Functional and molecular characterization of inherited platelet disorders in the Iberian Peninsula: results from a collaborative study

BACKGROUND: The diagnostic evaluation of inherited platelet disorders (IPDs) is complicated and time-consuming, resulting in a relevant number of undiagnosed and incorrectly classified patients. In order to evaluate the spectrum of IPDs in individuals with clinical suspicion of these disorders, and to provide a diagnostic tool to centers not having access to specific platelets studies, we established the project "Functional and Molecular Characterization of Patients with Inherited Platelet Disorders" under the scientific sponsorship of the Spanish Society of Thrombosis and Haemostasis. PATIENTS/METHODS: Subjects were patients from a prospective cohort of individuals referred for clinical suspicion of IPDs as well as healthy controls. Functional studies included light transmission aggregation, flow cytometry, and when indicated, Western-blot analysis of platelet glycoproteins, and clot retraction analysis. Genetic analysis was mainly performed by sequencing of coding regions and proximal regulatory regions of the genes of interest. RESULTS: Of the 70 cases referred for study, we functionally and molecularly characterized 12 patients with Glanzmann Thrombasthenia, 8 patients with Bernard Soulier syndrome, and 8 with other forms of IPDs. Twelve novel mutations were identified among these patients. The systematic study of patients revealed that almost one-third of patients had been previously misdiagnosed. CONCLUSIONS: Our study provides a global picture of the current limitations and access to the diagnosis of IPDs, identifies and confirms new genetic variants that cause these disorders, and emphasizes the need of creating reference centers that can help health care providers in the recognition of these defects

Integrating magnetic capabilities to intracellular chips for cell trapping

Current microtechnologies have shown plenty of room inside a living cell for silicon chips. Microchips as barcodes, biochemical sensors, mechanical sensors and even electrical devices have been internalized into living cells without interfering their cell viability. However, these technologies lack from the ability to trap and preconcentrate cells in a specific region, which are prerequisites for cell separation, purification and posterior studies with enhanced sensitivity. Magnetic manipulation of microobjects, which allows a non-contacting method, has become an attractive and promising technique at small scales. Here, we show intracellular Ni-based chips with magnetic capabilities to allow cell enrichment. As a proof of concept of the potential to integrate multiple functionalities on a single device of this technique, we combine coding and magnetic manipulation capabilities in a single device. Devices were found to be internalized by HeLa cells without interfering in their viability. We demonstrated the tagging of a subpopulation of cells and their subsequent magnetic trapping with internalized barcodes subjected to a force up to 2.57 pN (for magnet-cells distance of 4.9 mm). The work opens the venue for future intracellular chips that integrate multiple functionalities with the magnetic manipulation of cells

The importance of learning in supporting energy efficiency technologies: A Case Study on Policy Intervention for Improved Insulation in Germany, the UK and Sweden

To combat climate change, different types of initiatives and policy instruments are required to support the development and dissemination of new energy efficient technologies. What type of policy instruments shall be used is, however, not pre-determined. To advance knowledge in how to design successful policy instruments, evaluations and deep-analyses are needed; this to better understand the role policy instruments have on technical change, changes in the innovation system and essential learning processes. The objective of this study is to analyze the introduction of emergent energy efficiency technologies, focusing on improved insulation in Germany, in the UK and in Sweden. The study has assessed the effect policy instruments have had on different learning processes, such as learning-bysearching, learning-by-doing, learning-by-using and learning-by-interacting. The assessment shows that learning-by-searching has been supported through private funded initiatives and thus being an essential driver for improved technologies. Learning-by-doing has been intense due to the highly concentrated market and resulted in significant production cost reductions. Processes of learning-by-using have mainly got private support, often in a very fragmented way, through intermediaries and thus with a lack of involvement of end-users, which led to limited learning. Today, European initiatives and voluntary schemes are the main facilitators of learning-by-interaction and further technology change

tbx2a Is Required for Specification of Endodermal Pouches during Development of the Pharyngeal Arches

10.1371/journal.pone.0077171PLoS ONE810-POLN