A Spitzer IRS Low-Resolution Spectroscopic Search for Buried AGNs in Nearby Ultraluminous Infrared Galaxies - A Constraint on Geometry between Energy Sources and Dust -

We present the results of Spitzer IRS low-resolution infrared 5-35 micron spectroscopy of nearby ultraluminous infrared galaxies (ULIRGs) at z < 0.15. We focus on the search for the signatures of buried active galactic nuclei (AGNs) in the complete sample of ULIRGs classified optically as non-Seyferts (LINERs or HII-regions). In addition to polycyclic aromatic hydrocarbon (PAH) emission features at 6.2 micron, 7.7 micron, and 11.3 micron, the conventional tool of starburst-AGN separation, we use the optical depths of the 9.7 micron and 18 micron silicate dust absorption features to infer the geometry of energy sources and dust at the nuclei of these ULIRGs, namely, whether the energy sources are spatially well mixed with dust(a normal starburst) or are more centrally concentrated than the dust (a buried AGN). Infrared spectra of at least 30%, and possibly 50%, of the observed optical non-Seyfert ULIRGs are naturally explained by emission consisting of (1) energetically insignificant, modestly obscured (Av < 20-30 mag) PAH-emitting normal starbursts, and (2) energetically dominant, highly dust-obscured, centrally concentrated energy sources with no PAH emission. We interpret the latter component as a buried AGN. The fraction of ULIRGs showing some buried AGN signatures is higher in LINER ULIRGs than in HII-region ULIRGs. Most of the luminous buried AGN candidates are found in ULIRGs with cool far-infrared colors. Where the absorption-corrected intrinsic AGN luminosities are derivable with little uncertainty, they are found to be of the order of 10^12Lsun, accounting for the bulk of the ULIRGs' luminosities. The 5-35 micron spectroscopic starburst/AGN classifications are generally consistent with our previous classifications based on 3-4 micron spectra for the same sample.Comment: 67 pages, 13 figures, accepted for publication in Ap

A Camera Phone Localised Surface Plasmon Biosensing Platform Towards Low-Cost Label-Free Diagnostic Testing

Developmental work towards a camera phone diagnostic platform applying localized surface plasmon resonance (LSPR) labelfree sensing is presented. The application of spherical gold nanoparticles and nanorods are considered and assessed against ease of application, sensitivity, and practicality for a sensor for the detection of CCL2 (chemokine ligand 2). The sensitivity of the platform is compared with that of a commercial UV/Vis spectrometer. The sensitivity of the camera phone platform is found to be 30% less than that of the commercial system for an equivalent incubation time, but approaches that of the commercial system as incubation time increases. This suggests that the application of LSPR sensing on a portable camera phone devices may be a highly effective label-free approach for point-of-care use as a low-cost diagnostic sensing tool in environments where dedicated equipment is not available

Modeling the Dust Properties of z ~ 6 Quasars with ART^2 -- All-wavelength Radiative Transfer with Adaptive Refinement Tree

The detection of large quantities of dust in z ~ 6 quasars by infrared and radio surveys presents puzzles for the formation and evolution of dust in these early systems. Previously (Li et al. 2007), we showed that luminous quasars at z > 6 can form through hierarchical mergers of gas-rich galaxies. Here, we calculate the dust properties of simulated quasars and their progenitors using a three-dimensional Monte Carlo radiative transfer code, ART^2 -- All-wavelength Radiative Transfer with Adaptive Refinement Tree. ART^2 incorporates a radiative equilibrium algorithm for dust emission, an adaptive grid for inhomogeneous density, a multiphase model for the ISM, and a supernova-origin dust model. We reproduce the SED and dust properties of SDSS J1148+5251, and find that the infrared emission are closely associated with the formation and evolution of the quasar host. The system evolves from a cold to a warm ULIRG owing to heating and feedback from stars and AGN. Furthermore, the AGN has significant implications for the interpretation of observation of the hosts. Our results suggest that vigorous star formation in merging progenitors is necessary to reproduce the observed dust properties of z~6 quasars, supporting a merger-driven origin for luminous quasars at high redshifts and the starburst-to-quasar evolutionary hypothesis. (Abridged)Comment: 26 pages, 22 figures, accepted by ApJ. Version with full resolution images is available at http://www.cfa.harvard.edu/~yxli/ARTDUST/astroph0706.3706.pd

Low-grade inflammation, diet composition and health: current research evidence and its translation

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims

Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy

Acknowledgements The authors are grateful to Nils Lindstrom and members of the Gillingwater laboratory for advice and assistance with this study and helpful comments on the manuscript; Neil Cashman for the NSC-34 cell line; and Ji-Long Liu for the DrosophilasmnA and smnB lines. This work was supported by grants from the SMA Trust (to T.H. Gillingwater, P.J. Young, and R. Morse), BDF Newlife (to T.H. Gillingwater and S.H. Parson), the Anatomical Society (to T.H. Gillingwater and S.H. Parson), the Muscular Dystrophy Campaign (to T.H. Gillingwater), the Jennifer Trust for Spinal Muscular Atrophy (to H.R. Fuller), the Muscular Dystrophy Association (to G.E. Morris), the Vandervell Foundation (to P.J. Young), the Medical Research Council (GO82208 to I.M. Robinson), Roslin Institute Strategic Grant funding from the BBSRC (to T.M. Wishart), the BBSRC (to C.G. Becker), the Deutsche Forschungsgemeinschaft and EU FP7/2007-2013 (grant no. 2012-305121, NeurOmics, to B. Wirth), the Center for Molecular Medicine Cologne (to B. Wirth and M. Hammerschmidt), and SMA Europe (to M.M. Reissland). We would also like to acknowledge financial support to the Gillingwater lab generated through donations to the SMASHSMA campaign.Peer reviewedPublisher PD

Fossil Carder Bee's nest from the Hominin locality of Taung, South Africa

The Buxton-Norlim Limeworks southwest of Taung, South Africa, is renowned for the discovery of the first Australopithecus africanus fossil, the ‘Taung Child’. The hominin was recovered from a distinctive pink calcrete that contains an abundance of invertebrate ichnofauna belonging to the Coprinisphaera ichnofacies. Here we describe the first fossil bee’s nest, attributed to the ichnogenus Celliforma, from the Plio-Pleistocene of Africa. Petrographic examination of a cell lining revealed the preservation of an intricate organic matrix lined with the calcitic casts of numerous plant trichomes–a nesting behaviour unique to the modern-day carder bees (Anthidiini). The presence of Celliforma considered alongside several other recorded ichnofossils can be indicative of a dry, savannah environment, in agreement with recent work on the palaeoenvironment of Plio-Pleistocene southern Africa. Moreover, the occurrence of ground-nesting bees provides further evidence that the pink calcrete deposits are of pedogenic origin, rather than speleogenic origin as has previously been assumed. This study demonstrates the potential value of insect trace fossils as palaeoenvironmental indicators

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance

Semaphorin 3A Suppresses Tumor Growth and Metastasis in Mice Melanoma Model

<div><h3>Background</h3><p>Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A) acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation.</p> <h3>Methodology/Principal Findings</h3><p>In this study, using multiple <em>in vitro</em> and <em>in vivo</em> approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor <em>in vitro</em> and <em>in vivo</em> mice (C57BL/6) models. Mouse melanoma (B16F10) cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of <em>in vivo</em> tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents.</p> <h3>Conclusions</h3><p>Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.</p> </div

The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Obesity and insulin resistance are two major risk factors underlying the metabolic syndrome. The development of these metabolic disorders is frequently studied, but mainly in liver, skeletal muscle, and adipose tissue. To gain more insight in the role of the small intestine in development of obesity and insulin resistance, dietary fat-induced differential gene expression was determined along the longitudinal axis of small intestines of C57BL/6J mice.</p> <p>Methods</p> <p>Male C57BL/6J mice were fed a low-fat or a high-fat diet that mimicked the fatty acid composition of a Western-style human diet. After 2, 4 and 8 weeks of diet intervention small intestines were isolated and divided in three equal parts. Differential gene expression was determined in mucosal scrapings using Mouse genome 430 2.0 arrays.</p> <p>Results</p> <p>The high-fat diet significantly increased body weight and decreased oral glucose tolerance, indicating insulin resistance. Microarray analysis showed that dietary fat had the most pronounced effect on differential gene expression in the middle part of the small intestine. By overrepresentation analysis we found that the most modulated biological processes on a high-fat diet were related to lipid metabolism, cell cycle and inflammation. Our results further indicated that the nuclear receptors Ppars, Lxrs and Fxr play an important regulatory role in the response of the small intestine to the high-fat diet. Next to these more local dietary fat effects, a secretome analysis revealed differential gene expression of secreted proteins, such as Il18, Fgf15, Mif, Igfbp3 and Angptl4. Finally, we linked the fat-induced molecular changes in the small intestine to development of obesity and insulin resistance.</p> <p>Conclusion</p> <p>During dietary fat-induced development of obesity and insulin resistance, we found substantial changes in gene expression in the small intestine, indicating modulations of biological processes, especially related to lipid metabolism. Moreover, we found differential expression of potential signaling molecules that can provoke systemic effects in peripheral organs by influencing their metabolic homeostasis. Many of these fat-modulated genes could be linked to obesity and/or insulin resistance. Together, our data provided various leads for a causal role of the small intestine in the etiology of obesity and/or insulin resistance.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London