Updating genome annotation for the microbial cell factory Aspergillus niger using gene co-expression networks.

A significant challenge in our understanding of biological systems is the high number of genes with unknown function in many genomes. The fungal genus Aspergillus contains important pathogens of humans, model organisms, and microbial cell factories. Aspergillus niger is used to produce organic acids, proteins, and is a promising source of new bioactive secondary metabolites. Out of the 14,165 open reading frames predicted in the A. niger genome only 2% have been experimentally verified and over 6,000 are hypothetical. Here, we show that gene co-expression network analysis can be used to overcome this limitation. A meta-analysis of 155 transcriptomics experiments generated co-expression networks for 9,579 genes (∼65%) of the A. niger genome. By populating this dataset with over 1,200 gene functional experiments from the genus Aspergillus and performing gene ontology enrichment, we could infer biological processes for 9,263 of A. niger genes, including 2,970 hypothetical genes. Experimental validation of selected co-expression sub-networks uncovered four transcription factors involved in secondary metabolite synthesis, which were used to activate production of multiple natural products. This study constitutes a significant step towards systems-level understanding of A. niger, and the datasets can be used to fuel discoveries of model systems, fungal pathogens, and biotechnology.

[Hepatitis B vaccination and multiple sclerosis: from medical uncertainty to compensation for victims]. / Vaccination hépatite B et sclérose en plaques: de l'incertitude médicale à l'indemnisation des victimes.

Cases of multiple sclerosis appearing after a mass hepatitis B vaccination program can lead to claims for compensation. The legal jurisdiction under which such claims will be examined depends on whether the vaccination was carried out as part of a mandatory program (implying liability of the State or employers) or in application of recommendations (implying responsibility of the vaccine manufacturer). In the literature, there is no evidence demonstrating a statistically significant relationship between anti-hepatitis B vaccination and the onset or exacerbation of multiple sclerosis, questioning even the notion of compensation. The analysis of the jurisprudence shows that, in a first period, the scientific uncertainty of a link between vaccination and onset of multiple sclerosis precluded any compensation to victims. Subsequently, judicial and administrative courts ignored this scientific uncertainty, which enabled them to examine claims for compensation by adopting a presumptive reasoning based on specific criteria and different regulations depending on the legal jurisdiction. According to the French high courts (Cour de cassation and Conseil d'État) scientific causality and legal causality do not necessarily have to be consistent, such that medical uncertainty should not be an obstacle to compensation for victims.

A case of sequential anti-stress medication in a patient with major depression resistant to amine-reuptake inhibitors.

One of the predictive factors of treatment-resistant depression is the syndrome of relative insulin resistance, i.e. adipositas, mild hypertension and a family history of type-2 diabetes. Such a case is here reported with a good outcome to anti-stress medication, including ketoconazole and lithium.