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  • American Association for the Advancement of Science (AAAS)  (6)
  • Institute of Physics (IOP)  (5)
  • 1
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    Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-06-25
    Description: The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER + (estrogen receptor–positive)/PR + human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PR modulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER + /PR + breast cancers should be explored.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    A hidden state in the turnover of a functioning membrane protein complex (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Most membrane proteins exist in complexes that carry out critical cellular functions and exhibit rich dynamics. The bacterial flagellar motor, a large membrane-spanning ion-driven rotary motor that propels the bacteria to swim, provides a canonical example. Rotation of the motor is driven by multiple torque-generating units (stators). Turnover of the stators has been shown previously, demonstrating the exchange of stator units between the motor and a membrane pool. But the details of the turnover kinetics remain unclear. Here, we directly measured the kinetics of stator turnover in individual motors via analysis of a large dataset of long-term high-resolution recordings of motor speed at high load. We found that the dwell time distribution of the stator units exhibits a multi-exponential shape, suggesting the existence of a hidden state in the turnover of the stators.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Assimilation of microwave brightness temperatures for soil moisture estimation using particle filter (2014)
    Institute of Physics (IOP)
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    Publication Date: 2014-03-19
    Description: Soil moisture plays a significant role in global water cycles. Both model simulations and remote sensing observations have their limitations when estimating soil moisture on a large spatial scale. Data assimilation (DA) is a promising tool which can combine model dynamics and remote sensing observations to obtain more precise ground soil moisture distribution. Among various DA methods, the particle filter (PF) can be applied to non-linear and non-Gaussian systems, thus holding great potential for DA. In this study, a data assimilation scheme based on the residual resampling particle filter (RR-PF) was developed to assimilate microwave brightness temperatures into the macro-scale semi-distributed Variance Infiltration Capacity (VIC) Model to estimate surface soil moisture. A radiative transfer model (RTM) was used to link brightness temperatures with surface soil moisture. Finally, the data assimilation scheme was validated by experimental data obtained at Arizona during the Soil...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 4
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    Contemporary condition and conservation of wetland resource in Pingshan, Hebei Province (2018)
    Institute of Physics (IOP)
    Details
    Publication Date: 2018-08-31
    Description: The current work envisages the use of Remote sensing,Geography information systems and Global positioning systems literature analysis of precipitation, field investigation and laboratory analysis to perform a comprehensive investigation on the present situation of wetland resources of Pingshan Wetland in Hebei Province. The results showed that there were 5 types of wetlands, including the riverine wetland, flood plain, reservoir and pond, water-conveyance canal, and paddy field, with a total area of 162.61 km 2 . There were 311 species of wetland higher plants in Pingshan County, including 10 species of bryophytes, 296 angiosperm species, 5 species of ferns, and 81 phytoplankton species. There were 186 wetland birds, 35 species of fish, 5 species of amphibians, 14 species of reptiles, and 19 species of mammals in Pingshan County. In view of the present situation and the threat of wetland in Pingshan County, certain suggestions have been proposed to strengthen the protec...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 5
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    Plasmodium gametocytes display homing and vascular transmigration in the host bone marrow (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-05-24
    Description: Transmission of Plasmodium parasites to the mosquito requires the formation and development of gametocytes. Studies in infected humans have shown that only the most mature forms of Plasmodium falciparum gametocytes are present in circulation, whereas immature forms accumulate in the hematopoietic environment of the bone marrow. We used the rodent model Plasmodium berghei to study gametocyte behavior through time under physiological conditions. Intravital microscopy demonstrated preferential homing of early gametocyte forms across the intact vascular barrier of the bone marrow and the spleen early during infection and subsequent development in the extravascular environment. During the acute phase of infection, we observed vascular leakage resulting in further parasite accumulation in this environment. Mature gametocytes showed high deformability and were found entering and exiting the intact vascular barrier. We suggest that extravascular gametocyte localization and mobility are essential for gametocytogenesis and transmission of Plasmodium to the mosquito.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Low-input and multiplexed microfluidic assay reveals epigenomic variation across cerebellum and prefrontal cortex (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-04-19
    Description: Extensive effort is under way to survey the epigenomic landscape of primary ex vivo tissues to establish normal reference data and to discern variation associated with disease. The low abundance of some tissue types and the isolation procedure required to generate a homogenous cell population often yield a small quantity of cells for examination. This difficulty is further compounded by the need to profile a myriad of epigenetic marks. Thus, technologies that permit both ultralow input and high throughput are desired. We demonstrate a simple microfluidic technology, SurfaceChIP-seq, for profiling genome-wide histone modifications using as few as 30 to 100 cells per assay and with up to eight assays running in parallel. We applied the technology to profile epigenomes using nuclei isolated from prefrontal cortex and cerebellum of mouse brain. Our cell type–specific data revealed that neuronal and glial fractions exhibited profound epigenomic differences across the two functionally distinct brain regions.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Thermodynamic Simulation of Viscosity of TiO 2 -Ti 2 O 3 -CaO Ternary Slag (2017)
    Institute of Physics (IOP)
    Details
    Publication Date: 2017-12-22
    Description: The viscosity of high titanium slag at high temperature is one of the key factors of slag-iron separation. Based on the Einstein-Roscoe equation, thermodynamic simulation of viscosity of TiO 2 -Ti 2 O 3 -CaO ternary slag is studied by using FactSage ® software, and the effects of temperature, CaO content and solid-phase particles on the viscosity of slag were studied. The results show that the increase of CaO content has the effect of reducing melting temperature and viscosity of TiO 2 -Ti 2 O 3 -CaO ternary slag. After the TiO 2 -Ti 2 O 3 -CaO ternary slag is completely melted, the increase of temperature has little effect on viscosity of slag, and the viscosity is about 110~125mPa·s. When the temperature is lower than melting temperature, TiO 2 -Ti 2 O 3 -CaO ternary slag will precipitate solid-phase particles, and the precipitation process is carried out in st...
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Institute of Physics (IOP)
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  • 8
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    On Fusing Mechanism Involving the Fuses at Secondary Winding of PT Induced by VFTO (2017)
    Institute of Physics (IOP)
    Details
    Publication Date: 2017-11-03
    Description: The impact of very fast transient over-voltage(VFTO) on the primary and secondary equipment in gas insulated station(GIS) should not be ignored. In this paper, the research on fusing mechanism involving the fuses at secondary winding of PT induced by VFTO is carried out based on an actual case from the 500kV GIS substation belonged to Guizhou Tianshengqiao No.2 hydro power plant. As for the high voltage side, the transfer function about over-voltage can be formed in order to analyse the characteristics about high frequency over-voltage. As for the low voltage side, a three-phase equivalent model for secondary circuit of PT with the parallel arrangement at the A, B and C phases may be built for simulating the current distribution of the low voltage fuses in the situation of high frequency voltage and current. The results show that the maximum allowable current of fuse might be reduced greatly in the high-frequency circumstance due to skin effect and proximity effect, in compariso...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 9
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    Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains (2017)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2017-04-13
    Description: -Secretase cleavage of the Notch receptor transmembrane domain is a critical signaling event for various cellular processes. Efforts to develop inhibitors of -secretase cleavage of the amyloid-β precursor C99 protein as potential Alzheimer’s disease therapeutics have been confounded by toxicity resulting from the inhibition of normal cleavage of Notch. We present biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99. The Notch-TMD and C99 have very different conformations, adapt differently to changes in model membrane hydrophobic span, and exhibit different cholesterol-binding properties. These differences may be exploited in the design of agents that inhibit cleavage of C99 while allowing Notch cleavage.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Structure and dynamics of the active human parathyroid hormone receptor-1 (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉The parathyroid hormone receptor-1 (PTH1R) is a class B G protein–coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo–electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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