Chemically and thermally stable silica nanowires with a β-sheet peptide core for bionanotechnology

Background: A series of amyloidogenic peptides based on the sequence KFFEAAAKKFFE template the silica precursor, tetraethyl orthosilicate to form silica-nanowires containing a cross-β peptide core. Results: Investigation of the stability of these fibres reveals that the silica layers protect the silica-nanowires allowing them to maintain their shape and physical and chemical properties after incubation with organic solvents such as 2-propanol, ethanol, and acetonitrile, as well as in a strong acidic solution at pH 1.5. Furthermore, these nanowires were thermally stable in an aqueous solution when heated up to 70 °C, and upon autoclaving. They also preserved their conformation following incubation up to 4 weeks under these harsh conditions, and showed exceptionally high physical stability up to 1000 °C after ageing for 12 months. We show that they maintain their β-sheet peptide core even after harsh treatment by confirming the β-sheet content using Fourier transform infrared spectra. The silica nanowires show significantly higher chemical and thermal stability compared to the unsiliconised fibrils. Conclusions: The notable chemical and thermal stability of these silica nanowires points to their potential for use in microelectromechanics processes or fabrication for nanotechnological devices

Characteristics of the fission fragments induced by the 129Xe + natSn reactions at E = 8–15A MeV

The study of nuclear multifragmentation is important for understanding the reaction mechanisms in heavy-ion collisions. In the present work, we study the nuclear reaction 129Xe + natSn in the energy range E = 8 to 15 AMeV. This experiment was performed at GANIL with the multidetector INDRA. We study the charge distributions produced in this reaction, which are broad and cover a large atomic number range. By using the data of this experiment, we identify four channels differing by the number of fragments: 1, 2, 3 and 4 fragments. In this contribution we will show a method to reconstruct the average size and excitation energy of the primary fission fragments, before their decay. The method employed is based on the fragment-light charged particles relative velocity correlation functions. Preliminary results will be presented

The ASY-EOS experiment at GSI: investigating the symmetry energy at supra-saturation densities

The elliptic-flow ratio of neutrons with respect to protons in reactions of neutron rich heavy-ions systems at intermediate energies has been proposed as an observable sensitive to the strength of the symmetry term in the nuclear Equation Of State (EOS) at supra-saturation densities. The recent results obtained from the existing FOPI/LAND data for $^{197}$Au+$^{197}$Au collisions at 400 MeV/nucleon in comparison with the UrQMD model allowed a first estimate of the symmetry term of the EOS but suffer from a considerable statistical uncertainty. In order to obtain an improved data set for Au+Au collisions and to extend the study to other systems, a new experiment was carried out at the GSI laboratory by the ASY-EOS collaboration in May 2011.Comment: Talk given by P. Russotto at the 11th International Conference on Nucleus-Nucleus Collisions (NN2012), San Antonio, Texas, USA, May 27-June 1, 2012. To appear in the NN2012 Proceedings in Journal of Physics: Conference Series (JPCS

Faecal metabolome and its determinants in inflammatory bowel disease

OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.</p

The CDR1 and other regions of immunoglobulin light chains are hot spots for amyloid aggregation

Immunoglobulin light chain-derived (AL) amyloidosis is a debilitating disease without known cure. Almost nothing is known about the structural factors driving the amyloidogenesis of the light chains. This study aimed to identify the fibrillogenic hotspots of the model protein 6aJL2 and in pursuing this goal, two complementary approaches were applied. One of them was based on several web-based computational tools optimized to predict fibrillogenic/aggregation-prone sequences based on different structural and biophysical properties of the polypeptide chain. Then, the predictions were confirmed with an ad-hoc synthetic peptide library. In the second approach, 6aJL2 protein was proteolyzed with trypsin, and the products incubated in aggregation-promoting conditions. Then, the aggregation-prone fragments were identified by combining standard proteomic methods, and the results validated with a set of synthetic peptides with the sequence of the tryptic fragments. Both strategies coincided to identify a fibrillogenic hotspot located at the CDR1 and β-strand C of the protein, which was confirmed by scanning proline mutagenesis analysis. However, only the proteolysis-based strategy revealed additional fibrillogenic hotspots in two other regions of the protein. It was shown that a fibrillogenic hotspot associated to the CDR1 is also encoded by several κ and λ germline variable domain gene segments. Some parts of this study have been included in the chapter “The Structural Determinants of the Immunoglobulin Light Chain Amyloid Aggregation”, published in Physical Biology of Proteins and Peptides, Springer 2015 (ISBN 978-3-319-21687-4)

The metabolomics of asthma control: a promising link between genetics and disease

Short-acting β agonists (e.g., albuterol) are the most commonly used medications for asthma, a disease that affects over 300 million people in the world. Metabolomic profiling of asthmatics taking β agonists presents a new and promising resource for identifying the molecular determinants of asthma control. The objective is to identify novel genetic and biochemical predictors of asthma control using an integrative “omics” approach. We generated lipidomic data by liquid chromatography tandem mass spectrometry (LC-MS), ­ using plasma samples from 20 individuals with asthma. The outcome of interest was a binary indicator of asthma control defined by the use of albuterol inhalers in the preceding week. We integrated metabolomic data with genome-wide genotype, gene expression, and methylation data of this cohort to identify genomic and molecular indicators of asthma control. A Conditional Gaussian Bayesian Network (CGBN) was generated using the strongest predictors from each of these analyses. Integrative and metabolic pathway over-representation analyses (ORA) identified enrichment of known biological pathways within the strongest molecular determinants. Of the 64 metabolites measured, 32 had known identities. The CGBN model based on four SNPs (rs9522789, rs7147228, rs2701423, rs759582) and two metabolites—monoHETE_0863 and sphingosine-1-phosphate (S1P) could predict asthma control with an AUC of 95%. Integrative ORA identified 17 significantly enriched pathways related to cellular immune response, interferon signaling, and cytokine-related signaling, for which arachidonic acid, PGE2 and S1P, in addition to six genes (CHN1, PRKCE, GNA12, OASL, OAS1, and IFIT3) appeared to drive the pathway results. Of these predictors, S1P, GNA12, and PRKCE were enriched in the results from integrative and metabolic ORAs. Through an integrative analysis of metabolomic, genomic, and methylation data from a small cohort of asthmatics, we implicate altered metabolic pathways, related to sphingolipid metabolism, in asthma control. These results provide insight into the pathophysiology of asthma control

eHealth and mHealth initiatives in Bangladesh: A scoping study

BACKGROUND: The health system of Bangladesh is haunted by challenges of accessibility and affordability. Despite impressive gains in many health indicators, recent evidence has raised concerns regarding the utilization, quality and equity of healthcare. In the context of new and unfamiliar public health challenges including high population density and rapid urbanization, eHealth and mHealth are being promoted as a route to cost-effective, equitable and quality healthcare in Bangladesh. The aim of this paper is to highlight such initiatives and understand their true potential. METHODS: This scoping study applies a combination of research tools to explore 26 eHealth and mHealth initiatives in Bangladesh. A screening matrix was developed by modifying the framework of Arksey & O’Malley, further complemented by case study and SWOT analysis to identify common traits among the selected interventions. The WHO health system building blocks approach was then used for thematic analysis of these traits. RESULTS: Findings suggest that most eHealth and mHealth initiatives have proliferated within the private sector, using mobile phones. The most common initiatives include tele-consultation, prescription and referral. While a minority of projects have a monitoring and evaluation framework, less than a quarter have undertaken evaluation. Most of the initiatives use a health management information system (HMIS) to monitor implementation. However, these do not provide for effective sharing of information and interconnectedness among the various actors. There are extremely few individuals with eHealth training in Bangladesh and there is a strong demand for capacity building and experience sharing, especially for implementation and policy making. There is also a lack of research evidence on how to design interventions to meet the needs of the population and on potential benefits. CONCLUSION: This study concludes that Bangladesh needs considerable preparation and planning to sustain eHealth and mHealth initiatives successfully. Additional formative and operational research is essential to explore the true potential of the technology. Frameworks for regulation in regards to eHealth governance should be the aim of future research on the integration of eHealth and mHealth into the Bangladesh health system.DFI

A review on autoimmune diseases Myasthenia Gravis: Causes, pathogenesis, symptoms and treatment

Abstract Native and foreign microorganisms, such as viruses, bacteria, and parasites, are actively protected by the immune system. This defense can however be improperly misdirected against tissues and cells in some people, giving rise to autoimmunity and eventually autoimmune diseases. Autoimmune disorders are a wide variety of illnesses which can affect any part of the body, either localized (such as thyroiditis) or systemic to specific organs or tissues and affect several organs or tissues (such as systemic lupus erythematosus). As an example of autoimmune diseases that affect the voluntary muscles, myasthenia gravis (MG) is an autoimmune neuromuscular junction disease (NMJ) triggered by antibodies that target postsynaptic membrane components, impede neuromuscular transmission and contribute to skeletal muscle weakness and fatigue. Here is a review of the past and clinical aspects of MG to explain the mechanisms of AChR, MuSK and Lrp4 antibodies, the history and clinical aspects of MG are explored with an emphasis on the structure and role of myasthenic autoantigens at the NMJ and how they are influenced by the pathogenic mechanisms of the autoantibodies.</jats:p

Polyaniline doping with nanoparticles: A review on the potential of electrical properties

Abstract During this decade, there is a growing interest of the conducting polymers owing to their exceptional and outstanding electrical properties which makes them potentially applicable in a wide range such as electrochromic displays electronic devices, modified electrodes, chemical and bio-sensors. Here we aimed to examine the reported polyaniline doping (PANI) with graphene oxide (GO) and carbon nanotubes (CNT) by insitu polymerization. The molecular structure of PANI and its composites was characterized using FTIR, X-ray diffraction and their morphologies described by scanning electron microscopy (SEM). Previous results showed that the strength of composite peaks was higher than pure PANI due to charge transfer between PANI and graphic allotropes, and the aniline molecules have been physically adsorbed and polymerized on the surface of GO and CNT due to the interaction of p – p * electron. PANI describes a multi-diameter external layer of composites depending on the PANI degree of deposition, where the core GO and CNT participate. The conductivity calculation explained that 0.1 wt % of PANI with CO matrix has conductivity 17 folds higher than that without GO.</jats:p

Metformin compounds: A review on the importance and the possible applications

Abstract Metformin is a particular compound able to coordinate metal ions and form complexes with Schiff bases that have unique properties and high stability, for a wide range of applications. This review describes and discusses organic and inorganic several reactions of synthesis of metformin complexes that coordinate some metal ions such as Ni, Co, Nd, Cr, Cu. These synthesis methods of metformin complexes are shown by the published results and characterization analyses. In medicine and pharmacy, these complexes are commonly applied and have shown a positive reaction in the fields. These complexes have been recommended to lower blood glucose levels and suggested as anti-cancer, anti-bacterial, and anti-leukemia compounds, and some have been used against leukemia. It has also been documented that the addition of specific ligands to metformin has also improved metformin’s pharmacokinetic activity. Therefore, the preparation of many of the Schiff bases and complexes of metformin, such as [Nd (III) metformin Schiff Base, Co(TMP)(MET)(H2O)Cl2], [Ni(TMP)(MET)(H2O)Cl2, grapheneoxide-metformin-nickel, tetrachloro (metfo-rmin) platinum (IV) dimethyl, Cr(III)-2Mfn. HCl and others are described and discussed here. These complexes have the potential to be used for some biological activities, in addition to their potent as a catalyst of the carbon-carbon coupling reaction.</jats:p