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Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types of stress, including viral infection. Here we show that, in primary human fibroblasts, adenovirus small e1a triggered derepression of hundreds of individual Alus by promoting TFIIIB recruitment by Alu-bound TFIIIC. Epigenome profiling revealed an e1a-induced decrease of H3K27 acetylation and increase of H3K4 monomethylation at derepressed Alus, making them resemble poised enhancers. The enhancer nature of e1a-targeted Alus was confirmed by the enrichment, in their upstream regions, of the EP300/CBP acetyltransferase, EP400 chromatin remodeler and YAP1 and FOS transcription factors. The physical interaction of e1a with EP400 was critical for Alu derepression, which was abrogated upon EP400 ablation. Our data suggest that e1a targets a subset of enhancer Alus whose transcriptional activation, which requires EP400 and is mediated by the e1a-EP400 interaction, may participate in the manipulation of enhancer activity by adenoviruses.

During alcoholic fermentation, ethanol accumulation significantly impacts yeast cells by disrupting membrane integrity, increasing permeability, and reducing cell viability. This study evaluated the effects of ethanol stress on the growth, membrane fluidity, and cell surface morphology of Saccharomyces cerevisiae and non-Saccharomyces yeast strains, specifically Torulaspora delbrueckii and Metschnikowia pulcherrima. These strains, commercialized by AEB SpA and preserved at the Unimore Microbial Culture Collection (UMCC), were tested for fermentative performance in grape must and grown under varying ethanol concentrations. Membrane fluidity was measured using Laurdan generalized polarization (GP), while Atomic Force Microscopy (AFM) assessed cell surface morphology. Results indicated that at 10% ethanol, membrane fluidity increased, particularly in strains able to tolerate up to 16% ethanol, which also demonstrated superior fermentative performance. Less tolerant strains, such as T. delbrueckii UMCC 5 and M. pulcherrima UMCC 15, showed smaller increases in fluidity. At 18% ethanol, these strains exhibited severely altered surface morphology and larger surface roughness values, suggesting increased instability under high ethanol stress, while more tolerant strains displayed better-preserved surface morphology and lower roughness values, reflecting enhanced adaptability. These findings offer insights into yeast responses to ethanol stress, supporting the development of more resilient strains for improved fermentation.

Bacterial resistance represents a major health problem worldwide and there is an urgent need to develop first-in-class compounds directed against new therapeutic targets. We previously developed a drug-discovery platform to identify new antimicrobials able to disrupt the protein-protein interaction between the β' subunit and the σ70 initiation factor of bacterial RNA polymerase, which is essential for transcription. As a follow-up to such work, we have improved the discovery strategy to make it less time-consuming and more cost-effective. This involves three sequential assays, easily scalable to a high-throughput format, and a subsequent in-depth characterization only limited to hits that passed the three tests. This optimized workflow, applied to the screening of 5360 small molecules from three synthetic and natural compound libraries, led to the identification of six compounds interfering with the β'-σ70 interaction, and thus was capable of inhibiting promoter-specific RNA transcription and bacterial growth. Upon supplementation with a permeability adjuvant, the two most potent transcription-inhibiting compounds displayed a strong antibacterial activity against Escherichia coli with minimum inhibitory concentration (MIC) values among the lowest (0.87-1.56 μM) thus far reported for β'-σ PPI inhibitors. The newly identified hit compounds share structural feature similarities with those of a pharmacophore model previously developed from known inhibitors.

Background Idiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential. The bleomycin (BLM) intratracheal murine model is the most commonly used preclinical assay to evaluate new potential therapies for IPF. Here, we present the findings derived from an integrated histomorphometric and transcriptomic analysis to investigate the development of lung fibrosis in a time-course study in a BLM rat model and to evaluate its translational value in relation to IPF.Methods Rats were intratracheally injected with a double dose of BLM (days 0–4) and sacrificed at days 7, 14, 21, 28 and 56. Histomorphometric analysis of lung fibrosis was performed on left lung sections. Transcriptome profiling by RNAseq was performed on the right lung lobes and results were compared with nine independent human gene-expression IPF studies.Results The histomorphometric and transcriptomic analyses provided a detailed overview in terms of temporal gene-expression regulation during the establishment and repair of the fibrotic lesions. Moreover, the transcriptomic analysis identified three clusters of differentially coregulated genes whose expression was modulated in a time-dependent manner in response to BLM. One of these clusters, centred on extracellular matrix (ECM)-related process, was significantly correlated with histological parameters and gene sets derived from human IPF studies.Conclusions The model of lung fibrosis presented in this study lends itself as a valuable tool for preclinical efficacy evaluation of new potential drug candidates. The main finding was the identification of a group of persistently dysregulated genes, mostly related to ECM homoeostasis, which are shared with human IPF.

Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression modulators, may be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblasts and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry. Accordingly, Alu overexpression was found to promote transition from G1 to S phase, as revealed by flow cytometry. Therefore, increased Alu RNA may contribute to sustained cell proliferation, which is an important factor of cancer development and progression.

The arts sector in South Africa is portrayed as a multiracial, emancipatory and inclusive sector that promises to reduce youth unemployment and to mitigate inequality. In post- apartheid art institutions, artistic merit and perseverance are deemed to be sufficient in order to access the art sector and its market. The paths of individual black artists from poor areas who have succeeded in accessing the institutional art circuit are praised by the media, policymakers and curators. A romanticisation of their efforts is coupled with identifying them as role models for younger generations. Despite emphasis on the inclusivity of the art sector and the hailing of successful paths, black artists report a long-standing difficulty in gaining access to, and being fully accredited in, the institutional art circuit. The ambiguity of the art sector, which claims to be inclusive in word but is de facto exclusionary, deeply affects young black artists whose first steps into the art sector are often accompanied by a feeling of uneasiness and bewilderment. Drawing on the multivocal accounts of the everyday life of young black artists who work in the field of performance art in Gqeberha, this article unveils the ‘entrance fees’ that black artists have to negotiate in order to access the institutional art circuit, i.e. the obstacles they have to overcome, but also the deals and concessions they have to make in order to build their career and be fully recognised as artists. Moreover, the article sheds light on a double invisibility in the performing arts sector: on one side the economic, spatial and reputational obstacles that artists deal with are dismissed as part of the everyday life of individuals coming from marginal areas; on the other side, the performing arts and spaces that young black artists create within alternative or complementary circuits are not considered part of the city’s artistic production.

During alcoholic fermentation, ethanol accumulation significantly impacts yeast cells by disrupting membrane integrity, increasing permeability, and reducing cell viability. This study evaluated the effects of ethanol stress on the growth, membrane fluidity, and cell surface morphology of Saccharomyces cerevisiae and non-Saccharomyces yeast strains, specifically Torulaspora delbrueckii and Metschnikowia pulcherrima. These strains, commercialized by AEB SpA and preserved at the Unimore Microbial Culture Collection (UMCC), were tested for fermentative performance in grape must and grown under varying ethanol concentrations. Membrane fluidity was measured using Laurdan generalized polarization (GP), while Atomic Force Microscopy (AFM) assessed cell surface morphology. Results indicated that at 10% ethanol, membrane fluidity increased, particularly in strains able to tolerate up to 16% ethanol, which also demonstrated superior fermentative performance. Less tolerant strains, such as T. delbrueckii UMCC 5 and M. pulcherrima UMCC 15, showed smaller increases in fluidity. At 18% ethanol, these strains exhibited severely altered surface morphology and larger surface roughness values, suggesting increased instability under high ethanol stress, while more tolerant strains displayed better-preserved surface morphology and lower roughness values, reflecting enhanced adaptability. These findings offer insights into yeast responses to ethanol stress, supporting the development of more resilient strains for improved fermentation. [ABSTRACT FROM AUTHOR]

Tuberaceae is one of the most diverse lineages of symbiotic truffle-forming fungi. To understand the molecular underpinning of the ectomycorrhizal truffle lifestyle, we compared the genomes of Piedmont white truffle (Tuber magnatum), Périgord black truffle (Tuber melanosporum), Burgundy truffle (Tuber aestivum), pig truffle (Choiromyces venosus) and desert truffle (Terfezia boudieri) to saprotrophic Pezizomycetes. Reconstructed gene duplication/loss histories along a time-calibrated phylogeny of Ascomycetes revealed that Tuberaceae-specific traits may be related to a higher gene diversification rate. Genomic features in Tuber species appear to be very similar, with high transposon content, few genes coding lignocellulose-degrading enzymes, a substantial set of lineage-specific fruiting-body-upregulated genes and high expression of genes involved in volatile organic compound metabolism. Developmental and metabolic pathways expressed in ectomycorrhizae and fruiting bodies of T. magnatum and T. melanosporum are unexpectedly very similar, owing to the fact that they diverged ~100 Ma. Volatile organic compounds from pungent truffle odours are not the products of Tuber-specific gene innovations, but rely on the differential expression of an existing gene repertoire. These genomic resources will help to address fundamental questions in the evolution of the truffle lifestyle and the ecology of fungi that have been praised as food delicacies for centuries.

CorrectionAfter publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

The structural collapse of a street lighting pole represents an aspect that is often underestimated and unpredictable, but of relevant importance for the safety of people and things. These events are complex to evaluate since several sources of damage are involved. In addition, traditional inspection methods are ineffective, do not correctly quantify the residual life of poles, and are inefficient, requiring enormous costs associated with the vastness of elements to be investigated. An advantageous alternative is to adopt a distributed type of Structural Health Monitoring (SHM) technique based on the Internet of Things (IoT). This paper proposes the design of a low-cost system, which is also easy to integrate in current infrastructures, for monitoring the structural behavior of street lighting poles in Smart Cities. At the same time, this device collects previous structural information and offers some secondary functionalities related to its application, such as meteorological information. Furthermore, this paper intends to lay the foundations for the development of a method that is able to avoid the collapse of the poles. Specifically, the implementation phase is described in the aspects concerning low-cost devices and sensors for data acquisition and transmission and the strategies of information technologies (ITs), such as Cloud/Edge approaches, for storing, processing and presenting the achieved measurements. Finally, an experimental evaluation of the metrological performance of the sensing features of this system is reported. The main results highlight that the employment of low-cost equipment and open-source software has a double implication. On one hand, they entail advantages such as limited costs and flexibility to accommodate the specific necessities of the interested user. On the other hand, the used sensors require an indispensable metrological evaluation of their performance due to encountered issues relating to calibration, reliability and uncertainty.

The mutational drift of SARS-CoV-2 and the appearance of multiple variants, including the latest Omicron variant and its sub-lineages, has significantly reduced (and in some cases abolished) the protective efficacy of Wuhan spike-antigen-based vaccines and therapeutic antibodies. One of the most functionally constrained and thus largely invariable regions of the spike protein is the one involved in the interaction with the ACE2 receptor mediating the cellular entry of SARS-CoV-2. Engineered ACE2, both as a full-length protein or as an engineered polypeptide fragment, has been shown to be capable of preventing the host-cell binding of all viral variants and to be endowed with potent SARS-CoV-2 neutralization activity both in vitro and in vivo. Here, we report on the biochemical and antiviral properties of rationally designed ACE2 N-terminal, three-helix fragments that retain a native-like conformation. One of these fragments, designated as PRP8_3H and produced in recombinant form, bears structure-stabilizing and binding-affinity enhancing mutations in α-helix-I and in both α-helix I and II, respectively. While the native-like, unmodified three α-helices ACE2 fragment proved to be thermally unstable and without any detectable pseudovirion neutralization capacity, PRP8_3H was found to be highly thermostable and capable of binding to the SARS-CoV-2 spike receptor-binding domain with nanomolar affinity and to neutralize both Wuhan and Omicron spike-expressing pseudovirions at (sub)micromolar concentrations. PRP8_3H thus lends itself as a highly promising ACE2 decoy prototype suitable for a variety of formulations and prophylactic applications. [ABSTRACT FROM AUTHOR]

The growth and popularization of platforms on scientific production has been the subject of several studies, producing relevant analyses of co-authorship behavior among groups of researchers. Researchers and their scientific productions can be analysed as co-authorship social networks, so researchers are linked through common publications. In this context, co-authoring networks can be analysed to find patterns that can describe or characterize them. This work presents the analysis and characterization of co-authorship networks of academic Brazilian graduate programs in computer science. Data from Brazilian researchers were collected and modeled as co-authoring networks among the graduate programs that researchers take part in. Each network topology was analysed with complex network measurements and three proposed qualitative indices that evaluate the publication's quality. In addition, the co-authorship networks of the computer science graduate programs were characterized in relation to the assessment received by CAPES, which attributes a qualitative grade to the graduate programs in Brazil. The results show the most relevant topological measurements for the program's characterization and the evaluations received by the programs in different qualitative degrees, relating the main topological patterns of the co-authorship networks and the CAPES grades of the Brazilian graduate programs in computer science.

Abstract To unveil how forearc lithosphere cools and re‐equilibrates, we carried out a comprehensive geothermometric investigation of the New Caledonia ophiolite, which represents a rare example of proto‐arc section generated during subduction infancy. A large data set, including more than 80 samples (peridotites and mafic‐ultramafic intrusives), was considered. Closure temperatures calculated for the lherzolites using slow (TREE‐Y) and fast diffusing (TCa‐in‐Opx, TBKN, TCa‐in‐Ol, TOl‐Sp) geothermometers provide some of the highest values ever documented for ophiolitic peridotites, akin to modern sub‐oceanic mantle. Cooling rates deduced from TREE‐Y and TBKN yield values of ≈10−3°C/y, similar to those obtained with TCa‐in‐Ol. These features are consistent with a post‐melting history of emplacement, possibly along a transform fault, and thermal re‐equilibration via conduction. Cpx‐free harzburgites register a high‐T evolution, followed by quenching and obduction. The relatively high TCa‐in‐Ol, TOl‐Sp and cooling rates computed from TCa‐in‐Ol (≈10−3°C/y) are atypical for this geodynamic setting, mirroring the development of an ephemeral subduction system, uplift and emplacement of the Peridotite Nappe. Temperature profiles across the crust‐mantle transect point to high closure temperatures, with limited variations with depth. These results are indicative of injection and crystallization of non‐cogenetic magma batches in the forearc lithosphere, followed by thermal re‐equilibration at rates of ≈10−4–10−3°C/y. Our study shows that the thermal conditions recorded by forearc sequences are intimately related to specific areal processes and previous lithospheric evolution. Thus, detailed sampling and exhaustive knowledge of the geological background are critical to unravel the cooling mechanisms in this geodynamic setting.

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5(me)C levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo.

Here, the authors report that exhausted HCV-specific CD8+ T cells are marked by upregulation of p53 signaling already detectable in an early phase of chronic HCV infection and by a later development of a repressive chromatin state, and show that chemical targeting of these pathways improves CD8+ T cell metabolism and antiviral function.

BackgroundTuber melanosporum, also known in the gastronomic community as "truffle", features one of the largest fungal genomes (125 Mb) with an exceptionally high transposable element (TE) and repetitive DNA content (>58%). The main purpose of DNA methylation in fungi is TE silencing. As obligate outcrossing organisms, truffles are bound to a sexual mode of propagation, which together with TEs is thought to represent a major force driving the evolution of DNA methylation. Thus, it was of interest to examine if and how T. melanosporum exploits DNA methylation to maintain genome integrity.FindingsWe performed whole-genome DNA bisulfite sequencing and mRNA sequencing on different developmental stages of T. melanosporum; namely, fruitbody ("truffle"), free-living mycelium and ectomycorrhiza. The data revealed a high rate of cytosine methylation (>44%), selectively targeting TEs rather than genes with a strong preference for CpG sites. Whole genome DNA sequencing uncovered multiple TE-enriched, copy number variant regions bearing a significant fraction of hypomethylated and expressed TEs, almost exclusively in free-living mycelium propagated in vitro. Treatment of mycelia with 5-azacytidine partially reduced DNA methylation and increased TE transcription. Our transcriptome assembly also resulted in the identification of a set of novel transcripts from 614 genes.ConclusionsThe datasets presented here provide valuable and comprehensive (epi)genomic information that can be of interest for evolutionary genomics studies of multicellular (filamentous) fungi, in particular Ascomycetes belonging to the subphylum, Pezizomycotina. Evidence derived from comparative methylome and transcriptome analyses indicates that a non-exhaustive and partly reversible methylation process operates in truffles.

BackgroundWe investigated how an extremely transposon element (TE)-rich organism such as the plant-symbiotic ascomycete truffle Tuber melanosporum exploits DNA methylation to cope with the more than 45,000 repeated elements that populate its genome.ResultsWhole-genome bisulfite sequencing performed on different developmental stages reveals a high fraction of methylated cytosines with a strong preference for CpG sites. The methylation pattern is highly similar among samples and selectively targets TEs rather than genes. A marked trend toward hypomethylation is observed for TEs located within a 1 kb distance from expressed genes, rather than segregated in TE-rich regions of the genome. Approximately 300 hypomethylated or unmethylated TEs are transcriptionally active, with higher expression levels in free-living mycelium compared to fruitbody. Indeed, multiple TE-enriched, copy number variant regions bearing a significant fraction of hypomethylated and expressed TEs are found almost exclusively in free-living mycelium. A reduction of DNA methylation, restricted to non-CpG sites and accompanied by an increase in TE expression, is observed upon treatment of free-living mycelia with 5-azacytidine.ConclusionsEvidence derived from analysis of the T. melanosporum methylome indicates that a non-exhaustive, partly reversible, methylation process operates in truffles. This allows for the existence of hypomethylated, transcriptionally active TEs that are associated with copy number variant regions of the genome. Non-exhaustive TE methylation may reflect a role of active TEs in promoting genome plasticity and the ability to adapt to sudden environmental changes.

Purpose: To investigate the [68Ga]DOTATOC PET radiomic profile of head and neck paragangliomas (HNPGLs) and identify radiomic characteristics useful as predictors of succinate dehydrogenase genes (SDHx) pathogenic variants. Methods: Sporadic and SDHx HNPGL patients, who underwent [68Ga]DOTATOC PET/CT, were retrospectively included. HNPGLs were analyzed using LIFEx software, and extracted features were harmonized to correct for batch effects and confronted testing for multiple comparison. Stepwise discriminant analysis was conducted to remove redundancy and identify best discriminating features. ROC analysis was used to define optimal cut-offs. Multivariate decision-tree analysis was performed using CHAID method. Results: 34 patients harboring 60 HNPGLs (51 SDHx in 25 patients) were included. Three sporadic and nine SDHx HNPGLs were metastatic. At stepwise discriminant analysis, both GLSZM-Zone Size Non-Uniformity (ZSNU, reflecting tumor heterogeneity) and IB-TLSRE (total lesion somatostatin receptor expression) were independent predictors of genetic status, with 96.4% of lesions and 91.6% of patients correctly classified after cross validation (p < 0.001). Among non-metastatic patients, GLSZM-ZSNU and IB-TLSRE were significantly higher in sporadic than SDHx HNPGLs (p < 0.001). No differences were revealed in metastatic patients. Decision-tree analysis highlights multifocality and IB-TLSRE as useful variables, correctly identifying 6/9 sporadic and 24/25 SDHx patients. Model failed to classify one SDHA and three sporadic patients (2 metastatic). Conclusion: Radiomics features GLSZM-ZSNU and IB-TLSRE appear to reflect HNPGLs SDHx status and tumor behavior (metastatic vs. non-metastatic). If validated, especially IB-TLSRE might represent a simple and time-efficient radiomic index for SDHx variants early screening and prediction of tumor behavior in HNPGL cases. [ABSTRACT FROM AUTHOR]

The franciscana, Pontoporia blainvillei, is an endemic dolphin off the east coast of South America and is considered the most endangered cetacean in the western South Atlantic. In the present study, we analyzed the muscle tissue of 24 franciscana dolphins found on the coast of Espírito Santo (ES) between 2010 and 2019 to investigate trophic ecology using carbon and nitrogen stable isotope analysis. In addition, 127 prey were analyzed to identify the preferred prey. The most important prey species in the diet of the franciscana dolphins were Trichiurus lepturus, Chirocentrodon bleekerianus, and Pellona harroweri. The franciscana dolphins were grouped into three subareas according to where they were collected throughout the distribution: 1 (North), 2 (Center), and 3 (South). In subarea 1, the preferred prey were Stellifer spp., Isopisthus parvipinnis, and P. harroweri, while in subareas 2 and 3, the prey were similar, changing the order of preference among them (Stellifer spp., T. lepturus, and C. bleekerianus). Finally, we identify two possible ecological groups of franciscana dolphins on the coast of ES, influenced by different carbon sources. Our results improve our understanding of the franciscana dolphin's trophic ecology and habitat use, providing new information and guidelines for species conservation in the region. [ABSTRACT FROM AUTHOR]

In this study we investigated the spatio-temporal distribution of gurnards (8 species of Triglidae and one species of Peristediidae) in the northern Mediterranean Sea using 22 years of MEDITS bottom trawl survey data (1994-2015). Gurnards showed significant differences in terms of abundance, dominance and composition among geographical sub-areas and ecoregions, with the highest relative biomass (BIy) being found in Malta, eastern Corsica, the Balearic Islands and the eastern Ionian Sea. The lowest gurnards BIy were observed in the highly exploited areas of the western Mediterranean and the Adriatic Sea, where the largest number of species with a negative linear trend in BIy was also found. The temporal trends in species abundances highlighted a general decrease for the coastal species (C. lucerna, C. lastoviza, C. obscurus) as compared with the species inhabiting the deep continental shelf and slope (T. lyra, P. cataphractum). The results provide for the first time an overview of the spatiotemporal trend in the abundance of gurnards over the wide spatial scale of the northern Mediterranean Sea, also suggesting the possible use of these species as indicators for monitoring the impact of fishing pressure on demersal fish assemblages.

Bacterial resistance represents a major health problem worldwide and there is an urgent need to develop first-in-class compounds directed against new therapeutic targets. We previously developed a drug-discovery platform to identify new antimicrobials able to disrupt the protein–protein interaction between the β’ subunit and the σ70 initiation factor of bacterial RNA polymerase, which is essential for transcription. As a follow-up to such work, we have improved the discovery strategy to make it less time-consuming and more cost-effective. This involves three sequential assays, easily scalable to a high-throughput format, and a subsequent in-depth characterization only limited to hits that passed the three tests. This optimized workflow, applied to the screening of 5360 small molecules from three synthetic and natural compound libraries, led to the identification of six compounds interfering with the β’–σ70 interaction, and thus was capable of inhibiting promoter-specific RNA transcription and bacterial growth. Upon supplementation with a permeability adjuvant, the two most potent transcription-inhibiting compounds displayed a strong antibacterial activity against Escherichia coli with minimum inhibitory concentration (MIC) values among the lowest (0.87–1.56 μM) thus far reported for β’–σ PPI inhibitors. The newly identified hit compounds share structural feature similarities with those of a pharmacophore model previously developed from known inhibitors.