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101.
Prion permissive pathways: extracellular matrix genes control susceptibility to prion infection 下载免费PDF全文
There are wide variations in the susceptibility of humans, animals, and cultured cell lines to infection by prions. In this issue of The EMBO Journal, Marbiah et al ( 2014 ) identified a gene regulatory network that regulates the susceptibility of cultured cells to prion infection. Surprisingly, a number of these genes impact the structure of the extracellular matrix. These results have important implications for understanding mechanisms of prion infection and also suggest new therapeutic targets. 相似文献
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Eric Lombaert Thomas Guillemaud Jonathan Lundgren Robert Koch Benoît Facon Audrey Grez Antoon Loomans Thibaut Malausa Oldrich Nedved Emma Rhule Arnstein Staverlokk Tove Steenberg Arnaud Estoup 《Molecular ecology》2014,23(24):5979-5997
Inferences about introduction histories of invasive species remain challenging because of the stochastic demographic processes involved. Approximate Bayesian computation (ABC) can help to overcome these problems, but such method requires a prior understanding of population structure over the study area, necessitating the use of alternative methods and an intense sampling design. In this study, we made inferences about the worldwide invasion history of the ladybird Harmonia axyridis by various population genetics statistical methods, using a large set of sampling sites distributed over most of the species’ native and invaded areas. We evaluated the complementarity of the statistical methods and the consequences of using different sets of site samples for ABC inferences. We found that the H. axyridis invasion has involved two bridgehead invasive populations in North America, which have served as the source populations for at least six independent introductions into other continents. We also identified several situations of genetic admixture between differentiated sources. Our results highlight the importance of coupling ABC methods with more traditional statistical approaches. We found that the choice of site samples could affect the conclusions of ABC analyses comparing possible scenarios. Approaches involving independent ABC analyses on several sample sets constitute a sensible solution, complementary to standard quality controls based on the analysis of pseudo‐observed data sets, to minimize erroneous conclusions. This study provides biologists without expertise in this area with detailed methodological and conceptual guidelines for making inferences about invasion routes when dealing with a large number of sampling sites and complex population genetic structures. 相似文献
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Vitor C. Pacheco da Silva Aline Bertin Aurélie Blin Jean-Fran?ois Germain Daniel Bernardi Guylène Rignol Marcos Botton Thibaut Malausa 《PloS one》2014,9(7)
Mealybugs (Hemiptera: Pseudococcidae) are pests constraining the international trade of Brazilian table grapes. They damage grapes by transmitting viruses and toxins, causing defoliation, chlorosis, and vigor losses and favoring the development of sooty mold. Difficulties in mealybug identification remain an obstacle to the adequate management of these pests. In this study, our primary aim was to identify the principal mealybug species infesting the major table grape-producing regions in Brazil, by morphological and molecular characterization. Our secondary aim was to develop a rapid identification kit based on species-specific Polymerase Chain Reactions, to facilitate the routine identification of the most common pest species. We surveyed 40 sites infested with mealybugs and identified 17 species: Dysmicoccus brevipes (Cockerell), Dysmicoccus sylvarum Williams and Granara de Willink, Dysmicoccus texensis (Tinsley), Ferrisia cristinae Kaydan and Gullan, Ferrisia meridionalis Williams, Ferrisia terani Williams and Granara de Willink, Phenacoccus baccharidis Williams, Phenacoccus parvus Morrison, Phenacoccus solenopsis Tinsley, Planococcus citri (Risso), Pseudococcus viburni (Signoret), Pseudococcus cryptus Hempel, four taxa closely related each of to Pseudococcus viburni, Pseudococcus sociabilis Hambleton, Pseudococcus maritimus (Ehrhorn) and Pseudococcus meridionalis Prado, and one specimen from the genus Pseudococcus Westwood. The PCR method developed effectively identified five mealybug species of economic interest on grape in Brazil: D. brevipes, Pl. citri, Ps. viburni, Ph. solenopsis and Planococcus ficus (Signoret). Nevertheless, it is not possible to assure that this procedure is reliable for taxa that have not been sampled already and might be very closely related to the target species. 相似文献
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Jodie L. Rummer Christine S. Couturier Jonathan A. W. Stecyk Naomi M. Gardiner Jeff P. Kinch Göran E. Nilsson Philip L. Munday 《Global Change Biology》2014,20(4):1055-1066
Equatorial populations of marine species are predicted to be most impacted by global warming because they could be adapted to a narrow range of temperatures in their local environment. We investigated the thermal range at which aerobic metabolic performance is optimum in equatorial populations of coral reef fish in northern Papua New Guinea. Four species of damselfishes and two species of cardinal fishes were held for 14 days at 29, 31, 33, and 34 °C, which incorporated their existing thermal range (29–31 °C) as well as projected increases in ocean surface temperatures of up to 3 °C by the end of this century. Resting and maximum oxygen consumption rates were measured for each species at each temperature and used to calculate the thermal reaction norm of aerobic scope. Our results indicate that one of the six species, Chromis atripectoralis, is already living above its thermal optimum of 29 °C. The other five species appeared to be living close to their thermal optima (ca. 31 °C). Aerobic scope was significantly reduced in all species, and approached zero for two species at 3 °C above current‐day temperatures. One species was unable to survive even short‐term exposure to 34 °C. Our results indicate that low‐latitude reef fish populations are living close to their thermal optima and may be more sensitive to ocean warming than higher‐latitude populations. Even relatively small temperature increases (2–3 °C) could result in population declines and potentially redistribution of equatorial species to higher latitudes if adaptation cannot keep pace. 相似文献
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Cécile Batandier Laurent Poulet Isabelle Hininger Karine Couturier Eric Fontaine Anne‐Marie Roussel Frédéric Canini 《Journal of neurochemistry》2014,131(3):314-322
Since emotional stress elicits brain activation, mitochondria should be a key component of stressed brain response. However, few studies have focused on mitochondria functioning in these conditions. In this work, we aimed to determine the effects of an acute restraint stress on rat brain mitochondrial functions, with a focus on permeability transition pore (PTP) functioning. Rats were divided into two groups, submitted or not to an acute 30‐min restraint stress (Stress, S‐group, vs. Control, C‐group). Brain was removed immediately after stress. Mitochondrial respiration and enzymatic activities (complex I, complex II, hexokinase) were measured. Changes in PTP opening were assessed by the Ca2+ retention capacity. Cell signaling pathways relevant to the coupling between mitochondria and cell function (adenosine monophosphate‐activated protein kinase, phosphatidylinositol 3‐kinase, glycogen synthase kinase 3 beta, MAPK, and cGMP/NO) were measured. The effect of glucocorticoids was also assessed in vitro. Stress delayed (43%) the opening of PTP and resulted in a mild inhibition of complex I respiratory chain. This inhibition was associated with significant stress‐induced changes in adenosine monophosphate‐activated protein kinase signaling pathway without changes in brain cGMP level. In contrast, glucocorticoids did not modify PTP opening. These data suggest a rapid adaptive mechanism of brain mitochondria in stressed conditions, with a special focus on PTP regulation.
108.
Sebastian Miethe Christine Rasetti-Escargueil Yvonne Liu Siham Chahboun Thibaut Pelat Arnaud Avril Andrè Frenzel Thomas Schirrmann Philippe Thullier Dorothea Sesardic Michael Hust 《MABS-AUSTIN》2014,6(2):446-459
Botulinum toxins (BoNTs) are among the most toxic substances on earth, with serotype A toxin being the most toxic substance known. They are responsible for human botulism, a disease characterized by flaccid muscle paralysis that occurs naturally through food poisoning or the colonization of the gastrointestinal tract by BoNT-producing clostridia. BoNT has been classified as a category A agent by the Centers for Disease Control, and it is one of six agents with the highest potential risk of use as bioweapons. Human or human-like neutralizing antibodies are thus required for the development of anti-botulinum toxin drugs to deal with this possibility. In this study, Macaca fascicularis was hyperimmunized with a recombinant light chain of BoNT/A. An immune phage display library was constructed and, after multistep panning, several scFv with nanomolar affinities that inhibited the endopeptidase activity of BoNT/A1 in vitro as scFv-Fc, with a molar ratio (ab binding site:toxin) of up to 1:1, were isolated. The neutralization of BoNT/A-induced paralysis by the SEM120-IID5, SEM120-IIIC1 and SEM120-IIIC4 antibodies was demonstrated in mouse phrenic nerve-hemidiaphragm preparations with the holotoxin. The neutralization observed is the strongest ever measured in the phrenic nerve-hemidiaphragm assay for BoNT/A1 for a monoclonal antibody. Several scFv-Fc inhibiting the endopeptidase activity of botulinum neurotoxin A were isolated. For SEM120-IID5, SEM120-IIIC1, and SEM120-IIIC4, inhibitory effects in vitro and protection against the toxin ex vivo were observed. The human-like nature of these antibodies makes them promising lead candidates for further development of immunotherapeutics for this disease. 相似文献
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Electrophysiology of a chick neuronal nicotinic acetylcholine receptor expressed in Xenopus oocytes after cDNA injection 总被引:12,自引:0,他引:12
Brain nicotinic acetylcholine receptors (nAChRs) are made up of protein subunits that differ from those constituting muscle nAChRs. To characterize the physiological properties of one class of avian brain nicotinic receptor, we injected the nuclei of Xenopus oocytes with full-length cDNAs for the ligand binding (alpha 4) and structural (n alpha) subunits. Injected oocytes had large ACh-induced currents in the microampere range that were insensitive to alpha-bungarotoxin, as expected for neuronal nAChRs. We found that these brain nAChRs incorporate at least two alpha 4 subunits and that their functional properties differ from muscle nAChRs in at least two respects: the elementary conductance is considerably smaller (20 pS), and channels in outside out patches stop functioning within a few minutes. 相似文献
110.
Goel Asvin Vidal Thibaut Kok Adrianus Leendert 《Flexible Services and Manufacturing Journal》2021,33(4):879-913
Flexible Services and Manufacturing Journal - The last decades have seen a tremendous amount of research being devoted to effectively managing vehicle fleets and minimizing empty mileage. However,... 相似文献