DNA Damage and Transcriptional Changes in the Gills of Mytilus galloprovincialis Exposed to Nanomolar Doses of Combined Metal Salts (Cd, Cu, Hg)

[ENG]Aiming at an integrated and mechanistic view of the early biological effects of selected metals in the marine sentinel organism Mytilus galloprovincialis, we exposed mussels for 48 hours to 50, 100 and 200 nM solutions of equimolar Cd, Cu and Hg salts and measured cytological and molecular biomarkers in parallel. Focusing on the mussel gills, first target of toxic water contaminants and actively proliferating tissue, we detected significant dose-related increases of cells with micronuclei and other nuclear abnormalities in the treated mussels, with differences in the bioconcentration of the three metals determined in the mussel flesh by atomic absorption spectrometry. Gene expression profiles, determined in the same individual gills in parallel, revealed some transcriptional changes at the 50 nM dose, and substantial increases of differentially expressed genes at the 100 and 200 nM doses, with roughly similar amounts of up- and down-regulated genes. The functional annotation of gill transcripts with consistent expression trends and significantly altered at least in one dose point disclosed the complexity of the induced cell response. The most evident transcriptional changes concerned protein synthesis and turnover, ion homeostasis, cell cycle regulation and apoptosis, and intracellular trafficking (transcript sequences denoting heat shock proteins, metal binding thioneins, sequestosome 1 and proteasome subunits, and GADD45 exemplify up-regulated genes while transcript sequences denoting actin, tubulins and the apoptosis inhibitor 1 exemplify down-regulated genes). Overall, nanomolar doses of co-occurring free metal ions have induced significant structural and functional changes in the mussel gills: the intensity of response to the stimulus measured in laboratory supports the additional validation of molecular markers of metal exposure to be used in Mussel Watch programsWork granted by MIUR and Co.Ri.La. to PV. LV is currently supported by the FP7-KBBE-2010-4-266157 Bivalife project. Work in the laboratory of MPC is funded by grants to consolidated research groups (ref GIC07/26-IT-393-07, Basque Government), and to the unit of formation and research (UFI ref 11/37, University of the Basque Country) and projects Nanoretox (ref CP-FP 214478-2, UE 7th FP) and Nanocancer (ref CTM2009-13477, Spanish Ministry of Science and Innovation

Interactions between diurnal winds and floodplain mosaics control the insect boundary layer in a river corridor

Insect flight along river corridors is a fundamental process that facilitates sustainable succession and diversity of aquatic and terrestrial insect communities in highly dynamic fluvial environments. This study examines variations in the thickness of the insect boundary layer (i.e., the pre-surface atmosphere layer in which air velocity does not exceed the sustained speed of flying insects) caused by interactions between diurnal winds and the heterogenous habitat mosaics in the floodplain of a braided river. Based on advective–diffusive theory, we develop and test a semi-empirical model that relates vertical flux of flying insects to vertical profiles of diurnal winds. Our model suggests that, in the logarithmic layer of wind, the density of insect fluxes decreases exponentially with the altitude due to the strong physical forcing. Inside the insect boundary layer, the insect fluxes can increase with the altitude while the winds speed remains nearly constant. We suggest a hypothesis that there is a close correspondence between the height of discontinuity points in the insect profiles (e.g. points with abrupt changes of the insect flux) and the displacement heights of the wind profiles (e.g. points above which the wind profile is logarithmic). Vertical profiles were sampled during three time-intervals at three different habitat locations in the river corridor: a bare gravel bar, a gravel bar with shrubs, and an island with trees and shrubs. Insects and wind speed were sampled and measured simultaneously over each location at 1.5-m intervals up to approximately 17 m elevation. The results support our working hypothesis on close correspondence between discontinuity and displacement points. The thickness of the insect boundary layer matches the height of the discontinuity points and was about 5 m above the bare gravel bar and the gravel bar with shrubs. Above the island, the structure of the insect boundary layer was more complex and consisted of two discontinuity points, one at the mean height of the trees’ crowns (ca. 15 m), and a second, internal boundary layer at the top of the shrubs (ca. 5 m). Our findings improve the understanding of how vegetation can influence longitudinal and lateral dispersal patterns of flying insects in river corridors and floodplain systems. It also highlights the importance of preserving terrestrial habitat diversity in river floodplains as an important driver of both biotic and abiotic (i.e., morphology and airscape) heterogeneit

Interactions between diurnal winds and floodplain mosaics control the insect boundary layer in a river corridor

Insect flight along river corridors is a fundamental process that facilitates sustainable succession and diversity of aquatic and terrestrial insect communities in highly dynamic fluvial environments. This study examines variations in the thickness of the insect boundary layer (i.e., the pre-surface atmosphere layer in which air velocity does not exceed the sustained speed of flying insects) caused by interactions between diurnal winds and the heterogenous habitat mosaics in the floodplain of a braided river. Based on advective–diffusive theory, we develop and test a semi-empirical model that relates vertical flux of flying insects to vertical profiles of diurnal winds. Our model suggests that, in the logarithmic layer of wind, the density of insect fluxes decreases exponentially with the altitude due to the strong physical forcing. Inside the insect boundary layer, the insect fluxes can increase with the altitude while the winds speed remains nearly constant. We suggest a hypothesis that there is a close correspondence between the height of discontinuity points in the insect profiles (e.g. points with abrupt changes of the insect flux) and the displacement heights of the wind profiles (e.g. points above which the wind profile is logarithmic). Vertical profiles were sampled during three time-intervals at three different habitat locations in the river corridor: a bare gravel bar, a gravel bar with shrubs, and an island with trees and shrubs. Insects and wind speed were sampled and measured simultaneously over each location at 1.5-m intervals up to approximately 17 m elevation. The results support our working hypothesis on close correspondence between discontinuity and displacement points. The thickness of the insect boundary layer matches the height of the discontinuity points and was about 5 m above the bare gravel bar and the gravel bar with shrubs. Above the island, the structure of the insect boundary layer was more complex and consisted of two discontinuity points, one at the mean height of the trees’ crowns (ca. 15 m), and a second, internal boundary layer at the top of the shrubs (ca. 5 m). Our findings improve the understanding of how vegetation can influence longitudinal and lateral dispersal patterns of flying insects in river corridors and floodplain systems. It also highlights the importance of preserving terrestrial habitat diversity in river floodplains as an important driver of both biotic and abiotic (i.e., morphology and airscape) heterogeneity

Pseudo solid-appearing pancreatic serous microcystic adenomas: Histologic diagnosis with the EUS core biopsy fork-tip needle

Background and Objectives: Despite rarely, serous cystic adenoma (SCA) can assume a pseudo-solid aspect mimicking other pancreatic neoplasm as neuroendocrine tumor. EUS-FNA cytology has low diagnostic accuracy due to the scant cellularity of the collected samples. Histological diagnosis is usually made after resection. Recently, end-cutting needles for EUS-fine-needle biopsy (EUS-FNB), which obtain tissue cores by penetrating the lesions, have been developed. We aimed to assess the capability of EUS-FNB with SharkCore (TM) needles in the preoperative diagnosis of serous cystic adenoma pseudo-solid-appearing on imaging (Sa-SCA). Materials and Methods: Between January 2016 and January 2018, data from consecutive adult patients, who were referred for EUS-FNB of a solid pancreatic lesion and were diagnosed with having SCA, were retrieved from a single-center institutional database. Results: Two patients were excluded because of microcystic aspect at EUS. Histological diagnosis of SCA was made by EUS-FNB in the remaining 7 patients (5 females; mean age of 62.5 years). Lesions (mean size of 19.8 mm) were hypervascular on cross-sectional imaging, slightly hyperdense magnetic resonance imaging with T2-weighted images can, and negative at Ga-68-somatostatin receptor positron emission tomography and (18)fluoro-deoxyglucose positron emission tomography. EUS-FNB samples were judged adequate for a definitive diagnosis in all cases, achieving specimens suitable for histological evaluation and several ancillary stains. Histochemical positivity for periodic acid-Schiff (PAS) and PAS with diastase digestion was observed in 7/7 cases. Immunohistochemical positivity for alpha-inhibin (7/7), GLUT1 (6/6), MUC6 (5/5), and negativity for synaptophysin (7/7) and chromogranin A (2/2) favored SCA diagnosis. Conclusions: In the case of preoperative workup suspected for Sa-SCA, a "forward acquiring" needle could improve the rate of preoperative histological diagnosis

Comparison between invasive breast cancer with extensive peritumoral vascular invasion and inflammatory breast carcinoma: a clinicopathologic study of 161 cases.

Objectives: Extensive peritumoral neoplastic lymphovascular invasion (ePVI) is a marker of aggressiveness in invasive breast carcinoma (BC). Methods: We explored the impact of ePVI on different BC subtypes. In a total of 2,116 BCs, 91 ePVI-BCs, 70 inflammatory breast carcinomas (IBCs), and 114 casual BCs as a control group (CG-BC) were recruited. Results: Patients affected by ePVI-BC were younger, had larger tumors, higher histologic grade, elevated Ki-67 score, Her2/neu overexpressed, and more lymph node metastases compared with CG-BC ( P < .001). Interestingly, only younger mean age at diagnosis differentiated patients with ePVI-BC from patients affected by IBC. ePVI-BC showed a clinical outcome intermediate between the prognoses of IBC and CG-BC. Conclusions: Results suggest that ePVI-BC and IBC may share some pathologic processes, providing a novel perspective on the heterogeneity of BC. Epidemiologic data and molecular studies on gene expression features are needed to rationally classify these tumors into their identified subtypes

Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4

Cancer cells rely on dysregulated gene expression. This establishes specific transcriptional addictions that may be therapeutically exploited. Yet, the mechanisms that are ultimately responsible for these addictions are poorly understood. Here, we investigated the transcriptional dependencies of transformed cells to the transcription factors YAP and TAZ. YAP/TAZ physically engage the general coactivator bromodomain-containing protein 4 (BRD4), dictating the genome-wide association of BRD4 to chromatin. YAP/TAZ flag a large set of enhancers with super-enhancer-like functional properties. YAP/TAZ-bound enhancers mediate the recruitment of BRD4 and RNA polymerase II at YAP/TAZ-regulated promoters, boosting the expression of a host of growth-regulating genes. Treatment with small-molecule inhibitors of BRD4 blunts YAP/TAZ pro-tumorigenic activity in several cell or tissue contexts, causes the regression of pre-established, YAP/TAZ-addicted neoplastic lesions and reverts drug resistance. This work sheds light on essential mediators, mechanisms and genome-wide regulatory elements that are responsible for transcriptional addiction in cancer and lays the groundwork for a rational use of BET inhibitors according to YAP/TAZ biology

THE PRATI DI STUORES/STUORES WIESEN SECTION (DOLOMITES, ITALY): A CANDIDATE GLOBAL STRATOTYPE SECTION AND POINT FOR THE BASE OF THE CARNIAN STAGE

The Prati di Stuores/Stuores Wiesen section (Dolomites, Italy) is proposed as a candidate Global Stratotype Section and Point for the base of the Carnian Stage. In addition to being a famous, richly fossiliferous locality, it includes the type-section of the Cordevolian substage. The section is located near Pralongià, along the southern slope of the crest separating the Badia/Abtei and Cordevole valleys. Below the levels with Trachyceras aon, the section contains a rich ammonoid fauna that chacterizes the lower part of the Regoledanus Subzone and subsequently records the first appearances of the mid-high latitude genus Daxatina (Daxatina sp., D. cf. canadensis) and of traditional Trachyceras with species different from T. aon. Moreover, the Daxatina cf. canadensis Subzone is recognised above the Regoledanus Subzone. Very rare conodonts of the Budurovignatus group and species of Gladigondolella from the diebeli Assemblage Zone occur. Gondolella polygnatyformis, already known from the Aon Subzone, is absent. Palynomorphs, foraminifers, gastropods, bivalves, brachiopods, microcrinoids and holothurian sclerites were studied. Variations in frequency and taxonomic diversity of these faunas suggest anaerobic-disaerobic bottom conditions for the lower-middle part of the section (0-105 m), followed by a more stable oxygen content in the upper portion. Magnetostratigraphy showed four intervals with normal polarity and three intervals with reversed polarity. The Daxatina cf. canadensis Subzone falls close to the normal polarity interval S2n. The present study proposes the FAD of the cosmopolitan genus Daxatina as a marker of the base of the Carnian Stage, placing it at a lower stratigraphic level than previously indicated in the Stuores area. The Prati di Stuores section is proposed as GSSP of the Ladinian-Carnian boundary.&nbsp

Mount control system of the ASTRI SST-2M prototype for the Cherenkov Telescope Array

The ASTRI SST-2M telescope is an end-to-end prototype proposed for the Small Size class of Telescopes (SST) of the future Cherenkov Telescope Array (CTA). The prototype is installed in Italy at the INAF observing station located at Serra La Nave on Mount Etna (Sicily) and it was inaugurated in September 2014. This paper presents the software and hardware architecture and development of the system dedicated to the control of the mount, health, safety and monitoring systems of the ASTRI SST-2M telescope prototype. The mount control system installed on the ASTRI SST-2M telescope prototype makes use of standard and widely deployed industrial hardware and software. State of the art of the control and automation industries was selected in order to fulfill the mount related functional and safety requirements with assembly compactness, high reliability, and reduced maintenance. The software package was implemented with the Beckhoff TwinCAT version 3 environment for the software Programmable Logical Controller (PLC), while the control electronics have been chosen in order to maximize the homogeneity and the real time performance of the system. The integration with the high level controller (Telescope Control System) has been carried out by choosing the open platform communications Unified Architecture (UA) protocol, supporting rich data model while offering compatibility with the PLC platform. In this contribution we show how the ASTRI approach for the design and implementation of the mount control system has made the ASTRI SST-2M prototype a standalone intelligent machine, able to fulfill requirements and easy to be integrated in an array configuration such as the future ASTRI mini-array proposed to be installed at the southern site of the Cherenkov Telescope Array (CTA)

Evaluation of the prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy

Whilst renal dysfunction, especially mild impairment (60 die;ve (Icona) Foundation Study collected between January 2000 and February 2014 with at least two creatinine values available. eGFR (CKD-epi) and renal dysfunction defined using a priori cut-offs of 60 (severely impaired) and 90 ml/min/1.73m2 (mildly impaired). Characteristics of patients were described after stratification in these groups and compared using chi-square test (categorical variables) or Kruskal Wallis test comparing median values. Follow-up accrued from baseline up to the date of the CCVD or AIDS related events or death or last available visit. Kaplan Meier curves were used to estimate the cumulative probability of occurrence of the events over time. Adjusted analysis was performed using a proportional hazards Cox regression model. We included 7,385 patients, observed for a median follow-up of 43 months (interquartile range [IQR]: 21-93 months). Over this time, 130 cerebro-cardiovascular events (including 11 deaths due to CCVD) and 311 AIDS-related events (including 45 deaths) were observed. The rate of CCVD events among patients with eGFR &gt;90, 60-89, &lt;60 ml/min, was 2.91 (95% CI 2.30-3.67), 4.63 (95% CI 3.51-6.11) and 11.9 (95% CI 6.19-22.85) per 1,000 PYFU respectively, with an unadjusted hazard ratio (HR) of 4.14 (95%CI 2.07-8.29) for patients with eGFR &lt;60 ml/min and 1.58 (95%CI 1.10-2.27) for eGFR 60-89 compared to those with eGFR ≥90. Of note, these estimates are adjusted for traditional cardiovascular risk factors (e.g. smoking, diabetes, hypertension, dyslipidemia). Incidence of AIDS-related events was 9.51 (95%CI 8.35-10.83), 6.04 (95%CI 4.74-7.71) and 25.0 (95% CI 15.96-39.22) per 1,000 PYFU, among patients with eGFR &gt;90, 60-89, &lt;60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR &lt;60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90&lt;60)&gt