RIO Country Report 2016: Ireland

The 2016 series of the RIO Country Report analyses and assesses the development and performance of the national research and innovation system of the EU-28 Member States and related policies with the aim of monitoring and evaluating the EU policy implementation as well as facilitating policy learning in the Member States.JRC.B.7-Knowledge for Finance, Innovation and Growt

Molecular mechanism of orlistat hydrolysis by the thioesterase of human fatty acid synthase for targeted drug discovery

Indiana University-Purdue University Indianapolis (IUPUI)Fatty acid synthase (FASN) is over-expressed in many cancers, and novel inhibitors that target FASN may find use in the treatment of cancers. It has been shown that orlistat, an FDA approved drug for weight loss, inhibits the thioesterase (TE) of FASN, but can be hydrolyzed by TE. To understand the mechanisms of TE action and for designing better FASN inhibitors, I examined the mechanism of orlistat hydrolysis by TE using molecular dynamics simulations. I found that the hexyl tail of orlistat undergoes a conformational transition, destabilizing a hydrogen bond that forms between orlistat and the active site histidine. A water molecule can then hydrogen bond with histidine and become activated to hydrolyze orlistat. These findings suggest that rational design of inhibitors that block hexyl tail transition may lead to a more potent TE inhibitor. To search for novel inhibitors of TE, I performed virtual DOCK screening of FDA approved drugs followed by a fluorogenic assay using recombinant TE protein and found that proton pump inhibitors (PPIs) can competitively inhibit TE. PPIs, which are used for the treatment of gastroesophageal reflux and peptic ulcers, work to decrease gastric acid production by binding irreversibly with gastric hydrogen potassium ATPase in the stomach. Recently, PPIs have been reported to reduce drug resistance in cancer cells when used in combination with chemotherapeutics, although the mechanism of resistance reduction is unknown. Further investigation showed that PPIs are able to decrease FASN activity and cancer cell proliferation in a dose-dependent manner. These findings provide new evidence that FDA approved PPIs may synergistically suppress cancer cells by inhibiting TE of FASN and suggests that the use of PPIs in combinational therapies for the treatment of many types of cancer, including pancreatic cancer, warrants further investigation

RIO Country Report 2017: Ireland

The R&I Observatory country report 2017 provides a brief analysis of the R&I system covering the economic context, main actors, funding trends & human resources, policies to address R&I challenges, and R&I in national and regional smart specialisation strategies. Data is from Eurostat, unless otherwise referenced and is correct as at January 2018. Data used from other international sources is also correct to that date. The report provides a state-of-play and analysis of the national level R&I system and its challenges, to support the European Semester.JRC.B.7-Knowledge for Finance, Innovation and Growt

An examination of the role of the Public Library in Cape Town, in support of Early Childhood Development, with special reference to Harare Public Library, Khayelitsha

The purpose of this study was to investigate the role of the Harare Public Library, Khayelitsha, in empowering Early Childhood Development Centres (crèches and nursery schools) in its community. The researcher focused on the relationships the library has with Early Childhood Development Centres in its community, and the non-profit organisation (NPO) providing educational services. It is argued that the provision of ECD will help reduce the cycle of poverty by strengthening the educational foundation of South Africa’s children. The main finding of the study is that strong relationships between libraries and other community stakeholders are critical in offering a better future for the children of disadvantaged communities