By David N. Leff
Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.
So naturalists observe, a flea
Hath smaller fleas that on him prey;
And these have smaller still to bite ¿em;
And so proceed ad infinitum.
In turn, molecular biologists observe that all groups of bacteria have viruses on their backs to bite ¿em. These microbial parasites, better known as bacteriophages, are highly sophisticated machines for pushing a hollow needle through the bacterium¿s cell wall and injecting its viral DNA or RNA. This then proliferates inside its condemned host, to generate scads of second-generation ¿phages, which go off to infect thousands more bacteria, after filling its bacterial host till it bursts.
A typical ¿phage packages its tightly coiled viral genome inside a hard-shell hexagonal protein capsid called the prohead. Once the virus touches down on its bacterial target, it unspools its DNA strand down a hollow tail sheath and needle-nose core, which penetrates the bacterium¿s cell wall. During this maneuver, viral tail fibers splay out on the bacterial surface to hold the ¿phage stable and vertical.
This refueling operation requires a lot of energy on a submicroscopic scale. Just how much pressure is reported in Nature dated Oct. 18, 2001, under the title: ¿The bacteriophage f29 portal motor can package DNA against a large internal force.¿ Its authors are microbiologists at the University of Minnesota in Minneapolis and biophysicists at the University of California at Berkeley.
Their experiment centered on the soil bacterium Bacillus subtilis and its parasitical f29 bacteriophage, which packs a 19.3-kilobase genome.
The co-authors commented that the DNA inside some viruses is packed so tightly that the internal pressure reaches 10 times the six atmospheres in a champagne bottle, with its wire-reinforced cork. They report that such tight packing is achieved by one of the most powerful molecular motors ever observed. It¿s stronger than the motors that power mammalian muscles, or the nanoscale prime movers that transcribe DNA into RNA.
¿Pound for pound,¿ observed the paper¿s senior author, biophysicist Carlos Bustamante, ¿this is stronger than any known molecular motor, and can pack DNA to a pressure of about 60 atmospheres ¿ equal to nearly 100 pounds per square inch. Many human viruses, such as the herpes viruses that cause herpes simplex, chicken pox and shingles, are thought to pack their DNA in the same way. Understanding how this process works could help us design better drugs to interfere with, and perhaps halt, the packing part of the viral infection cycle.¿ Adenoviruses, too, popular as gene therapy vectors, are suspected of packing their genes under such pressures.
As it starts to self-assemble, the first viral component made is the empty prohead with a protein complex, the portal motor, at its mouth. This grabs the double-stranded DNA and pushes it into the capsid, where it compacts to nearly 6,000 times its normal volume. Geared up to human dimensions, Bustamante pointed out, ¿this would be enough to lift six aircraft carriers.¿
Statistical Analysis Predicts Creutzfeldt-Jakob Disease Cases Leveling Off In Thousands
Variant Creutzfeldt-Jakob disease (vCJD) is the human counterpart of mad cow disease ¿ bovine spongiform encephalitis (BSE). Both are caused by a pathogenic version of prions ¿ proteinaceous infectious particles. Since the first cases of vCJD surfaced in England five years ago, 100 victims have died of the disease. The suspicion is that they ate or came into contact with BSE cattle. Person-to-person contagion has not been reported.
There is no test to determine if symptomless individuals are infected, there is an uncertain incubation period, and there is no treatment ¿ all of which make predicting the extent of the epidemic difficult.
A fast-track, electronically released report in Science dated Oct. 26, 2001, carries the title: ¿Predictability of the UK variant Creutzfeldt-Jakob disease epidemic.¿ Its authors are at the London School of Hygiene and Tropical Medicine. They have employed back-calculation statistical analysis ¿ developed for the HIV/AIDS epidemic ¿ to suggest that the number of infected individuals could range from thousands up to several millions. But their model predicts an average incubation period for the disease, if millions are indeed affected, that is well beyond the human life span, so it appears likely there will be at most only a few thousand clinical cases in the future.
Molecular Aphrodisiac Turns On Female Rats To Come On To Male Sexual Charms
¿Not tonight, dear. I have a headache.¿
This often-cited excuse for putting off sex now has a medical name: desire disorder. A synonymous term is female sexual dysfunction. It¿s apparently to women what erectile dysfunction is in men, and at least one biotech company has a female counterpart to Viagra in the works.
Palatin Technologies Inc., of Edison, N.J., was to present preclinical efficacy studies of its product, PT-141, at a female sexual function forum in Boston on Saturday. The abstract is titled: ¿A-MSH analogue facilitates appetitive sexual behavior in female rats.¿
The report, co-authored by behavioral neurobiologists at Concordia University in Montreal, was to be presented by Annette Shadiack, Palatin¿s director of biological research.
A-MSH stands for ¿a-melanocyte stimulating hormone,¿ which has ¿pronounced effects on the sexual behavior of females and males of a variety of species,¿ the abstract notes. It cites experimental evidence that, ¿In female rats, systemic administration of a-MSH appears to facilitate lordosis if the baselines are low, but to inhibit this reflex if the baselines are high.¿ (Lordosis means arching of the rodent¿s spine to signify desire and facilitate copulation.)
Receptors for this class of molecules (melanocortin receptors) play a role in several behaviors, including appetite and sexual arousal, according to the abstract.
¿These data,¿ the abstract concludes, ¿reveal a selective effect of this a-MSH analogue on a measure of precopulatory sexual motivation and solicitation. Implications for the analysis and treatment of sexual desire disorders in women will be discussed.¿