed among studied parameters, thus showing the importance of studying the effects of temperature on multiple parameters [START_REF] Mordecai | Thermal biology of mosquito-borne disease[END_REF][START_REF] Sinclair | Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures?[END_REF]. When larval and pupal survival rates responded moderately to temperatures varying from 23 to 29°C, the development of S. littoralis dramatically accelerated, particularly between 23 and 27°C. This strong thermal sensitivity of the development rate explains why this species can complete two to seven generations per year depending on regional climatic conditions [START_REF] Khafagi | Effects of temperature on the development, food consumption and utilization parameters of the last two larval instars of Spodoptera littoralis (Boisd.)[END_REF]. Moreover, it was found that adults of S. littoralis cannot reproduce at a constant temperature of 30 °C [START_REF] Sidibé | Incidence des thermopériodes et de températures constantes sur quelques critères biologiques de Spodoptera littoralis Boisduval [Lepidoptera Noctuidae][END_REF]. This value of CTmax for reproduction also seems close to CTmax for pupal survival, which Sidibé and Laugé estimated to be low at 30°C. This response is in contrast to the high pupal survival rates observed at 29 °C in our previous studies (Bagni et al., 2022;[START_REF] Massot | Combined influences of transgenerational effects, temperature and insecticide on the moth Spodoptera littoralis[END_REF] and provides evidence for the proximity of Topt and CTmax.

Experimental setup

The S. littoralis used in the study were obtained from a laboratory strain maintained at 23 °C, 60-70 % relative humidity, and a 16:8 light/dark photoperiod, with larvae fed ad libitum with semiartificial food [START_REF] Hinks | Biosystematics of the genus Euxoa (Lepidoptera: Noctuidae): V. Rearing procedures, and life cycles of 36 species[END_REF]. We obtained experimental clutches by mating pairs of one female and one male (two-day-old adults) in plastic boxes (10 cm in diameter) with sugar water (20 g/L) as food and a strip of filter paper to more easily collect the clutches. We made 105 mating pairs to obtain 56 clutches. Clutches were collected at the peak of egg laying 24 hours after mating [START_REF] Kehat | Mating, longevity, fertility and fecundity of the cotton leaf-worm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae)[END_REF]. Clutches were divided into two parts to rear them under the two different thermal regimes (constant versus fluctuating regimes) of the same mean temperature (25, 29 or 33°C). We used this design to avoid a sampling bias related to clutch effects [START_REF] Massot | Combined influences of transgenerational effects, temperature and insecticide on the moth Spodoptera littoralis[END_REF] in our comparison between constant and fluctuating regimes. The fluctuating regime was a daily temperature fluctuation of ± 5°C (Appendix B). The daily fluctuation of ± 5°C is common in natural environments [START_REF] Wang | Recent geographic convergence in diurnal and annual temperature cycling flattens global thermal profiles[END_REF] and commonly used in studies on fluctuating thermal regimes [START_REF] Verheyen | Daily temperature fluctuations can magnify the toxicity of pesticides[END_REF]. Six environmental test chambers (Panasonic MLR-352H) were used in parallel (one per experimental temperature) to control temperatures independent of relative humidity, which was maintained at 70 %.

We performed a daily survey of experimental boxes (225 x 145 x 72 mm) to monitor larvae and pupae until adult emergence. We standardized the density to 30 larvae per experimental box when larvae reached the 4 th larval instar. The larval survival rate (hereafter called late larval survival rate) was measured from the 4 th larval instar to pupation. Sex was identified at pupation, and pupal survival was quantified. From this survey, we also measured the developmental rate as 1/developmental duration (days -1 ) (Lyons et al., 2013;Paaijmans et al., 2013) between the egg stage and adult emergence. Developmental rate can be used as a fitness proxy for generation time [START_REF] Huey | Temperature, demography, and ectotherm fitness[END_REF]. Finally, we estimated the mating rate of two-day-old adults from mating pairs of one female and one male that were exposed to the same temperature treatment (called final mating rate, and computed as the proportion of mating pairs which produce a clutch after 24 hours), as well as the hatching rate of clutches they produced (called final hatching rate). This experiment was performed in February 2020.

It was complemented with an experiment in May-June 2022 to quantify the initial hatching rate of eggs at the beginning of the temperature treatments and the early larval survival rate of larvae between the 1 st and 4 th instars. These parameters were obtained using estimates of the number of eggs we obtained from the clutch mass (Appendix C: R 2 = 0.95 for the relationship between the number of eggs and clutch mass). We counted the number of hatched eggs to quantify the hatching rate and the number of larvae that reached the 4 th larval instar to quantify the early larval survival rate.

Data analyses

Appendix D provides the sample sizes for all our variables in each of our six experimental treatments that crossed the two thermal regimes and three mean temperatures.

We tested the effects of the thermal regimes, mean temperatures, and their interaction. We analysed all our variables using logistic models. In particular, we discretized our continuous variables (hatching rate, early larval survival rate, developmental rate) that did not satisfy normality or homoscedasticity, even when log transformed. Hatching rate and early larval survival rate were discretized into binomial variables with regard to their median value. We had to discretize the developmental rate with regard to the median values of each mean temperature to maintain variation in analyses. Indeed, the overlap between the developmental times of mean temperatures was very limited. The 99 % confidence interval of the developmental time for females was 0.0321-0.0324 days -1 at 25 °C, 0.0416-0.0422 days -1 at 29 °C, and 0.0459-0.0474 days -1 at 33 °C, and the 99 % confidence interval of the developmental time for males was 0.0319-0.0323 days -1 at 25 °C, 0.0418-0.0424 days -1 at 29 °C, and 0.0452-0.0464 days -1 at 33 °C. Analyses were carried out with JMP software (JMP Pro 15, SAS Institute Inc., Cary, NC), using stepwise removal of terms with P > 0.10.

We estimated the multiplication rate at the population level using demographic models [START_REF] Caswell | Matrix population models: Construction, analysis, and interpretation[END_REF]. We parameterised these models with all our fitness estimates: developmental rate, survival rate from 1 st to 4 th larval instars, survival rate from 4 th larval instar to pupation, pupal survival rate, mating rate and hatching rate. In brief, the life cycle of S. littoralis was modelled with an age-structured matrix (where each age class was of 1 day) following the methodology detailed in [START_REF] Massot | Combined influences of transgenerational effects, temperature and insecticide on the moth Spodoptera littoralis[END_REF]. The age-structured matrix projects how the number of individuals in each age change between successive generations and the asymptotic population growth rate is quantified by the dominant eigenvalue of the matrix [START_REF] Caswell | Matrix population models: Construction, analysis, and interpretation[END_REF]. Modelling was achieved with the program ULM ('Unified Life Models') [START_REF] Ferrière | Matrix population models applied to viability analysis and conservation: Theory and practice using the ULM software[END_REF][START_REF] Legendre | ULM, a software for conservation and evolutionary biologists[END_REF]. The models corresponding to the six experimental treatments were parameterised with the fitness estimates of the study provided in Appendix E.

We performed two sets of models to estimate the multiplication rates considering the initial or final hatching rate of the experiment. Indeed, the thermal sensitivity of the hatching rate of eggs at the beginning of the experiment differed dramatically with the hatching rate of eggs after the full life cycle under the temperature treatments.

Literature review on fitness traits in insects

We searched the literature using the keywords 'temperature', 'thermal', 'fluctuating', 'variability' and 'variation'. Our selection criteria were for studies on fitness traits in insects that compared constant and daily fluctuating temperatures with the same mean temperature between the two thermal regimes. In addition, we did not select studies with a marked asymmetrical fluctuation around the mean temperature or studies based on daily alternating temperatures (i.e., with a rapid shift between only two temperatures). Although we observed an increasing number of studies that compared constant and daily fluctuating temperatures during the last decade, we found only 22 studies with our selection criteria (see the references listed in Appendix A). Because thermal sensitivity differs between species (Angilletta, 2009), we defined classes of temperatures with regard to the optimal range of species (Cold, Optimum and Hot classes for values inferior, around or superior to the range of optimal temperatures, respectively).

RESULTS

Comparison of constant and fluctuating temperatures in Spodoptera littoralis

Table 1 shows the tests of the effects of mean temperatures (25, 29, and 33°C), thermal regimes (constant versus fluctuating regimes), and their interaction. The nine fitness parameters tested were influenced by mean temperature (P < 0.001 in all tests). If the developmental rates of females and males increased with temperature (Fig. 2E andF), the seven other fitness parameters decreased at the highest temperature of 33°C (Fig. 2A to D for the four survival rates tested, and Fig. 3A to C for the three reproductive parameters tested).

As we expected, these detrimental effects indicated that the developmental temperature of 33°C was close to the CTmax of S. littoralis. In addition, the analyses revealed significant interactions between the effects of mean temperature and thermal regime on the female pupal survival rate and the developmental rates of females and males (Table 1). At the highest temperature of 33°C, these fitness parameters were lower under the fluctuating thermal regime than under the constant temperature regime (Fig. 2C, E andF). Moreover, we found a significant effect of thermal regime on the late larval survival rate (Table 1). However, the late larval survival rate was particularly lower under the fluctuating regime than at constant temperature at the mean temperature of 33°C (Fig. 2B), as supported by the marginally significant interaction between the mean temperature and thermal regime (Table 1) and local tests per mean temperature (thermal regime effect with P < 0.001 at 33°C, and P > 0.10 at 25 and 29°C).

Integrative estimate of fitness traits

Our fitness estimates were integrated into demographic models based on the life cycle of S. littoralis. We simulated the six experimental scenarios that crossed the three mean experimental temperatures with the two thermal regimes (values used to fix parameters are reported in Appendix E) to obtain their corresponding population multiplication rate. The multiplication rate of the simulated populations was the highest at 29°C, and its decrease at the higher temperature of 33°C was more marked under the fluctuating thermal regime (Fig. 4A). Therefore, the overall impact of the high temperature appeared to be underestimated under the constant thermal regime. This result was obtained from the modelling of the effects of mean temperatures and thermal regimes from the egg stage to adult emergence (using the estimates of the initial hatching rate reported in Fig. 3A). However, multiplication rates are to consider in fine as nil at 33°C for both thermal regimes (Fig. 4B) because adults were not able to reproduce after the full life cycle at this temperature (Fig. 3C).

Review of fitness traits in insects

We reviewed the literature for studies on fitness traits in insects that provide statistical tests comparing constant and daily fluctuating temperatures (see our selection criteria in Materials and Methods). As an encouraging sign, we observed an increasing number of studies that compared constant and daily fluctuating temperatures during the last decade (Appendix A). Overall, constant and daily fluctuating temperatures commonly differed.

Significant differences between temperature regimes were found in 81 out of 145 tests (Fig. 5). These differences were found in 70% of tests on cold temperatures, 46% of tests on temperatures around optimum, and 68% of tests on hot temperatures. The other finding of the review is the reverse patterns between cold and hot temperatures (Fig. 5). The fitness traits observed to be higher in the fluctuating than constant regime were the most frequent in tests of cold temperatures. In contrast, the fitness traits were more frequently lower in the fluctuating regime than in the constant regime in tests of hot temperatures.

DISCUSSION

We studied S. littoralis at relatively high temperatures of 25, 29 and 33°C, a thermal range around Topt that we found to be close to 29°C with multiplication rate estimates (Fig. 4). The maximal limit of our thermal range was also close to CTmax, as highlighted by the steep decrease in the multiplication rate under the fluctuating thermal regime at 33°C when considering fitness components from the egg stage to adult emergence (Fig. 4A). The study species can have a positive population multiplication rate even with a low hatching rate and a low early larval survival as in our experiment because of the low sensitivity of population multiplication rate to these parameters [START_REF] Massot | Combined influences of transgenerational effects, temperature and insecticide on the moth Spodoptera littoralis[END_REF]. In fact, CTmax is below 33°C because adults were not able to reproduce after a full life cycle at 33°C (Fig. 3C and4B). This result is in accordance with the finding of [START_REF] Sidibé | Incidence des thermopériodes et de températures constantes sur quelques critères biologiques de Spodoptera littoralis Boisduval [Lepidoptera Noctuidae][END_REF] on the lack of reproduction of S. littoralis at a constant temperature of 30 °C. The narrow thermal range between Topt and CTmax is typical in ectotherms [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Martin | Why "suboptimal" is optimal: Jensen's inequality and ectotherm thermal preferences[END_REF][START_REF] Paaijmans | Temperature variation makes ectotherms more sensitive to climate change[END_REF][START_REF] Sinclair | Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures?[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF]. Investigating the fitness responses of ectotherms around this range is crucial because a small temperature variation around the tipping points of the maximal and nil fitness values leads to a severe fitness decline. It is also critical to study this range of high temperatures because heat waves are becoming more frequent and severe with climate change [START_REF] Fischer | Consistent geographical patterns of changes in high-impact European heatwaves[END_REF][START_REF] Wang | Recent geographic convergence in diurnal and annual temperature cycling flattens global thermal profiles[END_REF], and even a modest climate warming might have a large negative impact on many ectotherms [START_REF] Jørgensen | Extreme escalation of heat failure rates in ectotherms with global warming[END_REF].

We predicted lower fitness in the fluctuating thermal regime than in the constant regime at optimal and high temperatures, but with a clearer difference at high than optimal temperature because of higher metabolic cost and CTmax closeness (Fig. 1). We found a lower fitness in the fluctuating than constant regime at our high temperature of 33°C, providing evidence for the predominant effect of metabolic cost or/and CTmax closeness (injuries caused by heat stress, costs to repair injuries or/and costs of HSPs) at high temperature. Indeed, we did not find a difference between fluctuating and constant regimes at the optimal temperature of 29°C. This lack of difference at the optimal temperature seems to provide evidence for the limited effects of Jensen's inequality and metabolic cost (Fig. 1A).

An alternative to the hypothesis of limited effects of Jensen's inequality and metabolic cost around the optimal temperature is that trade-offs between fitness traits and delayed responses of acclimation may influence the effects of fluctuating temperatures. Indeed, the response of a fitness trait can depend on another fitness trait because of energetic or evolutionary trade-offs (Arias et al., 2011;[START_REF] Marshall | Repeated stress exposure results in a survival-reproduction trade-off in Drosophila melanogaster[END_REF], such as trade-offs between survival and reproduction or between early and late survival [START_REF] Stearns | The evolution of life histories[END_REF]. The negative relationships between fitness traits associated with these trade-offs might alter the difference between fluctuating and constant thermal regimes. The delayed responses of acclimation could also obscure the effects of fluctuating temperatures because past stressful temperatures can increase the thermal range of organisms [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF] or variable temperatures can decrease the thermal sensitivity of metabolism [START_REF] Carter | Life stages differ in plasticity to temperature fluctuations and uniquely contribute to adult phenotype in Onthophagus taurus dung beetles[END_REF][START_REF] Williams | Thermal variability increases the impact of autumnal warming and drives metabolic depression in an overwintering butterfly[END_REF]. This complexity challenges the predictions for temperatures distant from the extreme critical temperatures CTmin and CTmax where detrimental effects should predominate, and this complexity might explain the diversity of results under experimental temperatures around optimum (Fig. 5).

Our literature review showed that fitness traits commonly differed between constant and daily fluctuating temperatures. Moreover, the review revealed opposite patterns between cold and hot temperatures. Compared to constant regimes, fitness traits were more frequently higher in fluctuating regimes of cold temperatures and lower in fluctuating regimes of hot temperatures (Fig. 5). Therefore, ignoring daily fluctuations in temperature in studies using constant temperatures often leads to underestimations of fitness traits in cold conditions and overestimations of fitness traits in hot conditions. This reverse pattern was predicted by [START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF] based on the influence of Jensen's inequality and critical temperature CTmax, and observed in Drosophila melanogaster [START_REF] Bozinovic | The mean and variance of environmental temperature interact to determine physiological tolerance and fitness[END_REF].

CONCLUSIONS

Although there is an increasing number of studies investigating the effects of daily fluctuations in temperature [START_REF] Colinet | Insects in fluctuating thermal environments[END_REF][START_REF] Stoks | Daily temperature variation and extreme high temperatures drive performance and biotic interactions in a warming world[END_REF], most laboratory studies are still carried out under constant temperatures. In the context of climate warming that is expected to be highly threatening for many ectotherms [START_REF] Jørgensen | Extreme escalation of heat failure rates in ectotherms with global warming[END_REF], the usual practice to ignore daily fluctuations in temperature will often overestimate fitness traits in hot conditions. As a consequence, this bias will lead to underestimations of the expected impact of climate warming on fitness traits. Furthermore, climate warming is associated with an increase in daily thermal fluctuations [START_REF] Wang | Recent geographic convergence in diurnal and annual temperature cycling flattens global thermal profiles[END_REF] that could more expose organisms to the negative effects of high temperatures [START_REF] Vasseur | Increased temperature variation poses a greater risk to species than climate warming[END_REF]. Based on a theoretical thermal performance curve (TPC) under the constant regime, the expected deviations of the fluctuating regime are indicated by the red arrows associated with the fitness axis. The double red arrow on the temperature axis indicates an example of range of fluctuating temperatures. TPC is characterised by the optimal temperature T opt where the value of the fitness trait is the highest and by critical temperatures CT min and CT max where the value of the fitness trait is nil. A: Predictions for temperatures close to T opt , B: predictions for high temperatures (T high ). Although the fluctuating regime is predicted to be more detrimental than the constant regime in the two scenarios, we expect this negative effect to be higher in the T high than T opt scenario because of a higher metabolic cost and CTmax closeness.

FIGURE 1 .

 1 FIGURE 1. Expected responses of a fitness trait to constant and fluctuating thermal regimes.

FIGURE 2 .

 2 FIGURE 2. Influence of mean temperature and thermal regime on survival and development.

FIGURE 3 .

 3 FIGURE 3. Influence of mean temperature and thermal regime on reproduction. Thermal

FIGURE 4 .

 4 FIGURE 4. The multiplication rate of simulated populations as a function of mean

FIGURE 5 .

 5 FIGURE 5. Synthesis from studies in insects that compared fitness traits between fluctuating

FIGURE

  FIGURE 1

Acknowledgments

This research was supported by the Région Ile-de-France (DIM R2DS 2014 to M.M.) to purchase environmental test chambers.

gene expression in an insect along the ontogeny: Effect of temperature variability. J. Therm. Biol. 36, 355-362. https://doi.org/10.1016/j.jtherbio.2011.06.011. Bagni, T., Siaussat, D., Maria, A., Couzi, P., Maïbèche, M., Massot, M., 2022 (25, 29, and 33°C), experimental thermal regime (constant versus fluctuating regimes ± 5°C), and their interaction. Significant and marginally effects are reported in bold. The tests of the effect of mean temperature tested on female and male developmental rates were not reported because we had to discretize these variables with regard to the median value of each mean temperature (see Materials and Methods where the non-overlapping 99% confidence intervals between mean temperatures are indicated).

Mean temperature

Temperature

APPENDIX D -Sample sizes


Christine Reynier

Joseph Wiesenfarth Ford

Madox Ford

Women Violet Hunt

Jean Rhys

Stella Bowen

Janice Biala

Texte

Modernist period as one continuous period, "Victorian Modernism", questioning both the periodization of literary studies and the definition of Modernism in terms of crisis and rupture. She also proposes to connect hitherto separate critical discourses such as those of sentiment, sublimity, domesticity and aestheticism, chronologically separate categories such as aestheticism and decadence or Pre-Raphaelitism and Abstractionism, and to connect the arts of various countries. She also shows how the public and private spheres-usually said to be masculine and feminine-have never been separate in Victorian and Modernist culture; how art is neither simply mimetic nor sleekly autonomous. Acknowledging that she is not the first to tread that ground, she sets to explore "the pleasurable swoons and feelings of reverence that sometimes occur as we experience art" instead of analyzing Victorianism and Modernism in terms of resistance, strife, loss and rupture, of economic, social and psychological agon and alienation. Her whole enterprise means to go beyond the dualism that haunts talk about art.

Starting from the opposing definitions usually given of "the aesthetic" in nineteenth and twentieth-century thought-"as a self-contained realm entirely apart from everyday concerns or reality, and as the whole of reality, the tendency to see 'art' or 'language' or 'discourse' or 'text'as constituting the primary realm of human experience"-she suggests the word aesthetics should be abandoned in favor of aestheticism-"the beliefs, customs, experiments, and actual creations in words and paint of nineteenth-century artists such as Ruskin and Rossetti". Which leads her to analyze the relation between the works of art and the lives artists led. To make her point, she selects a poet and painter (Dante Gabriel Rossetti), a popular and domestic novelist (Augusta Evans), a scientist and philosopher (William James) and an art critic (John Ruskin), who having been read by the other three, provides the link between them all. The analysis is tentative, bearing mainly on nineteenth-century artists and not on twentieth-century ones and grounded on somewhat arbitrarily chosen authors. However the premises laid in the introduction are challenging and any reader interested in the period will be able to pursue the analysis for herself by focusing on other artists and testing the value of Feldman's theory. As she writes, Victorian Modernism is, in the words of William James, a "live option" and her own goal is "to chart coherences that begin and end with critical scintillations, not solid blocks".

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The book itself is far from being a solid block, divided as it is into 4 chapters, each dedicated to a different artist and followed by "Meditations" on key concepts such as sentimentality, domesticity or sublimity. The first chapter, "A sweet continuance", offers to re-read Ruskin taking into account his excesses and digressions as part of his method, a method of "exploration rather than system, of intricate and spreading mazes rather than hierarchical orderings". Acknowledging Ruskin's confusions as his insights and confronting the intricacies of his work with his life, Feldman first looks at the way the artist and critic interweaves, from juvenilia through Praeterita (1885), the conventional rhetoric of domesticity and sentiment while developing a notion of artistic impersonality that was to influence Yeats and Joyce, and she comes to understand impersonality as sublime sentimentality. Ruskin's world thus provides a picture of Victorian Modernism in the making. Indeed, even if seen somewhat abstractedly at a distance, domesticity matters for him because it is infused with sentiment and sentiment itself is a necessary quality of true art. Feldman points out that for all his talk about sentiment, Ruskin resorts to a form of indirection to say what he feels, a pre-Eliotian form of impersonality: domestic images (homes scrutinized yet seldom entered) as well as clichés and conventions of sentimentality are read as expressions of personal feeling in abstract terms. Feldman then proceeds to show how Ruskin interweaves the traditions of sentiment and sublimity, a revised form of sublimity that can apply to Turner's paintings of storms at sea as well as to pastoral scenes, mountains and cathedrals but also to mere hills and cottages, household objects and truths, that is, a sublimity of ordinary life. The chapter ends with a close-reading of Roadside Songs of Tuscany (1884-85), a rarely mentioned work in which Ruskin is shown to question the unity of the self and the categories of high and low art, thus paving the way for Modernist literature.

The first Meditation is on "Aestheticism and Pragmatism". Perhaps because of the ambiguities of some artists like Ruskin, Feldman remarks that aestheticism has been defined in many conflicting ways and its chronological limits are debated. It is often understood as centering on art for art's sake and predicated on disinterestedness while pragmatists choose to explore the usefulness to artists and critics of the concepts of the purity, uselessness and autonomy of art. "Pure" beauty is often the target of marxist criticism but, Feldman argues, aestheticism will only be understood when we posit that beauty is dependent on dominant ideologies. As a pragmatist, she wishes to revise some critical standpoints and to draw the reader's attention to the texts as such rather than as illustrations of critical viewpoints. She also points out that aestheticism exceeds the limits of the end of the 19th century.

Feldman then undertakes to demonstrate that sentimental domesticity was central to the aestheticism of D. G. Rossetti who not only decorated the interiors of his homes but also kept depicting domestic spaces and objects in his poetry and painting, fraught with tender sentiments. He thus created a domestic sublimity-eliciting sentiment in the audience and looking back to the 18th century tradition of sensibility-that relieved a life of pain and terror. The aesthetic values Rossetti defended would, according to Feldman, influence Modernism and art nouveau in France. She draws the portrait of a more balanced Rossetti, hovering between elitist separatism and popular participation, and revises his relation to women, pointing out that if he objectified women, he also celebrated female virtue.

The ensuing "Meditation" is on "domesticity". For the Victorian Modernist, art and life are not categories apart but are brought together through the activities of domesticity, in the domus. The hawthorn vase in Rossetti's paintings and the hawthorn vase he buys from his friend Murray Marks overlap in the artist's experience. Experiences at home and aesthetic views are intertwined.

Wishing to connect English and American literature as well as elite and popular writings, Feldman focuses on Augusta Evans and her novel St Elmo (1866), which tells about the trials of a writing, scholarly woman. She appraises the shortcomings and strengths of this bestseller of the 19th century as well as its creation of a decadent domestic aestheticism, especially through its recasting of public history as private experience. This is followed by a meditation on sentimentality. Although Victorian sentimentality is often seen in derogatory terms as debased art, Ruskin, Rossetti, Augusta Evans and William James explore sentimentality as a source of rich possibility and so will twentieth-century writers. Sentimentality is not always a sign of aesthetic weakness but can at times enable an artist to fly wide and high. Feldman argues that sentimentality is intricately connected with impersonality, artists like Ruskin preaching the need for heartfelt art while fearing to reveal themselves in their work. And challenging T. S. Eliot, she wonders whether in Victorian Modernism, the man who suffers can really separate himself from the mind that creates.

In the last chapter, Feldman turns to William James. The choice of the psychologist and philosopher stems from her desire to confuse the categories of art and philosophy as well as from the fact that James, according to Feldman, captures the spirit of Victorian Modernism: "its propensity towards interesting confusions, its pursuit of tender relations, and its certainty that our actual, lived, felt experience cannot and should not be separated from the work of art". Like Ruskin, Rossetti and Evans, he worked as a pragmatist, with materials close to hand to respond to abstract philosophical questions through artistic undertakings. He was interested in the same topics as they were and especially, in domesticity and its relation to aesthetic experience, which he explored in his essay "On a Certain Blindness in Human Beings", an essay that Feldman analyses at length.

The book closes on a meditation on sublimity. Challenging the assumption that the sublime remains constant over time, Feldman shows, basing her argument on Longinus

Droits d'auteur

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and Kant, that sublimity changes with Ruskin and becomes an experience of things both high and low. Ruskin thus paves the way for the twentieth-century sublime, the sublime of everyday life, a form of sublimity which can be linked with domesticity and ordinary life in true Victorian Modernist fashion.

Feldman's study is certainly rich and worth reading. Even if the whole book reads more like a collection of essays than a full-length study, even if the choice of the artists seems somewhat contrived and arbitrary, even if many ideas still await development, the book is compelling and thought-provoking. Going against the grain as it does, it does not mean to provide neat conclusions but undoubtedly gives food for thought.

Introduction

  [Texte intégral] The Transformative Power of the Arts in Victorian and Edwardian Culture and Society Paru dans Cahiers victoriens et édouardiens, 89 Spring | 2019 Michael Robertson. The Last Utopians. Four Late Nineteenth-Century Visionaries and their Legacy [Texte intégral] Princeton & Oxford: Princeton UP, 2018, 318 p. ISBN-13: 978-0-691-15416-9 Paru dans Cahiers victoriens et édouardiens, 89 Spring | 2019 Martin Hipsky (éd.), Modernism and the Women's Popular Romance in Britain, 1885-1925 [Texte intégral] Paru dans Cahiers victoriens et édouardiens, 76 Automne | 2012


Christine Reynier

Joseph Wiesenfarth Ford

Madox Ford

Women Violet Hunt

Jean Rhys

Stella Bowen

Janice Biala

Texte Intégral

Afficher l'image Martin Hipsky addresses the popular romances of the late nineteenth and early twentieth-century, that is, the best-selling novels of the time which, however, have not yet found their (rightful) place in literary history. Redressing the "romance gap"mostly the work of women romance writers-aims at a better understanding of literary modernism and its connections with fin-de-siècle fiction. Studying the "low modern" shows how the traditional romance developed into new forms and how canonical

modernist writers (Joyce, Mansfield, Woolf) borrowed from it. It ends up in a rethinking of the notions of "high" and "low", both being intent, according to the author, on representing interiority. Martin Hipsky's study participates in the recent revisionist critical movement that tries to reconfigure the "low modern". It draws our attention to the fact that when romance writers of the turn of the century wrote, they did not believe their novels to be gendered and addressed male as well as female readers.

Starting from Beer's definition of romance as a genre that remakes the world in the image of desire, Martin Hipsky reads the romances of Ward, Corelli, Orczy, Glyn, Barclay, Cross, Dell and Hull as encoding female androgynous desires, both libidinal and spiritual-what Felski calls "the popular sublime", which can be compared with the sense of rapture evinced by modernist texts-while eliciting features of melodramatic intensity ("respectability" in the Edwardian period being a matter not of the moral content of one's fiction but of the volume of one's sales). He traces lines of continuity between what was censoriously called "the sex novel" (Glynn's Three Weeks, a torrid affair between a young man and an older married woman) and D. H. Lawrence's or Joyce's novels, lines of continuity between "low" and "high" that wouldn't have surprised the readers of 1915.

2

While some critics (Keating) claim that there were no women publishing fiction between George Eliot and Virginia Woolf, in the so-called "Interregnum", others (J. E. Miller) point out that some New Woman fiction writers of the period "forged a modernism of social content, if not of literary form". Drawing on Bourdieu's definition of capitalism, he shows that by the late Victorian period, women writers were either regarded as "great", in the wake of Jane Austen and George Eliot, or as "silly lady novelists" (G. Eliot), with a low symbolic capital in the eyes of the masculine arbiters of culture but very large sales (a very useful chart illustrates this). Mary Ward published Robert Elsmere in 1888, a religious romance which in a way asked the readers to take its author as seriously as the most controversial thinkers of the time, Froude or Newman. A somewhat favourable review by Walter Pater owed Ward an interview with Gladstone who later reviewed her novel and criticized its theism and agnosticism, thus legitimating her; it was a popular success in England and the States.

Martin Hipsky shows how active Ward was in the marketing of her book-a feature common to successful women romancists of the turn of the century. He argues that far from being a domestic romance, Ward's book is a tale of psychological transcendence characteristic of the discursive intensities that can be found in Marie Corelli or Elinor Glyn's works. He broaches the history of the reception of Ward's novels. Because she defended marriage she was not perceived as a New Woman novelist in her time; she also opposed women's suffrage and was a staunch imperialist, which flattered her readers' prejudices. Her later fiction took on a more melodramatic and commercial turn.

4

The reprint of Marcella coincided with the adoption of the single-volume format by big publishers and the end of the three-decker; it also helped to curtail the circulating libraries' censorious control of women's production and consumption of fiction. After the mid-1890s, there would be no mediating institutions between popular women writers and market forces. Ironically enough, by bypassing the lending libraries, Ward enabled the widespread distribution of woman-authored "sex novels" (V. Cross, E. Glynn), the embryos of the contemporary mass-market romance. Mills and Boon was founded in 1908 and published romances about taboo topics (divorce, premarital encounters, etc.). Highbrow modernists would then react against Ward's conservatism and scorn her style, her "mot injuste" (Rebecca West).

Marie Corelli, prolific writer of "mystical" or "fantastic" romance and author of The Sorrows of Satan (1898), defended anti-elitist views and had a huge mass-market appeal. After a period of neglect, her work, which deals with class-antagonism, has been reappraised since the 1970s. Hipsky combines feminist and historicist approaches, draws on Felski as well as Jameson and reads Corelli's ideological messages concerning gender, class and capitalism in her use of melodrama; he analyses the contradictions and the correlations Corelli establishes between vice, virtue, wealth and poverty, reconciling the Christian discourse of virtue with the emergent free-market. In The Treasure of Heaven, Corelli's protagonist is poisoned by the evil city and redeemed by a rural community and in Innocent, the heroine who comes from an Edenic place, is victimized by the city. Corelli was ridiculed in Blast and regarded as degraded popular culture. However, the author argues, Modernist writers present parallels with Corelli because they reacted, mostly after World War One, against realism, as she did in her romances and Corelli writes "romances of interiority" just as the Modernists focus on the interior world but through experiments with form.

In Victorian times, romance meant moralizing; in the twentieth century, it emits more contradictory messages. In chapter 4, Hipsky discusses the generic relations of romance to realism and to emergent modernist discourses. How romance shares some features with historical realism as well as with the sublime, a "popular" version of it where transcendence is secular and the divine dwells in intimacy, in desire and interiority. He points out that the precursors of the Edwardian "sex novel" were not romance writers but late nineteenth-century realists (Hardy, Gissing, Meredith, New Woman novelists such as Sarah Grand, etc.); the "sex novel" was not a "sentimental" (i.e., "effeminate") but a more realist representation of the female libido and psychology, as in Glyn's Three Weeks.

In chapter 5, Hipsky looks at the Imperial erotic romance and more particularly, at the texts published in the years bridging the decline of the moralizing Victorian romance and the rise of the mass-market woman's romance (Cross, Dell, Hull). He shows how their eroticism is constructed through connections between sexual desire and the exoticizing of colonized "Eastern" lands. He draws parallels between these romances and modernist texts like Woolf's The Voyage Out, D. H. Lawrence's Women in Love and Mansfield's engagement with "the primitive".

In the last chapter, Hipsky reminds us that in her influential Fiction and the Reading Public (1932), Q. D. Leavis opposed "serious" literature (Joyce, Woolf, Conrad and D. H. Lawrence) to popular novels as well as sophisticated readers of realist or modernist novels to poorly educated readers of fantasy fiction. She passes negative aesthetic judgments on these popular novelists, suggests these novels act as artificial stimulation or bogus religiosity on the common readers, diverting them from the troubles of daily life, compensating for the pain of the reality principle. Interestingly enough, the author suggests that Q. D. Leavis's argument can be read as pointing to similarities between popular fiction and modernist fiction. Modernism, indeed, borrows from religious tropes to exalt art (in his epiphanies, for example) and may perform the same compensatory psychic function as popular fiction. The sublime quest of the modernist artist may find a parallel in the ecstatic transports of the romance protagonist and reader, which would bring the two conventionally opposed types of fiction together. Modernist moments are no less an anodyne than the escapism of romance. They act therapeutically on the readers' anxieties, whether they be "elite" or common readers. This is what modernist and romance narratives share and what differentiates them from nineteenth-century realism, meant to awaken and educate. Romance, like modernism, is non referential and metaphorical. On the whole, instead of defining modernism through its differences from mass culture, as critics like A. Huyssens or P. Bürger have tended to do, Hipsky yokes them together very convincingly.

Droits d'auteur

Le texte seul est utilisable sous licence CC BY-NC-ND 4.0. Les autres éléments (illustrations, fichiers annexes importés) sont « Tous droits réservés », sauf mention contraire.

Introduction

  [Texte intégral] The Transformative Power of the Arts in Victorian and Edwardian Culture and Society Paru dans Cahiers victoriens et édouardiens, 89 Spring | 2019 Michael Robertson. The Last Utopians. Four Late Nineteenth-Century Visionaries and their Legacy [Texte intégral] Princeton & Oxford: Princeton UP, 2018, 318 p. ISBN-13: 978-0-691-15416-9 Paru dans Cahiers victoriens et édouardiens, 89 Spring | 2019 Jessica Feldman, Victorian Modernism. Pragmatism and the Varieties of Aesthetic Experience [Texte intégral] Paru dans Cahiers victoriens et édouardiens, 74 Automne | 2011


Joseph Wiesenfarth Ford

Madox Violet Ford

Women Violet Hunt

Jean Rhys

Stella Bowen

Janice Biala

F E V E / Congrès De La

Jean Hunt

Stella Rhys

Janice Bowen

Biala

Christine Reynier

Texte intégral

Afficher l'image Joseph Wiesenfarth emprunte le titre de son ouvrage au pamphlet que Ford Madox Ford écrivit en 1913 pour la Women's Freedom League, This Monstrous Regiment of Women, titre qui lui-même reprend ironiquement celui de la diatribe de John Knox contre Mary Tudor et les femmes. Ford Madox Ford and the Regiment of Women explore la complexité des relations de Ford avec les femmes et dresse le portrait de celui qui put déclarer publiquement son soutien au suffrage des femmes -« I am an ardent, I am an enraged suffragette » (Ancient Lights) -tout en refusant de se soumettre à l'emprise d'une seule et unique femme. Joseph Wiesenfarth retrace la liaison romanesque de Ford avec Violet Hunt et examine la fiction de Hunt, en particulier The Flurried Years, où elle stigmatise les infidélités de Ford, se présentant en femme victime d'un Ford qu'elle voit sous les traits du Edward Ashburnham de The Good Soldier, « the rather pathetic, rather ridiculous, sentimental swashbuckler of a lover » (50). Ford, quant à lui, sera très critique de l'oeuvre de Hunt qu'il jugera bavarde et s'abstiendra de tout commentaire sur leur liaison dans ses mémoires portant sur cette période : « to report details of private history, affections or intimacies is usually infamous », écrira-t-il dans Thus to Revisit. Ces pages nous laissent entrevoir l'écart esthétique qui sépare les deux auteurs et leur conception diamétralement opposée de ce que doit être la littérature.

En abordant la liaison que Ford eut avec Stella Bowen, puis avec Janice Biala, Joseph Wiesenfarth change de méthode, sans doute parce que l'oeuvre picturale de ces deux artistes se prête moins facilement à une lecture biographique. Il présente l'activité de critique de Bowen ainsi que ses tableaux, proches de ceux des Nabis, de Vuillard, en particulier. Trente-deux pages au centre de l'ouvrage offrent des reproductions des couvertures que Bowen a dessinées pour certains livres de Ford ainsi que de ses tableaux, essentiellement des auto-portraits, des portraits de Ford et des commandes du Ministère des Armées australien pendant la seconde guerre mondiale. Les peintures de Biala, son admiration pour Cézanne sont ensuite présentées. L'auteur souligne que Ford, sensibilisé dès son plus jeune âge à l'art pictural par son grand-père, Ford Madox Brown, joua un grand rôle dans la carrière de ces deux femmes, les encourageant constamment à s'adonner à leur art.

Joseph Wiesenfarth a tenté dans cet ouvrage de se démarquer du travail des biographes de Ford en s'intéressant davantage aux femmes qui ont tour à tour partagé la vie de l'écrivain et en les présentant non seulement comme ses maîtresses mais aussi comme des artistes. On regrettera cependant que la lecture de la fiction de Hunt et Rhys n'aille pas au-delà d'une lecture biographique et que la présentation des tableaux de Bowen soit plutôt descriptive. Au vu de l'excellent premier chapitre qui retrace la carrière de Ford et dessine très bien la place qu'il occupe dans la littérature moderniste qu'il contribua tant à promouvoir dans The English Review et The Transatlantic Review, on regrettera également que l'influence que Ford a pu avoir en tant qu'écrivain sur ces femmes artistes ou que celles-ci ont pu avoir sur son écriture, ne soit pas davantage explorée. Des possibilités d'interaction sont pourtant ébauchées lorsque l'auteur compare les portraits que Bowen fit de Ford avec les images verbales que Ford transcrivit dans son poème dramatique A House. L'art de ces femmes-peintres aide-t-il à mieux lire les descriptions qui émaillent les textes de Ford, à mieux saisir la fragmentation de certains de ses textes ou la technique qu'il se plaisait à baptiser du nom d'« impressionniste » ? Si Joseph Wiesenfarth ne répond pas à ces questions, il donne en tout cas les moyens au lecteur qui le désirera de le faire, en reproduisant de nombreux tableaux de Bowen. À moins qu'il ne faille chercher ailleurs les affinités de Ford avec la peinture...

Droits d'auteur

Le texte seul est utilisable sous licence CC BY-NC-ND 4.0. Les autres éléments (illustrations, fichiers annexes importés) sont « Tous droits réservés », sauf mention contraire.

Introduction

  [Texte intégral] The Transformative Power of the Arts in Victorian and Edwardian Culture and Society Paru dans Cahiers victoriens et édouardiens, 89 Spring | 2019 Michael Robertson. The Last Utopians. Four Late Nineteenth-Century Visionaries and their Legacy [Texte intégral] Princeton & Oxford: Princeton UP, 2018, 318 p. ISBN-13: 978-0-691-15416-9 Paru dans Cahiers victoriens et édouardiens, 89 Spring | 2019 Jessica Feldman, Victorian Modernism. Pragmatism and the Varieties of Aesthetic Experience [Texte intégral] Paru dans Cahiers victoriens et édouardiens, 74 Automne | 2011 Martin Hipsky (éd.), Modernism and the Women's Popular Romance in Britain, 1885-1925 [Texte intégral] Paru dans Cahiers victoriens et édouardiens, 76 Automne | 2012

Cependant, lorsque Joseph Wiesenfarth aborde ensuite la liaison de Ford et Jean Rhys, il suggère que Rhys a fait de cette relation le coeur de Quartet (Heidler représenterait Ford et Lois, Stella Bowen) et analyse le désir de Rhys de se mettre en scène en tant que victime d'un homme calculateur et d'une femme maquerelle (ce qui, en retour, donnerait des clés de lecture de certains personnages de The Good Soldier). Il devient clair que Joseph Wiesenfarth privilégie une lecture biographique de la fiction qui tend à discuter la véracité des faits relatés dans des romans présentés comme autant de romans à clef. Si, en suivant l'avis éclairé que Virginia Woolf donne dans son essai intitulé « The Flurried Years », on est prêt à accepter que l'oeuvre de Hunt soit réduite à une oeuvre autobiographique, dans le cas de Rhys, le lecteur est plus réticent.