Georges Dagher

The role of a bioresource research impact factor as an incentive to share human bioresources

The role of a bioresource research impact factor as an incentive to share human bioresources

BBMRI-ERIC as a resource for pharmaceutical and life science industries: the development of biobank-based Expert Centres.

Biological resources (cells, tissues, bodily fluids or biomolecules) are considered essential raw material for the advancement of health-related biotechnology, for research and development in life sciences, and for ultimately improving human health. Stored in local biobanks, access to the human biological samples and related medical data for transnational research is often limited, in particular for the international life science industry. The recently established pan-European Biobanking and BioMolecular resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC) aims to improve accessibility and interoperability between academic and industrial parties to benefit personalized medicine, disease prevention to promote development of new diagnostics, devices and medicines. BBMRI-ERIC is developing the concept of Expert Centre as public–private partnerships in the precompetitive, not-for-profit field to provide a new structure to perform research projects that would face difficulties under currently established models of academic–industry collaboration. By definition, Expert Centres are key intermediaries between public and private sectors performing the analysis of biological samples under internationally standardized conditions. This paper presents the rationale behind the Expert Centres and illustrates the novel concept with model examples.

The Effect of Propofol on Angiotensin Ii-induced Ca2+ Mobilization in Aortic Smooth Muscle Cells from Normotensive and Hypertensive Rats

We studied the effect of propofol (5.6–560 &mgr;mol/L; 1–100 &mgr;g/mL) on the mechanisms involved in Ca2+ mobilization elicited by angiotensin II (AngII) in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We studied the variations in intracellular Ca2+ ([Ca2+]i) concentrations in cultured aortic vascular smooth muscle cells (VSMCs) isolated from 6-wk-old WKY and SHR rats loaded with the Ca2+-sensitive fluorescent dye, Fura-2, using fluorescent imaging microscopy. In the absence of external Ca2+, AngII (1 &mgr;mol/L) induced a transient [Ca2+]i mobilization from internal stores that was larger in SHR than in WKY rats. Ca2+ influx was assessed after external Ca2+ (1 mmol/L) reintroduction. Propofol (1–100 &mgr;g/mL) added 5 min before the experiments did not alter AngII-induced Ca2+ release from internal stores in either strain. By contrast, Ca2+ influx elicited by AngII was significantly decreased by propofol. This effect occurred at a smaller concentration of propofol in the SHR than in the WKY rats. When Ca2+ stores were depleted by exposure of cells to thapsigargin, an inhibitor of the sarcoendoplasmic reticulum Ca2+-ATPase, reintroduction of Ca2+ to the medium induced a capacitative Ca2+ influx of similar magnitude than that elicited by AngII. This influx was also significantly decreased by propofol at 100 &mgr;g/mL ( WKY: 27 ± 3% of control values, n = 107; SHR: 16 ± 3%, n = 47;P < 0.001). In conclusion, propofol decreased AngII-induced Ca2+ influx through voltage-independent channels, without altering Ca2+ release from internal stores in aortic VSMCs. The hypertensive rats were found to be more sensitive to the effect of propofol than the normotensive rats. This suggests that the response of VSMCs to AngII may be altered by propofol. Implications: In rat aortic vascular smooth muscle cells, propofol reduced angiotensin II-elicited Ca2+ entry through capacitative Ca2+ channels without altering Ca2+ release from intracellular stores. Spontaneously hypertensive rats were more sensitive to these effects of propofol than normotensive rats. The response of vascular smooth muscle cells to angiotensin II may be altered by propofol.

Public Biobanks: Calculation and Recovery of Costs

A group of experts aided development of a cost-related tool for biobank access prices and tested it in three partnership models. A calculation grid developed by an international expert group was tested across biobanks in six countries to evaluate costs for collections of various types of biospecimens. The assessment yielded a tool for setting specimen-access prices that were transparently related to biobank costs, and the tool was applied across three models of collaborative partnership.

Extracellular Signal-Regulated Kinase Pathway Is Involved in Basic Fibroblast Growth Factor Effect on Angiotensin II–Induced Ca2+ Transient in Vascular Smooth Muscle Cell From Wistar-Kyoto and Spontaneously Hypertensive Rats

Abstract —We studied the effect of basic fibroblast growth factor (b-FGF) on different Ca 2+ mechanisms elicited by angiotensin II (Ang II) in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Intracellular Ca 2+ (Ca 2+ i ) variations were studied in cultured vascular smooth muscle cells (VSMCs) isolated from the aorta of 5- to 6-week-old WKY rats and SHR. Ca 2+ i was assessed in Fura-2–loaded cells with fluorescent imaging microscopy. Ang II subtype 1 receptor activation by Ang II (1 μmol/L) induced a transient increase in Ca 2+ i that was partially attenuated by genistein, a tyrosine kinase inhibitor. Pretreatment of VSMCs with b-FGF for 24 hours markedly stimulated the Ang II–induced Ca 2+ i release from the internal stores in WKY rats, whereas it was without effect in SHR. This was not consequent to a change in the affinity of Ang II subtype 1 receptors or an increase in their density. Inhibition of mitogen-activated protein kinase with PD 98059 reduced this stimulatory effect of the cytokine in the WKY rats. On the other hand, b-FGF stimulated the Ang II–induced Ca 2+ influx in both strains. Similar results were observed when Ca 2+ influx was induced with thapsigargin. Genistein and PD 98059 abolished the effect of b-FGF. These results show for the first time that b-FGF regulates Ca 2+ mechanisms induced by Ang II and that this regulation is different in SHR than in normotensive control animals. The extracellular signal-regulated kinase cascade is implicated in this cross-regulation with G protein–signaling pathway at 2 levels and possibly more: 1 at the tyrosine kinases and the other downstream of the extracellular signal–regulated kinase family. These results may prove useful in understanding the interaction between these 2 pathways and their implication in genetic hypertension.

Public–private relationships in biobanking: a still underestimated key component of open innovation

Access to human bioresources is essential to the understanding of human diseases and to the discovery of new biomarkers aimed at improving the diagnosis, prognosis, and the predictive response of patients to treatments. The use of biospecimens is strictly controlled by ethical assessment, which complies with the laws of the country. These laws regulate the partnerships between the biobanks and industrial actors. However, private–public partnerships (PPP) can be limiting for several reasons, which can hamper the discovery of new biological tests and new active molecules targeted to human diseases. The bottlenecks and roadblocks in establishing these partnerships include: poor organization of the biobank in setting up PPP, evaluation of the cost of human samples, the absence of experience on the public side in setting up contracts with industry, and the fact that public and private partners may not share the same objectives. However, it is critical, in particular for academic biobanks, to establish strong PPP to accelerate translational research for the benefits of patients, and to allow the sustainability of the biobank. The purpose of this review is to discuss the main bottlenecks and roadblocks that can hamper the establishment of PPP based on solid and trusting relationships.

Measuring the contribution of tumor biobanks to research in oncology: surrogate indicators and bibliographic output.

The number of biobanks, in particular hospital-integrated tumor biobanks (HITB), is increasing all around the world. This is the consequence of an increase in the need for human biological resources for scientific projects and more specifically, for translational and clinical research. The robustness and reproducibility of the results obtained depend greatly on the quality of the biospecimens and the associated clinical data. They also depend on the number of patients studied and on the expertise of the biobank that supplied the biospecimens. The quality of a research biobank is undoubtedly reflected in the number and overall quality of the research projects conducted with biospecimens provided by the biobank. Since the quality of a research project can be measured from the impact factor of resulting publications, this also provides some indication of the quality of a research biobank. It is necessary for the biobank community to define surrogate quality indicators, and to establish systems of evaluation in relation to current and future resource requirements. These indicators will help in the realistic assessment of biobanks by institutions and funding bodies, and they will help biobanks demonstrate their value, raise their quality standards, and compete for funding. Given that biobanks are expensive structures to maintain, funding issues are particularly important, especially in the current economic climate. Use of performance indicators may also contribute to the development of a biobank impact factor or bioresource research impact factor (BRIF). Here we review four major categories of indicators that appear to be useful for the evaluation of a(m) HITB (quality, activity, scientific productivity, and visibility). In addition, we propose a scoring system to measure the chosen indicators.

ANG II-induced Ca(2+) increase in smooth muscle cells from SHR is regulated by actin and microtubule networks.

We hypothesized that the cytoskeletal network in vascular smooth muscle cells (VSMC) is critical to the signaling pathways from angiotensin (ANG) II-receptor subtype 1 (AT1) activation to intracellular Ca2+([Formula: see text]) release from internal stores and Ca2+ influx. This was tested in spontaneously hypertensive rats (SHR), in which differences were reported in cultured aortic VSMC [Formula: see text]regulation and G protein function compared with those in normotensive Wistar-Kyoto (WKY) rats. In cultured aortic VSMC, disorganization of actin filaments with cytochalasin D (2 μmol/l) decreased the ANG II-induced [Formula: see text] release from internal stores and the ANG II-induced Ca2+influx in SHR in a reversible fashion, whereas it was without effect in WKY rats. On the other hand, blocking the dynamic state of the microtubule network significantly reduced ANG II-induced[Formula: see text] release from internal stores but was without effect on Ca2+ influx in either SHR or WKY rats. This study demonstrates for the first time that, in the SHR, actin filaments play a major role in linking AT1-receptor activation to both[Formula: see text] release mechanisms and capacitative Ca2+ influx. Furthermore, a functionally intact microtubule system is a necessary prerequisite for ANG II-induced [Formula: see text] release in both strains.We hypothesized that the cytoskeletal network in vascular smooth muscle cells (VSMC) is critical to the signaling pathways from angiotensin (ANG) II-receptor subtype 1 (AT(1)) activation to intracellular Ca(2+) (Ca(2+)(i)) release from internal stores and Ca(2+) influx. This was tested in spontaneously hypertensive rats (SHR), in which differences were reported in cultured aortic VSMC Ca(2+)(i) regulation and G protein function compared with those in normotensive Wistar-Kyoto (WKY) rats. In cultured aortic VSMC, disorganization of actin filaments with cytochalasin D (2 micromol/l) decreased the ANG II-induced Ca(2+)(i) release from internal stores and the ANG II-induced Ca(2+) influx in SHR in a reversible fashion, whereas it was without effect in WKY rats. On the other hand, blocking the dynamic state of the microtubule network significantly reduced ANG II-induced Ca(2+)(i) release from internal stores but was without effect on Ca(2+) influx in either SHR or WKY rats. This study demonstrates for the first time that, in the SHR, actin filaments play a major role in linking AT(1)-receptor activation to both Ca(2+)(i) release mechanisms and capacitative Ca(2+) influx. Furthermore, a functionally intact microtubule system is a necessary prerequisite for ANG II-induced Ca(2+)(i) release in both strains.

Les biobanques : quels enjeux en 2017 ?

Resume Les biobanques ou centres de ressources biologiques (CRB) sont les maillons essentiels de la recherche translationnelle. Ces structures beneficient de financements publics recurrents afin d’etablir des collections d’echantillons biologiques utilisees dans le cadre de projets de recherche. Plus de 100 biobanques ont ete developpees sur le territoire national au sein des hopitaux universitaires et des centres de lutte contre le cancer. Le developpement de nouvelles techniques et de nouvelles methodes d’analyses dans la recherche medicale bouleversent les pratiques et soulevent de nouveaux defis scientifiques et organisationnels dans la collecte, la transformation et la conservation des echantillons. Relever ces defis devient un enjeu primordial pour les biobanques. La mise en place d’une strategie dynamique pour anticiper les besoins des utilisateurs est necessaire et repose sur de nouveaux modes de fonctionnement. Cet article decrit les enjeux a court et a moyen terme pour les biobanques francaises et propose des elements d’organisation pour y repondre.

Biobank sustainability: current status and future prospects

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