A Point Mutation in Suppressor of Cytokine Signalling 2 (Socs2) Increases the Susceptibility to Inflammation of the Mammary Gland while Associated with Higher Body Weight and Size and Higher Milk Production in a Sheep Model

Mastitis is an infectious disease mainly caused by bacteria invading the mammary gland. Genetic control of susceptibility to mastitis has been widely evidenced in dairy ruminants, but the genetic basis and underlying mechanisms are still largely unknown. We describe the discovery, fine mapping and functional characterization of a genetic variant associated with elevated milk leukocytes count, or SCC, as a proxy for mastitis. After implementing genome-wide association studies, we identified a major QTL associated with SCC on ovine chromosome 3. Fine mapping of the region, using full sequencing with 12X coverage in three animals, provided one strong candidate SNP that mapped to the coding sequence of a highly conserved gene, suppressor of cytokine signalling 2 (Socs2). The frequency of the SNP associated with increased SCC was 21.7% and the Socs2 genotype explained 12% of the variance of the trait. The point mutation induces the p.R96C substitution in the SH2 functional domain of SOCS2 i.e. the binding site of the protein to various ligands, as well-established for the growth hormone receptor GHR. Using surface plasmon resonance we showed that the p.R96C point mutation completely abrogates SOCS2 binding affinity for the phosphopeptide of GHR. Additionally, the size, weight and milk production in p.R96C homozygote sheep, were significantly increased by 24%, 18%, and 4.4%, respectively, when compared to wild type sheep, supporting the view that the point mutation causes a loss of SOCS2 functional activity. Altogether these results provide strong evidence for a causal mutation controlling SCC in sheep and highlight the major role of SOCS2 as a tradeoff between the host’s inflammatory response to mammary infections, and body growth and milk production, which are all mediated by the JAK/STAT signaling pathway.     

1H, 13C and 15N resonance assignments of the PDZ of microtubule-associated serine/threonine kinase 205 (MAST205) in complex with the C-terminal motif from the rabies virus glycoprotein

Most of microbes hijack the cellular machinery to their advantage by interacting with specific target of the host cell. Glycoprotein of rabies virus is a key factor controlling the homeostasis of infected neuronal cells and proteins belonging to the human microtubule associated serine threonine kinase family have been identified as potential cellular partners. As a first step towards its structural study, we have assigned the backbone and side chain nuclei resonances of the PDZ domain (PSD-95, Discs Large, ZO-1) of MAST205 in complex with the C-terminal residues of the glycoprotein of rabies virus. The BMRB accession code is 155972.     

Osmotic adaptation in Brevibacterium linens: differential effect of proline and glycine betaine on cytoplasmic osmolyte pool

In the coryneform Brevibacterium linens, ectoine constitutes the major intracellular solute accumulated under elevated medium osmolarity. Here we report that exogenously supplied proline, choline, glycine betaine, and even ectoine, protected bacterial cells against deleterious effects of a hyperosmotic constraint (i.e. 1.5 M NaCl). In all cases, a significant improvement of growth was observed; in parallel, intracellular osmolyte pools composed mainly of glutamate and ectoine substantially increased, either with added glycine betaine (under limiting supply) or with proline. However, these two osmoprotectants behaved differently: glycine betaine acted as a genuine osmoprotectant, whereas proline was accumulated only transiently and participated actively in the biosynthesis of glutamate, ectoine, and trehalose. The strategy developed by B. linens cells allows the proposal of a novel role for proline in the osmoprotection process through its conversion to the apparently preferred endogenous osmolyte ectoine.     

Two-dimensional electrophoresis study of Lactobacillus delbrueckii subsp. bulgaricus thermotolerance

The response of Lactobacillus delbrueckii subsp. bulgaricus cells to heat stress was studied by use of a chemically defined medium. Two-dimensional electrophoresis (2-DE) analysis was used to correlate the kinetics of heat shock protein (HSP) induction with cell recovery from heat injury. We demonstrated that enhanced viability, observed after 10 min at 65 degrees C, resulted from the overexpression of HSP and from mechanisms not linked to protein synthesis. In order to analyze the thermoadaptation mechanisms involved, thermoresistant variants were selected. These variants showed enhanced constitutive tolerance toward heat shock. However, contrary to the wild-type strain, these variants were poorly protected after osmotic or heat pretreatments. This result suggests that above a certain threshold, cells reach a maximum level of protection that cannot be easily exceeded. A comparison of protein patterns showed that the variants were able to induce more rapidly their adaptive mechanisms than the original strain. In particular, the variants were able to express constitutively more HSP, leading to the higher level of thermoprotection observed. This is the first report of the study by 2-DE of the heat stress response in L. delbrueckii subsp. bulgaricus.     

Emotional Meaning in Context in Relation to Hypomanic Personality Traits: An ERP Study

The ability to integrate contextual information is important for the comprehension of emotional and social situations. While some studies have shown that emotional processes and social cognition are impaired in people with hypomanic personality trait, no results have been reported concerning the neurophysiological processes mediating the processing of emotional information during the integration of contextual social information in this population. We therefore chose to conduct an ERP study dealing with the integration of emotional information in a population with hypomanic personality trait. Healthy participants were evaluated using the Hypomanic Personality Scale (HPS), and ERPs were recorded during a linguistic task in which participants silently read sentence pairs describing short social situations. The first sentence implicitly conveyed the positive or negative emotional state of a character. The second sentence was emotionally congruent or incongruent with the first sentence. We analyzed the difference in the modulation of two components (N400 and LPC) in response to the emotional word present at the end of the “target” sentences as a function of the HPS score and the emotional valence of the context. Our results showed a possible modulation of the N400 component in response to both positive and negative context among the participants who scored high on the Mood Volatility subscale of the Hypomanic Personality Scale. These results seem to indicate that the participants with hypomanic personality traits exhibited specificities in the integration of emotions at the level of the early-mobilized neurocognitive processes (N400). Participants with hypomanic personality traits found it difficult to integrate negative emotional contexts, while simultaneously exhibiting an enhanced integration of positive emotional contexts.     

Competition and facilitation among fungal plant parasites affect their life-history traits

Multi-infections may result in either competitive exclusion or coexistence on the same host of pathogen genotypes belonging to the same or different species. Epidemiological consequences of multiple infections, particularly how the development and transmission of a pathogen can be modified by the presence of another pathogen, are well documented. However, understanding how life history strategies of each pathogen modulate co-infection outcomes remains quite elusive. To analyze how co-infection drives changes in life history traits and affects co-existence in epidemic pathogens, we infected detached pea stipules with two fungal species, Peyronellaea pinodes and Phoma medicaginis var. pinodella (considering two strains per species), part of the ascochyta blight complex but presenting different life history strategies. All pairwise combinations (including self-pairs) between two strains of each species were tested. Strains were inoculated simultaneously, but apart from one another on the stipule. For each strain, four life history traits were measured: incubation period, necrosis area six days after inoculation, latent period and offspring production. Results show that, in co-infection, when resources are highly allocated to lesion development, the time between inoculation and the appearance of reproduction structures (latent period) and offspring production decreased, and vice-versa relative to single infections. The direction and/or magnitude of these responses to co-infection depend on the co-infecting strains. Moreover, these changes were always higher in self-pairs than in mixed co-infections. These results suggest facilitation between co-infecting strains, resulting in the selection of an intermediate level of virulence (here measured as the lesion development) at the expense of pathogen offspring production. This strategy allows the development and reproduction of each co-infecting strain when sharing limited resources. However, the direction and strength of these life history traits variations in co-infection depend on the life history strategy of the co-infecting strains, with a clear difference between ‘opportunists', ‘scavengers' and ‘pioneer colonisers'.     

Carbon dynamics, development and stress responses in Arabidopsis: involvement of the APL4 subunit of ADP-glucose pyrophosphorylase (starch synthesis)

An Arabidopsis thaliana T-DNA insertional mutant was identified and characterized for enhanced tolerance to the singlet-oxygen-generating herbicide atrazine in comparison to wild-type. This enhanced atrazine tolerance mutant was shown to be affected in the promoter structure and in the regulation of expression of the APL4 isoform of ADP-glucose pyrophosphorylase, a key enzyme of the starch biosynthesis pathway, thus resulting in decrease of APL4 mRNA levels. The impact of this regulatory mutation was confirmed by the analysis of an independent T-DNA insertional mutant also affected in the promoter of the APL4 gene. The resulting tissue-specific modifications of carbon partitioning in plantlets and the effects on plantlet growth and stress tolerance point out to specific and non-redundant roles of APL4 in root carbon dynamics, shoot-root relationships and sink regulations of photosynthesis. Given the effects of exogenous sugar treatments and of endogenous sugar levels on atrazine tolerance in wild-type Arabidopsis plantlets, atrazine tolerance of this apl4 mutant is discussed in terms of perception of carbon status and of investment of sugar allocation in xenobiotic and oxidative stress responses.