An oncogenic role for sphingosine kinase 2

While both human sphingosine kinases (SK1 and SK2) catalyze the generation of the pleiotropic signaling lipid sphingosine 1-phosphate, these enzymes appear to be functionally distinct. SK1 has well described roles in promoting cell survival, proliferation and neoplastic transformation. The roles of SK2, and its contribution to cancer, however, are much less clear. Some studies have suggested an antiproliferative/ pro-apoptotic function for SK2, while others indicate it has a prosurvival role and its inhibition can have anti-cancer effects. Our analysis of gene expression data revealed that SK2 is upregulated in many human cancers, but only to a small extent (up to 2.5-fold over normal tissue). Based on these findings, we examined the effect of different levels of cellular SK2 and showed that high-level overexpression reduced cell proliferation and survival, and increased cellular ceramide levels. In contrast, however, low-level SK2 overexpression promoted cell survival and proliferation, and induced neoplastic transformation in vivo. These findings coincided with decreased nuclear localization and increased plasma membrane localization of SK2, as well as increases in extracellular S1P formation. Hence, we have shown for the first time that SK2 can have a direct role in promoting oncogenesis, supporting the use of SK2-specific inhibitors as anti-cancer agents.Heidi A. Neubauer, Duyen H. Pham, Julia R. Zebol, Paul A.B. Moretti, Amanda L. Peterson, Tamara M. Leclercq, Huasheng Chan, Jason A. Powell, Melissa R. Pitman, Michael S. Samuel, Claudine S. Bonder, Darren J. Creek, Briony L. Gliddon and Stuart M. Pitso

The use of micro-XRD for the study of glaze color decorations

The compounds responsible for the colours and decorations in glass and glazed ceramics include: colouring agents (transition metal ions), pigments (micro-and nano-precipitates of compounds that either do not dissolve or recrystallize in the glassy matrix) and opacifiers (microcrystalline compounds with high light scattering capability). Their composition, structure and range of stability are highly dependent not only on the composition but also on the procedures followed to obtain them. Chemical composition of the colorants and crystallites may be obtained by means of SEM-EDX and WDX. Synchrotron Radiation micro-X-ray Diffraction has a small beam size adequate (10 to 50 microns footprint size) to obtain the structural information of crystalline compounds and high brilliance, optimal for determining the crystallites even when present in low amounts. In addition, in glass decorations the crystallites often appear forming thin layers (from 10 to 100 micrometers thick) and they show a depth dependent composition and crystal structure. Their nature and distribution across the glass/glazes decorations gives direct information on the technology of production and stability and may be related to the color and appearance. A selection of glass and glaze coloring agents and decorations are studied by means of SR-micro- XRD and SEM-EDX including: manganese brown, antimony yellow, red copper lusters and cobalt blue. The selection includes Medieval (Islamic, and Hispano Moresque) and renaissance tin glazed ceramics from the 10th to the 17th century AD

United classification of cosmic gamma-ray bursts and their counterparts

United classification of gamma-ray bursts and their counterparts is established on the basis of measured characteristics: photon energy E and emission duration T. The founded interrelation between the mentioned characteristics of events consists in that, as the energy increases, the duration decreases (and vice versa). The given interrelation reflects the nature of the phenomenon and forms the E-T diagram, which represents a natural classification of all observed events in the energy range from 10E9 to 10E-6 eV and in the corresponding interval of durations from about 10E-2 up to 10E8 s. The proposed classification results in the consequences, which are principal for the theory and practical study of the phenomenon.Comment: Keywords Gamma rays: burst

Supersymmetry Without Prejudice at the LHC

The discovery and exploration of Supersymmetry in a model-independent fashion will be a daunting task due to the large number of soft-breaking parameters in the MSSM. In this paper, we explore the capability of the ATLAS detector at the LHC ($\sqrt s=14$ TeV, 1 fb$^{-1}$) to find SUSY within the 19-dimensional pMSSM subspace of the MSSM using their standard transverse missing energy and long-lived particle searches that were essentially designed for mSUGRA. To this end, we employ a set of $\sim 71$k previously generated model points in the 19-dimensional parameter space that satisfy all of the existing experimental and theoretical constraints. Employing ATLAS-generated SM backgrounds and following their approach in each of 11 missing energy analyses as closely as possible, we explore all of these $71$k model points for a possible SUSY signal. To test our analysis procedure, we first verify that we faithfully reproduce the published ATLAS results for the signal distributions for their benchmark mSUGRA model points. We then show that, requiring all sparticle masses to lie below 1(3) TeV, almost all(two-thirds) of the pMSSM model points are discovered with a significance $S>5$ in at least one of these 11 analyses assuming a 50\% systematic error on the SM background. If this systematic error can be reduced to only 20\% then this parameter space coverage is increased. These results are indicative that the ATLAS SUSY search strategy is robust under a broad class of Supersymmetric models. We then explore in detail the properties of the kinematically accessible model points which remain unobservable by these search analyses in order to ascertain problematic cases which may arise in general SUSY searches.Comment: 69 pages, 40 figures, Discussion adde

Global distribution of a key trophic guild contrasts with common latitudinal diversity patterns

Most hypotheses explaining the general gradient of higher diversity toward the equator are implicit or explicit about greater species packing in the tropics. However, global patterns of diversity within guilds, including trophic guilds (i.e., groups of organisms that use similar food resources), are poorly known. We explored global diversity patterns of a key trophic guild in stream ecosystems, the detritivore shredders. This was motivated by the fundamental ecological role of shredders as decomposers of leaf litter and by some records pointing to low shredder diversity and abundance in the tropics, which contrasts with diversity patterns of most major taxa for which broad-scale latitudinal patterns haven been examined. Given this evidence, we hypothesized that shredders are more abundant and diverse in temperate than in tropical streams, and that this pattern is related to the higher temperatures and lower availability of high-quality leaf litter in the tropics. Our comprehensive global survey (129 stream sites from 14 regions on six continents) corroborated the expectedlatitudinal pattern and showed that shredder distribution (abundance, diversity and assemblage composition) was explained by a combination of factors, including water temperature (some taxa were restricted to cool waters) and biogeography (some taxa were more diverse in particular biogeographic realms). In contrast to our hypothesis, shredder diversity was unrelated to leaf toughness, but it was inversely related to litter diversity. Our findings markedly contrast with global trends of diversity for most taxa, and with the general rule of higher consumer diversity at higher levels of resource diversity. Moreover, they highlight the emerging role of temperature in understanding global patterns of diversity, which is of great relevance in the face of projected global warming. © 2011 by the Ecological Society of America.Peer Reviewe

Higgs Boson Decay into Hadronic Jets

The remarkable agreement of electroweak data with standard model (SM) predictions motivates the study of extensions of the SM in which the Higgs boson is light and couples in a standard way to the weak gauge bosons. Postulated new light particles should have small couplings to the gauge bosons. Within this context it is natural to assume that the branching fractions of the light SM-like Higgs boson mimic those in the standard model. This assumption may be unwarranted, however, if there are non-standard light particles coupled weakly to the gauge bosons but strongly to the Higgs field. In particular, the Higgs boson may effectively decay into hadronic jets, possibly without important bottom or charm flavor content. As an example, we present a simple extension of the SM, in which the predominant decay of the Higgs boson occurs into a pair of light bottom squarks that, in turn, manifest themselves as hadronic jets. Discovery of the Higgs boson remains possible at an electron-positron linear collider, but prospects at hadron colliders are diminished substantially.Comment: 30 pages, 7 figure

Cytoplasmic dynein regulates the subcellular localization of sphingosine kinase 2 to elicit tumor-suppressive functions in glioblastoma

While the two mammalian sphingosine kinases, SK1 and SK2, both catalyze the generation of pro-survival sphingosine 1-phosphate (S1P), their roles vary dependent on their different subcellular localization. SK1 is generally found in the cytoplasm or at the plasma membrane where it can promote cell proliferation and survival. SK2 can be present at the plasma membrane where it appears to have a similar function to SK1, but can also be localized to the nucleus, endoplasmic reticulum or mitochondria where it mediates cell death. Although SK2 has been implicated in cancer initiation and progression, the mechanisms regulating SK2 subcellular localization are undefined. Here, we report that SK2 interacts with the intermediate chain subunits of the retrograde-directed transport motor complex, cytoplasmic dynein 1 (DYNC1I1 and -2), and we show that this interaction, particularly with DYNC1I1, facilitates the transport of SK2 away from the plasma membrane. DYNC1I1 is dramatically downregulated in patient samples of glioblastoma (GBM), where lower expression of DYNC1I1 correlates with poorer patient survival. Notably, low DYNC1I1 expression in GBM cells coincided with more SK2 localized to the plasma membrane, where it has been recently implicated in oncogenesis. Re-expression of DYNC1I1 reduced plasma membrane-localized SK2 and extracellular S1P formation, and decreased GBM tumor growth and tumor-associated angiogenesis in vivo. Consistent with this, chemical inhibition of SK2 reduced the viability of patient-derived GBM cells in vitro and decreased GBM tumor growth in vivo. Thus, these findings demonstrate a tumor-suppressive function of DYNC1I1, and uncover new mechanistic insights into SK2 regulation which may have implications in targeting this enzyme as a therapeutic strategy in GBM.Heidi A. Neubauer, Melinda N. Tea, Julia R. Zebol, Briony L. Gliddon, Cassandra Stefanidis, Paul A.B. Moretti, Melissa R. Pitman, Maurizio Costabile, Jasreen Kular, Brett W. Stringer, Bryan W. Day, Michael S. Samuel, Claudine S. Bonder, Jason A. Powell, Stuart M. Pitso

WW Production Cross Section and W Branching Fractions in e+e- Collisions at 189 GeV

From a data sample of 183 pb^-1 recorded at a center-of-mass energy of roots = 189 GeV with the OPAL detector at LEP, 3068 W-pair candidate events are selected. Assuming Standard Model W boson decay branching fractions, the W-pair production cross section is measured to be sigmaWW = 16.30 +- 0.34(stat.) +- 0.18(syst.) pb. When combined with previous OPAL measurements, the W boson branching fraction to hadrons is determined to be 68.32 +- 0.61(stat.) +- 0.28(syst.) % assuming lepton universality. These results are consistent with Standard Model expectations.Comment: 22 pages, 5 figures, submitted to Phys. Lett.

Latitudinal gradient of nestedness and its potential drivers in stream detritivores

Understanding what mechanisms shape the diversity and composition of biological assemblages across broad-scale gradients is central to ecology. Litter-consuming detritivorous invertebrates in streams show an unusual diversity gradient, with α-diversity increasing towards high latitudes but no trend in γ -diversity. We hypothesized this pattern to be related to shifts in nestedness and several ecological processes shaping their assemblages (dispersal, environmental filtering and competition). We tested this hypothesis, using a global dataset, by examining latitudinal trends in nestedness and several indicators of the above processes along the latitudinal gradient. Our results suggest that strong environmental filtering and low dispersal in the tropics lead to often species-poor local detritivore assemblages, nested in richer regional assemblages. At higher latitudes, dispersal becomes stronger, disrupting the nested assemblage structure and resulting in local assemblages that are generally more species-rich and non-nested subsets of the regional species pools. Our results provide evidence that mechanisms underlying assemblage composition and diversity of stream litter-consuming detritivores shift across latitudes, and provide an explanation for their unusual pattern of increasing α-diversity with latitude. When we repeated these analyses for whole invertebrate assemblages of leaf litter and for abundant taxa showing reverse or no diversity gradients we found no latitudinal patterns, suggesting that function-based rather than taxon-based analyses of assemblages may help elucidate the mechanisms behind diversity gradients