Suppression of c-ras transformation by GTPase-activating protein

The ras genes are required for normal cell growth and mediate transformation by oncogenes encoding protein tyrosine kinases. Normal ras can transform cells in vitro and in vivo, but mutationally activated ras does so much more efficiently, and highly transforming mutant versions of ras have been isolated from a variety of human and animal tumours. The ras genes encode membrane-associated, guanine nucleotide-binding proteins that are active when GTP is bound and inactive when GDP is bound. The slow intrinsic GTPase activity of normal mammalian Ras proteins can be greatly accelerated by the GTPase-activating protein (GAP), which is predominantly cytoplasmic. This activity of GAP, which can increase with cell density in contact-inhibited cells, suggests that it functions as a negative, upstream regulator of ras. Other studies, however, show that GAP interacts with a region of ras-encoded protein implicated in ras effector function, which raises the possibility that GAP might also be a downstream target of ras. Mutationally activated ras-encoded proteins also interact with GAP, although they are resistant to its catalytic activity. In an attempt to define the role of GAP in ras-mediated transformation, we examined the effects on transformation of normal or mutant ras when cells overexpress GAP. We found that GAP suppresses transformation of NIH 3T3 cells by normal Ha-ras (c-ras) but does not inhibit transformation by activated Ha-ras (v-ras). These results support the hypothesis that GAP functions as a negative regulator of normal ras and make it unlikely that GAP alone is the ras target.     

Structure assignments of two new C-18-oxygenated steroidal ketals isolated from a pacific soft coral of the genusSinularia

Summary Two new C-18-oxygenated sterols possessing a spiroketal function (1 and2) have been isolated from a soft coral of the genusSinularia. The proposed structures are based on spectral data.     

Interpreting animal wall-following behavior

Summary Using computer simulations and behavioral experiments with the American cockroach, we found that active vs passive (barrier-directed) wall-following can be readily distinguished and quantified by incorporating a range of convex curves into test arenas. Although previously considered strongly thigmotactic, more than 50% of running American cockroaches depart convex curves with diameters, less than 1 m. A new framework for evaluating wall-following behaviors is presented.     

A newTrichoplusia ni antennal receptor neuron that responds to attomolar concentrations of a minor pheromone component

Summary A newly discovered third class of sensillum trichodea on the antenna ofTrichoplusia ni contains an olfactory receptor neuron that responds to (Z)-9-tetradecen-1-ol acetate at 1×10^–18 M. The threshold of this neuron is 100–1000 times lower than the thresholds of two previously described pheromone-sensitive neurons that detect (Z)-7-dodecen-1-ol acetate and (Z)-7-tetradecen-1-ol acetate. The sensitivity and selectivity of this receptor neuron is evidence that (Z)-9-tetradecen-1-ol acetate may be important for sexual behavior.     

Cryopreservation of Drosophila melanogaster embryos

There is an urgent need to preserve the ever-increasing number (greater than 30,000) of different genetic strains of D. melanogaster that are maintained in national and international stock centres and in the laboratories of individual investigators. In all cases, the stocks are maintained as adult populations and require transfer to fresh medium every two to four weeks. This is not only costly in terms of materials, labour and space, but unique strains are vulnerable to accidental loss, contamination, and changes in genotype that can occur during continuous culture through mutation, genetic drift or selection. Although cryopreservation of Drosophila germ-plasm would be an enormous advantage, many attempts using conventional procedures have been unsuccessful. D. melanogaster embryos are refractory to conventional cryopreservation procedures because of the contravening conditions required to minimize mortality resulting from both intracellular ice formation and chilling injury at subzero temperatures. To overcome these obstacles, we have developed a vitrification procedure that precludes intracellular ice formation so that the embryos can be cooled and warmed at ultra-rapid rates to minimize chilling injury, and have recovered viable embryos following storage in liquid nitrogen. In a series of 53 experiments, a total of 3,711 larvae emerged from 17,280 eggs that were cooled in liquid nitrogen (18.4 +/- 8.8%). Further, using a subset from this population, approximately 3% of the surviving larvae (24/800) developed into adults. These adults were fertile and produced an F1 generation.     

Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains.

The structure of an N-terminal fragment of CD4 has been determined to 2.4 A resolution. It has two tightly abutting domains connected by a continuous beta strand. Both have the immunoglobulin fold, but domain 2 has a truncated beta barrel and a non-standard disulphide bond. The binding sites for monoclonal antibodies, class II major histocompatibility complex molecules, and human immunodeficiency virus gp120 can be mapped on the molecular surface.     

Covalent binding of aflatoxin B1 to liver DNA in rats pretreated with ethanol

Summary Male Fischer F-344 rats were given ethanol in the drinking water and/or by single oral administration. Following this, the animals received p.o. 100 ng/kg of the hepatocarcinogen [³H]aflatoxin B₁ (AFB₁). 24 h later, the level of DNA-bound AFB₁ was determined in the liver and was found not to be affected by any type of ethanol pretreatment. A cocarcinogenic effect of ethanol in the liver is therefore unlikely to be due to an effect on the metabolic activation and inactivation processes governing the formation of DNA-binding AFB₁ metabolites.To whom correspondence should be addressed.Acknowledgment. We thank the European Science Foundation for the Toxicology Research Fellowship awarded to M.M.     

Organophosphate-mediated inhibition of choline acetyltransferase activity in rat brain tissue

Administration of the organophosphate compound soman in rats resulted in an inhibition of choline acetyltransferase activity in almost all brain regions examined. Enzyme activity was inhibited by 20-50% in various brain regions 30 min after soman injection (94-120 micrograms/kg). Enzyme activity in two regions decreased with time to a near zero level by 3 h after injection.     

Wind and orientation of migrating birds: A review

Summary Migratory flights are strongly affected by wind, and birds have developed many adaptations to cope with wind effects. By day, overland migrants at high altitudes may often allow crosswinds to drift their tracks laterally from the preferred heading. In contrast, many birds at low altitude adjust their headings to compensate for drift, and may overcompensate to allow for previous drift. The relative motion of landscape features is probably used to sense drift, at least by day. By night, some overland migrants compensate fully for drift but others do not; no pattern is obvious. Over the sea, compensation is rarely if ever total; wave patterns may allow partial compensation. Other adaptations can include reduction of drift by flying at times and/or altitudes without strong crosswinds. Some birds recognize the need to change course to allow for previous wind displacement, and reorient at least roughly toward the original route or destination. Some juveniles en route to previously-unvisited wintering grounds seem to have this ability, but corroboration is needed. Such reorientation may not require a true navigation ability. However, some birds have unexplained abilities to sense the wind while aloft.