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In This Issue
GEOPHYSICS, ECOLOGY
Delayed upwelling disturbs ecosystem off the coast of Northern California and Oregon
Along the west coasts of North and South America, winds toward the equator move warm surface waters offshore. The warm water is replaced by cold, nutrient-rich water from the deep ocean, giving rise to rich coastal marine ecosystems and productive fisheries. Off the coast of Northern California and Oregon, the upwelling of cold, nutrient-rich water is seasonally restricted to the spring and summer. John Barth et al. report that, in 2005, the upwelling season was delayed by 1 month compared with the 20-year average, and this delay was followed by stronger-than-average upwelling later in the season. The lack of upwelling in spring led to high water temperatures, low nutrient availability, and low production of phytoplankton. The authors also found that recruitment of mussels and barnacles was reduced early during the upwelling season but rebounded later in the season. These organisms feed as free-swimming larvae for 2–4 weeks before settling. The authors suggest that low food supply may cause the limited survival of mussels and barnacles. Understanding the ecological consequences of altered coastal upwelling will be relevant to the future because climate models of global warming predict delayed and stronger late-season upwelling as observed by Barth et al. — F.A.H.
Gooseneck barnacles surrounding mussels.
“Delayed upwelling alters nearshore coastal ocean ecosystems in the northern California current” by John A. Barth, Bruce A. Menge, Jane Lubchenco, Francis Chan, John M. Bane, Anthony R. Kirincich, Margaret A. McManus, Karina J. Nielsen, Stephen D. Pierce, and Libe Washburn (see pages 3719–3724)
GENETICS
Potassium channel mutations and cardiac arrhythmias in Drosophila
Cardiovascular disease remains the leading cause of death for people in industrialized nations, with disease progression dramatically increasing with age. The mechanisms underlying arrhythmias and heart failure have not been well understood. Karen Ocorr et al. studied the Drosophila homolog of the human KCNQ potassium channel, involved in myocardial repolarization. Alterations in the channel's function are associated with an increased risk for arrhythmias and sudden death in humans. Young fruit flies with mutations to the pore-forming region of the KCNQ channel exhibited heart arrhythmias typically observed in older, wild-type flies. Mutant flies had prolonged contractions, nonsustained fibrillations similar to human arrhythmias, and an increased susceptibility to stress-induced cardiac dysfunction. These fibrillations correlated with a delayed relaxation of the myocardium. Overexpression of the wild-type KCNQ channel reversed both mutant KCNQ- and age-related arrhythmias. These findings suggest that potassium currents mediated by the channel may play a role in the progression of cardiovascular disease in humans as well as in Drosophila. — F.A.
Heart wall movements in Drosophila.
“KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging” by Karen Ocorr, Nick L. Reeves, Robert J. Wessells, Martin Fink, H.-S. Vincent Chen, Takeshi Akasaka, Soichiro Yasuda, Joseph M. Metzger, Wayne Giles, James W. Posakony, and Rolf Bodmer (see pages 3943–3948)
GENETICS
WWOX protein suppresses tumor growth
The gene encoding the WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site on the human genome, and the WWOX protein has been found to be altered in many types of cancers, including breast, prostate, and lung. By generating mice lacking the oxidoreductase, Rami Aqeilan et al. reveal that WWOX acts as a tumor suppressor in vivo. Homozygous mouse mutants without the Wwox gene rapidly developed osteosarcomas and died within 4 weeks. Although Wwox heterozygous animals lived into adulthood, these mice had up to a 5-fold increase in the incidence and multiplicity of spontaneous lung carcinomas and lymphomas compared with wild-type littermates. These tumors expressed the oxidoreductase, which suggests that haploinsuffiency of WWOX is itself cancer-predisposing. This research by Aqeilan et al. demonstrates that WWOX plays a pivotal role in carcinogenesis and may be a target for potential therapeutics. — F.A.
Lung nodule of Wwox +/− mouse showing positive Wwox expression.
“Targeted deletion of Wwox reveals a tumor suppressor function” by Rami I. Aqeilan, Francesco Trapasso, Sadiq Hussain, Stefan Costinean, Dean Marshall, Yuri Pekarsky, John P. Hagan, Nicola Zanesi, Mohamed Kaou, Gary S. Stein, Jane B. Lian, and Carlo M. Croce (see pages 3949–3954)
IMMUNOLOGY
Interleukin-12 induces antiangiogenesis in melanoma cells
Secreted by macrophages and dendritic cells, the cytokine interleukin-12 (IL-12) bridges innate and adaptive immunity. Irma Airoldi et al. found that IL-12 also has antiangiogenic effects on B16 melanoma cells. The authors transplanted melanoma cells expressing the IL-12 receptor into mice that could not produce the functional receptor. Mutant mice produced endogenous IL-12 at higher levels than wild-type animals and developed smaller B16 tumors, which displayed increased levels of apoptosis and decreased proliferation abilities. These lesions were also unable to properly form microvessels. IL-12 delivery further reduced the ability of the melanoma cells to form tumors. In B16 cells expressing IL-12 receptor, PCR arrays identified the up-regulation of the antiangiogenic molecules IFN-γ and epiregulin and the down-regulation of a set of proangiogenic genes including cadherin-5, laminin, and neuropilin, which were previously thought to be unrelated to IL-12. Airoldi et al. say that IL-12 may be an effective therapeutic agent for other human malignancies that functionally express the cytokine's receptor. — F.A.
Vasculature of melanoma tumors in wild-type (a) and IL-12 receptor knockout (b) mice.
“Endogenous IL-12 triggers an antiangiogenic program in melanoma cells” by Irma Airoldi, Emma Di Carlo, Claudia Cocco, Giuseppe Taverniti, Tommaso D'Antuono, Emanuela Ognio, Morihiro Watanabe, Domenico Ribatti, and Vito Pistoia (see pages 3996–4001)
MEDICAL SCIENCES
Selective siRNA delivery to activated leukocytes
Small interfering RNAs (siRNAs) are important experimental tools and have potential as therapeutic substances because siRNAs specifically decrease the translation of the mRNAs they target. A challenge associated with siRNAs has been their delivery into specific cell populations. Dan Peer et al. developed an antibody fragment–protamine fusion protein that delivers siRNAs to activated leukocytes. Protamine, a DNA-binding protein from sperm cells, binds siRNAs. The antibody fragment used to target the protamine–siRNA complex to activated leukocytes recognizes the high-affinity form of LFA-1, a cell adhesion molecule expressed on leukocytes. LFA-1 changes its conformation to the high-affinity form only upon leukocyte activation. Peer et al. injected immunodeficient mice with human leukemia cells and showed that fluorescently labeled siRNAs could be delivered in vivo to the leukemia cells if the cells expressed high-affinity LFA-1. The authors suggest that therapies based on this targeting method will result in fewer side effects because only activated leukocytes, such as the ones mediating inflammation, would be affected by the siRNA. — F.A.H.
Selective delivery of siRNA to activated lymphocytes by targeting integrin LFA-1.
“Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1” by Dan Peer, Pengcheng Zhu, Christopher V. Carman, Judy Lieberman, and Motomu Shimaoka (see pages 4095–4100)
