Functional Relationship between Protein Disulfide Isomerase Family Members during the Oxidative Folding of Human Secretory Proteins

We systematically depleted PDI family members and show that whereas ERp72 and P5 contributed minimally to oxidative protein folding, PDI and ERp57 were the predominant catalysts. Depletion of PDI or ERp57 alone modestly delayed folding, but depletion of both led to generalized protein misfolding and degradation

Profiles of Small Non-Coding RNAs in Schistosoma japonicum during Development

Schistosomiasis, a debilitating disease, caused by agents of the genus Schistosoma afflicts more than 200 million people worldwide. Schistosomes could serve as an interesting model to explore gene regulation due to its evolutional position, complex life cycle and sexual dimorphism. We previously indicated that sncRNA profile in the parasite S. japonicum was developmentally regulated in hepatic and adult stages. In this study, we systematically investigated mircoRNA (miRNA) and endogenous siRNA (endo-siRNA) profile in this parasite in more detailed developmental stages (cercariae, lung-stage schistosomula, separated adult worms, and liver tissue-trapped eggs) using high-throughput RNA sequencing technology. We observed that the ratio of miRNAs to endo-siRNAs was dynamically changed throughout different developmental stages of the parasite. MiRNAs were expressed dominantly in cercariae, while endo-siRNAs accumulated in adult female worms and hepatic eggs. We demonstrated that miRNAs were mostly derived from intergenic regions whereas siRNAs were mostly derived from transposable elements. We also annotated miRNAs and siRNAs with stage- and gender- biased expression. Our findings would facilitate to understand the gene regulation mechanism of this parasite and discover novel targets for anti-parasite drugs

Minimal in vivo efficacy of iminosugars in a lethal Ebola virus guinea pig model

The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated. A pilot study treating infected animals three times within an 8 hour period was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected guinea pigs were treated. On histopathological examination, animals treated with NB-DNJ had reduced lesion severity in liver and spleen. However, a second study, in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not confirm drug-associated benefits. Neither was any antiviral effect of iminosugars detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a lethal EBOV-infection at the dose levels and regimens tested. However, the one surviving animal and signs of improvements in three animals of the NB-DNJ treated cohort could indicate that NB-DNJ at these levels may have a marginal beneficial effect. Future work could be focused on the development of more potent iminosugars

Effets de l'application massive de boue à très forte charge en cadmium et en nickel sur des cultures de maïs et de laitue

International audienc

Incidence d'une modification de la localisation des metaux lourds du sol sur leur disponibilite.

National audienc

Valeur agronomique des lombricomposts d'ordures ménagères

National audienc

Influence de l'addition de differentes matieres fertilisantes sur la biodisponibilite du cadmium, du manganese, du nickel contenus dans un sol sableux amende par des boues de station d'epuration

National audienceThe effect of various materials (ammonium sulphate, iron hydrous oxide, calcium carbonate, acid peat and steel shot) on the bioavailability of heavy metals (Cd. Ni, Zn, Mn) pre-existing in a sludge treated soil was investigated using a pot experiment procedure with Italian ryegrass as test-plant. Metal bioavailability (expressed as the plant metal content) was increased as a result of acidification due to ammonium sulphate addition (tables 2, 4, 5 and 9) ; calcium carbonate incorporation increased the soil pH and consequently diminished heavy metal content in the plant. The changes in bioavailability were strongly correlated with amounts of metals solubilized using 0.1 N BaCl2 or 0.1 N CaCl2 as extracting solutions (tables 6, 7 and 9). However it was not possible, using chemical extractants, to explain the drop of Cd bioavailability due to acid peat, iron hydrous oxide or steel shot addition to soil. For the first cut of the ryegrass, the fertilizing power of ammonium nitrogen probably alleviated a possible detrimental effect originating from the increase in metal bioavailability and, thus, enhanced the yield of ryegrass (table 3). In contrast, Mn deficiency induced by CaCO3 incorporation into the soil prevented an expected beneficial effect due to a lack of toxic metal bioavailability and, on the contrary, decreased dry matter production. However, it was obvious that peat acid, iron hydrous oxide or steel shot addition to soil resulted in a noticeable increase of dry matter yield at the last cuts of the ryegrass ; this beneficial effect was strongly correlated with a lack of cadmium and nickel content in ryegrass (table 10). The drop of bioavailability of such potentially hazardous metals as cadmium in soil treated with various iron components represents an interesting finding with a view to a better control of soil metal contamination.En mettant en oeuvre une culture expérimentale de Ray-grass d’Italie conduite en serre, en petits vases de végétation, on a mesuré l’influence de divers matériaux (engrais azoté ammoniacal, carbonate de calcium, tourbe blonde acide, hydroxyde de fer, grenailles d’acier) sur la biodisponibilité des métaux lourds (Cd, Ni, Mn, Zn) d’un sol provenant d’un dispositif expérimental de plein champ où ont été épandues des boues à forte charge métallique. La biodisponibilité des métaux, estimée par leur concentration dans le végétal, est augmentée par l’acidification résultant de l’addition de l’engrais azoté ammoniacal et diminuée par l’effet alcalinisant du carbonate de calcium. Ces variations de biodisponibilité sont bien corrélées avec les quantités de métal extraites du sol par CACl2 ou BACl2 en solution décinormale mais pas avec celles extraites par HCl 0,1 N, en raison de la trop grande agressivité de ce réactif. Les réactifs chimiques mis en oeuvre ne permettent cependant pas d’interpréter l’action dépressive exercée sur la biodisponibilité du cadmium par la tourbe et surtout par les différentes sources de fer expérimentées. Lors des premières coupes, l’action bénéfique de l’azote de l’engrais ammoniacal ne permet pas de mettre en évidence un effet des métaux sur la production de matière sèche du ray-grass ; cette dernière est diminuée par la carence en manganèse induite par l’apport de CaCO3. Par contre, pour la dernière coupe, il existe une bonne relation entre la décroissance des concentrations en Cd et Ni du végétal, provoquée par l’ajout de tourbe, d’hydroxyde de fer ou de grenaille d’acier, et la plus grande production de matière sèche enregistrée en présence de ces 3 amendements. L’effet dépressif important exercé par les différentes sources de fer sur la biodisponibilité de métaux toxiques comme le cadmium pourrait avoir des retombées pratiques intéressantes pour la lutte contre la pollution métalique des sols cultivés