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Early-life stages play a key role in the dynamics of bipartite life cycle marine fish populations. Difficult to monitor, observations of these stages are often scattered in space and time. While Mediterranean coastlines have often been surveyed, no effort has been made to assemble historical observations. Here we build an exhaustive compilation of dispersal traits for coastal fish species, considering in situ observations and growth models (Di Stefano et al., 2023; https://doi.org/10.17882/91148). Our database contains over 110 000 entries collected from 1993 to 2021 in various subregions. All observations are harmonized to provide information on dates and geolocations of both spawning and settlement, along with pelagic larval durations. When applicable, missing data and associated confidence intervals are reconstructed from dynamic energy budget theory. Statistical analyses allow traits’ variability to be revisited and sampling biases to be revealed across taxa, space and time, hence providing recommendations for future studies and sampling. Comparison of observed and modelled entries provides suggestions to improve the feed of observations into models. Overall, this extensive database is a crucial step to investigate how marine fish populations respond to global changes across environmental gradients.

Diffuse midline gliomas (DMGs) are aggressive and fatal pediatric tumors of the central nervous system that are highly resistant to treatments. Lysine to methionine substitution of residue 27 on histone H3 (H3-K27M) is a driver mutation in DMGs, reshaping the epigenetic landscape of these cells to promote tumorigenesis. H3-K27M gliomas are characterized by deregulation of histone acetylation and methylation pathways, as well as the oncogenic MYC pathway. In search of effective treatment, we examined the therapeutic potential of dual targeting of histone deacetylases (HDACs) and MYC in these tumors. Treatment of H3-K27M patient-derived cells with Sulfopin, an inhibitor shown to block MYC-driven tumors in vivo, in combination with the HDAC inhibitor Vorinostat, resulted in substantial decrease in cell viability. Moreover, transcriptome and epigenome profiling revealed synergistic effect of this drug combination in downregulation of prominent oncogenic pathways such as mTOR. Finally, in vivo studies of patient-derived orthotopic xenograft models showed significant tumor growth reduction in mice treated with the drug combination. These results highlight the combined treatment with PIN1 and HDAC inhibitors as a promising therapeutic approach for these aggressive tumors.

Abstract Background Whole genome amplification (WGA) and laser assisted micro-dissection represent two recently developed technologies that can greatly advance biological and medical research. WGA allows the analysis of multiple genomic loci from a single genome and has been performed on single cells from cell suspensions and from enzymatically-digested tissues. Laser micro-dissection makes it possible to isolate specific single cells from heterogeneous tissues. Results Here we applied for the first time WGA on laser micro-dissected single cells from stained tissue sections, and developed a protocol for sequentially performing the two procedures. The combined procedure allows correlating the cell's genome with its natural morphology and precise anatomical position. From each cell we amplified 122 genomic and mitochondrial loci. In cells obtained from fresh tissue sections, 64.5% of alleles successfully amplified to ~700000 copies each, and mitochondrial DNA was amplified successfully in all cells. Multiplex PCR amplification and analysis of cells from pre-stored sections yielded significantly poorer results. Sequencing and capillary electrophoresis of WGA products allowed detection of slippage mutations in microsatellites (MS), and point mutations in P53. Conclusion Comprehensive genomic analysis of single cells from stained tissue sections opens new research opportunities for cell lineage and depth analyses, genome-wide mutation surveys, and other single cell assays.

Objectives: Ivermectin, an antiparasitic agent, also has antiviral properties. In this study, we aimed to assess whether ivermectin has anti-SARS-CoV-2 activity. Methods: In this double-blinded trial, we compared patients receiving ivermectin for 3 days versus placebo in nonhospitalized adult patients with COVID-19. A reverse transcriptase-polymerase chain reaction from a nasopharyngeal swab was obtained at recruitment and every 2 days for at least 6 days. The primary endpoint was a reduction of viral load on the sixth day as reflected by cycle threshold level >30 (noninfectious level). The primary outcome was supported by the determination of viral-culture viability. Results: Of 867 patients screened, 89 were ultimately evaluated per-protocol (47 ivermectin and 42 placeboes). On day 6, the odds ratio (OR) was 2.62 (95% confidence interval [CI]: 1.09-6.31) in the ivermectin arm, reaching the endpoint. In a multivariable logistic regression model, the odds of a negative test on day 6 were 2.28 times higher in the ivermectin group but reached significance only on day 8 (OR 3.70; 95% CI: 1.19-11.49, P = 0.02). Culture viability on days 2 to 6 was positive in 13.0% (3/23) of ivermectin samples versus 48.2% (14/29) in the placebo group (P = 0.008). Conclusion: There were lower viral loads and less viable cultures in the ivermectin group, which shows its anti-SARS-CoV-2 activity. It could reduce transmission in these patients and encourage further studies with this drug.

IntroductionCoastal detrital bottoms (CDB) are one of the most extensive habitats of the continental shelf worldwide, in the upper levels of the circalittoral zone. Hosting a diverse community structured by sediment grain size, trophic interactions and calcified organisms, CDB exhibit important ecological functions. In the Mediterranean Sea, CDB are constituted by recent elements partly provided by adjacent infralittoral and circalittoral ecosystems. Since the 2010s, the offshore extension of many Marine Protected Areas (MPAs) has resulted in the incorporation of vast areas of CDB, raising the issue of their management. The Marine Strategy Framework Directive (MSFD) has embraced the concept of an ecosystem-based approach involving taking into account the functioning of marine habitats and their related ecosystem services. The purpose of this paper is to propose an ecosystem-based quality index (EBQI) tested on CDB from the north-western Mediterranean Sea, focusing mainly on epibenthic assemblages.MethodsThe first step has been to define a conceptual model of the CDB functioning, including the main trophic compartments and their relative weighting, then to identify appropriate assessment methods and potential descriptors. Twenty-nine sites were sampled along the coast of Provence and French Riviera (Southern France). Study sites were chosen with a view to encompassing a wide range of hydrological conditions and human pressures.ResultsVery well-preserved sites were found in Provence in areas without trawling and terrigenous inputs, while impacted and low-ES sites were located in the vicinity of urbanized areas. The cover of rhodoliths characterizes the seascape and might be an indicator of the good ES of CDB and reduced human pressure. However, the absence of rhodoliths may also be induced by natural phenomena.DiscussionThe EBQI designed for CDB proved representative and useful for a functional assessment based on epibenthic assemblages. However, some descriptors have shown their limitations and should be further explored. We highlight here the priority of establishing an index corresponding to a societal demand (e.g., European Directives, Barcelona convention) as a basis for a broad and large-scale assessment, for practical reasons. We stress the need to better apprehend the role of the macro-infauna and to extend this index over a wider geographical scale.

Abstract Coastal zones are ecosystems of high economic value but exposed to numerous disturbances, while they represent nurseries for many fish species, raising the issue of the preservation of their functions and services. In this context, the juvenile fish assemblages of all types of habitats present in shallow coastal zones were studied on the south-east coast of France using underwater visual censuses in warm (June–July 2014) and cold (April 2015) periods. A total of fourteen habitat types were characterized, which could be grouped into three broad categories, rocky substrates (natural and artificial), sedimentary bottoms with all levels of granulometry, and seagrass beds including Cymodocea nodosa and Posidonia oceanica meadows; the ecotones or interfaces between the three broad habitat categories were individualized as particular habitat types. The abiotic and biotic descriptors of the 14 habitat types individualized did not vary with time, except for a higher cover percentage and canopy height of macrophytes in the warm period, which increased the three-dimensional structure of some habitats. The taxonomic composition and density of juvenile fish assemblages were analyzed using both multivariate and univariate descriptors, after grouping the 57 fish species recorded into 41 well-individualized taxa. Juvenile fishes were recorded in all habitat types, with higher mean species richness and abundance during the warm than the cold period. The richest habitats in terms of both fish species richness and abundance were the natural rocky substrates and the interfaces between Posidonia beds and the other habitats. Although juvenile fish assemblage composition differed among habitat types and between periods, the most abundant fish species were Atherina sp., Sarpa salpa, Gobiidae, Symphodus spp., Pagellus spp. and several Diplodus species, which colonized 7 up to 14 different habitat types (depending on taxa) during their juvenile life. Most species settled in one or a few specific habitats but rapidly colonized adjacent habitats when growing. This study provided evidence of the role of all types of shallow coastal habitats as fish nurseries and their varying pattern of occupation in space and time by the different juvenile stages. It highlighted the importance of the mosaic of habitats and interfaces for the complete development of all juvenile life stages of fishes, and for the preservation of a high diversity of coastal fish assemblages and fisheries resources in the Mediterranean Sea.

We found that pediatric glioblastoma (PED-GBM) cell lines from diffuse intrinsic pontine glioma (DIPG) carrying the H3K27M mutation or from diffuse hemispheric glioma expressing the H3G34R mutation are sensitive to the combination of vorinostat (a histone deacetylase inhibitor) and PARP-1 inhibitors. The combined treatment increased the phosphorylation of eIF2α (P-eIF2α) relative to each drug alone and enhanced the decrease in cell survival. To explore the role played by increased P-eIF2α in modulating PED-GBM survival and response to treatments, we employed brain-penetrating inhibitors of P-eIF2α dephosphorylation: salubrinal and raphin-1. These drugs increased P-eIF2α, DNA damage, and cell death, similarly affecting the sensitivity of DIPG cells and derived neurospheres to PARP-1 inhibitors. Interestingly, these drugs also decreased the level of eIF2Bϵ (the catalytic subunit of eIF2B) and increased its phosphorylation, thereby enhancing the effect of increased P-eIF2α. Transient transfection with the S51D phosphomimetic eIF2α variant recapitulated the effect of salubrinal and raphin-1 on PED-GBM survival and sensitivity to PARP-1 inhibitors. Importantly, either salubrinal or raphin-1 dramatically increased the sensitivity of DIPG cells to radiation, the main treatment modality of PED-GBM. Finally, PED-GBM was more sensitive than normal human astrocytes to salubrinal, raphin-1, and the treatment combinations described herein. Our results indicate that combinations of histone deacetylase inhibitors and PARP-1 inhibitors should be evaluated for their toxicity and efficacy in PED-GBM patients and point to drugs that increase P-eIF2α or modulate its downstream effectors as a novel means of treating PED-GBM.

Marine noise is an emerging pollutant inducing a variety of negative impacts on many animal taxa, including fish. Fish population persistence and dynamics rely on the supply of early life stages, which are often very sensitive to disturbance. Impacts of marine noise pollution (MNP) on juvenile fish have rarely been investigated in temperate regions. This is particularly true for the Mediterranean Sea, which is considered as an MNP hotspot due to intensive maritime traffic. In this study, we investigate the relationship between MNP related to boat traffic and (i) assemblage structure and (ii) the density of juvenile fishes (post-settlers at different stages) belonging to the Sparidae family. We quantified MNP produced by boating at four coastal locations in the French Riviera (NW Mediterranean Sea) by linearly combining five variables into a ‘noise index’ (NI): (i) boat visitation, (ii) number of boat passages/hour, (iii) the instantaneous underwater noise levels of passing boats, (iv) continuous boat underwater noise levels and (v) duration of exposure to boat noise. Then, using the NI, we identified an MNP gradient. By using juvenile fish visual censuses (running a total of 1488 counts), we found that (i) the assemblage structure and (ii) the density patterns of three fish species (i.e., Diplodus sargus, D. puntazzo, D. vulgaris) changed along the MNP gradient. Specifically, the density of early D. sargus post-settlers was negatively related to MNP, while late post-settler densities of D. puntazzo and, less evidently, D. vulgaris tended to decrease more rapidly with decreasing MNP. Our findings suggest the following potential impacts of MNP on juvenile sparids related to coastal boat traffic: (i) idiosyncratic effects on density depending on the species and the developmental stage (early vs. late post-settlers); (ii) negative effects on recruitment, due to possible alteration of late post-settlement movement patterns.

The taxonomy of cyclostome bryozoans is founded on characters of the skeleton, but molecular sequence data have increasingly shown that established higher taxa are not monophyletic. Here we describe the skeletal morphology of a new species from Guadeloupe (French West Indies) with erect ramose colonies consisting of long, curved zooids that are typical of the suborder Cerioporina among living cyclostomes. However, molecular evidence from nuclear ribosomal RNA genes 18S and 28S places the new taxon in the suborder Rectangulata, where this colony-form has not been previously recorded. It nests firmly within the genus Disporella Gray, 1848, in a strongly supported clade that also includes Plagioecia patina (Lamarck, 1816) (Tubuliporina) and the sister taxa Doliocoitis cyanea Gordon & Taylor, 2001 (Rectangulata) and Favosipora rosea Gordon & Taylor, 2001 (Cerioporina). The short and robust branches of the new Guadeloupe cyclostome, here named Disporella guada Harmelin, Taylor & Waeschenbach sp. nov., are well adapted to life in shallow rocky sites exposed to severe wave action, which appear to be its exclusive habitat.