Articles in 2009

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  • After injury to the spinal cord, hemorrhages occur both near and far from the initial lesion. J. Marc Simard and his colleagues demonstrate that spinal cord injury induces expression of the channel Trpm4 on endothelial cells in the spinal cord, which leads to their fragmentation and the spread of the hemorrhage.

    • Volodymyr Gerzanich
    • S Kyoon Woo
    • J Marc Simard
    Article
  • By capitalizing on copy number variation, Wu and his colleagues offer an approach for detecting cellular chimerism with fluorescent in situ hybridization probes that target polymorphic deletion loci. These probes can determine the fate of donor cells in situ, irrespective of gender, and should prove useful in understanding the dynamics of cellular chimerism after solid organ, bone marrow and hematopoietic stem cell transplantation.

    • David Wu
    • Quynh Vu
    • A John Iafrate
    Technical Report
  • TNF is a key pathogenic cytokine in sepsis. Oberdan Leo and colleagues show that production of TNF during sepsis is regulated by the coenzyme NAD and that inhibition of the enzyme NAMPT, which generates NAD from nicotinamide, can improve survival during sepsis in mice. NAD seems to act via sirtuin-6 to increase the translation of TNF.

    • Frédéric Van Gool
    • Mara Gallí
    • Oberdan Leo
    Letter
  • Cerebral cavernous malformation (CCM) is a life-threatening disorder in which blood vessels in the brain dilate and frequently hemorrhage. Benjamin Kleaveland et al. now provide evidence that CCM arises from defects in a signaling pathway involving the KRIT1 and CCM2 intracellular proteins (which have been previously implicated in CCM) and the HEG1 receptor; this pathway acts in endothelial cells and is required for vascular integrity. The role of the CCM2 protein in the endothelium is also explored in another paper published in this issue of Nature Medicine, by Kevin Whitehead et al.

    • Benjamin Kleaveland
    • Xiangjian Zheng
    • Mark L Kahn
    Article
  • Cerebral cavernous malformation (CCM) is a life-threatening disorder in which blood vessels in the brain are prone to hemorrhage. Kevin Whitehead et al. now show that CCM2, mutations in which are associated with CCM, is needed for specific aspects of endothelial cell function involving RhoA GTPase. These defects can be partially restored by statin treatment, suggesting a potential therapeutic intervention for individuals with CCM. The role of CCM2 in the endothelium is also explored in another paper published in this issue of Nature Medicine, by Benjamin Kleaveland et al

    • Kevin J Whitehead
    • Aubrey C Chan
    • Dean Y Li
    Article
  • Ethylmalonic encephalopathy is an autosomal recessive developmental disorder that is characterized by chronic diarrhea and multiple neurological deficits. It is associated with loss-of-function mutations in the ETHE1 gene. Now, Massimo Zeviani and his colleagues report that ETHE1 is a dioxygenase that is responsible for breaking down toxic sulfide in a variety of organs.

    • Valeria Tiranti
    • Carlo Viscomi
    • Massimo Zeviani
    Letter
  • Identifying factors that influence response to cancer chemotherapy is crucial for improving its efficacy. Mauro Delorenzi and his colleagues report that a stromal gene expression signature predicts resistance to a commonly used chemotherapy regimen in individuals with estrogen receptor–negative breast tumors. These findings underline the potential of the tumor microenvironment to modulate tumor phenotype and the clinical response to treatment.

    • Pierre Farmer
    • Hervé Bonnefoi
    • Mauro Delorenzi
    Article
  • There is a need for mouse tumor models that more closely recapitulate the pathophysiology of human cancers. Here, a mouse model of glioblastoma multiforme (GBM) is generated with Cre-loxP controlled, lentiviral-mediated delivery of the oncogenes H-Ras and AKT. Transduction of the oncogenes in a small number of cells in adult immunocompetent mice led to the formation of GBM-like tumors, particularly when combined with loss of p53.

    • Tomotoshi Marumoto
    • Ayumu Tashiro
    • Inder M Verma
    Technical Report
  • The chemokines CCL5 and CXCL4 promote monocyte recruitment to atherosclerotic plaques. Recent findings in vitro have shown that heteromerization of CCL5 and CXCL4 increases their potency in stimulating monocyte adhesion and chemotaxis. Koenen et al. now show that this heteromerization has functional consequences in vivo. Treatment of atherosclerotic mice with a cyclic peptide that specifically disrupts the CCL5-CXCL4 interaction inhibited monocyte recruitment to atherosclerotic plaques. Moreover, selective inhibition of heteromer formation may offer therapeutic advantages compared to complete blockade of chemokine function.

    • Rory R Koenen
    • Philipp von Hundelshausen
    • Christian Weber
    Letter
  • Here are a few of the things that Nature Medicine is looking forward to during 2009.

    Editorial