Thrombin Protease-activated Receptor-1 Signals through Gq- and G13-initiated MAPK Cascades Regulating c-Jun Expression to Induce Cell Transformation

Although the ability of G protein-coupled receptors to stimulate normal and aberrant cell growth has been intensely investigated, the precise nature of the molecular mechanisms underlying their transforming potential are still not fully understood. In this study, we have taken advantage of the potent mitogenic effect of thrombin and the focus-forming activity of one of its receptors, protease-activated receptor-1, to dissect how this receptor coupled to Gi, Gq/11, and G12/13 transduces signals from the membrane to the nucleus to initiate transcriptional events involved in cell transformation. Using endogenous and transfected thrombin receptors in NIH 3T3 cells, ectopic expression of muscarinic receptors coupled to Gq and Gi, and chimeric G protein subunits and murine fibroblasts deficient in Gq/11, and G12/13, we show here that, although coupling to Gi is sufficient to induce ERK activation, the ability to couple to Gq and/or G13 is necessary to induce c-jun expression and cell transformation. Furthermore, we show that Gq and G13 can initiate the activation of MAPK cascades, including JNK, p38, and ERK5, which in turn regulate the activity of transcription factors controlling expression from the c-jun promoter. We also present evidence that c-Jun and the kinases regulating its expression are integral components of the transforming pathway initiated by protease-activated receptor-1

Shrinking the lymphatic filariasis map of Ethiopia: reassessing the population at risk through nationwide mapping

BACKGROUND Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. METHODOLOGY/PRINCIPAL FINDING A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. CONCLUSIONS We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale

\require{mhchem}Misfit phase \ce{(BiSe)_{1.10}NbSe2} as the origin of superconductivity in nobium-doped bismuth selenide

\require{mhchem}Topological superconductivity is of great contemporary interest and has been proposed in doped \ce{Bi2Se3} in which electron-donating atoms such as Cu, Sr or Nb have been intercalated into the \ce{Bi2Se3} structure. For \ce{Nb_{x}Bi2Se3}, with $\text{T}_\text{c} \sim 3 \ \text{K}$, it is assumed in the literature that Nb is inserted in the van der Waals gap. However, in this work an alternative origin for the superconductivity in Nb-doped \ce{Bi2Se3} is established. In contrast to previous reports, it is deduced that Nb intercalation in \ce{Bi2Se3} does not take place. Instead, the superconducting behaviour in samples of nominal composition \ce{Nb_{x}Bi2Se3} results from the \ce{(BiSe)_{1.10}NbSe2} misfit phase that is present in the sample as an impurity phase for small $x$ ($0.01 \leq x \leq 0.10$) and as a main phase for large $x$ ($x = 0.50$). The structure of this misfit phase is studied in detail using a combination of X-ray diffraction and transmission electron microscopy techniques

A Global Plate Model Including Lithospheric Deformation Along Major Rifts and Orogens Since the Triassic

Global deep‐time plate motion models have traditionally followed a classical rigid plate approach, even though plate deformation is known to be significant. Here we present a global Mesozoic–Cenozoic deforming plate motion model that captures the progressive extension of all continental margins since the initiation of rifting within Pangea at ~240 Ma. The model also includes major failed continental rifts and compressional deformation along collision zones. The outlines and timing of regional deformation episodes are reconstructed from a wealth of published regional tectonic models and associated geological and geophysical data. We reconstruct absolute plate motions in a mantle reference frame with a joint global inversion using hot spot tracks for the last 80 million years and minimizing global trench migration velocities and net lithospheric rotation. In our optimized model, net rotation is consistently below 0.2°/Myr, and trench migration scatter is substantially reduced. Distributed plate deformation reaches a Mesozoic peak of 30 × 106 km2 in the Late Jurassic (~160–155 Ma), driven by a vast network of rift systems. After a mid‐Cretaceous drop in deformation, it reaches a high of 48 x 106 km2 in the Late Eocene (~35 Ma), driven by the progressive growth of plate collisions and the formation of new rift systems. About a third of the continental crustal area has been deformed since 240 Ma, partitioned roughly into 65% extension and 35% compression. This community plate model provides a framework for building detailed regional deforming plate networks and form a constraint for models of basin evolution and the plate‐mantle system

Massive Stars in Molecular Clouds Rich in High-energy Sources: The Bridge of G332.809-0.132 and CS 78 in NGC 6334

Detections of massive stars in the direction of the H II region CS 78 in NGC 6334 and of G332.809-0.132 are here presented. The region covered by the G332.809-0.132 complex coincides with the RCW 103 stellar association. In its core (40' in radius), approximately 110 OB candidate stars (Ks < 10 mag and 0.4 < AKs < 1.6 mag) were identified using 2MASS, DENIS, and GLIMPSE data. This number of OB stars accounts for more than 50% of the observed number of Lyman continuum photons from this region. Medium-resolution K-band spectra were obtained for seven early types, including one WN 8 star and one Ofpe/WN 9 star; the latter is located near the RCW 103 remnant and its luminosity is consistent with a distance of about 3 kpc. The area analyzed encloses 9 of the 34 OB stars previously known in RCW 103, as well as IRAS 16115-5044, which we reclassify as a candidate luminous blue variable. The line of sight is particularly interesting, crossing three spiral arms; a molecular cloud at -50 (with RCW 103 in the Scutum-Crux arm) and another at -90 km s-1 (in the Norma arm) are detected, both rich in massive stars and supernova remnants. We also report the detection of a B supergiant as the main ionizing source of CS 78, 2MASS J17213513-3532415. Medium-resolution H and K band spectra display H I and He I lines, as well as Fe II lines. By assuming a distance of 1.35 kpc, we estimate a bolometric magnitude of -6.16, which is typical of supergiants.Comment: 44 pages, 15 figure