DigiArt: towards a virtualization of Cultural Heritage

DigiArt is a Europe-wide project aimed at providing a new, cost efficient solution to the capture, processing and display of cultural artefacts. The project will change the ways in which the public interact with cultural objects and spaces in a dramatic way. This project is unique in its collaborative approach: cultural heritage professionals working directly with electrical, mechanical, optical and software engineers to develop a solution to current issues faced by the museum sector. The innovations created by the engineers are driven by the demand of the cultural heritage sector. The diversity of the objects and spaces of the three test museums are challenging the engineers to provide a tool useful for a broad variety of indoor and outdoor museums in the future. This goes from using Unmanned Aerial Vehicle (UAVs or drones) to fly and record large sites, to using scanners to record fine jewellery. As a case study, we present here the use-case of Scladina Cave. At the end of the project, the Scladina Cave Archaeological Centre will offer two different visitor experiences. The first uses virtual reality, which will be available anytime, anywhere, to anyone with an internet connected device. The second will use augmented reality technologies within the cave site. The augmented reality visit of the cave will enhance the tour of Scladina by offering visits that would not be possible where it not for the augmented reality, where 3D objects and animations will contribute to offer a new 3D-immersive experience

The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer

MAb 4C5 is a cell impermeable, anti-HSP90 murine monoclonal antibody, originally produced using hybridoma technology. We have previously shown that mAb 4C5 specifically recognizes both the α- and to a lesser extent the β-isoform of HSP90. Additionally, in vitro and in vivo studies revealed that by selectively inhibiting the function of cell-surface HSP90, mAb 4C5 significantly impairs cancer cell invasion and metastasis. Here we describe the reconstitution of mAb 4C5 into a mouse-human chimera. More importantly we report that mAb 4C5 and consequently its chimeric counterpart are completely devoid of heavy chain and consist only of a functional kappa light chain dimer. The chimeric antibody is shown to retain the original antibody's specificity and functional properties. Thus it is capable of inhibiting the function of surface HSP90, leading to reduced cancer cell invasion in vitro. Finally, we present in vivo evidence showing that the chimeric 4C5 significantly inhibits the metastatic deposit formation of MDA-MB-453 cells into the lungs of SCID mice. These data suggest that a chimeric kappa light chain antibody could be potentially used as an anti-cancer agent, thereby introducing a novel type of antibody fragment, with reduced possible adverse immunogenic effects, into cancer therapeutics

Gap junctions in the adult cerebral cortex: regional differences in their distribution and cellular expression of connexins

Gap junctions are membrane channels that mediate electrical and metabolic coupling between adjacent cells. Immunocytochemical analysis by using a panel of anti-connexin antibodies, as well as electron microscopy of thin sections and freeze-fracture replicas, has shown that gap junctions and their constituent proteins are abundant in the cerebral cortex of the adult rat. Their frequency and distribution vary in different cortical regions, which may reflect differences in the cellular and functional organization of these areas of the cortex. Gap junctions were identified between glial cells and, less frequently, between neuronal elements. Heterologous junctions were also identified between astrocytes and oligodendrocytes and between neurons and glia; the latter category included abundant junctions between astrocytic processes and neurons. Double-antibody labelling experiments in tissue sections and in acutely dissociated cells showed that connexin 32 was expressed in neurons and oligodendrocytes, whereas connexin 43, widely believed to be expressed only in astrocytes, was also localized in a population of cortical neurons. These results show that gap junctions can provide a major nonsynaptic means of communication between cortical cell types

Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons

Strategies to enhance neural stem/precursor cell (NPC) capacity to yield multipotential, proliferative, and migrating pools of cells that can efficiently differentiate into neurons could be crucial for structural repair after neurodegenerative damage. Here, we have generated a lentiviral vector for expression of insulin-like growth factor-I (IGF-1) and investigated the impact of IGF-1 transduction on the properties of cultured NPCs (IGF-1-NPCs). Under proliferative conditions, IGF-1 transduction promoted cell cycle progression via cyclin D1 up-regulation and Akt phosphorylation. Remarkably upon differentiation-inducing conditions, IGF-1-NPCs cease to proliferate and differentiate to a greater extent into neurons with significantly longer neurites, at the expense of astrocytes. Moreover, using live imaging we provide evidence that IGF-1 transduction enhances the motility and tissue penetration of grafted NPCs in cultured cortical slices. These results illustrate the important consequence of IGF-1 transduction in regulating NPC functions and offer a potential strategy to enhance the prospective repair potential of NPCs. © 2010 International Society for Neurochemistry

BM88 is an early marker of proliferating precursor cells that will differentiate into the neuronal lineage.

Progression of progenitor cells towards neuronal differentiation is tightly linked with cell cycle control and the switch from proliferative to neuron-generating divisions. We have previously shown that the neuronal protein BM88 drives neuroblastoma cells towards exit from the cell cycle and differentiation into a neuronal phenotype in vitro. Here, we explored the role of BM88 during neuronal birth, cell cycle exit and the initiation of differentiation in vivo. By double- and triple-labelling with the S-phase marker BrdU or the late G2 and M-phase marker cyclin B1, antibodies to BM88 and markers of the neuronal or glial cell lineages, we demonstrate that in the rodent forebrain, BM88 is expressed in multipotential progenitor cells before terminal mitosis and in their neuronal progeny during the neurogenic interval, as well as in the adult. Further, we defined at E16 a cohort of proliferative progenitors that exit S phase in synchrony, and by following their fate for 24 h we show that BM88 is associated with the dynamics of neuron-generating divisions. Expression of BM88 was also evident in cycling cortical radial glial cells, which constitute the main neurogenic population in the cerebral cortex. In agreement, BM88 expression was markedly reduced and restricted to a smaller percentage of cells in the cerebral cortex of the Small eye mutant mice, which lack functional Pax6 and exhibit severe neurogenesis defects. Our data show an interesting correlation between BM88 expression and the progression of progenitor cells towards neuronal differentiation during the neurogenic interval

Combining RANK/RANKL and ERBB-2 targeting as a novel strategy in ERBB-2-positive breast carcinomas

Background: ERBB-2 is overexpressed in about 20% of breast cancers (BCs), indicating poor prognosis. The receptor activator of nuclear factor-κB (RANK) pathway is implicated in ERBB-2 (+) BC. The purpose of this study was to elucidate the underlying molecular mechanism of this interaction and the beneficial impact of dual targeting of RANK and ERBB-2 pathways. Methods: We used SKBR3, MCF7, MDA-MB-453, and BT-474 human BC cell lines. We examined RANK and RANKL expression using RT-PCR, Western blot, and immunofluorescence. The evaluation of RANK expression in a cohort of BC patients was performed using immunohistochemistry. The interaction between RANK and ERBB family members was detected using proximity ligation assay (PLA), which enables the visualization of interacting proteins. We used inhibitors of both pathways [trastuzumab (T), pertuzumab (P), denosumab (D)]. NF-κB pathway activation was studied using Western blot. Cell growth and viability was evaluated using XTT, flow cytometry, and clonogenic assay. For cell migration evaluation, scratch assay was performed. Data were analyzed by one-way ANOVA. Results: Cell lines express RANK and RANKL. RANK immunostaining was also detected in human BC tissue samples. RANK receptor dimerizes with ERBB family members. RANK/ERBB-2 dimer number seems to be associated with ERBB-2 expression (SKBR3, 5.4; BT-474, 8.2; MCF7, 0.7; MDA-MB-453, 0.3). RANK/ERBB-2 dimers were decreased in the presence of the inhibitors D, T, and P, while they were increased after RANKL (R) treatment in SKBR3 (m, 5.4; D, 1.2; T, 1.9; DT, 0.6; TP, 1; DTP, 0.4; R, 11.8) and BT-474 (m, 8.2; D, 3.1; T, 4.3; DT, 0.7; TP, 3.4; DTP, 3.2; R, 11.6). Combination targeting of SKBR3 further decreased NF-κB pathway activation compared to single targeting. In SKBR3, RANKL and ERBB-2 blockage resulted in reduced cell proliferation, increased apoptosis, and lower metastatic potential compared to mock cells (m) and reversed values in RANKL presence. The combination treatment of SKBR3 with D, T, and P had an advantage in functional traits compared to single targeting. Denosumab suppressed NF-κB signaling and diminished proliferation rate in MDA-MB-453 cells. MCF7 did not correspond to inhibitors. Conclusions: The results indicate a novel physical and molecular association between ERBB-2 and RANK pathways that affects ERBB-2 (+) BC growth. We also present data suggesting that the combination of anti-ERBB-2 agents and RANKL inhibitors have a potential direct anti-tumor effect and should be further tested in certain BC patients. © 2019 The Author(s)

Neotectonic study of the Western Crete. Seismic risk evaluation of the active faults

A detailed study has been realized in the framework of a large-scale seismotectonic survey in Western Crete (Southern Greece), for the creation of a revised neotectonic map in a scale of 1:50.000, including the recognition and mapping of the main neotectonic faults and the evaluation of their seismic potential. For this reason, the faults under investigation were distinguished as active, possible active and inactive. Kinematic data and striations were used to estimate the corresponding stress field geometry. Two distinctive stress phases were recognized, operating after the Middle Miocene extensional exhumation of deep crustal rocks. The first N-S extension phase (D1) took place during Mid-Upper Miocene to Lower Pliocene, forming large normal faults, trending mainly E-W, that bound the large Neogene basins. The second phase (D2) took place during late Pliocene-Quaternary times, forming medium-to-large normal faults that trend mainly N-S, related to an E-W extension. In the E-W trending D1 faults, a younger strike-slip striation usually occurs, compatible with the later D2 kinematics. Smaller, mainly NE-SW trending faults, with significant lateral displacement, indicate a kinematic compatibility to the more recent D2 phase. Some of these faults act as transfer zones between the larger N-S trending D2 faults. Considering the fault length and the using several geological criteria for their seismic risk evaluation, we recognized 13 large major fault zones in the study area, six of which were considered as active, while three as possible active faults. Results obtained from the analysis of fault plane solution information verify both the determined active (D2 phase) stress field results, as well as the local kinematic behavior of the neotectonic faulting. Moreover, a detailed seismic hazard analysis, involving both probabilistic and deterministic approaches, shows a significant spatial variation of the various hazard measures, with the seismic hazard of the westernmost part of study area being controlled by the neighboring higher seismicity neotectonic fault