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911.
ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth 总被引:1,自引:0,他引:1
Zhang S Chen L Cui B Chuang HY Yu J Wang-Rodriguez J Tang L Chen G Basak GW Kipps TJ 《PloS one》2012,7(3):e31127
Receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is expressed during embryogenesis and by certain leukemias, but not by normal adult tissues. Here we show that the neoplastic cells of many human breast cancers express the ROR1 protein and high-level expression of ROR1 in breast adenocarcinoma was associated with aggressive disease. Silencing expression of ROR1 in human breast cancer cell lines found to express this protein impaired their growth in vitro and also in immune-deficient mice. We found that ROR1 could interact with casein kinase 1 epsilon (CK1ε) to activate phosphoinositide 3-kinase-mediated AKT phosphorylation and cAMP-response-element-binding protein (CREB), which was associated with enhanced tumor-cell growth. Wnt5a, a ligand of ROR1, could induce ROR1-dependent signaling and enhance cell growth. This study demonstrates that ROR1 is expressed in human breast cancers and has biological and clinical significance, indicating that it may be a potential target for breast cancer therapy. 相似文献
912.
TS Peat DI Rhodes N Vandegraaff G Le JA Smith LJ Clark ED Jones JA Coates N Thienthong J Newman O Dolezal R Mulder JH Ryan GP Savage CL Francis JJ Deadman 《PloS one》2012,7(7):e40147
A fragment-based screen against human immunodeficiency virus type 1 (HIV) integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF) binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme. 相似文献
913.
R Ahmad W Wolber S Eckardt P Koch J Schmitt R Semechkin C Geis M Heckmann O Brüstle JK McLaughlin AL Sirén AM Müller 《PloS one》2012,7(8):e42800
Parent of origin imprints on the genome have been implicated in the regulation of neural cell type differentiation. The ability of human parthenogenetic (PG) embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific differentiation is undefined. We determined the potential of hpESCs to differentiate into various neural subtypes. Concurrently, we examined DNA methylation and expression status of imprinted genes. Under culture conditions promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave rise to glia and neuron-like cells that expressed subtype-specific markers and generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs revealed that maternal-specific gene expression patterns and imprinting marks were generally maintained in PG cells upon differentiation. Our results demonstrate that despite the lack of a paternal genome, hpESCs generate proliferating NSCs that are capable of differentiation into physiologically functional neuron-like cells and maintain allele-specific expression of imprinted genes. Thus, hpESCs can serve as a model to study the role of maternal and paternal genomes in neural development and to better understand imprinting-associated brain diseases. 相似文献
914.
915.
For those stricken with malaria, the classic clinical symptoms are caused by the parasite's cyclic infection of red blood cells. However, this erythrocytic phase of the parasite's life cycle initiates from an asymptomatic pre-erythrocytic phase: the injection of sporozoites via the bite of a parasite-carrying Anopheline mosquito, and the ensuing infection of the liver. With the increased capabilities of studying liver stages in mice, much progress has been made elucidating the cellular and molecular basis of the parasite's progression through this bottleneck of its life cycle. Here we review relevant findings on how sporozoites prepare for infection of the liver and factors crucial to liver stage development as well as key host/parasite interactions. 相似文献
916.
Timothy J. Langlois Ben T. Radford Kimberley P. Van Niel Jessica J. Meeuwig Alan F. Pearce Cecile S. G. Rousseaux Gary A. Kendrick Euan S. Harvey 《Global Ecology and Biogeography》2012,21(9):886-897
Aim Macroecological theory predicts that along direct physiological gradients there will be unimodal abundance distributions of species and consistent rates of assemblage turnover. However, the majority of marine studies that have investigated the realized distribution of species along latitudinal or temperature gradients have generally found unimodal distributions to be rare. We assess fish distributions along a temperature gradient in a stable oligotrophic seascape and suggest that unimodal distributions will be more common. Location Nearshore demersal fish habitat extending 1500 km along the coast of south‐western Australia. Methods The relative abundances of demersal fish species were sampled off the coast of south‐western Australia along a temperature gradient. The confounding influence of other environmental variables was tested, and the assemblage was found to be highly correlated with temperature. For the 20 most abundant species, quantile regression spline models were used to construct a model within which 95% of their abundance was expected to fall. We compared the results from this study with the proportion of unimodal species abundance distributions observed in other studies. Results Of the 20 most abundant species, 19 displayed patterns that indicated temperature was an important factor influencing their range and relative abundance; with 15 species exhibiting unimodal abundance distributions, four having ramped distribution to one end of the sampled range and one showing no consistent pattern. Main conclusions The high diversity and percentage of endemic species in terrestrial and marine habitats of south‐western Australia is likely to be due to the stable geological and oceanographic history of the region. In comparison, studies of abundance distribution in other marine systems have been conducted in relatively heterogeneous and productive environments. The old, climatically buffered, oligotrophic seascape of south‐western Australia has provided a simple system in which the consistent influence of physiological gradients on the abundance distribution of fish species can be observed. 相似文献
917.
Schneider J Rupp O Trost E Jaenicke S Passoth V Goesmann A Tauch A Brinkrolf K 《FEMS yeast research》2012,12(3):382-386
The ascomycetous yeast Wickerhamomyces anomalus (formerly Pichia anomala and Hansenula anomala) exhibits antimicrobial activities and flavoring features that are responsible for its frequent association with food, beverage and feed products. However, limited information on the genetic background of this yeast and its multiple capabilities are currently available. Here, we present the draft genome sequence of the neotype strain W.?anomalus DSM 6766. On the basis of pyrosequencing, a de novo assembly of this strain resulted in a draft genome sequence with a total size of 25.47?Mbp. An automatic annotation using RAPYD generated 11?512 protein-coding sequences. This annotation provided the basis to analyse metabolic capabilities, phylogenetic relationships, as well as biotechnologically important features and yielded novel candidate genes of W.?anomalus DSM 6766 coding for proteins participating in antimicrobial activities. 相似文献
918.
Williams JS Clausen AR Nick McElhinny SA Watts BE Johansson E Kunkel TA 《DNA Repair》2012,11(8):649-656
We have investigated the ability of the 3′ exonuclease activity of Saccharomyces cerevisiae DNA polymerase ? (Pol ?) to proofread newly inserted ribonucleotides (rNMPs). During DNA synthesis in vitro, Pol ? proofreads ribonucleotides with apparent efficiencies that vary from none at some locations to more than 90% at others, with rA and rU being more efficiently proofread than rC and rG. Previous studies show that failure to repair ribonucleotides in the genome of rnh201Δ strains that lack RNase H2 activity elevates the rate of short deletions in tandem repeat sequences. Here we show that this rate is increased by 2–4-fold in pol2-4 rnh201Δ strains that are also defective in Pol ? proofreading. In comparison, defective proofreading in these same strains increases the rate of base substitutions by more than 100-fold. Collectively, the results indicate that although proofreading of an ‘incorrect’ sugar is less efficient than is proofreading of an incorrect base, Pol ? does proofread newly inserted rNMPs to enhance genome stability. 相似文献
919.
Christopher G. Shuttle Neil D. Treat Jessica D. Douglas Jean M. J. Fréchet Michael L. Chabinyc 《Liver Transplantation》2012,2(1):111-119
The nature of energetic disorder in organic semiconductors is poorly understood. In photovoltaics, energetic disorder leads to reductions in the open circuit voltage and contributes to other loss processes. In this work, three independent optoelectronic methods were used to determine the long‐lived carrier populations in a high efficiency N‐alkylthieno[3,4‐c]pyrrole‐4,6‐dione (TPD) based polymer: fullerene solar cell. In the TPD co‐polymer, all methods indicate the presence of a long‐lived carrier population of ~ 1015 cm?3 on timescales ≥ 100 μs. Additionally, the behavior of these photovoltaic devices under optical bias is consistent with deep energetic lying trap states. Comparative measurements were also performed on high efficiency poly‐3‐hexylthiophene (P3HT): fullerene solar cells; however a similar long‐lived carrier population was not observed. This observation is consistent with a higher acceptor concentration (doping) in P3HT than in the TPD‐based copolymer. 相似文献
920.
Cho YS Dobos KM Prenni J Yang H Hess A Rosenkrands I Andersen P Ryoo SW Bai GH Brennan MJ Izzo A Bielefeldt-Ohmann H Belisle JT 《Proteomics》2012,12(7):979-991
Purified protein derivative (PPD) has served as a safe and effective diagnostic reagent for 60 years and is the only broadly available material to diagnose latent tuberculosis infections. This reagent is also used as a standard control for a number of in vitro immunological assays. Nevertheless, the molecular composition and specific products that contribute to the extraordinary immunological reactivity of PPD are poorly defined. Here, a proteomic approach was applied to elucidate the gene products in the U.S. Food and Drug Administration (FDA) standard PPD-S2. Many known Mycobacterium tuberculosis T-cell antigens were detected. Of significance, four heat shock proteins (HSPs) (GroES, GroEL2, HspX, and DnaK) dominated the composition of PPD. The chaperone activities and capacity of these proteins to influence immunological responses may explain the exquisite solubility and immunological potency of PPD. Spectral counting analysis of three separate PPD reagents revealed significant quantitative variances. Gross delayed-type hypersensitivity (DTH) responses in M. tuberculosis infected guinea pigs were comparable among these PPD preparations; however, detailed histopathology of the DTH lesions exposed unique differences, which may be explained by the variability observed in the presence and abundance of early secretory system (Esx) proteins. Variability in PPD reagents may explain differences in DTH responses reported among populations. 相似文献