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Characterization of AJH-836, a diacylglycerol-lactone with selectivity for novel PKC isozymes
Cooke, Mariana,Zhou, Xiaoling,Casado-Medrano, Victoria,Lopez-Haber, Cynthia,Baker, Martin J.,Garg, Rachana,Ann, Jihyae,Lee, Jeewoo,Blumberg, Peter M.,Kazanietz, Marcelo G. American Society for Biochemistry and Molecular Bi 2018 The Journal of biological chemistry Vol.293 No.22
<P>Diacylglycerol (DAG) is a key lipid second messenger downstream of cellular receptors that binds to the C1 domain in many regulatory proteins. Protein kinase C (PKC) isoforms constitute the most prominent family of signaling proteins with DAG-responsive C1 domains, but six other families of proteins, including the chimaerins, Ras-guanyl nucleotide-releasing proteins (RasGRPs), and Munc13 isoforms, also play important roles. Their significant involvement in cancer, immunology, and neurobiology has driven intense interest in the C1 domain as a therapeutic target. As with other classes of targets, however, a key issue is the establishment of selectivity. Here, using [H-3]phorbol 12,13-dibutyrate ([H-3]PDBu) competition binding assays, we found that a synthetic DAG-lactone, AJH-836, preferentially binds to the novel PKC isoforms PKC and PKCE relative to classical PKC and PKCII. Assessment of intracellular translocation, a hallmark for PKC activation, revealed that AJH-836 treatment stimulated a striking preferential redistribution of PKCE to the plasma membrane relative to PKC. Moreover, unlike with the prototypical phorbol ester phorbol 12-myristate 13-acetate (PMA), prolonged exposure of cells to AJH-836 selectively down-regulated PKC and PKCE without affecting PKC expression levels. Biologically, AJH-836 induced major changes in cytoskeletal reorganization in lung cancer cells, as determined by the formation of membrane ruffles, via activation of novel PKCs. We conclude that AJH-836 represents a C1 domain ligand with PKC-activating properties distinct from those of natural DAGs and phorbol esters. Our study supports the feasibility of generating selective C1 domain ligands that promote novel biological response patterns.</P>
Generalized Fibonacci-Feinberg sequences
A.G. Shannon,C. K. Cook 장전수학회 2011 Advanced Studies in Contemporary Mathematics Vol.21 No.2
This paper considers some properties of types of recurrence relations which generalize the well-known Fibonacci, Pell and Feinberg sequences. Some of the properties are analogous to those of some of the special functions.
Andrew G. Cecere,Rachel A. Cook,Tim I. Miyashiro 한국실험동물학회 2023 Laboratory Animal Research Vol.39 No.3
Background: The symbiosis between the Hawaiian bobtail squid Euprymna scolopes and bacterium Vibrio fischeri serves as a model for investigating the molecular mechanisms that promote the initial formation of animal-bacterial symbioses. Research with this system frequently depends on freshly hatched E. scolopes, but the husbandry factors that promote hatchling production in a mariculture facility remain underreported. Here we report on the reproductive performance of E. scolopes in response to decreased mating frequency. Results: One animal cohort was maintained in a mariculture facility for 107 days, with females assigned to either a control group (mating once every 14 days) or an experimental group (mating once every 21 days). No differences between the groups were observed in survival, the number of egg clutches laid, or hatchling counts. Each group featured multiple females that were hyper-reproductive, i.e., they generated more than 8 egg clutches while in captivity. Examination of the distributions for daily hatchling counts of individual egg clutches revealed significant variation in the hatching patterns among clutches that was independent of mating frequency. Finally, an assessment of hatchling production showed that 93.5% of total hatchlings produced by the cohort were derived from egg clutches laid within the first 70 days. Conclusions: These results suggest a lower mating frequency does not impede hatchling production. Furthermore, the variation in hatchling production among egg clutches provides new insight into the reproductive performance of E. scolopes as a lab animal for microbiology research.
Ahn, G-One,Seita, Jun,Hong, Beom-Ju,Kim, Young-Eun,Bok, Seoyeon,Lee, Chan-Ju,Kim, Kwang Soon,Lee, Jerry C.,Leeper, Nicholas J.,Cooke, John P.,Kim, Hak Jae,Kim, Il Han,Weissman, Irving L.,Brown, J. Mar National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.7
<P>Emerging evidence indicates that myeloid cells are essential for promoting new blood vessel formation by secreting various angiogenic factors. Given that hypoxia-inducible factor (HIF) is a critical regulator for angiogenesis, we questioned whether HIF in myeloid cells also plays a role in promoting angiogenesis. To address this question, we generated a unique strain of myeloid-specific knockout mice targeting HIF pathways using human S100A8 as a myeloid-specific promoter. We observed that mutant mice where HIF-1 is transcriptionally activated in myeloid cells (by deletion of the von Hippel–Lindau gene) resulted in erythema, enhanced neovascularization in matrigel plugs, and increased production of vascular endothelial growth factor (VEGF) in the bone marrow, all of which were completely abrogated by either genetic or pharmacological inactivation of HIF-1. We further found that monocytes were the major effector producing VEGF and S100A8 proteins driving neovascularization in matrigel. Moreover, by using a mouse model of hindlimb ischemia we observed significantly improved blood flow in mice intramuscularly injected with HIF-1–activated monocytes. This study therefore demonstrates that HIF-1 activation in myeloid cells promotes angiogenesis through VEGF and S100A8 and that this may become an attractive therapeutic strategy to treat diseases with vascular defects.</P>
Preparation of ferroelectric nanoparticles for their use in liquid crystalline colloids
Atkuri, H,Cook, G,Evans, D R,Cheon, C-I,Glushchenko, A,Reshetnyak, V,Reznikov, Yu,West, J,Zhang, K Institute of Physics Publishing in association wit 2009 Journal of optics A, Pure and applied optics Vol.11 No.2
<P>In this paper we summarize our many years of experience in the preparation and optimization of stable colloids of ferroelectric nanoparticles dispersed in an isotropic carrier and in a liquid crystal host. The colloids are of interest for use in electro-optic devices, photorefractive hybrids and nonlinear optical elements. We also outline some of the most interesting features the nanoparticles bring to liquid crystals, along with the potential of these relatively new colloids.</P>
Fritsche, Lars G.,Igl, Wilmar,Cooke Bailey, Jessica N.,Grassmann, Felix,Sengupta, Sebanti,Bragg-Gresham, Jennifer L.,Burdon, Kathryn P.,Hebbring, Scott J.,Wen, Cindy,Gorski, Mathias,Kim, Ivana K.,Cho, Nature Pub. Co 2016 Nature genetics Vol.48 No.2
<P>Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10<SUP>–8</SUP>) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near <I>MMP9</I> (difference-P = 4.1×10<SUP>–10</SUP>). Very rare coding variants (frequency < 0.1%) in <I>CFH</I>, <I>CFI</I>, and <I>TIMP3</I> suggest causal roles for these genes, as does a splice variant in <I>SLC16A8</I>. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.</P>