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JCI early table of contents for April 15, 2013

Researchers untangle molecular pathology of giant axonal neuropathy

Giant axonal neuropathy (GAN) is a rare genetic disorder that causes central and peripheral nervous system dysfunction. GAN is known to be caused by mutations in the gigaxonin gene and is characterized by tangling and aggregation of neural projections, but the mechanistic link between the genetic mutation and the effects on neurons is unclear. In this issue of the Journal of Clinical Investigation, Robert Goldman and colleagues at Northwestern University uncover how mutations in gigaxonin contribute to neural aggregation.They demonstrated that gigaxonin regulates the degradation of neurofilament proteins, which help to guide outgrowth and morphology of neural projections. Loss of gigaxonin in either GAN patient cells or transgenic mice increased levels of neurofilament proteins, causing tangling and aggregation of neural projections. Importantly, expression of gigaxonin allowed for clearance of neurofilament proteins in neurons. These findings demonstrate that mutations in gigaxonin cause accumulation of neurofilament proteins and shed light on the molecular pathology of GAN.

TITLE: Giant axonal neuropathy-assoicated gigaxonin mutations impair intermediate filament protein degradation

Robert Goldman
Northwestern University Medical School, Chicago, IL, USA
Phone: 312-503-4215; E-mail:

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Resistance is futile: researchers identify gene that mediates cisplatin resistance in ovarian cancer

Platinum compounds, such as cisplatin and carboplatin, induce DNA cross-linking, prohibiting DNA synthesis and repair in rapidly dividing cells. They are first line therapeutics in the treatment of many solid tumors, but cancer cells frequently develop resistance to these drugs. Mechanisms of resistance typically include reduced platinum uptake and increased platinum export. In this issue of the Journal of Clinical Investigation, Anil Sood and colleagues at M.D. Anderson Cancer Center identified a cellular membrane protein, ATP11B, that mediates cisplatin resistance in ovarian cancer cells. They found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin-resistance in human ovarian cancer cell lines. Further, loss of ATP11B restored the sensitivity of ovarian cancer cell lines to cisplatin and reduced ovarian tumor growth in mice. These findings suggest that ATP11B could serve as a therapeutic target to overcome cisplatin resistance.

TITLE: ATP11B mediates platinum resistance in ovarian cancer

Anil Sood
M. D. Anderson Cancer Center, Houston, TX, USA
Phone: 713-745-5266; Fax: 713-792-7586; E-mail:

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TITLE: RNA binding protein PCBP2 modulates glioma growth by regulating FHL3

Xiaozhong Peng
Institute of Basic Medical Sciences & School of Basic Medicine,Chinese Acad, Beijing, CHN
Phone: 0086-010-65296434; E-mail:

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TITLE: IL-33 dependent induction of allergic lung inflammation by FcγRIII signaling

Anne Sperling
University of Chicago, Chicago, IL, USA
Phone: 773-834-1211; Fax: 773-702-4736; E-mail:

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TITLE: WNT signaling underlies the pathogenesis of neuropathic pain in rats

Xue-Jun Song
Parker University Research Institue, Dallas, , USA
Phone: 9734386932 EXT 7144

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TITLE: Defective telomere elongation and hematopoiesis from telomerase-mutant aplastic anemia iPSCs

Cynthia E. Dunbar
NIH, National Heart, Lung and Blood Institute, Bethesda, MD, USA
Phone: 301 496 1434; Fax: 301-496-8396

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TITLE: Opposing chemokine gradients control human thymocyte migration in situ

Ellen Robey
University of California, Berkeley, Berkeley, CA, USA
Phone: 510-642-8669

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TITLE: GM-CSF contributes to aortic aneurysms resulting from SMAD3 deficiency

Jiahong Xia
Union Hospital, Tongji Medical College, Huazhong University of Science and, Wuhan, CHN
Phone: 0086-13971038472; Fax: 0086-27- 85726337; E-mail:

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TITLE: Mer receptor tyrosine kinase is a novel therapeutic target in melanoma

Douglas Graham
Univ of Colorado Anschutz Medical Campus, Aurora, CO, USA
Phone: 303-724-4006; Fax: 303-724-4015; E-mail:

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Contact: Jillian Hurst
Journal of Clinical Investigation

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