Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Anthrax infection is caused by the bacterial toxin's so-called "lethal factor" (LF). This metalloprotease enzyme component of the toxin is produced by the spore-forming Bacillus anthracis. It binds to and degrades a key signaling protein inside cells. Besides LF, the toxin contains an antigen, "protective factor" (PF), which enables LF to enter macrophages and other target cells. (See BioWorld Today, July 15, 2002, p.5.)

In a "Brief Correspondence" section of Nature, dated July 25, 2002, scientists at the University of Padua, Italy, report "Screening inhibitors of anthrax lethal factor." They describe creating substrate molecules for LF that permit high-throughput screening of potential inhibitors for use in anthrax treatment. They make the point that the clinical presentation and outcome of anthrax in humans depend on the spore's route of entry into the body. Cutaneous anthrax, they note, is rarely fatal, whereas systemic inhalation of bacterial spores "is more serious." It led to the deaths of five Americans last year.

The Nature paper describes two LF peptide substrates that can assay LF activity "on plate-readers with visible-light or fluorescence detectors (available in most hospital and research laboratories)." They report detecting 1 to 2 nanograms of LF in 200 microliters of buffer. The co-authors also modified their LF substrates slightly to produce molecules that prevent LF from attacking its natural targets. They do so by entering white blood cells and blocking LF's toxicity. These peptides inhibited LF's cytotoxicity in macrophage cell lines, which are commonly used to assay the factor. "Our assay," the authors conclude, "should help to answer the urgent call for new and specific therapies to combat this pathogen after its recent emergence as a terrorist bioweapon."

Newly Reported Mechanism Explains How Gene Interaction Postpones HIV's Advance To AIDS

A combination of two gene variants stalls the progression of HIV-1 infection to full-blown AIDS. One of the genes encodes a receptor on natural killer (NK) cells, which play a part in the immune system's innate - first-line - defense against infection. The other gene expresses a human leukocyte protein located on the surface of white blood cells and other tissues in the body.

The research paper reporting this finding appears in the journal Nature Genetics, published online July 22, 2002. Its title: "Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS." The article's co-authors are at the National Cancer Institute in Frederick, Md.

"Epistatic" refers to a form of gene interaction in which one gene masks or interferes with the phenotypic expression of genes at other loci of the genome. The gene whose phenotype is expressed is said to be epistatic. KIR stands for "killer immunoglobulin-like receptors" on NK cells. Expressed by the KIR gene on the long arm of chromosome 19, their receptors regulate the inhibition and activation of NK-cell responses.

The co-authors examined the genes encoding the NK receptor and human leukocyte antigens in more than 900 HIV-infected patients. They report that neither of the two genes assists delayed progression to AIDS when each is considered on its own. But the co-incidence of particular variants of each gene contributes to an extended period between HIV infection and AIDS development. Further research, they suggest, "may provide new approaches to therapeutic and vaccine development."

New Player Joins Leptin At Table In Body Weight Gain Game; Leptin Finesses SCD-1 Gene In Liver

The hormone leptin, derived from fat cells, is well known for curbing body weight by suppressing appetite. But it has additional anorectic effects on the body's metabolism that are less well known.

The metabolic program that leptin elicits is not explained by its effects on food intake alone. Molecular geneticists at the Rockefeller University in New York report one such candidate obesity player in Science dated July 12, 2002, in a paper titled: "Role for Stearoyl-CoA Desaturase-1 [SCD-1] in leptin-mediated weight loss." Their finding determines that leptin represses expression of this SCD-1 gene in the liver, which encodes an enzyme needed for synthesizing certain fatty acids.

Mutant mice that produced neither leptin nor SCD-1, they report, showed a 40 percent reduction in fat mass and a 75 percent increase in energy expenditure, compared to mice lacking only leptin. Both groups of animals ate the same amount of food. The authors attributed these effects to enhanced oxidation, or "burning," of fatty acids in the liver

These findings "suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions. If researchers can design drugs that have a similar effect, the co-authors suggest, these therapies might be useful for treating obesity.

Why Homo sapiens' Brain Is Four Times Size Of Chimps', And Humans Live A Lot Longer

An American anthropologist and a Canadian economist have teamed up to tackle the evolutionary question: How did humans acquire such big brains and such long life spans? Their answer, in the Proceedings of the National Academy of Sciences (PNAS) released online July 15, 2002, is titled: "The emergence of humans: The coevolution of intelligence and longevity with intergenerational transfers."

Their theory rests on a mathematical model of human evolution in which physical and mental abilities rate as "embodied capital." Neural tissue, such as the brain's neocortex, is a special embodied capital that increases in value over time as new information is acquired and new skills learned. In the African savannah where human evolution began, "learning by doing" was crucial to survival. It selected for both larger brains and lower mortality. The synergy between life span and brain size eventually resulted in humans living twice the length of their closest relatives, chimpanzees and gorillas - and growing a brain almost four times larger.

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