Cross-Platform Comparison of Untargeted and Targeted Lipidomics Approaches on Aging Mouse Plasma.

Lipidomics - the global assessment of lipids - can be performed using a variety of mass spectrometry (MS)-based approaches. However, choosing the optimal approach in terms of lipid coverage, robustness and throughput can be a challenging task. Here, we compare a novel targeted quantitative lipidomics platform known as the Lipidyzer to a conventional untargeted liquid chromatography (LC)-MS approach. We find that both platforms are efficient in profiling more than 300 lipids across 11 lipid classes in mouse plasma with precision and accuracy below 20% for most lipids. While the untargeted and targeted platforms detect similar numbers of lipids, the former identifies a broader range of lipid classes and can unambiguously identify all three fatty acids in triacylglycerols (TAG). Quantitative measurements from both approaches exhibit a median correlation coefficient (r) of 0.99 using a dilution series of deuterated internal standards and 0.71 using endogenous plasma lipids in the context of aging. Application of both platforms to plasma from aging mouse reveals similar changes in total lipid levels across all major lipid classes and in specific lipid species. Interestingly, TAG is the lipid class that exhibits the most changes with age, suggesting that TAG metabolism is particularly sensitive to the aging process in mice. Collectively, our data show that the Lipidyzer platform provides comprehensive profiling of the most prevalent lipids in plasma in a simple and automated manner

Les limites à la liberté d'expression dans l'entreprise

Cette étude constitue une synthèse des différentes limites à la liberté d'expression des parties à une relation de travail. Elle expose les dispositions législatives et réglementaires pertinentes, fédérales et québécoises, qu'elles soient de portée générale ou, au contraire, spécifiques à une relation de travail. Elle examine aussi les dispositions des contrats individuels et collectifs de travail afin d'y déceler les limites qu'elles imposent à l'expression des salariés, de l'employeur, du syndicat ou des représentants de ces derniers. Ces limites tiennent tantôt au contenu du message véhiculé par les parties, tantôt à des circonstances de temps et de lieu.This study is a synthesis of the various limits to freedom of speech of parties involved in a labour relationship. It deals with relevant federal and Quebec statutory provisions, whether of general or specific import to the labour relationship. The study also examines the provisions found in individual and collective labour agreements in order to discover the limits they impose on the free speech of wage-earners, employers, unions or union representatives. These limits may depend on the message conveyed by the parties or on circumstances relating to time and place

Loss of CaMKI function disrupts salt aversive learning in C. elegans

The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior is likely advantageous to avoid areas without food. While some genes have been implicated in this salt aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt aversive learning behavior in C. elegans. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of cmk-1 leads to an altered pattern of sensory- evoked calcium responses that may underlie salt aversive learning. Our study implicates the conserved CaMKI/CMK-1 as an essential cell-autonomous regulator for behavioral plasticity to environmental salt in C. elegans

Prenatal Maternal Stress Predicts Childhood Asthma in Girls: Project Ice Storm

Little is known about how prenatal maternal stress (PNMS) influences risks of asthma in humans. In this small study, we sought to determine whether disaster-related PNMS would predict asthma risk in children. In June 1998, we assessed severity of objective hardship and subjective distress in women pregnant during the January 1998 Quebec Ice Storm. Lifetime asthma symptoms, diagnoses, and corticosteroid utilization were assessed when the children were 12 years old (N = 68). No effects of objective hardship or timing of the exposure were found. However, we found that, in girls only, higher levels of prenatal maternal subjective distress predicted greater lifetime risk of wheezing (OR = 1.11; 90% CI = 1.01–1.23), doctor-diagnosed asthma (OR = 1.09; 90% CI = 1.00–1.19), and lifetime utilization of corticosteroids (OR = 1.12; 90% CI = 1.01–1.25). Other perinatal and current maternal life events were also associated with asthma outcomes. Findings suggest that stress during pregnancy opens a window for fetal programming of immune functioning. A sex-based approach may be useful to examine how prenatal and postnatal environments combine to program the immune system. This small study needs to be replicated with a larger, more representative sample

Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons

The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation

Listeners Exploit Syntactic Structure On-Line to Restrict Their Lexical Search to a Subclass of Verbs

Many experiments have shown that listeners actively build expectations about up-coming words, rather than simply waiting for information to accumulate. The online construction of a syntactic structure is one of the cues that listeners may use to construct strong expectations about the possible words they will be exposed to. For example, speakers of verb-final languages use pre-verbal arguments to predict on-line the kind of arguments that are likely to occur next (e.g., Kamide, 2008, for a review). Although in SVO languages information about a verb's arguments typically follows the verb, some languages use pre-verbal object pronouns, potentially allowing listeners to build on-line expectations about the nature of the upcoming verb. For instance, if a pre-verbal direct object pronoun is heard, then the following verb has to be able to enter a transitive structure, thus excluding intransitive verbs. To test this, we used French, in which object pronouns have to appear pre-verbally, to investigate whether listeners use this cue to predict the occurrence of a transitive verb. In a word detection task, we measured the number of false alarms to sentences that contained a transitive verb whose first syllable was homophonous to the target monosyllabic verb (e.g., target “dort” /dɔʁ/ to sleep and false alarm verb “dorlote” /dɔʁlɔt/ to cuddle). The crucial comparison involved two sentence types, one without a pre-verbal object clitic, for which an intransitive verb was temporarily a plausible option (e.g., “Il dorlote” / He cuddles) and the other with a pre-verbal object clitic, that made the appearance of an intransitive verb impossible (“Il le dorlote” / He cuddles it). Results showed a lower rate of false alarms for sentences with a pre-verbal object pronoun (3%) compared to locally ambiguous sentences (about 20%). Participants rapidly incorporate information about a verb's argument structure to constrain lexical access to verbs that match the expected subcategorization frame