Single Crystalline Cadmium Sulfide Nanowires with Branched Structure

In this article, we report the synthesis of branched single crystal CdS nanowires. This branched CdS nanostructure is prepared by a simple surfactant-directing method, which is of particular interest as it uses readily available reagents and provides a convenient route to high-yield single crystal nanowires but with branched shape. These branched nanowires have an average diameter of about 40 nm and length up to several micrometers. A possible mechanism has been proposed and the addition of surfactant dodecylthiol into the two mixed-solvents would play an importance effect on the structure of the product. Based on the mechanism, by controlling the synthesis conditions, such as the ratios between the surfactant, inorganic solvent, and organic solvent, other kinds of nanostructures based on CdS nanowires were also prepared. Photoluminescence (PL) measurement reveals that the branched CdS nanowires have a strong emission at about 700 nm which might be due to its special structure

ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity

B-cell lymphoma 2 (Bcl-2) homology 3 (BH3)-only proteins represent a class of pro-apoptotic factors that neutralize pro-survival Bcl-2 proteins, and, in some cases, directly activate Bax. The mechanisms of control and the role of BH3-only proteins, such as Bcl-2 like protein 11 extra large and Bad are well studied. By contrast, relatively little is known about the regulation and role of Bcl-2 modifying factor (Bmf). The B-RAF oncogene is mutated in ∼8% of human tumors. We have previously shown that Bmf is upregulated at the transcript level and is required for apoptosis induced by targeting B-RAF signaling in tumor cells harboring mutant B-RAF. In this study, we show that Bmf is regulated at the post-translational level by mutant B-RAF-MEK-ERK2 signaling. Extracellular signal-regulated kinase (ERK2) directly phosphorylates Bmf on serine 74 and serine 77 residues with serine 77 being the predominant site. In addition, serine 77 phosphorylation reduces Bmf pro-apoptotic activity likely through a mechanism independent of altering Bmf localization to the mitochondria and/or interactions with dynein light chain 2 and the pro-survival proteins, B-cell lymphoma extra large, Bcl-2 and Mcl-1. These data identify a novel mode of regulation in Bmf that modulates its pro-apoptotic activity in mutant B-RAF tumor cells

The luxS mutation causes loosely-bound biofilms in Shewanella oneidensis

<p>Abstract</p> <p>Background</p> <p>The <it>luxS </it>gene in <it>Shewanella oneidensis </it>was shown to encode an autoinducer-2 (AI-2)-like molecule, the postulated universal bacterial signal, but the impaired biofilm growth of a <it>luxS </it>deficient mutant could not be restored by AI-2, indicating it might not have a signalling role in this organism.</p> <p>Findings</p> <p>Here, we provide further evidence regarding the metabolic role of a <it>luxS </it>mutation in <it>S. oneidensis</it>. We constructed a <it>luxS </it>mutant and compared its phenotype to a wild type control with respect to its ability to remove AI-2 from the medium, expression of secreted proteins and biofilm formation. We show that <it>S. oneidensis </it>has a cell-dependent mechanism by which AI-2 is depleted from the medium by uptake or degradation at the end of the exponential growth phase. As AI-2 depletion is equally active in the <it>luxS </it>mutant and thus does not require AI-2 as an inducer, it appears to be an unspecific mechanism suggesting that AI-2 for <it>S. oneidensis </it>is a metabolite which is imported under nutrient limitation. Secreted proteins were studied by iTraq labelling and liquid chromatography mass spectrometry (LC-MS) detection. Differences between wild type and mutant were small. Proteins related to flagellar and twitching motility were slightly up-regulated in the <it>luxS </it>mutant, in accordance with its loose biofilm structure. An enzyme related to cysteine metabolism was also up-regulated, probably compensating for the lack of the LuxS enzyme. The <it>luxS </it>mutant developed an undifferentiated, loosely-connected biofilm which covered the glass surface more homogenously than the wild type control, which formed compact aggregates with large voids in between.</p> <p>Conclusions</p> <p>The data confirm the role of the LuxS enzyme for biofilm growth in <it>S. oneidensis </it>and make it unlikely that AI-2 has a signalling role in this organism.</p

Universal scaling in the branching of the Tree of Life

Understanding the patterns and processes of diversification of life in the planet is a key challenge of science. The Tree of Life represents such diversification processes through the evolutionary relationships among the different taxa, and can be extended down to intra-specific relationships. Here we examine the topological properties of a large set of interspecific and intraspecific phylogenies and show that the branching patterns follow allometric rules conserved across the different levels in the Tree of Life, all significantly departing from those expected from the standard null models. The finding of non-random universal patterns of phylogenetic differentiation suggests that similar evolutionary forces drive diversification across the broad range of scales, from macro-evolutionary to micro-evolutionary processes, shaping the diversity of life on the planet.Comment: 6 pages + 19 of Supporting Informatio

Reversing Melanoma Cross-Resistance to BRAF and MEK Inhibitors by Co-Targeting the AKT/mTOR Pathway

The sustained clinical activity of the BRAF inhibitor vemurafenib (PLX4032/RG7204) in patients with BRAF(V600) mutant melanoma is limited primarily by the development of acquired resistance leading to tumor progression. Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway.The sensitivity to vemurafenib or the MEK inhibitor AZD6244 was tested in sensitive and resistant human melanoma cell lines exploring differences in activation-associated phosphorylation levels of major signaling molecules, leading to the testing of co-inhibition of the AKT/mTOR pathway genetically and pharmacologically. There was a high degree of cross-resistance to vemurafenib and AZD6244, except in two vemurafenib-resistant cell lines that acquired a secondary mutation in NRAS. In other cell lines, acquired resistance to both drugs was associated with persistence or increase in activity of AKT pathway. siRNA-mediated gene silencing and combination therapy with an AKT inhibitor or rapamycin partially or completely reversed the resistance.Primary and acquired resistance to vemurafenib in these in vitro models results in frequent cross resistance to MEK inhibitors, except when the resistance is the result of a secondary NRAS mutation. Resistance to BRAF or MEK inhibitors is associated with the induction or persistence of activity within the AKT pathway in the presence of these drugs. This resistance can be potentially reversed by the combination of a RAF or MEK inhibitor with an AKT or mTOR inhibitor. These combinations should be available for clinical testing in patients progressing on BRAF inhibitors

Influence of surface atomic structure demonstrated on oxygen incorporation mechanism at a model perovskite oxide

Perovskite oxide surfaces catalyze oxygen exchange reactions that are crucial for fuel cells, electrolyzers, and thermochemical fuel synthesis. Here, by bridging the gap between surface analysis with atomic resolution and oxygen exchange kinetics measurements, we demonstrate how the exact surface atomic structure can determine the reactivity for oxygen exchange reactions on a model perovskite oxide. Two precisely controlled surface reconstructions with (4 × 1) and (2 × 5) symmetry on 0.5 wt.% Nb-doped SrTiO3(110) were subjected to isotopically labeled oxygen exchange at 450 °C. The oxygen incorporation rate is three times higher on the (4 × 1) surface phase compared to the (2 × 5). Common models of surface reactivity based on the availability of oxygen vacancies or on the ease of electron transfer cannot account for this difference. We propose a structure-driven oxygen exchange mechanism, relying on the flexibility of the surface coordination polyhedra that transform upon dissociation of oxygen molecules.Austrian Science Fund (SFB “ Functional Oxide Surfaces and Interfaces ” - FOXSI, Project F 45)European Research Council Advanced Grant (“OxideSurfaces” (Project ERC-2011-ADG_20110209))National Science Foundation (U.S.). Division of Materials Research (CAREER Award Grant No. 1055583

Conservation of Gene Order and Content in the Circular Chromosomes of ‘Candidatus Liberibacter asiaticus’ and Other Rhizobiales

‘Ca. Liberibacter asiaticus,’ an insect-vectored, obligate intracellular bacterium associated with citrus-greening disease, also called “HLB," is a member of the Rhizobiales along with nitrogen-fixing microsymbionts Sinorhizobium meliloti and Bradyrhizobium japonicum, plant pathogen Agrobacterium tumefaciens and facultative intracellular mammalian pathogen Bartonella henselae. Comparative analyses of their circular chromosomes identified 514 orthologous genes shared among all five species. Shared among all five species are 50 identical blocks of microsyntenous orthologous genes (MOGs), containing a total of 283 genes. While retaining highly conserved genomic blocks of microsynteny, divergent evolution, horizontal gene transfer and niche specialization have disrupted macrosynteny among the five circular chromosomes compared. Highly conserved microsyntenous gene clusters help define the Rhizobiales, an order previously defined by 16S RNA gene similarity and herein represented by the three families: Bartonellaceae, Bradyrhizobiaceae and Rhizobiaceae. Genes without orthologs in the other four species help define individual species. The circular chromosomes of each of the five Rhizobiales species examined had genes lacking orthologs in the other four species. For example, 63 proteins are encoded by genes of ‘Ca. Liberibacter asiaticus’ not shared with other members of the Rhizobiales. Of these 63 proteins, 17 have predicted functions related to DNA replication or RNA transcription, and some of these may have roles related to low genomic GC content. An additional 17 proteins have predicted functions relevant to cellular processes, particularly modifications of the cell surface. Seventeen unshared proteins have specific metabolic functions including a pathway to synthesize cholesterol encoded by a seven-gene operon. The remaining 12 proteins encoded by ‘Ca. Liberibacter asiaticus’ genes not shared with other Rhizobiales are of bacteriophage origin. ‘Ca. Liberibacter asiaticus’ shares 11 genes with only Sinorhizobium meliloti and 12 genes are shared with only Bartonella henselae

Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions

Mapping of the longitudinal relaxation time (T1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson- Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field. Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions. Available from: https://www.researchgate.net/publication/317548806_Towards_accurate_and_precise_T1_and_extracellular_volume_mapping_in_the_myocardium_a_guide_to_current_pitfalls_and_their_solutions [accessed Jun 13, 2017]

Inferring Epidemic Contact Structure from Phylogenetic Trees

Contact structure is believed to have a large impact on epidemic spreading and consequently using networks to model such contact structure continues to gain interest in epidemiology. However, detailed knowledge of the exact contact structure underlying real epidemics is limited. Here we address the question whether the structure of the contact network leaves a detectable genetic fingerprint in the pathogen population. To this end we compare phylogenies generated by disease outbreaks in simulated populations with different types of contact networks. We find that the shape of these phylogenies strongly depends on contact structure. In particular, measures of tree imbalance allow us to quantify to what extent the contact structure underlying an epidemic deviates from a null model contact network and illustrate this in the case of random mixing. Using a phylogeny from the Swiss HIV epidemic, we show that this epidemic has a significantly more unbalanced tree than would be expected from random mixing