PNAS | March 25, 2008 | vol. 105 | no. 12 | 4531-4532
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COMPUTER SCIENCES, SOCIAL SCIENCES
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Detailing flow of Internet information
Epidemic-type spreading models, in which each person "infects" some number of others, do not describe how e-mail chain letters propagate. David Liben-Nowell and Jon Kleinberg show that extra factors are necessary when one models this type of information flow. From Internet mailing-list archives, the authors collected 637 copies of an antiwar petition and 316 copies of a petition to save National Public Radio. Reconstructing the spread from the individual e-mails was a computational challenge, because some signers had altered the list of names, introducing changes that the authors classified as similar to DNA mutations. Accordingly, the authors employed DNA-sequencing techniques to produce a weighted consensus "tree" for each petition. The authors attempted to reproduce the structure of the trees by using a basic model in which each e-mail recipient chooses randomly to forward or delete a message. To test this model, the authors simulated it on the social network of the LiveJournal web site. The results, however, did not match the tree derived from the petition data. To obtain realistic trees, the authors had to desynchronize the sending times and allow for the possibility that recipients of a message would send the petition to all corecipients of the message rather than to their own contacts. — K.M.
"Tracing information flow on a global scale using Internet chain-letter data" by David Liben-Nowell and Jon Kleinberg (see pages 4633–4638)
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ENVIRONMENTAL SCIENCES
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Quick action called for in a flu pandemic
Many factors complicate the work of researchers seeking to model an influenza pandemic; every pandemic is different. In addition to the "Spanish flu" of 1918, there were lesser outbreaks in 1957 and 1968. A chief difference among the three was the case fatality ratio: the proportion of people contracting influenza who die from it. M. Elizabeth Halloran et al. developed three independent models of the spread of an avian-type influenza pandemic in a city like Chicago, IL, and how it might be countered by both pharmaceutical and social measures. The three models each estimated the "attack rate," or percentage population infected, for a virus over a range of R0 values. Factors such as viral pathogenicity, diagnosis accuracy, and pharmaceutical effectiveness were given numerical values, as were the proportion of contacts in schools and workplaces. The authors also assumed that not all patients would obey instructions and take their medicine or stay home. Rather than using their results as a concrete measure of effective strategies, the authors caution that planners should use the data to structure their thinking. However, all three models agree that authorities should act quickly and decisively and that closing schools will be important. — K.M.
"Modeling targeted layered containment of an influenza pandemic in the United States" by M. Elizabeth Halloran, Neil M. Ferguson, Stephen Eubank, Ira M. Longini, Jr., Derek A. T. Cummings, Bryan Lewis, Shufu Xu, Christophe Fraser, Anil Vullikanti, Timothy C. Germann, Diane Wagener, Richard Beckman, Kai Kadau, Chris Barrett, Catherine A. Macken, Donald S. Burke, and Philip Cooley (see pages 4639–4644)
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IMMUNOLOGY
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Chemokines required for cerebral malaria
One of the most common infectious diseases, malaria, remains a significant public health problem around the world. Cerebral malaria, one of the disease's lethal complications, causes more than one million deaths per year, mainly among vulnerable sub-Saharan African children under the age of five. The pathogenesis of the disease has not been well understood, although recent research has suggested a key role for chemokines, chemoattractant cytokine proteins that induce the delivery of immune and inflammatory responses. Using a mouse model, Gabriele Campanella et al. discovered that the chemokine receptor CXCR3 and its ligands, the chemokines CXCL9 and CXCL10, are essential for the development of cerebral malaria. They infected the animals with a plasmodium parasite related to Plasmodium falciparum, which causes the disease in humans, and observed the molecular activity as the infected mice developed cerebral complications, including paralysis and coma that eventually led to death. The animals had elevated levels of CXCL9 and CXCL10, similar to that observed in studies of Ghanaian children with cerebral malaria. Mice lacking the CXCR3 receptor or either of the cytokines, however, had few signs of the disease, with brain T cell counts lower than wild-type animals infected with plasmodium. The authors suggest that these chemokines and their receptor may emerge as potential therapeutic targets to treat this malarial complication. — F.A.
"Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria" by Gabriele S. V. Campanella, Andrew M. Tager, Joseph K. El Khoury, Seddon Y. Thomas, Tabitha A. Abrazinski, Lindsay A. Manice, Richard A. Colvin, and Andrew D. Luster (see pages 4814–4819)
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MICROBIOLOGY
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Microevolution and virulence in Escherichia coli
The bacterial strain Escherichia coli O157:H7 is notorious for causing outbreaks of gastrointestinal illness. However, O157 comprises many different varieties of bacteria, some much more virulent than others. Shannon Manning et al. show that single nucleotide polymorphisms (SNPs) can be used to parse O157 into nine distinct clades, linked to different types of toxin genes and clinical disease. The authors acknowledge that many mutations in O157 consist of multinucleotide insertions or deletions, but they choose SNPs as a metric that is best suited to evolutionary analysis. They studied SNPs at 96 loci in >500 strains of O157 from human disease and subjected their results to an algorithm that separated the bacteria into nine clades. An evolutionary tree reveals parallel paths, suggesting that either recombination or recurrent mutation has contributed to clade emergence. The motivation for the study was to determine why O157 appears to be evolving increasing virulence. Accordingly, the authors sequenced the whole genome of TW14539, an E. coli strain from the 2006 food-borne illness attributed to spinach. TW14539 and many other strains in clade 8 possess the Shiga toxin genes stx2 and stx2c. However, this does not fully explain why clade 8 bacteria are so virulent, the authors say; other factors remain to be identified. — K.M.
"Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaks" by Shannon D. Manning, Alifiya S. Motiwala, A. Cody Springman, Weihong Qi, David W. Lacher, Lindsey M. Ouellette, Janice M. Mladonicky, Patricia Somsel, James T. Rudrik, Stephen E. Dietrich, Wei Zhang, Bala Swaminathan, David Alland, and Thomas S. Whittam (see pages 4868–4873)
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Related articles in PNAS:
- Tracing information flow on a global scale using Internet chain-letter data
- David Liben-Nowell and Jon Kleinberg
PNAS 2008 105: 4633-4638.
[Abstract]
[Full Text]
- Modeling targeted layered containment of an influenza pandemic in the United States
- M. Elizabeth Halloran, Neil M. Ferguson, Stephen Eubank, Ira M. Longini, Jr., Derek A. T. Cummings, Bryan Lewis, Shufu Xu, Christophe Fraser, Anil Vullikanti, Timothy C. Germann, Diane Wagener, Richard Beckman, Kai Kadau, Chris Barrett, Catherine A. Macken, Donald S. Burke, and Philip Cooley
PNAS 2008 105: 4639-4644.
[Abstract]
[Full Text]
- Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria
- Gabriele S. V. Campanella, Andrew M. Tager, Joseph K. El Khoury, Seddon Y. Thomas, Tabitha A. Abrazinski, Lindsay A. Manice, Richard A. Colvin, and Andrew D. Luster
PNAS 2008 105: 4814-4819.
[Abstract]
[Full Text]
- From the Cover: Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaks
- Shannon D. Manning, Alifiya S. Motiwala, A. Cody Springman, Weihong Qi, David W. Lacher, Lindsey M. Ouellette, Janice M. Mladonicky, Patricia Somsel, James T. Rudrik, Stephen E. Dietrich, Wei Zhang, Bala Swaminathan, David Alland, and Thomas S. Whittam
PNAS 2008 105: 4868-4873.
[Abstract]
[Full Text]
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