Mapping the dynamic interactions between vortex species in highly anisotropic superconductors

Here we use highly sensitive magnetisation measurements performed using a Hall probe sensor on single crystals of highly anisotropic high temperature superconductors $Bi_{2}Sr_{2}CaCu_{2}O_{8}$ to study the dynamic interactions between the two species of vortices that exist in such superconductors. We observe a remarkable and clearly delineated high temperature regime that mirrors the underlying vortex phase diagram. Our results map out the parameter space over which these dynamic interaction processes can be used to create vortex ratchets, pumps and other fluxonic devices.Comment: 7 pages, 3 figures, to be published in Supercond. Sci. Techno

Guar gum/borax hydrogel: Rheological, low field NMR and release characterizations

Guar gum (GG) and Guar gum/borax (GGb) hydrogels are studied by means of rheology, Low Field Nuclear Magnetic Resonance (LF NMR) and model drug release tests. These three approaches are used to estimate the mesh size (ζ) of the polymeric network. A comparison with similar Scleroglucan systems is carried out. In the case of GGb, the rheological and Low Field NMR estimations of ζ lead to comparable results, while the drug release approach seems to underestimate ζ. Such discrepancy is attributed to the viscous effect of some polymeric chains that, although bound to the network to one end, can freely fluctuate among meshes. The viscous drag exerted by these chains slows down drug diffusion through the polymeric network. A proof for this hypothesis is given by the case of Scleroglucan gel, where the viscous contribution is not so significant and a good agreement between the rheological and release test approaches was found

Fault structure and slip localization in carbonate-bearing normal faults: An example from the Northern Apennines of Italy

Carbonate-bearing normal faults are important structures for controlling fluid flow and seismogenesis within the brittle upper crust. Numerous studies have tried to characterize fault zone structure and earthquake slip processes along carbonate-bearing faults. However, due to the different scales of investigation, these studies are not often integrated to provide a comprehensive fault image. Here we present a multi-scale investigation of a normal fault exhumed from seismogenic depths. The fault extends for a length of 10 km with a maximum width of about 1.5 km and consists of 5 sub-parallel and interacting segments. The maximum displacement (370e650 m) of each fault segment is partitioned along sub-parallel slipping zones extending for a total width of about 50 m. Each slipping zone is characterized by slipping surfaces exhibiting different slip plane phenomena. Fault rock development is controlled by the protolith lithology. In massive limestone, moving away from the slip surface, we observe a thin layer (<2 cm) of ultracataclasite, cataclasite (2e10 cm) and fault breccia. In marly limestone, the fault rock consists of a cataclasite with hydrofractures and smectite-rich pressure solution seams. At the micro-nanoscale, the slip surface consists of a continuous and thin (<300 mm) layer composed of coarse calcite grains (~5e20 mm in size) associated with sub-micrometer grains showing fading grain boundaries, voids and/or vesicles, and suggesting thermal decomposition processes. Micrometer-sized calcite crystals show nanoscale polysynthetic twinning affected by the occurrence of subgrain boundaries and polygonalized nanostructures. Investigations at the kilometres-tens of meter scale provide fault images that can be directly compared with high-resolution seismological data and when combined can be used to develop a comprehensive characterization of seismically active fault structures in carbonate lithologies. Micro and nanoscale investigations along the principal slipping zone suggest that different deformation processes, including plastic deformation and thermal decomposition, were active during seismic slip

New national and regional Annex I Habitat records: from #60 to #82

New Italian data on the distribution of the Annex I Habitats are reported in this contribution. Specifically, 8 new occurrences in Natura 2000 sites are presented and 49 new cells are added in the EEA 10 km × 10 km reference grid. The new data refer to the Italian administrative regions of Campania, Calabria, Marche, Piedmont, Sardinia, Sicily, Tuscany and Umbria. Relevés and figures are provided as Supplementary material respectively 1 and 2. Copyright Antonio Morabito et al

Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo

Substantial evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have potential as chemopreventative/therapeutic agents. However, these agents cannot be universally recommended for prevention purposes due to their potential side-effect profiles. Here, we compared the growth inhibitory and mechanistic activity of aspirin to two novel analogues, diaspirin (DiA) and fumaryl diaspirin (F-DiA). We found that the aspirin analogues inhibited cell proliferation and induced apoptosis of colorectal cancer cells at significantly lower doses than aspirin. Similar to aspirin, we found that an early response to the analogues was a reduction in levels of cyclin D1 and stimulation of the NF-κB pathway. This stimulation was associated with a significant reduction in basal levels of NF-κB transcriptional activity, in keeping with previous data for aspirin. However, in contrast to aspirin, DiA and F-DiA activity was not associated with nucleolar accumulation of RelA. For all assays, F-DiA had a more rapid and significant effect than DiA, identifying this agent as particularly active against colorectal cancer. Using a syngeneic colorectal tumour model in mice, we found that, while both agents significantly inhibited tumour growth in vivo, this effect was particularly pronounced for F-DiA. These data identify two compounds that are active against colorectal cancer in vitro and in vivo. They also identify a potential mechanism of action of these agents and shed light on the chemical structures that may be important for the antitumour effects of aspirin

Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines

INTRODUCTION: The aim of the study was to evaluate the activity of a combination of doxorubicin (Dox), paclitaxel (Pacl) and 5-fluorouracil (5-FU), to define the most effective schedule, and to investigate the mechanisms of action in human breast cancer cells. METHODS: The study was performed on MCF-7 and BRC-230 cell lines. The cytotoxic activity was evaluated by sulphorhodamine B assay and the type of drug interaction was assessed by the median effect principle. Cell cycle perturbation and apoptosis were evaluated by flow cytometry, and apoptosis-related marker (p53, bcl-2, bax, p21), caspase and thymidylate synthase (TS) expression were assessed by western blot. RESULTS: 5-FU, used as a single agent, exerted a low cytotoxic activity in both cell lines. The Dox→Pacl sequence produced a synergistic cytocidal effect and enhanced the efficacy of subsequent exposure to 5-FU in both cell lines. Specifically, the Dox→Pacl sequence blocked cells in the G2-M phase, and the addition of 5-FU forced the cells to progress through the cell cycle or killed them. Furthermore, Dox→Pacl pretreatment produced a significant reduction in basal TS expression in both cell lines, probably favoring the increase in 5-FU activity. The sequence Dox→Pacl→48-h washout→5-FU produced a synergistic and highly schedule-dependent interaction (combination index < 1), resulting in an induction of apoptosis in both experimental models regardless of hormonal, p53, bcl-2 or bax status. Apoptosis in MCF-7 cells was induced through caspase-9 activation and anti-apoptosis-inducing factor hyperexpression. In the BRC-230 cell line, the apoptotic process was triggered only by a caspase-dependent mechanism. In particular, at the end of the three-drug treatment, caspase-8 activation triggered downstream executioner caspase-3 and, to a lesser degree, caspase-7. CONCLUSION: In our experimental models, characterized by different biomolecular profiles representing the different biology of human breast cancers, the schedule Dox→Pacl→48-h washout→5-FU was highly active and schedule-dependent and has recently been used to plan a phase I/II clinical protocol

Zinc-bound metallothioneins and immune plasticity: lessons from very old mice and humans

The capacity of the remodelling immune responses during stress (named immune plasticity) is fundamental to reach successful ageing. We herein report two pivotal experimental models in order to demonstrate the relevance of the immune plasticity in ageing and successful ageing. These two experimental models will be compared with the capacity in remodelling the immune response in human centenarians. With regard to experimental models, one model is represented by the circadian rhythms of immune responses, the other one is the immune responses during partial hepatectomy/liver regeneration (pHx). The latter is suggestive because it mimics the immunosenescence and chronic inflammation 48 h after partial hepatectomy in the young through the continuous production of IL-6, which is the main cause of immune plasticity lack in ageing. The constant production of IL-6 leads to abnormal increments of zinc-bound Metallothionein (MT), which is in turn unable in zinc release in ageing. As a consequence, low zinc ion bioavailability appears for thymic and extrathymic immune efficiency, in particular of liver NKT cells bearing TCR γδ. The remodelling during the circadian cycle and during pHx of zinc-bound MT confers the immune plasticity of liver NKT γδ cells and NK cells in young and very old mice, not in old mice. With regard to human centenarians and their capacity in remodelling the immune response with respect to elderly, these exceptional individuals display low zinc-bound MT associated with: a) satisfactory intracellular zinc ion availability, b) more capacity in zinc release by MT, c) less inflammation due to low gene expression of IL-6 receptor (gp130), d) increased levels of IFN-gamma and number of NKT cell bearing TCR γδ. Moreover, some polymorphisms for MT tested in PBMCs from human donors are related to successful ageing. In conclusion, zinc-bound MT homeostasis is fundamental to confer the immune plasticity that is a condition "sine qua non" to achieve healthy ageing and longevity

Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer

The activity of the following drugs was investigated in two established NSCLC cell lines: docetaxel, gemcitabine, vinorelbine, paclitaxel, doxorubicin (0.01, 0.1, 1 μg ml−1), cisplatin, ifosfamide (1, 2, 3 μg ml−1) and carboplatin (2, 4, 6 μg ml−1). The cytotoxic activity was evaluated by the sulphorhodamine B assay. The two most active drugs, docetaxel and gemcitabine, used singly and in association, were investigated as a function of treatment schedule. The sequence docetaxel→gemcitabine produced only a weak synergistic interaction in RAL but a strong synergism in CAEP cells. The synergistic interaction increased in both cell lines after a 48-h washout between the drug administrations. Flow cytometric analysis showed that in docetaxel→gemcitabine sequence, docetaxel produced a block in G2/M phase and, after 48 h, provided gemcitabine with a large fraction of recovered synchronized cells in the G1/S boundary, which is the specific target phase for gemcitabine. Conversely, simultaneous treatment induced an antagonistic effect in both cell lines, and the sequential scheme gemcitabine→docetaxel produced a weak synergistic effect only in RAL cells. Moreover, the synergistic interaction disappeared when washout periods of 24 or 48 h between two drug administrations were adopted. The synergistic activity of docetaxel→ 48-h washout→gemcitabine was confirmed in 11 of 14 primary cultures, which represents an important means of validating experimental results before translating them into clinical practice. © 1999 Cancer Research Campaig

The relevance of fungi in astrobiology research – Astromycology

Since the very first steps of space exploration, fungi have been recorded as contaminants, hitchhikers, or as part of missions’ crews and payloads. Because fungi can cause human disease and are highly active decomposers, their presence in a space-linked context has been a source of major concern given their possible detrimental effects on crews and space structures. However, fungi can also be beneficial and be used for many space applications. The exact effects on fungi are not always clear as they possess high adaptability and plasticity, and their phenotypes and genotypes can undergo several changes under the extreme conditions found in space, thus leading to different results than those we would have on Earth. Understanding and analysing these aspects is the subject of astromycology, a research field within astrobiology. The impending situation of a resurgent space race is expected to boost astromycology’s visibility and importance. However, researchers lack both a framework and a solid base of knowledge from which to contextualise their work. This critical review addresses this gap by conceptualising the field of astromycology, covering key research and current questions pertaining to the field, and providing a relevant research instrument for future work