Discrimination between wave-ravinement surfaces and bedset boundaries in Pliocene shallow-marine deposits, Crotone Basin, southern Italy: An integrated sedimentological, micropalaeontological and mineralogical approach

4siThe lower Pliocene Belvedere Formation, cropping out in the Crotone Basin, southern Italy, exhibits a metre-scale to decametre-scale shallow-marine cyclicity that shares features of both high-frequency sequences linked to shoreline shifts and controlled by minor relative sea-level and/or sediment supply changes, and sedimentological cycles unrelated to shoreline shifts. In order to better understand the high-frequency sequence stratigraphic framework of this succession, an integration of sedimentological, micropalaeontological (microforaminifera assemblages) and mineralogical (heavy mineral abundance) data is used. From a sedimentological/stratigraphic point of view, wave-ravinement surfaces bounding high-frequency sequences, and associated substrate-controlled ichnofacies, are prominent in outcrop and document environmental and water-depth changes, whereas bedset boundaries separating sedimentological cycles have a more subtle field appearance and are only associated with changes of environmental energy. Moreover, condensed deposits are present only above wave-ravinement surfaces, and the high-frequency sequences bounded by these surfaces have a thickness that is an order of magnitude greater than that of the bedsets. Micro-foraminifera assemblages may change, and the content of heavy minerals usually increases, across wave-ravinement surfaces, whereas both parameters do not change significantly across bedset boundaries. The abundance of heavy minerals is systematically higher, with respect to the underlying and overlying deposits, in the condensed shell beds that overlie wave-ravinement surfaces. An integrated sedimentological, micropalaeontological and mineralogical approach represents a powerful tool to discriminate between wave-ravinement surfaces bounding high-frequency sequences and bedset boundaries, and in general to investigate at the intra high-frequency sequence scale. This integrated approach is expected to be very useful in the study of potentially all shallow-marine successions composed of small-scale cycles, in order to delineate a detailed sequence stratigraphic framework and understand the factors that controlled the cyclicity.partially_openopenZecchin, Massimo; Caffau, Mauro; Catuneanu, Octavian; Lenaz, DavideZecchin, Massimo; Caffau, Mauro; Catuneanu, Octavian; Lenaz, David

First evidence of testate amoebae in Lago fagnano (54\ub0S), Tierra del Fuego (Argentina): Proxies to reconstruct environmental changes

We report here the first findings of testate amoebae at high southern latitudes (54 S) from four gravity cores recovered in the Lago Fagnano (Tierra del Fuego, Argentina), where twelve taxa have been recognized. Among them, Centropyxis constricta \u201cconstricta\u201d, Centropyxis elongata, Difflugia globulus, Difflugia oblonga \u201coblonga\u201d, and Difflugia protaeiformis \u201camphoralis\u201d are always present, while other taxa are randomly distributed. According to the sand/silt ratio in the different cores, the Total Organic Carbon content and the Carbon/Nitrogen ratio, as well as the presence/disappearance and abundance of testate amoebae from cluster analysis, we infer a correlation between major textural/granulometrical changes found in the cores and environmental changes. A seismic event occurred on 1949, which substantially modified the morphology of the eastern Lago Fagnano shoreline and the supply pattern from two main eastern tributaries of the lake, is recorded in the studied cores. This event has in part modified the distribution of testate amoebae taxa within the studied cores. Present results show that testate amoebae represent important indicators to detect changes occurring in the environment in which they live

The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase

CDT2/L2DTL/RAMP is one of the substrate receptors of the Cullin Ring Ubiquitin Ligase 4 that targets for ubiquitin mediated degradation a number of substrates, such as CDT1, p21 and CHK1, involved in the regulation of cell cycle and survival. Here we show that CDT2 depletion was alone able to induce the apoptotic death in 12/12 human cancer cell lines from different tissues, regardless of the mutation profile and CDT2 expression level. Cell death was associated to rereplication and to loss of CDT1 degradation. Conversely, CDT2 depletion did not affect non-transformed human cells, such as immortalized kidney, lung and breast cell lines, and primary cultures of endothelial cells and osteoblasts. The ectopic over-expression of an activated oncogene, such as the mutation-activated RAS or the amplified MET in non-transformed immortalized breast cell lines and primary human osteoblasts, respectively, made cells transformed in vitro, tumorigenic in vivo, and susceptible to CDT2 loss. The widespread effect of CDT2 depletion in different cancer cells suggests that CDT2 is not in a synthetic lethal interaction to a single specific pathway. CDT2 likely is a non-oncogene to which transformed cells become addicted because of their enhanced cellular stress, such as replicative stress and DNA damage

Modeling Tumor Progression by the Sequential Introduction of Genetic Alterations into the Genome of Human Normal Cells

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Tracking the genomic evolution of breast cancer metastasis

Therapeutic choices for metastatic tumors are, in most cases, based upon the histological and molecular analysis of the corresponding primary tumor. Understanding whether and to what extent the genomic landscape of metastasis differs from the tumors from which they originated is critical yet largely unknown. A recent report tackled this key issue by comparing the genomic and transcriptional profile of a metastatic lobular breast tumor with that of the primary tumor surgically removed 9 years earlier. The extent of the differences suggests a high degree of mutational heterogeneity between primary and metastatic lesions and indicates that significant evolution occurs during breast cancer progression

Remote multiparametric monitoring and management of heart failure patients through cardiac implantable electronic devices

In this review we focus on heart failure (HF) which, as known, is associated with a substantial risk of hospitalizations and adverse cardiovascular outcomes, including death. In recent years, systems to monitor cardiac function and patient parameters have been developed with the aim to detect subclinical pathophysiological changes that precede worsening HF. Several patient-specific parameters can be remotely monitored through cardiac implantable electronic devices (CIED) and can be combined in multiparametric scores predicting patients' risk of worsening HF with good sensitivity and moderate specificity. Early patient management at the time of pre-clinical alerts remotely transmitted by CIEDs to physicians might prevent hospitalizations. However, it is not clear yet which is the best diagnostic pathway for HF patients after a CIED alert, which kind of medications should be changed or escalated, and in which case in-hospital visits or in-hospital admissions are required. Finally, the specific role of healthcare professionals involved in HF patient management under remote monitoring is still matter of definition. We analyzed recent data on multiparametric monitoring of patients with HF through CIEDs. We provided practical insights on how to timely manage CIED alarms with the aim to prevent worsening HF. We also discussed the role of biomarkers and thoracic echo in this context, and potential organizational models including multidisciplinary teams for remote care of HF patients with CIEDs

Left Ventricular Response to Cardiac Resynchronization Therapy: Insights From Hemodynamic Forces Computed by Speckle Tracking

Aims: Despite continuous efforts in improving the selection process, the rate of non-responders to cardiac resynchronization therapy (CRT) remains high. Recent studies on intraventricular blood flow suggested that the alignment of hemodynamic forces (HDFs) may be a reproducible biomarker of mechanical dyssynchrony. We aimed to explore the relationship between pacing-induced realignment of HDFs and positive response to CRT. Methods and results: We retrospectively analyzed 38 patients from the CRT database of our institution fulfilling the inclusion criteria for HDFs-related echocardiographic assessment early pre and post CRT implantation, with available mid-term follow-up ( 65 6 months) evaluation. Standard echocardiographic and deformation parameters early pre and post CRT implantation were integrated with the measurement of HFDs through novel methods based on speckle-tracking analysis. At midterm follow-up 71% of patients were classified as responders (reduction of Left Ventricular Systolic Volume Indexed 65 15%). Patients did not display significant changes between close evaluations pre and post-implant in terms of ejection fraction and strain metrics. A significant reduction of the ratio between the amplitudes of transversal and longitudinal force components was found. The variation of this ratio strongly correlates (R2 =0.60) with Left Ventricular (LV) end-systolic volume variation at mid-term follow up. Conclusion: Pacing-induced realignment of HDFs is associated with CRT efficacy at follow up. These preliminary results claim for dedicated prospective clinical studies testing the potential impact of HDFs study for patient selection and pacing optimization in CRT

Antiviral mechanisms of two broad-spectrum monoclonal antibodies for rabies prophylaxis and therapy

Rabies is an acute and lethal encephalomyelitis caused by lyssaviruses, among which rabies virus (RABV) is the most prevalent and important for public health. Although preventable through the post-exposure administration of rabies vaccine and immunoglobulins (RIGs), the disease is almost invariably fatal since the onset of clinical signs. Two human neutralizing monoclonal antibodies (mAbs), RVC20 and RVC58, have been shown to be effective in treating symptomatic rabies. To better understand how these mAbs work, we conducted structural modeling and in vitro assays to analyze their mechanisms of action, including their ability to mediate Fc-dependent effector functions. Our results indicate that both RVC20 and RVC58 recognize and lock the RABV-G protein in its pre-fusion conformation. RVC58 was shown to neutralize more potently the extra-cellular virus, while RVC20 mainly acts by reducing viral spreading from infected cells. Importantly, RVC20 was more effective in promoting effector functions compared to RVC58 and 17C7-RAB1 mAbs, the latter of which is approved for human rabies post-exposure treatment. These results provide valuable insights into the multiple mechanisms of action of RVC20 and RVC58 mAbs, offering relevant information for the development of these mAbs as treatment for human rabies