Bioavailability and spatial distribution of fatty acids in the rat retina after dietary omega-3 supplementation

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined by LC coupled to MS/MS and MALDI coupled to MS imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that PLs as well as TGs are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain PUFAs (more than 28 carbons) following PL-EPA and TG-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of FAs in the rat retina.     

A population facing climate change: joint influences of Allee effects and environmental boundary geometry

As a result of climate change, many populations have to modify their range to follow the suitable areas—their “climate envelope”—often risking extinction. During this migration process, they may face absolute boundaries to dispersal because of external environmental factors. Consequently, not only the position, but also the shape of the climate envelope can be modified. We use a reaction-diffusion model to analyse the effects on population persistence of simultaneous changes in the position and shape of the climate envelope. When the growth term is of logistic type, we show that extinction and persistence are principally conditioned by the species mobility and the speed of climate change, but not by the shape of the climate envelope. However, with a growth term taking an Allee effect into account, we find a high sensitivity to variations in the shape of the climate envelope. In this case, the species which have a high mobility, although they could more easily follow the migration of the climate envelope, would be at risk of extinction when encountering a local narrowing of the boundary geometry. This effect can be attenuated by a progressive opening at the exit of the narrowing into the available space, even though this leads temporarily to a diminished area of the climate envelope.     

Seeing Circles and Drawing Ellipses: When Sound Biases Reproduction of Visual Motion

The perception and production of biological movements is characterized by the 1/3 power law, a relation linking the curvature and the velocity of an intended action. In particular, motions are perceived and reproduced distorted when their kinematics deviate from this biological law. Whereas most studies dealing with this perceptual-motor relation focused on visual or kinaesthetic modalities in a unimodal context, in this paper we show that auditory dynamics strikingly biases visuomotor processes. Biologically consistent or inconsistent circular visual motions were used in combination with circular or elliptical auditory motions. Auditory motions were synthesized friction sounds mimicking those produced by the friction of the pen on a paper when someone is drawing. Sounds were presented diotically and the auditory motion velocity was evoked through the friction sound timbre variations without any spatial cues. Remarkably, when subjects were asked to reproduce circular visual motion while listening to sounds that evoked elliptical kinematics without seeing their hand, they drew elliptical shapes. Moreover, distortion induced by inconsistent elliptical kinematics in both visual and auditory modalities added up linearly. These results bring to light the substantial role of auditory dynamics in the visuo-motor coupling in a multisensory context.     

Multimarker Proteomic Profiling for the Prediction of Cardiovascular Mortality in Patients with Chronic Heart Failure

Risk stratification of patients with systolic chronic heart failure (HF) is critical to better identify those who may benefit from invasive therapeutic strategies such as cardiac transplantation. Proteomics has been used to provide prognostic information in various diseases. Our aim was to investigate the potential value of plasma proteomic profiling for risk stratification in HF. A proteomic profiling using surface enhanced laser desorption ionization - time of flight - mass spectrometry was performed in a case/control discovery population of 198 patients with systolic HF (left ventricular ejection fraction <45%): 99 patients who died from cardiovascular cause within 3 years and 99 patients alive at 3 years. Proteomic scores predicting cardiovascular death were developed using 3 regression methods: support vector machine, sparse partial least square discriminant analysis, and lasso logistic regression. Forty two ion m/z peaks were differentially intense between cases and controls in the discovery population and were used to develop proteomic scores. In the validation population, score levels were higher in patients who subsequently died within 3 years. Similar areas under the curves (0.66 – 0.68) were observed for the 3 methods. After adjustment on confounders, proteomic scores remained significantly associated with cardiovascular mortality. Use of the proteomic scores allowed a significant improvement in discrimination of HF patients as determined by integrated discrimination improvement and net reclassification improvement indexes. In conclusion, proteomic analysis of plasma proteins may help to improve risk prediction in HF patients.     

p38 Regulates Pigmentation via Proteasomal Degradation of Tyrosinase

The synthesis of melanin pigments, or melanogenesis, is regulated by the balance of a variety of signal transduction pathways. Among these pathways, p38 MAPK signaling was found to be involved in stress-induced melanogenesis and to be activated by α-melanocyte-stimulating hormone (α-MSH) and ultraviolet irradiation. Previous studies have shown that α-MSH-stimulated melanogenesis can be inhibited by blocking p38 MAPK activity with SB203580, a pyridinyl imidazole compound. Consistent with this, we observed that pyridinyl imidazoles (SB203580 and SB202190) inhibited both basal and α-MSH-induced melanogenesis in B16 melanoma cells. However, SB202474, which has no ability to inhibit p38 MAPK activity and is usually used as a negative control compound in p38 MAPK studies, also suppressed melanin synthesis induction. Furthermore, the independence of the p38 kinase pathway from the repression of melanogenesis by pyridinyl imidazole compounds was also confirmed by small interfering RNA experiments. Interfering with p38 MAPK expression surprisingly stimulated melanogenesis and tyrosinase family protein expression. Although the molecular mechanism(s) by which p38 promotes the degradation of melanogenic enzymes remain to be determined, the involvement of the ubiquitin-proteasome pathway was demonstrated by co-treatment with the proteasome-specific inhibitor MG132 and the relative decrease in the ubiquitination of tyrosinase in cells transfected with p38-specific small interfering RNA.     

Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and β1 integrin receptors

Activation of Kit receptor protein-tyrosine kinase (PTK) by its ligand Stem Cell Factor (SCF) is required for the development of mast cells, and for the regulation of mast cell proliferation, migration and modulation of inflammatory mediator release. Recent studies have implicated the non-receptor PTK Fps/Fes (hereafter referred to as Fes) in signaling downstream of oncogenic Kit, however, the potential role of Fes in regulating Kit signaling is not well defined. In this study, we show that SCF induces transient tyrosine phosphorylation of wild-type Fes as well as kinase-dead Fes in bone marrow-derived mast cells (BMMCs). The latter finding implicates an upstream kinase acting on Fes, which we identified as Fyn PTK. SCF treatment of BMMCs promoted recruitment of Fes to Kit, potentially via direct interaction of the Fes SH2 domain with phosphorylated Kit. While Fes was not required for SCF-induced signaling to Akt and Erk kinases, Fes-deficient (fes^?/?) BMMCs displayed a defect in sustained p38 kinase activation, compared to control cells. SCF-treated Fes-deficient BMMCs also displayed elevated β1 integrin-mediated cell adhesion and spreading on fibronectin, compared to control cells, and a reduction in cell polarization at later times of SCF treatment. Restoring Fes expression in fes^?/? BMMCs by retroviral transduction was sufficient to rescue cell spreading and polarization defects. Interestingly, SCF-induced chemotaxis of BMMCs was also defective in Fes-deficient BMMCs, and restored in Fes-rescue BMMCs. Overall, these results implicate Fes in regulating cross-talk between Kit and β1 integrins to promote cytoskeletal reorganization and motility of mast cells.     

Diversity analyses of Aeschynomene symbionts in Tropical Africa and Central America reveal that nod-independent stem nodulation is not restricted to photosynthetic bradyrhizobia

Tropical aquatic legumes of the genus Aeschynomene are unique in that they can be stem-nodulated by photosynthetic bradyrhizobia. Moreover, a recent study demonstrated that two Aeschynomene indica symbionts lack canonical nod genes, thereby raising questions about the distribution of such atypical symbioses among rhizobial-legume interactions. Population structure and genomic diversity were compared among stem-nodulating bradyrhizobia isolated from various Aeschynomene species of Central America and Tropical Africa. Phylogenetic analyses based on the recA gene and whole-genome amplified fragment length polymorphism (AFLP) fingerprints on 110 bacterial strains highlighted that all the photosynthetic strains form a separate cluster among bradyrhizobia, with no obvious structuring according to their geographical or plant origins. Nod-independent symbiosis was present in all sampling areas and seemed to be linked to Aeschynomene host species. However, it was not strictly dependent on photosynthetic ability, as exemplified by a newly identified cluster of strains that lacked canonical nod genes and efficiently stem-nodulated A.?indica, but were not photosynthetic. Interestingly, the phenotypic properties of this new cluster of bacteria were reflected by their phylogenetical position, as being intermediate in distance between classical root-nodulatingBradyrhizobium spp. and photosynthetic ones. This result opens new prospects about stem-nodulating bradyrhizobial evolution.     

Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells

Gram‐negative bacterial peptidoglycan is specifically recognized by the host intracellular sensor NOD1, resulting in the generation of innate immune responses. Although epithelial cells are normally refractory to external stimulation with peptidoglycan, these cells have been shown to respond in a NOD1‐dependent manner to Gram‐negative pathogens that can either invade or secrete factors into host cells. In the present work, we report that Gram‐negative bacteria can deliver peptidoglycan to cytosolic NOD1 in host cells via a novel mechanism involving outer membrane vesicles (OMVs). We purified OMVs from the Gram‐negative mucosal pathogens: Helicobacter pylori, Pseudomonas aeruginosa and Neisseria gonorrhoea and demonstrated that these peptidoglycan containing OMVs upregulated NF‐κB and NOD1‐dependent responses in vitro. These OMVs entered epithelial cells through lipid rafts thereby inducing NOD1‐dependent responses in vitro. Moreover, OMVs delivered intragastrically to mice‐induced innate and adaptive immune responses via a NOD1‐dependent but TLR‐independent mechanism. Collectively, our findings identify OMVs as a generalized mechanism whereby Gram‐negative bacteria deliver peptidoglycan to cytosolic NOD1. We propose that OMVs released by bacteria in vivo may promote inflammation and pathology in infected hosts.     

Microarray proteomic analysis discriminates tumorigenic mouse ovarian surface epithelial cells of divergent aggressive potential

Cancer is an intrinsically heterogeneous disease. Tumors classified under the same etiology and histological type may display divergent growth and invasion properties, resulting in different progression rates and clinical outcomes. Here, we approached this subject in a syngeneic mouse model of ovarian cancer. Antibody microarrays were applied to obtain the proteomic profiles of IF5 and IG10, two spontaneously transformed mouse ovarian surface epithelial (MOSE) cell lines of cognate clonal origin but different tumorigenic behavior in vivo. Repeated dye-swap allowed filter out about 40% of inconsistent signals from a total of 224 arrayed antibodies. Two-class comparison tests resulted in 31 differentially expressed proteins (adjusted p < 0.05). Proteins of the ErbB and focal adhesion signaling pathways showed higher levels in IG10, the most aggressive cell. In contrast, the less aggressive IF5 cell was enriched in proteins related to nuclear chromatin organization and cell-cycle. Additionally, comparison between protein levels and mRNA levels of MOSE cells resulted in a positive rank correlation for 50-60% of protein-mRNA pairs (p < 1.7 × 10(-5)). Importantly, the protein profile of IG10 is linked to invasion and chemotherapy response in human ovarian tumors while the IF5 profile is associated to growth control. The minimal IG10 network contained the proteins Jun, Smad4, Myc, Atf2, and Pak1 as major nodes while Chek2, Mdm2 and Ccna2 were the predominant nodes of the IF5 network. The molecular basis accounting for a high aggressive potential not necessarily related to an increased tumor growth capacity is discussed on a pathway-network basis.