Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation

Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism

A protocol paper: community engagement interventions for cardiovascular disease prevention in socially disadvantaged populations in the UK: an implementation research study

Background: Cardiovascular disorders (CVD) are the single greatest cause of mortality worldwide. In the UK, the National Health Service (NHS) has launched an initiative of health checks over and above current care to tackle CVD. However, the uptake of Health Checks is poor in disadvantaged communities. This protocol paper sets out a UK-based study (Sussex and Nottingham) aiming to co-produce a community delivered CVD risk assessment and coaching intervention to support community members to reduce their risk of CVD. The overall aim of the project is to implement a tailored-to-context community engagement (CE) intervention on awareness of CVD risks in vulnerable populations in high, middle and low-income countries. The specific objectives of the study are to enhance stakeholder' engagement; to implement lifestyle interventions for cardiovascular primary prevention, in disadvantaged populations and motivate uptake of NHS health checks. Methods: This study uses both qualitative and quantitative methods in three phases of evaluation, including pre-, per-and post-implementation. To ensure contextual appropriateness the 'Scaling-up Packages of Interventions for Cardiovascular disease prevention in selected sites in Europe and Sub-Saharan Africa: An implementation research' (SPICES) project will organize a multi-component community-engagement intervention. For the qualitative component, the pre-implementation phase will involve a contextual assessment and stakeholder mapping, exploring potentials for CVD risk profiling strategies and led by trained Community Health Volunteers (CHV) to identify accessibility and acceptability. The per-implementation phase will involve healthy lifestyle counselling provided by CHVs and evaluation of the outcome to identify fidelity and scalability. The post-implementation phase will involve developing sustainable community-based strategies for CVD risk reduction. All three components will include a process evaluation. A stepped wedge cluster randomised trial of the roll out will focus on implementation outcomes including uptake and engagement and changes in risk profiles. The quantitative component includes pre and post-intervention surveys. The theory of the socio-ecological framework will be applied to analyse the community engagement approach. Discussion: Based on the results ultimately a sustainable community engagement-based strategy for the primary prevention of CVD risk will be developed to enhance the performance of NHS health care in the UK. The Trial Registration number is ISRCTN68334579

Interplay between edge states and simple bulk defects in graphene nanoribbons

We study the interplay between the edge states and a single impurity in a zigzag graphene nanoribbon. We use tight-binding exact diagonalization techniques, as well as density functional theory calculations to obtain the eigenvalue spectrum, the eigenfunctions, as well the dependence of the local density of states (LDOS) on energy and position. We note that roughly half of the unperturbed eigenstates in the spectrum of the finite-size ribbon hybridize with the impurity state, and the corresponding eigenvalues are shifted with respect to their unperturbed values. The maximum shift and hybridization occur for a state whose energy is inverse proportional to the impurity potential; this energy is that of the impurity peak in the DOS spectrum. We find that the interference between the impurity and the edge gives rise to peculiar modifications of the LDOS of the nanoribbon, in particular to oscillations of the edge LDOS. These effects depend on the size of the system, and decay with the distance between the edge and the impurity.Comment: 10 pages, 15 figures, revtex

DNA nucleotide-specific modulation of \mu A transverse edge currents through a metallic graphene nanoribbon with a nanopore

We propose two-terminal devices for DNA sequencing which consist of a metallic graphene nanoribbon with zigzag edges (ZGNR) and a nanopore in its interior through which the DNA molecule is translocated. Using the nonequilibrium Green functions combined with density functional theory, we demonstrate that each of the four DNA nucleotides inserted into the nanopore, whose edge carbon atoms are passivated by either hydrogen or nitrogen, will lead to a unique change in the device conductance. Unlike other recent biosensors based on transverse electronic transport through DNA nucleotides, which utilize small (of the order of pA) tunneling current across a nanogap or a nanopore yielding a poor signal-to-noise ratio, our device concept relies on the fact that in ZGNRs local current density is peaked around the edges so that drilling a nanopore away from the edges will not diminish the conductance. Inserting a DNA nucleotide into the nanopore affects the charge density in the surrounding area, thereby modulating edge conduction currents whose magnitude is of the order of \mu A at bias voltage ~ 0.1 V. The proposed biosensor is not limited to ZGNRs and it could be realized with other nanowires supporting transverse edge currents, such as chiral GNRs or wires made of two-dimensional topological insulators.Comment: 6 pages, 6 figures, PDFLaTe

LABEC, the INFN ion beam laboratory of nuclear techniques for environment and cultural heritage

The LABEC laboratory, the INFN ion beam laboratory of nuclear techniques for environment and cultural heritage, located in the Scientific and Technological Campus of the University of Florence in Sesto Fiorentino, started its operational activities in 2004, after INFN decided in 2001 to provide our applied nuclear physics group with a large laboratory dedicated to applications of accelerator-related analytical techniques, based on a new 3 MV Tandetron accelerator. The new accelerator greatly improved the performance of existing Ion Beam Analysis (IBA) applications (for which we were using since the 1980s an old single-ended Van de Graaff accelerator) and in addition allowed to start a novel activity of Accelerator Mass Spectrometry (AMS), in particular for 14C dating. Switching between IBA and AMS operation became very easy and fast, which allowed us high flexibility in programming the activities, mainly focused on studies of cultural heritage and atmospheric aerosol composition, but including also applications to biology, geology, material science and forensics, ion implantation, tests of radiation damage to components, detector performance tests and low-energy nuclear physics. This paper describes the facilities presently available in the LABEC laboratory, their technical features and some success stories of recent applications

Nigerian cultural beliefs about mental health conditions and traditional healing: a qualitative study

Purpose: Cultural beliefs and traditions are integral to understanding indigenous mental health conditions (MHCs) and traditional healing. However, Nigerian cultural beliefs about MHCs and traditional healing are under-researched. Design/methodology/approach: The study adopted a qualitative design using a critical realist and social constructionist perspectives to explore Nigerian mental health care practitioners (MHCPs) and lay participants (LPs) views regarding mental health conditions and traditional healing. Purposive and snowball sampling techniques were employed to select 53 participants (MHCPs = 26; LPs = 27; male = 32; female = 21) in four Nigerian cities (Ado-Ekiti, Enugu, Jos and Zaria). Data were collected using semi-structured interviews and analysed through thematic analyses. Findings: The datasets revealed three overarching themes, namely: (i) existing cultural beliefs about MHCs as spiritual curse; (ii) description of traditional healing as the first treatment modality for MHCs; and (iii) perceived stigma associated with MHCs and help-seeking behaviours. Originality/Practical implications: A study of Nigerian cultural beliefs and traditional healing contribute meaningfully to mental health systems. Future research and policy initiatives could explore ways of optimising traditional healing practices and community awareness programmes to increase access to mental health care in Nigeria

Optical properties and charge-transfer excitations in edge-functionalized all-graphene nanojunctions

We investigate the optical properties of edge-functionalized graphene nanosystems, focusing on the formation of junctions and charge transfer excitons. We consider a class of graphene structures which combine the main electronic features of graphene with the wide tunability of large polycyclic aromatic hydrocarbons. By investigating prototypical ribbon-like systems, we show that, upon convenient choice of functional groups, low energy excitations with remarkable charge transfer character and large oscillator strength are obtained. These properties can be further modulated through an appropriate width variation, thus spanning a wide range in the low-energy region of the UV-Vis spectra. Our results are relevant in view of designing all-graphene optoelectronic nanodevices, which take advantage of the versatility of molecular functionalization, together with the stability and the electronic properties of graphene nanostructures.Comment: J. Phys. Chem. Lett. (2011), in pres

The role of insulin therapy and glucose normalisation in patients with acute coronary syndrome

Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose–insulin–potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemia improves outcome in patients with AMI, achievement of glucose regulation is difficult and carries the risk of hypoglycaemia. More research is needed to determine the optimal glucose target levels in AMI and to investigate whether computerised glucose protocols and continuous glucose sensors can improve safety and efficacy of IGL