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New Catalysts for Olefin Polymerization

Prof. Matthew Conley and colleagues at UCR have developed new single-site catalysts for olefin polymerization that are more efficient, active and selective than current catalysts. These catalysts may be used to create polymers with polar functional groups and to form polymers with tunable molecular weights, microstructures, and polydispersities. These catalysts are incorporated onto an inorganic support so that they may be used in gas-slurry processes which are used for the large scale industrial scale-up of polymers. Fig. 1 shows that methyl 10-undeconoate under 45 psi ethylene is copolymerized using catalysts [2][SZO300]/[2][SZO300]. The resulting copolymer has a low molecular weight and broad dispersity. Fig. 2 shows the reaction of (α-diamine)Ni(Me)2 with partially dehydroxylated sulfated zirconia (SZO300) in diethyl ether results in the formation of the new catalysts [2][SZO300]/[2][MeSZO300].  

Assay for Inhibitors of Nonsense-Mediated RNA Decay

Prof. Sika Zheng at UCR has developed a new endogenous NMD assay that is both sensitive and quantitative. The assay can be used on its own to assess changes in cellular NMD activity with high specificity and sensitivity. It can facilitate analysis of NMD controls by cellular pathways in response to stimuli or during development and is particularly suitable for unbiased screening of NMD modulators. The assay is designed to distinguish NMD regulation from transcriptional regulation and alternative splicing control.

Near-Infrared Fluorescent Probe for Monitoring Mitochondrial Membrane Potential

Prof. Hui-wang Ai and colleagues at UCR have developed a new near-infrared fluorescent MMP probe that provides a number of advantages over current probes. Due to its improved chemistry the new probe, named NIMAP, delivers high sensitivity given its high fluorescence contrast and low background fluorescence. It has optimal emissions (above 600 nm) for mammalian in vivo and in vitro studies and improved accumulation within mitochondria which improves its quantitative analysis possibilities. NIMAP is also extremely photostable and can be utilized to monitor MMP for an extended period. Given these properties, NIMAP may be a powerful tool for studying MMP and mitochondrial function in various biological settings.

Novel Method to Identify Unknown Viruses

Prof. Shou-wei Ding and colleagues at UCR have developed a new method for virus discovery that is independent of either amplification or purification of viral particles. Virus-derived siRNAs and piRNAs are produced by the host immune system as an antiviral response to viral infection. These viral siRNAs and piRNAs are overlapping in sequence and can be assembled back into long continuous fragments of the infecting viral RNA genome. A researcher may sequence the total small RNAs of 18 to 29 nucleotides in length in a disease sample and search a public database of viral sequences using the contiguous sequences assembled from the small RNAs to identify a new or known virus with homology to all or part of a known viral genome in the database.

Novel Assay to Screen for Antiviral Therapeutics

Prof. Shou-wei Ding and colleagues at UCR have developed three different assays to screen for a new class of antiviral therapies. RNA interference (RNAi) directs antiviral innate immunity by producing virus-derived siRNAs (vsiRNAs). These assays screen for compounds that may be used to inhibit the activity of a distinct group of viral proteins known as viral suppressors of RNAi (VSRs) essential for virus infection. The various assays may use Drosophila, rodent or human somatic cells. These same assays may also be used to identify new VSRs.

Potent And Highly Soluble Pegylated Compstatin Peptide

UCR researchers have developed novel compstatin peptides with polar amino acid extensions at the N-terminus and PEGylated extensions at the C-terminus. The new peptides have the following advantages compared to previously known compstatin peptides: (i) highly improved aqueous solubility while maintaining high inhibitory potency, and (ii) higher inhibitory efficacy against complement system activation in a human retinal pigmented epithelial cell-based assay that mimics the pathobiology of age-related macular degeneration. The combined solubility and inhibitory potency and efficacy properties render the new peptides excellent candidates to become therapeutics for the treatment of age-related macular degeneration.   A potent and highly soluble compstatin peptide shown in surface representation with an 8 PEG block C-terminal extension displayed in stick form. The surface of the compstatin analog is colored according to amino acid properties: gray for hydrophobic, green for polar neutral, blue for polar positively charged, red for polar negatively charged, yellow for cysteines of the disulfide bridge, and brown for glycine. The molecular image is generated using three-dimensional coordinates from a molecular dynamics simulation trajectory.    

Peptides for Enhanced Intranasal Vaccination

Brief description not available

Splice Modulating Oligonucleotides as a Breast Cancer Therapy

UCR researchers have designed novel splice modulating oligonucleotides (SMOs) that decrease expression of the long form of the prolactin receptor, thereby significantly inhibiting the metastatic spread of breast cancer to the lungs and liver. The SMO treatment also increased central death in the primary breast tumor. These SMOs may also target metastases produced by non-prolactin receptor-expressing primary tumors since all cancer stem cells examined so far are positive for the prolactin receptor. The researchers administered SMOs to two highly aggressive metastatic models of breast cancer, BT474 human xenografts, used for testing Herceptin, and a 4T1 syngeneic mouse model, which allows testing with an intact immune system.   Fig. A shows a reduction in the number of metastatic colonies upon treatment with the UCR SMOs.       Fig. B titled "Control" is a stain of the metastatic colonies without SMO treatment. Fig. B titled "PRLR SMO" is a stain of the colonies after 40 days treatment with the UCR SMOs.

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