Visualization of DNA G-quadruplexes in herpes simplex virus 1-infected cells

We have previously shown that clusters of guanine quadruplex (G4) structures can form in the human herpes simplex-1 (HSV-1) genome. Here we used immunofluorescence and immune-electron microscopy with a G4-specific monoclonal antibody to visualize G4 structures in HSV-1 infected cells. We found that G4 formation and localization within the cells was virus cycle dependent: viral G4s peaked at the time of viral DNA replication in the cell nucleus, moved to the nuclear membrane at the time of virus nuclear egress and were later found in HSV-1 immature virions released from the cell nucleus. Colocalization of G4s with ICP8, a viral DNA processing protein, was observed in viral replication compartments. G4s were lost upon treatment with DNAse and inhibitors of HSV-1 DNA replication. The notable increase in G4s upon HSV-1 infection suggests a key role of these structures in the HSV-1 biology and indicates new targets to control both the lytic and latent infection

Invasive Candida Infections in Patients With Haematological Malignancies and Hematopoietic Stem Cell Transplant Recipients: Current Epidemiology and Therapeutic Options.

In the last decades, the global epidemiological impact of invasive candidiasis (IC) in patients with hematologic malignancies (HM) and in hematopoietic stem cell transplant (HSCT) recipients has decreased and the incidence of invasive aspergillosis exceeded that of Candida infections. The use of prevention strategies, first of all antifungal prophylaxis with triazoles, contributed to the reduction of IC in these populations as demonstrated by several epidemiological studies. However, relatively little is known about the current epidemiological patterns of IC in HM and HSCT populations, because recent epidemiological data almost exclusively derive from retrospective experiences and few prospective data are available. Several prospective, controlled studies in the prophylaxis of invasive fungal diseases have been conducted in both the HM and HSCT setting. On the contrary, most of the prospective controlled trials that demonstrated the efficacy of the antifungal drugs echinocandins and voriconazole in the treatment of candidemia and invasive candidiasis mainly involved patients with underlying conditions other than HM or HSCT. For these reasons, international guidelines provided specific indications for the prophylaxis strategies in HM and HSCT patients, whereas the recommendations on therapy of documented Candida infections are based on the results observed in the general population and should be considered with caution

Synthesis, Binding and Antiviral Properties of Potent Core-Extended Naphthalene Diimides Targeting the HIV-1 Long Terminal Repeat Promoter G-Quadruplexes

We have previously reported that stabilization of the G-quadruplex structures in the HIV-1 long terminal repeat (LTR) promoter suppresses viral transcription. Here we sought to develop new G-quadruplex ligands to be exploited as antiviral compounds by enhancing binding toward the viral G-quadruplex structures. We synthesized naphthalene diimide derivatives with a lateral expansion of the aromatic core. The new compounds were able to bind/stabilize the G-quadruplex to a high extent, and some of them displayed clear-cut selectivity toward the viral G-quadruplexes with respect to the human telomeric G-quadruplexes. This feature translated into low nanomolar anti-HIV-1 activity toward two viral strains and encouraging selectivity indexes. The selectivity depended on specific recognition of LTR loop residues; the mechanism of action was ascribed to inhibition of LTR promoter activity in cells. This is the first example of G-quadruplex ligands that show increased selectivity toward the viral G-quadruplexes and display remarkable antiviral activity

Dianthus borbonicus (Caryophyllaceae), a new species from Sicily

Dianthus borbonicus a new species occurring in North-Western Sicily is described and illustrated. It is a rare chasmophyte belonging to the D. sylvestris group, which is exclusive of a rupestrian stand near Rocca Busambra (Ficuzza). Its macro- and micromorphological features (seed testa sculptures, and leaf anatomy), ecology, conservation status and a comparison with the related species are provided too

Limits on the violation of g-universality with a Galileo-type experiment

Abstract We present new results for a Galilean experiment using two masses of copper and tungsten in simultaneous free fall. The experiment searches for a possible difference in the free-fall acceleration Δ g and it is sensitive to any composition-dependent interaction between the test masses and the earth, whose range exceeds 10 km. The results show no evidence for any composition-dependent gravity-like interaction within Δg μ Gal

The Lower Miocene volcaniclastic sedimentation in the Sicilian sector of the Maghrebian Flysch Basin: geodynamic implications

Abstract Volcaniclastic debris-rich formations, characterising the Troina–Tusa Unit in the Sicilian Maghrebian Chain, are examined. The Troina–Tusa Unit terrains sedimented in the Maghrebian Flysch Basin, which, from Jurassic to Early Miocene, constituted the southernmost branch of the Western Tethys, located between Africa and the Mesomediterranean Terrane margins. New field, biostratigraphic and petrographic data enable a reconstruction of the palaeogeographic and structural evolution of the Flysch Basin immediately before its deformation. All the studied formations transpired to be Burdigalian in age. The sandstone compositions, showing different source areas (magmatic arc, recycled orogen and continental block), indicate a provenance for the clastic material from a crystalline basement with an active volcanic arc, replaced by a remnant volcanic arc, which was rapidly completely eroded. The source area that has been considered is Sardinia, where Upper Oligocene–Aquitanian calc-alkaline volcanites are widespread, but the sedimentological characteristics and the Burdigalian age do not fit with this provenance. The Burdigalian calc-alkaline arc should be located on the internal side of the Troina–Tusa Basin, above the already stacked Peloritanian units. A migration of the volcanic activity, connected with the subduction plain roll-back, can be envisaged from the Sardinia Block to the Peloritanian Chain, this latter still docked to the Sardinia–Corsica massif

A Prototype System for Time-Lapse Electrical Resistivity Tomographies

A prototype system for time-lapse acquisition of 2D electrical resistivity tomography (ERT) and time domain reflectometry (TDR) measurements was installed in a test site affected by a landslide in Basilicata region (southern Italy). The aim of the system is to monitor in real-time the rainwater infiltration into the soil and obtain information about the variation of the water content in the first layers of the subsoil and the possible influence of this variation on landslide activity. A rain gauge placed in the test site gives information on the rainfall intensity and frequency and suggests the acquisition time interval. The installed system and the preliminary results are presented in this paper

Outcome of Very Late Relapse in Patients with Hodgkin's Lymphomas

Recurrences of Hodgkin's Lymphoma (HL) 5 years after the initial therapy are rare. The aim of this study is to report a single centre experience of the clinical characteristics, outcome, and toxicity of pts who experienced very late relapses, defined as relapses that occurred 5 or more years after the achievement of first complete remission. Of 532 consecutive pts with classical HL treated at our Institute from 1985 to 1999, 452 pts (85%) achieved a complete remission. Relapse occurred in 151 pts: 135 (29.8%) within 5 years and 16 over 5 years (3.5%, very late relapses). Very late relapses occurred after a median disease-free interval of 7 years (range: 5–18). Salvage treatment induced complete remission in 14 pts (87.5%). At a median of 4 years after therapy for very late relapse, 10 pts (63%) are still alive and free of disease and 6 (37%) died (1 from progressive HL, 1 from cardiac disease, 1 from thromboembolic disease, 1 from HCV reactivation, and 2 from bacterial infection). The probability of failure-free survival at 5 years was 75%. The majority of deaths are due to treatment-related complications. Therapy regimens for very late relapse HL are warranted to minimize complications

Magnetic and solar effects on ionospheric absorption at high latitude

Some periods of intense solar events and of strong magnetic storms have been selected and their effects on the ionospheric D region have been investigated on the basis of ionospheric absorption data derived from riometer measurements made at the Italian Antarctic Base of Terra Nova Bay (geographic coordinates: 74.69 S, 164.12 E; geomagnetic coordinates: 77.34 S, 279.41 E). It was found that sharp increases in ionospheric absorption are mainly due to solar protons emission with an energy greater than 10 MeV. Moreover, the day to night ratios of the ionospheric absorption are greater than 2 in the case of strong events of energetic protons emitted by the Sun, while during magnetic storms, these ratios range between 1 and 2