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  • 1
    Publication Date: 2018-10-25
    Description: Extinction of conditioned fear necessitates the dynamic involvement of hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA), but key molecular players that regulate these circuits to achieve fear extinction remain largely unknown. Here, we report that acid-sensing ion channel 1a (ASIC1a) is a crucial molecular regulator of fear extinction, and that this function requires ASIC1a in ventral hippocampus (vHPC), but not dorsal hippocampus, mPFC, or BLA. While genetic disruption or pharmacological inhibition of ASIC1a in vHPC attenuated the extinction of conditioned fear, overexpression of the channel in this area promoted fear extinction. Channelrhodopsin-2–assisted circuit mapping revealed that fear extinction involved an ASIC1a-dependent modification of the long-range hippocampal-prefrontal correlates in a projection-specific manner. Gene expression profiling analysis and validating experiments identified several neuronal activity–regulated and memory-related genes, including Fos , Npas4 , and Bdnf , as the potential mediators of ASIC1a regulation of fear extinction. Mechanistically, genetic overexpression of brain-derived neurotrophic factor (BDNF) in vHPC or supplement of BDNF protein in mPFC both rescued the deficiency in fear extinction and the deficits on extinction-driven adaptations of hippocampal-prefrontal correlates caused by the Asic1a gene inactivation in vHPC. Together, these results establish ASIC1a as a critical constituent in fear extinction circuits and thus a promising target for managing adaptive behaviors.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 2
    Publication Date: 2018-07-03
    Description: Qiwei Wang, Yan Wang, and Fengwei Yu Pruning that selectively removes unnecessary neurites without causing neuronal death is essential for sculpting the mature nervous system during development. In Drosophila , ddaC sensory neurons specifically prune their larval dendrites with intact axons during metamorphosis. However, the important role of endoplasmic reticulum (ER)-to-Golgi transport in dendrite pruning remains unknown. Here, in a clonal screen, we have identified Yif1, an uncharacterized Drosophila homolog of Yif1p that is known to be a regulator of ER-to-Golgi transport in yeast. We show that Yif1 is required for dendrite pruning of ddaC neurons but not for apoptosis of ddaF neurons. We further identify that the Yif1-binding partner Yip1 is also crucial for dendrite pruning. Yif1 forms a protein complex with Yip1 in S2 cells and ddaC neurons. Yip1 and Yif1 colocalize on ER/Golgi and are required for the integrity of Golgi apparatus and outposts. Moreover, we show that two GTPases, Rab1 and Sar1, which are known to regulate ER-to-Golgi transport, are essential for dendrite pruning of ddaC neurons. Finally, our data reveal that ER-to-Golgi transport promotes endocytosis and downregulation of the cell-adhesion molecule Neuroglian and thereby dendrite pruning.
    Keywords: Neural development
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
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  • 3
    Publication Date: 2018-07-07
    Description: Plasticity of metallic nanowires is often controlled by the activities of single deformation mode. It remains largely unclear whether multiple deformation modes can be activated in an individual metallic nanowire and how much plasticity they can contribute. In situ nanomechanical testing reveals a superior plastic deformation ability of body-centered cubic (BCC) niobium nanowires, in which a remarkable elongation of more than 269% is achieved before fracture. This superplastic deformation originates from a synergy of consecutively nucleated multiple reorientation processes that occur for more than five times via three distinct mechanisms, that is, stress-activated phase transformation, deformation twinning, and slip-induced crystal rotation. These three coupled mechanisms work concurrently, resulting in sequential reorientations and therefore superplastic deformation of Nb nanowires. Our findings reveal a superior mechanical property of BCC Nb nanowires through the close coordination of multiple deformation modes, which may have some implications in other metallic nanowire systems.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 4
    Publication Date: 2018-12-14
    Description: Paired measurements of 14 C/ 12 C and 230 Th ages from two Hulu Cave stalagmites complete a precise record of atmospheric 14 C covering the full range of the 14 C dating method (~54,000 years). Over the last glacial period, atmospheric 14 C/ 12 C ranges from values similar to modern values to values 1.70 times higher (42,000 to 39,000 years ago). The latter correspond to 14 C ages 5200 years less than calibrated ages and correlate with the Laschamp geomagnetic excursion followed by Heinrich Stadial 4. Millennial-scale variations are largely attributable to Earth’s magnetic field changes and in part to climate-related changes in the oceanic carbon cycle. A progressive shift to lower 14 C/ 12 C values between 25,000 and 11,000 years ago is likely related, in part, to progressively increasing ocean ventilation rates.
    Keywords: Atmospheric Science, Geochemistry, Geophysics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2018-01-03
    Description: A genomic variant in the human ADTRP [androgen-dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vasculogenesis. In zebrafish, there are 2 paralogues for adtrp ( i.e. , adtrp1 and adtrp2 ). Knockdown of adtrp1 expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, etsrp , fli1a , and scl ; blocks primitive hematopoiesis, as shown by decreased expression of pu.1 , mpo , and l-plastin ; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of runx1 and c-myb . However, adtrp1 knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on gata1 or h-bae1 ) or vasculogenesis (no effect on kdrl , ephb2a, notch3 , dab2 , or flt4 ). Knockdown of adtrp2 expression does not have apparent effects on all markers tested. Knockdown of adtrp1 reduced the expression of tfpi , and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. These data suggest that the regulation of tfpi expression is one potential mechanism by which adtrp1 regulates primitive myelopoiesis and definitive hematopoiesis.—Wang, L., Wang, X., Wang, L., Yousaf, M., Li, J., Zuo, M., Yang, Z., Gou, D., Bao, B., Li, L., Xiang, N., Jia, H., Xu, C., Chen, Q., Wang, Q. K. Identification of a new adtrp1-tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
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  • 6
    Publication Date: 2018-02-02
    Description: Purpose: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression data sets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. Experimental Design: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-catenin pathway and its target binding gene. The animal model supported the experimental findings. Results: We found that NEAT1 levels were regulated by EGFR pathway activity, which was mediated by STAT3 and NFB (p65) downstream of the EGFR pathway. Moreover, we found that NEAT1 was critical for glioma cell growth and invasion by increasing β-catenin nuclear transport and downregulating ICAT, GSK3B, and Axin2. Taken together, we found that NEAT1 could bind to EZH2 and mediate the trimethylation of H3K27 in their promoters. NEAT1 depletion also inhibited GBM cell growth and invasion in the intracranial animal model. Conclusions: The EGFR/ NEAT1 /EZH2/β-catenin axis serves as a critical effector of tumorigenesis and progression, suggesting new therapeutic directions in glioblastoma. Clin Cancer Res; 24(3); 684–95. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 7
    Keywords: POPULATION ; RISK ; MELANOMA ; BRCA1 MUTATION CARRIERS ; CONSORTIUM ; TUMOR SUBTYPES
    Abstract: Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P 1 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR 1.16; P 1.1 10(8)) but showed a weaker association with overall breast cancer (OR 1.08, P 1.3 10(6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR 1.01, P 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR 1.12; P 1.1 10(9)), and with both ER-positive (OR 1.09; P 1.5 10(5)) and ER-negative (OR 1.16, P 2.5 10(7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.
    Type of Publication: Journal article published
    PubMed ID: 22976474
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  • 8
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 76 (1994), S. 3926-3928 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A new configuration of phase conjugation (PC) with three beams in BaTiO3 crystal is demonstrated. When two beams are incident, they can generate their own self-pumped PC or mutually pumped PC depending on their intensity ratio. Upon the application of a third beam, one of the two mutually pumped beams is changed into a self-pumped PC. The other forms a double PC with the new beam. This configuration has more flexibility and functionality than that in the two-beam case. The analysis of mode competitions between self-pumped, mutually pumped, and double PC is given.
    Type of Medium: Electronic Resource
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  • 9
    Publication Date: 2018-06-29
    Description: The ultrafast laser excitation of matters leads to nonequilibrium states with complex solid-liquid phase-transition dynamics. We used electron diffraction at mega–electron volt energies to visualize the ultrafast melting of gold on the atomic scale length. For energy densities approaching the irreversible melting regime, we first observed heterogeneous melting on time scales of 100 to 1000 picoseconds, transitioning to homogeneous melting that occurs catastrophically within 10 to 20 picoseconds at higher energy densities. We showed evidence for the heterogeneous coexistence of solid and liquid. We determined the ion and electron temperature evolution and found superheated conditions. Our results constrain the electron-ion coupling rate, determine the Debye temperature, and reveal the melting sensitivity to nucleation seeds.
    Keywords: Physics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2018-07-03
    Description: Transforming growth factor–β (TGF-β) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-β signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo . Trim33 was required for induction in vitro of Th17, but not T reg cells. Moreover, Smad4 and Trim33 play contrasting roles in the regulation of IL-10 expression; loss of Trim33 enhanced IL-10 production. Furthermore, Trim33 was recruited to the Il17a and Il10 gene loci, dependent on Smad2, and mediated their chromatin remodeling during Th17 differentiation. Trim33 thus promotes the proinflammatory function of Th17 cells by inducing IL-17 and suppressing IL-10 expression.
    Keywords: Autoimmunity
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
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