CORRELATIONAL SELECTION ON PRO‐ AND ANTI‐INFLAMMATORY EFFECTORS

Parasites impose a permanent threat for hosts. As a consequence, immune defenses are important for host fitness. However, the immune response can also produce self‐damage and impair host fitness if not properly regulated. Effectors that up‐ and downregulate the immune response should, therefore, evolve in concert, and be under the action of correlational selection. To address this issue, we assessed the shape of the selection operating on pro‐ and anti‐inflammatory effectors following an inflammatory challenge in laboratory mice. We found that selection acts on the combination of these two traits as individuals that produced large amount of pro‐inflammatory cytokines could achieve relatively high fitness (survival) only if also producing a large amount of anti‐inflammatory effectors. To our knowledge, this is the first study providing evidence for correlational selection on immunity.     

A Generic Model to Simulate Air-Borne Diseases as a Function of Crop Architecture

In a context of pesticide use reduction, alternatives to chemical-based crop protection strategies are needed to control diseases. Crop and plant architectures can be viewed as levers to control disease outbreaks by affecting microclimate within the canopy or pathogen transmission between plants. Modeling and simulation is a key approach to help analyze the behaviour of such systems where direct observations are difficult and tedious. Modeling permits the joining of concepts from ecophysiology and epidemiology to define structures and functions generic enough to describe a wide range of epidemiological dynamics. Additionally, this conception should minimize computing time by both limiting the complexity and setting an efficient software implementation. In this paper, our aim was to present a model that suited these constraints so it could first be used as a research and teaching tool to promote discussions about epidemic management in cropping systems. The system was modelled as a combination of individual hosts (population of plants or organs) and infectious agents (pathogens) whose contacts are restricted through a network of connections. The system dynamics were described at an individual scale. Additional attention was given to the identification of generic properties of host-pathogen systems to widen the model''s applicability domain. Two specific pathosystems with contrasted crop architectures were considered: ascochyta blight on pea (homogeneously layered canopy) and potato late blight (lattice of individualized plants). The model behavior was assessed by simulation and sensitivity analysis and these results were discussed against the model ability to discriminate between the defined types of epidemics. Crop traits related to disease avoidance resulting in a low exposure, a slow dispersal or a de-synchronization of plant and pathogen cycles were shown to strongly impact the disease severity at the crop scale.     

Competition and predation models applied to the case of the sibling birds species ofHippolais in Burgundy

We study the case of two sibling species ofHippolais(Aves). Very little differences can be observed in the morphology of both species. The breeding area of these species are complementary. Roughly, one species breeds North and East of Europe (Hippolais icterina) while the other breeds South and West of Europe (Hippolais polyglotta). There exitst a narrow zone of sympatry passing through Burgundy. Since several years, it has been observed that this area of sympatry was moving in the North-East direction at a European scale. This means that progressivelyH. icterina is declining and is replaced byH. polyglotta. Some assumptions can be made in order to explain this evolution, for instance competition or predation. Series of observations concerning the diets of nestlings of both species have been realized. These observations show some differences in the diet compositions. The breeding success of the two species has been studied. Numerical simulations of a competition model taking into account the observed differences between the food types eaten by the two species are presented. These simulations do not explain the regression ofH. icterina. Then, we present numerical simulations of a predation model with one predator attacking the nestlings of both species. These simulations show that with time one of the two preys must extinct. Predation rather than competition seems to be the right explanation.     

Qualitative and quantitative resistances to leaf rust finely mapped within two nucleotide-binding site leucine-rich repeat (NBS-LRR)-rich genomic regions of chromosome 19 in poplar

? R(US) is a major dominant gene controlling quantitative resistance, inherited from Populus trichocarpa, whereas R(1) is a gene governing qualitative resistance, inherited from P. deltoides. ? Here, we report a reiterative process of concomitant fine-scale genetic and physical mapping guided by the P. trichocarpa genome sequence. The high-resolution linkage maps were developed using a P. deltoides × P. trichocarpa progeny of 1415 individuals. R(US) and R(1) were mapped in a peritelomeric region of chromosome 19. Markers closely linked to R(US) were used to screen a bacterial artificial chromosome (BAC) library constructed from the P. trichocarpa parent, heterozygous at the locus R(US) . ? Two local physical maps were developed, one encompassing the R(US) allele and the other spanning r(US) . The alignment of the two haplophysical maps showed structural differences between haplotypes. The genetic and physical maps were anchored to the genome sequence, revealing genome sequence misassembly. Finally, the R(US) locus was localized within a 0.8-cM interval, whereas R(1) was localized upstream of R(US) within a 1.1-cM interval. ? The alignment of the genetic and physical maps with the local reorder of the chromosome 19 sequence indicated that R(US) and R(1) belonged to a genomic region rich in nucleotide-binding site leucine-rich repeat (NBS-LRR) and serine threonine kinase (STK) genes.     

An integrative study of a meromictic lake ecosystem in Antarctica

In nature, the complexity and structure of microbial communities varies widely, ranging from a few species to thousands of species, and from highly structured to highly unstructured communities. Here, we describe the identity and functional capacity of microbial populations within distinct layers of a pristine, marine-derived, meromictic (stratified) lake (Ace Lake) in Antarctica. Nine million open reading frames were analyzed, representing microbial samples taken from six depths of the lake size fractionated on sequential 3.0, 0.8 and 0.1 μm filters, and including metaproteome data from matching 0.1 μm filters. We determine how the interactions of members of this highly structured and moderately complex community define the biogeochemical fluxes throughout the entire lake. Our view is that the health of this delicate ecosystem is dictated by the effects of the polar light cycle on the dominant role of green sulfur bacteria in primary production and nutrient cycling, and the influence of viruses/phage and phage resistance on the cooperation between members of the microbial community right throughout the lake. To test our assertions, and develop a framework applicable to other microbially driven ecosystems, we developed a mathematical model that describes how cooperation within a microbial system is impacted by periodic fluctuations in environmental parameters on key populations of microorganisms. Our study reveals a mutualistic structure within the microbial community throughout the lake that has arisen as the result of mechanistic interactions between the physico-chemical parameters and the selection of individual members of the community. By exhaustively describing and modelling interactions in Ace Lake, we have developed an approach that may be applicable to learning how environmental perturbations affect the microbial dynamics in more complex aquatic systems.     

Prevalence of grey matter pathology in early multiple sclerosis assessed by magnetization transfer ratio imaging

The aim of the study was to assess the prevalence, the distribution and the impact on disability of grey matter (GM) pathology in early multiple sclerosis. Eighty-eight patients with a clinically isolated syndrome with a high risk developing multiple sclerosis were included in the study. Forty-four healthy controls constituted the normative population. An optimized statistical mapping analysis was performed to compare each subject''s GM Magnetization Transfer Ratio (MTR) imaging maps with those of the whole group of controls. The statistical threshold of significant GM MTR decrease was determined as the maximum p value (p<0.05 FDR) for which no significant cluster survived when comparing each control to the whole control population. Using this threshold, 51% of patients showed GM abnormalities compared to controls. Locally, 37% of patients presented abnormalities inside the limbic cortex, 34% in the temporal cortex, 32% in the deep grey matter, 30% in the cerebellum, 30% in the frontal cortex, 26% in the occipital cortex and 19% in the parietal cortex. Stepwise regression analysis evidenced significant association (p = 0.002) between EDSS and both GM pathology (p = 0.028) and T2 white matter lesions load (p = 0.019). In the present study, we evidenced that individual analysis of GM MTR map allowed demonstrating that GM pathology is highly heterogeneous across patients at the early stage of MS and partly underlies irreversible disability.     

Disrupting Immune Regulation Incurs Transient Costs in Male Reproductive Function

Background

Immune protection against pathogenic organisms has been shown to incur costs. Previous studies investigating the cost of immunity have mostly focused on the metabolic requirements of immune maintenance and activation. In addition to these metabolic costs, the immune system can induce damage to the host if the immune response is mis-targeted or over-expressed. Given its non-specific nature, an over-expressed inflammatory response is often associated with substantial damage for the host. Here, we investigated the cost of an over-expressed inflammatory response in the reproductive function of male mice.

Methodology/Principal Findings

We experimentally blocked the receptors of an anti-inflammatory cytokine (IL-10) in male mice exposed to a mild inflammatory challenge, with each treatment having an appropriate control group. The experiment was conducted on two age classes, young (3 month old) and old (15 month old) mice, to assess any age-related difference in the cost of a disrupted immune regulation. We found that the concomitant exposure to an inflammatory insult and the blockade of IL-10 induced a reduction in testis mass, compared to the three other groups. The frequency of abnormal sperm morphology was also higher in the group of mice exposed to the inflammatory challenge but did not depend on the blockade of the IL-10.

Conclusions

Our results provide evidence that immune regulation confers protection against the risk of inflammation-induced infertility during infection. They also suggest that disruption of the effectors involved in the regulation of the inflammatory response can have serious fitness consequences even under mild inflammatory insult and benign environmental conditions.     

The Reg3α (HIP/PAP) Lectin Suppresses Extracellular Oxidative Stress in a Murine Model of Acute Liver Failure

MethodsPrimary hepatocytes stressed with the reactive oxygen species (ROS) inducers TNFα and H₂O₂ were incubated with a recombinant Reg3α protein. ALF was induced in C57BL/6J mice by an anti-CD95 antibody. Livers and primary hepatocytes were harvested for deoxycholate separation of cellular and extracellular fractions, immunostaining, immunoprecipitation and malondialdehyde assays. Fibrin deposition was studied by immunofluorescence in frozen liver explants from patients with ALF.ResultsFibrin deposition occurs during experimental and clinical acute liver injuries. Reg3α bound the resulting transient fibrin network, accumulated in the inflammatory extracellular matrix (ECM), greatly reduced extracellular ROS levels, and improved cell viability. Hepatocyte treatment with ligands of death receptors, e.g. TNFα and Fas, resulted in a twofold increase of malondialdehyde (MDA) level in the deoxycholate-insoluble fractions. Reg3α treatment maintained MDA at a level similar to control cells and thereby increased hepatocyte survival by 35%. No antioxidant effect of Reg3α was noted in the deoxycholate-soluble fractions. Preventing fibrin network formation with heparin suppressed the prosurvival effect of Reg3α.ConclusionsReg3α is an ECM-targeted ROS scavenger that binds the fibrin scaffold resulting from hepatocyte death during ALF. ECM alteration is an important pathogenic factor of ALF and a relevant target for pharmacotherapy.