192 research outputs found

    On the evolution of elastic properties during laboratory stick-slip experiments spanning the transition from slow slip to dynamic rupture

    Get PDF
    The physical mechanisms governing slow earthquakes remain unknown, as does the relationship between slow and regular earthquakes. To investigate the mechanism(s) of slow earthquakes and related quasi-dynamic modes of fault slip we performed laboratory experiments on simulated fault gouge in the double direct shear configuration. We reproduced the full spectrum of slip behavior, from slow to fast stick slip, by altering the elastic stiffness of the loading apparatus (k) to match the critical rheologic stiffness of fault gouge (kc). Our experiments show an evolution from stable sliding, when k>kc, to quasi-dynamic transients when k ~ kc, to dynamic instabilities when k<kc. To evaluate the microphysical processes of fault weakening we monitored variations of elastic properties. We find systematic changes in P wave velocity (Vp) for laboratory seismic cycles. During the coseismic stress drop, seismic velocity drops abruptly, consistent with observations on natural faults. In the preparatory phase preceding failure, we find that accelerated fault creep causes a Vp reduction for the complete spectrum of slip behaviors. Our results suggest that the mechanics of slow and fast ruptures share key features and that they can occur on same faults, depending on frictional properties. In agreement with seismic surveys on tectonic faults our data show that their state of stress can be monitored by Vp changes during the seismic cycle. The observed reduction in Vp during the earthquake preparatory phase suggests that if similar mechanisms are confirmed in nature high-resolution monitoring of fault zone properties may be a promising avenue for reliable detection of earthquake precursors

    MAPK15 controls cellular responses to oxidative stress by regulating NRF2 activity and expression of its downstream target genes

    Get PDF
    Oxidation processes in mitochondria and different environmental insults contribute to unwarranted accumulation of reactive oxygen species (ROS). These, in turn, rapidly damage intracellular lipids, proteins, and DNA, ultimately causing aging and several human diseases. Cells have developed different and very effective systems to control ROS levels. Among these, removal of excessive amounts is guaranteed by upregulated expression of various antioxidant enzymes, through activation of the NF-E2-Related Factor 2 (NRF2) protein. Here, we show that Mitogen Activated Protein Kinase 15 (MAPK15) controls the transactivating potential of NRF2 and, in turn, the expression of its downstream target genes. Specifically, upon oxidative stress, MAPK15 is necessary to increase NRF2 expression and nuclear translocation, by inducing its activating phosphorylation, ultimately supporting transactivation of cytoprotective antioxidant genes. Lungs are continuously exposed to oxidative damages induced by environmental insults such as air pollutants and cigarette smoke. Interestingly, we demonstrate that MAPK15 is very effective in supporting NRF2-dependent antioxidant transcriptional response to cigarette smoke of epithelial lung cells. Oxidative damage induced by cigarette smoke indeed represents a leading cause of disability and death worldwide by contributing to the pathogenesis of different chronic respiratory diseases and lung cancer. Therefore, the development of novel therapeutic strategies able to modulate cellular responses to oxidative stress would be highly beneficial. Our data contribute to the necessary understanding of the molecular mechanisms behind such responses and identify new potentially actionable targets

    Reduced miR-184-3p expression protects pancreatic β-cells from lipotoxic and proinflammatory apoptosis in type 2 diabetes via CRTC1 upregulation

    Get PDF
    The loss of functional beta-cell mass in type 2 diabetes (T2D) is associated with molecular events that include beta-cell apoptosis, dysfunction and/or dedifferentiation. MicroRNA miR-184-3p has been shown to be involved in several beta-cell functions, including insulin secretion, proliferation and survival. However, the downstream targets and upstream regulators of miR-184-3p have not been fully elucidated. Here, we show reduced miR-184-3p levels in human T2D pancreatic islets, whereas its direct target CREB regulated transcription coactivator 1 (CRTC1) was increased and protects beta-cells from lipotoxicity- and inflammation-induced apoptosis. Downregulation of miR-184-3p in beta-cells leads to upregulation of CRTC1 at both the mRNA and protein levels. Remarkably, the protective effect of miR-184-3p is dependent on CRTC1, as its silencing in human beta-cells abrogates the protective mechanism mediated by inhibition of miR-184-3p. Furthermore, in accordance with miR-184-3p downregulation, we also found that the beta-cell-specific transcription factor NKX6.1, DNA-binding sites of which are predicted in the promoter sequence of human and mouse MIR184 gene, is reduced in human pancreatic T2D islets. Using chromatin immunoprecipitation analysis and mRNA silencing experiments, we demonstrated that NKX6.1 directly controls both human and murine miR-184 expression. In summary, we provide evidence that the decrease in NKX6.1 expression is accompanied by a significant reduction in miR-184-3p expression and that reduction of miR-184-3p protects beta-cells from apoptosis through a CRTC1-dependent mechanism

    Baseline genetic distinctiveness supports structured populations of thornback ray in the Mediterranean Sea

    Get PDF
    The thornback ray (Raja clavata) is the most important chondrichthyan in terms of landings in the Mediterranean Sea. Intense harvesting may induce negative genetic effects reducing the resilience of overfished species. For this reason, genetic diversity information should be considered in fisheries management and conservation policies. Microsatellite markers were used to unravel the genetic features (variability, connectivity, sex-biased dispersal) of R. clavata populations, both at the small (around the coast of Sardinia, western Mediterranean Sea) and larger spatial scales (at the pan-Mediterranean level, and between the Atlantic Ocean and the Mediterranean Sea). Individual clustering, multivariate and variance analyses rejected the hypothesis of genetic homogeneity, with significant genetic differences between Mediterranean and Atlantic rays, as well as within the Mediterranean Sea between its western and eastern basins. The data indicated that both the Strait of Gibraltar and the Sicilian Channel seem to be effective in limiting the dispersal of thornback ray individuals, but a further structuring was identified, with the significant genetic differentiation of the populations located in the Algero-Provençal and Tyrrhenian basins. Such a fine-scale arrangement suggests the occurrence of additional barriers to species dispersal. A lack of significant genetic differentiation, stable over the years, was measured at a local scale among R. clavata Sardinian samples. Several possible mechanisms, both biological and abiotic (e.g. migratory behaviour, waterfronts and oceanographic discontinuities), are discussed. Overall, the genetic data presented, both at the local and regional level, could represent the baseline information for the temporal monitoring of populations and assessing the effects of present or future fisheries-related management actions. The data obtained are information of paramount importance for minimizing the gaps in our current knowledge of the genetic diversity of thornback rays and maximizing the information needed for the correct protection of R. clavata populations

    Commercial sharks under scrutiny: baseline genetic distinctiveness supports structured populations of small-spotted catsharks in the Mediterranean Sea

    Get PDF
    The present study, based on microsatellite markers, describes a population genetic analysis of the small-spotted catshark Scyliorhinus canicula (Linnaeus, 1758), representing one of the most abundant and commonly caught cartilaginous fishes in the Mediterranean Sea and adjacent areas. The analyses were performed to unravel the genetic features (variability, connectivity, sex-biased dispersal) of their relative geographic populations, both at the small (around the coast of Sardinia, Western Mediterranean Sea) and at a larger spatial scale (pan-Mediterranean level and between the Atlantic Ocean and the Mediterranean Sea). Individual clustering, multivariate and variance analyses rejected the hypothesis of genetic homogeneity, with significant genetic differences between the Mediterranean and Atlantic, as well as within the Mediterranean area between the Western and Eastern basins. In details, our results seem to confirm that the Strait of Gibraltar could not represent a complete barrier to the exchange of individuals of small-spotted catshark between the Atlantic Ocean and the Mediterranean Sea. In the latter area, a complex genetic structuring for S. canicula was found. Apart from differences among the Western, Eastern and Adriatic sites, within the Western basin the small-spotted catsharks around Sardinian waters are strongly differentiated from all others (both from the eastern Tyrrhenian Sea and southernmost part of the Algerian basin) and are demographically stable. Several possible mechanisms, both biological and abiotic (e.g., migratory behavior, water fronts and oceanographic discontinuities), are discussed here to explain their peculiar characteristics. Overall, the genetic data presented, both at the local and regional level, could represent a baseline information, useful for the temporal monitoring of populations, and to assess the effects of present or future fishing/management/conservation measures

    Dimerization of the C-type lectin-like receptor CD93 promotes its binding to Multimerin-2 in endothelial cells

    Get PDF
    Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies

    Strongly structured populations and reproductive habitat fragmentation increase the vulnerability of the Mediterranean starry ray Raja asterias (Elasmobranchii, Rajidae)

    Get PDF
    1. The Mediterranean starry ray (Raja asterias) populations within the Mediterranean Sea are susceptible to high rates of bycatch in the multispecies trawl fisheries. Understanding its population structure and identifying critical habitats are crucial for assessing species vulnerability and setting the groundwork for specific management measures to prevent population decline. 2. To assess the population structure of R. asterias in the Mediterranean, the genetic variation in nine population samples at one mitochondrial marker and eight nuclear microsatellite loci was analysed. Moreover, 172 egg cases collected in the Strait of Sicily were identified at species level using integrated molecular and morphological approaches. 3. Genetic analyses revealed that the Mediterranean starry ray comprises three distinct units inhabiting the western, the central-western, and the central-eastern areas of the Mediterranean. An admixture zone occurs in the Strait of Sicily and the Ionian Sea, where individuals of the central-western and central-eastern population units intermingle. 4. The joint morphometric–genetic analyses of rajid egg cases confirmed the presence of more than one species in the admixture area, with a predominance of egg cases laid by R. asterias. DNA barcoding revealed that egg cases and embryos of R. asterias shared several haplotypes with adult individuals from the centralwestern and central-eastern Mediterranean Sea, revealing that females of both populations laid numerous eggs in this area. 5. According to these findings, detailed taxonomic determination of egg cases, when combined with seasonal migration studies, could improve the capability to identify important spawning or nursery areas for the Mediterranean starry ray, particularly in those admixture zones relevant to maintaining genetic diversity. 6. Finally, these new insights should be considered to update the Action Plan for the Conservation of Cartilaginous Fishes in the Mediterranean Sea with effective measures to reduce the impact of skate bycatch in trawling and safeguard egg cases in nursery areas

    La presa in carico della persona anziana vittima di maltrattamento: analisi del fenomeno in due contesti di emergenza di Regione Lombardia

    Get PDF
    BACKGROUND: Il maltrattamento della persona anziana è un fenomeno sottostimato, rappresenta una violazione dei diritti umani e un grave problema di salute globale che espone le vittime a pesanti conseguenze per la salute. Si stima che nei prossimi decenni le violenze sugli anziani siano destinate a crescere. OBIETTIVO: Indagare l’esperienza degli Infermieri del Pronto Soccorso di due contesti ospedalieri riguardo alla violenza contro gli anziani. METODI: È stata condotta un’indagine somministrando un questionario costruito partendo da un precedente studio realizzato dall’Università degli studi di Urbino. È stato selezionato un campione di convenienza sul gruppo di Infermieri afferenti alle due strutture regionali di Pronto Soccorso. RISULTATI: Sono stati reclutati 117 Infermieri, 41 (35%) hanno risposto al questionario. La forma di violenza maggiormente riscontrata è la negligenza, seguita da violenza psicologica, fisica, economica e sessuale. Età avanzata e non autosufficienza sono stati riconosciuti come fattori di rischio predisponenti alla violenza; mentre sembra che appartenere al genere femminile non predisponga ad agiti annoverabili come violenza. Tra gli autori del maltrattamento la vicinanza abitativa o affettiva sono elementi da considerare predisponenti; i familiari intimi o i caregiver sono spesso autori del reato. Appare significativa la percentuale degli operatori socio- sanitari (4%). CONCLUSIONI: La violenza e il maltrattamento contro la persona anziana sono argomenti poco esplorati, talvolta considerati una problematica assistenziale piuttosto che una riflessione della Comunità Scientifica Infermieristica. Risulta indispensabile adeguare i programmi formativi ai vari livelli in quest’ambito e sviluppare un modello di presa in carico condiviso basato sulla valutazione oggettiva del rischioBACKGROUND: Elderly maltreatment is an underestimated phenomenon, represents a human rights violation and a serious global health problem that exposes victims to heavy health consequences. We estimate that violence against the elderly is likely to increase in the coming decades. AIM: To investigate the Emergency Room Nurses experiences in two hospital regarding elderly violence. METHODS: The survey was conducted by administering a questionnaire revised from an earlier study performed by the University of Urbino. A convenience sample was selected on the group of nurses attached to the two regional Emergency Room facilities. RESULTS: A total of 117 nurses were recruited, 41 (35%) responded to the questionnaire. The most frequently encountered violence form is neglect, followed by psychological, physical, economic, and sexual violence. Advanced age and non-self-sufficiency were recognized as predisposing risk factors for violence, while it appears that belonging to the female gender does not predispose to acts that can be counted as violence. Among maltreatment perpetrators, living or emotional proximity is a predisposing element; close family members or caregivers are often the crime perpetrators. The social-health workers percentage (4 percent) appears significant. CONCLUSIONS: Elderly violence and mistreatment are still under-explored topics, sometimes considered a care issue rather than a consideration to be addressed in the Nursing Scientific Community. Adapting training programs regarding the elderly violence management and the development of a shared intake model based on objective risk assessment is essential

    Call me by my name: unravelling the taxonomy of the gulper shark genus Centrophorus in the Mediterranean Sea through an integrated taxonomic approach

    Get PDF
    The current shift of fishery efforts towards the deep sea is raising concern about the vulnerability of deep-water sharks, which are often poorly studied and characterized by problematic taxonomy. For instance, in the Mediterranean Sea the taxonomy of genus Centrophorus has not been clearly unravelled yet. Since proper identification of the species is fundamental for their correct assessment and management, this study aims at clarifying the taxonomy of this genus in the Mediterranean Basin through an integrated taxonomic approach. We analysed a total of 281 gulper sharks (Centrophorus spp.) collected from various Mediterranean, Atlantic and Indian Ocean waters. Molecular data obtained from cytochrome c oxidase subunit I (COI), 16S ribosomal RNA (16S), NADH dehydrogenase subunit 2 (ND2) and a portion of a nuclear 28S ribosomal DNA gene region (28S) have highlighted the presence of a unique mitochondrial clade in the Mediterranean Sea. The morphometric results confirmed these findings, supporting the presence of a unique and distinct morphological group comprising all Mediterranean individuals. The data strongly indicate the occurrence of a single Centrophorus species in the Mediterranean, ascribable to C. cf. uyato, and suggest the need for a revision of the systematics of the genus in the area
    • …
    corecore