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

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

Pressure-dependent inverse bicontinuous cubic phase formation in a phosphatidylinositol 4-phosphate/phosphatidylcholine system

In this paper, we report the inositide-driven formation of an inverse bicontinuous cubic phase with space group Ia3d (QIIG, gyroid phase). The system under study consisted of distearoylphosphatidylinositol 4-phosphate (DSPIP) and dioleoylphosphatidylcholine at a molar ratio of 1:49, with a physiological concentration of magnesium ions at pH 7·4. The behaviour of the system was monitored as a function of temperature and pressure. The formation of the phase with Ia3d geometry was recorded repeatably at high pressure, and occurred more readily at higher temperatures. We conclude that the Ia3d phase formed is a thermodynamically stable structure, and that DSPIP is a potent source of membrane curvature that can drive the formation of mesophases with both 2- and 3D geometry

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

The evolution of spherical cell shape; progress and perspective

Bacterial cell shape is a key trait governing the extracellular and intracellular factors of bacterial life. Rod-like cell shape appears to be original which implies that the cell wall, division, and rod-like shape came together in ancient bacteria and that the myriad of shapes observed in extant bacteria have evolved from this ancestral shape. In order to understand its evolution, we must first understand how this trait is actively maintained through the construction and maintenance of the peptidoglycan cell wall. The proteins that are primarily responsible for cell shape are therefore the elements of the bacterial cytoskeleton, principally FtsZ, MreB, and the penicillin-binding proteins. MreB is particularly relevant in the transition between rod-like and spherical cell shape as it is often (but not always) lost early in the process. Here we will highlight what is known of this particular transition in cell shape and how it affects fitness before giving a brief perspective on what will be required in order to progress the field of cell shape evolution from a purely mechanistic discipline to one that has the perspective to both propose and to test reasonable hypotheses regarding the ecological drivers of cell shape change

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

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