Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS

In a study of genetic variation in the AIDS virus, HTLV-III/LAV, sequential virus isolates from persistently infected individuals were examined by Southern blot genomic analysis, molecular cloning, and nucleotide sequencing. Four to six virus isolates were obtained from each of three individuals over a 1-year or 2-year period. Changes were detected throughout the viral genomes and consisted of isolated and clustered nucleotide point mutations as well as short deletions or insertions. Results from genomic restriction mapping and nucleotide sequence comparisons indicated that viruses isolated sequentially had evolved in parallel from a common progenitor virus. The rate of evolution of HTLV-III/LAV was estimated to be at least 10(-3) nucleotide substitutions per site per year for the env gene and 10(-4) for the gag gene, values a millionfold greater than for most DNA genomes. Despite this relatively rapid rate of sequence divergence, virus isolates from any one patient were all much more related to each other than to viruses from other individuals. In view of the substantial heterogeneity among most independent HTLV-III/LAV isolates, the repeated isolation from a given individual of only highly related viruses raises the possibility that some type of interference mechanism may prevent simultaneous infection by more than one major genotypic form of the virus.     

Two-dimensional nanosheets produced by liquid exfoliation of layered materials

If they could be easily exfoliated, layered materials would become a diverse source of two-dimensional crystals whose properties would be useful in applications ranging from electronics to energy storage. We show that layered compounds such as MoS(2), WS(2), MoSe(2), MoTe(2), TaSe(2), NbSe(2), NiTe(2), BN, and Bi(2)Te(3) can be efficiently dispersed in common solvents and can be deposited as individual flakes or formed into films. Electron microscopy strongly suggests that the material is exfoliated into individual layers. By blending this material with suspensions of other nanomaterials or polymer solutions, we can prepare hybrid dispersions or composites, which can be cast into films. We show that WS(2) and MoS(2) effectively reinforce polymers, whereas WS(2)/carbon nanotube hybrid films have high conductivity, leading to promising thermoelectric properties.     

Chloroquine: physiological basis of drug resistance in Plasmodium berghei

Mouse erythrocytes, parasitized by chloroquine-sensitive plasmodia, concentrate this drug in vivo to levels over twice as high as erythrocytes parasitized by chloroquine-resistant plasmodia; nonparasitized red cells accumulate little chloroquine. Selective toxicity of this drug may depend upon a special drug-concentrating mechanism of plasmodic impairment of such mechanism.     

Berberine: complex with DNA

A complex of calf-thymus DNA with berberine sediments in the analytical ultracentrifuge. The DNA produced systematic changes in the absorption spectrum of berberine which suggest that single alkaloid molecules bind to DNA. Flow dichroism of purines and pyrimidines and of berberine in the complex with DNA had the same signs and magnitudes. Berberine shifted the thermal strand separation profile of DNA to higher temperatures. Therefore, the alkaloid forms a complex with DNA, probably by intercalation.     

Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Island biology and ecosystem functioning in epiphytic soil communities

Although island attributes such as size and accessibility to colonizing organisms can influence community structure, the consequences of these for ecosystem functioning are little understood. A study of the suspended soils of spatially discrete epiphytes or treetop "islands" in the canopies of New Zealand rainforest trees revealed that different components of the decomposer community responded either positively or negatively to island size, as well as to the tree species that the islands occurred in. This in turn led to important differences between islands in the rates of ecosystem processes driven by the decomposer biota. This system serves as a model for better understanding how attributes of both real and habitat islands may affect key ecosystem functions through determining the community structure of organisms that drive these functions.