Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma.

Background: ADAR enzymes convert adenosines to inosines within double-stranded RNAs, including microRNA (miRNA) precursors, with important consequences on miRNA retargeting and expression. ADAR2 activity is impaired in glioblastoma and its rescue has anti-tumoral effects. However, how ADAR2 activity may impact the miRNome and the progression of glioblastoma is not known. Results: By integrating deep-sequencing and array approaches with bioinformatics analyses and molecular studies, we show that ADAR2 is essential to edit a small number of mature miRNAs and to significantly modulate the expression of about 90 miRNAs in glioblastoma cells. Specifically, the rescue of ADAR2 activity in cancer cells recovers the edited miRNA population lost in glioblastoma cell lines and tissues, and rebalances expression of onco-miRNAs and tumor suppressor miRNAs to the levels observed in normal human brain. We report that the major effect of ADAR2 is to reduce the expression of a large number of miRNAs, most of which act as onco-miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with important effects on cell proliferation and migration. Conclusions: Our findings disclose an additional layer of complexity in miRNome regulation and provide information to better understand the impact of ADAR2 editing enzyme in glioblastoma. We propose that ADAR2 is a key factor for maintaining edited-miRNA population and balancing the expression of several essential miRNAs involved in cancer

Small Rural Enterprises and Innovative Business Models: A Case Study of the Turin Area

Small businesses and farms are today struggling to find an innovative solution to a globalizing market and a challenging society. Among different aspects, small businesses, especially in rural areas, need to find a balance among tailor-made innovative solutions, specific customers engagement strategies, creative value creation solutions, and new business concepts able to reshape existing markets. In this study, 16 small enterprises of rural areas near Turin belonging to different sectors collaborated to co-create innovative business models. To guide this discussion through a sustainable innovation path, a territorial Living Lab set up the four macro-topics of the co-creation workshops linked to the United Nations’ Sustainable Development Goals. Innovative business ideas were elaborated through the Brainstorming and Business Model Canvas tool and data were examined with SWOT and cross-case analysis. The results of the workshops pointed out four different innovative business ideas elaborated by the entrepreneurs, all linked by the need to translate innovation into sustainable adaptive solutions to local specificities. This case study showed that a range of enabling factors, such as the creation of a shared vision among local actors, can be codified to clear barriers and/or create innovative business solutions linked to economic, environmental, and social sustainability in rural areas

MOTOR DYSFUNCTION OF THE "NON AFFECTED" LOWER LIMB: A KINEMATIC COMPARATIVE STUDY BETWEEN HEMIPARETIC STROKE AND TOTAL KNEE PROSTHESIZED PATIENTS

In patients with hemispheric stroke, abnormal motor performances are described also in the ipsilateral limbs. They may be due to a cortical reorganization in the unaffected hemisphere; moreover, also peripheral mechanisms may play a role. To explore this hypothesis, we studied motor performances in 15 patients with hemispheric stroke and in 14 patients with total knee arthroplasty, which have a reduced motility in the prosthesized leg. Using the unaffected leg, they performed five superimposed circular trajectories in a prefixed pathway on a computerized footboard, while looking at a marker on the computer screen. The average trace error was significantly different between the groups of patients and healthy subjects [F ((2,25)) = 7.9; p = 0.003]; on the contrary, the test time execution did not vary significantly. In conclusion, both groups of patients showed abnormal motor performances of the unaffected leg; this result suggests a likely contribution of peripheral mechanisms

The Development of Sustainable Social Farming in Italy: A Case Studies Analysis

Social Farming (SF) is a rising practice that offers various typologies of initiatives involving different actors. Peculiarities consist of the types of networks organized at the territorial level and in the innovation processes they implement. In this study, through a cross-case analysis, we take into account six Italian social farms as case studies, interviewing them to understand the activities provided and their organization with the aim of highlighting both the strengths and the criticalities that may limit possible further development of Social Farming in Italy. The results of the analysis pointed out the specificities of the services offered by the social farms and the points of view of the farmers in the sector. Reflecting on these cases in light of the innovation system theory, it was possible to understand both the innovation system in which they developed and the enabling and the limiting aspects for Social Farming initiatives, as well as to codify useful lessons regarding the future organization of sustainable Social Farming services

CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation

The cytoplasmic element binding protein 1 (CPEB1) regulates many important biological processes ranging from cell cycle control to learning and memory formation, by controlling mRNA translation efficiency via 3' untranslated regions (3'UTR). In the present study, we show that CPEB1 is significantly downregulated in human Glioblastoma Multiforme (GBM) tissues and that the restoration of its expression impairs glioma cell lines growth. We demonstrate that CPEB1 promotes the expression of the cell cycle inhibitor p27(Kip1) by specifically targeting its 3'UTR, and competes with miR-221/222 binding at an overlapping site in the 3'UTR, thus impairing miR-221/222 inhibitory activity. Upon binding to p27(Kip1) 3'UTR, CPEB1 promotes elongation of poly-A tail and the subsequent translation of p27(Kip1) mRNA. This leads to higher levels of p27(Kip1) in the cell, in turn significantly inhibiting cell proliferation, and confers to CPEB1 a potential value as a tumor suppressor in Glioblastoma

Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

International audienceBiocharacterization of circulating tumor cells (CTCs) in the peripheral blood of advanced breast cancer (ABC) patients may represent a real-time tumor biopsy. We assessed HER2 status on CTCs from blood samples of ABC patients. CTCs were separated and stained using the CellSearch System. HER2 status was assessed by immunofluorescence and, when technically feasible, by fluorescence in situ hybridization. Blood samples were obtained from 66 ABC patients. Forty patients had a positive CTC sample (61%) and of these, 15 (37%) had HER2 + CTCs. We found non-concordant results in 32% of cases: 29% (8/28) of HER2-negative primary tumors had HER2-positive CTCs and 42% (5/12) of HER2-positive primary tumors had HER2-negative CTCs ( = 0.278). Our study suggests that a subset of patients with HER2-negative primary tumors develops HER2-positive CTCs during disease progression

The effect of latency on bone lengthening force and bone mineralization: an investigation using strain gauge mounted on internal distractor device

BACKGROUND: The purpose of this study was to investigate the effect of latency on the development of bone lengthening force and bone mineralization during mandible distraction osteogenesis. METHODS: Distraction tensions were investigated at different latency period in 36 rabbits using internal unilateral distractor. Strain gauges were prepared and attached to the distractor to directly assess the level of distraction tension during mandible lengthening. The tensile force environment of the mandible of rabbit during distraction was evaluated through in vivo experiments using two gauges. The animals were divided into 3 groups each containing 12 rabbits. Latency periods of 0, 4 and 7 days respectively were observed prior to beginning distraction. The distraction protocol consisted of a lengthening rate of 1 mm once daily for 8 days, followed by a consolidation phase of 2 weeks after which the animals were killed. Biopsies specimens were taken from the distracted area at the end of the distraction period. A non-distracted area of the mandible bone served as control. The specimens were analyzed by scanning electron microscopy to assess the ultrastructural pattern, and the bone mineralization. RESULTS: The resting tension acting on the distraction gap increases through distraction. The 7-day latency groups exhibit higher tension then those of 0-day and 4-days latency groups. Quantitative energy dispersive spectral analysis confirmed that immediate distractions were associated with lower calcium and phosphate atomic weight ratio. CONCLUSION: the latency periods could affect the bone lengthening tension and the bone mineralization process