In Vivo Availability of Pro-Resolving Lipid Mediators in Oxazolone Induced Dermal Inflammation in the Mouse

The activation and infiltration of polymorphonuclear neutrophils (PMN) are critical key steps in inflammation. PMN-mediated inflammation is limited by anti-inflammatory and pro-resolving mechanisms, including specialized pro-resolving lipid mediators (SPM). We examined the effects of 15-epi-LXA₄ on inflammation and the biosynthesis of pro-inflammatory mediators, such as prostaglandins, leukotriene B₄ and various hydroxyeicosatetraenoic acids and SPM, in an oxazolone (OXA)-induced hypersensitivity model for dermal inflammation. 15-epi-LXA₄ (100 μM, 5 μL subcutaneously injected) significantly (P < 0.05) reduced inflammation in skin, 24 hours after the OXA challenge, as compared to skin treated with vehicle. No significant influence on the biosynthesis of prostaglandins or leukotriene B₄ was observed, whereas the level of 15S-hydroxy-eicosatetraenoic acid was significantly (P < 0.05) lower in the skin areas treated with 15-epi-LXA₄. In spite of the use of a fully validated analytical procedure, no SPM were detected in the biological samples. To investigate the reason for the lack of analytical signal, we tried to mimic the production of SPM (lipoxins, resolvins, maresin and protectin) by injecting them subcutaneously into the skin of mice and studying the in vivo availability and distribution of the compounds. All analytes showed very little lateral distribution in skin tissue and their levels were markedly decreased (> 95%) 2 hours after injection. However, docosahexaenoic acid derivatives were biologically more stable than SPM derived from arachidonic acid or eicosapentaenoic acid.     

Sensitive capillary chromatography mass spectrometric methods for the determination of salcatonin in human biological matrices

New methods employing capillary liquid chromatography in combination with time-of-flight mass spectrometry (microLC-TOF/MS) were developed for the rapid determination of salcatonin in human urine and plasma. The present approaches utilize (13)C(6)-leucine (19)-labeled salcatonin as internal standard, small matrix volumes and simple sample preparation procedures. They allow TOF/MS to be used as a highly selective detector for providing accurate quantitation of salcatonin. Data acquisition was performed in enhanced mode optimizing the signal for the triply charged species of salcatonin and its internal standard. We demonstrate that the determination of salcatonin is straightforward and reliable and can be performed with excellent linearity (R(2)>0.999), precision and accuracy over the concentration ranges of 2.9-290 pmol/mL in human urine, and 7.3-730 pmol/mL in human plasma.     

A cognitive neurobiological account of deception: evidence from functional neuroimaging

An organism may use misinformation, knowingly (through deception) or unknowingly (as in the case of camouflage), to gain advantage in a competitive environment. From an evolutionary perspective, greater tactical deception occurs among primates closer to humans, with larger neocortices. In humans, the onset of deceptive behaviours in childhood exhibits a developmental trajectory, which may be regarded as 'normal' in the majority and deficient among a minority with certain neurodevelopmental disorders (e.g. autism). In the human adult, deception and lying exhibit features consistent with their use of 'higher' or 'executive' brain systems. Accurate detection of deception in humans may be of particular importance in forensic practice, while an understanding of its cognitive neurobiology may have implications for models of 'theory of mind' and social cognition, and societal notions of responsibility, guilt and mitigation. In recent years, functional neuroimaging techniques (especially functional magnetic resonance imaging) have been used to study deception. Though few in number, and using very different experimental protocols, studies published in the peer-reviewed literature exhibit certain consistencies. Attempted deception is associated with activation of executive brain regions (particularly prefrontal and anterior cingulate cortices), while truthful responding has not been shown to be associated with any areas of increased activation (relative to deception). Hence, truthful responding may comprise a relative 'baseline' in human cognition and communication. The subject who lies may necessarily engage 'higher' brain centres, consistent with a purpose or intention (to deceive). While the principle of executive control during deception remains plausible, its precise anatomy awaits elucidation.     

Vitamin E is essential for seed longevity and for preventing lipid peroxidation during germination

Tocopherols (vitamin E) are lipophilic antioxidants synthesized by all plants and are particularly abundant in seeds. Despite cloning of the complete suite of tocopherol biosynthetic enzymes and successful engineering of the tocopherol content and composition of Arabidopsis thaliana leaves and seeds, the functions of tocopherols in plants have remained elusive. To address this issue, we have isolated and characterized two VITAMIN E loci (VTE1 and VTE2) in Arabidopsis that when mutated result in tocopherol deficiency in all tissues. vte1 disrupts tocopherol cyclase activity and accumulates a redox-active biosynthetic intermediate, whereas vte2 disrupts homogentisate phytyl transferase activity and does not accumulate pathway intermediates. Mutations at either locus cause significantly reduced seed longevity compared with the wild type, indicating a critical role for tocopherols in maintaining viability during quiescence. However, only vte2 mutants exhibited severe seedling growth defects during germination and contained levels of lipid hydroperoxides and hydroxy fatty acids elevated up to 4- and 100-fold, respectively, relative to the wild type. These data demonstrate that a primary function of tocopherols in plants is to limit nonenzymatic lipid oxidation during seed storage, germination, and early seedling development. The vte mutant phenotypes also explain the strong selection for retention of tocopherol biosynthesis during the evolution of seed-bearing plants.     

Ancestral maximum likelihood of evolutionary trees is hard

Maximum likelihood (ML) (Neyman, 1971) is an increasingly popular optimality criterion for selecting evolutionary trees. Finding optimal ML trees appears to be a very hard computational task--in particular, algorithms and heuristics for ML take longer to run than algorithms and heuristics for maximum parsimony (MP). However, while MP has been known to be NP-complete for over 20 years, no such hardness result has been obtained so far for ML. In this work we make a first step in this direction by proving that ancestral maximum likelihood (AML) is NP-complete. The input to this problem is a set of aligned sequences of equal length and the goal is to find a tree and an assignment of ancestral sequences for all of that tree's internal vertices such that the likelihood of generating both the ancestral and contemporary sequences is maximized. Our NP-hardness proof follows that for MP given in (Day, Johnson and Sankoff, 1986) in that we use the same reduction from Vertex Cover; however, the proof of correctness for this reduction relative to AML is different and substantially more involved.