2D-SAR, Topomer CoMFA and molecular docking studies on avian influenza neuraminidase inhibitors
Not Available
Niu, Bing (ORCID:0000000312075184)↗
Engineering topics
Lu, Yi
Publications and source records attributed to Lu, Yi.
Circular RNA HIPK3 regulates human lens epithelial cells proliferation and apoptosis by targeting the miR-193a/CRYAA axis
Highlights: • CircRNA sequencing reveals 26 up-regulated and 75 down-regulated circRNAs in ARC. • CircHIPK3 is down-regulated in all three subtypes of ARC. • CircHIPK3 knockdown affects the cellular function in primary cultured HLECs. • CircHIPK3 exerts its role via modulation of circHIPK3/miR-193a/CRYAA axis in HLECs. Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated from back splicing. Accumulating evidence has demonstrated their vital regulation in several biological processes and ocular diseases. However, the role of circRNAs in age-related cataract (ARC), the leading cause of visual impairment worldwide, is still unknown. CircRNA sequencing reveals that 101 circRNAs are differentially expressed between the capsules of transparent and ARC lenses, including 75 down-regulated circRNAs and 26 up-regulated circRNAs transcripts. Eight of 10 differentially expressed circRNAs are further verified by quantitative RT-PCRs. One highly conserved circRNA, circHIPK3, is significantly down-regulated in all cortical, nuclear and posterior subcapsular subtypes of ARC. The silencing of circHIPK3, but not HIPK3 mRNA, significantly accelerates apoptosis development upon oxidative stress and decreases cell viability and proliferation in primary cultured human lens epithelial cells (HLECs). The expression of α-SMA and vimentin was downregulated, while the expression of E-cadherin and ZO-1was upregulated, suggesting the repression of epithelial-mesenchymal transition after circHIPK3 knockdown. CircHIPK3 silencing increases miR-193a expression. miR-193a regulates CRYAA expression by targeting the binding site within the 3′UTR. Moreover, miR-193a decreases the viability and proliferation, and increases the apoptosis of HLECs upon oxidative stress. This study suggests that circRNAs are the potential regulators in cataractogenesis. CircHIPK3 regulates HLECs function through miR-193a-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of ARC.
60 APPLIED LIFE SCIENCES↗
A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme
Multielectron redox reactions often require multicofactor metalloenzymes to facilitate coupled electron and proton movement, but it is challenging to design artificial enzymes to catalyze these important reactions, owing to their structural and functional complexity. Here, we report a designed heteronuclear heme-[4Fe-4S] cofactor in cytochrome c peroxidase as a structural and functional model of the enzyme sulfite reductase. The initial model exhibits spectroscopic and ligand-binding properties of the native enzyme, and sulfite reduction activity was improved—through rational tuning of the secondary sphere interactions around the [4Fe-4S] and the substrate-binding sites—to be close to that of the native enzyme. By offering insight into the requirements for a demanding six-electron, seven-proton reaction that has so far eluded synthetic catalysts, this study provides strategies for designing highly functional multicofactor artificial enzymes.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Data from A Designed Heme-[4Fe-4S] Metalloenzyme Catalyzes Sulfite Reduction Like the Native Enzyme
Enzymatic reduction of oxyanions such as sulfite (SO32−) requires the delivery of multiple electrons and protons, a feat accomplished by cofactors tailored for catalysis and electron transport. Replicating this strategy in protein scaffolds may expand the range of enzymes that can be designed de novo. Mirts et al. selected a scaffold protein containing a natural heme cofactor and then engineered a cavity suitable for binding a second cofactor—an iron-sulfur cluster (see the Perspective by Lancaster). The resulting designed enzyme was optimized through rational mutation into a catalyst with spectral characteristics and activity similar to that of natural sulfite reductases.
Catalysis↗
A new era for electron bifurcation
Electron bifurcation, or the coupling of exergonic and endergonic oxidation-reduction reactions, was discovered by Peter Mitchell and provides an elegant mechanism to rationalize and understand the logic that underpins the Q cycle of the respiratory chain. Thought to be a unique reaction of respiratory complex III for nearly 40 years, about a decade ago Wolfgang Buckel and Rudolf Thauer discovered that flavin-based electron bifurcation is also an important component of anaerobic microbial metabolism. Their discovery spawned a surge of research activity, providing a basis to understand flavin-based bifurcation, forging fundamental parallels with Mitchell's Q cycle and leading to the proposal of metal-based bifurcating enzymes. New insights into the mechanism of electron bifurcation provide a foundation to establish the unifying principles and essential elements of this fascinating biochemical phenomenon.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Protein disulfide isomerase enhances tissue factor-dependent thrombin generation
Protein disulfide isomerase (PDI) plays an important role in fibrin generation in vivo, but the underlying mechanism remains largely unknown. In this study, using thrombin generation assay (TGA), we investigated whether PDI contributes to tissue factor (TF)-mediated thrombin generation. Human peripheral blood mononuclear cells (PBMCs) were treated with 100 ng/ml lipopolysaccharide (LPS), the expression of TF on cell surface was analyzed by flow cytometry. After incubation with an inhibitory anti-TF antibody, recombinant PDI protein or a PDI inhibitor PACMA31, LPS-stimulated human PBMCs were incubated with human plasma, and thrombin generation was assessed by Ceveron Alpha TGA and a fluorescent thrombin substrate. Bone marrow mononuclear cells isolated from PDI-knockout and wild-type mice were stimulated by LPS, followed by measurement of thrombin generation. LPS stimulation increased expression of TF on PBMCs, and thrombin generation. Inhibitory anti-TF antibody almost completely suppressed thrombin generation of LPS-stimulated PBMCs, suggesting that thrombin generation was TF-dependent. Recombinant PDI protein increased thrombin generation, while PACMA31 attenuated thrombin generation. Compared with control cells, PDI-deficient marrow mononuclear cells had less capacity in thrombin generation. Taken together, these data suggest that PDI enhances TF-dependent thrombin generation.
60 APPLIED LIFE SCIENCES↗
Transition sum rules in the shell model
An important characterization of electromagnetic and weak transitions in atomic nuclei are sum rules. We focus on the non-energy-weighted sum rule (NEWSR), or total strength, and the energy- weighted sum rule (EWSR); the ratio of the EWSR to the NEWSR is the centroid or average energy of transition strengths from an nuclear initial state to all allowed final states. These sum rules can be expressed as expectation values of operators, in the case of the EWSR a double commutator. While most prior applications of the double-commutator have been to special cases, we derive general formulas for matrix elements of both operators in a shell model framework (occupation space), given the input matrix elements for the nuclear Hamiltonian and for the transition operator. With these new formulas, we easily evaluate centroids of transition strength functions, with no need to calculate daughter states. We then apply this simple tool to a number of nuclides, and demonstrate the sum rules follow smooth secular behavior as a function of initial energy, as well as compare the electric dipole (E1) sum rule against the famous Thomas-Reiche-Kuhn version. We also find surprising systematic behaviors for ground state electric quadrupole (E2) centroids in the $sd$-shell.
73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
2018 Metals in Biology Gordon Research Conference and 2018 Bioinorganic Chemistry Gordon Research Seminar
Final Conference Program & Registration List
Lu, Yi↗
Aqueous Superparamagnetic Magnetite Dispersions with Ultrahigh Initial Magnetic Susceptibilities
Superparamagnetic nanoparticles with a high initial magneti susceptibility χo are of great interest in a wide variety of chemical, biomedical, electronic, and subsurface energy applications. In order to achieve the theoretically predicted increase in χ o with the cube of the magnetic diameter, new synthetic techniques are needed to control the crystal structure, particularly for magnetite nanoparticles larger than 10 nm. Aqueous magnetite dispersions (Fe 3 O 4 ) with a χ o of 3.3 (dimensionless SI units) at 1.9 vol %, over 3- to 5-fold greater than those reported previously, were produced in a one-pot synthesis at 210 °C and ambient pressure via thermal decomposition of Fe(II) acetate in triethylene glycol (TEG). The rapid nucleation and focused growth with an unusually high precursor-to-solvent molar ratio of 1:12 led to primary particles with a volume average diameter of 16 nm and low polydispersity according to TEM. The morphology was a mixture of stoichiometric and substoichiometric magnetite according to X-ray diffraction (XRD) and Mössbauer spectroscopy. Finally, the increase in χ o with the cube of magnetic diameter as well as a saturation magnetization approaching the theoretical limit may be attributed to the highly crystalline structure and very small nonmagnetic layer (~1 nm) with disordered spin orientation on the surface.
77 NANOSCIENCE AND NANOTECHNOLOGY↗
Revealing the Cosmic Web-dependent Halo Bias
Halo bias is the one of the key ingredients of the halo models. It was shown at a given redshift to be only dependent, to the first order, on the halo mass. In this study, four types of cosmic web environments—clusters, filaments, sheets, and voids—are defined within a state-of-the-art high-resolution N-body simulation. Within these environments, we use both halo-dark matter cross correlation and halo-halo autocorrelation functions to probe the clustering properties of halos. The nature of the halo bias differs strongly between the four different cosmic web environments described here. With respect to the overall population, halos in clusters have significantly lower biases in the 10{sup 11.0}∼10{sup 13.5} h{sup −1} M{sub ⊙} mass range. In other environments, however, halos show extremely enhanced biases up to a factor 10 in voids for halos of mass ∼10{sup 12.0} h{sup −1} M{sub ⊙}. Such a strong cosmic web environment dependence in the halo bias may play an important role in future cosmological and galaxy formation studies. Within this cosmic web framework, the age dependency of halo bias is found to be only significant in clusters and filaments for relatively small halos ≲10{sup 12.5} h{sup −1} M{sub ⊙}.
79 ASTRONOMY AND ASTROPHYSICS↗
Mapping the real-space distributions of galaxies in SDSS DR7. I. Two-point correlation functions
Using a method to correct redshift-space distortion (RSD) for individual galaxies, we mapped the real-space distributions of galaxies in the Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7). We use an ensemble of mock catalogs to demonstrate the reliability of our method. Here, in the first paper in a series, we focus mainly on the two-point correlation function (2PCF) of galaxies. Overall the 2PCF measured in the reconstructed real space for galaxies brighter than {sup 0.1}M{sub r}−5logh=−19.0 agrees with the direct measurement to an accuracy better than the measurement error due to cosmic variance, if the reconstruction uses the correct cosmology. Applying the method to the SDSS DR7, we construct a real-space version of the main galaxy catalog, which contains 396,068 galaxies in the North Galactic Cap with redshifts in the range 0.01 ≤ z ≤ 0.12. The Sloan Great Wall, the largest known structure in the nearby universe, is not as dominant an overdense structure as it appears to be in redshift space. We measure the 2PCFs in reconstructed real space for galaxies of different luminosities and colors. All of them show clear deviations from single power-law forms, and reveal clear transitions from one-halo to two-halo terms. A comparison with the corresponding 2PCFs in redshift space nicely demonstrates how RSDs boost the clustering power on large scales (by about 40%–50% at scales ∼10 h{sup −1} Mpc) and suppress it on small scales (by about 70%–80% on a scale of 0.3 h{sup −1} Mpc).
79 ASTRONOMY AND ASTROPHYSICS↗
Galaxy groups in the 2MASS redshift survey
A galaxy group catalog is constructed from the 2MASS Redshift Survey (2MRS) with the use of a halo-based group finder. The halo mass associated with a group is estimated using a “GAP” method based on the luminosity of the central galaxy and its gap with other member galaxies. Tests using mock samples show that this method is reliable, particularly for poor systems containing only a few members. On average, 80% of all the groups have completeness >0.8, and about 65% of the groups have zero contamination. Halo masses are estimated with a typical uncertainty of ∼0.35 dex. The application of the group finder to the 2MRS gives 29,904 groups from a total of 43,246 galaxies at z⩽0.08, with 5286 groups having two or more members. Some basic properties of this group catalog is presented, and comparisons are made with other group catalogs in overlap regions. With a depth to z∼0.08 and uniformly covering about 91% of the whole sky, this group catalog provides a useful database to study galaxies in the local cosmic web, and to reconstruct the mass distribution in the local universe.
79 ASTRONOMY AND ASTROPHYSICS↗
Response of Ferroelectric Polyvinylidene Fluoride under Pulsed Fast Neutron Irradiation
Because the spontaneous polarization of a ferroelectric material is a function of temperature, heating or cooling it slightly will cause bound charge to accumulate on faces normal to the polarization, and the phenomenon is called pyroelectric effect. The pyroelectric detectors can uses pulsed gamma rays or neutrons as the heat source, and they do not require external power supply units and have a high radiation stability. Pb(Zr, Ti)O{sub 3}-based ceramics are widely used ferroelectrics and have a relatively high density of about 7.8 g/cm{sup 3}, which is promising for gamma-ray detection. To develop a pyroelectric thermal neutron detector, E.A. de Souza and L.P. Geraldo et al. prepared a layer of neutron converter on the surface of Pb(Zr, Ti)O{sub 3} ceramic pellet, and the neutron converter can be uranium (with 20% enrichment in {sup 235}U) or boron (with natural isotopic abundance or with 92.41% enrichment in {sup 10}B). The proposed pyroelectric neutron detector is interesting, but not suitable for fast neutron detection accompanied with gamma rays. As the polyvinylidene fluoride (PVDF) is also a kind of ferroelectric material, but with a low density about 1.78 g/cm{sup 3}, indicating a low sensitivity to gamma radiation. This material contains about 3.35 x 10{sup 22}/cm{sup 3} of H, which has a relatively large cross section with fast neutrons. The PVDF possibly has the potential for fast neutron detection, and the response of ferroelectric polyvinylidene fluoride under pulsed fast neutron irradiation was reported. (authors)
36 MATERIALS SCIENCE↗
Fluorescent nanoprobes for sensing and imaging of metal ions: Recent advances and future perspectives
Not Available
Zhang, JingJing↗
A Purple Cupredoxin from Nitrosopumilus maritimus Containing a Mononuclear Type 1 Copper Center with an Open Binding Site
Mononuclear cupredoxin proteins usually contain a coordinately saturated type 1 copper (T1Cu) center and function exclusively as electron carriers. Here we report a cupredoxin isolated from the nitrifying archaeon Nitrosopumilus maritimus SCM1, called Nmar1307, that contains a T1Cu center with an open binding site containing water. It displays a deep purple color due to strong absorptions around 413 nm (1880 M –1 cm –1 ) and 558 nm (2290 M –1 cm –1 ) in the UV–vis electronic spectrum. EPR studies suggest the protein contains two Cu(II) species of nearly equal population, one nearly axial, with hyperfine constant A∥ = 98 × 10 –4 cm –1 , and another more rhombic, with a smaller A∥ value of 69 × 10 –4 cm –1 . The X-ray crystal structure at 1.6 Å resolution confirms that it contains a Cu atom coordinated by two His and one Cys in a trigonal plane, with an axial H2O at 2.25 Å. Both UV–vis absorption and EPR spectroscopic studies suggest that the Nmar1307 can oxidize NO to nitrite, an activity that is attributable to the high reduction potential (354 mV vs SHE) of the copper site. These results suggest that mononuclear cupredoxins can have a wide range of structural features, including an open binding site containing water, making this class of proteins even more versatile.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Reversible S-nitrosylation in an engineered azurin
S-Nitrosothiols are known as reagents for NO storage and transportation and as regulators in many physiological processes. Although the S-nitrosylation catalysed by haem proteins is well known, no direct evidence of S-nitrosylation in copper proteins has been reported. Here, we report reversible insertion of NO into a copper–thiolate bond in an engineered copper centre in Pseudomonas aeruginosa azurin by rational design of the primary coordination sphere and tuning its reduction potential by deleting a hydrogen bond in the secondary coordination sphere. The results not only provide the first direct evidence of S-nitrosylation of Cu(II)-bound cysteine in metalloproteins, but also shed light on the reaction mechanism and structural features responsible for stabilizing the elusive Cu(I)–S(Cys)NO species. The fast, efficient and reversible S-nitrosylation reaction is used to demonstrate its ability to prevent NO inhibition of cytochrome bo3 oxidase activity by competing for NO binding with the native enzyme under physiologically relevant conditions.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Biochemical and biophysical understanding of metal ion selectivity of DNAzymes
This review summarizes research on the metal-binding properties of catalytic DNAzymes, towards the goal of understanding the structural properties leading to metal ion specificity. Progress made and insight gained from a range of biochemical and biophysical techniques are covered, and promising directions for future investigations are discussed.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗