myo-inositol 1,3,5-bicyclic phosphate

In the crystal structure of the title compound (4,6,10-trihydroxy- 2,8,9-trioxa- 1-phosphatricyclo[3.3.1.13,7 ]decan e P-oxide, C6H9OTP), the cyclohexane ring is in a chair conformation. Two hydroxy substituents are in axial orientations and the third is equatorial. There is an intramolecular hydrogen bond involving the two axial hydroxy groups

Liquid-phase synthesis of 2′-methyl-RNA on a homostar support through organic-solvent nanofiltration

Due to the discovery of RNAi, oligonucleotides (oligos) have re-emerged as a major pharmaceutical target that may soon be required in ton quantities. However, it is questionable whether solid-phase oligo synthesis (SPOS) methods can provide a scalable synthesis. Liquid-phase oligo synthesis (LPOS) is intrinsically scalable and amenable to standard industrial batch synthesis techniques. However, most reported LPOS strategies rely upon at least one precipitation per chain extension cycle to separate the growing oligonucleotide from reaction debris. Precipitation can be difficult to develop and control on an industrial scale and, because many precipitations would be required to prepare a therapeutic oligonucleotide, we contend that this approach is not viable for large-scale industrial preparation. We are developing an LPOS synthetic strategy for 2′-methyl RNA phosphorothioate that is more amenable to standard batch production techniques, using organic solvent nanofiltration (OSN) as the critical scalable separation technology. We report the first LPOS-OSN preparation of a 2′-Me RNA phosphorothioate 9-mer, using commercial phosphoramidite monomers, and monitoring all reactions by HPLC, (31)P NMR spectroscopy and MS

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ~5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression

State of Alaska Amount: $1,045,362.00

Dear Mr. Bader: The Exxon Valdez Trustee Council has unanimously detennined to expend $3,936,462.00 in joint trust funds for restoration purposes consistent with the tenns of the Memorandum of Agreement and Consent Decree entered by the federal district court in United States v. State ofAlaska, No. A91·081 eN (D. Alaska) on August 28,1991. Of this amount,$3,794,162.00 will come from the Research Investment Sub-Account. The Research Investment Sub-Account is currently held by the State of Alaska in the Exxon Valdez Oil Spill Investment Fund and invested by the Treasury Division, Alaska Department of Revenue. Under the terms of the Reimbursable Services Agreemen

Studies on insecticide resistance in Anophelene Mosquitoes

The resistance spectra of different populations of a number of anopheline vectors of malaria were studied using some organochlorine, organophosphate, carbamate and pyrethroid insecticides. The species tested were Anopheles culicifacies from Sri Lanka, Pakistan and India, A. stePhensi from India and Iran, A. sacharovi from Greece and Turkey, A. maculipennis and A. superpictus f'rom Greece, A. hyrcanus from Turkey, A. albimanus from Panama and El Salvador. There was a diversity in the response to diff'erent insecticides both within species as well as betteen different species. With the exception of A. superpictus all other species showed either one or more populations with already developed multiple resistance or the potential for such development. Of signifiicance may be the resistances shown by a number of these populations towards some OPs considered as potential alternatives to DDT in malaria control. Most of these variations were considered a result of the nature of the selection pressures exerted on the relevant populations. However, the differences observed in the response to malathion, in A. culicifacies and A. stephensi from that in the species A. sacharovi, A. maculipennis and A. hyrcanus, all f'rom the Mediterranean region were attributed to a possible difference in the predominance of this resistance factor/factors. The malathion resistance in the former was common whereas it was rare in the latter group of species. The high malathion resistance in a multiple resistant population of A. culicifacies from India was shown to be of an almost completely dominant nature. At least two genetic factors, one controlling the specific carboxyesterase mechanism and the other possibly a more generalised mechanism were suggested to be involved in this resistance, the latter in addition conferring cross resistance to fenitrothion. The resistance to this insecticide in the Iranian population of [...] A. stenhensi was of an incompletely dominant nature and a single gene involvement was suggested. The malathion selected (laboratory) Iranian population in which only the carboxyesterase mechanism could be demonstrated, showed no cross resistance to fenitrothion, and other OPs lacking the carboxyester bonds. Continued selection of the same population with fenitrothion, however, showed increasing trends in the tolerances to OP's, chlorphoxim, pirimiphos methyl and phoxim, suggesting a possible relationship between these resistances, In A, albimanus from El Salvador, evidence from use of synergists, only, had suggested possible involvement of carboxyesterases, and mfo 's in the malathion resistance. In A. sacharovi from Turkey, both fenitrothion and iodofenphos resistances were attributed to hydrolytic esterases as well as mixed function oxidases. While the DDT resistance in A. culicifacies. and A. stephensi was attributed to the specific DDT-ase mechanism, that in the populations of A. sacharovi from Turkey was suggested to involve DDT2.ss. mfo's and a third factor, possibly in the nature of a knockdown resistance mechanism. At least one or more of these mechanism were considered to have imparted cross reeistance to the pyrethroid insecticides

An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Stellar winds from Massive Stars

We review the various techniques through which wind properties of massive stars - O stars, AB supergiants, Luminous Blue Variables (LBVs), Wolf-Rayet (WR) stars and cool supergiants - are derived. The wind momentum-luminosity relation (e.g. Kudritzki et al. 1999) provides a method of predicting mass-loss rates of O stars and blue supergiants which is superior to previous parameterizations. Assuming the theoretical sqrt(Z) metallicity dependence, Magellanic Cloud O star mass-loss rates are typically matched to within a factor of two for various calibrations. Stellar winds from LBVs are typically denser and slower than equivalent B supergiants, with exceptional mass-loss rates during giant eruptions Mdot=10^-3 .. 10^-1 Mo/yr (Drissen et al. 2001). Recent mass-loss rates for Galactic WR stars indicate a downward revision of 2-4 relative to previous calibrations due to clumping (e.g. Schmutz 1997), although evidence for a metallicity dependence remains inconclusive (Crowther 2000). Mass-loss properties of luminous (> 10^5 Lo) yellow and red supergiants from alternative techniques remain highly contradictory. Recent Galactic and LMC results for RSG reveal a large scatter such that typical mass-loss rates lie in the range 10^-6 .. 10^-4 Mo/yr, with a few cases exhibiting 10^-3 Mo/yr.Comment: 16 pages, 2 figures, Review paper to appear in Proc `The influence of binaries on stellar population studies', Brussels, Aug 2000 (D. Vanbeveren ed.), Kluwe