Transferrin receptor 2 is emerging as a major player in the control of iron metabolism

Abstract Our knowledge of mammalian iron metabolism has advanced dramatically over recent years. Iron is an essential element for virtually all living organisms. Its intestinal absorption and accurate cellular regulation is strictly required to ensure the coordinated synthesis of the numerous iron-containing proteins involved in key metabolic processes, while avoiding the uptake of excess iron that can lead to organ damage. A range of different proteins exist to ensure this fine control within the various tissues of the body. Among these proteins, transferrin receptor (TFR2) seems to play a key role in the regulation of iron homeostasis. Disabling mutations in TFR2 are responsible for type 3 hereditary hemochromatosis (Type 3 HH). This review describes the biological properties of this membrane receptor, with a particular emphasis paid to the structure, function and cellular localization. Although much information has been garnered on TFR2, further efforts are needed to elucidate its function in the context of the iron regulatory network

Salinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell lines

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to exhibit therapeutic activity in cancer. However, many tumors remain resistant to treatment with TRAIL. Therefore, small molecules that potentiate the cytotoxic effects of TRAIL could be used for combinatorial therapy. Here we found that the ionophore antibiotic salinomycin acts in synergism with TRAIL, enhancing TRAIL-induced apoptosis in glioma cells. Treatment with low doses of salinomycin in combination with TRAIL augmented the activation of caspase-3 and increased TRAIL-R2 cell surface expression. TRAIL-R2 upmodulation was required for mediating the stimulatory effect of salinomycin on TRAIL-mediated apoptosis, since it was abrogated by siRNA-mediated TRAIL-R2 knockdown. Salinomycin in synergism with TRAIL exerts a marked anti-tumor effect in nude mice xenografted with human glioblastoma cells. Our results suggest that the combination of TRAIL and salinomycin may be a useful tool to overcome TRAIL resistance in glioma cells and may represent a potential drug for treatment of these tumors. Importantly, salinomycin+TRAIL were able to induce cell death of well-defined glioblastoma stem-like lines

The European Research Infrastructures of the ESFRI Roadmap in Biological and Medical Sciences: status and perspectives

Introduction. Since 2002, the European Strategy Forum on Research Infrastructures  identified  the  needs  for  Research  Infrastructures  (RIs)  in  Europe  in  priority  fields  of  scientific research and drafted a strategic document, the ESFRI Roadmap, defining the  specific RIs essential to foster European research and economy. The Biological and Medical Sciences RIs (BMS RIs) were developed thanks to the active participation of many  institutions  in  different  European  member  states  associated  to  address  the  emerging  needs in biomedicine and, among these, the Italian National Institute of Health (ISS),  in virtue of its role in public health and research, has been specifically involved in the  national development and implementation of three RIs: the Biobanking and Biomolecu-lar Resources Research Infrastructure (BBMRI), the European Advanced Translational  Research Infrastructure in Medicine (EATRIS) and the European Clinical Research Infrastructures Network (ECRIN). Aim.  This  article  outlines  the  design  and  development  of  these  RIs  up  to  the  recent  achievement of the ERIC status, their importance in the Horizon 2020 programme and  their societal and economic potential impact, with special attention to their development  and significance in Italy. Conclusions.  The  ISS  plays  a  unique  role  in  fostering  a  coordinated  participation  of  excellence Italian institutes/facilities to different European biomedical RIs, thus contributing to health innovation, healthcare optimization, and healthcare cost containment.

Economics, strategy and performance of Italian performing arts: when advertising and intangible matter

At crisis times advertising is a strategic priority for Italian Performing Arts. Both the marketing and the fundraising effort, they are maximized in order to exploit willingness-to-pay and willingness-to-donate. If these efforts are maximized, increasing Advertising Expense and Intangible Assets positively affect Revenues, Gains and Net Assets. We clustered a sample of 100 Italian theatres whose reports were collected from the database AIDA. We collected 2013, 2012 and 2011 data for Investments, Intangible Assets, Total Assets, Net Assets, Total Revenues, Own Revenues (of sales), Sponsorships, Public Grants, Total Expenses, Advertising Expense, Gain or Loss. We calculated 2013-2012 and 2012-2011 variations in order to understand the strategic choice and how increasing or decreasing promotion effort affect the latest performances. Clusters in time series analysis show that, there is a strategic shift (increase vs. decrease) for Italian Performing Arts from 2011 to 2013. Most of theatres are concentrated in one cluster both for the analysis with 2013-2012 variations and with 2012-2011 ones. When theatres have increased Advertising Expense and Intangible Assets, Revenues and especially, Own Revenues, they both increase. The positive impact of the marketing effort is on Revenues and at a lesser extent, on Net Assets and Gains

It’s a matter of attention: the marketing of theatres in the age of social media

This study is aimed at understanding how theatres might adjust their marketing in order to capture the attention of audiences and stakeholders in the age of social media. Effective utilization of social networks enhances the success of marketing efforts in terms of both revenues and revenue diversification. The authors report the results of a cluster analysis of economic performance in a time series (2011–13) of a sample of 100 Italian theatres. The focus then moved to stakeholder engagement. A subsample of Milan theatres were surveyed about their use of social media. The authors conclude that offline and online marketing efforts must be maximized in the age of social media. They report on evidence in the realm of economic performance

Regulation of transferrin receptor 2 in human cancer cell lines.

In a recent study we have explored TfR2 expression in a panel of cancer cell lines and we observed that about 40% of these cell lines clearly express TfR2. Taking advantage of this observation and considering the frequent overexpression of c-Myc in cancer cells we have explored the existence of a possible relationship between c-Myc and TfR2 in these cell lines. Our results provided evidence that TfR2(+) cell lines express low c-Myc levels and low TfR1 levels, while TfR2(-) cell lines express high c-Myc and TfR1 levels. Using the erythroleukemic K562 TfR2(+) cells as a model, we observed that agents that enhance c-Myc expression, such as iron, determine a decrease of TfR2 expression, while molecules that induce a decreased c-Myc expression, such as the iron chelator desferoxamine or the kinase inhibitor ST 1571, induce an enhanced TfR2 expression. On the other hand, we have evaluated a possible effect of hypoxia and nitric oxide on TfR2 expression in erythroleukemia K526 and hepatoma HepG2 cells, providing evidence that: (i) agents inducing cellular hypoxia, such as CoCl(2), elicited a marked upmodulation of TfR1, but a downmodulation of TfR2 expression; (ii) NO(+) donors, such as sodium nitroprusside (SNP), induced a moderate decrease of TfR1, associated with a marked decline of TfR2 expression; (iii) NO donors, such as S-Nitroso-N-Acetylpenicillamine (SNAP), induced a clear increase of TfR1, associated with a moderate upmodulation of TfR2 expression. The ensemble of these observations suggests that in cancer cell lines TfR2 expression can be modulated through stimuli similar to those known to act on TfR1 and these findings may have important implications for our understanding of the role of TfR2 in the regulation of iron homeostasis

Developing a guideline to standardize the citation of bioresources in journal articles (CoBRA)

International audienceBackground: Many biomedical publications refer to data obtained from collections of biosamples. Sharing such bioresources (biological samples, data, and databases) is paramount for the present governance of research. Recognition of the effort involved in generating, maintaining, and sharing high quality bioresources is poorly organized, which does not encourage sharing. At publication level, the recognition of such resources is often neglected and/or highly heterogeneous. This is a true handicap for the traceability of bioresource use. The aim of this article is to propose, for the first time, a guideline for reporting bioresource use in research articles, named CoBRA: Citation of BioResources in journal Articles. Methods: As standards for citing bioresources are still lacking, the members of the journal editors subgroup of the Bioresource Research Impact Factor (BRIF) initiative developed a standardized and appropriate citation scheme for such resources by informing stakeholders about the subject and raising awareness among scientists and in science editors' networks, mapping this topic among other relevant initiatives, promoting actions addressed to stakeholders, launching surveys, and organizing focused workshops. Results: The European Association of Science Editors has adopted BRIF's suggestion to incorporate statements on biobanks in the Methods section of their guidelines. The BRIF subgroup agreed upon a proposed citation system: each individual bioresource that is used to perform a study and that is mentioned in the Methods section should be cited as an individual "reference [BIORESOURCE]" according to a delineated format. The EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network mentioned the proposed reporting guideline in their "guidelines under development" section

Biobankers: Treat the Poison of Invisibility with CoBRA, a Systematic Way of Citing Bioresources in Journal Articles

International audienceEven though an increasing portion of biomedical research today relies on the use of bioresources, at present biobankers are not able to trace this use in scientific literature and measure its impact with a variety of citation metrics. The "BRIF (Bioresource Research Impact Factor) and journal editors" subgroup was created precisely with the aim to study this issue and to build a standardized system to cite bioresources in journal articles. This report aims at presenting a guideline for Citation of BioResources in journal Articles (CoBRA). The guideline offers for the first time a standard for citing bioresources (including biobanks) within journal articles. It will increase their visibility and promote their sharing