Translational challenges and opportunities in biofilm science:a BRIEF for the future

Biofilms are increasingly recognised as a critical global issue in a multitude of industries impacting health, food and water security, marine sector, and industrial processes resulting in estimated economic cost of $5 trillion USD annually. A major barrier to the translation of biofilm science is the gap between industrial practices and academic research across the biofilms field. Therefore, there is an urgent need for biofilm research to notice and react to industrially relevant issues to achieve transferable outputs. Regulatory frameworks necessarily bridge gaps between different players, but require a clear, science-driven non-biased underpinning to successfully translate research. Here we introduce a 2-dimensional framework, termed the Biofilm Research-Industrial Engagement Framework (BRIEF) for classifying existing biofilm technologies according to their level of scientific insight, including the understanding of the underlying biofilm system, and their industrial utility accounting for current industrial practices. We evidence the BRIEF with three case studies of biofilm science across healthcare, food & agriculture, and wastewater sectors highlighting the multifaceted issues around the effective translation of biofilm research. Based on these studies, we introduce some advisory guidelines to enhance the translational impact of future research

Depletion of somatic mutations in splicing-associated sequences in cancer genomes

Abstract Background An important goal of cancer genomics is to identify systematically cancer-causing mutations. A common approach is to identify sites with high ratios of non-synonymous to synonymous mutations; however, if synonymous mutations are under purifying selection, this methodology leads to identification of false-positive mutations. Here, using synonymous somatic mutations (SSMs) identified in over 4000 tumours across 15 different cancer types, we sought to test this assumption by focusing on coding regions required for splicing. Results Exon flanks, which are enriched for sequences required for splicing fidelity, have ~ 17% lower SSM density compared to exonic cores, even after excluding canonical splice sites. While it is impossible to eliminate a mutation bias of unknown cause, multiple lines of evidence support a purifying selection model above a mutational bias explanation. The flank/core difference is not explained by skewed nucleotide content, replication timing, nucleosome occupancy or deficiency in mismatch repair. The depletion is not seen in tumour suppressors, consistent with their role in positive tumour selection, but is otherwise observed in cancer-associated and non-cancer genes, both essential and non-essential. Consistent with a role in splicing modulation, exonic splice enhancers have a lower SSM density before and after controlling for nucleotide composition; moreover, flanks at the 5’ end of the exons have significantly lower SSM density than at the 3’ end. Conclusions These results suggest that the observable mutational spectrum of cancer genomes is not simply a product of various mutational processes and positive selection, but might also be shaped by negative selection

The effect of the main physicochemical properties of polycyclic aromatic hydrocarbons on their water/sediments distribution

International audiencePolycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that continue to attract researchers' attention until these days due to their toxicity and their multisource emission. In this study, levels of 17 active molecules of PAHs were investigated in marine and continental Lebanese aquatic systems. The results showed that Lebanese seawater is more contaminated than several other sites on the Mediterranean Sea. On the marine side, the total concentration of PAHs ranges from 55.7 to 2683.8 ng L−1 in water and from 19.09 to 2025.03 ng g−1 in sediments. On the continental side, the total concentration ranges from 465.7 to 1399.9 ng L−1 in water and from 72.6 to 1074.7 ng g−1 in sediments presenting higher contamination and detection frequency than the marine sites. Pearson test was applied to determine the preference of PAHs toward one of the phases and showed that when the number of rings, the molecular mass and the log Ko/w increase, PAHs accumulate in sediments, and when the water solubility and the vapor pressure of PAHs increase, they tend to remain in the aqueous phase. Moreover, PAHs in Lebanese sediments were combustion-originated and resulted mainly from industrial sites set next to aquatic systems and heavy traffic especially along the Lebanese coastline. Regarding the toxicity effect, the use of the ERL/ERM approach revealed that few sites have individual PAHs levels that may occasionally cause biological adverse effects to benthic organisms; nevertheless, the ecosystem risk of PAHs in Lebanese sediments is low

Clin Sci (Lond)

Autosomal dominant inherited Protein S deficiency (PSD) (MIM 612336) is a rare disorder caused by rare mutations, mainly located in the coding sequence of the structural PROS1 gene, and associated with an increased risk of venous thromboembolism. To identify the molecular defect underlying PSD observed in an extended French pedigree with seven PSD affected members in whom no candidate deleterious PROS1 mutation was detected by Sanger sequencing of PROS1 exons and their flanking intronic regions or via an multiplex ligation-dependent probe amplification (MLPA) approach, a whole genome sequencing strategy was adopted. This led to the identification of a never reported C to T substitution at c.-39 from the natural ATG codon of the PROS1 gene that completely segregates with PSD in the whole family. This substitution ACG→ATG creates a new start codon upstream of the main ATG. We experimentally demonstrated in HeLa cells that the variant generates a novel overlapping upstream open reading frame (uORF) and inhibits the translation of the wild-type PS. This work describes the first example of 5′UTR PROS1 mutation causing PSD through the creation of an uORF, a mutation that is not predicted to be deleterious by standard annotation softwares, and emphasizes the need for better exploration of such type of non-coding variations in clinical genomics