Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a Drosophila model of Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein (αSyn) aggregation and associated with abnormalities in lipid metabolism. The accumulation of lipids in cytoplasmic organelles called lipid droplets (LDs) was observed in cellular models of PD. To investigate the pathophysiological consequences of interactions between αSyn and proteins that regulate the homeostasis of LDs, we used a transgenic Drosophila model of PD, in which human αSyn is specifically expressed in photoreceptor neurons. We first found that overexpression of the LD-coating proteins Perilipin 1 or 2 (dPlin1/2), which limit the access of lipases to LDs, markedly increased triacylglyclerol (TG) loaded LDs in neurons. However, dPlin-induced-LDs in neurons are independent of lipid anabolic (diacylglycerol acyltransferase 1/midway, fatty acid transport protein/dFatp) and catabolic (brummer TG lipase) enzymes, indicating that alternative mechanisms regulate neuronal LD homeostasis. Interestingly, the accumulation of LDs induced by various LD proteins (dPlin1, dPlin2, CG7900 or Klarsicht^LD-BD) was synergistically amplified by the co-expression of αSyn, which localized to LDs in both Drosophila photoreceptor neurons and in human neuroblastoma cells. Finally, the accumulation of LDs increased the resistance of αSyn to proteolytic digestion, a characteristic of αSyn aggregation in human neurons. We propose that αSyn cooperates with LD proteins to inhibit lipolysis and that binding of αSyn to LDs contributes to the pathogenic misfolding and aggregation of αSyn in neurons.     

Diel Pattern of Photosynthate Partitioning in Phytoplankton Population in an Oligomesotrophic Lake

The aim of this study was to measure the short-term changes in inorganic carbon allocation into various macromolecular compounds (proteins, polysaccharides and lipids) throughout a diurnal cycle in the oligomesotrophic Lake Pavin (Massif Central of France) at the depths of 5, 15 and 30 m. Biochemical fractionation was done by consecutive differential extractions in order to separate proteins, polysaccharides, lipids and low molecular weight compounds (LMW) by virtue of their relative solubilities in different extraction solvents. Over the entire diurnal cycle inorganic carbon was preferentially incorporated into proteins (M = 30%), then into polysaccharides (M = 28%), LMWs (M = 27%) and lipids (M = 15%). However, at 5 m, diurnal variations were reflected by the high percentage of the inorganic carbon incorporated into polysaccharides during periods of high light intensity and decreased at dawn and dusk. The reverse pattern was observed for the allocation of inorganic carbon to proteins.     

Chirality of the γ-lactones produced by Sporidiobolus salmonicolor grown in two different media

Sporidiobolus salmonicolor is an aroma-producing yeast which gives a peach-like smell to the culture media. The enantiomeric ratios of the five γ-lactones produced by this yeast cultivated in two different media were determined by multidimensional gas chromatography (MDGC) on a fused silica capillary column coupled to a modified β-cyclodextrin column. These ratios remain constant during growth and are not affected by the composition of the medium. The (R)-enantiomer is highly predominant (99%) for γ-decalactone and predominant (68–88%) for γ-octalactone, γ-nonalactone, and (Z6)-γ-dodecenolactone. A ratio close to racemic was found for γ-dodecalactone. A discussion on the metabolic origin of these lactones is based on the analysis of the enantiomeric ratios obtained. With respect to consumers' preference for products considered as “natural,” microbial lactone production may represent a valuable alternative to fruit flavors. The enantiomeric lactone ratios produced by Sporidiobolus salmonicolor are compared with those reported from some fruits. Chirality 9:667–671, 1997. © 1997 Wiley-Liss, Inc.     

Helicobacter pylori Physiology Predicted from Genomic Comparison of Two Strains

Helicobacter pylori is a gram-negative bacteria which colonizes the gastric mucosa of humans and is implicated in a wide range of gastroduodenal diseases. This paper reviews the physiology of this bacterium as predicted from the sequenced genomes of two unrelated strains and reconciles these predictions with the literature. In general, the predicted capabilities are in good agreement with reported experimental observations. H. pylori is limited in carbohydrate utilization and will use amino acids, for which it has transporter systems, as sources of carbon. Energy can be generated by fermentation, and the bacterium possesses components necessary for both aerobic and anaerobic respiration. Sulfur metabolism is limited, whereas nitrogen metabolism is extensive. There is active uptake of DNA via transformation and ample restriction-modification activities. The cell contains numerous outer membrane proteins, some of which are porins or involved in iron uptake. Some of these outer membrane proteins and the lipopolysaccharide may be regulated by a slipped-strand repair mechanism which probably results in phase variation and plays a role in colonization. In contrast to a commonly held belief that H. pylori is a very diverse species, few differences were predicted in the physiology of these two unrelated strains, indicating that host and environmental factors probably play a significant role in the outocme of H. pylori-related disease.     

In vivo induction of CTL responses by recombinant adenylate cyclase of Bordetella pertussis carrying multiple copies of a viral CD8+ T-cell epitope

Bordetella pertussis adenylate cyclase toxin (ACT) is one of the few known protein toxins penetrating directly into the cytosol of target cells across their cytoplasmic membrane without the need for endocytosis. This capacity of ACT was recently exploited for in vivo delivery of single viral CD8(+) T-epitopes into MHC class I-presenting cells and induction of protective antiviral cytotoxic T-cell (CTL) responses. Here, we have explored the potential of the cell-invasive adenylate cyclase domain of the toxin to deliver larger antigens by evaluating the epitope-specific CTL responses induced by constructs bearing one to four copies of the CD8(+) T-epitope from the nucleoprotein of the lymphocytic choriomeningitis virus. The increase in the number of copies of the epitope was accompanied by a moderate decrease of the specific cell invasiveness of the ACT protein and did not lead to further enhancement of the level of induced epitope-specific CTL cells in mice, as compared to ACT with a single copy of the epitope. These results demonstrate the capacity of ACT to deliver larger heterologous antigens comprising several epitopes for antigenic presentation in vivo.     

Exposure,hazard, and vulnerability all contribute to Schistosoma haematobium re-infection in northern Senegal

BackgroundInfectious disease risk is driven by three interrelated components: exposure, hazard, and vulnerability. For schistosomiasis, exposure occurs through contact with water, which is often tied to daily activities. Water contact, however, does not imply risk unless the environmental hazard of snails and parasites is also present in the water. By increasing reliance on hazardous activities and environments, socio-economic vulnerability can hinder reductions in exposure to a hazard. We aimed to quantify the contributions of exposure, hazard, and vulnerability to the presence and intensity of Schistosoma haematobium re-infection.Methodology/Principal findingsIn 13 villages along the Senegal River, we collected parasitological data from 821 school-aged children, survey data from 411 households where those children resided, and ecological data from all 24 village water access sites. We fit mixed-effects logistic and negative binomial regressions with indices of exposure, hazard, and vulnerability as explanatory variables of Schistosoma haematobium presence and intensity, respectively, controlling for demographic variables. Using multi-model inference to calculate the relative importance of each component of risk, we found that hazard (Ʃw_{i =} 0.95) was the most important component of S. haematobium presence, followed by vulnerability (Ʃw_i = 0.91). Exposure (Ʃw_i = 1.00) was the most important component of S. haematobium intensity, followed by hazard (Ʃw_i = 0.77). Model averaging quantified associations between each infection outcome and indices of exposure, hazard, and vulnerability, revealing a positive association between hazard and infection presence (OR = 1.49, 95% CI 1.12, 1.97), and a positive association between exposure and infection intensity (RR 2.59–3.86, depending on the category; all 95% CIs above 1)Conclusions/SignificanceOur findings underscore the linkages between social (exposure and vulnerability) and environmental (hazard) processes in the acquisition and accumulation of S. haematobium infection. This approach highlights the importance of implementing both social and environmental interventions to complement mass drug administration.     

A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis

Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylate-bridged di-iron domain, At1g24340 is homologous to FAD-dependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone''s ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of horizontal gene transfer between a green alga and a bacterium.     

Preen oil composition of Pied Flycatchers is similar between partners but differs between sexes and breeding stages

Preen oil, the secretion of the uropygial gland, may be an important source of body odour in birds. By characterizing the chemical composition of preen oil, we can describe the olfactory phenotypes of birds and investigate whether odours could have a function in sexual signalling or other chemical communication. Here we analysed the preen oil of a wild passerine, the European Pied Flycatcher Ficedula hypoleuca, to find out whether it holds socially relevant information. We sampled both the female and male of breeding pairs during nestling rearing to test for sex differences and within-pair similarity. We additionally sampled the females during incubation to test for changes across breeding stages and for individual repeatability of chemical profiles. Pair mates had similar chemical profiles in comparison with other breeding adults. Furthermore, we found evidence for sex differences and for changes across breeding stages. Notably, the preen oil of females was more diverse and more volatile than that of males, and the preen oil secreted by females during incubation was more volatile than that secreted during nestling rearing. However, we found no evidence for individual repeatability of chemical profiles across breeding stages in females. Our results point towards a function of preen oil in sexual signalling, although other functions should not be excluded. Our study is a first step towards understanding the role of odours in the social life of an important avian model species used in the study of mate choice and sexual selection.     

Autumnal nitrogen nutrition affects the C and N storage and architecture of young peach trees

Nitrogen fertilisation is a regular practice in orchards. Its effect on tree development, N and C acquisition and allocation were evaluated simultaneously, while coupling on the same trees in situ measurements of N uptake and shoot development and destructive determinations of organ composition in N and Total Non structural Carbohydrates (TNC). An hydroponic set-up was designed that could grow young peach trees at constant NO₃ concentration while measuring N uptake. Forty-eight trees were raised outdoors under excessive N supply. Between October 2 and December 7, half of them were then N-limited to reduce N uptake by 75%. Organ N concentrations remained stable in the controls but were halved in N-limited trees. Growth (390 vs. 353 g DW tree⁻¹) was less affected by the treatment than N uptake (10.6 vs. 2.7 g N tree⁻¹). Growth was affected only in terms of axillary bud development, which was restricted to the median and upper crown parts. The number of buds which transformed into elongating axes (44 vs. 84 tree⁻¹) was halved, thus reducing leaf area by one-third (10,464 vs. 15,568 cm²). Tree TNC content was not impacted. The difference in C acquisition likely balanced the C costs of N uptake. In N-limited trees, more TNC was stored as starch (73 vs. 56%), and the allocation patterns of TNC and N were altered in favour of the roots. Our results provide deeper insights into the tree integrated response to autumnal N fertilisation, focusing on an alteration of the balance between storage and growth.     

Rapid restoration of a species-rich ecosystem assessed from soil and vegetation indicators: The case of calcareous grasslands restored from forest stands

Calcareous grasslands have long been recognized as biodiversity hotspots in Europe. However, in recent decades these ecosystems have seen rapid decline. In Belgium, more than 100 ha of calcareous grasslands have been restored from oak coppices and pine forests since the 1990s. The aim of the present study was to provide a quantitative assessment of the success of these restoration efforts, using two sets of indicators: one related to soil conditions, the other related to vascular plant communities. Soil conditions were evaluated by comparing soil samples from pre-restoration forest stands, restored grasslands (3-age classes: 2–4 years; 5–8 years, and 10–15 years) and reference grasslands. The analysis revealed no significant differences in soil N, P, and K contents between pre-restoration forests and restored and reference grasslands. We observed a decrease in the mineralization rate indicators in both pre-restoration forests and recent grassland restorations, which was resorbed in older restorations. Floristic surveys revealed that plant species composition of older restorations was most like reference grasslands. However, some differences in species composition persisted after 15 years. Moreover, a few rare species did not colonize restored grasslands despite a close seed source. Non-recolonization by a set of species expected on calcareous grasslands may be due to dispersal limitation and higher cover by native invasive grasses in restored parcels. These results were discussed in term of implications for management.