Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease

In Huntington disease (HD), there is increasing evidence for a link between mutant huntingtin expression, mitochondrial dysfunction, energetic deficits and neurodegeneration but the precise nature, causes and order of these events remain to be determined. In this work, our objective was to evaluate mitochondrial respiratory function in intact, non-permeabilized, neurons derived from a transgenic rat model for HD compared to their wild type littermates by measuring oxygen consumption rates and extracellular acidification rates. Although HD striatal neurons had similar respiratory capacity as those from their wild-type littermates when they were incubated in rich medium containing a supra-physiological glucose concentration (25 mM), pyruvate and amino acids, respiratory defects emerged when cells were incubated in media containing only a physiological cerebral level of glucose (2.5 mM). According to the concept that glucose is not the sole substrate used by the brain for neuronal energy production, we provide evidence that primary neurons can use lactate as well as pyruvate to fuel the mitochondrial respiratory chain. In contrast to glucose, we found no major deficits in HD striatal neurons’ capacity to use pyruvate as a respiratory substrate compared to wild type littermates. Additionally, we used extracellular acidification rates to confirm a reduction in anaerobic glycolysis in the same cells. Interestingly, the metabolic disturbances observed in striatal neurons were not seen in primary cortical neurons, a brain region affected in later stages of HD. In conclusion, our results argue for a dysfunction in glycolysis, which might precede any defects in the respiratory chain itself, and these are early events in the onset of disease.     

Rapid and Extensive Alteration of Phosphorus Speciation during Oxic Storage of Wet Sediment Samples

The chemical forms of phosphorus (P) in sediments are routinely measured in studies of P in modern and ancient marine environments. However, samples for such analyses are often exposed to atmospheric oxygen during storage and handling. Recent work suggests that long-term exposure of pyrite-bearing sediments can lead to a decline in apatite P and an increase in ferric Fe-bound P. Here, we report on alterations in P speciation in reducing modern Baltic Sea sediments that we deliberately exposed to atmospheric oxygen for a period of either one week or one year. During oxidation of the sediment, extensive changes occurred in all measured P reservoirs. Exchangeable P all but disappeared during the first week of exposure, likely reflecting adsorption of porewater PO₄ by Fe(III) (oxyhydr)oxides (i.e. ferric Fe-bound P formation). Detrital and organic P were also rapidly affected: decreases in both reservoirs were already observed after the first week of exposure to atmospheric oxygen. This was likely because of acidic dissolution of detrital apatite and oxidation of organic matter, respectively. These processes produced dissolved PO₄ that was then scavenged by Fe(III) (oxyhydr)oxides. Interestingly, P in authigenic calcium phosphates (i.e. apatite: authigenic Ca-P) remained unaffected after the first week of exposure, which we attributed to the shielding effect of microfossils in which authigenic Ca-P occurs in Baltic Sea sediments. This effect was transient; a marked decrease in the authigenic Ca-P pool was observed in the sediments after one year of exposure to oxygen. In summary, we show that handling and storage of wet sediments under oxic conditions can lead to rapid and extensive alteration of the original sediment P speciation.     

MyD88 Deficiency Markedly Worsens Tissue Inflammation and Bacterial Clearance in Mice Infected with Treponema pallidum,the Agent of Syphilis

Research on syphilis, a sexually transmitted infection caused by the non-cultivatable spirochete Treponema pallidum, has been hampered by the lack of an inbred animal model. We hypothesized that Toll-like receptor (TLR)-dependent responses are essential for clearance of T. pallidum and, consequently, compared infection in wild-type (WT) mice and animals lacking MyD88, the adaptor molecule required for signaling by most TLRs. MyD88-deficient mice had significantly higher pathogen burdens and more extensive inflammation than control animals. Whereas tissue infiltrates in WT mice consisted of mixed mononuclear and plasma cells, infiltrates in MyD88-deficient animals were predominantly neutrophilic. Although both WT and MyD88-deficient mice produced antibodies that promoted uptake of treponemes by WT macrophages, MyD88-deficient macrophages were deficient in opsonophagocytosis of treponemes. Our results demonstrate that TLR-mediated responses are major contributors to the resistance of mice to syphilitic disease and that MyD88 signaling and FcR-mediated opsonophagocytosis are linked to the macrophage-mediated clearance of treponemes.     

A Model for Sclerotinia sclerotiorum Infection and Disease Development in Lettuce,Based on the Effects of Temperature,Relative Humidity and Ascospore Density

The plant pathogen Sclerotinia sclerotiorum can cause serious losses on lettuce crops worldwide and as for most other susceptible crops, control relies on the application of fungicides, which target airborne ascospores. However, the efficacy of this approach depends on accurate timing of these sprays, which could be improved by an understanding of the environmental conditions that are conducive to infection. A mathematical model for S. sclerotiorum infection and disease development on lettuce is presented here for the first time, based on quantifying the effects of temperature, relative humidity (RH) and ascospore density in multiple controlled environment experiments. It was observed that disease can develop on lettuce plants inoculated with dry ascospores in the absence of apparent leaf wetness (required for spore germination). To explain this, the model conceptualises an infection court area containing microsites (in leaf axils and close to the stem base) where conditions are conducive to infection, the size of which is modified by ambient RH. The model indicated that minimum, maximum and optimum temperatures for ascospore germination were 0.0, 29.9 and 21.7°C respectively and that maximum rates of disease development occurred at spore densities >87 spores cm⁻². Disease development was much more rapid at 80–100% RH at 20°C, compared to 50–70% RH and resulted in a greater proportion of lettuce plants infected. Disease development was also more rapid at 15–27°C compared to 5–10°C (85% RH). The model was validated by a further series of independent controlled environment experiments where both RH and temperature were varied and generally simulated the pattern of disease development well. The implications of the results in terms of Sclerotinia disease forecasting are discussed.     

LTR-Retrotransposons in R. exoculata and Other Crustaceans: The Outstanding Success of GalEa-Like Copia Elements

Transposable elements are major constituents of eukaryote genomes and have a great impact on genome structure and stability. They can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution among several genomes is an essential condition to study their dynamics and to better understand their role in species evolution. LTR-retrotransposons have been reported in many diverse eukaryote species, describing a ubiquitous distribution. Given their abundance, diversity and their extended ranges in C-values, environment and life styles, crustaceans are a great taxon to investigate the genomic component of adaptation and its possible relationships with TEs. However, crustaceans have been greatly underrepresented in transposable element studies. Using both degenerate PCR and in silico approaches, we have identified 35 Copia and 46 Gypsy families in 15 and 18 crustacean species, respectively. In particular, we characterized several full-length elements from the shrimp Rimicaris exoculata that is listed as a model organism from hydrothermal vents. Phylogenic analyses show that Copia and Gypsy retrotransposons likely present two opposite dynamics within crustaceans. The Gypsy elements appear relatively frequent and diverse whereas Copia are much more homogeneous, as 29 of them belong to the single GalEa clade, and species- or lineage-dependent. Our results also support the hypothesis of the Copia retrotransposon scarcity in metazoans compared to Gypsy elements. In such a context, the GalEa-like elements present an outstanding wide distribution among eukaryotes, from fishes to red algae, and can be even highly predominant within a large taxon, such as Malacostraca. Their distribution among crustaceans suggests a dynamics that follows a “domino days spreading” branching process in which successive amplifications may interact positively.     

Mitochondrial morphodynamics alteration induced by influenza virus infection as a new antiviral strategy

Influenza virus infections are major public health threats due to their high rates of morbidity and mortality. Upon influenza virus entry, host cells experience modifications of endomembranes, including those used for virus trafficking and replication. Here we report that influenza virus infection modifies mitochondrial morphodynamics by promoting mitochondria elongation and altering endoplasmic reticulum-mitochondria tethering in host cells. Expression of the viral RNA recapitulates these modifications inside cells. Virus induced mitochondria hyper-elongation was promoted by fission associated protein DRP1 relocalization to the cytosol, enhancing a pro-fusion status. We show that altering mitochondrial hyper-fusion with Mito-C, a novel pro-fission compound, not only restores mitochondrial morphodynamics and endoplasmic reticulum-mitochondria contact sites but also dramatically reduces influenza replication. Finally, we demonstrate that the observed Mito-C antiviral property is directly connected with the innate immunity signaling RIG-I complex at mitochondria. Our data highlight the importance of a functional interchange between mitochondrial morphodynamics and innate immunity machineries in the context of influenza viral infection.     

Comparative proteomics of Geobacter sulfurreducens PCAT in response to acetate,formate and/or hydrogen as electron donor

Geobacter sulfurreducens is a model bacterium to study the degradation of organic compounds coupled to the reduction of Fe(III). The response of G. sulfurreducens to the electron donors acetate, formate, hydrogen and a mixture of all three with Fe(III) citrate as electron acceptor was studied using comparative physiological and proteomic approaches. Variations in the supplied electron donors resulted in differential abundance of proteins involved in the citric acid cycle (CAC), gluconeogenesis, electron transport, and hydrogenases and formate dehydrogenase. Our results provided new insights into the electron donor metabolism of G. sulfurreducens. Remarkably, formate was the preferred electron donor compared to acetate, hydrogen, or acetate plus hydrogen. When hydrogen was the electron donor, formate was formed, which was associated with a high abundance of formate dehydrogenase. Notably, abundant proteins of two CO₂ fixation pathways (acetyl-CoA pathway and the reversed oxidative CAC) corroborated chemolithoautotrophic growth of G. sulfurreducens with formate or hydrogen and CO₂, and provided novel insight into chemolithoautotrophic growth of G. sulfurreducens.