Characterization of a nuclear pore protein sheds light on the roles and composition of the Toxoplasma gondii nuclear pore complex

International audienceThe nuclear pore is a key structure in eukaryotes regulating nuclear-cytoplasmic transport as well as a wide range of cellular processes. Here, we report the characterization of the first Toxoplasma gondii nuclear pore protein, named TgNup302, which appears to be the orthologue of the mammalian Nup98-96 protein. We produced a conditional knock-down mutant that expresses TgNup302 under the control of an inducible tetracycline-regulated promoter. Under ATc treatment, a substantial decrease of TgNup302 protein in inducible knock-down (iKD) parasites was observed, causing a delay in parasite proliferation. Moreover, the nuclear protein TgENO2 was trapped in the cytoplasm of ATc-treated mutants, suggesting that TgNup302 is involved in nuclear transport. Fluorescence in situ hybridization revealed that TgNup302 is essential for 18S RNA export from the nucleus to the cytoplasm, while global mRNA export remains unchanged. Using an affinity tag purification combined with mass spectrometry, we identified additional components of the nuclear pore complex, including proteins potentially interacting with chromatin. Furthermore, reverse immunoprecipitation confirmed their interaction with TgNup302, and structured illuminated microscopy confirmed the NPC localization of some of the TgNup302-interacting proteins. Intriguingly, facilitates chromatin transcription complex (FACT) components were identified, suggesting the existence of an NPC-chromatin interaction in T. gondii. Identification of TgNup302-interacting proteins also provides the first glimpse at the NPC structure in Apicomplexa, suggesting a structural conservation of the NPC components between distant eukaryotes

Transcriptome profiling of the honeybee parasite Varroa destructor provides new biological insights into the mite adult life cycle

Background: The parasite Varroa destructor represents a significant threat to honeybee colonies. Indeed, development of Varroa infestation within colonies, if left untreated, often leads to the death of the colony. Although its impact on bees has been extensively studied, less is known about its biology and the functional processes governing its adult life cycle and adaptation to its host. We therefore developed a full life cycle transcriptomic catalogue in adult Varroa females and included pairwise comparisons with males, artificially-reared and non-reproducing females (10 life cycle stages and conditions in total). Results: Extensive remodeling of the Varroa transcriptome was observed, with an upregulation of energetic and chitin metabolic processes during the initial and final phases of the life cycle (e.g. phoretic and post-oviposition stages), whereas during reproductive stages in brood cells genes showing functions related to transcriptional regulation were overexpressed. Several neurotransmitter and neuropeptide receptors involved in behavioural regulation, as well as active compounds of salivary glands, were also expressed at a higher level outside the reproductive stages. No difference was detected between artificially-reared phoretic females and their counterparts in colonies, or between females who failed to reproduce and females who successfully reproduced, indicating that phoretic individuals can be reared outside host colonies without impacting their physiology and that mechanisms underlying reproductive failure occur before oogenesis. Conclusions: We discuss how these new findings reveal the remarkable adaptation of Varroa to its host biology and notably to the switch from living on adults to reproducing in sealed brood cells. By spanning the entire adult life cycle, our work captures the dynamic changes in the parasite gene expression and serves as a unique resource for deciphering Varroa biology and identifying new targets for mite control

Breaking the Mold: Disability Stereotyping is Shaped by Stigma Characteristics

The aim of this work was to investigate disability stereotypes as a key aspect of the stigmatisation by considering two of its features, i.e., its visibility, centrally and its controllability, more peripherally. The literature suggests that people with invisible disabilities face more social difficulties than those with visible disabilities. Accordingly, we hypothesised more negative stereotypes towards invisible disabilities. This hypothesis was tested using between- (pilot study) and within-subject (Studies 1a and 1b) designs. Stereotypes associated with disabilities were also measured according to their onset controllability (Study 2). Our results support the hypothesis that stereotypes associated with disabilities vary according to visibility. Specifically, people with invisible disabilities are perceived to be less warm but more competent than those with visible disabilities. These findings highlight the importance of considering the features of a disability when studying stereotypes and stigmatization

The Tip of the Iceberg: Uncovering Attitudes towards Invisible Disability

Invisible disabilities account for 80% of all disabilities, but are mostly overlooked in the disability research field. Existing literature indicates that social inclusion of individuals with invisible disabilities is particularly challenging, potentially leading to heightened experiences of discrimination compared to individuals with visible disabilities. Related to these difficulties, we hypothesized that attitudes towards invisible disabilities are more negative than towards visible disabilities. In three studies (Ntotal = 444), we used the VAAST (Visual Approach Avoidance by the Self Task), an immersive approach-avoidance paradigm to test this hypothesis. In Study 1, approach-avoidance tendencies towards visible and invisible disabilities were compared, and Study 2 replicated these findings among a population of teachers. Study 3 employed an Incident-VAAST, allowing indirect evaluations of approach-avoidance tendencies, to address potential participants’ control bias and the artificiality of direct comparisons between visible and invisible disabilities. Our results, supported by frequentist and Bayesian statistics, as well as a mini meta-analysis, consistently showed faster avoidance tendencies towards invisible disabilities, indicating stronger negative attitudes, compared to visible disabilities. This research brings evidence concerning the social exclusion specifically faced by people with invisible disabilities, nuancing the actual state of knowledge and raising awareness about the experiences of the majority of individuals with disabilities

Tout enfant handicapé est de droit un élève

« Tout enfant handicapé est de droit un élève[i] », tel est le message au cœur de la loi Handicap en France. A l’instar de cette volonté politique, les pouvoirs publics français, comme la plupart des pays occidentaux, ont progressivement mis en place ces vingt dernières années, des mesures visant à mieux inclure les personnes en situation de handicap dans notre société. Malgré cet effort important, comment expliquer que les difficultés d’inclusion des élèves avec un handicap persistent en contexte scolaire ? Comment les représentations subjectives sur le handicap peuvent expliquer ces persistances ? De quoi sont nourries ces représentations, comment résistent-elles aux informations objectives, comment influencent-elles les comportements 

Non-stationary extreme value analysis applied to seismic fragility assessment for nuclear safety analysis

International audienc

Identifying uncertainty contributions to the seismic fragility assessment of a nuclear reactor steam line

International audienceIn nuclear applications, fragility curves are an essential element of the seismic probabilistic safety assessment that is performed at the level of the power plant. These statistical tools establish the link between the probabilistic seismic hazard loading at the site and the required performance of the plant's safety functions. In this context, the fragility model formalized by Kennedy & Ravindra (1984) proposes to account for the aleatory randomness and the epistemic uncertainty generated by various sources of variability, such as the representation of the seismic input or the assumptions in the structural model and in the loading patterns. Therefore, this study investigates the relative contributions of such variables to the dispersion of the resulting fragility functions, while ensuring the separation between aleatory and epistemic uncertainty sources, as advocated by the standards in effect in the nuclear industry. To this end, a coupled model of a supporting structure and an anchored steam line is considered and computed with the finite-element CAST3M software (Rahni et al., 2017). The failure criterion is related to the exceedance of a given effort value at a point of the steam line corresponding to a vertical stop. A coupled of hundreds of three-component ground-motion records are applied at the base of the model, in order to perform non-linear time-history analyses. The record selection follows the conditional spectrum method (Lin et al., 2013), in order to scale the records while ensuring the hazard consistency, through the identification of reference earthquake scenarios for each predefined hazard level. As a result, dozens of ground-motion parameters are tested as potential intensity measures (IMs), with respect to state-of-the-art indicators measuring efficiency or sufficiency. Some couples of ground-motion parameters are assembled as vector-valued IMs, in order to generate so-called fragility surfaces: these multi-variate functions may then be reinterpreted as single-IM fragility curves, where the conditional distribution of the secondary IM with respect to the main one generates additional confidence intervals for the fragility curve. It is thus shown that the aleatory randomness due to record-to-record variability may be partially transferred to an epistemic uncertainty contribution. This variability is then put in perspective with other sources of uncertainty due to modelling assumptions, such as the variability in the mechanical parameters of the model or the angle of loading of the seismic input

The development of spasticity with age in 4,162 children with cerebral palsy : a register-based prospective cohort study

Background and purpose — Spasticity is often regarded as a major cause of functional limitation in children with cerebral palsy (CP). We analyzed the spasticity development with age in the gastrosoleus muscle in children with CP. Children and methods — This is a longitudinal cohort study of 4,162 children (57% boys) with CP born in 1990–2015, monitored using standardized follow-up examinations in the Swedish surveillance program for CP. The study is based on 57,953 measurements of spasticity of the gastrosoleus muscle assessed using the Ashworth scale (AS) in participants between 0 and 15 years of age. The spasticity was analyzed in relation to age, sex, and Gross Motor Function Classification System (GMFCS) levels using a linear mixed model. Development of spasticity with age was modeled as a linear spline. Results — The degree of spasticity increased in most children over the first 5 years of life. At 5 years of age, 38% had an AS level of ≥ 2. The spasticity then decreased for 65% of the children during the remaining study period. At 15 years of age only 22% had AS ≥ 2. The level of spasticity and the rate of increase and decrease before and after 5.5 years of age were higher in children at GMFCS IV–V. Interpretation — The degree of spasticity of the gastrosoleus muscle often decreases after 5 years of age, which is important for long-term treatment planning and should be considered in spasticity management

Antennae hold a key to <em>Varroa</em>-sensitive hygiene behaviour in honey bees

International audienceIn honey bees, Varroa sensitive hygiene (VSH) behaviour, which involves the detection and removal of brood parasitised by the mite Varroa destructor, can actively participate in the survival of colonies facing Varroa outbreaks. This study investigated the mechanisms of VSH behaviour, by comparing the antennal transcriptomes of bees that do and do not perform VSH behaviour. Results indicate that antennae likely play a key role in the expression of VSH behaviour. Comparisons with the antennal transcriptome of nurse and forager bees suggest that VSH profile is more similar to that of nurse bees than foragers. Enhanced detection of certain odorants in VSH bees may be predicted from transcriptional patterns, as well as a higher metabolism and antennal motor activity. Interestingly, Deformed wing virus/Varroa destructor virus infections were detected in the antennae, with higher level in non-VSH bees; a putative negative impact of viral infection on bees’ ability to display VSH behaviour is proposed. These results bring new perspectives to the understanding of VSH behaviour and the evolution of collective defence by focusing attention on the importance of the peripheral nervous system. In addition, such data might be useful for promoting marker-assisted selection of honey bees that can survive Varroa infestations

Transcriptome profiling of the honeybee parasite <em>Varroa destructor</em> provides new biological insights into the mite adult life cycle

International audienc