299 research outputs found

    WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors

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    Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1-8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12-20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis

    Yield scaling, size hierarchy and fluctuations of observables in fragmentation of excited heavy nuclei

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    Multifragmentation properties measured with INDRA are studied for single sources produced in Xe+Sn reactions in the incident energy range 32-50 A MeV and quasiprojectiles from Au+Au collisions at 80 A MeV. A comparison for both types of sources is presented concerning Fisher scaling, Zipf law, fragment size and fluctuation observables. A Fisher scaling is observed for all the data. The pseudo-critical energies extracted from the Fisher scaling are consistent between Xe+Sn central collisions and Au quasi-projectiles. In the latter case it also corresponds to the energy region at which fluctuations are maximal. The critical energies deduced from the Zipf analysis are higher than those from the Fisher analysis.Comment: 30 pages, accepted for publication in Nuclear Physics A, references correcte

    Comparative analysis of the secretome and interactome of Trypanosoma cruzi and Trypanosoma rangeli reveals species specific immune response modulating proteins

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    Chagas disease, a zoonosis caused by the flagellate protozoan Trypanosoma cruzi, is a chronic and systemic parasitic infection that affects ~5–7 million people worldwide, mainly in Latin America. Chagas disease is an emerging public health problem due to the lack of vaccines and effective treatments. According to recent studies, several T. cruzi secreted proteins interact with the human host during cell invasion. Moreover, some comparative studies with T. rangeli, which is non-pathogenic in humans, have been performed to identify proteins directly involved in the pathogenesis of the disease. In this study, we present an integrated analysis of canonical putative secreted proteins (PSPs) from both species. Additionally, we propose an interactome with human host and gene family clusters, and a phylogenetic inference of a selected protein. In total, we identified 322 exclusively PSPs in T. cruzi and 202 in T. rangeli. Among the PSPs identified in T. cruzi, we found several trans-sialidases, mucins, MASPs, proteins with phospholipase 2 domains (PLA2-like), and proteins with Hsp70 domains (Hsp70-like) which have been previously characterized and demonstrated to be related to T. cruzi virulence. PSPs found in T. rangeli were related to protozoan metabolism, specifically carboxylases and phosphatases. Furthermore, we also identified PSPs that may interact with the human immune system, including heat shock and MASP proteins, but in a lower number compared to T. cruzi. Interestingly, we describe a hypothetical hybrid interactome of PSPs which reveals that T. cruzi secreted molecules may be down-regulating IL-17 whilst T. rangeli may enhance the production of IL-15. These results will pave the way for a better understanding of the pathophysiology of Chagas disease and may ultimately lead to the identification of molecular targets, such as key PSPs, that could be used to minimize the health outcomes of Chagas disease by modulating the immune response triggered by T. cruzi infection

    Optical symmetries and anisotropic transport in high-Tc superconductors

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    A simple symmetry analysis of in-plane and out-of-plane transport in a family of high temperature superconductors is presented. It is shown that generalized scaling relations exist between the low frequency electronic Raman response and the low frequency in-plane and out-of-plane conductivities in both the normal and superconducting states of the cuprates. Specifically, for both the normal and superconducting state, the temperature dependence of the low frequency B1gB_{1g} Raman slope scales with the cc-axis conductivity, while the B2gB_{2g} Raman slope scales with the in-plane conductivity. Comparison with experiments in the normal state of Bi-2212 and Y-123 imply that the nodal transport is largely doping independent and metallic, while transport near the BZ axes is governed by a quantum critical point near doping p0.22p\sim 0.22 holes per CuO2_{2} plaquette. Important differences for La-214 are discussed. It is also shown that the cc- axis conductivity rise for TTcT\ll T_{c} is a consequence of partial conservation of in-plane momentum for out-of-plane transport.Comment: 16 pages, 8 Figures (3 pages added, new discussion on pseudogap and charge ordering in La214

    Influence of Grain Boundary Character on Creep Void Formation in Alloy 617

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    Alloy 617, a high temperature creep-resistant, nickel-based alloy, is being considered for the primary heat exchanger for the Next Generation Nuclear Plant (NGNP) which will operate at temperatures exceeding 760oC. Orientation imaging microscopy (OIM) is used to characterize the grain boundaries in the vicinity of creep voids that develop during high temperature creep tests (800-1000oC at creep stresses ranging from 20-85 MPa) terminated at creep strains ranging from 5-40%. Observations using optical microscopy indicate creep rate does not significantly influence the creep void fraction at a given creep strain. Preliminary analysis of the OIM data indicates voids tend to form on grain boundaries parallel, perpendicular or 45o to the tensile axis, while few voids are found at intermediate inclinations to the tensile axis. Random grain boundaries intersect most voids while CSL-related grain boundaries did not appear to be consistently associated with void development

    The composition of the protosolar disk and the formation conditions for comets

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    Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today. This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.Comment: To appear in Space Science Reviews. The final publication is available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

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    A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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