464 research outputs found

    HuR overexpression in MB231 breast cancer cells

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    Abstract only availableCancer cells share acquired capabilities necessary for their malignant transformation. These "hallmarks of cancer" include increased proliferation, self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apoptosis, angiogenesis and metastasis (Hanahan and Weinberg 2000). HuR is a RNA-binding protein which has been implicated in regulating mRNAs involved in each of these characteristics. We hypothesize that HuR maintains the growth characteristics of malignant cancer cells through the stabilization and increased translation of cancer relevant genes. If HuR does enhance malignancy then the overexpression of HuR would amplify the capabilites of malignant cancer cells and increase cell proliferation. This hypothesis was tested by creating a breast cancer cell line that stably overexpresses HuR. A vector overexpressing HuR was created by ligating a PCR amplified insert containing HuR and a HA hemagluttin tag into a Zeocin resistant episomal plasmid. Cells normally express HuR, so the tag was used to distinguish the overexpressed HuR from endogenous HuR. This plasmid was used to transfect MB-231 estrogen receptor-negative breast cancer cells. After transfection, Zeocin selected against the cells that did not incorporate the plasmid. Western Blots for the surviving cells revealed that HA HuR was expressed, implying that the cells were overexpressing HuR. Proliferation assays of heterogenous populations of both HA HuR-containing and normal MB231 cells yield no difference in cell division. Further experiments will use homogenous populations that highly overexpress HuR to see if HuR overexpression alters the proliferation and cell cycle capabilities of these cells. References: "Hallmarks of Cancer" Hanahan, Douglas and Weinberg, Robert A. Cell. Vol. 100, 57-70. 200

    Overexpression of the RNA-binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis [abstract]

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    Breast cancer is the second most common cancer in women and causes the death of 519,000 people worldwide. Many cancer genes are posttranscriptionally regulated by RNA-binding proteins (RBPs) and microRNAs. The RBP HuR binds to the AU-rich (ARE) regions of labile mRNAs, such as proto-oncogenes, stabilizing their mRNA and facilitating their translation into protein. HuR has been described to control genes in multiple areas of the acquired capabilities model of cancer and has been hypothesized to be a tumor maintenance gene, allowing for cancers to proliferate once they are established. We investigated the role of HuR in aggressive and difficult to treat triple-negative breast cancer

    The role of demonstrator familiarity and language cues on infant imitation from television

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    An imitation procedure was used to investigate the impact of demonstrator familiarity and language cues on infant learning from television. Eighteen-month-old infants watched two pre-recorded videos showing an adult demonstrating a sequence of actions with two sets of stimuli. Infants' familiarity with the demonstrator and the language used during the demonstration varied as a function of experimental condition. Immediately after watching each video, infants' ability to reproduce the target actions was assessed. A highly familiar demonstrator did not enhance infants' performance. However, the addition of a narrative, developed from mothers' naturalistic description of the event, facilitated learning from an unfamiliar demonstrator. We propose that the differential effect of demonstrator familiarity and language cues may reflect the infants' ability to distinguish between important and less important aspects in a learning situation. (C) 2010 Elsevier Inc. All rights reserved

    Systematic evaluation of an atomic clock at 2e-18 total uncertainty

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    The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, new insights in quantum science, tighter limits on fundamental constant variation, and improved tests of relativity. The record for the best stability and accuracy is currently held by optical lattice clocks. This work takes an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Our 87Sr optical lattice clock now achieves fractional stability of 2.2e-16 at 1 s. With this improved stability, we perform a new accuracy evaluation of our clock, reducing many systematic uncertainties that limited our previous measurements, such as those in the lattice ac Stark shift, the atoms' thermal environment, and the atomic response to room-temperature BBR. Our combined measurements have reduced the total uncertainty of the JILA Sr clock to 2.1e-18 in fractional frequency units.Comment: Full published versio

    Charge Ordering and Phase Competition in the Layered Perovskite Lasr2mn2o7

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    Charge-lattice fluctuations are observed in the layered perovskite manganite LaSr2Mn2O7 by Raman spectroscopy as high as 340 K and with decreasing temperature they become static and form a charge ordered (CO) phase below TCO=210 K. In the static regime, superlattice reflections are observed through neutron and x-ray diffraction with a propagation vector (h+1/4,k-1/4,l). Crystallographic analysis of the CO state demonstrates that the degree of charge and orbital ordering in this manganite is weaker than the charge ordering in three dimensional perovskite manganites. A TN=170K a type-A antiferromagnetism (AF) develops and competes with the charge ordering, that eventually melts below T*=100K. High resolution diffraction measurements suggest that that CO- and AF-states do not coincide within the same region in the material but rather co-exist as separate phases. The transition to type-A antiferromagnetism at lower temperatures is characterized by the competition between these two phases.Comment: 9 pages, 6 figure

    Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke

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    'Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6-4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA
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