In This Issue

Geophysics

Convections over Tibetan Plateau short-circuited

Rong Fu et al. analyze satellite data to show that summer convection over the Tibetan Plateau allows water vapor and carbon monoxide (CO) to travel directly into the lower stratosphere rather than following a slower path across the cold tropical tropopause over the South Asian monsoon region. The authors used measurements from the NASA Aura Microwave Limb Sounder and Aqua and Tropical Rainfall Measuring Mission satellites and showed that elevated surface heating over the Tibetan Plateau drives a deep tropospheric moist convection that transfers out more water vapor, CO, and ice at the tropopause than over the monsoon region. Furthermore, a combination of warmer tropopause temperatures and slower-falling, smaller cirrus cloud particles in less-saturated ambient air at the tropopause allows more water vapor to travel into the lower stratosphere over the Tibetan Plateau. This movement effectively short circuits the slower ascent of water vapor across the cold tropical tropopause over the monsoon area. Thus, air rich in water vapor and CO is injected into the lower stratosphere over the Tibetan Plateau and travels toward the equator and toward the monsoon area, where it can mix into tropical lower stratosphere air and disperse into the large-scale global stratospheric circulation. — R.N.

Concentration of high-CO air samples.

“Short circuit of water vapor and polluted air to the global stratosphere by convective transport over the Tibetan Plateau” by Rong Fu, Yuanlong Hu, Jonathon S. Wright, Jonathan H. Jiang, Robert E. Dickinson, Mingxuan Chen, Mark Filipiak, William G. Read, Joe W. Waters, and Dong L. Wu (see pages 5664–5669)

Ecology

Slight warming may contribute to malaria resurgence

Mercedes Pascual et al. report that a half-degree rise in temperature may be a factor in the increased incidence of malaria in the East African highlands. Larval development of malaria-transmitting mosquitoes is extremely sensitive to changes in temperature. Although researchers have proposed that global warming may be responsible for the increase in malaria in the highlands of East Africa, previous research has failed to demonstrate a significant change in average temperature in these regions. Pascual et al. analyzed updated temperature data from four sites in the highlands of East Africa and found a statistically significant half-degree increase in average temperature from 1950 to 2002. By using a mathematical model, the biological response of mosquito populations to warming was found to be more than an order of magnitude larger than the measured change in temperature. Because mosquito populations in these high-altitude regions are normally low, any increase in population driven by a temperature increase could dramatically affect malaria transmission. Although the results do not imply that climate change is the primary or unique cause of rising malaria cases, the authors suggest that its role can no longer be ruled out. — M.M.

Malaria incidence and temperature.

“Malaria resurgence in the East African highlands: Temperature trends revisited” by M. Pascual, J. A. Ahumada, L. F. Chaves, X. Rodó, and M. Bouma (see pages 5829–5834)

Medical Sciences

Simulation of interventions in U.S. influenza pandemic

Timothy Germann et al. use a large-scale stochastic simulation model to investigate the spatiotemporal dynamics of spread of a pandemic strain of influenza virus among an artificial U.S. population of 281 million people. Germann et al.’s model combines an individual-level description of influenza viral infection and transmission dynamics with high-fidelity U.S. Census Bureau and Department of Transportation data on population demographics and mobility. The researchers modeled the impact that a variety of levels and combinations of influenza viral agents, vaccines, and modified mobility have on the timing and magnitude of the spread, for values of R₀ (the basic reproductive number) ranging from 1.6 to 2.4. The results suggest that using influenza antiviral agents alone, through a targeted prophylaxis deployment of several million courses, could contain a nascent outbreak with R₀ < 1.9. Alternatively, for low R₀, the rapid production and distribution of vaccines, even if poorly matched to circulating strains, could significantly slow disease spread and limit the number ill to <10% of the population, particularly if children are preferentially vaccinated. However, outbreaks with a higher R₀ would require a combination of strategies, including both social modifications and medical interventions, the authors say. — R.N.

“Mitigation strategies for pandemic influenza in the United States” by Timothy C. Germann, Kai Kadau, Ira M. Longini, Jr., and Catherine A. Macken (see pages 5935–5940)

Medical Sciences

Genetics of pancreatic cancer progression in mice

Nabeel Bardeesy et al. describe how different sets of mutations in three tumor-suppressor genes influence pancreatic tumor biology and progression. Pancreatic ductal adenocarcinoma (PDAC) is the fourth-leading cause of cancer deaths in the United States. Activating mutations in the protooncogene KRAS initiate precancerous lesions, and later inactivation of tumor-suppressor genes turns these lesions malignant. Bardeesy et al. assessed different combinations of inactivating tumor-suppressor mutations (p16^Ink4a, p19^Arf, and p53) in mice with an activating KRAS mutation. The researchers found that homozygous deletion of p53 or p16^Ink4a were associated with rapid disease progression, with p53 mutant tumors arising earlier. Disease progression in mice heterozygous for p53 plus p16^Ink4a or for p16^Ink4a/p19^Arf was slower, but the tumors were more likely to metastasize. Furthermore, the different tumor-suppressor genotypes produced tumors with distinct clinical and histological features, reflecting the range of tumor pathology seen in humans with PDAC. Genomic analysis revealed amplifications and deletions in regions altered in human PDAC. The findings provide insight into the genetic pathways underlying pancreatic cancer progression and may point to potential targets for antitumor therapies. — M.M.

Mouse ductal adenocarcinoma.

“Both p16^Ink4a and the p19^Arf-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse” by Nabeel Bardeesy, Andrew J. Aguirre, Gerald C. Chu, Kuang-hung Cheng, Lyle V. Lopez, Aram F. Hezel, Bin Feng, Cameron Brennan, Ralph Weissleder, Umar Mahmood, Douglas Hanahan, Mark S. Redston, Lynda Chin, and Ronald A. DePinho (see pages 5947–5952)

Microbiology

Poxvirus enters by shedding outer membrane

Mansun Law et al. report that the extracellular enveloped (EEV) form of vaccinia virus (VACV), a poxvirus and the vaccine used against smallpox, enters cells in a two-step process: ligands on the cell surface first disrupt the virus’s fragile outer lipid membrane, and then the viral inner membrane fuses with the cell’s plasma membrane, allowing entry. VACV EEV consists of a viral core surrounded by an inner and outer lipid membrane. This outer envelope protects the virus from immune surveillance and may contribute to the virus’s ability to infect a variety of cell types. Law et al. observed viral entry and found that, unlike other enveloped viruses, the outer envelope of VACV did not fuse with the cell’s plasma membrane but remained outside the cell, shrouding the inner membrane-covered virus. By studying a panel of mutant viruses, the authors showed that membrane rupture required the viral A34 and B5 outer envelope proteins. Also, the administration of polyanions synergized with anti-VACV antibody to protect VACV-infected mice from disease symptoms, including weight loss and pneumonia. — F.A.

EEV membrane rupture at point of contact with cell.

“Ligand-induced and nonfusogenic dissolution of a viral membrane” by Mansun Law, Gemma C. Carter, Kim L. Roberts, Michael Hollinshead, and Geoffrey L. Smith (see pages 5989–5994)