The marine environment harbors a number of macro and micro organisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. Several of these metabolites are high-value commercial products for the pharmaceutical and cosmeceutical industries. The aim of this review is to outline the paths of marine natural products discovery and development, with a special focus on the compounds that successfully reached the market and particularly looking at the approaches tackled by the pharmaceutical and cosmetic companies that succeeded in marketing those products. The main challenges faced during marine bioactives discovery and development programs were analyzed and grouped in three categories: biodiversity (accessibility to marine resources and efficient screening), supply and technical (sustainable production of the bioactives and knowledge of the mechanism of action) and market (processes, costs, partnerships and marketing). Tips to surpass these challenges are given in order to improve the market entry success rates of highly promising marine bioactives in the current pipelines, highlighting what can be learned from the successful and unsuccessful stories that can be applied to novel and/or ongoing marine natural products discovery and development programs.

This paper gives an overview of development of the EU-bioeconomy, 2014–2020. The Vision of the new Circular Bio-based Economy, CBE is presented: Unlocking the full potential of all types of sustainably sourced biomass, crop residues, industrial side-streams, and wastes by transforming it into value-added products. The resulting product portfolio consists of a wide spectrum of value-added products, addressing societal and consumer needs. Food and feed, bio-based chemicals, materials, health-promoting products; and bio-based fuels. The pillars of CBE are described, including biotechnology, microbial production, enzyme technology, green chemistry, integrated physical/chemical processing, policies, conducive framework conditions and public private partnerships. Drivers of CBE are analyzed: Biomass supply, biorefineries, value chain clusters, rural development, farmers, foresters and mariners; urgent need for climate change mitigation and adaptation, and stopping biodiversity loss. Improved framework conditions can be drivers but also obstacles if not updated to the era of circularity. Key figures, across the entire BBI-JU project portfolio (2014–2020) are provided, including expansion into biomass feedstocks, terrestrial and aquatic, and an impressive broadening of bio-based product portfolio, including higher-value, health-promoting products for man, animal, plants and soil. Parallel to this, diversification of industrial segments and types of funding instruments developed, reflecting industrial needs and academic research involvement. Impact assessment is highlighted. A number of specific recommendations are given; e.g., including international win/win CBE-collaborations, as e.g., expanding African EU collaboration into CBE. In contrast to fossil resources biological resources are found worldwide. In its outset, circular bio-based economy, can be implemented all over, in a just manner, not the least stimulating rural development.

Syndromic Hirschsprung disease has been associated with mutations in ZFHX1B, a Smad-interacting transcriptional repressor protein. Tissue in situ hybridization has demonstrated strong expression of ZFHX1B in the developing eye, suggesting that some mutations in this gene may cause visual loss. However, none of the reported mutations have been associated with an ocular phenotype. We describe a patient with Down syndrome and Hirschsprung disease with high myopia and ocular coloboma affecting the iris and retina. In addition to trisomy 21, a novel, de novo heterozygous A to G transition in exon 8 of the ZFHX1B gene was identified, which results in a R953G amino acid substitution. This abnormality was not seen in a screen of 200 chromosomes from ethnically matched, normal controls. The arginine residue at position 953 is an extremely conserved amino acid throughout evolution. This is the first report associating Hirschsprung disease and severe eye defects with a specific genetic mutation and is the first report of a mutation in ZFHX1B causing a developmental ocular anomaly.

Several studies revealed consistent overlap between synucleinopathies and tauopathies, demonstrating that α-synuclein (ASYN) and tau co-localize in neurofibrillary tangles and in Lewy bodies from Alzheimer’s and Parkinson’s disease patients and corresponding animal models. Additionally, it has been shown that ASYN can act as an initiator of tau aggregation and phosphorylation and that these two proteins directly interact. Despite these evidences, the cellular pathway implicated in this synergistic interaction remains to be clarified. The aim of this study was to create a yeast model where the concomitant expression of ASYN and tau can be used to perform genome wide screenings for the identification of genes that modulate this interaction, in order to shed light into the pathological mechanism of cell dysfunction and to provide new targets for future therapeutic intervention. We started by validating the synergistic toxicity of tau and ASYN co-expression in yeast, by developing episomal and integrative strains expressing WT and mutant forms of both proteins, alone or in combination. The episomal strains showed no differences in growth delay upon expression of ASYN isoforms (WT or A53T) alone or in combination with tau 2N/4R isoforms (WT or P301L). However, in these strains, the presence of ASYN led to increased tau insolubility and correlated with increased tau phosphorylation in S396/404, which is mainly mediated by RIM11, the human homolog of GSK3β in yeast. On the other hand, the integrative strains showed a strong synergistic toxic effect upon co-expression of ASYN WT and tau WT, which was related to high levels of intracellular ASYN inclusions and increased tau phosphorylation and aggregation. Taken together, the strains described in the present study are able to mimic relevant pathogenic features involved in neurodegeneration and are powerful tools to identify potential target genes able to modulate the synergistic pathway driven by ASYN and tau interaction.