Molecular response to toxic diatom-derived aldehydes in the sea urchin Paracentrotus lividus.

Diatoms are dominant photosynthetic organisms in the world's oceans and represent a major food source for zooplankton and benthic filter-feeders. However, their beneficial role in sustaining marine food webs has been challenged after the discovery that they produce secondary metabolites, such as polyunsaturated aldehydes (PUAs), which negatively affect the reproductive success of many invertebrates. Here, we report the effects of two common diatom PUAs, heptadienal and octadienal, which have never been tested before at the molecular level, using the sea urchin, Paracentrotus lividus, as a model organism. We show that both PUAs are able to induce teratogenesis (i.e., malformations), as already reported for decadienal, the better-studied PUA of this group. Moreover, post-recovery experiments show that embryos can recover after treatment with all three PUAs, indicating that negative effects depend both on PUA concentrations and the exposure time of the embryos to these metabolites. We also identify the time range during which PUAs exert the greatest effect on sea urchin embryogenesis. Finally, we report the expression levels of thirty one genes (having a key role in a broad range of functional responses, such as stress, development, differentiation, skeletogenesis and detoxification processes) in order to identify the common targets affected by PUAs and their correlation with morphological abnormalities. This study opens new perspectives for understanding how marine organisms afford protection from environmental toxicants through an integrated network of genes

First Morphological and Molecular Evidence of the Negative Impact of Diatom-Derived Hydroxyacids on the Sea Urchin Paracentrotus lividus.

Oxylipins (including polyunsaturated aldehydes PUAs, hydoxyacids and epoxyalcohols) are the end-products of a lipoxygenase/hydroperoxide lyase metabolic pathway in diatoms. To date very little information is available on oxylipins other than PUAs, even though they represent the most common oxylipins produced by diatoms. Here, we report, for the first time, on the effects of two hydroxyacids, 5-and 15-HEPE, which have never been tested before, using the sea urchin Paracentrotus lividus as a model organism. We show that HEPEs do induce developmental malformations but at concentrations higher when compared to PUAs. Interestingly, HEPEs also induced a marked developmental delay in sea urchin embryos, which has not hitherto been reported for PUAs. Recovery experiments revealed that embryos do not recover following treatment with HEPEs. Finally, we report the expression levels of 35 genes (involved in stress, development, differentiation, skeletogenesis and detoxification processes) to identify the molecular targets affected by HEPEs. We show that the two HEPEs have very few common molecular targets, specifically affecting different classes of genes and at different times of development. In particular, 15-HEPE switched on fewer genes than 5-HEPE, up-regulating mainly stress-related genes at a later pluteus stage of development. 5-HEPE was stronger than 15-HEPE, targeting twenty-four genes, mainly at the earliest stages of embryo development (at the blastula and swimming blastula stages). These findings highlight the differences between HEPEs and PUAs and also have important ecological implications because many diatom species do not produce PUAs but rather these other chemicals derived from the oxidation of fatty acids

Food safety objectives, criteria, ranking and hierarchization

The paper describes the terminology of risk in the view of food safety objectives, criteria, ranking and hierarchization: the terms Performance Criterion, Process Criteria, Product Criterion, Microbiological Criteria, Food Safety Objective, Performance standard, Food safety policy objectives, Risk Assessment Policies, Weighing, Precaution, Prevention, Precautionary principle, Prevention principle, Principle of separation between risk assessment and management, Rank, Ranking, Categorization, Ranking, Priorization, ALARA (As Low Reasonably Achievable), ALOP (Appropriate level of protection), Risk Management, Risk management in the public function are reported and discussed

Occurence and Bioactivities of Funicone-Related Compounds

Studies on production of secondary metabolites by fungi have received a substantial boost lately, particularly with reference to applications of their biological properties in human medicine. Funicones represent a series of related compounds for which there is accumulating evidence supporting their possible use as pharmaceuticals. This paper provides a review on the current status of knowledge on these fungal extrolites, with special reference to aspects concerning their molecular structures and biological activities

The Logic of Fashion Cycles

Many cultural traits exhibit volatile dynamics, commonly dubbed fashions or fads. Here we show that realistic fashion-like dynamics emerge spontaneously if individuals can copy others' preferences for cultural traits as well as traits themselves. We demonstrate this dynamics in simple mathematical models of the diffusion, and subsequent abandonment, of a single cultural trait which individuals may or may not prefer. We then simulate the coevolution between many cultural traits and the associated preferences, reproducing power-law frequency distributions of cultural traits (most traits are adopted by few individuals for a short time, and very few by many for a long time), as well as correlations between the rate of increase and the rate of decrease of traits (traits that increase rapidly in popularity are also abandoned quickly and vice versa). We also establish that alternative theories, that fashions result from individuals signaling their social status, or from individuals randomly copying each other, do not satisfactorily reproduce these empirical observations

Diatom-derived oxylipins induce cell death in sea urchin embryos activating caspase-8 and caspase 3/7

Diatoms are an important class of unicellular algae that produce bioactive secondary metabolites withcytotoxic activity collectively termed oxylipins, including polyunsaturated aldehydes (PUAs), hydroxy-acids (HEPEs), oxo-acids and epoxyalcohols. Previous results showed that at higher concentrations, thePUA decadienal induced apoptosis on copepods and sea urchin embryos via caspase-3 activation; atlower concentrations decadienal affected the expression levels of the caspase-8 gene in embryos of thesea urchin Paracentrotus lividus. In the present work, we studied the effects of other common oxylip-ins produced by diatoms: two PUAs (heptadienal and octadienal) and four hydroxyacids (5-, 9- 11- and15-HEPE) on P. lividus cell death and caspase activities. Our results showed that (i) at higher concentra-tions PUAs and HEPEs induced apoptosis in sea urchin embryos, detected by microscopic observationand through the activation of caspase-3/7 and caspase-8 measured by luminescent assays; (ii) at lowconcentrations, PUAs and HEPEs affected the expression levels of caspase-8 and caspase-3/7 (isolated forthe first time here in P. lividus) genes, detected by Real Time qPCR. These findings have interesting impli-cations from the ecological point of view, given the importance of diatom blooms in nutrient-rich aquaticenvironments

Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins.

Marine organisms possess a series of cellular strategies to counteract the negative effects of toxic compounds, including the massive reorganization of gene expression networks. Here we report the modulated dose-dependent response of activated genes by diatom polyunsaturated aldehydes (PUAs) in the sea urchin Paracentrotus lividus. PUAs are secondary metabolites deriving from the oxidation of fatty acids, inducing deleterious effects on the reproduction and development of planktonic and benthic organisms that feed on these unicellular algae and with anti-cancer activity. Our previous results showed that PUAs target several genes, implicated in different functional processes in this sea urchin. Using interactomic Ingenuity Pathway Analysis we now show that the genes targeted by PUAs are correlated with four HUB genes, NF-κB, p53, δ-2-catenin and HIF1A, which have not been previously reported for P. lividus. We propose a working model describing hypothetical pathways potentially involved in toxic aldehyde stress response in sea urchins. This represents the first report on gene networks affected by PUAs, opening new perspectives in understanding the cellular mechanisms underlying the response of benthic organisms to diatom exposure

Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility