Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains

AbstractWe previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al., Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions

Thermogravimetric and kinetic analysis to discern synergy during the co-pyrolysis of microalgae and swine manure digestate

Background: Co-pyrolysis of wastes with other feedstock can synergistically improve the rate of biomass decomposition and also help to resolve the issues related to limited availability feedstock. In this regards, synergistic interaction between feedstock during co-pyrolysis is an important aspect of research. As the constituents of aquatic and lignocellulosic biomass are different, and the decomposition pattern of aquatic biomass is dissimilar when compared to lignocellulosic biomass, it is important to understand whether these two biomasses interact during co-pyrolysis. Results: Synergism in the co-pyrolysis of microalgae (MA), swine manure digestate (SWD), and their blends (MA/SWD) (w/w %), 2.5/7.5 (MD-1), 5/5 (MD-2), and 7.5/2.5 (MD-3), was evaluated based on decomposition behavior, gas yields, extent of thermal degradation, and kinetics. Extractives and volatiles in biomass enhanced the reaction kinetics and products yields, as indicated by the reduction in apparent activation energy of the blends, accompanied by an increase in H2, total gas yield, and extent in degradation. Thermogravimetric data, via isoconversional methods, were interpreted to achieve the apparent activation energies for the thermal degradation of the MA, SWD, and their blends. The best fit reaction models were identified using compensation effect and generalized master plots methods. Semi-quantitative method was used to quantify the evolved gas species. H2, CO, and CO2 were noted to be the dominant gases, implying that tar cracking and reforming reactions were predominant. Conclusions: Overall, synergy was noticed with respect to the pyrolysis of SWD biomass to gas products in the presence of MA biomass, whereas synergy was witnessed up to 50 w/w % MA in view of kinetic parameters as evaluation criteria

Distributions of deposits and hydrogen on the upper and lower TDUs3 target elements of Wendelstein 7-X

Distributions of deposits and hydrogen (H) on the graphite divertor target elements TM4h4 and TM3v5 in the test divertor units 3 (TDUs3) of Wendelstein 7-X (W7-X) are studied. The TM4h4 and TM3v5 are located at the magnetically symmetric positions in the upper and lower divertor. The microstructure of the deposition layer is characterized by a transmission electron microscope (TEM) combined with a focused ion beam (FIB). Metallic deposits such as iron (Fe), molybdenum (Mo), chromium (Cr) are detected in the deposition layer by energy-dispersive x-ray spectroscopy (EDS). The depth-resolved distribution patterns of boron (B) and metallic deposits on upper and lower horizontal (h) divertor target elements TDUs3-TM4h4 as well as upper and lower vertical (v) divertor target elements TDUs3-TM3v5 are clarified by glow discharge optical emission spectrometry (GDOES). Results for both TDUs3-TM4h4 and TDUs3-TM3v5 show that the B deposition regions exhibit higher H retention due to the co-deposition with deposits. On the other hand, up-down asymmetries in B deposition caused by particle drift exist on both TDUs3-TM4h4 and TDUs3-TM3v5. The B deposition amount on upper TDUs3-TM4h4 is 40% smaller than that on lower TDUs3-TM4h4. While for the vertical target elements, the B deposition amount on upper TDUs3-TM3v5 is 35% larger than that on lower TDUs3-TM3v5. Meanwhile, a shift of around 3 cm in B deposition peaks is observed on upper and lower TDUs3-TM4h4 and TDUs3-TM3v5. Results of numerical simulation of carbon deposition/erosion profiles on the target elements using ERO2.0 code and power flux measured by infrared cameras are shown and compared with the above mentioned B profiles

Creating, moving and merging Dirac points with a Fermi gas in a tunable honeycomb lattice

Dirac points lie at the heart of many fascinating phenomena in condensed matter physics, from massless electrons in graphene to the emergence of conducting edge states in topological insulators [1, 2]. At a Dirac point, two energy bands intersect linearly and the particles behave as relativistic Dirac fermions. In solids, the rigid structure of the material sets the mass and velocity of the particles, as well as their interactions. A different, highly flexible approach is to create model systems using fermionic atoms trapped in the periodic potential of interfering laser beams, a method which so far has only been applied to explore simple lattice structures [3, 4]. Here we report on the creation of Dirac points with adjustable properties in a tunable honeycomb optical lattice. Using momentum-resolved interband transitions, we observe a minimum band gap inside the Brillouin zone at the position of the Dirac points. We exploit the unique tunability of our lattice potential to adjust the effective mass of the Dirac fermions by breaking inversion symmetry. Moreover, changing the lattice anisotropy allows us to move the position of the Dirac points inside the Brillouin zone. When increasing the anisotropy beyond a critical limit, the two Dirac points merge and annihilate each other - a situation which has recently attracted considerable theoretical interest [5-9], but seems extremely challenging to observe in solids [10]. We map out this topological transition in lattice parameter space and find excellent agreement with ab initio calculations. Our results not only pave the way to model materials where the topology of the band structure plays a crucial role, but also provide an avenue to explore many-body phases resulting from the interplay of complex lattice geometries with interactions [11, 12]

Lattice defect induced nanorod growth in YBCO films deposited on an advanced IBAD-MgO template

We have studied the growth of self-assembled BaHfO3 (BHO), BaZrO3 (BZO) and BaSnO3 (BSO) dopants in YBa2Cu3O6 + x (YBCO) films grown on CeO2 cap layered IBAD-MgO based metallic template by pulsed layer deposition process. The substrate induced defect formation and its impact on the growth of columnar-type of nanorods within the YBCO matrix is structurally investigated and their effect on critical current anisotropy is studied via molecular dynamics simulation model. We observed that the developed template greatly directs the growth mechanisms of different nanorods and thus modifies the critical current anisotropy of differently doped YBCO thin films.</p

PP1A-Mediated Dephosphorylation Positively Regulates YAP2 Activity

Background: The Hippo/MST1 signaling pathway plays an important role in the regulation of cell proliferation and apoptosis. As a major downstream target of the Hippo/MST1 pathway, YAP2 (Yes-associated protein 2) functions as a transcriptional cofactor that has been implicated in many biological processes, including organ size control and cancer development. MST1/Lats kinase inhibits YAP2’s nuclear accumulation and transcriptional activity through inducing the phosphorylation at serine 127 and the sequential association with 14-3-3 proteins. However, the dephosphorylation of YAP2 is not fully appreciated. Methodology/Principal Findings: In the present study, we demonstrate that PP1A (catalytic subunit of protein phosphatase-1) interacts with and dephosphorylates YAP2 in vitro and in vivo, and PP1A-mediated dephosphorylation induces the nuclear accumulation and transcriptional activation of YAP2. Inhibition of PP1 by okadiac acid (OA) increases the phosphorylation at serine 127 and cytoplasmic translocation of YAP2 proteins, thereby mitigating its transcription activity. PP1A expression enhances YAP2’s pro-survival capability and YAP2 knockdown sensitizes ovarian cancer cells to cisplatin treatment. Conclusions/Significance: Our findings define a novel molecular mechanism that YAP2 is positively regulated by PP1mediate

Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells

Epstein-Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB 23-431. Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells. © 2014 Macmillan Publishers Limited. All rights reserved.published_or_final_versio

Complete mitochondrial genomes and nuclear ribosomal RNA operons of two species of Diplostomum (Platyhelminthes: Trematoda): a molecular resource for taxonomy and molecular epidemiology of important fish pathogens

© 2015 Brabec et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Fully gapped topological surface states in Bi2_2Se3_3 films induced by a d-wave high-temperature superconductor

Topological insulators are a new class of materials, that exhibit robust gapless surface states protected by time-reversal symmetry. The interplay between such symmetry-protected topological surface states and symmetry-broken states (e.g. superconductivity) provides a platform for exploring novel quantum phenomena and new functionalities, such as 1D chiral or helical gapless Majorana fermions, and Majorana zero modes which may find application in fault-tolerant quantum computation. Inducing superconductivity on topological surface states is a prerequisite for their experimental realization. Here by growing high quality topological insulator Bi$_2$Se$_3$ films on a d-wave superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ using molecular beam epitaxy, we are able to induce high temperature superconductivity on the surface states of Bi$_2$Se$_3$ films with a large pairing gap up to 15 meV. Interestingly, distinct from the d-wave pairing of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$, the proximity-induced gap on the surface states is nearly isotropic and consistent with predominant s-wave pairing as revealed by angle-resolved photoemission spectroscopy. Our work could provide a critical step toward the realization of the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274

Viral integration drives multifocal HCC during the occult HBV infection

© 2019 The Author(s). Background & Aims: Although the prognosis of patients with occult hepatitis B virus (HBV) infection (OBI) is usually benign, a small portion may undergo cirrhosis and subsequently hepatocellular carcinoma (HCC). We studied the mechanism of life-long Integration of virus DNA into OBI host's genome, of which may induce hepatocyte transformation. Methods: We applied HBV capture sequencing on single cells from an OBI patient who, developed multiple HCC tumors and underwent liver resection in May 2013 at Tongji Hospital in China. Despite with the undetectable virus DNA in serum, we determined the pattern of viral integration in tumor cells and adjacent non-tumor cells and obtained the details of the viral arrangement in host genome, and furthermore the HBV integrated region in cancer genome. Results: HBV captured sequencing of tissues and individual cells revealed that samples from multiple tumors shared two viral integration sites that could affect three host genes, including CSMD2 on chr1 and MED30/EXT1 on chr8. Whole genome sequencing further indicated one hybrid chromosome formed by HBV integrations between chr1 and chr8 that was shared by multiple tumors. Additional 50 poorly differentiated liver tumors and the paired adjacent non-tumors were evaluated and functional studies suggested up-regulated EXT1 expression promoted HCC growth. We further observed that the most somatic mutations within the tumor cell genome were common among the multiple tumors, suggesting that HBV associated, multifocal HCC is monoclonal in origin. Conclusion: Through analyzing the HBV integration sites in multifocal HCC, our data suggested that the tumor cells were monoclonal in origin and formed in the absence of active viral replication, whereas the affected host genes may subsequently contribute to carcinogenesis