This Week in PNAS
ENGINEERING
Scale-free models and robustness of the Internet
John Doyle et al. suggest that using scale-free network models to make predictions about the Internet can yield inaccurate results. The authors investigated the line of research portraying the Internet as scale-free, simultaneously unaffected by random losses of nodes yet vulnerable to targeted attacks on the hubs. Doyle et al. specifically examined the conclusion that the Internet has hubs through which most traffic flows, loss of which would fragment the Internet and leave it vulnerable to targeted attacks. Based on technological, economic, and graph theoretic reasons, however, the authors report that this model is not the case for a functioning router-level Internet. At the router level, the Internet does not appear to exhibit a degree distribution with a power-tail, and if it did, the other network properties would be unaffected. Most properties of the Internet were found not to correspond with those predicted by scale-free models. Scale-free network models are appealing in that they can generalize easily without incorporating Internet-specific structures such as protocol stacks and user heterogeneity, the authors say. However, predictions from these models yield results that appear to fall short when tested with actual data or when examined by domain experts. — R.N.
“The `robust yet fragile' nature of the Internet” by John C. Doyle, David L. Alderson, Lun Li, Steven Low, Matthew Roughan, Stanislav Shalunov, Reiko Tanaka, and Walter Willinger (see pages 14497–14502)
MEDICAL SCIENCES
Fetal marker may aid noninvasive prenatal diagnosis
Stephen Chim et al. report the identification of an epigenetic marker in maternal plasma that distinguishes fetal DNA from maternal DNA. This marker may allow for improved noninvasive methods of fetal diagnosis and monitoring. Although low concentrations of fetal DNA have been detected in the blood plasma of pregnant women, the lack of a specific fetal marker to differentiate it from the high levels of maternal DNA has limited its clinical usefulness. Because the primary source of fetal DNA in maternal blood likely comes from placental cells, Chim et al. searched for epigenetic differences between placental and maternal blood cells. Focusing on the maspin gene, a tumor suppressor expressed in the placenta, the fetal maspin gene was found to be highly hypomethylated compared with the maternal version. The unmethylated fetal DNA sequences were detected in maternal blood plasma in all three trimesters and were cleared from the maternal plasma within 24 h of delivery, indicating that it is a marker specific to pregnancy. — M.M.
“Detection of the placental epigenetic signature of the maspin gene in maternal plasma” by Stephen S. C. Chim, Yu K. Tong, Rossa W. K. Chiu, Tze K. Lau, Tse N. Leung, Lisa Y. S. Chan, Cees B. M. Oudejans, Chunming Ding, and Y. M. Dennis Lo (see pages 14753–14758)
MEDICAL SCIENCES
Hox-associated transcription factor binds RNA polymerase
Thomas Milne et al. demonstrate that the mixed lineage leukemia protein (MLL) interacts with RNA polymerase II (pol II) to promote the transcription of target genes. MLL has been shown to bind and up-regulate Hox gene clusters, which are essential for normal embryonic development. Early hematopoietic progenitor cells express the Hox genes Hoxa9, Hoxa7, and Meis1, whereas these genes are down-regulated in differentiated cell types, though MLL is continuously expressed. To investigate how MLL is regulated, Milne et al. examined MLL activity in myeloblastic cells, mouse embryonic fibroblasts, and neutrophils. The authors observed that MLL associated only with Hox gene loci actively being transcribed and only with genes known to be regulated by MLL in the given cell type. MLL and pol II colocalized in vivo at Hoxa9 and Hoxc8 loci in early hematopoietic cells and mouse embryonic fibroblasts, but not in neutrophils. In MLL-null cells, pol II phosphorylation patterns were abnormal at Hox loci, although MLL was not required as a general transcription factor. MLL-independent loci were unaffected. — F.A.
“MLL associates specifically with a subset of transcriptionally active target genes” by Thomas A. Milne, Yali Dou, Mary Ellen Martin, Hugh W. Brock, Robert G. Roeder, and Jay L. Hess (see pages 14765–14770)
MEDICAL SCIENCES
Crossing blood–brain barrier with high-dose enzyme therapy
Carole Vogler et al. report that a therapeutic enzyme can be delivered across the blood–brain barrier in adult mucopolysaccharidosis type VII (MPS VII) mice by administering higher doses than conventionally used in enzyme replacement therapy. The authors measured the distribution and reduction in storage of recombinant human β-glucuronidase (rhGUS) in MPS VII mice immunotolerant to the enzyme. Weekly doses of rhGUS (0.3–40 mg/kg) were administered intravenously over 1–13 weeks. Mice given 20–40 mg/kg three times over 1 week showed no reduction in storage in the CNS, except in the meninges. The most marked and consistent decrease in storage in meningeal and perivascular cells occurred in mice receiving 4 mg/kg per week for 13 weeks; these mice showed clearance in meninges, parietal neo-cortical and hippocampal neurons, and glia. Mice given 20 mg/kg once weekly for 4 weeks also had decreased neuronal, glial, and meningeal storage, and averaged 2.5% of wild-type hGUS activity in the brain. The authors speculate that delivery through the “extracellular route” or saturation of the relatively low number of mannose/galactose receptors in the adult mouse brain drives enough enzyme into the brain to achieve correction, in at least some areas. — R.N.
“Overcoming the blood–brain barrier with high-dose enzyme ment therapy in murine mucopolysaccharidosis VII” by Vogler, Beth Levy, Jeffrey H. Grubb, Nancy Galvin, Yun Tan, Kakkis, Nadine Pavloff, and William S. Sly (see pages 14777–14782)
PSYCHOLOGY
Training improves attention in young children
Rosario Rueda et al. demonstrate that a brief, 5-day educational intervention improves executive attention and intelligence in normally developing children. The brain's executive attention network helps resolve conflicting information, and this capacity develops between the ages of 3 and 7 years. Rueda et al. examined how attention training and genotype influence the development of executive attention and intelligence in 4- and 6-year-old children (n = 73). During the 5 days of training, the children completed a series of increasingly difficult attention tasks. The authors measured attention, event-related potentials, and intelligence before and after the intervention. The children were also genotyped for the dopamine transporter 1 gene, DAT1, a gene previously linked to the efficiency of executive attention. Compared with control groups, children given attention training more closely resembled adult performance on measures of attention, brain activity, and intelligence. Additionally, children with the long form of DAT1 exhibited stronger attention control and thus might benefit less from such an intervention. — M.M.
“Training, maturation, and genetic influences on the development of executive attention” by M. Rosario Rueda, Mary K. Rothbart, Bruce D. McCandliss, Lisa Saccomanno, and Michael I. Posner (see pages 14931–14936)
Figures and Tables
Internet network graph.
Schematic diagram of maspin gene promoter.
MPS VII mice given rhGUS 20–40 mg/kg three times over 1 week show no reduction in storage in glia (arrowhead) or neurons (arrow).
Brain activity changes in trained 4-year-old children during Child Attention Network Test.
