UTILLdb, a Pisum sativum in silico forward and reverse genetics tool

UTILLdb is a database of phenotypic and sequence information on mutant genes from a reference Pisum sativum EMS-mutant population

Distinct Changes in cAMP and Extracellular Signal-Regulated Protein Kinase Signalling in L-DOPA-Induced Dyskinesia

Background: In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP- protein kinase A and of the Rasextracellular signal-regulated kinase (ERK) signalling pathways. However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia. Methodology/Results: We here studied, in the gold-standard non-human primate model of Parkinson’s disease, the changes in PKA-dependent phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced preferentially after acute L-DOPA administration and decreased during the course of chronic treatment. Conclusion: Dysregulation of cAMP signalling is maintained during the course of chronic L-DOPA administration, while abnormal ERK signalling peaks during the initial phase of L-DOPA treatment and decreases following prolonged exposure

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain

AbstractOmega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.Infrastructure de Recherche Translationnelle pour les Biothérapies en NeurosciencesProgram Initiative d’Excellenc

Advancing justice for children: innovations to strengthen accountability for violations and crimes affecting children in conflict

One in six children globally live in areas affected by armed conflict, facing a range of threats and challenges as a result. They are consistently killed and injured, subject to sexual violence, denied access to life-saving support, recruited and used by armed groups, forced to flee their homes and prevented from fulfilling their fundamental human rights. Too often, perpetrators of heinous acts involving children are not held to account. This research paper deals with how those responsible for crimes and serious violations against children in conflict can be brought to justice. It looks at why, to date, such few examples exist of accountability for crimes against children. Specifically, it explores how governments, legal institutions, civil society and UN agencies can set a new path – one which prioritises and upholds children’s rights. This study finds there are a few reasons why those committing crimes against children seldom face consequences for their actions. Perhaps the most important, is that governments are simply not making crimes against children a priority. As a result, neither is the international justice system. Without political and financial backing from governments, there are big gaps in expertise, tools, and structures which would deliver justice for children. Importantly, the research focuses on lessons and recommendations for action. This includes how sexual and gender-based violence became a central theme of the international justice system, as well as how the international community can put its weight behind innovation and the examples of best practice which already exist

Resolvin D1 and E1 promote resolution of inflammation in microglial cells in vitro

Sustained inflammation in the brain together with microglia activation can lead to neuronal damage. Hence limiting brain inflammation and activation of microglia is a real therapeutic strategy for inflammatory disease. Resolvin D1 (RvD1) and resolvin E1 (RvE1) derived from n-3 long chain polyunsaturated fatty acids are promising therapeutic compounds since they actively turn off the systemic inflammatory response. We thus evaluated the anti-inflammatory activities of RvD1 and RvE1 in microglia cells in vitro. BV2 cells were pre-incubated with RvD1 or RvE1 before lipopolysaccharide (LPS) treatment. RvD1 and RvE1 both decreased LPS-induced proinflammatory cytokines (TNF-α, IL-6 and IL-1β) gene expression, suggesting their proresolutive activity in microglia. However, the mechanisms involved are distinct as RvE1 regulates NFκB signaling pathway and RvD1 regulates miRNAs expression. Overall, our findings support that pro-resolving lipids are involved in the resolution of brain inflammation and can be considered as promising therapeutic agents for brain inflammation

New fluorescent bis-dithienylethene (DTE)-based bipyridines as reverse interrupters: single vs. double photochromism

International audienceThe synthesis and characterization of a series of fluorescent bis-dithienylethene (DTE)-based bipyridines, where the donor (D) and acceptor (A) groups are located on the same thiophene ring of the DTE unit, and their zinc(II) and rhenium(I) complexes are reported. Their photochromic properties have been investigated by UV-visible and H-1 NMR spectroscopy. These studies reveal that in non-polar solvents it is possible to modulate the photoreactivity, single vs. double ring-closure, by changing the nature of the donor group. The solvent effect, as well as the influence of the organometallic moieties on the photochromic behavior of these molecules, is also discussed. Finally, upon photoconversion to the photostationary state (PSS), a quenching of fluorescence is observed for the bipyridine ligands, due to disruption of the conjugation upon ring-closing