Recombinant myelin oligodendrocyte glycoprotein quality modifies evolution of experimental autoimmune encephalitis in macaques

The authors describe quantitatively and qualitatively different forms of experimental autoimmune encephalitis (EAE) in cynomolgus macaques. They found that bacterial contaminants within recombinant human myelin oligodendrocyte glycoprotein seemed to aggravate disease evolution. They provide anatomopathological features of fulminant and progressive forms of EAE, allowing them to distinguish specific factors influencing the evolution of this model of autoimmune demyelinating disease. Experimental autoimmune encephalitis (EAE) is a well-recognized model for the study of human acquired demyelinating diseases (ADD), a group of inflammatory disorders of the central nervous system (CNS) characterized by inflammation, myelin loss, and neurological impairment of variable severity. In rodents, EAE is typically induced by active immunization with a combination of myelin-derived antigen and a strong adjuvant as complete Freund's adjuvant (CFA), containing components of the mycobacterial wall, while myelin antigen alone or associated with other bacterial components, as lipopolysaccharides (LPS), often fails to induce EAE. In contrast to this, EAE can be efficiently induced in non-human primates by immunization with the recombinant human myelin oligodendrocyte glycoprotein (rhMOG), produced in Escherichia coli (E. coli), purified and formulated with incomplete Freund's adjuvant (IFA), which lacks bacterial elements. Here, we provide evidence indicating how trace amounts of bacterial contaminants within rhMOG may influence the course and severity of EAE in the cynomolgus macaque immunized with rhMOG/IFA. The residual amount of E. coli contaminants, as detected with mass spectrometry within rhMOG protein stocks, were found to significantly modulate the severity of clinical, radiological, and histologic hallmarks of EAE in macaques. Indeed, animals receiving the purest rhMOG showed milder disease severity, increased numbers of remissions, and reduced brain damage. Histologically, these animals presented a wider diversity of lesion types, including changes in normal-appearing white matter and prephagocytic lesions. Non-human primates EAE model with milder histologic lesions reflect more accurately ADD and permits to study of the pathogenesis of disease initiation and progression

Evoked Potentials in Motor Cortical Local Field Potentials Reflect Task Timing and Behavioral Performance

Evoked potentials (EPs) are observed in motor cortical local field potentials (LFPs) during movement execution (movement-related potentials [MRPs]) and in response to relevant visual cues (visual evoked potentials [VEPs]). Motor cortical EPs may be directionally selective, but little is known concerning their relation to other aspects of motor behavior, such as task timing and performance. We recorded LFPs in motor cortex of two monkeys during performance of a precued arm-reaching task. A time cue at the start of each trial signaled delay duration and thereby the pace of the task and the available time for movement preparation. VEPs and MRPs were strongly modulated by the delay duration, VEPs being systematically larger in short-delay trials and MRPs larger in long-delay trials. Despite these systematic modulations related to the task timing, directional selectivity was similar in short and long trials. The behavioral reaction time was positively correlated with MRP size and negatively correlated with VEP size, within sessions. In addition, the behavioral performance improved across sessions, in parallel with a slow decrease in the size of VEPs and MRPs. Our results clearly show the strong influence of the behavioral context and performance on motor cortical population activity during movement preparation and execution

Development of a rapid multiplex SSR genotyping method to study populations of the fun-gal plant pathogen Zymoseptoria tritici

Background Zymoseptoria tritici is a hemibiotrophic ascomycete fungus causing leaf blotch of wheat that often decreases yield severely. Populations of the fungus are known to be highly diverse and poorly differentiated from each other. However, a genotyping tool is needed to address further questions in large collections of isolates, regarding regional population structure, adaptation to anthropogenic selective pressures, and dynamics of the recently discovered accessory chromosomes. This procedure is limited by costly and time-consuming simplex PCR genotyping. Recent development of genomic approaches and of larger sets of SSRs enabled the optimization of microsatellite multiplexing. Findings We report here a reliable protocol to amplify 24 SSRs organized in three multiplex panels, and covering all Z. tritici chromosomes. We also propose an automatic allele assignment procedure, which allows scoring alleles in a repeatable manner across studies and laboratories. All together, these tools enabled us to characterize local and worldwide populations and to calculate diversity indexes consistent with results reported in the literature. Conclusion This easy-to-use, accurate, repeatable, economical, and faster technical strategy can provide useful genetic information for evolutionary inferences concerning Z. tritici populations. Moreover, it will facilitate the comparison of studies from different scientific groups

Different behavioural strategies among seven highly invasive ant species

Ants figure prominently among the worst invasive species because of their enormous ecological and economic impacts. However, it remains to be investigated which species would be behaviourally dominant when confronted with another invasive ant species, should two species be introduced in the same area. In the future, many regions might have suitable environmental conditions for several invasive ant species, as predicted under climate change scenarios. Here, we explored interactions among several highly invasive ant species, which have been shown to have overlapping suitable areas. The aim of this study was to evaluate the performance in interference competition of seven of the world's worst invasive ant species (Anoplolepis gracilipes, Paratrechina longicornis, Myrmica rubra, Linepithema humile, Lasius neglectus, Wasmannia auropunctata and Pheidole megacephala). We conducted pairwise confrontations, testing the behaviour of each species against each of the six other species (in total 21 dyadic confrontations). We used single worker confrontations and group interactions of 10 versus 10 individuals to establish a dominance hierarchy among these invasive ant species. We discovered two different behavioural strategies among these invasive ants: three species displayed evasive or indifferent behaviour when individuals or groups were confronted (A. gracilipes, Pa. longicornis, M. rubra), while the four remaining species were highly aggressive during encounters and formed a linear dominance hierarchy. These findings contrast with the widespread view that invasive ants form a homogeneous group of species displaying the 'invasive syndrome', which includes generally aggressive behaviour. The dominance hierarchy among the four aggressive species may be used to predict the outcome of future competitive interactions under some circumstances. Yet, the existence of several behavioural strategies renders such a prediction less straightforward

Different behavioural strategies among seven highly invasive ant species. Biol. Invasions

Abstract Ants figure prominently among the worst invasive species because of their enormous ecological and economic impacts. However, it remains to be investigated which species would be behaviourally dominant when confronted with another invasive ant species, should two species be introduced in the same area. In the future, many regions might have suitable environmental conditions for several invasive ant species, as predicted under climate change scenarios. Here, we explored interactions among several highly invasive ant species, which have been shown to have overlapping suitable areas. The aim of this study was to evaluate the performance in interference competition of seven of the world's worst invasive ant species (Anoplolepis gracilipes, Paratrechina longicornis, Myrmica rubra, Linepithema humile, Lasius neglectus, Wasmannia auropunctata and Pheidole megacephala). We conducted pairwise confrontations, testing the behaviour of each species against each of the six other species (in total 21 dyadic confrontations). We used single worker confrontations and group interactions of 10 versus 10 individuals to establish a dominance hierarchy among these invasive ant species. We discovered two different behavioural strategies among these invasive ants: three species displayed evasive or indifferent behaviour when individuals or groups were confronted (A. gracilipes, Pa. longicornis, M. rubra), while the four remaining species were highly aggressive during encounters and formed a linear dominance hierarchy. These findings contrast with the widespread view that invasive ants form a homogeneous group of species displaying the 'invasive syndrome', which includes generally Electronic supplementary material The online version of this articl

A first glimpse into the genetic architecture of pathogenicity of Zymoseptoria tritici on bread wheat

Zymoseptoria tritici is a fungal pathogen of wheat responsible for the septoria leaf blotch disease. This disease is a major concern in bread and durum wheats growing areas worldwide. It can be controlled by fungicide treatments and the use of resistant wheat cultivars. To date, 21 resistance genes and 89 QTLs for resistance to septoria leaf blotch have been mapped in bread wheat. Despite this large availability of resistant sources, it remains a challenge to improve the resistance levels of wheat elite cultivars because of the mostly quantitative nature of wheat-septoria interactions and of the very high level of genetic diversity within pathogen populations. Our objective is to understand the genetic architecture of pathogenicity in Z. tritici by identifying its determinants and revealing the specificity of their interaction with resistance determinants in wheat. We have undertaken a genome wide association mapping approach (GWAS) to identify pathogenicity genes in Z. tritici. A collection of more than 2000 isolates has been established in France. The genetic diversity has been characterized in this collection, and 109 isolates selected for resequencing and pathogenicity assays. In so doing, we obtained the virulence spectra of the 109 French isolates, revealing the efficiency of known resistance STB genes in France, and allowing to detect known and unknown STB genes present in French elite cultivars. Furthermore, combining the precision of our pathology assays, the selection of wheat genotypes well characterized for their resistance determinants, and the precision of GWAS in our Z. tritici population, we have identified several candidate avirulence genes interacting with known resistance genes in bread wheat. Thus far, the small secreted protein AvrStb6 is the first avirulence gene to be identified and functionally validated in this important wheat pathogen

Quantitative pathogenicity and host adaptation in a fungal plant pathogen revealed by whole-genome sequencing

Abstract Knowledge of genetic determinism and evolutionary dynamics mediating host-pathogen interactions is essential to manage fungal plant diseases. Studies on the genetic architecture of fungal pathogenicity often focus on large-effect effector genes triggering strong, qualitative resistance. It is not clear how this translates to predominately quantitative interactions. Here, we use the Zymoseptoria tritici-wheat model to elucidate the genetic architecture of quantitative pathogenicity and mechanisms mediating host adaptation. With a multi-host genome-wide association study, we identify 19 high-confidence candidate genes associated with quantitative pathogenicity. Analysis of genetic diversity reveals that sequence polymorphism is the main evolutionary process mediating differences in quantitative pathogenicity, a process that is likely facilitated by genetic recombination and transposable element dynamics. Finally, we use functional approaches to confirm the role of an effector-like gene and a methyltransferase in phenotypic variation. This study highlights the complex genetic architecture of quantitative pathogenicity, extensive diversifying selection and plausible mechanisms facilitating pathogen adaptation

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

International audienceStroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization