High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France

BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management

Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans

Lifespan extension induced by germline ablation in C. elegans is regulated by the nuclear hormone receptor NHR-80 in a process that requires the production of oleic acid by activation of the lipid desaturase FAT-6/SCD1

Étude des mécanismes moléculaires liant la lignée germinale au vieillissement chez Caenorhabditis elegans

Un nouveau gène de la longévité ouvre de nouvelles pistes pour vieillir mieux. L'accroissement de la longévité induit par la suppression des tissus reproducteurs a été observé chez la drosophile et chez le ver. Chez ce dernier, l'opération lui donne 60% de vie en plus et lui permet un vieillissement harmonieux et en bonne santé. Les mécanismes moléculaires qui induisent cette réponse font l'objet d'intenses recherches. Certains gènes étaient déjà connus pour être associés à l'accroissement de la longévité des vers sans lignée germinale, et nous avons démontré l'existence d'une nouvelle voie impliquant le récepteur nucléaire NHR-80. Les nématodes dépourvus de lignée germinale et dont nhr-80 est muté ne voient pas leur longévité augmenter. En outre, la surexpression du gène allonge davantage leur durée de vie: elle est 150% plus longue que celle de leurs congénères sauvages. Cela démontre l'importance de ce récepteur nucléaire dont l'activation par une hormone encore inconnue enclenche l'expression ou la mise sous silence de centaines d'autres gènes. Notamment, nous avons montré que l'une des cibles de NHR-80, l'enzyme FAT-6 qui transforme l'acide stéarique en acide oléique est fondamentale, puisque les vers dépourvus de lignée germinale ne présentent plus aucun gain en longévité en l'absence de FAT-6. À terme, nous espérons pouvoir récapituler les effets de l'ablation de la lignée germinale chez un organisme fertile, c'est à dire, d'induire les réarrangements métaboliques qui ont lieu suite à cette opération afin d'en tirer les effets positifs sur la santé, sans affecter la reproduction.Discovery of a key longevity gene opens new perspectives for healthy aging.Increased longevity induced by reproductive tissues removal (germline ablation) is observed in the fly Drosophila melanogaster and in the worm Caenorhabditis elegans. In the latter, the operation increases lifespan by 60%, and enables the nematode to age harmoniously and in good health. The molecular mechanisms that induce this response are subject of intensive research. Our study reveals the existence of a new powerful longevity gene, nhr-80, which mediates this longevity effect. We have shown that inactivation of nhr-80 prevents lifespan increase. Furthermore, nhr-80 overexpression lengthens the nematodes' lifespan by 150%! nhr-80 encodes a nuclear receptor, which activation by a still unknown hormone controls the expression of hundreds of other genes. We showed that one of the critical NHR-80 targets, the enzyme FAT-6, which transforms stearic acid into oleic acid, is necessary to prolong lifespan since a mutation of the fat-6 gene suppresses the effects of germline ablation on longevity. The next step will be to determine how an increase in the level of oleic acid induces an adaptive response resulting in increased longevity. This research may lead to the exciting possibility of recapitulating the benefits of germline ablation in fertile animals; in other words, to activate the longevity effects normally triggered by germline ablation in order to fight, in one go, a host of diseases associated with aging, without affecting reproduction

Étude des mécanismes moléculaires liant la lignée germinale au vieillissement chez Caenorhabditis elegans

Un nouveau gène de la longévité ouvre de nouvelles pistes pour vieillir mieux. L'accroissement de la longévité induit par la suppression des tissus reproducteurs a été observé chez la drosophile et chez le ver. Chez ce dernier, l'opération lui donne 60% de vie en plus et lui permet un vieillissement harmonieux et en bonne santé. Les mécanismes moléculaires qui induisent cette réponse font l'objet d'intenses recherches. Certains gènes étaient déjà connus pour être associés à l'accroissement de la longévité des vers sans lignée germinale, et nous avons démontré l'existence d'une nouvelle voie impliquant le récepteur nucléaire NHR-80. Les nématodes dépourvus de lignée germinale et dont nhr-80 est muté ne voient pas leur longévité augmenter. En outre, la surexpression du gène allonge davantage leur durée de vie: elle est 150% plus longue que celle de leurs congénères sauvages. Cela démontre l'importance de ce récepteur nucléaire dont l'activation par une hormone encore inconnue enclenche l'expression ou la mise sous silence de centaines d'autres gènes. Notamment, nous avons montré que l'une des cibles de NHR-80, l'enzyme FAT-6 qui transforme l'acide stéarique en acide oléique est fondamentale, puisque les vers dépourvus de lignée germinale ne présentent plus aucun gain en longévité en l'absence de FAT-6. À terme, nous espérons pouvoir récapituler les effets de l'ablation de la lignée germinale chez un organisme fertile, c'est à dire, d'induire les réarrangements métaboliques qui ont lieu suite à cette opération afin d'en tirer les effets positifs sur la santé, sans affecter la reproduction.Discovery of a key longevity gene opens new perspectives for healthy aging.Increased longevity induced by reproductive tissues removal (germline ablation) is observed in the fly Drosophila melanogaster and in the worm Caenorhabditis elegans. In the latter, the operation increases lifespan by 60%, and enables the nematode to age harmoniously and in good health. The molecular mechanisms that induce this response are subject of intensive research. Our study reveals the existence of a new powerful longevity gene, nhr-80, which mediates this longevity effect. We have shown that inactivation of nhr-80 prevents lifespan increase. Furthermore, nhr-80 overexpression lengthens the nematodes' lifespan by 150%! nhr-80 encodes a nuclear receptor, which activation by a still unknown hormone controls the expression of hundreds of other genes. We showed that one of the critical NHR-80 targets, the enzyme FAT-6, which transforms stearic acid into oleic acid, is necessary to prolong lifespan since a mutation of the fat-6 gene suppresses the effects of germline ablation on longevity. The next step will be to determine how an increase in the level of oleic acid induces an adaptive response resulting in increased longevity. This research may lead to the exciting possibility of recapitulating the benefits of germline ablation in fertile animals; in other words, to activate the longevity effects normally triggered by germline ablation in order to fight, in one go, a host of diseases associated with aging, without affecting reproduction.LYON-ENS Sciences (693872304) / SudocSudocFranceF

Carbonylated proteins are eliminated during reproduction in C. elegans

Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699Oxidatively damaged proteins accumulate with age in many species (Stadtman (1992) Science257, 1220-1224). This means that damage must be reset at the time of reproduction. To visualize this resetting in the roundworm Caenorhabditis elegans, a novel immunofluorescence technique that allows the detection of carbonylated proteins in situ was developed. The application of this technique revealed that carbonylated proteins are eliminated during C. elegans reproduction. This purging occurs abruptly within the germline at the time of oocyte maturation. Surprisingly, the germline was markedly more oxidized than the surrounding somatic tissues. Because distinct mechanisms have been proposed to explain damage elimination in yeast and mice (Aguilaniu et al. (2003) Science299, 1751-1753; Hernebring et al. (2006) Proc Natl Acad Sci USA103, 7700-7705), possible common mechanisms between worms and one of these systems were tested. The results show that, unlike in yeast (Aguilaniu et al. (2003) Science299, 1751-1753; Erjavec et al. (2008) Proc Natl Acad Sci USA105, 18764-18769), the elimination of carbonylated proteins in worms does not require the presence of the longevity-ensuring gene, SIR-2.1. However, similar to findings in mice (Hernebring et al. (2006) Proc Natl Acad Sci USA103, 7700-7705), proteasome activity in the germline is required for the resetting of carbonylated proteins during reproduction in C. elegans. Thus, oxidatively damaged proteins are eliminated during reproduction in worms through the proteasome. This finding suggests that the resetting of damaged proteins during reproduction is conserved, therefore validating the use of C. elegans as a model to study the molecular basis of damage elimination

Molecular Self-Assembly of Jointed Molecules on a Metallic Substrate: From Single Molecule to Monolayer

International audienceBecause of its promising contribution to the bottom-up approach for nanofabrication of complex molecular architectures, self-organization is widely studied nowadays. Numerous studies have tackled supramolecular chirality or low-dimensional molecular nanostructures using in most cases small and rigid molecules adsorbed on metallic substrates. In this situation, self-assembled structures can be understood in relative simple terms considering molecule-molecule versus molecule-substrate interactions. In contrast, the case of large and three-dimensional molecules which can adopt different adsorption conformations is more complex. Here, we investigate the self-assembly of V-Landers molecules (C108H104) on Cu(100) by STM at room temperature under ultrahigh vacuum. This molecule is constituted of a central poly-aromatic board linked by sigma bonds to four 3,5-di-tert-butylphenyl legs

Coelomocytes regulate starvation-induced fat catabolism and lifespan extension through the lipase LIPL-5 in Caenorhabditis elegans

International audienceDietary restriction is known to extend the lifespan and reduce fat stores in most species tested to date, but the molecular mechanisms linking these events remain unclear. Here, we found that bacterial deprivation of Caenorhabditis elegans leads to lifespan extension with concomitant mobilization of fat stores. We find that LIPL-5 expression is induced by starvation and that the LIPL-5 lipase is present in coelomocyte cells and regulates fat catabolism and longevity during the bacterial deprivation response. Either LIPL-5 or coelomocyte deficiency prevents the rapid mobilization of intestinal triacylglycerol and enhanced lifespan extension in response to bacterial deprivation, whereas the combination of both defects has no additional or synergistic effect. Thus, the capacity to mobilize fat via LIPL-5 is directly linked to an animal's capacity to withstand long-term nutrient deprivation. Our data establish a role for LIPL-5 and coelomocytes in regulating fat consumption and lifespan extension upon DR

Generation of metal composition gradients by means of bipolar electrodeposition

International audienc

Split-wrmScarlet and split-sfGFP: tools for faster, easier fluorescent labeling of endogenous proteins in Caenorhabditis elegans

<p>Zenodo hosts the archival version of this document; for convenient viewing, please visit <a href="http://andrewgyork.github.io/split_wrmscarlet" target="_blank" rel="noopener">andrewgyork.github.io/split_wrmscarlet </a>or <a href="http://marimar128.github.io/split_wrmscarlet" target="_blank" rel="noopener">marimar128.github.io/split_wrmscarlet</a>.</p> <h4><a href="https://andrewgyork.github.io/split_wrmscarlet/#Abstract" target="_self">Abstract</a></h4> <p>We create and share a new red fluorophore, along with a set of strains, reagents and protocols, to make it faster and easier to label endogenous <em>C. elegans</em> proteins with fluorescent tags. CRISPR-mediated fluorescent labeling of <em>C. elegans</em> proteins is an invaluable tool, but it is much more difficult to insert fluorophore-size DNA segments than it is to make small gene edits. In principle, high-affinity asymmetrically-split fluorescent proteins solve this problem in <em>C. elegans</em>: the small fragment can quickly and easily be fused to almost any protein of interest and can be detected wherever the large fragment is expressed and complemented. However, there is currently only one available strain stably expressing the large fragment of a split fluorescent protein, restricting this solution to a single tissue (the germline) in the highly autofluorescent green channel. No available <em>C. elegans</em> lines express unbound large fragments of split red fluorescent proteins, and even state-of-the-art split red fluorescent proteins are dim compared to the canonical split-sfGFP protein. In this study, we engineer a bright, high-affinity new split red fluorophore, <a href="https://www.addgene.org/138966/">split-wrmScarlet</a>. We generate transgenic <em>C. elegans</em> lines to allow easy <a href="https://cgc.umn.edu/strain/CF4582">single-color</a> labeling in <a href="https://cgc.umn.edu/strain/CF4610">muscle</a> or <a href="https://cgc.umn.edu/strain/DUP237">germline</a> and <a href="https://cgc.umn.edu/strain/CF4588">dual-color</a> labeling in somatic cells. We also describe 'glonads', a novel expression strategy for the germline, where traditional expression strategies struggle. We validate these strains by targeting split-wrmScarlet to several genes whose products label distinct organelles, and we provide a <a href="https://doi.org/10.17504/protocols.io.bamkic4w">protocol</a> for easy, cloning-free CRISPR/Cas9 editing. As the collection of split-FP strains for labeling in different tissues or organelles expands, we will post updates at <a href="https://doi.org/10.5281/zenodo.3993663">doi.org/10.5281/zenodo.3993663</a></p&gt