Insects and incest: sib-mating tolerance in natural populations of a parasitoid wasp

International audienc

Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) beyond SMARCA4 Mutations: A Comprehensive Genomic Analysis.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, is characterized by recurrent loss-of-function mutations in the SMARCA4 gene, and for which effective treatments options are lacking. The aim of this study was to broaden the knowledge on this rare malignancy by reporting a comprehensive molecular analysis of an independent cohort of SCCOHT cases. We conducted Whole Exome Sequencing in six SCCOHT, and RNA-sequencing and array comparative genomic hybridization in eight SCCOHT. Additional immunohistochemical, Sanger sequencing and functional data are also provided. SCCOHTs showed remarkable genomic stability, with diploid profiles and low mutation load (mean, 5.43 mutations/Mb), including in the three chemotherapy-exposed tumors. All but one SCCOHT cases exhibited 19p13.2-3 copy-neutral LOH. SMARCA4 deleterious mutations were recurrent and accompanied by loss of expression of the SMARCA2 paralog. Variants in a few other genes located in 19p13.2-3 (e.g., PLK5) were detected. Putative therapeutic targets, including MAGEA4, AURKB and CLDN6, were found to be overexpressed in SCCOHT by RNA-seq as compared to benign ovarian tissue. Lastly, we provide additional evidence for sensitivity of SCCOHT to HDAC, DNMT and EZH2 inhibitors. Despite their aggressive clinical course, SCCOHT show remarkable inter-tumor homogeneity and display genomic stability, low mutation burden and few somatic copy number alterations. These findings and preliminary functional data support further exploration of epigenetic therapies in this lethal disease

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Under control or under influence? Wolbachia invasions, cytoplasmic incompatibility, and Drosophila suzukii population dynamics

Wolbachia pipientis est une bactérie qui infecte de nombreux arthropodes et nématodes. Localisée dans le cytoplasme de ses hôtes, elle est transmise de la mère à ses descendants. Wolbachia manipule la reproduction de ses hôtes en faveur de sa propre transmission, le mécanisme le plus répandu étant l'incompatibilité cytoplasmique (IC). Dans sa forme la plus simple, l'IC se traduit par la stérilité des croisements entre mâles infectés et femelles non infectées. A ce titre, Wolbachia pourrait servir dans des programmes de gestion d'espèces nuisibles. Nous présentons ici les premiers développements expérimentaux d'un tel programme de lutte contre la mouche des fruits Drosophila suzukii.En théorie, une souche incompatible de Wolbachia devrait envahir la population d'hôtes dans laquelle elle est introduite, causer une augmentation des croisements stériles et donc un déclin de la population. Une telle stratégie, combinée à d'autres mécanismes déstabilisants tels que l'effet Allee, permettrait d'éradiquer la population nuisible.Afin de mettre à l'épreuve cette théorie, nous avons mené des recherches expérimentales sur D. suzukii et trois souches de Wolbachia : wSuz, souche sauvage n'induisant pas d'IC, wTei et wHa, souches transfectées artificiellement et induisant de l'IC. Pour des grandes populations de mouches à capacité de charge, nous n'avons pas observé la baisse d'effectif attendue en théorie. Nous avons donc fait l'hypothèse d'un mécanisme négligé par les modèles : la compensation par densité-dépendance. En diminuant la proportion d'œuf viables, l'IC pourrait provoquer un relâchement de la compétition entre les larves et ainsi conduire au même nombre d'adultes que sans IC. Nous avons validé cette nouvelle hypothèse et obtenus deux résultats majeurs : (1) au sein de populations de D. suzukii soumises à une manipulation factorielle de la compétition densité-dépendante et de l'IC, un relâchement de la compétition entraine un fort effet de l'IC sur le taux de reproduction ; (2) dans des populations en croissance, l'IC cause une baisse du nombre de mouches qui perdure tant que la compétition est modérée. Ainsi, nous montrons que les populations de D. suzukii est sous l'influence d'une compensation par densité-dépendance qui interfère avec une stratégie de contrôle utilisant l'incompatibilité cytoplasmique. En parallèle, des expériences à faible effectif montrent un accroissement exponentiel des petites populations, sans effet Allee déstabilisateur. Ainsi, nos recherches suggèrent que le développement de nouvelles méthodes de biocontrôle ne pourra se passer de recherches fondamentales sur les processus complexes qui déterminent la dynamique éco-évolutive des populations, au risque de produire des échecs incompris.Wolbachia pipientis is a bacterium that infects numerous arthropods and nematodes. It is located in the cytoplasm of its host cells and is transmitted from mother to offspring. Wolbachia manipulate host reproduction in favor of their own transmission, the most common mechanism being cytoplasmic incompatibility (CI). In its simplest form, CI results in sterility of crosses between infected males and uninfected females. In this context, Wolbachia could be used in programs aimed at controlling pest species. In this thesis, we present initial experimental advancements for such a control program targeting the fruit fly Drosophila suzukii.Theoretically, an incompatible strain of Wolbachia should invade the host population into which it is introduced, causing an increase in sterile crosses and thus a decline of the population. Such a strategy, combined with other destabilizing mechanisms such as the Allee effect, could eradicate the pest population.To test this theory, we conducted experimental research on D. suzukii and three Wolbachia strains: wSuz, a wild strain that does not induce CI, and wTei and wHa, two artificially transfected strains that induce CI. For large insect populations at carrying capacity, we did not observe the predicted decline in numbers. We therefore hypothesized a mechanism neglected by theoretical models: density-dependence compensation. By reducing the proportion of viable eggs, CI could trigger a relaxation of competition among larvae, leading to similar number of adults as in the absence of CI. We tested this new hypothesis and obtained two major results. First, in D. suzukii populations subjected to a factorial manipulation of density-dependent competition and CI, a relaxation of competition leads to a strong effect of CI on reproductive rate. Second, in growing populations, CI causes a decrease in fly numbers that persists as long as competition is moderate. Thus, we show that D. suzukii populations are under the influence of a density-dependent compensation that interferes with a control strategy based on cytoplasmic incompatibility. In parallel, experiments at low numbers shows an exponential increase of small populations, with no destabilizing Allee effect. Our research therefore suggests that the development of new biocontrol methods that bypass fundamental research into the complex processes that determine the eco-evolutionary dynamics of populations run a high risk of producing misunderstood failures

Sous contrôle ou sous influence ? Invasions de Wolbachia, incompatibilité cytoplasmique, et dynamique des populations de Drosophila suzukii

Wolbachia pipientis is a bacterium that infects numerous arthropods and nematodes. It is located in the cytoplasm of its host cells and is transmitted from mother to offspring. Wolbachia manipulate host reproduction in favor of their own transmission, the most common mechanism being cytoplasmic incompatibility (CI). In its simplest form, CI results in sterility of crosses between infected males and uninfected females. In this context, Wolbachia could be used in programs aimed at controlling pest species. In this thesis, we present initial experimental advancements for such a control program targeting the fruit fly Drosophila suzukii.Theoretically, an incompatible strain of Wolbachia should invade the host population into which it is introduced, causing an increase in sterile crosses and thus a decline of the population. Such a strategy, combined with other destabilizing mechanisms such as the Allee effect, could eradicate the pest population.To test this theory, we conducted experimental research on D. suzukii and three Wolbachia strains: wSuz, a wild strain that does not induce CI, and wTei and wHa, two artificially transfected strains that induce CI. For large insect populations at carrying capacity, we did not observe the predicted decline in numbers. We therefore hypothesized a mechanism neglected by theoretical models: density-dependence compensation. By reducing the proportion of viable eggs, CI could trigger a relaxation of competition among larvae, leading to similar number of adults as in the absence of CI. We tested this new hypothesis and obtained two major results. First, in D. suzukii populations subjected to a factorial manipulation of density-dependent competition and CI, a relaxation of competition leads to a strong effect of CI on reproductive rate. Second, in growing populations, CI causes a decrease in fly numbers that persists as long as competition is moderate. Thus, we show that D. suzukii populations are under the influence of a density-dependent compensation that interferes with a control strategy based on cytoplasmic incompatibility. In parallel, experiments at low numbers shows an exponential increase of small populations, with no destabilizing Allee effect. Our research therefore suggests that the development of new biocontrol methods that bypass fundamental research into the complex processes that determine the eco-evolutionary dynamics of populations run a high risk of producing misunderstood failures.Wolbachia pipientis est une bactérie qui infecte de nombreux arthropodes et nématodes. Localisée dans le cytoplasme de ses hôtes, elle est transmise de la mère à ses descendants. Wolbachia manipule la reproduction de ses hôtes en faveur de sa propre transmission, le mécanisme le plus répandu étant l'incompatibilité cytoplasmique (IC). Dans sa forme la plus simple, l'IC se traduit par la stérilité des croisements entre mâles infectés et femelles non infectées. A ce titre, Wolbachia pourrait servir dans des programmes de gestion d'espèces nuisibles. Nous présentons ici les premiers développements expérimentaux d'un tel programme de lutte contre la mouche des fruits Drosophila suzukii.En théorie, une souche incompatible de Wolbachia devrait envahir la population d'hôtes dans laquelle elle est introduite, causer une augmentation des croisements stériles et donc un déclin de la population. Une telle stratégie, combinée à d'autres mécanismes déstabilisants tels que l'effet Allee, permettrait d'éradiquer la population nuisible.Afin de mettre à l'épreuve cette théorie, nous avons mené des recherches expérimentales sur D. suzukii et trois souches de Wolbachia : wSuz, souche sauvage n'induisant pas d'IC, wTei et wHa, souches transfectées artificiellement et induisant de l'IC. Pour des grandes populations de mouches à capacité de charge, nous n'avons pas observé la baisse d'effectif attendue en théorie. Nous avons donc fait l'hypothèse d'un mécanisme négligé par les modèles : la compensation par densité-dépendance. En diminuant la proportion d'œuf viables, l'IC pourrait provoquer un relâchement de la compétition entre les larves et ainsi conduire au même nombre d'adultes que sans IC. Nous avons validé cette nouvelle hypothèse et obtenus deux résultats majeurs : (1) au sein de populations de D. suzukii soumises à une manipulation factorielle de la compétition densité-dépendante et de l'IC, un relâchement de la compétition entraine un fort effet de l'IC sur le taux de reproduction ; (2) dans des populations en croissance, l'IC cause une baisse du nombre de mouches qui perdure tant que la compétition est modérée. Ainsi, nous montrons que les populations de D. suzukii est sous l'influence d'une compensation par densité-dépendance qui interfère avec une stratégie de contrôle utilisant l'incompatibilité cytoplasmique. En parallèle, des expériences à faible effectif montrent un accroissement exponentiel des petites populations, sans effet Allee déstabilisateur. Ainsi, nos recherches suggèrent que le développement de nouvelles méthodes de biocontrôle ne pourra se passer de recherches fondamentales sur les processus complexes qui déterminent la dynamique éco-évolutive des populations, au risque de produire des échecs incompris

Degradation reactions of D-galacturonic acid and its polymers as main components of pectin and their influence on browning.

Uronic acids are ubiquitarily distributed in nature and function as the basis of the pectin molecule and other geling agents. The thermal treatment of D-Galacturonic acid show the high browning potential during caramelization of sugar acids especially in comparison to reducing sugars. The ring opening velocity may play an important role for understanding the drastic differences in the reaction speeds. Wegener et al. postulated that carboxyl groups influence the mutarotation velocity of carbohydrates and thus lead to an enhanced degradation. To investigate whether the carboxylic group of uronic acids also influences the ring opening speed polarimetric experiments where performed. These measurements show that the speed of mutarotation of D-Galacturonic acid exceeds that of D-Galactose by nearly 4.5 times. Investigations of D-Galactose in combination with formic lead to an enhancement of a factor of 1.7. Not only the ring opening velocity differs between D-Galacturonic acid and reducing sugars. One other factor influencing the degradation reactions is the release of CO2.Experiments measuring the concentration of CO2 during a time series of heated D-Galacturonic acid at 60 °C show a steady increase that correlates with a decrease of the D-Galacturonic acid concentration. One of the degradation reactions postulated for the release of CO2 leads to α-ketoglutaraldehyde which is responsible for the formation of several chromophoric substances. Apart from an enhanced ring opening velocity and the release of CO2 GC-MS investigations of thermal treated aquatic model systems of D-Galacturonic acid show next to the typical degradation products such as norfuraneol and furfural, that are also generated during the degradation of D-Galactose, the formation of 2,3-dihydroxybenzaldehyde, catechol and 3,8-Dihydroxy-2-methyl-4H-chromen-4-on. Model systems of 2,3-dihydroxybenzaldehyde already show an intense colour formation. These results indicate that the formation of chromophoric substances within uronic acid model-systems derive from two different pathways. One leading from the formation of caramelization reactions typical for sugar degradation and the other one resulting from oxidative polyphenolic coupling reactions that do not take place within model systems of reducing sugars.Pektine gehören zu den essenziellen Bestandteilen aller höheren Landpflanzen. Sie spielen deshalb auch eine bedeutende Rolle in der Lebensmittelindustrie vor allem bei der Verarbeitung, der Lagerung und dem Transport von pflanzlichen Lebensmitteln. Hauptbestandteil der Pektine sind die Uronsäuren, davon ca. 65% α-D-Galacturonsäure und ihre Oligo- und Polymere. Der Schwerpunkt dieser wissenschaftlichen Arbeit liegt auf Untersuchungen zur Reaktivität von D-Galacturonsäure und ihren oligo- und polymeren Strukturen unter dem Einfluss verschiedener äußerer Faktoren, wie zum Beispiel Temperatur und Feuchtigkeit. Untersucht wird unter anderem das Abbauverhalten von D-Galacturonsäure unter thermischer Behandlung im Vergleich mit reduzierenden Zuckern, wie z. B. D-Galactose. Dabei wird festgestellt, dass D-Galacturonsäure ein wesentlich höheres Bräunungspotential als die reduzierenden Zucker aufweist. Als mögliche Gründe für diesen Reaktivitätsunterschied kommen verschiedene Ursachen in Betracht. So kann die verschiedene Geschwindigkeit der Ringöffnung von Uron-säuren und reduzierenden Zuckern dieser Unterschied begründen. Untersuchungen von Wegener et al. weisen in diesem Zusammenhang auf eine gesteigerte Mutarotationsgeschwindigkeit bei reduzierenden Zuckern unter Anwesenheit einer Carboxylfunktion auf, die auch zu einer erhöhten Farbbildung in erhitzten Modellsystemen führt. Die durchgeführten polarimetrischen Messungen zeigen, dass die Mutarotationsgeschwindigkeit von D-Galacturonsäure, die von D-Galactose um einen Faktor von 4,5 übersteigt. Entsprechend intensiver ist auch das chromophore Verhalten der Abbauprodukte von D-Galacturonsäure. Untersuchungen von D-Galactose in Kombination mit Ameisensäure weisen zwar eine Erhöhung um einen Faktor von 1,7 im Vergleich zur Reinsubstanz auf, ist aber dennoch wesentlich geringer als die von D-Galacturonsäure. Neben der Ringöffnungsgeschwindigkeit gibt es noch weitere Faktoren, die die Unter-schiede in der Reaktivität von D-Galacturonsäure und von D-Galactose bewirken und damit auch ihre unterschiedlichen chromophoren Eigenschaften aufweisen. Dazu gehört vor allem die unter bestimmten Bedingungen vermehrte Freisetzung von CO2 aus D-Galacturonsäure. Messungen der freigesetzten CO2 Konzentration bei 60 °C zeigen einen stetigen Anstieg über einen zeitlichen Verlauf, welcher mit dem Abbau an D-Galacturonsäure korreliert. Einer der postulierten Abbauwege zur Bildung von CO2 führt dabei über α-Ketoglutaraldehyd, das für die Bildung zahlreicher chromophorer Verbindungen verantwortlich ist. Darüber hinaus zeigen GC-MS Untersuchungen von thermisch behandelten wässrigen D-Galacturonsäure-Modellsystemen nicht nur die Bildung von Norfuraneol und Furfural, welche auch in Modellsystemen von D-Galactose nachweisbar sind, sondern auch die Bildung von phenolischen Verbindungen wie 2,3-Dihydroxybenzaldehyd, das in diesem Zusammenhang zum ersten Mal in dieser Arbeit beschrieben wird, dazu kommen noch Catechol und 3,8-Dihydroxy-2-methyl-4H-chromen-4-on. Besonders die Modellsysteme von 2,3-Dihydroxybenzaldehyd weisen eine sehr starke Farbbildung auf. Diese Ergebnisse deuten darauf hin, dass die Bildung chromophorer Verbindungen in Uronsäure-Modellsystemen über zwei grundsätzlich verschiedene Reaktionswege verläuft. Ein Reaktionsweg führt dabei über Abbaureaktionen der D-Galacturonsäure, die der Karamellisierung reduzierender Zucker sehr ähnlich ist und zu vergleichbaren Produkten führt. Ein zweiter Weg verläuft über oxidative phenolische Kupplungsreaktionen, die in Modellsystemen reduzierender Zucker bisher nicht beobachtet wurden und nur bei Uronsäuren zu finden sind. Die praktische Relevanz dieser Untersuchungen ergibt sich aus der Tatsache, dass Pektine und damit auch ihr Hauptbestandteil, die Uronsäuren und ihre Oligo- und Polymere, in den meisten pflanzlichen Lebensmitteln vorkommen. Die Kenntnisse über das milieuabhängige reaktive Verhalten von D-Galacturonsäure und ihrer Polymere ist deshalb von signifikanter Bedeutung für die Qualität pflanzlicher Lebensmittel, ihre Verarbeitung, Lagerung und dem Transport.DFG, 268547215, Strukturabhängige Abbaureaktionen von Pektinen und deren Auswirkungen auf nicht-enzymatische Bräunung und technologische Funktionalitä

Sterile males in a parasitoid wasp with complementary sex determination: from fitness costs to population extinction

Background: Single-locus complementary sex determination (sl-CSD), which occurs in some insects of the order Hymenoptera, imposes a heavy genetic load that can drive small populations to extinction. The core process in these species is the development of individuals homozygous at the sex-determining locus into unfit diploid males. The risk of extinction of populations with sl-CSD is theoretically much higher if diploid males are viable and capable of mating but sterile, because diploid males then decrease the reproductive output of both their parents and the females with which they mate. Results: In the parasitoid wasp Venturia canescens (Hymenoptera: Ichneumonidae), diploid males resembled their haploid counterparts in most respects, but their mating success was nevertheless lower than that of haploid males, especially when the two types of males were placed in competition. Furthermore, although diploid males transferred viable sperm during copulation, they sired no daughters: the females with which they mated produced only sons, like virgin females. A simulation model combining behavior, genetics and demography demonstrated that for two alternative hypotheses concerning the fertilization success of diploid sperm, the mating success of diploid males strongly affected population dynamics. Conclusion: The performance of diploid males should be estimated in competitive situations. It is a crucial determinant of the probability of extinction

Synergy in information use for mate finding: demonstration in a parasitoid wasp

International audienceIn many animals, mating takes place after natal dispersal. Consequently, use of reliable information is required to increase the probability of encounters between the sexes. Most of the studies on mate finding in parasitoid insects have focused on the role of a single information source: a sex pheromone. Other sources have been mostly ignored. We studied the nature of olfactory information used for mate finding by the parasitoid Venturia canescens both at a distance and at host patch level, and investigated how this information is used. We tested which sex attracts the other and whether mate location is improved by combining different sources of information. We found that males simultaneously used two types of olfactory cues to find their mate: information directly related to females and an environmental cue provided by hosts. Male efficiency in locating virgin females was enhanced threefold by the association of females with hosts, whereas host patches, on their own, were unattractive to males. Our results also suggest that females emit a volatile pheromone. At the host patch level, males used chemical marks left by females foraging for hosts. These results led us to consider the distinction between signals and cues and we suggest that the volatile pheromone emitted by the females, always described as a signal, could rather be a cue. Although evidence for a volatile sex pheromone is pervasive in parasitoids, our study stresses the role of other cues in mate-finding strategies

Distinct brain networks for remote episodic memory depending on content and emotional experience

International audienceThe mechanisms that underlie the storage of old nontraumatic episodic memories remain enigmatic because of the difficulty in modelling this particular type of memory in humans and animals. Episodic memories combine incidental and occasional “What-Where-When/In which context” multisensory information and can be stored for long periods of time. Here, using a task in rodents that models human episodic memory, including odour/place/context components, we applied advanced behavioural and computational analyses and brain imaging of c-Fos and Zif268 to characterize remote episodic memories and their engrams for the first time. We show that the content and accuracy of memories vary across individuals and depend on the emotional relationship with odours experienced during episodes. Activated brain networks reflect the nature and content of remote episodic memories and their transformation over time, and emotional cortico-hippocampal networks play critical roles in maintaining vivid memories