Integration is not necessary for expression of human immunodeficiency virus type 1 protein products.

A common feature in the life cycle of cytocidal retroviruses, including human immunodeficiency virus type 1 (HIV-1), is the accumulation of large amounts of unintegrated viral DNA. As yet, the role of unintegrated viral DNA in the cytopathogenesis of cytocidal retrovirus infections remains unresolved. HIV-1 mutants which were deleted in the integrase/endonuclease gene and which were unable to establish an integrated form of the virus were constructed. Despite an inability to integrate, these mutants were fully competent templates for HIV-1 core and envelope antigen production. HIV-1 antigen could be detected in the supernatants of lymphocyte cultures infected with HIV-1 integrase mutants. However, an inability to rescue infectious virus from these cultures indicated that HIV-1 integration was required for the production of infectious HIV-1. On the basis of the ability of unintegrated HIV-1 DNA to serve as a template for HIV-1 antigen production, it is plausible that unintegrated viral DNA can contribute to the HIV-1 antigen pool during HIV-1 replication.     

Benzyl-functionalized cycloSal-d4T monophosphates

Synthetic routes to benzyl-functionalized cycloSal-d4T monophosphates (7CH2X-cycloSal-d4TMP) have been developed. Their hydrolytic behavior in basic aqueous solution (pH = 7.3) was studied and their hydrolysis half-lives were determined. It turned out that two different degradation pathways are leading to different products: beside the formation of the expected d4TMP and a styrene type derivative, a phenyl-d4T-phosphodiester was obtained as well. The product distribution was specified.     

Structural and functional studies of the nicotinic acetylcholine receptor by solid-state NMR

Over the last seven years, solid-state NMR has been widely employed to study structural and functional aspects of the nicotinic acetylcholine receptor. These studies have provided detailed structural information relating to both the ligand binding site and the transmembrane domain of the receptor. Studies of the ligand binding domain have elucidated the nature and the orientation of the pharmacophores responsible for the binding of the agonist acetylcholine within the agonist binding site. Analyses of small transmembrane fragments derived from the nicotinic acetylcholine receptor have also revealed the secondary structure and the orientation of these transmembrane domains. These experiments have expanded our understanding of the channels structural properties and are providing an insight into how they might be modulated by the surrounding lipid environment. In this article we review the advances in solid-state NMR applied to the nicotinic acetylcholine receptor and compare the results with recent electron diffraction and X-ray crystallographic studies.Presented at the Biophysical Society Meeting on Ion channels – from structure to disease held in May 2003, Rennes, France     

Chemical defense by the native winter ant (Prenolepis imparis) against the invasive Argentine ant (Linepithema humile)

The invasive Argentine ant (Linepithema humile) is established worldwide and displaces native ant species. In northern California, however, the native winter ant (Prenolepis imparis) persists in invaded areas. We found that in aggressive interactions between the two species, P. imparis employs a potent defensive secretion. Field observations were conducted at P. imparis nest sites both in the presence and absence of L. humile. These observations suggested and laboratory assays confirmed that P. imparis workers are more likely to secrete when outnumbered by L. humile. Workers of P. imparis were also more likely to secrete near their nest entrances than when foraging on trees. One-on-one laboratory trials showed that the P. imparis secretion is highly lethal to L. humile, causing 79% mortality. The nonpolar fraction of the secretion was chemically analyzed with gas chromatography/mass spectrometry, and found to be composed of long-chain and cyclic hydrocarbons. Chemical analysis of dissected P. imparis workers showed that the nonpolar fraction is derived from the Dufour's gland. Based on these conclusions, we hypothesize that this chemical defense may help P. imparis to resist displacement by L. humile.     

Isolation of a subfraction of rough endoplasmic reticulum closely associated with mitochondria : Evidence for its role in cytochrome P450 synthesis

A subfraction of rough endoplasmic reticulum (RER) structurally associated with mitochondria (mito-RER complexes) was isolated from crude nuclear fractions of rat liver homogenate. When apocytochrome P450 synthesis (which presumably occurs in RER) and mitochondrial heme synthesis was dissociated by concomitant treatment of rats with phenobarbital and cobaltous chloride, apocytochrome P450 accumulated predominantly in mito-RER complexes. These data suggest that cytochrome P450 synthesis requires structural interaction of mitochondria and RER.     

Lethal mutagenesis in a structured environment

We analyze how lethal mutagenesis operates in a compartmentalized host. We assume that different compartments receive different amounts of mutagen and that virions can migrate among compartments. We address two main questions: (1) To what extent can refugia, i.e., compartments that receive little mutagen, prevent extinction? (2) Does migration among compartments limit the effectiveness of refugia? We find that if there is little migration, extinction has to be achieved separately in all compartments. In this case, the total dose of mutagen administered to the host needs to be so high that the mutagen is effective even in the refugia. By contrast, if migration is extensive, then lethal mutagenesis is effective as long as the average growth in all compartments is reduced to below replacement levels. The effectiveness of migration is governed by the ratio of virion replication and death rates, R₀. The smaller R₀, the less migration is necessary to neutralize refugia and the less mutagen is necessary to achieve extinction at high migration rates.