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In the terrestrial isopod Armadillidium vulgare, many females produce progenies with female-biased sex ratios due to two feminizing sex ratio distorters (SRD): Wolbachia endosymbionts and a nuclear non-mendelian locus called the f element. To investigate the potential impact of these SRD on the evolution of host sex determination, we analyzed their temporal distribution in six A. vulgare populations sampled between 2003 and 2017, for a total of 29 time points. SRD distribution was heterogeneous among populations despite their close geographic locations, so that when one SRD was frequent in a population, the other SRD was rare. In contrast with spatial heterogeneity, our results overall did not reveal substantial temporal variability in SRD prevalence within populations, suggesting equilibria in SRD evolutionary dynamics may have been reached or nearly so. Temporal stability was also generally reflected in mitochondrial and nuclear variation. Nevertheless, in a population, a Wolbachia strain replacement coincided with changes in mitochondrial composition but no change in nuclear composition, thus constituting a typical example of mitochondrial sweep caused by endosymbiont rise in frequency. Rare incongruence between Wolbachia strains and mitochondrial haplotypes suggested the occurrence of intraspecific horizontal transmission, making it a biologically relevant parameter for Wolbachia evolutionary dynamics in A. vulgare. Overall, our results provide an empirical basis for future studies on SRD evolutionary dynamics in the context of multiple sex determination factors co-existing within a single species, to ultimately evaluate the impact of SRD on the evolution of host sex determination mechanisms and sex chromosomes.
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The crayfish plague pathogen Aphanomyces astaci has been implicated in a number of mass mortalities and irreversible population declines of native crayfish across Europe. At present, the reservoirs of the pathogen in Europe are mainly populations of invasive North American crayfish species. In southwestern Europe, including France, a particularly widespread invader is the red swamp crayfish Procambarus clarkii. Recent distribution data confirm that P. clarkii is present in at least 75 French departments, i.e. more than 78% of those in metropolitan France. We analysed the prevalence and pathogen load of A. astaci in 42 populations of this species in western France (Nouvelle Aquitaine region), where the species is most densely distributed, particularly in a wide range of environments around the Gironde estuary. The pathogen was detected by two different quantitative PCR assays in more than three quarters of the populations studied (34 out of 42); 163 out of 480 analysed crayfish individuals tested positive for the presence of A. astaci. In most cases, individual infection levels were very low, detectable with quantitative PCR but not sufficient for pathogen genotyping. In seven P. clarkii individuals from four populations, however, we were able to assess A. astaci variation by microsatellite markers and sequencing of mitochondrial markers. All these host specimens carried A. astaci genotype group D, haplotype d1, which has caused the majority of crayfish plague outbreaks in neighbouring Spain. In contrast, the French outbreaks genotyped to date (including eight newly analysed in this study) were mostly caused by strains of genotype group B, specific to the signal crayfish Pacifastacus leniusculus. Haplotype d1 found in P. clarkii was involved in one of the newly characterised outbreaks. Our study confirms that P. clarkii is a potentially important reservoir of the crayfish plague pathogen in France, but not the main source of the pathogen in mass mortalities of A. pallipes, probably due to different ecological requirements of the different invasive host crayfish. However, as P. clarkii continues to spread, the threat posed by this species to native crayfish is likely to increase.
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Aphanomyces , Astacoidea , Animales , Astacoidea/microbiología , Aphanomyces/genética , Aphanomyces/fisiología , Francia/epidemiología , Prevalencia , Especies Introducidas , BlancoRESUMEN
The pace of biological invasions has increased in recent decades, leading to multiple invasions and the potential dominance of invasive species, destabilizing local ecological networks. This provides opportunities to study new ecological species interactions, including predation. Tropical freshwaters have been particularly concerned by aquatic invasions and we focused here on the Martinique island (Lesser Antilles). We examined the predator-prey relationships involving invasive Thiarid snails (Tarebia granifera and Melanoides tuberculata) and the native Neritina punctulata, both confronted with a newcomer predator, the redclaw crayfish (Cherax quadricarinatus). We conducted several mesocosm experiments to assess the impact of crayfish predation on snail survival and the passive and active antipredator responses of snails. A first experiment indicated snail survival rates between 50% and 80%, depending on crayfish size and sex. Notably, there was a negative correlation between snail survival and male crayfish size and the predation method (shell crushing vs. "body sucking") varied with crayfish size. The second experiment suggested no refuge size for snails, with both very small (<5 mm) and very large (>5 mm) unable to escape predation, regardless of crayfish size (from 77 to 138 mm) or sex. Finally, we investigated the escape behavior of Thiarids regarding three crayfish cues. Melanoides tuberculata tend to bury in the substrate and T. granifera to climb up aquarium walls, what was expected from their shell morphologies, and both responding to crayfish cues within minutes. Overall, C. quadricarinatus proves to be an efficient snail predator with limited escape options for snails, potentially contributing to the decline of certain snail populations in Martinique. This omnivorous predator might impact other native species across different groups, including shrimps and fish. Our study underscores the urgent need for monitoring efforts, solidifying the redclaw crayfish reputation as a dangerous invasive species for freshwater macrobenthic faunas worldwide.
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The ARID1A and ARID1B subunits are mutually exclusive components of the BAF variant of SWI/SNF chromatin remodeling complexes. Loss of function mutations in ARID1A are frequently observed in various cancers, resulting in a dependency on the paralog ARID1B for cancer cell proliferation. However, ARID1B has never been targeted directly, and the high degree of sequence similarity to ARID1A poses a challenge for the development of selective binders. In this study, we used mRNA display to identify peptidic ligands that bind with nanomolar affinities to ARID1B and showed high selectivity over ARID1A. Using orthogonal biochemical, biophysical, and chemical biology tools, we demonstrate that the peptides engage two different binding pockets, one of which directly involves an ARID1B-exclusive cysteine that could allow covalent targeting by small molecules. Our findings impart the first evidence of the ligandability of ARID1B, provide valuable tools for drug discovery, and suggest opportunities for the development of selective molecules to exploit the synthetic lethal relationship between ARID1A and ARID1B in cancer.
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Proteínas de Unión al ADN , Péptidos , ARN Mensajero , Factores de Transcripción , Humanos , Ligandos , Péptidos/química , Péptidos/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , Unión Proteica , Sitios de UniónRESUMEN
INTRODUCTION: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. MATERIALS AND METHODS: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. RESULTS: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. CONCLUSION: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.
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Land managers must find a compromise between rapidly changing landscapes and biodiversity conservation through ecological networks. Estimating ecological networks is a key approach to enhance or maintain functional connectivity by identifying the nodes and links of a graph, which represent habitats and their corresponding functional corridors, respectively. To understand the current state of biodiversity, it is necessary to consider dynamic landscape connectivity while relying on relevant land cover maps. Although a current land cover map is relatively easy to produce using existing data, this is challenging for past landscapes. Here we investigated the impact of changes in landscape connectivity in an urban landscape at a fine scale on the habitat availability of two bird species: the tree pipit Anthus trivialis and the short-toed treecreeper Certhia brachydactyla. These species, exhibiting different niche ecologies, have shown contrasting population trends at a medium-term scale. The occurrences of C. brachydactyla were better correlated with resistance values that maximise the use of corridors, whereas the occurrences of A. trivialis better fitted with intermediate resistance values. The statistical approach indirectly highlighted relevant information about the ecology the capacity of both species to use urban habitats. Landscape connectivity increased for both species over the 24-year study period and may have implications for local abundances, which could explain, at the national scale, the increase in populations of C. brachydactyla, but not the decrease in populations of A. trivialis. Thus, more attention must be paid on rural habitats and their associated species that are more impacted by human activities, but efforts could also be achieved in urban areas especially for highly corridor-dependent species. Studying dynamic landscape connectivity at a fine scale is essential for estimating past and future land cover changes and their associated impacts on ecological networks, to better reconcile human and biodiversity concerns in land management.
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Conservación de los Recursos Naturales , Ecosistema , Animales , Humanos , Biodiversidad , Aves , Actividades HumanasRESUMEN
Ornamental trade has become an important introduction pathway of non-native aquatic species worldwide. Correspondingly, there has been an alarming increase in the number of established crayfish of aquarium origin in Europe over the previous decade. The oomycete Aphanomyces astaci, the pathogen causing crayfish plague responsible for serious declines of European crayfish populations, is dispersed with introduced North American crayfish. The role of ornamental taxa in introducing and spreading different genotypes of this pathogen in open waters remains unclear. We investigated the distribution, prevalence, and diversity of A. astaci in Budapest, Hungary, which became a hotspot of aquarium crayfish introductions. Their establishment in this area was facilitated by locally abundant thermal waters. We screened for A. astaci in six host taxa from 18 sites sampled between 2018 and 2021: five cambarids (Cambarellus patzcuarensis, Faxonius limosus, Procambarus alleni, P. clarkii, P. virginalis) and one native astacid (Pontastacus leptodactylus). The pathogen was confirmed at five sampled sites in four host taxa: P. virginalis, P. clarkii, F. limosus, and for the first time in European open waters also in P. alleni. Genotyping was successful only in individuals from two different brooks where multiple host species coexisted but revealed unexpected patterns. Mitochondrial B-haplogroup of A. astaci, previously usually reported from Pacifastacus leniusculus or infected European species, was detected in P. virginalis at both sites, and in both F. limosus and P. virginalis sampled from a thermally stable tributary of Barát brook in 2018. In contrast, A-haplogroup of A. astaci was detected in coexisting F. limosus, P. virginalis and P. clarkii sampled in the same watercourse just a few hundred meters downstream in 2020. Additional genotyping methods indicated that a previously unknown A. astaci strain was associated with the latter haplogroup. One P. virginalis individual from 2020 was apparently co-infected by strains representing both mitochondrial haplogroups. The results indicated multiple sources of A. astaci in Budapest, likely directly associated with the introduction of ornamental species, interspecific transmission of this pathogen among ornamental hosts, and potential for a quick spatial or temporal turnover of dominant A. astaci strains at a certain locality. This highlights that in regions with high richness of potential A. astaci hosts, host taxon/pathogen genotype combinations become unpredictable, which might prevent reliable genotyping of pathogen sources in local crayfish mass mortalities.
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Aphanomyces , Astacoidea , Humanos , Animales , Aphanomyces/genética , Europa (Continente) , Genotipo , Técnicas de GenotipajeRESUMEN
The land cover data presented here is a reconstruction of the past landscape (1993) at Very High Resolution (VHR) for the city of Poitiers, France. This reconstruction is based on multiple sources of images and data. We combined the strengths of both mono-temporal and multi-temporal classifications. Orthophotos were created at a spatial resolution of 0.5 m using aerial raw images from the French National Geographic Institute (IGN), taken during two aerial missions in July and August 1993. These orthophotos were merged at a spatial resolution of 5 m to conduct a first object-based classification using Landsat-5 TM images. The goal was to identify croplands, grasslands, coniferous and deciduous forests, urban areas, water bodies, and shadows. This learning-based classification employed a dataset consisting of 1371 polygons and demonstrated strong classification performances, achieving an overall accuracy of 86.31% and a kappa index of 0.832. On the other hand, mono-temporal classifications at a 0.5 m spatial resolution were carried out on each orthophoto to extract trees and herbaceous vegetation, especially in urban contexts. As mono-temporal classifications contained less information, we used a larger number of polygons for the learning step: 3849 and 5173 polygons for the northern and southern classifications, respectively. The segmentation step performed better in urban areas compared to rural areas. Consequently, the performance of classifications was evaluated separately for both contexts. Urban areas exhibited excellent performances, achieving kappa indices of 0.897 and 0.881 for the northern and southern classifications, respectively, whereas only tree vegetation was accurately detected in rural areas. To compensate for the lack of information such as buildings, railways, or roads, we modified the BD Topoâ dataset from IGN. This land cover map provides highly detailed information, facilitating the understanding of urban sprawl and changes in urban and rural vegetation surrounding the city of Poitiers. Due to these reasons, this freely accessible map can be utilized by researchers, land managers, and private companies for addressing urban and ecological challenges.
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OBJECTIVE: In Belgium there is no centralization of surgery for ovarian cancer, with more than 100 centers treating around 800 cases per year. In 2017 a network with several collaborating hospitals was established to centralize surgery for ovarian cancer (UCLouvain Network of Gynecological Oncology; UNGO) following publication of the European Society of Gynecological Oncology (ESGO) recommendations and quality criteria for surgery of advanced ovarian cancer. We obtained ESGO accreditation in 2019. METHODS: We retrospectively collected data associated with patients undergoing surgery in our institution from 2007 to 2016, before the creation of the network (cohort 1) and, following the establishment of UNGO (2017-2021), patients undergoing surgery were prospectively registered in a REDCap database (cohort 2). The outcomes of the two cohorts were compared. RESULTS: A total of 314 patients underwent surgery in our institution from 2007 and 2021: 7.5 patients/year in cohort 1 (retrospective, 2007-2016) and 40.8 patients/year in cohort 2 (after network creation, 2017-2021). Median disease-free survival was increased from 16.5 months (range 13.2-20.4) in cohort 1 to 27.1 months (range 21.5-33.2) in cohort 2 (p=0.0004). In cohort 2, the rate of patients with residual disease at the end of the surgery was significantly less (18.7% vs 8.8%, p=0.023), although more patients in cohort 1 received neoadjuvant chemotherapy (89% vs 54%, p<0.001). However, there was a higher rate of complications in the patients in cohort 2 (18.8% vs 30%, p=0.041). CONCLUSION: Our study shows that, with the help of ESGO and its recommendations, we have been able to create an efficient advanced ovarian cancer centralized network and this may provide an improvement in the quality of care.
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In the isopod Armadillidium vulgare, many females produce progenies with female-biased sex ratios, owing to two feminizing sex ratio distorters (SRD): Wolbachia endosymbionts and the f element. We investigated the distribution and population dynamics of these SRD and mitochondrial DNA variation in 16 populations from Europe and Japan. Confirming and extending results from the 1990s, we found that the SRD are present at variable frequencies in populations and that the f element is overall more frequent than Wolbachia. The two SRD never co-occur at high frequency in any population, suggesting an apparent mutual exclusion. We also detected Wolbachia or the f element in some males, which probably reflects insufficient titer to induce feminization or presence of masculinizing alleles. Our results are consistent with a single integration event of a Wolbachia genome in the A. vulgare genome at the origin of the f element, which contradicts an earlier hypothesis of frequent losses and gains. We identified strong linkage between Wolbachia strains and mitochondrial haplotypes, but no association between the f element and mitochondrial background. Our results open new perspectives on SRD evolutionary dynamics in A. vulgare, the evolution of genetic conflicts and their impact on the variability of sex determination systems.
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Isópodos , Wolbachia , Masculino , Animales , Femenino , Isópodos/genética , Razón de Masculinidad , Haplotipos , Europa (Continente) , Japón , Wolbachia/genéticaRESUMEN
Minnows of the genus Phoxinus are common and an often highly abundant fish species in Palearctic freshwater habitats. Phoxinus species have a complex evolutionary history, phylogenetic relationships are not well understood and there are a number of unresolved taxonomic problems. There are currently 23 different mitochondrial genetic lineages identified in the genus Phoxinus, 13 of which are recognized as valid species. The taxonomic status of these lineages requires resolution, including the degree to which they can interbreed. Suitable nuclear molecular markers for studies of population divergence and interbreeding between morphotypes and mitochondrial lineages are lacking for Phoxinus species. Therefore, the authors developed a set of microsatellite markers using genomic information from Phoxinus lumaireul and tested their suitability for this and two related species, Phoxinus krkae and Phoxinus marsilii. Out of 16 microsatellite candidate loci isolated, 12 were found to be in Hardy-Weinberg equilibrium when tested on two P. lumaireul senso lato populations. Seven loci amplified across the three species, enabling the study of intraspecific genetic diversity and population structure within P. marsilii and P. krkae. The markers were able to clearly resolve differences among the three tested species, including the recently described P. krkae, and are therefore suitable for the detection of introgression and hybridization among populations consisting of mixtures of two or more of P. lumaireul s. l., P. marsilii and P. krkae.
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Cyprinidae , Cipriniformes , Animales , Filogenia , Cipriniformes/genética , Repeticiones de Microsatélite , Cyprinidae/genética , Genes MitocondrialesRESUMEN
Pioneering investigations on the effects of introduced populations on community structure, ecosystem functioning and services have focused on the effects of invaders on taxonomic diversity. However, taxonomic-based diversity metrics overlook the heterogeneity of species roles within and among communities. As the homogenizing effects of biological invasions on community and ecosystem processes can be subtle, they may require the use of functional diversity indices to be properly evidenced. Starting from the listing of major functional diversity indices, alongside the presentation of their strengths and limitations, we focus on studies pertaining to the effects of invasive species on native communities and recipient ecosystems using functional diversity indices. By doing so, we reveal that functional diversity of the recipient community may strongly vary at the onset of the invasion process, while it stabilizes at intermediate and high levels of invasion. As functional changes occurring during the lag phase of an invasion have been poorly investigated, we show that it is still unknown whether there are consistent changes in functional diversity metrics that could indicate the end of the lag phase. Thus, we recommend providing information on the invasion stage under consideration when computing functional diversity metrics. For the existing literature, it is also surprising that very few studies explored the functional difference between organisms from the recipient communities and invaders of the same trophic levels, or assessed the effects of non-native organism establishment into a non-analogue versus an analogue community. By providing valuable tools for obtaining in-depth diagnostics of community structure and functioning, functional diversity indices can be applied for timely implementation of restoration plans and improved conservation strategies. To conclude, our work provides a first synthetic guide for their use in hypothesis testing in invasion biology.
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Ecosistema , Especies Introducidas , Biodiversidad , Proyectos de InvestigaciónRESUMEN
The newly described horned iguanaIguanainsularis from the southern Lesser Antilles is separated in two easily recognized subspecies: I.insularissanctaluciae from St. Lucia and I.insularisinsularis from the Grenadines. Its former description is completed by the use of 38 new samples for genetic and morphological analysis. Seventeen microsatellites were used to estimate genetic diversity, population structure and the level of introgression with other Iguana species over nearly the whole range of the species. ND4 and PAC sequences were also used to better characterize hybridization and to complete the description of this lineage. The I.insularis population of St. Vincent shows a high level of introgression from I.iguana whereas in the Grenadines, most islands present pure insularis populations but several show evidence of introgressions. Of the two remaining populations of I.insularissanctaluciae, only one is still purebred. The recent identification of this and other distinct insular species and subspecies in the eastern Caribbean, and evaluation of where hybridization has occurred, are timely and important because the native iguanas are in urgent need of conservation action. Among the greatest threats is the ongoing human-mediated spread of invasive iguanas from Central and South America, which are destroying the endemic insular lineages through multiple diachronic introgression events.
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The redclaw crayfish, Cherax quadricarinatus, was introduced to Martinique Island for aquaculture purposes at the beginning of the 21st century, in an attempt to revitalize the freshwater crustacean aquaculture sector. Mainly due to its high economical value, it was intentionally released in the wild and was caught and sold by fishermen. Martinican rivers are polluted by chlordecone, considered as one of the worst Persistant Organic Pollutants (POP). Despite its dangerousness, it was used until 1993 in the French West Indies against a banana pest and was always found in the ecosystems. This study aimed to investigate the level of contamination in the muscle of crayfish caught in the wild, as well as the potential of bioconcentration and depuration in the C. quadricarinatus muscle. This study could allow us to quantify the risk for consumers but also, to evaluate a depuration process to reduce the risk related to its consumption. Using both in-vitro and in-situ experiments, results highlighted the importance of the chlordecone concentration in the water and the time of exposure to the pollutant. The bioconcentration seems to be very quick and continuous in crayfish muscle, as chlordecone can be detectable as early as 6 h of exposure, whatever the concentration tested. Finally, it appears that, even after 20 days of depuration in chlordecone-free water, chlordecone concentrations remained higher to the residual maximum limit (i.e. 20 ng/g wet weight), concluding that the decontamination of the muscle seems not very efficient, and the risk for the Martinican people could be serious.
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Clordecona , Insecticidas , Animales , Astacoidea , Bioacumulación , Clordecona/análisis , Ecosistema , Humanos , Insecticidas/análisis , MartinicaRESUMEN
BACKGROUND: The noble crayfish (Astacus astacus) is a native European species in decline, with a contracting range and diminishing populations and abundance. Previous studies revealed this species significant genetic diversity in the south-eastern Europe, with populations from the western and the southern part of the Balkan Peninsula being the most divergent. However, sampling of populations from the western part of the Balkans was limited and insufficient for investigating genetic diversity and population divergence for the purpose of conservation planning and management. Thus, the major aim of this study was to fill in this knowledge gap by studying mitochondrial and microsatellite DNA diversity, using 413 noble crayfish from 18 populations from waterbodies in the western part of the Balkan Peninsula. METHODS: Phylogenetic analysis of studied populations and their mitochondrial diversity were studied using COI and 16S sequences and population genetic structure was described using 15 microsatellite loci. RESULTS: Phylogeographic analysis revealed new divergent mitochondrial haplotypes for the populations in the westernmost part of the Balkan Peninsula in the tributaries of the Sava and Drava rivers. Microsatellite data indicated that these populations harbour an important component of genetic diversity within A. astacus. The results suggest that the western part of the Balkans played an important role as microrefugia during the Pleistocene climate fluctuations, allowing the long term persistence of A. astacus populations in this region. These results will also be important to supporting conservation decision making and planning.
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We announce the draft genome sequences of two pathogenic microsporidia of European freshwater crustaceans, Thelohania contejeani (the causative agent of porcelain disease) and Cucumispora dikerogammari Both species are implicated in mass mortalities in natural populations of their crayfish and amphipod hosts, respectively.
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Although most acute skin wounds heal rapidly, non-healing skin ulcers represent an increasing and substantial unmet medical need that urgently requires effective therapeutics. Keratinocytes resurface wounds to re-establish the epidermal barrier by transitioning to an activated, migratory state, but this ability is lost in dysfunctional chronic wounds. Small-molecule regulators of keratinocyte plasticity with the potential to reverse keratinocyte malfunction in situ could offer a novel therapeutic approach in skin wound healing. Utilizing high-throughput phenotypic screening of primary keratinocytes, we identify such small molecules, including bromodomain and extra-terminal domain (BET) protein family inhibitors (BETi). BETi induce a sustained activated, migratory state in keratinocytes in vitro, increase activation markers in human epidermis ex vivo and enhance skin wound healing in vivo. Our findings suggest potential clinical utility of BETi in promoting keratinocyte re-epithelialization of skin wounds. Importantly, this novel property of BETi is exclusively observed after transient low-dose exposure, revealing new potential for this compound class.
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Proteínas de Ciclo Celular/genética , Epidermis/efectos de los fármacos , Repitelización/efectos de los fármacos , Úlcera Cutánea/tratamiento farmacológico , Bibliotecas de Moléculas Pequeñas/farmacología , Factores de Transcripción/genética , Heridas no Penetrantes/tratamiento farmacológico , Animales , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Modelos Animales de Enfermedad , Epidermis/metabolismo , Epidermis/patología , Transferencia Resonante de Energía de Fluorescencia , Regulación de la Expresión Génica , Ensayos Analíticos de Alto Rendimiento , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Cultivo Primario de Células , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Precursores de Proteínas/antagonistas & inhibidores , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Repitelización/genética , Úlcera Cutánea/genética , Úlcera Cutánea/metabolismo , Úlcera Cutánea/patología , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Transcripción Genética , Heridas no Penetrantes/genética , Heridas no Penetrantes/metabolismo , Heridas no Penetrantes/patologíaRESUMEN
Cherax destructor, the yabby, is an iconic Australian freshwater crayfish species, which, similar to other major invertebrate groups, is grossly under-represented in genomic databases. The yabby is also the principal commercial freshwater crustacean species in Australia subject to explotation via inland fisheries and aquaculture. To address the genomics knowledge gap for this species and explore cost effective and efficient methods for genome assembly, we generated 106.8 gb of Nanopore reads and performed a long-read only assembly of the Cherax destructor genome. On a mini-server configured with an ultra-fast swap space, the de novo assembly took 131 h (â¼5.5 days). Genome polishing with 126.3 gb of PCR-Free Illumina reads generated an assembled genome size of 3.3 gb (74.6% BUSCO completeness) with a contig N50 of 80,900 bp, making it the most contiguous for freshwater crayfish genome assemblies. We found an unusually large number of cellulase genes within the yabby genome which is relevant to understanding the nutritional biology, commercial feed development, and ecological role of this species and crayfish more generally. These resources will be useful for genomic research on freshwater crayfish and our methods for rapid and super-efficient genome assembly will have wide application.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Biosynthesis of glycosylphosphatidylinositol (GPI) is required for anchoring proteins to the plasma membrane, and is essential for the integrity of the fungal cell wall. Here, we use a reporter gene-based screen in Saccharomyces cerevisiae for the discovery of antifungal inhibitors of GPI-anchoring of proteins, and identify the oligocyclopropyl-containing natural product jawsamycin (FR-900848) as a potent hit. The compound targets the catalytic subunit Spt14 (also referred to as Gpi3) of the fungal UDP-glycosyltransferase, the first step in GPI biosynthesis, with good selectivity over the human functional homolog PIG-A. Jawsamycin displays antifungal activity in vitro against several pathogenic fungi including Mucorales, and in vivo in a mouse model of invasive pulmonary mucormycosis due to Rhyzopus delemar infection. Our results provide a starting point for the development of Spt14 inhibitors for treatment of invasive fungal infections.