11,312 research outputs found

    GPER-induced signaling is essential for the survival of breast cancer stem cells.

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    G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

    Dual Gate Graphene FETs with fT of 50 GHz

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    A dual-gate graphene field-effect transistors is presented, which shows improved RF performance by reducing the access resistance using electrostatic doping. With a carrier mobility of 2700 cm2/Vs, a cutoff frequency of 50 GHz is demonstrated in a 350-nm gate length device. This fT value is the highest frequency reported to date for any graphene transistor, and it also exceeds that of Si MOSFETs at the same gate length, illustrating the potential of graphene for RF applications

    Quantitative evaluation for spasticity of calf muscle after botulinum toxin injection in patients with cerebral palsy: a pilot study

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    BACKGROUND: Cerebral palsy (CP) is the most common pediatric disease to cause motor disability. Two common symptoms in CP are spasticity and contracture. If this occurred in the ankle plantar flexors of children with CP, it will impair their gait and active daily living profoundly. Most children with CP receive botulinum toxin type A (BoNT-A) injection to reduce muscle tone, but a knowledge gap exists in the understanding of changes of neural and non-neural components of spasticity after injection. The purpose of this study was to determine if our device for quantitative modified Tardieu approach (QMTA) is a valid method to assess spasticity of calf muscles after botulinum toxin injection. METHODS: In this study, we intended to develop a device for quantitative measurement of spasticity in calf muscles based on the modified Tardieu scale (MTS) and techniques of biomedical engineering. Our QMTA measures the angular displacement and resistance of stretched joint with a device that is light, portable and can be operated similar to conventional approaches for MTS. The static (R2), dynamic (R1) and R2-R1 angles derived from the reactive signals collected by the miniature sensors are used to represent the non-neural and neural components of stretched spastic muscles. Four children with CP were recruited to assess the change in spasticity in their gastrocnemius muscles before and 4 weeks after BoNT-A injection. RESULTS: A simulated ankle model validated the performance of our device in measuring joint displacement and estimating the angle of catch. Data from our participants with CP showed that R2 and R2-R1 improved significantly after BoNT-A administration. It indicates both neural and non-neural components of the spastic gastrocnemius muscles improved at four weeks after BoNT-A injection in children with CP. CONCLUSION: Our device for QMTA can objectively measure the changes in spasticity of the gastrocnemius muscle in children with cerebral palsy after BoNT-A injection

    Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.

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    Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2's preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate

    Hemispheric dispersion of radioactive plume laced with fission nuclides from the Fukushima nuclear event

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    Radioactivities of particulate 131I and 137Cs released from the Fukushima nuclear accident were monitored in a regional aerosol network including two high mountain sites (central Taiwan and Tibetan Plateau). The results were integrated with data measured elsewhere around the world, with special focus on the mid-latitudes. The hemispheric transport of the Fukushima radiation clouds (FRCs) by the westerlies took 18days,displayinganexponentiallikedecreaseeastward,withadilutionfactorofatleastfiveordersofmagnitudefollowingafullcircuitaroundtheglobe.TheinitialtwowavesofFRCsmaytravelatdifferentatitudes:thefirstoneat18 days, displaying an exponential-like decrease eastward, with a dilution factor of at least five orders of magnitude following a full circuit around the globe. The initial two waves of FRCs may travel at different atitudes: the first one at 3–4 km, whereas the second one up to 5 km or more. 131I and 137Cs were fractionated during transport, with 137Cs concentrated in the shallower layer, susceptible to depositional removal, while 131I moving faster and higher. This accident may be exemplified to identify some atmospheric processes on the hemispheric scale
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