Is quorum sensing involved in lovastatin production in the filamentous fungus Aspergillus terreus?

A novel role for butyrolactone I as a quorum sensing molecule in the filamentous fungus Aspergillus terreus is proposed based on its ability to affect both lovastatin and its own production. In this work, the exogenous addition of 100 nM butyrolactone I at 96 h post-inoculation to submerged cultures of A. terreus in 5 L bioreactors resulted in 2.5-fold increase in lovastatin production as compared to control cultures at 168 h. An increase in endogenous butyrolactone I levels (2.5-fold) is also detected in cultures supplemented with butyrolactone I, thus suggesting an auto-stimulatory function. Molecular analysis of butyrolactone I-mediated enhancement of lovastatin production revealed induction of lovastatin biosynthetic genes, lovB and lovF, at the transcriptional level. Microarray analysis of A. terreus transcriptome depicted a growth phase-specific response to butyrolactone I addition as the majority of the expressed genes showed differential expression during the specific growth phase (p < 0.01). This study demonstrates for the first time the potential of butyrolactone I as a growth phase-specific inducer of the secondary metabolite lovastatin production and shows the auto-stimulatory effect of this molecule on its own production in the filamentous fungus A. terreus

Transnational access to large prospective cohorts in Europe: Current trends and unmet needs.

Biobank samples and data from studies of large prospective cohorts (LPC) represent an invaluable resource for health research. Efficient sharing and pooling of samples and data is a central pre-requisite for new advances in biomedical science. This requirement, however, is not compatible with the present scattered and traditional access governance structures, where legal and ethical frameworks often form an obstacle for effective sharing. Moreover, the EU General Data Protection Regulation (GDPR) is demanding increasingly rigorous administration from all those organisations processing personal data. The BBMRI-LPC project (Biobanking and Biomolecular Research Infrastructure ― Large Prospective Cohorts) assembled 21 LPCs from 10 countries and two EU-wide multinational cohort networks with a key objective to promote collaborative innovative transnational research proposed by external researchers on the broad field of common chronic diseases, and analyze the gaps and needs involved. BBMRI-LPC organized three scientific calls to offer European investigators an opportunity to gain free of charge transnational access to research material available in the participating cohorts. A total of 11 high-quality research proposals involving multiple prospective cohorts were granted, and the access process in the individual projects carefully monitored. Divergent access governance structures, complex legal and ethical frameworks and heterogeneous procedures were identified as currently constituting substantial obstacles for sample and data transfer in Europe. To optimize the scientific value and use of these research resources, practical solutions for more streamlined access governance in collaborative projects are urgently needed. A number of infrastructure developments could be made to improve time-efficiency in access provision

Breast cancer hypothesis: a single cause for the majority of cases

STUDY OBJECTIVE—The main cause of breast cancer remains unknown. Numerous causal factors or predisposing conditions have been proposed, but account for only a small percentage of the total disease. The current search for multiple causes is unavailing. This report explores whether any single aetiological agent may be responsible for the majority of cases, and attempts to define its properties.
METHODS—Examination of all relevant epidemiological and biological evidence.
MAIN RESULTS—Genetic inheritance is not the main cause of breast cancer because most cases are sporadic, there is a low prevalence of family history, and genetically similar women have differing rates after migration. Environmental exposure, such as pollution by industrialisation, is not a major cause, as deduced from a spectrum of epidemiological data. The possibility of infection as cause is not persuasive as there is no direct biological evidence and no epidemiological support. Oestrogen status is closely related to breast cancer risk, but there are numerous inconsistencies and paradoxes. It is suggested that oestrogens are not the proximate agent but are promoters acting in concert with the causal agent. Dietary factors, and especially fat, are associated with the aetiology of breast cancer as shown by intervention and ecological correlation studies, but the evidence from case-control and cohort studies is inconsistent and contradictory.
CONCLUSIONS—The hypothesis that best fits the epidemiological data is that dietary fat is not itself the causal agent, but produces depletion of an essential factor that is normally protective against the development of breast cancer. Many of the observed inconsistencies in the epidemiology are explainable if deficiency of this agent is permissive for breast cancer to develop. Some properties of the putative agent are outlined, and research investigations proposed.


Keywords: breast cance

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

10.1038/s41467-020-20851-4Nature Communications121125