Mammalian tumor xenografts induce neovascularization in zebrafish embryos.

The zebrafish (Danio rerio)/tumor xenograft model represents a powerful new model system in cancer. Here, we describe a novel exploitation of the zebrafish model to investigate tumor angiogenesis, a pivotal step in cancer progression and target for antitumor therapies. Human and murine tumor cell lines that express the angiogenic fibroblast growth factor (FGF) 2 and/or vascular endothelial growth factor (VEGF) induce the rapid formation of a new microvasculature when grafted close to the developing subintestinal vessels of zebrafish embryos at 48 h postfertilization. Instead, no angiogenic response was exerted by related cell clones defective in the production of these angiogenic growth factors. The newly formed blood vessels sprout from the subintestinal plexus of the zebrafish embryo, penetrate the tumor graft, and express the transcripts for the zebrafish orthologues of the early endothelial markers Fli-1, VEGF receptor-2 (VEGFR2/KDR), and VE-cadherin. Accordingly, green fluorescent protein–positive neovessels infiltrate the graft when tumor cells are injected in transgenic VEGFR2:G-RCFP zebrafish embryos that express green fluorescent protein under the control of the VEGFR2/KDR promoter. Systemic exposure of zebrafish embryos immediately after tumor cell injection to prototypic antiangiogenic inhibitors, including the FGF receptor tyrosine kinase inhibitor SU5402 and the VEGFR2/KDR tyrosine kinase inhibitor SU5416, suppresses tumor-induced angiogenesis without affecting normal blood vessel development. Accordingly, VE-cadherin gene inactivation by antisense morpholino oligonucleotide injection inhibits tumor neovascularization without affecting the development of intersegmental and subintestinal vessels. These data show that the zebrafish/ tumor xenograft model represents a novel tool for investigating the neovascularization process exploitable for drug discovery and gene targeting in tumor angiogenesis

A COLLABORATIVE VIRTUAL ENVIRONMENT FOR TRAINING OF SECURITY AGENTS IN NUCLEAR EMERGENCIES

In face the recently observed security menaces related to terrorist actions and natural disasters, there is a need for a major qualification and training of the agents responsible for avoid any problems regarding to abnormal conditions. In the conventional training procedures, however, field simulations are associated to logistical and operational constraints regarded to the execution of the tests which can expose the user to risk. On the other hand, the use of virtual simulations provides an alternative to such limitations besides of promote the qualifying of professionals with a great reliability. For this reason, this paper proposes the development of a collaborative virtual environment that will be used to prepare the security agents on identifying individuals suspected of carrying radioactive materials. The development of the virtual environment consisted on modeling using Autodesk 3ds Max, where the scene itself and the scene objects were modeled besides the terrain creation and basic features programming using the Game Engine Unity 3D. In the Engine Game were included radiation detectors and avatars. The security agents were able to communicate to each other by means of auxiliary external tools like a headset software that makes possible the communication, coordination and cooperation required for an effective collaboration. Experimental tests of the virtual simulations were performed with the participation of CNEN radiological protection agents and collaborators. The tests have shown that the proposed method can contribute to improve the training results of the basic collaborative skills required for a CNEN agent in an emergency situation without the need to espose him to any kind of risk. In face of that, we hope that it can contribute to minimize the demand for qualified security professionals

Aging, sex and cognitive Theory of Mind: a transcranial direct current stimulation study

Aging is accompanied by changes in cognitive abilities and a great interest is spreading among researchers about aging impact on social cognition skills, such as the Theory of Mind (ToM). Transcranial direct current stimulation (tDCS) has been used in social cognition studies founding evidence of sex-related different effects on cognitive ToM task in a young people sample. In this randomized, double-blind, sham-controlled study, we applied one active and one sham tDCS session on the medial prefrontal cortex (mPFC) during a cognitive ToM task, including both social (i.e., communicative) and nonsocial (i.e., private) intention attribution conditions, in sixty healthy aging individuals (30 males and 30 females). In half of the participants the anode was positioned over the mPFC, whereas in the other half the cathode was positioned over the mPFC. The results showed that: (i) anodal tDCS over the mPFC led to significant slower reaction times (vs. sham) for social intention attribution task only in female participants; (ii) No effects were found in both females and males during cathodal stimulation. We show for the first time sex-related differences in cognitive ToM abilities in healthy aging, extending previous findings concerning young participants

Theory of mind performance predicts tdcs-mediated effects on the medial prefrontal cortex: A pilot study to investigate the role of sex and age

Transcranial Direct Current Stimulation (tDCS) has become an increasingly promising tool for understanding the relationship between brain and behavior. The purpose of this study was to investigate whether the magnitude of sex-and age-related tDCS effects previously found in the medial prefrontal cortex (mPFC) during a Theory of Mind (ToM) task correlates with social cognition performance; in particular, we explored whether different patterns of activity would be detected in high-and low-performing participants. For this, young and elderly, male and female participants were categorized as a low-or high-performer according to their score on the Reading the Mind in the Eyes task. Furthermore, we explored whether sex-and age-related effects associated with active tDCS on the mPFC were related to cognitive functioning. We observed the following results: (i) elderly participants experience a significant decline in ToM performance compared to young participants; (ii) low-performing elderly females report slowing of reaction time when anodal tDCS is applied over the mPFC during a ToM task; and (iii) low-performing elderly females are characterized by lower scores in executive control functions, verbal fluency and verbal short-term memory. The relationship between tDCS results and cognitive functioning is discussed in light of the neuroscientific literature on sex-and age-related differences

Recommending video content for use in group-based reminiscence therapy

REMPAD is a semi-automated cloud-based system used to facilitate digital reminiscence therapy for patients with mild-to-moderate dementia, enacted in a group setting. REMPAD uses profiles for participants and groups to proactively recommend interactive video content from the Internet to match these profiles. In this chapter, we focus on the design of the system and then the system architecture, the system build, data curation, and usage scenarios. We also report a series of steps carried out as part of our user-centered design approach to system development, and a series of analyses on interaction logs which indicate various levels of effectiveness for different configurations of the recommendation algorithm we use. The results indicate high user satisfaction when using the system, and strong tendency towards repeated use in future

Functional MRI evidence for the decline of word retrieval and generation during normal aging

International audienceThis fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing , due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming , and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automa-tisms and overlearned information. In terms of behav-ioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuro-psychological scores, and the overactivation of these uncorrelated regions would simply reveal dedifferentia-tion that occurs with aging. Altogether, our results suggest that normal aging is associated with a more difficult access to lexico-semantic operations and representations by a slowdown in executive functions, without any conceptual loss

ADAP2 in heart development: a candidate gene for the occurrence of cardiovascular malformations in NF1 microdeletion syndrome

Background Cardiovascular malformations have a higher incidence in patients with NF1 microdeletion syndrome compared to NF1 patients with intragenic mutation, presumably owing to haploinsufficiency of one or more genes included in the deletion interval and involved in heart development. In order to identify which genes could be responsible for cardiovascular malformations in the deleted patients, we carried out expression studies in mouse embryos and functional studies in zebrafish. Methods and results The expression analysis of three candidate genes included in the NF1 deletion interval, ADAP2, SUZ12 and UTP6, performed by in situ hybridisation, showed the expression of ADAP2 murine ortholog in heart during fundamental phases of cardiac morphogenesis. In order to investigate the role of ADAP2 in cardiac development, we performed loss-of-function experiments of zebrafish ADAP2 ortholog, adap2, by injecting two different morpholino oligos (adap2-MO and UTR-adap2-MO). adap2-MOs-injected embryos (morphants) displayed in vivo circulatory and heart shape defects. The molecular characterisation of morphants with cardiac specific markers showed that the injection of adap2-MOs causes defects in heart jogging and looping. Additionally, morphological and molecular analysis of adap2 morphants demonstrated that the loss of adap2 function leads to defective valvulogenesis, suggesting a correlation between ADAP2 haploinsufficiency and the occurrence of valve defects in NF1-microdeleted patients. Conclusions Overall, our findings indicate that ADAP2 has a role in heart development, and might be a reliable candidate gene for the occurrence of cardiovascular malformations in patients with NF1 microdeletion and, more generally, for the occurrence of a subset of congenital heart defects

THREE-DIMENSIONAL SPORT MOVEMENT ANALYSIS BY MEANS OF FREE FLOATING TV CAMERAS WITH VARIABLE OPTICS

INTRODUCTION: Video analysis and off-line manual digitalization is usually used for 2-D and 3-D studies of human movement in sport science. The main advantage of this approach, with respect to the recourse to opto-electronic automatic motion analyzers, is the high flexibility in system set-up, the avoidance of marking procedures and the possibility of successful operation in a wide range of environmental situations. Such features turn out to be particularly important for recordings to be performed in the frame of high-level competition, when the experimental set-up must be adapted to a pre-defined competitive environment, without interfering with the performances of the athletes. However, when methods proper to conventional close-range photogrammetry are used, most of the advantages offered by the flexibility of video analysis are not obtained. Particularly critical is the restriction of the useful calibrated volume to the field of view made possible by fixed pairs of TV cameras. In this case the useful sequence of images (where the dimension of the acquired subject allows one to limit macroscopic digitalization errors) is often insufficient for the analysis of a complete movement cycle. This limitation hinders a fruitful application of video analysis in the frame of sport activities (alpine and Nordic skiing, swimming, track and field) in which the execution of the particular technical movement is performed within a large physical space. A solution to the problem is proposed based on the use of free moving and zooming cameras. The corresponding dedicated software for repeated calibration based on Direct Linear Transformation (DLT)(Abdel Aziz and Karara, 1971) is described. Results of recording performed in the laboratory are discussed aiming at the validation of the implemented method. The description of the methodology for the recording of sport activities and the presentation of the related results confirm the operational feasibility of the proposed method and the reliability of the resulting quantitative kinematics analysis