In vitro anti-HIV activity of phosphorothioate alpha-anomeric oligodeoxynucleotides

Oligonucleotide analogs consisting exclusively of alpha-anomeric deoxynucleoside units bridged with phosphorothioate linkages have been synthesized and tested in vitro as antiviral agents against human immunodeficiency virus (HIV) in human T cells. Two 28-mers, an homopolymer alpha-S-dC28 and an oligomer alpha-S-anti-rev complementary to the initiation site of the regulatory viral gene rev exhibited antiviral activities comparable to those reported for the corresponding beta-anomeric phosphorothioate analogs. In contrast, a nuclease-resistant homopolymer, alpha-dC28 was inactive. Their preliminary results would indicate that the origin of oligonucleotide phosphorothioate anti-HIV activity is not exclusively correlated with their higher nuclease resistance.     

p103 and A60: novel proteins of the neuronal membrane-associated cytoskeleton.

Associated with the neuronal plasma membrane are cytoskeletal proteins which probably control the specialization of the membrane into axonal and dendritic domains. Specialized isoforms of the proteins spectrin and ankyrin are located in each region and provide molecular mechanisms for locating specific transmembrane proteins at required points. However, spectrin and ankyrin were defined by extensions of the model for the erythrocyte membrane, an analogy unlikely to provide a complete account of the neuronal membrane skeleton. We have defined two new proteins of the neuronal membrane skeleton, designated p103 and A60. p103 is enriched in post-synaptic densities and binds with high affinity to integral membrane proteins--we suggest that it may have a role in linking the cytoskeleton to synaptic glycoproteins. A60 is a 60 kDa axonal protein, which appears to form a lining to the axolemma. It is almost exclusively axonal, although some neurons (such as Purkinje cells) appear to contain it in the cell body and initial dendrite segment. A60 binds both ankyrin and neurofilaments, and may have a role in transmitting information critical to axonal morphology to the membrane.     

Antiviral activity of conjugates between poly(L-lysine) and synthetic oligodeoxyribonucleotides

Short (14 to 20-mer range) synthetic oligodeoxyribonucleotides (oligos) allow to modulate specifically viral or cellular gene expression at various stages thus providing a versatile tool for fundamental studies and a rational approach to antiviral chemotherapy. Several problems, such as metabolic stability and efficient cell internalization of oligos, still limit this approach appreciably, as briefly discussed here. We demonstrate here that the conjugation of 15-mer (beta)-anomeric oligos to poly(L-lysine) allows a specific protection of various cell lines against vesicular stomatitis virus infection at concentrations lower than 1 microM. This can be achieved with oligos complementary to the viral N-protein mRNA initiation site or to viral intergenic sequences, i.e., to untranscribed regions. No antiviral activity can be obtained with (alpha)-anomeric oligos directed against the same targets, although such analogues are much more resistant to nuclease degradation and form stable hybrids, at least in cell-free experiments.     

Alpha-DNA. IV: Alpha-anomeric and beta-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physicochemical properties and poly (rA) binding

A new set of molecules made of an intercalating agent (oxazolopyridocarbazole, OPC) covalently linked through a polymethylene chain of various length to the 3' end of alpha-anomeric or beta-anomeric tetradeoxynucleotides (alpha- or beta-T4) have been synthesized. The beta-thymidylate modified compound (beta-T4C5OPC) is able to interact with the complementary sequence, beta-poly (rA); this interaction is strongly stabilized compared to the parent compound, beta-oligo(dT)4 and is specific for poly (rA). The molecule synthesized from the unnatural alpha-anomer, alpha-T4C5OPC, is also able to interact with poly (rA) leading to the formation of an alpha-beta hybrid stabilized by the energy provided by the OPC moiety. The stoechiometry of the binding reaction shows that an A-T pairing occurs in the alpha-beta heterohybrids. Tm studies reveal that the alpha-beta heterohybrids are more stable than their beta-beta counterparts.     

Tropodiaptomus zambeziensis,T. bhangazii and T. capriviensis,three new species of Tropodiaptomus (Copepods,Calanoida) from southern Africa

Three new species of Tropodiaptomus from southern Africa are described, Tropodiaptomus zambeziensis, T. bhangazii, and T. capriviensis. Type localities are a rice paddy on the Zambezi river delta, a coastal lake in Zululand, and temporary pools in Bushmanland and the eastern Caprivi in Namibia. Speciation of Tropodiaptomus in the warm inland waters of southern Africa is much more extensive than was formerly realised.     

Temperature-related distributions of Metadiaptomus and Tropodiaptomus (Copepoda: Calanoida), particularly in southern Africa

Updated locality records of species of Metadiaptomus and Tropodiaptomus on the African continent confirm the generally disjunct distribution of these two taxa as recognised by Dumont (1980) in North Africa. Distributional data for southern Africa reveal little range overlap between these two genera. Apart from two south western Cape taxa, species of Metadiaptomus are largely confined to upland, higher latitude, semi-arid or arid warm subtemperate regions, while species of Tropodiaptomus generally occupy moist, lower-lying, lower latitude subtropical regions. Separation along latitudinal and/or altitudinal axes implicates temperature as a controlling factor, while separation on the precipitation axis suggests the importance of habitat permanence. Using a multiple regression equation derived for African waters to predict water temperature from latitude and altitude, it is shown that the two genera tend to separate around the 20 °C mean annual temperature isotherm. Additional factors influencing distribution (habitat permanence, water quality, competition and predation) are discussed.     

Aerodynamic corrections for the flight of birds and bats in wind tunnels

Few wind tunnel studies of animal flight have controlled or corrected for distortions to behaviour, physiology or flight aerodynamics representing the difference between flight in the tunnel and flight in free air. Aerodynamic correction factors are derived based on lifting-line theory and the method of images for an animal flying freely within closed- and open-section wind tunnels; the method is very similar to that used to model flight in ground effect, and as in ground effect the corrections to induced drag may be substantial. These correction factors are used to estimate bound wing circulation, drag and mechanical power for comparison with free flight, and to derive testable predictions of optimum flight strategies for an animal in a tunnel. In an open-section tunnel, mechanical power is increased compared to free flight, and the animal should fly at the tunnel centre. In a closed tunnel mechanical power is usually reduced, and substantial savings are available, particularly at low speeds, if the animal flies close to the tunnel roof. Anecdotal observations confirm that birds and bats adopt this strategy. The mechanical power-speed curve in a closed tunnel is flatter than the curve for free flight, and this may explain the flat metabolic power-speed curves for birds and bats obtained in some measurements.     

The flight of pipistrelle bats Pipistrellus pipistrellus during pregnancy and lactation

A group of 20 pipistrelle bats were taken into captivity and allowed free flight and association within a flight room where they gave birth to and successfully reared 17 young. The flight of the females was recorded during pregnancy, early lactation and post-lactation by using stroboscopic stereophotogrammetry (153 flights reconstructed in total). During the investigation body mass was altering owing to reproductive condition, and changes in mass were recorded daily for all (adult and juvenile) bats during the entire study period, which lasted from two weeks before the last birth until release, when the oldest baby was 43 days old. All bats were individually marked, and detailed morphological measurements were made. Pregnant and post-lactating bats were heavier than lactating bats, which showed the lowest wingbeat frequencies. The flight speeds of pregnant, lactating and post-lactating bats showed no significant differences, and this may be because the pregnant bats appeared to have a wider scope for selecting flight speed than the other two reproductive groups, or than animals studied previously. The group of bats as a whole decreased flight speed (scaling as M^-043) and increased wingbeat frequency (scaling as M^0.58) as their mass increased. Wingbeat amplitude showed no relation to body mass, wing area or span, flight speed or frequency. A flight performance model applied to the experimental results and optimum flight conditions is used to predict cost of transport and mechanical power for steady flight, and equilibrium wingbeat amplitude which is compared with observations.