The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies

<p>Abstract</p> <p>Background</p> <p>Germline specific promoters are an essential component of potential vector control strategies which function by genetic drive, however suitable promoters are not currently available for the main human malaria vector <it>Anopheles gambiae</it>.</p> <p>Results</p> <p>We have identified the <it>Anopheles gambiae vasa</it>-like gene and found its expression to be specifically localized to both the male and female gonads in adult mosquitoes. We have functionally characterised using transgenic reporter lines the regulatory regions required for driving transgene expression in a pattern mirroring that of the endogenous <it>vasa </it>locus. Two reporter constructs indicate the existence of distinct <it>vasa </it>regulatory elements within the 5' untranslated regions responsible not only for the spatial and temporal but also for the sex specific germline expression. <it>vasa </it>driven eGFP expression in the ovary of heterozygous mosquitoes resulted in the progressive accumulation of maternal protein and transcript in developing oocytes that were then detectable in all embryos and neonatal larvae.</p> <p>Conclusion</p> <p>We have characterized the <it>vasa </it>regulatory regions that are not only suited to drive transgenes in the early germline of both sexes but could also be utilized to manipulate the zygotic genome of developing embryos via maternal deposition of active molecules. We have used computational models to show that a homing endonuclease-based gene drive system can function in the presence of maternal deposition and describe a novel non-invasive control strategy based on early <it>vasa </it>driven homing endonuclease expression.</p

Glargine and degludec: solution behaviour of higher dose synthetic insulins

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers (“multi-hexamerisation”). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24–40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes

The East India Company’sFarmān, 1622‒1747

The East India Company’s presence and ongoing trade in Persia was reliant on the privileges outlined in the Farmān, granted after the capture of Hormuz in 1622. The relationship between these two powers was cemented in the rights enshrined in the Farmān, which was used by both to regulate their varying needs and expectations over the course of 125 years. This article explores the Company’s records of the Farmān and how changes to its terms were viewed from both sides. As a Persian document, the Farmān gives a clear view of the attitudes of native officials and rulers to the Company and how these terms were used as a means of control

Exciton Theory for Supramolecular Chlorosomal Aggregates: 1. Aggregate Size Dependence of the Linear Spectra

The interior of chlorosomes of green bacteria forms an unusual antenna system organized without proteins. The steady-spectra (absorption, circular dichroism, and linear dichroism) have been modeled using the Frenkel Hamiltonian for the large tubular aggregates of bacteriochlorophylls with geometries corresponding to those proposed for Chloroflexus aurantiacus and Chlorobium tepidum chlorosomes. For the Cf. aurantiacus aggregates we apply a structure used previously (V. I. Prokhorenko., D. B. Steensgaard, and A. R. Holzwarth, Biophys. J. 2000, 79:2105–2120), whereas for the Cb. tepidum aggregates a new extended model of double-tube aggregates, based on recently published solid-state nuclear magnetic resonance studies (B.-J. van Rossum, B. Y. van Duhl, D. B. Steensgaard, T. S. Balaban, A. R. Holzwarth, K. Schaffner, and H. J. M. de Groot, Biochemistry 2001, 40:1587–1595), is developed. We find that the circular dichroism spectra depend strongly on the aggregate length for both types of chlorosomes. Their shape changes from “type-II” (negative at short wavelengths to positive at long wavelengths) to the “mixed-type” (negative-positive-negative) in the nomenclature proposed in K. Griebenow, A. R. Holzwarth, F. van Mourik, and R. van Grondelle, Biochim. Biophys. Acta 1991, 1058:194–202, for an aggregate length of 30–40 bacteriochlorophyll molecules per stack. This “size effect” on the circular dichroism spectra is caused by appearance of macroscopic chirality due to circular distribution of the transition dipole moment of the monomers. We visualize these distributions, and also the corresponding Frenkel excitons, using a novel presentation technique. The observed size effects provide a key to explain many previously puzzling and seemingly contradictory experimental data in the literature on the circular and linear dichroism spectra of seemingly identical types of chlorosomes

Exciton dynamics in the chlorosomal antennae of the green bacteria Chloroflexus aurantiacus and Chlorobium tepidum.

The energy transfer processes in isolated chlorosomes from green bacteria Chlorobium tepidum and Chloroflexus aurantiacus have been studied at low temperatures (1.27 K) by two-pulse photon echo and one-color transient absorption techniques with approximately 100 fs resolution. The decay of the coherence in both types of chlorosomes is characterized by four different dephasing times stretching from approximately 100 fs up to 300 ps. The fastest component reflects dephasing that is due to interaction of bacteriochlorophylls with the phonon bath, whereas the other components correspond to dephasing due to different energy transfer processes such as distribution of excitation along the rod-like aggregates, energy exchange between different rods in the chlorosome, and energy transfer to the base plate. As a basis for the interpretation of the excitation dephasing and energy transfer pathways, a superlattice-like structural model is proposed based on recent experimental data and computer modeling of the Bchl c aggregates (1994. Photosynth. Res. 41:225-233.) This model predicts a fine structure of the Q(y) absorption band that is fully supported by the present photon echo data