Canine NAPEPLD-associated models of human myelin disorders

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people

Canine NAPEPLD-associated models of human myelin disorders

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.</p

Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation

Motion sickness is a complex condition that includes both overt signs (e.g., vomiting) and more covert symptoms (e.g., anxiety and foreboding). The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos)-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activated during this stimulus paradigm from functional correlations between Fos labeling in different nuclei. This analysis identified five principal components (neural networks) that accounted for greater than 95% of the variance in Fos labeling. Two of the components were correlated with the severity of motion sickness symptoms, and likely participated in generating the overt signs of the condition. One of these networks included neurons in locus coeruleus, medial, inferior and lateral vestibular nuclei, lateral nucleus tractus solitarius, medial parabrachial nucleus and periaqueductal gray. The second included neurons in the superior vestibular nucleus, precerebellar nuclei, periaqueductal gray, and parabrachial nuclei, with weaker associations of raphe nuclei. Three additional components (networks) were also identified that were not correlated with the severity of motion sickness symptoms. These networks likely mediated the covert aspects of motion sickness, such as affective components. The identification of five statistically independent component networks associated with the development of motion sickness provides an opportunity to consider, in network activation dimensions, the complex progression of signs and symptoms that are precipitated in provocative environments. Similar methodology can be used to parse the neural networks that mediate other complex responses to environmental stimuli. © 2014 Balaban et al

Effects of Climate and Atmospheric Nitrogen Deposition on Early to Mid-Term Stage Litter Decomposition Across Biomes

open263siWe acknowledge support by the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, funded by the German Research Foundation (FZT 118), Scientific Grant Agency VEGA(GrantNo.2/0101/18), as well as by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (Grant Agreement No. 677232)Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1-3.5% and of the more stable substrates by 3.8-10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4-2.2% and that of low-quality litter by 0.9-1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate.openKwon T.; Shibata H.; Kepfer-Rojas S.; Schmidt I.K.; Larsen K.S.; Beier C.; Berg B.; Verheyen K.; Lamarque J.-F.; Hagedorn F.; Eisenhauer N.; Djukic I.; Caliman A.; Paquette A.; Gutierrez-Giron A.; Petraglia A.; Augustaitis A.; Saillard A.; Ruiz-Fernandez A.C.; Sousa A.I.; Lillebo A.I.; Da Rocha Gripp A.; Lamprecht A.; Bohner A.; Francez A.-J.; Malyshev A.; Andric A.; Stanisci A.; Zolles A.; Avila A.; Virkkala A.-M.; Probst A.; Ouin A.; Khuroo A.A.; Verstraeten A.; Stefanski A.; Gaxiola A.; Muys B.; Gozalo B.; Ahrends B.; Yang B.; Erschbamer B.; Rodriguez Ortiz C.E.; Christiansen C.T.; Meredieu C.; Mony C.; Nock C.; Wang C.-P.; Baum C.; Rixen C.; Delire C.; Piscart C.; Andrews C.; Rebmann C.; Branquinho C.; Jan D.; Wundram D.; Vujanovic D.; Adair E.C.; Ordonez-Regil E.; Crawford E.R.; Tropina E.F.; Hornung E.; Groner E.; Lucot E.; Gacia E.; Levesque E.; Benedito E.; Davydov E.A.; Bolzan F.P.; Maestre F.T.; Maunoury-Danger F.; Kitz F.; Hofhansl F.; Hofhansl G.; De Almeida Lobo F.; Souza F.L.; Zehetner F.; Koffi F.K.; Wohlfahrt G.; Certini G.; Pinha G.D.; Gonzlez G.; Canut G.; Pauli H.; Bahamonde H.A.; Feldhaar H.; Jger H.; Serrano H.C.; Verheyden H.; Bruelheide H.; Meesenburg H.; Jungkunst H.; Jactel H.; Kurokawa H.; Yesilonis I.; Melece I.; Van Halder I.; Quiros I.G.; Fekete I.; Ostonen I.; Borovsk J.; Roales J.; Shoqeir J.H.; Jean-Christophe Lata J.; Probst J.-L.; Vijayanathan J.; Dolezal J.; Sanchez-Cabeza J.-A.; Merlet J.; Loehr J.; Von Oppen J.; Loffler J.; Benito Alonso J.L.; Cardoso-Mohedano J.-G.; Penuelas J.; Morina J.C.; Quinde J.D.; Jimnez J.J.; Alatalo J.M.; Seeber J.; Kemppinen J.; Stadler J.; Kriiska K.; Van Den Meersche K.; Fukuzawa K.; Szlavecz K.; Juhos K.; Gerhtov K.; Lajtha K.; Jennings K.; Jennings J.; Ecology P.; Hoshizaki K.; Green K.; Steinbauer K.; Pazianoto L.; Dienstbach L.; Yahdjian L.; Williams L.J.; Brigham L.; Hanna L.; Hanna H.; Rustad L.; Morillas L.; Silva Carneiro L.; Di Martino L.; Villar L.; Fernandes Tavares L.A.; Morley M.; Winkler M.; Lebouvier M.; Tomaselli M.; Schaub M.; Glushkova M.; Torres M.G.A.; De Graaff M.-A.; Pons M.-N.; Bauters M.; Mazn M.; Frenzel M.; Wagner M.; Didion M.; Hamid M.; Lopes M.; Apple M.; Weih M.; Mojses M.; Gualmini M.; Vadeboncoeur M.; Bierbaumer M.; Danger M.; Scherer-Lorenzen M.; Ruek M.; Isabellon M.; Di Musciano M.; Carbognani M.; Zhiyanski M.; Puca M.; Barna M.; Ataka M.; Luoto M.; H. Alsafaran M.; Barsoum N.; Tokuchi N.; Korboulewsky N.; Lecomte N.; Filippova N.; Hlzel N.; Ferlian O.; Romero O.; Pinto-Jr O.; Peri P.; Dan Turtureanu P.; Haase P.; Macreadie P.; Reich P.B.; Petk P.; Choler P.; Marmonier P.; Ponette Q.; Dettogni Guariento R.; Canessa R.; Kiese R.; Hewitt R.; Weigel R.; Kanka R.; Cazzolla Gatti R.; Martins R.L.; Ogaya R.; Georges R.; Gaviln R.G.; Wittlinger S.; Puijalon S.; Suzuki S.; Martin S.; Anja S.; Gogo S.; Schueler S.; Drollinger S.; Mereu S.; Wipf S.; Trevathan-Tackett S.; Stoll S.; Lfgren S.; Trogisch S.; Seitz S.; Glatzel S.; Venn S.; Dousset S.; Mori T.; Sato T.; Hishi T.; Nakaji T.; Jean-Paul T.; Camboulive T.; Spiegelberger T.; Scholten T.; Mozdzer T.J.; Kleinebecker T.; Runk T.; Ramaswiela T.; Hiura T.; Enoki T.; Ursu T.-M.; Di Cella U.M.; Hamer U.; Klaus V.; Di Cecco V.; Rego V.; Fontana V.; Piscov V.; Bretagnolle V.; Maire V.; Farjalla V.; Pascal V.; Zhou W.; Luo W.; Parker W.; Parker P.; Kominam Y.; Kotrocz Z.; Utsumi Y.Kwon T.; Shibata H.; Kepfer-Rojas S.; Schmidt I.K.; Larsen K.S.; Beier C.; Berg B.; Verheyen K.; Lamarque J.-F.; Hagedorn F.; Eisenhauer N.; Djukic I.; Caliman A.; Paquette A.; Gutierrez-Giron A.; Petraglia A.; Augustaitis A.; Saillard A.; Ruiz-Fernandez A.C.; Sousa A.I.; Lillebo A.I.; Da Rocha Gripp A.; Lamprecht A.; Bohner A.; Francez A.-J.; Malyshev A.; Andric A.; Stanisci A.; Zolles A.; Avila A.; Virkkala A.-M.; Probst A.; Ouin A.; Khuroo A.A.; Verstraeten A.; Stefanski A.; Gaxiola A.; Muys B.; Gozalo B.; Ahrends B.; Yang B.; Erschbamer B.; Rodriguez Ortiz C.E.; Christiansen C.T.; Meredieu C.; Mony C.; Nock C.; Wang C.-P.; Baum C.; Rixen C.; Delire C.; Piscart C.; Andrews C.; Rebmann C.; Branquinho C.; Jan D.; Wundram D.; Vujanovic D.; Adair E.C.; Ordonez-Regil E.; Crawford E.R.; Tropina E.F.; Hornung E.; Groner E.; Lucot E.; Gacia E.; Levesque E.; Benedito E.; Davydov E.A.; Bolzan F.P.; Maestre F.T.; Maunoury-Danger F.; Kitz F.; Hofhansl F.; Hofhansl G.; De Almeida Lobo F.; Souza F.L.; Zehetner F.; Koffi F.K.; Wohlfahrt G.; Certini G.; Pinha G.D.; Gonzlez G.; Canut G.; Pauli H.; Bahamonde H.A.; Feldhaar H.; Jger H.; Serrano H.C.; Verheyden H.; Bruelheide H.; Meesenburg H.; Jungkunst H.; Jactel H.; Kurokawa H.; Yesilonis I.; Melece I.; Van Halder I.; Quiros I.G.; Fekete I.; Ostonen I.; Borovsk J.; Roales J.; Shoqeir J.H.; Jean-Christophe Lata J.; Probst J.-L.; Vijayanathan J.; Dolezal J.; Sanchez-Cabeza J.-A.; Merlet J.; Loehr J.; Von Oppen J.; Loffler J.; Benito Alonso J.L.; Cardoso-Mohedano J.-G.; Penuelas J.; Morina J.C.; Quinde J.D.; Jimnez J.J.; Alatalo J.M.; Seeber J.; Kemppinen J.; Stadler J.; Kriiska K.; Van Den Meersche K.; Fukuzawa K.; Szlavecz K.; Juhos K.; Gerhtov K.; Lajtha K.; Jennings K.; Jennings J.; Ecology P.; Hoshizaki K.; Green K.; Steinbauer K.; Pazianoto L.; Dienstbach L.; Yahdjian L.; Williams L.J.; Brigham L.; Hanna L.; Hanna H.; Rustad L.; Morillas L.; Silva Carneiro L.; Di Martino L.; Villar L.; Fernandes Tavares L.A.; Morley M.; Winkler M.; Lebouvier M.; Tomaselli M.; Schaub M.; Glushkova M.; Torres M.G.A.; De Graaff M.-A.; Pons M.-N.; Bauters M.; Mazn M.; Frenzel M.; Wagner M.; Didion M.; Hamid M.; Lopes M.; Apple M.; Weih M.; Mojses M.; Gualmini M.; Vadeboncoeur M.; Bierbaumer M.; Danger M.; Scherer-Lorenzen M.; Ruek M.; Isabellon M.; Di Musciano M.; Carbognani M.; Zhiyanski M.; Puca M.; Barna M.; Ataka M.; Luoto M.; H. Alsafaran M.; Barsoum N.; Tokuchi N.; Korboulewsky N.; Lecomte N.; Filippova N.; Hlzel N.; Ferlian O.; Romero O.; Pinto-Jr O.; Peri P.; Dan Turtureanu P.; Haase P.; Macreadie P.; Reich P.B.; Petk P.; Choler P.; Marmonier P.; Ponette Q.; Dettogni Guariento R.; Canessa R.; Kiese R.; Hewitt R.; Weigel R.; Kanka R.; Cazzolla Gatti R.; Martins R.L.; Ogaya R.; Georges R.; Gaviln R.G.; Wittlinger S.; Puijalon S.; Suzuki S.; Martin S.; Anja S.; Gogo S.; Schueler S.; Drollinger S.; Mereu S.; Wipf S.; Trevathan-Tackett S.; Stoll S.; Lfgren S.; Trogisch S.; Seitz S.; Glatzel S.; Venn S.; Dousset S.; Mori T.; Sato T.; Hishi T.; Nakaji T.; Jean-Paul T.; Camboulive T.; Spiegelberger T.; Scholten T.; Mozdzer T.J.; Kleinebecker T.; Runk T.; Ramaswiela T.; Hiura T.; Enoki T.; Ursu T.-M.; Di Cella U.M.; Hamer U.; Klaus V.; Di Cecco V.; Rego V.; Fontana V.; Piscov V.; Bretagnolle V.; Maire V.; Farjalla V.; Pascal V.; Zhou W.; Luo W.; Parker W.; Parker P.; Kominam Y.; Kotrocz Z.; Utsumi Y

Effects of climate and atmospheric nitrogen deposition on early to mid-term stage litter decomposition across biomes

Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1-3.5% and of the more stable substrates by 3.8-10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4-2.2% and that of low-quality litter by 0.9-1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate. © Copyright © 2021 Kwon, Shibata, Kepfer-Rojas, Schmidt, Larsen, Beier, Berg, Verheyen, Lamarque, Hagedorn, Eisenhauer, Djukic and TeaComposition Network

Genome-wide analysis of TNF-alpha response in pigs challenged with porcine circovirus 2b

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine with a role in activating adaptive immunity to viral infections. By inhibiting the capacity of plasmacytoid dendritic cells to produce interferon-α and TNF-α, porcine circovirus 2 (PCV2) limits the maturation of myeloid dendritic cells and impairs their ability to recognize viral and bacterial antigens. Previously, we reported QTL for viremia and immune response in PCV2- infected pigs. In this study, we analyzed phenotypic and genetic relationships between TNFα protein levels, a potential indicator of predisposition to PCV2 co-infection, and PCV2 susceptibility. Following experimental challenge with PCV2b, TNF-α reached the peak at 21 days post-infection (dpi), at which time a difference was observed between pigs that expressed extreme variation in viremia and growth (P \u3c 0.10). A genome-wide association study (n = 297) revealed that genotypes of 56 433 SNPs explained 73.9% of the variation in TNF-α at 21 dpi. Major SNPs were identified on SSC8, SSC10 and SSC14. Haplotypes based on SNPs from a SSC8 (9 Mb) 1-Mb window were associated with variation in TNF-α (P \u3c 0.02), IgG (P = 0.05) and IgM (P \u3c 0.13) levels at 21 dpi. Potential overlap of regulatory mechanisms was supported by the correlations between genomic prediction values of TNF-α and PCV2 antibodies (21 dpi, r \u3e 0.22), viremia (14–21 dpi, P \u3e 0.29) and viral load (r = 0.31, P \u3c 0.0001). Characterization of the QTL regions uncovered genes that could influence variation in TNF-α levels as well as T- and B-cell development, which can affect disease susceptibility

Prise en charge des kystes de l’ovaire pendant la grossesse : expérience lilloise et revue de la littérature

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