Abstract:. The dissemination of AAC(6)-I-type acetyltransferases have rendered amikacin and other aminoglycosides all but useless in some parts of the world. Antisense technologies could be an alternative to extend the life of these antibiotics. External guide sequences are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. Thirteen-nucleotide external guide sequences complementary to locations within five regions accessible for interaction with antisense oligonucleotides in the mRNA that encodes AAC(6)-Ib were analyzed. While small variations in the location targeted by different external guide sequences resulted in big changes in efficiency of binding to native aac(6)-Ib mRNA, most of them induced high levels of RNase P-mediated cleavage in vitro. Recombinant plasmids coding for selected external guide sequences were introduced into Escherichia coli harboring aac(6)-Ib, and the transformant strains were ...

Valero CEO Bill Klesse fires a shot across the bow of proposed cap-and-trade legislation winding its way through U.S. Congress, as the chief of the largest...

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The C. elegans JNK pathway is composed of MLK-1 MAPKKK, MEK-1 MAPKK, and KGB-1-JNK and regulates both the stress response to heavy metals and axon regeneration (Mizuno et al., 2004; Nix et al., 2011). MLK-1 is activated by phosphorylation of Ser-355 in the activation loop of its kinase domain. In the stress response to heavy metals, phosphorylation of MLK-1 on Ser-355 is catalyzed by the Ste20-related kinase MAX-2 (Fujiki et al., 2010), whereas in the axon regeneration pathway, MLK-1 Ser-355 phosphorylation is catalyzed by the PKC homolog TPA-1 (Pastuhov et al., 2012). Therefore, two different kinases, MAX-2 and TPA-1, can activate MLK-1 by phosphorylating the same Ser-355 site. Do these kinases function redundantly or independently? We have demonstrated previously that max-2-null mutants, unlike animals harboring mutations in kgb-1, mek-1, or mlk-1, remained partially resistant to heavy metal stress (Fujiki et al., 2010). Furthermore, the max-2 mutation caused a smaller decrease in KGB-1 ...

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Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) also known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin is an enzyme that in humans is encoded by the NAMPT gene. This protein is the rate-limiting enzyme in the Nicotinamide adenine dinucleotide (NAD+) salvage pathway that converts nicotinamide to nicotinamide mononucleotide in mammals to enable NAD+ biosynthesis. NAMPT has also been reported to be a cytokine (PBEF) that promotes B cell maturation and inhibits neutrophil apoptosis. NAMPT is downregulated by an increase of miR-34a in obesity via a 3UTR functional binding site of NAMPT mRNA resulting in a reduction of NAD(+) and decreased SIRT1 activity. NAMPT catalyzes the following chemical reaction: nicotinamide + 5-phosphoribosyl-1-pyrophosphate (PRPP) ⇌ {\displaystyle \rightleftharpoons } nicotinamide mononucleotide (NMN) + pyrophosphate (PPi) Thus, the two substrates of this enzyme are nicotinamide and 5-phosphoribosyl-1-pyrophosphate (PRRP), whereas its two ...

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d {\displaystyle L>d} , U 1 , … , U d {\displaystyle U_{1},\ldots ,U_{d}} be the eigenvectors (left singular vectors of the L {\displaystyle L} -trajectory matrix), which are provided by the SVD step of SSA. Then this series is governed by an LRR x n = ∑ k = 1 L − 1 a k x n − k {\displaystyle x_{n}=\sum _{k=1}^{L-1}a_{k}x_{n-k}} , where ( a L − 1 , … , a 1 ) T {\displaystyle (a_{L-1},\ldots ,a_{1})^{\mathrm {T} }} are expressed through U 1 , … , U d {\displaystyle U_{1},\ldots ,U_{d}} (Golyandina et al., 2001, Ch.5), and can be continued by the same LRR. This provides the basis for SSA recurrent and vector forecasting algorithms (Golyandina et al., 2001, Ch.2). In practice, the signal is corrupted by a perturbation, e.g., by noise, and its subspace is estimated by SSA approximately. Thus, SSA forecasting can be applied for forecasting of a time series component that is approximately governed by an LRR and is approximately separated from the residual. Multi-channel, Multivariate SSA ...

Antisense molecules do not readily cross cell membranes. This has limited the use of antisense to systems where techniques have been worked out to introduce the molecules into cells, such as embryos and cell cultures. Uncharged antisense bearing a group of guanidinium moieties on either a linear pep …

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As a target for gene therapy, Duchenne muscular dystrophy (DMD) presents many obstacles but also an unparalleled prospect for correction by alternative splicing. The majority of mutations in the dystrophin gene occur in the region encoding the spectrin-like central rod domain, which is largely dispensable. Thus, splicing around mutations can generate a shortened but in-frame transcript, permitting translation of a partially functional dystrophin protein. We have tested this idea in vivo in the mdx dystrophic mouse (carrying a mutation in exon 23 of the dystrophin gene) by combining a potent transfection protocol with a 2-O-methylated phosphorothioated antisense oligoribonucleotide (2OMeAO) designed to promote skipping of the mutated exon*. The treated mice show persistent production of dystrophin at normal levels in large numbers of muscle fibers and show functional improvement of the treated muscle. Repeated administration enhances dystrophin expression without eliciting immune responses. Our ...

Nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B-cell colony-enhancing factor, is the rate-limiting enzyme that converts nicotinamide to nicotinamide mononucleotide (NMN) from nicotinamide in the salvage pathway of NAD+ biosynthesis in mammals. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) converts NMN to NAD+. The expression of NAMPT is upregulated during activation of immune cells such as monocytes, macrophages, dendritic cells, T and B cells, as well as in amniotic epithelial cells upon stimulation with several inflammatory cytokines. NAMPT-specific inhibitor, FK866 was found to deplete intracellular NAD content, resulting in apoptotic cell death in many cancer cell lines without any DNA damaging effect. Recently, Nakahata K et al, demonstrated that NAMPT is required to modulate circadian gene expression and circadian oscillation of NAD+.. ...

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KONE Inc. today announced that it has been awarded a three-year contract to supply elevator and escalator service and maintenance through the U.S. Communities Government Purchasing Alliance. The City and County of Denver, Colorado served as the lead public agency and awarded KONE the contract after carefully evaluating proposals from several other distributors. This is the second contract award for KONE as the elevator service and maintenance provider through U.S. Communities. We value our long-standing relationship with the City and County of Denver, and with U.S. Communities, said Larry Wash, KONE EVP and Area Director for KONE Americas. Existing U.S. Communities customers will enjoy expanded services, as we add the additional benefit of escalator maintenance to the contract. Together with our commitment to environmental excellence, we can help U.S. Communities and its participating agencies to lower their carbon footprint while at the same time improving their overall people flow ...

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Hasbro, Inc. (HAS), together with its subsidiaries, provides childrens and family leisure time products and services worldwide. It operates through U.S. and Canada, International, Entertainment and Licensing, and Global Operations segments. The company raised its quarterly dividend by 11.80% to 57 cents/share. This marked the 14th consecutive annual dividend increase for this dividend contender. Over the past decade, the company has managed to boost annual dividends at a rate of 18.60%/year. This was supported by an increase in earnings per share from $1.97 in 2007 to $4.43/share in 2016. The company is expected to earn $4.66/share in 2017 and $4.97/share in 2018. The stock is overvalued at 21 times forward earnings and yields 2.40%. In general, I have been hesitant to buy into companies from that industry, because I view them as cyclical, overly dependent on the success of hit toys and shifts in consumer tastes, and the difficulty in identifying the one player with recurring income streams. ...

Oct 24, 2013 Noting several Save the Children initiatives to raise awareness and funds to combat child mortality, including the World Marathon Challenge, a relay race where kids team up and attempt to run a full marathon distance and to beat the world marathon record, Save the Children President and CEO Carolyn Miles writes in the Huffington Posts Global Motherhood blog, Through U.S. government leadership and global commitment, the number of deaths to children under five declined to 6.6 million in 2012, from 12.6 million in 1990. She continues, While this is good news, we need to do better. … [W]e need to do more in three areas where we have not yet made sufficient headway: reaching the poorest children with life-saving measures, ensuring all newborns get proper care; and providing children with good nutrition so they stay healthy and strong enough to fight off life-threatening illnesses. Miles adds, With adequate public support and appropriate levels of government investment in ...

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Complete information for ADCY6 gene (Protein Coding), Adenylate Cyclase 6, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

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