Syndecan-2 induces filopodia and dendritic spine formation via the neurofibromin–PKA–Ena/VASP pathway

Syndecan-2 induced filopodia before spinogenesis; therefore, filopodia formation was used here as a model to study the early downstream signaling of syndecan-2 that leads to spinogenesis. Screening using kinase inhibitors indicated that protein kinase A (PKA) is required for syndecan-2–induced filopodia formation in both human embryonic kidney cells and hippocampal neurons. Because neurofibromin, a syndecan-2–binding partner, activates the cyclic adenosine monophosphate pathway, the role of neurofibromin in syndecan-2–induced filopodia formation was investigated by deletion mutant analysis, RNA interference, and dominant-negative mutant. The results showed that neurofibromin mediates the syndecan-2 signal to PKA. Among actin-associated proteins, Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) were predicted as PKA effectors downstream of syndecan-2, as Ena/VASP, which is activated by PKA, induces actin polymerization. Indeed, when the activities of Ena/VASP were blocked, syndecan-2 no longer induced filopodia formation. Finally, in addition to filopodia formation, neurofibromin and Ena/VASP contributed to spinogenesis. This study reveals a novel signaling pathway in which syndecan-2 activates PKA via neurofibromin and PKA consequently phosphorylates Ena/VASP, promoting filopodia and spine formation

Complete chloroplast genome sequence of a tree fern Alsophila spinulosa: insights into evolutionary changes in fern chloroplast genomes

<p>Abstract</p> <p>Background</p> <p>Ferns have generally been neglected in studies of chloroplast genomics. Before this study, only one polypod and two basal ferns had their complete chloroplast (cp) genome reported. Tree ferns represent an ancient fern lineage that first occurred in the Late Triassic. In recent phylogenetic analyses, tree ferns were shown to be the sister group of polypods, the most diverse group of living ferns. Availability of cp genome sequence from a tree fern will facilitate interpretation of the evolutionary changes of fern cp genomes. Here we have sequenced the complete cp genome of a scaly tree fern <it>Alsophila spinulosa </it>(Cyatheaceae).</p> <p>Results</p> <p>The <it>Alsophila </it>cp genome is 156,661 base pairs (bp) in size, and has a typical quadripartite structure with the large (LSC, 86,308 bp) and small single copy (SSC, 21,623 bp) regions separated by two copies of an inverted repeat (IRs, 24,365 bp each). This genome contains 117 different genes encoding 85 proteins, 4 rRNAs and 28 tRNAs. Pseudogenes of <it>ycf66 </it>and <it>trnT-UGU </it>are also detected in this genome. A unique <it>trnR-UCG </it>gene (derived from <it>trnR-CCG</it>) is found between <it>rbcL </it>and <it>accD</it>. The <it>Alsophila </it>cp genome shares some unusual characteristics with the previously sequenced cp genome of the polypod fern <it>Adiantum capillus-veneris</it>, including the absence of 5 tRNA genes that exist in most other cp genomes. The genome shows a high degree of synteny with that of <it>Adiantum</it>, but differs considerably from two basal ferns (<it>Angiopteris evecta </it>and <it>Psilotum nudum</it>). At one endpoint of an ancient inversion we detected a highly repeated 565-bp-region that is absent from the <it>Adiantum </it>cp genome. An additional minor inversion of the <it>trnD-GUC</it>, which is possibly shared by all ferns, was identified by comparison between the fern and other land plant cp genomes.</p> <p>Conclusion</p> <p>By comparing four fern cp genome sequences it was confirmed that two major rearrangements distinguish higher leptosporangiate ferns from basal fern lineages. The <it>Alsophila </it>cp genome is very similar to that of the polypod fern <it>Adiantum </it>in terms of gene content, gene order and GC content. However, there exist some striking differences between them: the <it>trnR-UCG </it>gene represents a putative molecular apomorphy of tree ferns; and the repeats observed at one inversion endpoint may be a vestige of some unknown rearrangement(s). This work provided fresh insights into the fern cp genome evolution as well as useful data for future phylogenetic studies.</p

Design of Synchronous “Plug & Play” QKD-WDM-PON for Efficient Quantum Communications

We propose a new design of quantum key distribution (QKD) - WDM-PON with "plug & play" scheme and synchronization. Simulations show that the design can improve the quantum key generation rate 3-4 times over conventional scheme

Water-Soluble Flexible Organic Frameworks That Include and Deliver Proteins.

Four water-soluble hydrazone-based three-dimensional (3D) flexible organic frameworks FOF-1-4 have been synthesized from a semirigid tetracationic tetraaldehyde and four flexible dihydrazides. 1H NMR spectroscopy indicated the quantitative formation of FOF-1-4 in D2O, while dynamic light scattering experiments revealed that, depending on the concentration, these porous frameworks display hydrodynamic diameters ranging from 50 to 120 nm. The porosity of the frameworks is confirmed by ethanol vapor adsorption experiments of the solid samples as well as the high loading capacity for a 2.3 nm porphyrin guest in water. The new water-soluble frameworks exhibit low cytotoxicity and form inherent pores with diameters of 5.3 or 6.7 nm, allowing rapid inclusion of proteins such as bovine serum albumin and green and orange fluorescent proteins, and efficient delivery of the proteins into normal and cancer cells. Flow cytometric analysis reveals percentages of the delivered cells up to 99.8%

Water-Soluble 3D Covalent Organic Framework that Displays an Enhanced Enrichment Effect of Photosensitizers and Catalysts for the Reduction of Protons to H2.

Covalent organic frameworks (COFs) are emerging porous polymers that have 2D or 3D long-range ordering. Currently available COFs are typically insoluble or decompose upon dissolution, which remarkably restricts their practical implementations. For 3D COFs, the achievement of noninterpenetration, which maximizes their porosity-derived applications, also remains a challenge synthetically. Here, we report the synthesis of the first highly water-soluble 3D COF (sCOF-101) from irreversible polymerization of a preorganized supramolecular organic framework through cucurbit[8]uril (CB[8])-controlled [2 + 2] photodimerization. Synchrotron X-ray scattering and diffraction analyses confirm that sCOF-101 exhibits porosity periodicity, with a channel diameter of 2.3 nm, in both water and the solid state and retains the periodicity under both strongly acidic and basic conditions. As an ordered 3D polymer, sCOF-101 can enrich [Ru(bpy)3]2+ photosensitizers and redox-active polyoxometalates in water, which leads to remarkable increase of their photocatalytic activity for proton reduction to produce H2

Activated N-Ras signaling regulates arterial-venous specification in zebrafish

Background: The aberrant activation of Ras signaling is associated with human diseases including hematological malignancies and vascular disorders. So far the pathological roles of activated Ras signaling in hematopoiesis and vasculogenesis are largely unknown. Methods: A conditional Cre/loxP transgenic strategy was used to mediate the specific expression of a constitutively active form of human N-Ras in zebrafish endothelial and hematopoietic cells driven by the zebrafish lmo2 promoter. The expression of hematopoietic and endothelial marker genes was analyzed both via whole mount in situ hybridization (WISH) assay and real-time quantitative PCR (qPCR). The embryonic vascular morphogenesis was characterized both by living imaging and immunofluorescence on the sections with a confocal microscopy, and the number of endothelial cells in the embryos was quantified by flow cytometry. The functional analyses of the blood circulation were carried out by fluorescence microangiography assay and morpholino injection. Results: In the activated N-Ras transgenic embryos, the primitive hematopoiesis appeared normal, however, the definitive hematopoiesis of these embryos was completely absent. Further analysis of endothelial cell markers confirmed that transcription of arterial marker ephrinB2 was significantly decreased and expression of venous marker flt4 excessively increased, indicating the activated N-Ras signaling promotes the venous development at the expense of arteriogenesis during zebrafish embryogenesis. The activated N-Ras-expressing embryos showed atrophic axial arteries and expansive axial veins, leading to no definitive hematopoietic stem cell formation, the blood circulation failure and subsequently embryonic lethality. Conclusions: Our studies revealed for the first time that activated N-Ras signaling during the endothelial differentiation in vertebrates can disrupt the balance of arterial-venous specification, thus providing new insights into the pathogenesis of the congenital human vascular disease and tumorigenic angiogenesis

Two-stage soil infiltration treatment system for treating ammonium wastewaters of low COD/TN ratios

Soil infiltration treatment (SIT) is ineffective to treat ammonium wastewaters of total nitrogen (TN) > 100 mg l−1. This study applied a novel two-stage SIT process for effective TN removal from wastewaters of TN > 100 mg l−1 and of chemical oxygen demand (COD)/TN ratio of 3.2–8.6. The wastewater was first fed into the soil column (stage 1) at hydraulic loading rate (HLR) of 0.06 m3 m−2 d−1 for COD removal and total phosphorus (TP) immobilization. Then the effluent from stage 1 was fed individually into four soil columns (stage 2) at 0.02 m3 m−2 d−1 of HLR with different proportions of raw wastewater as additional carbon source. Over the one-year field test, balanced nitrification and denitrification in the two-stage SIT revealed excellent TN removal (>90%) from the tested wastewaters

Exploring the Interaction between Vancomycin/Teicoplanin and Receptor Binding Domain (RBD) of SARS-CoV-2

The recent pandemic caused by SARS-CoV-2 has spread to over 100 countries, infected more than 47 million people and resulted in more than 1.2 million deaths worldwide until October. It is well known that, the SARS-CoV-2 starts an infection by binding its Receptor Binding Domain (RBD) of spike protein to human Angiotensin converting enzyme 2 (ACE2) receptor, and strenuous efforts had been made to prevent the infection. However, no successful drugs or vaccines have appeared. Herein, molecular docking and molecular simulations were carried out to study the interaction between RBD and two glycopeptide antibiotics (Vancomycin and Teicoplanin). Key residues in binding pocket were highlighted and the binding free energies were calculated. Our results suggested that Vancomycin and Teicoplanin, as natural and accepted antibiotics, could block the interaction between RBD of spike protein and human ACE2 receptor, which might be developed to potential drugs against the SARS-CoV-2