Bioprospection of Natural Sources of Polyphenols with Therapeutic Potential for Redox-Related Diseases

Funding: iNOVA4Health-UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged. This work was supported by Fundação para a Ciência e Tecnologia (IF/01097/2013 to C.N.S.), by The Scottish Government Rural and Environment Science and Analytical Services Division (A.F. and D.S.), and BacHBerry FP7-KBBE-2013-613793 (R.M., A.F., C.J., I.C., G.G., R.R.-R., J.P., A.M., C.D., D.S. and C.N.S.). T.F.O. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), and is currently supported by the DFG under Germany’s Excellence Strategy—EXC 2067/1-390729940.Plants are a reservoir of high-value molecules with underexplored biomedical applications. With the aim of identifying novel health-promoting attributes in underexplored natural sources, we scrutinized the diversity of (poly)phenols present within the berries of selected germplasm from cultivated, wild, and underutilized Rubus species. Our strategy combined the application of metabolomics, statistical analysis, and evaluation of (poly)phenols' bioactivity using a yeast-based discovery platform. We identified species as sources of (poly)phenols interfering with pathological processes associated with redox-related diseases, particularly, amyotrophic lateral sclerosis, cancer, and inflammation. In silico prediction of putative bioactives suggested cyanidin-hexoside as an anti-inflammatory molecule which was validated in yeast and mammalian cells. Moreover, cellular assays revealed that the cyanidin moiety was responsible for the anti-inflammatory properties of cyanidin-hexoside. Our findings unveiled novel (poly)phenolic bioactivities and illustrated the power of our integrative approach for the identification of dietary (poly)phenols with potential biomedical applications.publishersversionpublishe

Verified Synthesis of Optimal Safety Controllers for Human-Robot Collaboration

In human-robot collaboration, software-based safety controllers are used to improve operational safety, e.g., by triggering shutdown mechanisms or emergency stops to avoid accidents. Complex robotic tasks and increasingly close human-robot interaction pose new challenges to controller developers and certification authorities. Key among these challenges is the need to assure the correctness of safety controllers under explicit (and preferably weak) assumptions. To address this need, we introduce and evaluate a tool-supported approach for safety controller synthesis and deployment. The new approach focuses on human-robot collaboration in manufacturing, and is informed by the process, risk analysis, and relevant safety regulations for the target application. Controllers are selected from a design space of feasible controllers according to a set of optimality criteria, formally verified against correctness criteria, and translated into executable code and validated in a digital twin. The resulting controller can detect the occurrence of hazards, move the process into a safe state, and, in certain circumstances, return the process to an operational state from which it can resume its original task

StrategyNZ: mapping our future strategy maps - from Te Papa to the Legislative Council Chamber

This report explains the inputs, processes and outputs of the StrategyNZ workshop held in March 2011. The aim was to encourage a conversation about our long-term future. Consensus emerged that New Zealand should work to ‘create a place where talent wants to live’. See Report 12 and the workshop booklet

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible

The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer

The Anthropocene is functionally and stratigraphically distinct from the Holocene

Human activity is leaving a pervasive and persistent signature on Earth. Vigorous debate continues about whether this warrants recognition as a new geologic time unit known as the Anthropocene. We review anthropogenic markers of functional changes in the Earth system through the stratigraphic record. The appearance of manufactured materials in sediments − including aluminum, plastics and concrete − coincides with global spikes in fallout radionuclides and particulates from fossil-fuel combustion. Carbon, nitrogen, and phosphorus cycles have been substantially modified over the last century. Rates of sea-level rise, and the extent of human perturbation of the climate system, exceed Late Holocene changes. Biotic changes include species invasions worldwide and accelerating rates of extinction. These combined signals render the Anthropocene stratigraphically distinct from the Holocene and earlier epochs

“What if There's Something Wrong with Her?”‐How Biomedical Technologies Contribute to Epistemic Injustice in Healthcare

While there is a steadily growing literature on epistemic injustice in healthcare, there are few discussions of the role that biomedical technologies play in harming patients in their capacity as knowers. Through an analysis of newborn and pediatric genetic and genomic sequencing technologies (GSTs), I argue that biomedical technologies can lead to epistemic injustice through two primary pathways: epistemic capture and value partitioning. I close by discussing the larger ethical and political context of critical analyses of GSTs and their broader implications for just and equitable healthcare delivery