Articles in 2009

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  • High blood sugar can lead to diabetic retinopathy and subsequent blindness. Glucose is now found to quench a growth factor that keeps pericytes alive. Without these key support cells, the retinal vasculature degenerates (pages 1298–1306).

    • David Antonetti
    News & Views
  • Intellectual-property protection is a key driver of innovation, and researchers are always keen to file patents to shield their discoveries. Yet scientists often have an uninformed view of the value of their intellectual property. This naiveté slows down translational research.

  • Injection of activated protein C (APC) is the last resort to rescue a patient with severe sepsis. Research into how APC works reveals that the drug inactivates histones (pages 1318–1321), which are toxic during severe sepsis.

    • Catherine Chaput
    • Arturo Zychlinsky
    News & Views
  • Flu remains a major killer because of imperfect vaccines and widespread resistance to existing antivirals—problems particularly acute during a pandemic. New findings at the bedside and at the bench could lead to improvements on both fronts. Grace Chen and Kanta Subbarao discuss the implications of research identifying human antibodies than can neutralize a range of viral subtypes. The findings may help lead to a 'universal' vaccine against these diverse and rapidly evolving viruses. Estanislao Nistal-Villán and Adolfo García-Sastre examine two recent studies that reveal the crystal structure of a promising viral drug target, the unique endonuclease domain of the viral polymerase. The findings open the door to the rational design of new influenza virus inhibitors.

    • Grace L Chen
    • Kanta Subbarao
    Between Bedside and Bench
  • The Genetics & Public Policy Center (GPPC), located within the Johns Hopkins Berman Institute of Bioethics in Washington, DC, monitors advances in human genetics, including genetic testing, and their translation into clinical medicine. In September 2009, Joan Scott was named the new director of the center. Scott spoke with Genevive Bjorn about the twists and turns of using information from the double helix.

    • Genevive Bjorn
  • Vascular defects resulting from pericyte cell death are thought to be a major underlying cause of diabetic retinopathy. Pedro Geraldes et al. investigate the signaling mechanisms by which hyperglycemia leads to pericyte death and delineate a pathway by which PKC-δ activation decreases antiapoptotic PDGF receptor signaling (pages 1248–1249).

    • Pedro Geraldes
    • Junko Hiraoka-Yamamoto
    • George L King
  • David Hassel et al. show that mutations affecting the protein nexilin underlie an unusual type of dilated cardiomyopathy characterized by disrupted Z-disk structures in cardiac muscle. Functional studies in zebrafish revealed that nexilin has an essential role in maintaining Z-disk stability and suggested that the disease-causing nexilin mutations found in humans encode proteins that act in a dominant-negative fashion.

    • David Hassel
    • Tillman Dahme
    • Wolfgang Rottbauer
  • Viral gene expression can be regulated by chromatin methylation and demethylation. Thomas Kristie and his colleagues have identified a histone demethylase that is required to remove repressive methylation from the immediate early promoters of two α-herpesviruses. Monoamine oxidase inhibitors, which block this demethylase, prevented lytic replication and reactivation from latency.

    • Yu Liang
    • Jodi L Vogel
    • Thomas M Kristie
  • Extracellular histones released in response to inflammatory challenge contribute to organ failure and death during sepsis. Histone-specific antibodies and activated protein C had beneficial effects in animal models of sepsis, pointing to extracellular histones as therapeutics targets for sepsis and other inflammatory conditions (pages 1245–1246).

    • Jun Xu
    • Xiaomei Zhang
    • Charles T Esmon
  • Notch signaling is known to modulate the phenotype of vascular smooth muscle cells. Xiaodong Li et al. now provide evidence for the importance of signaling through the NOTCH3 receptor and its downstream target HES-5 in pulmonary arterial smooth muscle cells for the development of pulmonary arterial hypertension, and they demonstrate the therapeutic potential of targeting this signaling pathway in a mouse model of pulmonary hypertension.

    • Xiaodong Li
    • Xiaoxue Zhang
    • Patricia A Thistlethwaite
  • Hepatic insulin resistance is often associated with mitochondrial dysfunction, leading to defects in cellular activity. Morris White and his colleagues have now found that continued activity of the transcription factor Foxo1, which is normally inhibited by insulin signaling, is at the crux of this dysfunction, and, when it is genetically deleted, proper mitochondrial function in two models of insulin resistance is restored.

    • Zhiyong Cheng
    • Shaodong Guo
    • Morris F White