Public Release:  JCI early table of contents for April 8, 2013

Journal of Clinical Investigation

Protecting against aging at the molecular level

High fidelity DNA replication during each cycle of cell division is required to maintain genomic stability and prevent chromosomal mutations and rearrangements that can cause disease and aging. Mutations in ATRX, a gene that encodes a protein that participates in DNA replication, are associated with X-linked mental retardation, various cancers, and developmental disorders, but the cellular functions of ATRX are still unclear. In this issue of the Journal of Clinical Investigation, researchers led by Nathalie Bérubé at the University of Western Ontario report on the effects of Atrx deficiency in mice. Using neural precursor cells (NPCs) from Atrx-deficient mice, Bérubé and colleagues found that loss of ATRX is associated with increased DNA damage. Additionally, mice lacking neural Atrx exhibited systemic endocrine dysfunction, shortened lifespans, and degenerative phenotypes similar to human premature aging disorders. These studies demonstrate that ATRX plays a critical role in maintaining the integrity of cellular DNA.

TITLE:
Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced lifespan

AUTHOR CONTACT:
Nathalie G Bérubé
Children's Health Research Institute, The University of Western Ontario, London, ON, CAN
Phone: 519-685-8500 x 55066; Fax: 519-685-8616; E-mail: nberube@uwo.ca

View this article at: http://www.jci.org/articles/view/65634?key=d3e4230ee774cca17a25


Researchers identify transcription factors that regulate retinal vascularization

The retina is a highly vascularized tissue, but too much or too little vascularization can lead to visual impairment and diseases such as familial exudative vitreoretinopathy or macular degeneration. In this issue of the Journal of Clinical Investigation, Alfred Nordheim and colleagues at Tuebingen University in Tuebingen, Germany, identified the DNA transcription factor SRF and its cofactors MRTF-A and MRTF-B as critical regulators of vascularization in the postnatal mouse eye. Loss of vascular Srf in adult mice led to the formation of microaneurysms and excess blood vessel formation similar to human retinal diseases such as retinal angiomatous proliferation and macular telangiectasia. These studies demonstrate that SRF plays an integral role in the development and homeostasis or the retinal vasculature and suggest that SRF could potentially serve as a therapeutic target in human retinal diseases.

TITLE:
Endothelial SRF/MRTF ablation causes vascular disease phenotypes in murine retinae

AUTHOR CONTACT:
Alfred Nordheim
Tuebingen University, Tuebingen, DEU
Phone: 4970712978898; E-mail: alfred.nordheim@uni-tuebingen.de

View this article at: http://www.jci.org/articles/view/64201?key=4dc1a65206b8018e0e4b


ALSO IN THIS ISSUE

TITLE:
Loss of acinar cell Ikka triggers spontaneous pancreatitis in mice

AUTHOR CONTACT:
Michael Karin
University of California, San Diego, La Jolla, CA, USA
Phone: 858-534-1361; Fax: 858-534-8158; E-mail: karinoffice@ucsd.edu

View this article at: http://www.jci.org/articles/view/64498?key=8da89eb7ab14951f7606

TITLE:
Natural variation in Fc glycosylation of HIV-specific antibodies impacts anti-viral activity

AUTHOR CONTACT:
Galit Alter
Massachusetts General Hospital, Charlestown, MA, USA
Phone: 617-724-0546; Fax: 617-726-5411; E-mail: galter@partners.org

View this article at: http://www.jci.org/articles/view/65708?key=259e1956bd16b3da2139

TITLE:
CCDC22 deficiency in humans blunts activation of pro-inflammatory NF-κB signaling

AUTHOR CONTACT:
Ezra Burstein
University of Texas Southwestern Medical Center, Dallas, TX, USA
Phone: 214-648-2008; Fax: 214-648-2022; E-mail: ezra.burstein@utsouthwestern.edu

View this article at: http://www.jci.org/articles/view/66466?key=e9513cca064259fdf788

TITLE:
HIF1α and HIF2α independently activate SRC to promote melanoma metastases

AUTHOR CONTACT:
William Kim
University of North Carolina, Chapel Hill, NC, USA
Phone: 919-966-4765; E-mail: wykim@med.unc.edu

View this article at: http://www.jci.org/articles/view/66715?key=f24859543559147acb78

TITLE:
Smoothened is a master regulator of adult liver repair

AUTHOR CONTACT:
Anna Mae Diehl
Duke University Medical Center, Durham, NC, USA
Phone: 919-684-4173; Fax: 919-684-4183; E-mail: diehl004@mc.duke.edu

View this article at: http://www.jci.org/articles/view/66904?key=05c91856cad4eb6a6fc7

TITLE:
Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica

AUTHOR CONTACT:
Alan Verkman
University of California, San Francisco, San Francisco, CA, USA
Phone: 415-476-8530; Fax: 415-665-3847; E-mail: Alan.Verkman@ucsf.edu

View this article at: http://www.jci.org/articles/view/67554?key=eb9bbcb11dc37e2fc635

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