Nonenzymatic lipid mediators, neuroprostanes, exert the antiarrhythmic properties of docosahexaenoic acid

postprin

Oxidative stress and mitochondrial responses to stress exposure suggest that king penguins are naturally equipped to resist stress

Exposure to unpredictable environmental stressors could influence animal health and fitness by inducing oxidative stress, potentially through downstream effects of glucocorticoid stress hormones (e.g. corticosterone) on mitochondrial function. Yet, it remains unclear whether species that have evolved in stochastic and challenging environments may present adaptations to alleviate the effects of stress exposure on oxidative stress. We tested this hypothesis in wild king penguins by investigating mitochondrial and oxidative stress responses to acute restraint-stress, and their relationships with baseline (potentially mirroring exposure to chronic stress) and stress-induced increase in corticosterone levels. Acute restraint-stress did not significantly influence mitochondrial function. However, acute restraint-stress led to a significant increase in endogenous antioxidant defences, while oxidative damage levels were mostly not affected or even decreased. High baseline corticosterone levels were associated with an up-regulation of the glutathione antioxidant system and a decrease in mitochondrial efficiency. Both processes might contribute to prevent oxidative damage, potentially explaining the negative relationship observed between baseline corticosterone and plasma oxidative damage to proteins. While stress exposure can represent an oxidative challenge for animals, protective mechanisms like up-regulating antioxidant defences and decreasing mitochondrial efficiency seem to occur in king penguins, allowing them to cope with their stochastic and challenging environment

Mosaic DNA imports with interspersions of recipient sequence after natural transformation of Helicobacter pylori

Helicobacter pylori colonizes the gastric mucosa of half of the human population, causing gastritis, ulcers, and cancer. H. pylori is naturally competent for transformation by exogenous DNA, and recombination during mixed infections of one stomach with multiple H. pylori strains generates extensive allelic diversity. We developed an in vitro transformation protocol to study genomic imports after natural transformation of H. pylori. The mean length of imported fragments was dependent on the combination of donor and recipient strain and varied between 1294 bp and 3853 bp. In about 10% of recombinant clones, the imported fragments of donor DNA were interrupted by short interspersed sequences of the recipient (ISR) with a mean length of 82 bp. 18 candidate genes were inactivated in order to identify genes involved in the control of import length and generation of ISR. Inactivation of the antimutator glycosylase MutY increased the length of imports, but did not have a significant effect on ISR frequency. Overexpression of mutY strongly increased the frequency of ISR, indicating that MutY, while not indispensable for ISR formation, is part of at least one ISR-generating pathway. The formation of ISR in H. pylori increases allelic diversity, and contributes to the uniquely low linkage disequilibrium characteristic of this pathogen

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Genetic Loci Involved in Antibody Response to Mycobacterium avium ssp. paratuberculosis in Cattle

Background: Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic enteritis in a wide range of animal species. In cattle, MAP causes a chronic disease called Johne's disease, or paratuberculosis, that is not treatable and the efficacy of vaccine control is controversial. The clinical phase of the disease is characterised by diarrhoea, weight loss, drop in milk production and eventually death. Susceptibility to MAP infection is heritable with heritability estimates ranging from 0.06 to 0.10. There have been several studies over the last few years that have identified genetic loci putatively associated with MAP susceptibility, however, with the availability of genome-wide high density SNP maker panels it is now possible to carry out association studies that have higher precision. Methodology/Principal Findings: The objective of the current study was to localize genes having an impact on Johne's disease susceptibility using the latest bovine genome information and a high density SNP panel (Illumina BovineSNP50 BeadChip) to perform a case/control, genome-wide association analysis. Samples from MAP case and negative controls were selected from field samples collected in 2007 and 2008 in the province of Lombardy, Italy. Cases were defined as animals serologically positive for MAP by ELISA. In total 966 samples were genotyped: 483 MAP ELISA positive and 483 ELISA negative. Samples were selected randomly among those collected from 119 farms which had at least one positive animal. Conclusion/Significance: The analysis of the genotype data identified several chromosomal regions associated with disease status: a region on chromosome 12 with high significance (P<5 710-6), while regions on chromosome 9, 11, and 12 had moderate significance (P<5 710-5). These results provide evidence for genetic loci involved in the humoral response to MAP. Knowledge of genetic variations related to susceptibility will facilitate the incorporation of this information into breeding programmes for the improvement of health status

A Novel PAN/Apple Domain-Containing Protein from Toxoplasma gondii: Characterization and Receptor Identification

Toxoplasma gondii is an intracellular parasite that invades nucleated cells, causing toxoplasmosis in humans and animals worldwide. The extremely wide range of hosts susceptible to T. gondii is thought to be the result of interactions between T. gondii ligands and receptors on its target cells. In this study, a host cell-binding protein from T. gondii was characterized, and one of its receptors was identified. P104 (GenBank Access. No. CAJ20677) is 991 amino acids in length, containing a putative 26 amino acid signal peptide and 10 PAN/apple domains, and shows low homology to other identified PAN/apple domain-containing molecules. A 104-kDa host cell-binding protein was detected in the T. gondii lysate. Immunofluorescence assays detected P104 at the apical end of extracellular T. gondii. An Fc-fusion protein of the P104 N-terminus, which contains two PAN/apple domains, showed strong affinity for the mammalian and insect cells evaluated. This binding was not related to protein-protein or protein-lipid interactions, but to a protein-glycosaminoglycan (GAG) interaction. Chondroitin sulfate (CS), a kind of GAG, was shown to be involved in adhesion of the Fc-P104 N-terminus fusion protein to host cells. These results suggest that P104, expressed at the apical end of the extracellular parasite, may function as a ligand in the attachment of T. gondii to CS or other receptors on the host cell, facilitating invasion by the parasite

The geometry of the magnetic field in the central molecular zone measured by PILOT

We present the first far infrared (FIR) dust emission polarization map covering the full extent of Milky Way’s central molecular zone (CMZ). The data, obtained with the PILOT balloon-borne experiment, covers the Galactic center region − 2° < ℓ < 2°, − 4° < b < 3° at a wavelength of 240 μm and an angular resolution of 2.2′. From our measured dust polarization angles, we infer a magnetic field orientation projected onto the plane of the sky (POS) that is remarkably ordered over the full extent of the CMZ, with an average tilt angle of ≃22° clockwise with respect to the Galactic plane. Our results confirm previous claims that the field traced by dust polarized emission is oriented nearly orthogonally to the field traced by GHz radio synchrotron emission in the Galactic center region. The observed field structure is globally compatible with the latest Planck polarization data at 353 and 217 GHz. Upon subtraction of the extended emission in our data, the mean field orientation that we obtain shows good agreement with the mean field orientation measured at higher angular resolution by the JCMT within the 20 and 50 km s−1 molecular clouds. We find no evidence that the magnetic field orientation is related to the 100 pc twisted ring structure within the CMZ. The low polarization fraction in the Galactic center region measured with Planck at 353 GHz combined with a highly ordered projected field orientation is unusual. This feature actually extends to the whole inner Galactic plane. We propose that it could be caused by the increased number of turbulent cells for the long lines of sight towards the inner Galactic plane or to dust properties specific to the inner regions of the Galaxy. Assuming equipartition between magnetic pressure and ram pressure, we obtain magnetic field strength estimates of the order of 1 mG for several CMZ molecular clouds

Phenomenology and physical origin of shear-localization and shear-banding in complex fluids

We review and compare the phenomenological aspects and physical origin of shear-localization and shear-banding in various material types, namely emulsions, suspensions, colloids, granular materials and micellar systems. It appears that shear-banding, which must be distinguished from the simple effect of coexisting static-flowing regions in yield stress fluids, occurs in the form of a progressive evolution of the local viscosity towards two significantly different values in two adjoining regions of the fluids in which the stress takes slightly different values. This suggests that from a global point of view shear-banding in these systems has a common physical origin: two physical phenomena (for example, in colloids, destructuration due to flow and restructuration due to aging) are in competition and, depending on the flow conditions, one of them becomes dominant and makes the system evolve in a specific direction.Comment: The original publication is available at http://www.springerlink.co

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Catherine Cornu and colleagues performed a meta-analysis of randomised controlled trials of metformin efficacy on cardiovascular morbidity or mortality in patients with type 2 diabetes and showed that although metformin is considered the gold standard, its benefit/risk ratio remains uncertain