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Frontlines Image: Erica Johnson Damage control Researchers have found that inosine, a naturally occurring nucleoside whose levels are elevated in the brain following trauma, can induce axonal reorganization following a stroke and improve the performance of several sensorimotor tasks (P. Chen et al., "Inosine induces axonal rewiring and improves behavioral outcome after stroke," Proceedings of the National Academy of Sciences, 99:9031-6, June 25, 2002). A stroke can cause massive damage to the brain, which has limited capabilities of rewiring itself to attain its previous level of function. Inosine was previously shown to induce regeneration in existing neurons by switching on numerous genes required for axon growth, says Larry Benowitz, associate professor of neuroscience at Harvard Medical School. Using a murine model, researchers induced a stroke in one of the cerebral hemispheres, which damaged the sensorimotor cortex, an area required for fine motor control of the limbs. Researchers applied a continuous infusion of inosine into the brain's undamaged side; the inosine then reached the cerebrospinal fluid. "The idea ... was to get the intact healthy cells to begin growing new connections to take the place of the ones lost from stroke," says Benowitz. Mice treated with inosine regained various abilities, such as using their paws to retrieve food. --Hal Cohen Photo: Courtesy of Scott Bauer, ARS Image Library Cloning smart cells Debate over therapeutic cloning has been so intense that there hasn't been much focus on the next step, which is getting those cells to function. Nuclear transplantation experiments in cows reveal that the degree to which such cells can self-assemble may be even greater than researchers had imagined (R. Lanza et al., "Generation of histocompatible tissues using nuclear transplantation," Nature Biotechnology, 20:689-96, July 2002). Researchers from Advanced Cell Technology (ACT) in Worcester, Mass., Harvard Medical School, the Mayo Clinic, and the University of Miami School of Medicine cultured fibroblasts from steers' ears and fused them with enucleated cow oocytes, transferring them as blastocysts to female cows. The investigators retrieved cardiac and skeletal muscle cells and renal cells from the cloned and control fetuses, combined them with synthetic polymers, and implanted the constructs into the flanks and under the skin of the nuclei donors. "We dissociated the cells onto a scaffold, and once in an animal, remarkable things happened," says Robert Lanza, ACT's vice president of medical and scientific development. "The renal cells formed glomeruli and tubules, and they removed toxins from blood. These cells are very smart." The researchers caution, however, that bovine fetal cells are not the same as human embryonic stem cells. Still, the work shows that nuclear transplantation can potentially alleviate problems with organ shortages and tissue rejection. --Ricki Lewis Image: Courtesy of Jay P. Schwantes, WebEFX.net Duke throws down the gauntlet Researchers at Duke University Medical Center have proposed a challenge for the First Annual Proteomics Datamining Conference: Define the differences in matrix-assisted laser desorption/ionization [MALDI] mass spectrometry data on blood sera from 40 patients. Twenty patients have the same disease, and the rest are either healthy or have another malady. Following on the heels of the successful Critical Assessment of Microarray Data Analysis competition (J. Kling, "The data analysis grand prix," The Scientist, 16[7]:44, April 1, 2002), this contest may help fill a void in proteomic data mining, says co-organizer Edward F. Patz Jr., professor of radiology and pathology at Duke. "There's very little software out there, very little tools to actually do bioinformatics and data mining of proteomics information." Emmanuel Petricoin, codirector of the Food and Drug Administration-National Cancer Institute Clinical Proteomics Program, developed proteomic diagnostics for early ovarian cancer (T. Hollon, "Software zeroes in on ovarian cancer," The Scientist, 16[8]:16, April 15, 2002). He lauds the conference and competition, but cautions in an E-mail: "Most likely everyone will do well segregating the data, and then everyone will talk about how their approach is the best without any real conclusions drawn." Registrants--about 25 so far--will submit abstracts in August, and reviewers will determine which groups speak and which present posters. As for the prize, Patz concedes, "We don't know [yet], but we're going to think of something very, very good." The journal Proteomics will publish selected abstracts. For more information see www.radweb.mc.duke.edu/cme/proteomics/proteomics.htm. --Jeffrey M. Perkel Image: Erica Johnson NIAID Funds AIDS Research in China As the spread of AIDS in China reaches epidemic proportions, the US government is offering scientific help--and money. To spur new research and infrastructure in China, the National Institute of Allergy and Infectious Diseases (NIAID) recently awarded a special grant to Chinese academic and government scientists. The grant is part of an NIAID initiative created last year called the Comprehensive International Program for Research on AIDS (CIPRA). This is the first multiproject CIPRA grant, the initiative's highest level of funding. CIPRA previously awarded $50,000 (US) planning grants to scientists in China, Peru, the Russian Federation, Trinidad, and Zambia for exploratory and developmental research. NIAID will now distribute $14.8 million over five years to China's Center for Disease Control and Prevention. Though not particularly large by National Institutes of Health standards, the grant significantly bolsters AIDS spending from China's Ministry of Health, which, as of last year, amounted to approximately $12 million--with an additional $36 million coming from individual Chinese provinces. "In the long run, what happens when you give money like this, it stimulates the host country to give comparable investments," says Rod Hoff, CIPRA's program manager and a senior epidemiologist for international research at NIAID. Guided in part by the advice of this country's HIV scientists, the research will include work on HIV pathogenesis, vaccine development, epidemiology, and behavioral intervention. Four cores are slated: a statistical data center, a general lab for epidemiology, primate facilities for vaccine testing, and an administrative core. --Eugene Russo Image: Erica Johnson Battle of the bugs Feeding infants beneficial bacteria can reduce allergic inflammation, according to a Finnish study (P.V. Kirjavainen et al., "Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning?" Gut, 51:51-5, July 2002). According to Pirkka Kirjavainen, this is most likely due to antagonism between the probiotics and inflammatory gut microbiota (See also Cover Story). The group previously observed that formula supplemented with beneficial bacteria, Bifidobacterium lactis, reduced the incidence of inflammatory outbreaks in infants. Various scenarios could explain how probiotic therapy might achieve this: The good bugs might enhance antigen elimination, change the rate of protein degradation and permeation, or down-regulate the immune system. Or, as this group suggests, probiotics could be altering the composition of the intestinal flora. Infants with food allergies have disturbances in the balance between beneficial and harmful bacteria, and repopulating the gut with beneficial bacteria might reverse such disturbances. Infants with histories of eczema and other atopic diseases were weaned onto a formula supplemented with bifidobacteria. A similar control group of infants was given unsupplemented formula. Harmful bacteria, such as enterococi, were found at higher levels in the stool samples of untreated infants. Bacterial counts for treated infants did not increase from preweaning levels. Although the study group was small (21 infants in all), the researchers say their results support the idea that modifying gut microflora could alleviate allergic inflammation. This might provide a new avenue for stemming the tide of allergic conditions on the rise in industrialized nations. --Laura DeFrancesco Image: Courtesy of Ekkehard Schulze, © 2002 Journal of Cell Science A cytoskeletal histone? Scientists know histones belong in the nucleus, yet researchers in Germany found a novel protein very much like linker histone H1 in the cytoplasm. Linker histones normally connect DNA-bound nucleosomes in the 30 nm chromatin fiber by which most eukaryotic genomes are organized. H1.X, found in Caenorhabditis elegans, associates with intermediate fibers in the cytoplasm and structures in the nucleolus, even though it shares the three-partite structure and nuclear localization signals of its histone brethren (M.A. Jedrusik et al., "A novel linker histone-like protein is associated with cytoplasmic filaments in Caenorhabditis elegans," Journal of Cell Science, 115:2881-91, July 2002). RNA interference experiments show that the protein is needed for muscle shape and coordination in nematodes. Disruption especially affects the pharynx, a muscular structure important for feeding. In the marginal cells of this organ, H1.X associates with highly organized fibers called tonofilaments. Ekkehard Schulze, principal investigator at the University of Gottingen, Department of Zoology and Developmental Biology, says that although some may regard the protein as a nematode-specific oddity, he thinks it has real evolutionary weight. "It's one of the unanswered riddles--how it happened that in eukaryotes a three-partite linker suddenly appears," Schulze says. "One speculation is that the evolutionary origin of the histone might be a fiber-associated protein." Unpublished results from his lab and another in the United States have shown dramatic up-regulation of the H1.X gene in dauer larvae. Nematodes form dauer larvae in response to environmental insults such as starvation or overcrowding. Schulze suggests H1.X may play a role in protecting the larvae from sheer force stressors. --Brendan A. Maher

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