Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma

Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence.     

S-Adenosylmethionine Inhibits Colorectal Cancer Cell Migration through Mirna-Mediated Targeting of Notch Signaling Pathway

Metastasis is a leading cause of mortality and poor prognosis in colorectal cancer (CRC). Thus, the identification of new compounds targeting cell migration represents a major clinical challenge. Recent findings evidenced a central role for dysregulated Notch in CRC and a correlation between Notch overexpression and tumor metastasis. MicroRNAs (miRNAs) have been reported to cross-talk with Notch for its regulation. Therefore, restoring underexpressed miRNAs targeting Notch could represent an encouraging therapeutic approach against CRC. In this context, S-adenosyl-L-methionine (AdoMet), the universal biological methyl donor, being able to modulate the expression of oncogenic miRNAs could act as a potential antimetastatic agent. Here, we showed that AdoMet upregulated the onco-suppressor miRNAs-34a/-34c/-449a and inhibited HCT-116 and Caco-2 CRC cell migration. This effect was associated with reduced expression of migration-/EMT-related protein markers. We also found that, in colorectal and triple-negative breast cancer cells, AdoMet inhibited the expression of Notch gene, which, by luciferase assay, resulted the direct target of miRNAs-34a/-34c/-449a. Gain- and loss-of-function experiments with miRNAs mimics and inhibitors demonstrated that AdoMet exerted its inhibitory effects by upregulating miRNAs-34a/-34c/-449a. Overall, these data highlighted AdoMet as a novel Notch inhibitor and suggested that the antimetastatic effects of AdoMet involve the miRNA-mediated targeting of Notch signaling pathway.     

The Role of NLRP3 Inflammasome Activation and Oxidative Stress in Varicocele-Mediated Male Hypofertility

Varicocele (VC) is the most common abnormality identified in men evaluated for hypofertility. Increased levels of reactive oxygen species (ROS) and reduced antioxidants concentrations are key contributors in varicocele-mediated hypofertility. Moreover, inflammation and alterations in testicular immunity negatively impact male fertility. In particular, NLRP3 inflammasome activation was hypothesized to lead to seminal inflammation, in which the levels of specific cytokines, such as IL-1β and IL-18, are overexpressed. In this review, we described the role played by oxidative stress (OS), inflammation, and NLRP3 inflammasome activation in VC disease. The consequences of ROS overproduction in testis, including inflammation, lipid peroxidation, mitochondrial dysfunction, chromatin damage, and sperm DNA fragmentation, leading to abnormal testicular function and failed spermatogenesis, were highlighted. Finally, we described some therapeutic antioxidant strategies, with recognized beneficial effects in counteracting OS and inflammation in testes, as possible therapeutic drugs against varicocele-mediated hypofertility.     

Supporting Scientific Collaboration: Methods, Tools and Concepts

This paper discusses the interrelationship between e-Science and CSCW in terms of key substantive, methodological and conceptual innovations made in both fields. In so doing, we hope to draw out the existing relationship between CSCW and e-Science research, and to map out some key future challenges where the two areas of research may become more closely aligned. In considering what may be required to draw the two more closely together, the paper focuses primarily on investigations that have been undertaken in two dedicated initiatives into e-Science, along with the key issues emerging from these studies.     

Modelling of Drop Size Distribution of Rain from Rain Rate and Attenuation Measurements at Millimeter and Optical Wavelengths

This paper describes a technique for modelling of rain drop size distributions at Calcutta in terms of negative exponential function, from the measurements of rain rate and attenuation over a dual wavelength LOS link at millimeter and optical frequencies. The DSD model obtained is then used to determine the attenuation at 94 GHz, for comparison with experimentally obtained attenuation at 94 GHz. This is also compared with the attenuation calculated by considering other experimentally obtained DSD models. The best fit negative exponential distribution function (modified M-P model) is presented along with some other experimentally obtained and reference models.     

Mechanical spectroscopy of nanocrystalline metals: Structure and anelastic behavior

Nanocrystalline aluminum and nickel were prepared by mechanical attrition in a planetary ball-milling apparatus working under a 10⁻⁴ Pa vacuum in the 150–300 K range. A detailed investigation of the mechanical behavior in the anelastic regime was accomplished by employing different mechanical spectroscopy apparatuses in the 0.01–10³ Hz range. Measurements of the elastic energy dissipation coefficient and of the dynamic elasticity modulus as a function of temperature and frequency have shown an enhanced damping at low temperatures and an anelastic relaxation peak tentatively assigned to the short range dynamics at the interfaces. Moreover the magnetic field dependence of the dynamic elastic modulus in nickel revealed a strict correlation between the microstrains confined at the interfaces and the magnitude of the magnetoelastic coupling.     

Future Strategy for the New Millennium Wireless World

Wireless Personal Communications -     

Joint spectrum and power optimization in the design of the UMTS satellite component

The paper provides a power and spectrum joint analysis of the universal mobile telecommunications system (UMTS) satellite component, based on the wideband code division multiple access (W‐CDMA) air interface. In fact, power and spectral efficiency may become highly conflicting requirements in a satellite system and a trade‐off analysis is needed to drive a proper dimensioning of the satellite. The proposed approach allows a dimensioning of the satellite component either in terms of orbit and power budget or in terms of additional capacity for the terrestrial section, for specified orbit and power limitations. The impact of candidate frequency bands, orbit type and diversity on both spectral and power requirements of the satellite component is evaluated. For given traffic requirements, power‐vs‐spectrum trade‐off is proposed which ensures a proper resources utilization. The efficiency evaluation accounts for: beams overlapping, ortho gonality, voice activity factor, diversity and cross‐polarization frequency reuse. Perfect power control is assumed and the effect of the excess power required by the shadowed users is accounted for in the interference calculation. Furthermore, still in the frame of a proper resource exploitation, a possible optimization of capacity through the use of unpaired bands in the two link directions is analysed. Copyright © 2001 John Wiley & Sons, Ltd.     

Insights on the Side Panels of the <Emphasis Type="Italic">Franciscan Triptych</Emphasis> by Fra Angelico Using Terahertz Time-Domain Imaging (THz-TDI)

The side panels of the Franciscan Triptych (St. Jerome, St. John the Baptist, and the Archangel Gabriel and St. Francis, St. Onofrio, and the Virgin Annunciate, by Fra Angelico, before 1429) were scanned by means of terahertz time-domain imaging (THz-TDI). THz analysis supplied information on the stratigraphy of the panel paintings and the associated construction, “gessoing” and gilding techniques. Furthermore, THz-TDI provided information regarding the location of restoration materials within the painting stratigraphy on St. Jerome, St. John the Baptist, and the Archangel Gabriel, as well as on the extension and nature of subsurface cracks in the panel painting of St. Francis, St. Onofrio, and the Virgin Annunciate.     

Composite Nanostructures of TiO2 and ZnO for Water Splitting Application: Atomic Layer Deposition Growth and Density Functional Theory Investigation

The commercialization of solar fuel devices requires the development of novel engineered photoelectrodes for water splitting applications which are based on redundant, cheap, and environmentally friendly materials. In the current study, a combination of titanium dioxide (TiO₂) and zinc oxide (ZnO) onto nanotextured silicon is utilized for a composite electrode with the aim to overcome the individual shortcomings of the respective materials. The properties of conformal coverage of TiO₂ and ZnO layers are designed on the atomic scale by the atomic layer deposition technique. The resulting photoanode shows not only promising stability but also nine times higher photocurrents than an equivalent photoanode with a pure TiO₂ encapsulation onto the nanostructured silicon. Density functional theory calculations indicate that segregation of TiO₂ at the ZnO surfaces is favorable and leads to the stabilization of the ZnO layers in water environments. In conclusion, the novel designed composite material constitutes a promising base for a stable and effective photoanode for the water oxidation reaction.