Frontlines

Frontlines Image: Erica P. Johnson Artificial cell signaling Cells rely on chemical signals triggered by external change to keep them informed. Christopher Hunter, Nick Williams, and colleagues at Sheffield University, England, tested the cells' abilities against a chemical system that transmits information signals into an artificial cell without a single molecule passing through the membrane (P. Barton et al., "Transmembrane signaling," Angewandte Chemie International Edition, 41:3878-81,

Nov 25, 2002
David Bradley

Frontlines

Image: Erica P. Johnson

Artificial cell signaling Cells rely on chemical signals triggered by external change to keep them informed. Christopher Hunter, Nick Williams, and colleagues at Sheffield University, England, tested the cells' abilities against a chemical system that transmits information signals into an artificial cell without a single molecule passing through the membrane (P. Barton et al., "Transmembrane signaling," Angewandte Chemie International Edition, 41:3878-81, Oct. 18, 2002). "The system," says Hunter, "may have applications in controlled drug-delivery systems or chemical sensors." The team created an artificial cell, a vesicle, using lipids found in egg yolk. In it, they built in a signal-carrying system using the natural cell components, cholenic acid and cysteine. "This is imaginative research," says supramolecular chemist Stefan Matile, University of Geneva. "Understanding how complex biological processes really work requires successful reconstruction of all the elements expected as crucial for function." When the researchers stimulate the outside of their artificial cell with a trigger molecule, it leads to a change inside the vesicle, says Hunter; the signal molecule does not have to travel into the cell. "At present, the external trigger is an oxidizing agent," he explains, "but in principle, the trigger could be binding any molecule, DNA, protein, whatever, and that is where potential applications lie in sensors." Matile agrees that this type of biomimicry could lead to such practical applications, although Hunter adds that work is underway to amplify the response so it can be measured using spectroscopy.

--David Bradley



Image: Anne MacNamara

Regionalizing schizophrenia Researchers at the recent 52nd annual meeting of the American Society of Human Genetics provided a closer look at genome regions associated with schizophrenia. Rockefeller University's Maria Karayiorgou, an associate professor in the laboratory of human neurogenetics, said that a 2-megabase stretch of chromosome 22 "is prone to deletion because of low copy repeats" that flank the region. The numbers are telling: 25-30% of people with the deletion have schizophrenia, compared with 1% in the general population. Brien Riley, director of the molecular laboratory at the Virginia Institute for Psychiatric and Behavioral Genetics, introduced a chromosome 6 region that houses the gene for dystrobrevin binding protein 1. "It is in the right place, is expressed in brain, and could be part of a signal transduction pathway," he said. And Kari Stefansson, CEO of deCODE Genetics of Reykjavik, Iceland, reported on neuregulin-2 (H. Stefansson et al., "Neuregulin 1 and susceptibility to schizophrenia," American Journal of Human Genetics, 71:877-92, October 2002). "This protein influences synaptic plasticity, which is one way that the brain responds to experience," he said. But schizophrenia, said Riley, is more than a single-gene story. "On a population level, dozens of genes influence schizophrenia. Within an individual, a subset of those genes drives genetic predisposition. The subsets of genes interact, perhaps at points where pathways cross." Stefansson added cryptically that it will soon make sense. "Divergent results will converge to show us one pathway to schizophrenia in the very near future."

--Ricki Lewis



Image: Courtesy of Deborah Yurgelun-Todd

Secretin and the amygdala Secretin, the digestive neuropeptide, boosts activity of the amygdala, according to findings presented at the recent International Meeting for Autism Research. In a double-blind, placebo-controlled study at Harvard Medical School and McLean Hospital, Deborah Yurgelun-Todd measured blood flow to the amygdala using functional magnetic resonance imaging. Healthy men given secretin injections showed increased flow compared with control subjects, when the men looked at pictures of people with fearful faces. "It suggests there may be a way of getting at what secretin is doing in the central nervous system. That, in turn, might be related to changes in behavior or socialization," she says. The study could add to the controversy surrounding secretin's possible role in treating autism, as well as the amygdala's role in this disorder. The amygdala could be involved because of its role in recognizing fearful and anxiety-provoking situations. Monkeys who have had amygdala lesions, however, do not show autistic behavior, according to studies by David Amaral (H. Black, "Amygdala's inner workings," The Scientist, 15[19]:20, Oct.1, 2001). Furthermore, two studies report that secretin had no effect on autistic behavior (A. Sandler et al., "Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder," New England Journal of Medicine, 341:1801-6, 1999; T. Owley et al., "A double-blind, placebo-controlled trial of secretin for the treatment of autistic disorder," General Medicine, 1:10, 1999). Yurgelun-Todd speaks cautiously about the study's implications for autism. "Our findings are simply saying there is a brain difference. This doesn't speak to anything about how well secretin alters any autism symptoms." Repligen, a Waltham, Mass., firm that is developing secretin for a Food and Drug Administration Phase III trial to treat autism, funded the research.

--Harvey Black



Image: Anne MacNamara

Antibiotic resistance Searching for the ultimate cause for antibiotic resistance is pointless, says the American Academy of Microbiology (AAM). Its recent report chronicles the findings of a three-day colloquium, held last year, on the risk of antimicrobials in agriculture. Emphasizing the issue's complexity, the 24-page report calls for efforts to develop new agricultural methods that reduce dependence on antibiotics, such as the use of so-called exclusion bacteria, which produce antimicrobials but are harmless to animals and people. Yet, scientists still puzzle over the development of resistance sans antibiotics. The University of Georgia's John Maurer, associate professor in the Center for Food Safety, says he studied a poultry farm for a year and saw antibiotic resistance develop, even though antibiotics were not used. "You have to ask yourself, is there another place where the selection pressure comes through," says Maurer, who spoke at the colloquium. He also notes that resistance can continue long after a drug is no longer used. "We haven't used streptomycin in poultry medicine for a long time ... and you can go out to any poultry farm and find E. coli and salmonellas that are streptomycin-resistant," he says. Kirk Smith, public health veterinarian at the Minnesota Department of Health, says that causes of resistance can be pinpointed, citing evidence that fluoroquinolones in poultry led to resistant Campylobacter in humans (K. Smith et al., "Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998," New England Journal of Medicine, 340:1525-32, 1999). His research was not referenced in the AAM report.

--Harvey Black



Image: Anne MacNamara

Toward 2n=44 Will the human chromosome number one day be 44? It's possible, said research professor Lisa Shaffer, Washington State University, Spokane, at the 52nd annual meeting of the American Society for Human Genetics. Her team examined 80 Robertsonian translocations, in which two different chromosomes fuse, joined by sticky repeat se-quences. People with one giant, fused chromosome, and therefore 45 in total, have sperm or eggs with missing or extra genetic material and cannot reproduce. However, people with two copies of the fused chromosome have 44, and have better luck in the fertility stakes because their gametes have a complete set of genes. Because translocations are common and are often preferentially inherited over normal chromosomes, such a scenario could happen. "I predict that humans are moving towards fewer chromosomes, and the changes will be Robertsonian," Shaffer said. "With 1 in 1,000 individuals carrying a Robertsonian translocation, the likelihood of two carriers getting together and both transmitting their translocation is 1 in 4 million--so they are out there, just phenotypically normal." Fracturing of humanity could happen faster if two different chromosome fusions occur and persist, says genetics professor Fernando de Villena, University of North Carolina, Chapel Hill. "Fixation of a single Robertsonian translocation would not have dramatic consequences. Yet, fixation of two different ones in two different populations would have huge effects." On reproduction, that is. Gametes with different chromosomal organization couldn't get beyond the fertilized egg stage. And that could mean subgroups of reproductively isolated people--the raw material for speciation.

--Ricki Lewis



Photo: Courtesy of ARS Image Gallery

Malaria in the United States Scientists at the Centers for Disease Control and Prevention have an epidemiological mystery on their hands. In August, two northern Virginia teenagers contracted malaria, the first insect-transmitted cases since 1999. They subsequently recovered, but CDC investigators uncovered an unexpectedly high rate of infection among area mosquitoes. Although there are 1,000-1,500 cases of malaria reported annually in the United States, most are typically travelers infected overseas. When health officials tested mosquitoes in Maryland and northern Virginia, they found that 5 in 800 mosquitoes tested carried the disease, an infection rate of 0.6%. Rates of infection in sub-Saharan Africa and Latin America range from a few percent to as much as 10%. "It really is confounding," says Robert A. Wirtz, CDC's entomology branch chief. The suspected reasons: Mosquitoes tested indicate a level of infestation far greater than expected; or the tests used, previously deemed foolproof, are faulty. Officials used the VecTest®, first developed by the military as a quick method for assessing malaria threat to troops in the field. The test looks for the parasite's circumsporozoite protein, which surrounds the infectious cells during one stage of its life. Next, researchers must extract DNA from the wick of the VecTest to look for a parasite signature. So far, CDC, Department of Defense, and Virginia Department of Health researchers haven't been able to confirm or negate the findings. The next step may be to change the assay by using monoclonal antibodies that recognize different amino acid sequences in the parasite. Says Wirtz, "It's going to take us some time to sort this out."

--Eugene Russo