Functional diversification of teleost Fads2 fatty acyl desaturases occurs independently of the trophic level

The long-chain (≥C20) polyunsaturated fatty acid biosynthesis capacity of fish varies among species, with trophic level hypothesised as a major factor. The biosynthesis capacity is largely dependent upon the presence of functionally diversified fatty acyl desaturase 2 (Fads2) enzymes, since many teleosts have lost the gene encoding a Δ5 desaturase (Fads1). The present study aimed to characterise Fads2 from four teleosts occupying different trophic levels, namely Sarpa salpa, Chelon labrosus, Pegusa lascaris and Atherina presbyter, which were selected based on available data on functions of Fads2 from closely related species. Therefore, we had insight into the variability of Fads2 within the same phylogenetic group. Our results showed that Fads2 from S. salpa and C. labrosus were both Δ6 desaturases with further Δ8 activity while P. lascaris and A. presbyter Fads2 showed Δ4 activity. Fads2 activities of herbivorous S. salpa are consistent with those reported for carnivorous Sparidae species. The results suggested that trophic level might not directly drive diversification of teleost Fads2 as initially hypothesised, and other factors such as the species’ phylogeny appeared to be more influential. In agreement, Fads2 activities from P. lascaris and A. presbyter were similar to their corresponding phylogenetic counterparts Solea senegalensis and Chirostoma estor

Effects of dietary fish oil substitution by Echium oil on enterocyte and hepatocyte lipid metabolism of gilthead seabream (Sparus aurata L.)

The fatty acid profile of vegetable oils (VOs), together with the poor ability of marine fish to convert polyunsaturated fatty acids (PUFA) to highly unsaturated fatty acids (HUFA), lead to important changes in the nutritional value of farmed fish fed VO, which include increased fat and 18:2n-6 and reduced n-3 HUFA. Echium oil (EO) has a good n-3/n-6 balance as well as an interesting profile with its high content of unusual fatty acids (SDA, 18:4n-3 and GLA, 18:3n-6) that are of increasing pharmacological interest. The effects of substituting 50 % of dietary fish oil (FO) by EO on gilthead seabream (Sparus aurata L.) enterocyte and hepatocyte lipid metabolism were studied. After 4 months of feeding, cell viability, total lipid contents and lipid class compositions were not affected by EO. The cells clearly reflected the fatty acid profile of the EO showing increased SDA, GLA and its elongation product 20:3n-6, and only minorly decreased n-3 HUFA compared to other VO. Metabolism of [1-14C]18:2n-6 and [1-14C]18:3n-3 was also unaffected by EO in terms of total uptake, incorporation, β-oxidation and elongation-desaturation activities

ICTV Virus Taxonomy Profile: Asfarviridae

The family Asfarviridae includes the single species African swine fever virus, isolates of which have linear dsDNA genomes of 170–194 kbp. Virions have an internal core, an internal lipid membrane, an icosahedral capsid and an outer lipid envelope. Infection of domestic pigs and wild boar results in an acute haemorrhagic fever with transmission by contact or ingestion, or by ticks of the genus Ornithodoros. Indigenous pigs act as reservoirs in Africa, where infection is endemic, and from where introductions occur periodically to Europe. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Asfarviridae, which is available at www.ictv.global/report/asfarviridae.info:eu-repo/semantics/publishedVersio

Lipid metabolism in Tinca tinca and its n-3 LC-PUFA biosynthesis capacity

Carps, barbels and other cyprinids are the major contributors to freshwater aquaculture at global scale. Nevertheless, freshwater fish aquaculture needs to diversify their production in order to offer consumers new species. Tench (Tinca tinca) is a freshwater species with great interest for the diversification of continental aquaculture. However, up to date, no commercial formulated diet exists for this species in order to optimize their nutritional requirements and the quality of its final product. Using multiple methodological approaches, the aim of this study was to evaluate the long chain polyunsaturated fatty acid (LC-PUFA) metabolism of T. tinca. Firstly, the molecular cloning and functional characterisation by heterologous expression in yeast of a desaturase (Fads2) and two elongases (Elovl2 and Elovl5) involved in LC-PUFA biosynthesis, and the analysis of gene expression among tissues were performed. Secondly, in order to confirm the LC-PUFA biosynthesis capacity of isolated hepatocytes and enterocytes, cells were incubated with [1-14C] labelled linoleic acid (18:2n-6, LA), linolenic acid (18:3n-3, ALA) and eicosapentaenoic acid (20:5n-3, EPA). In yeast, Fads2 showed a Δ6/Δ5 bifunctional activity. Elovl2 was more active over C20 and C22 substrates, whereas Elovl5 was over C18 and C20. Liver displayed the highest expression for the three target genes (fads2, elovl2 and elovl5). Incubated cells also showed Fads2 bifunctional activity as well as elongation products in concordance with yeast heterologous expression results. Importantly, our results demonstrated that tench is able to biosynthesise docosahexaenoic acid (DHA) from 18:3n-3 in both hepatocytes and enterocytes, a capacity that seems to explain in part the surprisingly high levels of DHA found in the fish flesh compared to its dietary supply. Tench is a promising freshwater species with a potential capacity to endogenously increase its flesh DHA contents, reducing the impact that the usage of fish oils from forage fisheries may have on the aquaculture industry

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir/ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an anti-apoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence

Assessment of stress and nutritional biomarkers in cultured Octopus vulgaris paralarvae: Effects of geographical origin and dietary regime

The common octopus (Octopus vulgaris) is a promising species for aquaculture diversification, but massive mortality during the first life-cycle stages (paralarvae) is the main bottleneck for its commercial production in captivity. The aim of this study was to assess stress and nutritional condition biomarkers (HSP70, ROS enzymes and lipid peroxidation) (RNA/DNA, RNA/protein, protein/DNA and protein) inO.vulgarisparalarvae from different geographical origins and fed withArtemiaenriched with marine phospholipids or microalgae (control group). To this end paralarvae were cultured for 30days, in three different centres in Spain (Tarragona-Mediterranean area, Tenerife-Central Atlantic area and Vigo-North Atlantic area), under the same protocol, and fed onArtemiaenriched with marine phospholipids (LC60) (Marine Lecithin LC 60®, PhosphoTech Laboratoires) or microalgae (control group). Dry weight and most biomarkers analysed in hatchlings showed significant differences related to their origin (centre). Fifteen day old paralarvae presented significant differences in specific growth rate (SGR) associated with their dietary regime, and also showed differences in biomarkers associated both with their geographical origin and dietary regime. The results suggest that the SGR of paralarvae were positively influenced by LC60, promoting growth and in agreement with the results of nutritional condition biomarkers (nucleic acids ratios). The antioxidant defences against oxidative damage were also boosted in the LC60 paralarvae group, possibly as a result of the elevated content in highly polyunsaturated fatty acids. In addition, the partial correlations found between biomarkers varied according to diet. However, no positive effect of LC60 on survival was observed. The high variability found among geographical origins, despite the use of the same rearing protocol, highlights the need to clarify the sources of such variability

Polyunsaturated fatty acid metabolism in three fish species with different trophic level

Reducing the dependency of fishfeed for marine ingredients and species diversification are both considered crucial factors for the sustainable development of aquaculture. The substitution of fish oil (FO) by vegetable oils (VO) in aquafeeds is an economically feasible solution. However, such substitution may compromise the fish flesh content of essential n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) and, therefore, its nutritional value for human consumption. Likewise, there is a wide range of strategies to select new target species for sector diversification, among which, the capacity to biosynthesize n-3 LC-PUFA from their C18 precursors abundant in VO might be considered as a fair preliminary strategy. Therefore, the aim of the present study was to analyze the metabolic fate of [1-14C] labeled 18:2n-6, 18:3n-3, 20:5n-3 and 22:6n-3 in isolated hepatocytes and enterocytes from wild individuals of three fish species with different trophic level: the marine herbivorous salema (Sarpa salpa), the strict carnivorous sand sole (Pegusa lascaris) and the omnivorous thicklip grey mullet (Chelon labrosus). These species were selected for their phylogenetic proximity to consolidated farmed species such as gilthead seabream (Sparus aurata), senegalese sole (Solea senegalensis), and golden grey mullet (Liza aurata), respectively. The study also assessed the molecular cloning, functional characterization and tissue distribution of the fatty acyl elongase (Elovl) gene, elovl5, involved in the biosynthetic metabolism of n-3 LC-PUFA. The three species were able to biosynthesize docosahexaenoic acid (22:6n-3). S. salpa seems to have similar biosynthetic capacity than S. aurata, with a fatty acyl desaturase 2 (Fads2), with 6, 8 and 5 activities. P. lascaris showed a wider Fads2 activity repertory than S. senegalensis, including 4 and residual 6/5 activities. In C. labrosus, both 8 and 5 activities but not the 6 described for L. aurata were detected in the incubated cells. Elongation from C18 and C20 precursors to C20 and C22 products occurred in hepatocytes and enterocytes as well as in the functional characterization of Elovl5 by heterologous expression in yeast. Elovl5 showed a species specific expression pattern, with the highest rates observed in the liver, gut and brain in S. salpa and P. lascaris, and in the brain for C. labrosus. In summary, the LC-PUFA biosynthesis capacity from S. salpa, P. lascaris and C. labrosus greatly resembled that of their phylogenetic closer species. The three studied species could be further explored as candidates for the aquaculture diversification from their potential ability to biosynthesize LC-PUFA

The African swine fever virus dynein-binding protein p54 induces infected cell apoptosis

AbstractA specific interaction of ASFV p54 protein with 8 kDa light chain cytoplasmic dynein (DLC8) has been previously characterized and this interaction is critical during virus internalization and transport to factory sites. During early phases of infection, the virus induces the initiation of apoptosis triggering activation of caspase-9 and -3. To analyze the role of the structural protein p54 in apoptosis, transient expression experiments of p54 in Vero cells were carried out which resulted in effector caspase-3 activation and apoptosis. Interestingly, p54 mutants, lacking the 13 aa dynein-binding motif lose caspase activation ability and pro-death function of p54. This is the first reported ASFV protein which induces apoptosis

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort

Cannabis use is highly prevalent in first-episode psychosis (FEP) and plays a critical role in its onset and prognosis, but the genetic underpinnings promoting both conditions are poorly understood. Current treatment strategies for cannabis cessation in FEP are clearly inefficacious. Here, we aimed to characterize the association between cannabis-related polygenic risk scores (PRS) on cannabis use and clinical course after a FEP. A cohort of 249 FEP individuals were evaluated during 12 months. Symptom severity was measured with the Positive and Negative Severity Scale and cannabis use with the EuropASI scale. Individual PRS for lifetime cannabis initiation (PRS) and cannabis use disorder (PRS) were constructed. Current cannabis use was associated with increased positive symptoms. Cannabis initiation at younger ages conditioned the 12-month symptom progression. FEP patients with higher cannabis PRS reported increased baseline cannabis use. PRS was associated with the course of negative and general symptomatology over follow-up. Cannabis use and symptom progression after a FEP were modulated by cannabis PRS, suggesting that lifetime initiation and use disorders may have partially independent genetic factors. These exploratory results may be the first step to identify those FEP patients more vulnerable to cannabis use and worse outcomes to ultimately develop tailored treatments