Total phenolic and flavonoid content and biological activities of extracts and isolated compounds of Cytisus villosus pourr.

© 2019 by the authors. Kadsura coccinea (Lem.) A.C. Smith is an evergreen, woody climbing plant that is widely distributed throughout southwest mainland China. Extracts of this plant are used in traditional Chinese medicine (TCM) for the treatment of various diseases, like cancer and dermatosis, and as an anodyne to relieve pain, while the leaves are used to treat eczema. In the current study, the toxicity of essential oil from its stem (EOKC) was studied against two strains of bed bugs (Cimex lectularius). Essential oil from the plant was obtained by hydrodistillation and analyzed by GC/MS. The major compound identified was β-caryophyllene (24.73%), followed by caryophyllene oxide (5.91%), α-humulene (3.48%), and β-pinene (2.54%). Preliminary screening was performed by topically delivering a 1 µL droplet of the treatments dissolved in acetone. At 24 h after treatment, the EOKC induced mortality rates of 61.9% and 66.7% in the Bayonne and Ft. Dix strains, respectively, at 100 µg/bug. Four major compounds—β-caryophyllene, caryophyllene oxide, α-humulene, and β-pinene—were selected based on their availability and were subjected to topical, residual, and fumigation methods. When applied topically, only β-caryophyllene induced high toxicity in both strains. None of the selected compounds induced significant toxicity in the residual and fumigation methods

Inhibitory effects associated with use of modified Photinus pyralis and Renilla reniformis luciferase vectors in dual reporter assays and implications for analysis of ISGs

Luciferase reporter constructs are widely used for analysis of gene regulation when characterizing promoter and enhancer elements. We report that the recently developed codon-modified Renilla luciferase construct included as an internal standard for cotransfection must be used with great caution with respect to the amount of DNA transfected. Also, the dual-luciferase reporter vectors encoding Photinus pyralis firefly or Renilla reniformis luciferase showed a linear increase in dose-response with increasing amounts of transfected DNA, but at higher levels of transfected DNA, a reduction in expressed levels of luciferase activity resulted. In addition, treatment with type I interferon (IFN) was found to significantly reduce levels of P. pyralis firefly and Renilla luciferase activity. In contrast, cells transfected with a green fluorescent protein (GFP) reporter construct showed no significant IFN-associated change. The reduction in luciferase activity resulting from IFN treatment was not due to IFN-mediated cytotoxicity, as no change in cellular propidium iodide (PI) staining was observed by flow cytometry. IFN treatment did not alter the levels of firefly luciferase activity in cell culture supernatants or the luciferase mRNA levels determined by quantitative real-time RT-PCR analysis. Based on these results, it is probable that the IFN-induced reduction in levels of luciferase activity detected in reporter assays occurs via a posttranscriptional mechanism. Thus, it is important to be aware of these complications when using luciferase reporter systems in general or for analyzing cytokine-mediated responsive regulation of target genes, particularly by the type I IFNs.No Full Tex

Discovery of Thienoquinolone Derivatives as Selective and ATP Non-Competitive CDK5/p25 Inhibitors by Structure-Based Virtual Screening

Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer’s disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2-c]quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP non-competitive CDK5/p25 inhibitors with good CDK2/E selectivity

Array-Based FMR1 Sequencing and Deletion Analysis in Patients with a Fragile X Syndrome–Like Phenotype

Background: Fragile X syndrome (FXS) is caused by loss of function mutations in the FMR1 gene. Trinucleotide CGG-repeat expansions, resulting in FMR1 gene silencing, are the most common mutations observed at this locus. Even though the repeat expansion mutation is a functional null mutation, few conventional mutations have been identified at this locus, largely due to the clinical laboratory focus on the repeat tract. Methodology/Principal Findings: To more thoroughly evaluate the frequency of conventional mutations in FXS-like patients, we used an array-based method to sequence FMR1 in 51 unrelated males exhibiting several features characteristic of FXS but with normal CGG-repeat tracts of FMR1. One patient was identified with a deletion in FMR1, but none of the patients were found to have other conventional mutations. Conclusions/Significance: These data suggest that missense mutations in FMR1 are not a common cause of the FXS phenotype in patients who have normal-length CGG-repeat tracts. However, screening for small deletions of FMR1 may be of clinically utility

[Fe15]: A Frustrated, Centred Tetrakis Hexahedron

The combination of two different FeIII salts in a solvothermal reaction with triethanolamine results in the formation of a high symmetry [FeIII15] cluster whose structure conforms to a centred, tetrakis hexahedron

Empirical Evaluation of Oligonucleotide Probe Selection for DNA Microarrays

DNA-based microarrays are increasingly central to biomedical research. Selecting oligonucleotide sequences that will behave consistently across experiments is essential to the design, production and performance of DNA microarrays. Here our aim was to improve on probe design parameters by empirically and systematically evaluating probe performance in a multivariate context. We used experimental data from 19 array CGH hybridizations to assess the probe performance of 385,474 probes tiled in the Duchenne muscular dystrophy (DMD) region of the X chromosome. Our results demonstrate that probe melting temperature, single nucleotide polymorphisms (SNPs), and homocytosine motifs all have a strong effect on probe behavior. These findings, when incorporated into future microarray probe selection algorithms, may improve microarray performance for a wide variety of applications

Gravitational Radiation from Coalescing Binary Neutron Stars

We calculate the gravitational radiation produced by the merger and coalescence of inspiraling binary neutron stars using 3-dimensional numerical simulations. The stars are modeled as polytropes and start out in the point-mass limit at wide separation. The hydrodynamic integration is performed using smooth particle hydrodynamics (SPH) with Newtonian gravity, and the gravitational radiation is calculated using the quadrupole approximation. We have run several simulations, varying both the neutron star radius and the equation of state. The resulting gravitational wave energy spectra $dE/df$ are rich in information about the hydrodynamics of merger and coalescence. In particular, our results demonstrate that detailed information on both $GM/Rc^2$ and the equation of state can in principle be extracted from the spectrum.Comment: 33 pages, LaTex with RevTex macros; 21 figures available in compressed PostScript format via anonymous ftp to ftp://zonker.drexel.edu/papers/ns_coll_1 ; in press, Phys. Rev. D (Nov 15, 1994 issue

Radiative multipole moments of integer-spin fields in curved spacetime

Radiative multipole moments of scalar, electromagnetic, and linearized gravitational fields in Schwarzschild spacetime are computed to third order in v in a weak-field, slow-motion approximation, where v is a characteristic velocity associated with the motion of the source. To zeroth order in v, a radiative moment of order l is given by the corresponding source moment differentiated l times with respect to retarded time. At second order in v, additional terms appear inside the spatial integrals. These are near-zone corrections which depend on the detailed behavior of the source. At third order in v, the correction terms occur outside the spatial integrals, so that they do not depend on the detailed behavior of the source. These are wave-propagation corrections which are heuristically understood as arising from the scattering of the radiation by the spacetime curvature surrounding the source. Our calculations show that the wave-propagation corrections take a universal form which is independent of multipole order and field type. We also show that in general relativity, temporal and spatial curvatures contribute equally to the wave-propagation corrections.Comment: 34 pages, ReVTe

Gravitational Radiation from the Coalescence of Binary Neutron Stars: Effects Due to the Equation of State, Spin, and Mass Ratio

We calculate the gravitational radiation produced by the coalescence of inspiraling binary neutron stars in the Newtonian regime using 3-dimensional numerical simulations. The stars are modeled as polytropes and start out in the point-mass regime at wide separation. The hydrodynamic integration is performed using smooth particle hydrodynamics (SPH) with Newtonian gravity, and the gravitational radiation is calculated using the quadrupole approximation. We have run a number of simulations varying the neutron star radii, equations of state, spins, and mass ratio. The resulting gravitational waveforms and spectra are rich in information about the hydrodynamics of coalescence, and show characteristic dependence on GM/Rc^2, the equation of state, and the mass ratio.Comment: 39 pages, uses Latex 2.09. To be published in the Dec. 15, 1996 issue of Physical Review D. 16 Figures (bitmapped). Originals available in compressed Postscript format at ftp://zonker.drexel.edu/papers/PAPER2