Optimization of ruthenium as a buffer layer for non-collinear antiferromagnetic Mn<inf>3</inf>X films

Two thin film deposition routes were studied for the growth of high quality single crystalline Ru (0001) epitaxial films on c-Al2O3 substrates using RF-magnetron sputtering. Such films are very important as buffer layers for the deposition of epitaxial non-collinear antiferromagnetic Mn3X films. The first route involved depositing Ru at 700 °C, leading to a smooth 30 nm thick film. Although, high resolution X-ray diffraction (HRXRD) revealed twinned Ru film orientations, the in-situ post-annealing eliminated one orientation, leaving the film orientation aligned with the substrate, with no in-plane lattice rotation and a large lattice mismatch (13.6%). The second route involved deposition of Ru at room temperature followed by in-situ post-annealing at 700 °C. Transmission electron microscopy confirmed a very high quality of these films, free of crystal twinning, and a 30° in-plane lattice rotation relative to the substrate, resulting in a small in-plane lattice mismatch of –1.6%. X-ray reflectivity demonstrated smooth surfaces for films down to 7 nm thickness. 30 nm thick high quality single-crystalline Mn3Ga and Mn3Sn films were grown on top of the Ru buffer deposited using the second route as a first step to realize Mn3X films for antiferromagnetic spintronics applications.H2020-MSCA-ITN-2014 SELECTA (grant agreement no. 642642 of the European Commission)

SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle

Small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) that reverse protein modification by SUMO are involved in the control of numerous cellular processes, including transcription, cell division, and cancer development. However, the physiological function of SENPs in energy metabolism remains unclear. Here, we investigated the role of SENP2 in fatty acid metabolism in C2C12 myotubes and in vivo. In C2C12 myotubes, treatment with saturated fatty acids, like palmitate, led to nuclear factor-B-mediated increase in the expression of SENP2. This increase promoted the recruitment of peroxisome proliferator-activated receptor (PPAR) and PPAR, through desumoylation of PPARs, to the promoters of the genes involved in fatty acid oxidation (FAO), such as carnitine-palmitoyl transferase-1 (CPT1b) and long-chain acyl-CoA synthetase 1 (ACSL1). In addition, SENP2 overexpression substantially increased FAO in C2C12 myotubes. Consistent with the cell culture system, muscle-specific SENP2 overexpression led to a marked increase in the mRNA levels of CPT1b and ACSL1 and thereby in FAO in the skeletal muscle, which ultimately alleviated high-fat diet-induced obesity and insulin resistance. Collectively, these data identify SENP2 as an important regulator of fatty acid metabolism in skeletal muscle and further implicate that muscle SENP2 could be a novel therapeutic target for the treatment of obesity-linked metabolic disorders.11116Ysciescopu

The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver

A tale of two societies : The doing of qualitative comparative research in Hong Kong and Britain

This article explores the challenges and opportunities for methodological innovation arising from an exploratory, cross-national, qualitative study of women’s lives in Hong Kong and Britain. We begin by briefly outlining the aims of our study and its original research design, based on life history interviews with young adult women and their mothers in each location.We then turn to a discussion of how this was modified as we recruited participants and conducted the interviews, including the use of vignettes. We aim to be transparent about some of the problems of implementing a symmetrical approach to generating qualitative data in very different socio-cultural settings compounded by the practical difficulties of geographical distance between team members. We argue for a flexible approach that takes account of local cultural sensibilities rather than trying to follow rigidly identical procedures, recognising also that, in any qualitative research team, there will be differences in approach that affect the data produced. We highlight some of the insights yielded by the problems we encountered and, in particular, an accidental innovation that occurred through an ad hoc decision to conduct focus groups with the young women, which we call ‘cross-cultural data feedback’. This innovation involved our participants in contributing to cross cultural comparison and also brought taken-for-granted assumptions in each setting into sharp relief, as well as sensitising us to issues that proved important in analysing our data. This leads us to raise issues of interpreting and analysing data from differing socio-cultural locations and translating between cultures. We conclude with some recommendations including the potential for the future development of our method of cross-cultural data feedback

Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation

Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet-fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosisopen0

Biological effects of rinsing morsellised bone grafts before and after impaction

Rinsing bone grafts before or both before and after impaction might have different effects on the incorporation of the graft. Rinsing again after impaction might negatively influence bone induction if growth factors released by impaction are washed away. We studied if transforming growth factor-βs (TGF-βs) and bone morphogenetic proteins (BMPs) are released from the mineralised matrix by impaction and if these released growth factors induce osteogenic differentiation in human mesenchymal stem cells (hMSCs). Rinsed morsellised bone allografts were impacted in a cylinder and the escaping fluid was collected. The fluid was analysed for the presence of TGF-βs and BMPs, and the osteoinductive capacity was tested on hMSCs. Abundant TGF-β was present in the fluid. No BMPs could be detected. Osteogenic differentiation of hMSCs was inhibited by the fluid. Results from our study leave us only able to speculate whether rinsing grafts again after impaction has a beneficial effect on the incorporation process or not

Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith

<p>Abstract</p> <p>Background</p> <p>Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of <it>M. fasciculata </it>geopropolis against oral pathogens, its effects on <it>S. mutans </it>biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on <it>S. mutans </it>and its immunotoxicological potential.</p> <p>Methods</p> <p>Antimicrobial activities of three hydroalcoholic extracts (HAEs) of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v) and chlorhexidine (0.12%, w/w) were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs.</p> <p>Results</p> <p>Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for <it>S. mutans </it>and <it>C. albicans</it>, but presented no activity against <it>L</it>. <it>acidophilus</it>. The MBCs for HAE-2 and HAE-3 against <it>S. mutans </it>were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on <it>S. mutans </it>biofilms after 3 h of treatment. Significant differences (p < 0.05) in total phenol and flavonoid concentrations were observed among the samples. Signs toxic effects were not observed after application of the geopropolis-based gel, but an increase in the production of IL-4 and IL-10, anti-inflammatory cytokines, was detected.</p> <p>Conclusions</p> <p>In summary, geopropolis produced by <it>M. fasciculata </it>can exert antimicrobial action against <it>S. mutans </it>and <it>C. albicans</it>, with significant inhibitory activity against <it>S. mutans </it>biofilms. The extract with the highest flavonoid concentration, HAE-2, presented the highest antimicrobial activity. In addition, a geopropolis-based gel is not toxic in an animal model and displays anti-inflammatory effect.</p

Formation of PbSe/CdSe Core/Shell Nanocrystals for Stable Near-Infrared High Photoluminescence Emission

PbSe/CdSe core/shell nanocrystals with quantum yield of 70% were obtained by the “successive ion layer adsorption and reaction” technology in solution. The thickness of the CdSe shell was exactly controlled. A series of spectral red shifts with the CdSe shell growth were observed, which was attributed to the combined effect of the surface polarization and the expansion of carriers’ wavefunctions. The stability of PbSe nanocrystals was tremendously improved with CdSe shells

Intracellular Invasion of Orientia tsutsugamushi Activates Inflammasome in ASC-Dependent Manner

Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular bacterium, which escapes from the endo/phagosome and replicates in the host cytoplasm. O. tsutsugamushi infection induces production of pro-inflammatory mediators including interleukin-1β (IL-1β), which is secreted mainly from macrophages upon cytosolic stimuli by activating cysteine protease caspase-1 within a complex called the inflammasome, and is a key player in initiating and maintaining the inflammatory response. However, the mechanism for IL-1β maturation upon O. tsutsugamushi infection has not been identified. In this study, we show that IL-1 receptor signaling is required for efficient host protection from O. tsutsugamushi infection. Live Orientia, but not heat- or UV-inactivated Orientia, activates the inflammasome through active bacterial uptake and endo/phagosomal maturation. Furthermore, Orientia-stimulated secretion of IL-1β and activation of caspase-1 are ASC- and caspase-1- dependent since IL-1β production was impaired in Asc- and caspase-1-deficient macrophages but not in Nlrp3-, Nlrc4- and Aim2-deficient macrophages. Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1β production, which is a critical innate immune response for effective host defense

Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens

There is accumulating evidence that the nucleus accumbens (NAc) has an important role in the pathophysiology of depression. As the NAc is a key component in the neural circuitry of reward, it has been hypothesized that anhedonia, a core symptom of depression, might be related to dysfunction of this brain region. Neuronal morphology and expression of plasticity-related molecules were examined in the NAc of rats displaying anhedonic behavior (measured in the sucrose-consumption test) in response to chronic mild stress. To demonstrate the relevance of our measurements to depression, we tested whether the observed changes were sensitive to reversal with antidepressants (imipramine and fluoxetine). Data show that animals displaying anhedonic behavior display an hypertrophy of medium spiny neurons in the NAc and, in parallel, have increased expression of the genes encoding for brain-derived neurotrophic factor, neural cell adhesion molecule and synaptic protein synapsin 1. Importantly, the reversal of stress-induced anhedonia by antidepressants is linked to a restoration of gene-expression patterns and dendritic morphology in the NAc. Using an animal model of depression, we show that stress induces anhedonic behavior that is associated with specific changes in the neuronal morphology and in the gene-expression profile of the NAc that are effectively reversed after treatment with antidepressants.The present work was funded by the Portuguese Foundation for Technology (FCT), project PTDC/SAU-NEU/105180/2008. FM and PL are recipients of postdoctoral fellowships and MM is recipient of a doctoral fellowship, all from FCT, Portugal