In situ GISAXS study of the growth of Pd on MgO(001)

The morphology of growing Pd nano-particles on MgO(001) surfaces have been investigated in situ, during growth, by grazing incidence small angle x-ray scattering, for different substrate temperatures. The 2D patterns obtained are quantitatively analyzed, and the average morphological parameters (shape, size) deduced. Above 650 K, the aggregates adopt their equilibrium shape of truncated octahedron, and the interfacial energy is deduced.Comment: 10 pages, 1 Table, 2 Figure

A Novel Role for ATM in Regulating Proteasome-Mediated Protein Degradation through Suppression of the ISG15 Conjugation Pathway

Ataxia Telangiectasia (A-T) is an inherited immunodeficiency disorder wherein mutation of the ATM kinase is responsible for the A-T pathogenesis. Although the precise role of ATM in A-T pathogenesis is still unclear, its function in responding to DNA damage has been well established. Here we demonstrate that in addition to its role in DNA repair, ATM also regulates proteasome-mediated protein turnover through suppression of the ISG15 pathway. This conclusion is based on three major pieces of evidence: First, we demonstrate that proteasome-mediated protein degradation is impaired in A-T cells. Second, we show that the reduced protein turnover is causally linked to the elevated expression of the ubiquitin-like protein ISG15 in A-T cells. Third, we show that expression of the ISG15 is elevated in A-T cells derived from various A-T patients, as well as in brain tissues derived from the ATM knockout mice and A-T patients, suggesting that ATM negatively regulates the ISG15 pathway. Our current findings suggest for the first time that proteasome-mediated protein degradation is impaired in A-T cells due to elevated expression of the ISG15 conjugation pathway, which could contribute to progressive neurodegeneration in A-T patients

Interferon-β Signaling Contributes to Ras Transformation

Increasing evidence has pointed to activated type I interferon signaling in tumors. However, the molecular basis for such activation and its role in tumorigenesis remain unclear. In the current studies, we report that activation of type I interferon (IFN) signaling in tumor cells is primarily due to elevated secretion of the type I interferon, IFN-β. Studies in oncogene-transformed cells suggest that oncogenes such as Ras and Src can activate IFN-β signaling. Significantly, elevated IFN-β signaling in Ras-transformed mammary epithelial MCF-10A cells was shown to contribute to Ras transformation as evidenced by morphological changes, anchorage-independent growth, and migratory properties. Our results demonstrate for the first time that the type I IFN, IFN-β, contributes to Ras transformation and support the notion that oncogene-induced cytokines play important roles in oncogene transformation

STM Spectroscopy of ultra-flat graphene on hexagonal boron nitride

Graphene has demonstrated great promise for future electronics technology as well as fundamental physics applications because of its linear energy-momentum dispersion relations which cross at the Dirac point. However, accessing the physics of the low density region at the Dirac point has been difficult because of the presence of disorder which leaves the graphene with local microscopic electron and hole puddles, resulting in a finite density of carriers even at the charge neutrality point. Efforts have been made to reduce the disorder by suspending graphene, leading to fabrication challenges and delicate devices which make local spectroscopic measurements difficult. Recently, it has been shown that placing graphene on hexagonal boron nitride (hBN) yields improved device performance. In this letter, we use scanning tunneling microscopy to show that graphene conforms to hBN, as evidenced by the presence of Moire patterns in the topographic images. However, contrary to recent predictions, this conformation does not lead to a sizable band gap due to the misalignment of the lattices. Moreover, local spectroscopy measurements demonstrate that the electron-hole charge fluctuations are reduced by two orders of magnitude as compared to those on silicon oxide. This leads to charge fluctuations which are as small as in suspended graphene, opening up Dirac point physics to more diverse experiments than are possible on freestanding devices.Comment: Nature Materials advance online publication 13/02/201

Estimation of solar prominence magnetic fields based on the reconstructed 3D trajectories of prominence knots

We present an estimation of the lower limits of local magnetic fields in quiescent, activated, and active (surges) promineces, based on reconstructed 3-dimensional (3D) trajectories of individual prominence knots. The 3D trajectories, velocities, tangential and centripetal accelerations of the knots were reconstructed using observational data collected with a single ground-based telescope equipped with a Multi-channel Subtractive Double Pass imaging spectrograph. Lower limits of magnetic fields channeling observed plasma flows were estimated under assumption of the equipartition principle. Assuming approximate electron densities of the plasma n_e = 5*10^{11} cm^{-3} in surges and n_e = 5*10^{10} cm^{-3} in quiescent/activated prominences, we found that the magnetic fields channeling two observed surges range from 16 to 40 Gauss, while in quiescent and activated prominences they were less than 10 Gauss. Our results are consistent with previous detections of weak local magnetic fields in the solar prominences.Comment: 14 pages, 12 figures, 1 tabl

CO excitation of normal star forming galaxies out to z=1.5 as regulated by the properties of their interstellar medium

We investigate the CO excitation of normal star forming galaxies at z=1.5 using IRAM PdBI observations of the CO[2-1], CO[3-2] and CO[5-4] transitions for 4 galaxies, and VLA observations of CO[1-0] for 3 of them, measuring reliable line fluxes with S/N>4-7 for individual transitions. While the average CO Spectral Line Energy Distribution (SLED) has a sub-thermal excitation similar to the Milky Way (MW) up to CO[3-2], we show that the average CO[5-4] emission is 4 times stronger than assuming MW excitation. This demonstrates the presence of an additional component of more excited, denser and possibly warmer molecular gas. The ratio of CO[5-4] to lower-J CO emission is however lower than in local (U)LIRGs and high-redshift starbursting SMGs, and appears to correlate closely with the average intensity of the radiation field and with the star formation surface density, but not with SF efficiency (SFE). This suggests that the overall CO excitation is at least indirectly affected by the metallicity of the ISM. The luminosity of the CO[5-4] transition is found to correlate linearly with the bolometric infrared luminosity over 4 orders of magnitudes, with BzK galaxies following the same linear trend as local spirals and (U)LIRGs and high redshift star bursting sub-millimeter galaxies. The CO[5-4] luminosity is thus related to the dense gas, and might be a more convenient way to probe it than standard high--density tracers. We see excitation variations among our sample galaxies, linked to their evolutionary state and clumpiness in optical rest frame images. In one galaxy we see spatially resolved excitation variations, the more highly excited part corresponds to the location of massive SF clumps. This provides support to models that suggest that giant clumps are the main source of the high excitation CO emission in high redshift disk-like galaxies

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes